TW200300349A - A 4-oxoqinoline derivative - Google Patents

Abstract

The present invention relates to a 4-oxoqinoline derivative of the formula (I) [wherein, R1: aryl group etc.; R2: a lower alkyl group etc.; R3: a group of the formula -A-D-E-Gn+(X-)n (wherein, A: oxygen atom etc.; D: a C1-12 alkylene group etc.; E: a single bond etc.); Gn+ : a substituted anmonio group etc.; X-: anion; n: an integer of 1 or 2; R4, R6 and R7: H etc.; R5: H etc.; ring Ar: aryl group etc.], or the pharmaceutically acceptable salts or esters, or the other derevatives thereof having an excellent ileum-type bile acid transporter inhibitory effect.

Description

200300349 声明 、 Declaration □ This case is in accordance with the provisions of Article XX of Article I of the Law of Interests □ Paragraph 1 of Paragraph 1 or □ Paragraph 2 of Paragraph 1, and the date is: _ Redundant This case has been filed with the following countries (regions) Patent application, application date and case number information are as follows: [format please follow: application country (region); application date; application case number sequence notes] 1. Japanese 2001.11.19 Special wishes 2001-353064_

LxJ advocates the priority of Article 24 of the Patent Law: [Please refer to the format: the receiving country (region); the date; the case number sequence notes] —One. □ The main priority of one of the twenty-fifth article of each patent of the main army: [Please follow the format: application date; note of application case order] Microorganism [Please follow the format: depository institution; date; note of number sequence] 2.

[□ Foreign microorganisms [Please follow the format: the name of the host country; organization; date; note of number sequence] Lu ΓΠ Those who are familiar with this technology are easy to obtain and do not need to be deposited. Mei, invention statement (invention description should be clear: the technical field to which the invention belongs, prior technology, content, embodiments and simple description of the drawings) TECHNICAL FIELD The present invention relates to 4-oxoquine with ileal bile acid carrier inhibitory effect Porphyrin derivatives, their pharmaceutically acceptable salts, their esters or other derivatives, 200300349 Pharmaceutical compositions containing these as effective ingredients, using these to make the pharmaceutical composition, or a pharmacologically effective amount thereof for warm-blooded animals (especially humans) Administration to prevent or treat hyperlipidemia, arteriosclerosis. Technical background Hyperlipidemia is one of the three major risk factors for hemorrhagic heart disease, and in particular, lowering cholesterol levels in high blood is helpful for the treatment or prevention of hemorrhagic heart disease. The currently available hyperlipidemia therapeutic agents are known, for example, Η MG-C ο A reductase inhibitors and anion exchange resins, and these agents are used for the treatment or prevention of hyperlipidemia and arteriosclerosis [Am. J. Cardiol ., 76, 899-905 (1995)]. Inhibition of HMG-CoA reductase! In addition to the inhibitory effect of cholesterol synthesis, LDL (low density lipoprotein) receptors in the liver are added to inhale cholesterol in the blood to promote excretion in bile [S cience, 2 3 2, 3 4 -4 7 (1 9 8 6)]. The usefulness and safety of these drugs are widely recognized and used by most patients. The anion exchange resin adsorbs bile acid and prevents the reabsorption of bile acid in the intestine to promote the conversion of cholesterol to bile acid in the liver. As a result, it lowers cholesterol in the blood. [N. Engl. J. Med., 302, 1219-1222 (1980) ° This anion exchange resin has a method such as the use of cholestyramine, which has been practically used, and is difficult to absorb in the body, so it is used in the treatment of hyperlipidemia in children who require more safety. For the first-choice drug. However, cholestyramine is taken in large amounts each time, and the rough feeling of the resin is left in the mouth when taking it, which has the disadvantage that it is very difficult for patients to take. Anion exchange resin also adsorbs and releases certain vitamins, minerals, and medicines. Therefore, it is necessary to consider the supply of vitamins and changes in the method of administration of commonly used medicines, 200300349, and many other problems. In recent years, the ileal-type bile acid carrier, the protein that acts on the initial steps of bile acid reabsorption in the ileum, has been selected [WongM.H. Etal, J. Biol.Chem .. 269.1340-1347 (1994)]. As long as the activity of ileal-type bile acid carriers can be inhibited, the same pharmacological effects as cholestyramine can be expected. From this background, an attempt is made to find an ileal-type bile acid carrier inhibitor [Wes s G. et al., J. Med. C hem., 37, 873-875 (1994)] ° Bile acid carrier inhibitors of the ileum type are known, for example, Japanese Patent Laid-Open No. 200 1 1 9 9 6 5 (W 0 0 1/3 4 5 7 0 Gazette) Compound R1b 0 of the formula (A) under the symbol

[In the above formula, Rlb, R2b, R3b, and R4b are hydrogen, etc., R5b is an aryl group which may have 1 to 3 substituents or a low alkoxy group, and R6b is a formula-CONR7bR8b group (where R8b is an alkyl group) Etc., R8b is an aryl group which may be substituted with halogen, etc.)]. The compound (A) is a quinoline skeleton having the same basic skeleton as the compound of the present invention. However, the compounds (I) and (Π) of the present invention are the 7-positions of the Ar or quinoline skeleton of each ring, and must be substituted with the group of the formula -A-D-E-G n + (X _) n, and the compound ( A) The compounds which are different in the structure of this bulletin and the compounds (I) or (II) of the present invention are not specifically disclosed. DISCLOSURE OF THE INVENTION The inventors have intensively studied the synthesis and pharmacological activity of derivative 200300349 with ileal bile acid carrier inhibitory effects over the years. The 4-oxoquinolinyl derivative of the present invention has ileal bile acid transport. It has excellent inhibitory effect and low side effects, and is expected to be a therapeutic and / or preventive agent for hyperlipidemia and arteriosclerosis, and finally completed the present invention. It is therefore an object of the present invention to provide a 4-oxoquinolinyl derivative, a pharmaceutically acceptable salt thereof, an ester thereof, or other derivatives thereof having an excellent ileal-type bile acid carrier inhibitory effect. Another object of the present invention is to provide a pharmaceutical composition containing the above 4-oxoquinolinyl derivative, a pharmaceutically acceptable salt thereof, an ester or other derivative thereof as an active ingredient, the use for manufacturing the above pharmaceutical composition, or a pharmacological effect thereof. A method of administration to warm-blooded animals (especially humans) to prevent or treat hyperlipidemia and arteriosclerosis. That is, (1) The 4-oxoquinolinyl derivative, pharmacologically acceptable salt, ester or other derivative thereof of the present invention can be represented by the following general formula (I) or general formula (Π). General formula (I) R7 〇 〇

N〆 R2 (I) General or

R 〆2 NIR 200300349 In the formula, R1 is an aryl group, or has one selected from the group consisting of halogen, lower alkyl, halogen lower alkyl, hydroxy, lower oxygen, lower sulfur, oxy, and -lower amino 1 ~ 3 groups substituted aryl, R2 is lower alkyl, lower alkenyl or lower alkynyl, R 3 is a group such as -A-D-E-G n + (X _) n, [wherein in the above formula , A is an oxygen atom, a sulfur atom, a group containing the formula -CH20-or a formula -CH2S-, D is a C 2: alkylene group, a C2-12 alkylene group having an oxygen atom or a sulfur atom in the carbon chain, or The carbon bond has an aryl C2-12 fluorenyl group, E is a single bond, the formula-NR8CO-group and the formula-CONR8-group (in the above formula, R8 is hydrogen or a lower alkyl group.)

Gn + is (i) an ammonium group substituted with a lower group selected from a group of substituent b and an interstitial or dissimilar group substituted with a lower group 3, (ii) an ammonium group in which a nitrogen atom on the ring is bound to E, and more Lower alkyl substituted with a group selected from the substituent b, and 1-pyridyl, 1-pyridyl, or 1- Pyridinyl, (iii) a carbon atom on the median ring combined with E, at least one nitrogen atom on the ring is substituted with a lower alkyl group or an oxy group to form an ammonium group, and a pyridyl group, which can be fused with a benzene ring An alkyl group or a pyrimidinyl group, (iv) a nitrogen atom on the meso ring is bonded to E, and the nitrogen atom is substituted with a lower alkyl group or an oxy group to form an ammonium group, a 1-piperidinyl group, a 1-piperidinyl group, or a 4- A morpholine 200300349 group, (V) may have a lower alkyl group substituted with a substituent b, a 1-U-azobicyclo [2.2.2] octyl group substituted with a substituent b and an oxy group, or 1- (4-acryl-1 -azobicyclo [2.2 · 2] octyl) group, (vi) the carbon atom on the secondary meso ring is bonded to E, and at least one nitrogen atom on the ring is substituted with a lower alkyl group or an oxy group, and Formation of (1-Azobicyclo [2.2 · 2] octyl) or ammonium 2 · 2 · 2] octyl) group, (νϋ) may have 1 to 3 substituted 1-tetrahydrothienyl or 1-tetrahydrothiopyranyl groups, and (viii) may have substituents selected b-substituted lower alkyl and lower alkyl are the same or different 2 substituted sulfofluorenyl, (i X) are the same or different from the lower alkyl and lower alkyl substituted with the group selected from the substituent b 3-Phosphonium group, or nitrogen atom on (X) secondary mesial ring is combined with E, and the nitrogen atom is substituted by lower alkyl or oxy group to form ammonium 1-pyrrolidinyl group, X-is an anion, η is An integer of 1 or 2. ] R4, R6 and R7 are the same or different, each is hydrogen or a substituent a, R5 is a group selected from hydrogen or a substituent b, and the ring Ar is 1 to 3 selected from an aryl or a substituent b Substituted aryl Λ Substituent a is halogen, lower alkyl, hydroxy, lower alkoxy and lower alkylthio, and substituent b is halogen, lower alkyl, cyano, nitro and formula -0 R9, 200300349 Formula -OC Ο NR 9 R 1 0, formula -NR 9 R 1 0, formula -NR 8 COR 9, formula -C Ο 2 R 9 and formula-CONR9R1 () the base (in the above formula, the definition of R8 is as above, R9 And R1G are the same or different and each is selected from the group consisting of hydrogen, lower alkyl, lower alkoxy, aryl, or substituents 1 to 3 substituted aryl.). Among the aforementioned compounds (1), the following compounds are preferred. (2) If (1) the compound, its pharmacologically acceptable salt, its ester or other derivative, wherein R1 is aryl, or is selected from halogen, lower alkyl, halogen lower alkyl, hydroxyl, lower alkoxy, and lower alkyl 1 to 3 substituted aryl groups of thio group, R 2 is lower alkyl, lower alkenyl or lower alkynyl, R 3 is a group of formula-ADE-Gn + (X_) n [wherein, A is an oxygen atom , A sulfur atom, a radical of the formula -CH20- and a radical of the formula -CH2S-, D is C ii 2 alkylene, C 2 _ i 2 alkylene containing an oxygen atom or a sulfur atom in the carbon chain, or in the carbon chain Aryl-containing C 2 _ i 2 alkylene, E is a single bond or a group of the formula-NR8CO-(in the above formula, R 8 is hydrogen or a lower alkyl group.)

Gn + control (i) is selected from the group consisting of lower alkyl substituted with substituent b and the same or different 3 substituted ammonium group of lower alkyl, (ii) an ammonium group in which a nitrogen atom on the ring is bound to E, and more A lower alkyl group substituted with a group selected from the substituent b, and a 1-pyridinyl group, a 1-pyridyl group, or a 1-pyridine group which may be substituted with a group 1 to 3 selected from the substituent b and fused with a benzene ring Ingot group, (iii) a carbon atom on the secondary meso ring is bonded to E, at least one nitrogen atom on the ring-11- 200300349 is substituted by a lower alkyl group or an oxy group to form an ammonium group, which can be fused with a benzene ring , Pyridyl or pyrimidyl, (iv) a nitrogen atom on the secondary mesogenic ring is bonded to E, and the nitrogen atom is substituted with a lower alkyl or oxy group to form an ammonium group, a 1-piperidyl group, a 1-piperidyl group, or 4 -morpholinyl, (v) may have 1- (1-azobicyclo [2.2.2] octyl) substituted with a lower alkyl group substituted with a substituent b, a substituent b and an oxy group substituted Or a 1- (4-acyl-1-azobicyclo [2 · 2 · 2] octyl) group, (vi) a carbon atom on the secondary meso ring is bonded to E, and at least one nitrogen atom on the ring is lower alkyl or (1-Azobicyclo [2.2.2] octyl) or ammonium-based 2] octyl) group, (vii) may have 1 to 3 substituted 1-tetrahydrothienyl or 1-tetrahydrothiopyranyl groups, and (viii) substituted with a group selected from substituent b The lower or lower radicals are the same or different radicals substituted by the same or different radicals 2 or (i X) are substituted with the radicals selected from the radicals of the substituent b and the lower or lower alkyl radicals are substituted with the same or different radicals 3 Phosphonium is an anion and η is an integer of 1 or 2. ] R4, R6 and R7 are the same or different, each is hydrogen or a substituent a, R5 is a group selected from hydrogen < or a substituent b, and ring A r is 1 selected from an aryl or a substituent b ~ 3 substituted aryl groups, substituent a is halogen, lower alkyl, hydroxy, lower alkoxy and lower alkylthio, -12-200300349 substituent b is halogen, lower alkyl, cyano, nitro and Formula-0 R9, Formula-Ο C Ο NR 9 R 1 Q, Formula -NR 9 R 1 °, Formula -NR 8 C 0 R 9, Formula -C Ο 2 R 9 and Formula-CONR9R1 () In the formula, R8 is as defined above, and R9 and Rig are the same or different, and each is selected from hydrogen, lower alkyl, aryl, or substituents a to 1 to 3 substituted aryl groups.) (3) Such as (1) or (2) a compound of general formula (I) or a pharmacologically acceptable salt thereof, (4) such as (1) or (2), a compound of general formula (11) or a pharmacologically acceptable salt thereof '(5) selected The compound according to any one of (1) to (4) or a pharmacologically acceptable salt thereof, wherein R1 is an aryl group, or an aryl group substituted with 1 to 3 groups selected from halogen, lower alkyl, and lower alkoxy (6) A compound or a pharmacologically acceptable salt thereof selected from any one of (1) to (4), wherein R 1 is phenyl, Or a phenyl group substituted with 1 to 3 groups selected from a fluorine atom, a chlorine atom, a C 2 alkyl group and a ci-2 alkoxy group, (7) a compound selected from any one of (1) to (4) Or a pharmacologically acceptable salt thereof, wherein R1 is a phenyl substituted with 1 to 3 groups selected from a fluorine atom or a chlorine atom, (8) a compound selected from any one of (1) to (4) or a pharmacologically acceptable Salt, wherein R 1 is 3-fluorophenyl, 3,5-dichlorophenyl, 3,4-difluorophenyl or 3,5-difluorophenyl, -13-200300349 (9) selected from (1 A compound or a pharmacologically acceptable salt thereof according to any one of (1) to (4), wherein R1 is 3,5-difluorophenyl, (10) a compound selected from any one of (1) to (9), or a pharmacological effect thereof Permissible salt, wherein R 2 is lower alkyl, C 2 _ 3 alkenyl or C 2 _ 3 alkynyl, (11) a compound selected from any one of (1) to (9) or a pharmacologically acceptable salt thereof, wherein R2 is a low alkyl group, (12) a compound selected from any one of (1) to (9) or a pharmacologically acceptable salt thereof, wherein R2 is a C4 alkyl group, and (13) is selected from (1) to ( 9) The compound according to any one or a pharmacologically acceptable salt thereof, wherein R 2 is a C! _2 alkyl group, and (14) is selected from (1) to A compound according to any one of (1) or a pharmacologically acceptable salt thereof, wherein A is an oxygen atom or a sulfur atom, (15) a compound selected from any one of (1) to (1 3) or a pharmacologically acceptable salt thereof, Wherein A is an oxygen atom, (16) a compound selected from any one of (1) to (1 5) or a pharmacologically acceptable salt thereof, wherein 0 is a C! _12 alkylene group, or an oxygen atom or sulfur in the carbon chain Atomic C 2-1 2 Shen Yuanji, -14- 200300349 (17) A compound selected from any one of (1) to (1 5) or a pharmacologically acceptable salt thereof, wherein D is C4_1Q alkylene, or carbon C 2 -6 alkylene group containing 1 to 2 oxygen atoms or sulfur atoms in the chain, (18) a compound selected from any one of (1) to (1 5) or a pharmacologically acceptable _, Yizhong

JTTL ·, ID is C 4-1 〇 丨 ^ ^, and (19) a compound selected from any one of (1) to (15) or a pharmacologically acceptable salt thereof, wherein D is hexamethylene, Methylene or octamethylene, (20) a compound selected from any one of (1) to (1 5) or a pharmacologically acceptable salt thereof, wherein D is 0: 2-12 An alkyl group, (21) a compound selected from any one of (1) to (1 5) or a pharmacologically acceptable salt thereof, wherein D is a C 2 _ 4 alkylene group containing an aryl group in the carbon chain, (2 2) A compound or a pharmacologically acceptable salt thereof selected from any one of (1) to (1 5), wherein D is a C2_4 alkylene group containing a phenyl group in the carbon chain, and (23) is selected from (1) to (22) A compound or a pharmacologically acceptable salt thereof according to any one, wherein E is a single bond, (24) a compound or a pharmacologically acceptable salt selected from any one of (1) to (2 3), wherein Gn + is: (i ) Selected from the group consisting of lower-alkyl and lower-15-200300349 alkyl groups substituted with -OR9 and -NR9R1 () groups, the same or different 3 substituted ammonium groups, (ii) a nitrogen atom on the ring combined with E An ammonium group, a lower alkyl group substituted with a group selected from the substituent b, and optionally a substituent b 1- to 3-substituted 1-pyridinyl, 1-pyridinyl, or 1-pyridinyl group which can be fused with benzene ring (iii) the carbon atom on the meso ring is bonded to E, and at least one nitrogen atom on the ring is Pyridinyl, pyridyl or pyrimidyl, which can be substituted with a lower alkyl or oxy group to form an ammonium group, which can be fused with a benzene ring, (iv) the nitrogen atom on the secondary mediating ring is bound to E, and the nitrogen atom is reduced Alkyl or oxo substituted to form ammonium, 1-piperidinyl, piperidinyl or 4-morpholinyl, (v) lower alkyl substituted with a group selected from substituent b, substituent b and 1- (1-azobicyclo [2.2.2] octyl) or ^ (4-az-1-azobicyclo [2.2.2] octyl), substituted with oxo group, (vi) secondary mesogenic ring The upper carbon atom is combined with E, and at least one nitrogen atom on the ring is substituted with a lower alkyl group or an oxy group to form an (1-azobicyclo [2.2.2] octyl) group or (4 -acyl-1- Azobicyclo [2 · 2 · 2] octyl), (νϋ) may have 1 or 3 substituted 1-tetrahydrothienyl groups, and (viii) is selected from the group containing formula-OR9 and formula- NR9R1 ()-substituted lower alkyl and lower alkyl groups which are the same or different from each other 2 substituted sulfofluorenyl, or (ix) is selected from the group containing formula-〇R9 and -NR9R1 () group-substituted lower alkyl group and the same or different 3 group substituted phosphino group of the lower alkyl group, (2 5) a compound selected from any one of (1) to (2 3) or a pharmacologically acceptable Salt, in which Gn + is, (i) selected from the group consisting of hydroxy or di-loweralkylamino-substituted lower alkyl and lower alkyl phase-16-200300349 iso-or isomeric 3 substituted ammonium group, (ii) nitrogen on the ring An ammonium group having an atom bonded to E, a lower alkyl group substituted with a group selected from substituent b, and a 1-pyridinyl group substituted with a group 1 to 3 selected from substituent b and fused with a benzene ring 1, 1-pyridyl or 1-pyridinyl (iii) the carbon atom on the secondary meso ring is bonded to E, at least one nitrogen atom on the ring is replaced by a lower alkyl group or an oxy group to form an ammonium group, and it can be thickened with a benzene ring Combined pyridinyl, pyridinyl, or pyridinyl, (iv) the nitrogen atom on the secondary median ring is combined with E, and the nitrogen atom is substituted with a lower alkyl or oxy group to form an ammonium group, 1-piperidinyl, 1 -Piperidinyl or 4-morpholinyl Λ (V) may have a 1- (1-azobicyclo substituted with a lower alkyl group substituted with a substituent b, a substituted b and an oxy group [2.2. 2] octyl) or 1-(4 -az-1 -azobicyclo [2.2 · 2] octyl) (Vi) The carbon atom on the secondary meso ring is combined with E, and at least one nitrogen atom on the ring is substituted with a lower alkyl group or an oxy group to form an (1-azobicyclo [2.2.2] octyl) group or ( 4-acyl-1-azobicyclo [2 · 2 · 2] octyl), (vii) 1-tetrahydrothienyl, (viii) selected from the group consisting of hydroxy or di-loweramino substituted low alkyl and low The same or different alkyl group substituted by sulfofluorenyl group, or (i X) is selected from the group consisting of hydroxy or di-loweralkylamino-substituted lower alkyl group and the same or different group of 3 substituted phosphino group, 26) A compound or a pharmacologically acceptable salt thereof selected from any one of (1) to (2 3), wherein G n + is, (i) a tri-low alkylammonium group, -17- 200300349 (ii) ring nitrogen An ammonium group having an atom bonded to E, a lower alkyl group substituted with a group selected from substituent b, and a 1-pyridinyl group substituted with a group 1 to 3 selected from substituent b and fused with a benzene ring , 1-pyridyl or 1-pyridinyl, (iii) the carbon atom on the secondary median ring is combined with E, at least one nitrogen atom on the ring is replaced by a lower alkyl group or an oxygen group to form an ammonium group, and it can also be bonded to a benzene ring Fused pyridinyl, pyridinyl or pyridinyl, (iv) nitrogen atom on secondary meso ring and E And the nitrogen atom is substituted with a lower alkyl group or an oxy group to form an ammonium group, a 1-piperidinyl group, a piperidinyl group, or a 4-morpholinyl group, (v) may be substituted with a group selected from the substituent b 1- (1-azobicyclo [2.2.2] octyl) or 1- (4-azo-; M-azabicyclo [2.2.2] octyl substituted with lower alkyl, substituent b and oxo groups Group), (vi) the carbon atom on the secondary meso ring is bonded to E, and at least one nitrogen atom on the ring is substituted with a lower alkyl group or an oxy group to form an ammonium group (1-azobicyclo [2.2.2] octyl) Or (4-az-1--1-azobicyclo [2.2.2] octyl), (viii) di-lowanesulfonyl, or (i X) tri-lowan phosphino, (27) selected from The compound of any one of (1) to (2 3) or a pharmacologically acceptable salt thereof, in which Gn + is, (ii) an ammonium group in which a nitrogen atom on the ring is bound to E, and further substituted with a group selected from substituent b Low alkyl, and 1- to 3-substituents selected from substituents b, which may be fused with a benzene ring, 1-pyridinyl, 1-pyridinyl, or 1-pyridinyl (iii) carbon on the secondary mesogenic ring Pyridine-18- 200300349 ingot that is bonded to E, at least one nitrogen atom on the ring is substituted by a lower alkyl group or an oxy group to form an ammonium group, and can be fused with a benzene ring Group, pyridyl group or pyrimidyl group, the nitrogen atom on the (i V) secondary mesogenic ring is combined with E, and the nitrogen atom is substituted by a lower alkyl group or an oxy group to form an ammonium group, a 1-piperidinyl group, a 1-piperidine Or 4-morpholinyl, (v) may have a 1- (1-azobicyclo [2.2.2] octyl substituted with a lower alkyl group substituted with a substituent b, a substituent b and an oxy group Or a 1- (4-acyl-1-azobicyclo [2 · 2.2] octyl) group, or (vi) a carbon atom on the secondary meso ring is bonded to E, and at least one nitrogen atom on the ring is lower alkyl (1 -Azobicyclo [2.2.2] octyl) or (4-Aza-1-azobicyclo [2.2.2] octyl), or (2 8) The compound according to any one of (1) to (2 3) or a pharmacologically acceptable salt thereof, wherein Gn + is: (i) a low-alkyl group substituted with a group selected from the substituent b, and may have a group selected from the substituent b 1-Pyridinyl, which is substituted by 1-3, and can be fused with a benzene ring, (iii) a carbon atom on the secondary meso ring is bonded to E, and at least one nitrogen atom on the ring is substituted by a lower alkyl group or an oxy group Ammonium group, pyridinium group which can be fused with benzene ring, nitrogen atom on (iv) ring is substituted with lower alkyl group or oxygen group to form ammonium group 1-piperazinyl, (v) may have a lower alkyl substituted with a substituent selected from the substituent b, a 1- (1-azobicyclo substituted with a substituent b and an oxy group [2 · 2 · 2] Octyl) group or 1- (4-acyl-1-azobicyclo [2.2.2] octyl) group, or (vi) the carbon atom on the secondary meso ring is bonded to E, and at least one nitrogen atom on the ring is lower alkyl (1-Azobicyclo [2 · 2.2] octyl) or ammonium group substituted to form an ammonium group, 200300349 (2 9) (1) The compound according to any one of (1) to (2 3) or a pharmacologically acceptable salt thereof, wherein Gn + is: (i) a 1-pyridinyl group substituted with a group 1 to 3 selected from substituent b, (iii ) The carbon atom on the secondary meso ring is combined with E, at least one nitrogen atom on the ring is substituted with a low alkyl group to form an ammonium pyridinium group, (iv) the nitrogen atom on the ring is substituted with a low alkyl group to form an ammonium group. The piperidinyl group or (v) may have a 1- (1-azobicyclo [2 · 2 · 2] octyl) group substituted with a group selected from the substituents b and an oxy group, or a 1- (4-acyl-1 -An azobicyclo [2 · 2 · 2] octyl) group, (3 0) a compound selected from any one of (1) to (2 3) or a pharmacologically acceptable salt thereof, wherein Gn + is: (ii) can Low alkyl, formula -OR9 and formula -NR9R1 () substituted 1-pyridinyl, or (v) may have low alkyl, formula -OR9, formula -NR9R1 () and oxy substituted 1 -(1 -Azobicyclo [2 · 2 · 2] octyl) yl or 1-(4 -acyl-1 -azobicyclo [2.2.2] octyl) yl, (3 1) selected from (1) The compound according to any one of (2 3) or a pharmacologically acceptable salt thereof, wherein Gn + is: (ii) 1-pyridine which may be substituted with a low-radical group, a molybdenyl group, a low-radical oxygen group, and a -loweramine group Ingot base, or (v) may have 1- (1- (azo-bicyclo [2.2.2] octyl) group substituted with low-radical, via radical, low-radical oxy, __ * low-radical amine and oxy, or 1- (4-acyl-azobicyclo [2.2.2] octyl) yl, (3 2) a compound selected from any one of (1) to (2 3) or a pharmacologically acceptable salt thereof-20- 200300349, Where Gn + is: (ii) may have a 1-laidyl group substituted by a radical and a low-oxyl group, or (ν) may have a low-radical, a low-oxyl group, a low-oxyl group, and a low-amino group And oxy-substituted 1- (1-azobicyclo [2.2.2] octyl) yl or 1- (4-azine-azobicyclo [2.2.2] octyl) yl (3 3) is selected from (1 ) To the compound of any one of (2 3) or its pharmacological capacity Xu salt, where ση + is: 1 -pyridinyl, 1-(1 -azobicyclo [2 · 2 · 2] octyl) and 1-(4 -acyl-1 -azobicyclo [2.2,2 ] Octyl) group, (3 4) a compound selected from any one of (1) to (2 3) or a pharmacologically acceptable salt thereof, wherein Gn + is: (iv) a nitrogen atom on the ring is substituted with a lower alkyl group and A 1-piperidyl (3 5) group forming an ammonium group is a compound selected from any one of (1) to (2 3) or a pharmacologically acceptable salt thereof, wherein Gn + is: (ii) a formula -C02R9 group and formula -CONR9R1 () group or aryl substituted 1-pyridinyl compound or a pharmacologically acceptable salt thereof, (3 6) a compound selected from any one of (1) to (2 3) or a pharmacologically acceptable salt thereof, wherein Gn + is, (ii) 1-pyridinyl substituted with aryl, (37) a compound selected from any one of (1) to (3 6) or a pharmacologically acceptable salt thereof, wherein X-is a peptidyl ion (3 8) A compound or a pharmacologically acceptable salt thereof selected from any one of (1) to (3 7), wherein -21-200300349 R 5 is hydrogen, formula -OR 9 group, and formula -NR 9 R 1 0 group, (39) a compound selected from any one of (1) to (37) or a pharmacologically acceptable salt thereof, wherein R5 is a group of formula -OR9, ( 40) a compound or a pharmacologically acceptable salt thereof selected from any one of (1) to (3 7), wherein R5 is a low alkoxy group, and (4 1) is selected from any of (1) to (4 0) Or a pharmacologically acceptable salt thereof, wherein R4, R6, and R7 are the same or different, each is hydrogen, halogen, lower alkyl, or lower alkoxide, (4 2) is selected from (1) to (4 0) The compound of any one or a pharmacologically acceptable salt thereof, wherein R4, R6, and R7 are the same or different, each is hydrogen, a fluorine atom, a chlorine atom, a Ci_2 group or a Ci_2 group, and (4 3) is selected from ( 1) A compound according to any one of (1) to (40) or a pharmacologically acceptable salt thereof, wherein R4, R6 and R7 are hydrogen, (44) a compound selected from any one of (1) to (40), or a pharmacological property thereof Allowable salt, wherein R4, R6, and R7 are methoxy groups, (45) A compound selected from any one of (1) to (4 4), or a pharmacologically acceptable salt thereof, wherein ring A r is selected from substituent b A substituted aryl group of 1 to 3, (4 6) a compound selected from any one of (1) to (4 4), or a pharmacologically acceptable salt thereof 200300349, wherein the ring Ar is selected from the group consisting of formula-OR9 and formula-NR9R1 The (1) group is substituted by an aryl group of 1 to 3, (47) is selected from (1 The compound according to any one of (1) to (44), or a pharmacologically acceptable salt thereof, wherein the ring Ar is an aryl group substituted with a group 1 to 3 of formula-OR9, (4 8) is selected from (1) to (4 4) A compound of any one or a pharmacologically acceptable salt thereof, wherein ring A is a square group substituted with a low-oxyl group 1 to 3, (49) a compound selected from any one of (1) to (44), or Pharmacologically acceptable salt, wherein ring A is 3-methoxyphenyl or 3,5-dimethoxyphenyl, (50) a compound selected from any one of (1) to (44) or a pharmacologically acceptable salt thereof, wherein Ring A is 3,5-diethoxyphenyl or 3-ethoxy-5-propoxyphenyl, (5 1) a compound selected from any one of (1) to (50) or a pharmacologically acceptable A salt, wherein η is an integer of 1, and (52) (1) or (2) may be selected from the following compounds or their pharmacologically acceptable salts are chlorinated 1- {2- {3- {3- [Ν- (3 , 5-difluorophenyl) -N-ethylaminomethylmethyl] -7-methoxy-4-oxo-4fluorene-quinoline-l-yl} -5-methoxyphenoxymethyl} benzyl 丨Pyridinium, 1- {2- {3- {3- [N- (3,5-difluorophenyl) -ethylaminomethylmethyl] -7-methoxy-4-oxo-4methyl-quinine Phenyl-1-ylbu 5 -methoxyphenoxymethyl} benzyl-23- 200300349 group 丨 azobis [2 · 2 · 2] octane, 1- {2- {3- {3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine 7-methoxy 4-oxo-4H-quinolin-1-yl} -5-methoxyphenoxymethyl} benzyl} -4 -acyl-1 -azobicyclo [2 · 2.2] octane, 1- {bromide 2- {3- {3- [N- (3,5-difluorophenyl) -N-ethylaminomethyl] -7-methoxy-4-oxo-4H-quinoline-l-yl} -5 -methoxyphenoxymethyl} benzyl}-4 -acyl-1 -azobicyclo [2 · 2 · 2] octane, bromide 1- {7- [3- [Ν- (3,5 -Difluorophenyl) -N-ethylaminomethylmethyl] -1- (3, 5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinolin-7-yloxy] heptyl Methyl} pyridine, 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -l- (3,5-dimethoxyphenyl) ) -4-oxo-l, 4-dihydroquinoline-7-yloxy] heptylbu-l-azobicyclo [2 · 2 · 2] octane, bromide 1- {7- [3- [ Ν- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7 -Yloxy] heptylb 1-azobicyclo [2.2 · 2] octane, 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylamine methyl chloride Fluorenyl] -1- (3, 5-dimethoxyphenyl) -4-oxo-I, 4-dihydroquinolin-7-yloxy] heptylb 4 -Acryl-1 -azobicyclo [2 · 2 · 2] octane, 1- {7- [3- [N- (3,5 -difluorophenyl) -N-ethylaminomethylammonyl bromide ] -1- (3,5 -dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7-yloxy] heptylbu 4 -acyl-1 -azobicyclo [2.2 · 2] octane, 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3,5-dimethoxyphenyl) bromide ) -4 -oxo-1,4-dihydroquinolin-7-ylsulfanyl] heptyl, pyridinium, 200300349 1- {7- [3- [N- (3,5-difluorobenzene) bromide ) -N-ethylaminomethylmethyl] -1- (3,5-dimethoxyphenyl) -4-oxy-1,4-dihydroquinolin-7-ylsulfanyl] heptyl 丨- 1-Azobicyclo [2.2.2] octane, and 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethyl]]-1- ( 3,5 -dimethoxyphenyl) -4 -oxo-1,4-dihydroquinolin-7-ylsulfanyl] heptylbu 4 -acyl-1 -azobicyclo [2 · 2.2] octane (53) In (1) or (2), it may be selected from the following compounds or their pharmacologically acceptable salts, brominated 1- (7- {1- (3,5-diethoxyphenyl) -3- [N -(3,5-difluorophenyl) -N-ethylaminomethyl] -4 -oxo-1,4-dihydroquinoline-7-yloxy 丨 heptyl) _ 4-acyl-bu Azobicyclo [2 · 2 · 2] Xin 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3,5-dimethoxyphenyl) -4 -Oxy-1,4-dihydroquinoline-7-yloxy] heptyl}-1-methylpiperidine, 1- (8- {1- (3,5-diethoxyphenyl)- 3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -4 -oxo-1,4-dihydroquinolin-7-yloxy} octyl) -1- Mepidol, _ 1- (7- {1- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine ] -5 -methoxy-4-oxo-1,4-dihydroquinoline-7-yloxy} heptyl) -1-methylpiperidine, 1- (7- {1- (3, 5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -5 -methoxy-4-oxo-1,4-dihydro Quinoline-7-yloxy 丨 heptyl) -4 -acyl-1 -azobicyclo [2 · 2 · 2] octane, 1- (8- (1- (3,5 -diethoxy) bromide Phenyl) -3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine 5-methoxy-4 -oxo-1,4-dihydroquinolin-7-yl Oxygen-25- 200300349 yl} octyl) -4 -acyl-1 -azobicyclo [2.2.2] octane, brominated 1-(7-{1-(3,5 -diethoxyphenyl) ) -3-[N-(3 5 5 -difluorophenyl) -N -ethylaminomethylmethyl] -4 -oxy-1,4 -Dihydroquinoline-7-yloxy} heptyl) -1 -methylpiperidine and 1- {7- {3- [N- (3,5-difluorophenyl) -N-ethyl bromide Aminemethyl] -1- (3-ethoxy-5 -propoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7-yloxy} heptyl}-4 -acyl- 1-Azobicyclo [2.2.2] octane, (54) (1) or (2), which may be selected from the following compounds or their pharmacologically acceptable salts, 1- (7- {1- ( 3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -4 -oxy-1,4-dihydroquinoline-7 -Alkyloxy} heptyl) 4 -acyl-1 -azobicyclo [2. 2 · 2] octane, 1- {7- [3- [N- (3,5-difluorophenyl) chloride ) -N-ethylaminomethylmethyl] -1-(3, 5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7 -yloxy] heptyl}-1- Mepidol, 1-(8-{1-(3,5-diethoxyphenyl) -3-[N-(3,5-difluorophenyl) -N -ethylaminomethyl)] -4 -oxo-1,4-dihydroquinoline-7-yloxy} octyl) -1-piperidine, 1- (7-{1-(3,5-diethoxyphenyl) chloride ) -3-[N-(3,5-difluorophenyl) -N -ethylaminomethyl] -5 -methoxy-4 -oxy-1,4-dihydroquinoline-7 -yloxy base} Heptyl) -1-methylpiperidine, 1-(7-{1-(3,5-diethoxyphenyl) -3-[N-(3 J -difluorophenyl) -N -ethyl Aminomethyl] -5 -methoxy-4 -oxo-1,4 -dihydroquinoline-7 -yloxy} heptyl)-4-acyl-1 -azobicyclo [2 · 2.2 ] Octane-26- 200300349 1- (8-{1- (3,5-diethoxyphenyl) -3-[N-(3,5-difluorophenyl) -N-ethylamine Alkyl] -5-methylamino-4-oxo-1,4-monoaminopyridine-7-yloxy} octyl) -4 -acyl-1 -azobicyclo [2 · 2 · 2] Octane, 1- (7- {1- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminemethyl]] 4-oxo-1,4-dihydroquinoline-7-yloxy} heptyl) -1-methylpiperidine, and 1- {7- {3- [N- (3,5-difluoro) Phenyl) -ethylaminomethylmethyl] -1- (3-ethoxy-5-propoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy} heptylb 4-Acryl-1 -azobicyclo [2.2.2] octane. Among the above compounds (I) or (II), it is preferred to be selected from (1) or (2); (3) or (4); (5) to (9); (10) to (13); (14) to (15); (16) ~ (22) :( 23); (24) ~ (36); (37); (38) ~ (40); (41) ~ (44) :( 45) ~ (50 ); And (51) a compound of any combination of-. In the above definitions, "aryl" in the definitions of R1, ring Ar, R9 and R1G, and "in the definition of R1" are selected from the group consisting of halogen, lower alkyl, halogen lower alkyl, hydroxy, lower alkoxy, lower alkylthio, cyano and Aryl group substituted with 1 to 3 groups of di-lower alkylamine group ", and the aryl moiety in the definition of ring A r, R 9 and R 1 ° selected from" aryl group substituted with 1 to 3 groups of substituent a " A C6_1G aromatic hydrocarbon group such as phenyl, indenyl or naphthyl, preferably phenyl. In the above formula, R2, R8, R9, R1G, Gn +, "lower alkyl" in the definition of substituent a and substituent b, and "selected from the group consisting of halogen, lower alkyl, halogen lower group, Aryl substituted with 1 ~ 3 groups of radical, low-oxyl, low-sulfan, amino and ~~ low-amino, "and the definition of" selected from low-substituted radical of substituent b "in Gn + The `` lower alkyl '' part is, for example, methyl, ethyl-27- 200300349, propyl, isopropyl, butyl, isobutyl, second butyl, third butyl, pentyl, isoamyl, 2 -Methylbutyl, neopentyl, 1-ethylpropyl, hexyl, isohexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, ¢: ^ 6 straight or branched alkyl such as 2,3-dimethylbutyl, 1-ethylbutyl or 2-ethylbutyl. R2 and Gn + are preferably a CH4 alkyl group, more preferably a Ci_2 alkyl group, and most preferably a methyl group or an ethyl group. R1, R8, substituent a and substituent b are preferably Ci_4 radicals, more preferably Ci_2 radicals, and most preferably methyl. R9 and R1 (3 is preferably Ci_4 radical, more preferably Ci_3 radical, most preferably methyl, ethyl or propyl. In the above definition of R2, "lower alkenyl" is, for example, vinyl, 1- Propenyl, 2-propenyl, 1-methyl-2-propenyl, 1-methyl-propenyl, 2-methyl-1-propenyl, 2-methyl-2-propenyl, 2- Ethyl-2-propenyl, butadiyl, 2-butenyl, 1-methyl-2-butanyl, 1-methyl-1-butenyl, 3-methyl-2-butyl Alkenyl, ethyl-2-butenyl, 3-butenyl, 1-methyl-3-butanyl, 2-methyl-3-butanyl, 1-ethyl-3-butanyl, 1-ethyl Pentyl, 2-pentyl, 1-methyl-2-pentyl, 2-methyl-2-pentyl, 3-pentyl, 1-methyl-3-pentyl, 2 -Methyl-3-pentanyl, 4-pentanyl, 1-methyl-4-pentyl, 2-methyl-4-pentyl, 1-hexyl, 2-hexenyl, 3 -Hexyl, 4-hexenyl or 5-hexenyl, C2-6 straight or branched alkynyl, preferably C 2-3 alkyl, most preferably 2-propenyl. In the above formula, R2 In the definition, `` lower alkynyl '' is, for example, ethynyl, 2-propynyl, methyl-2-propynyl, 2-butynyl, 1-methyl-2-butynyl, -28- 20030034 9 1-ethyl-2 -butynyl, 3 -butynyl, 1 -methyl-3 -butynyl, 2-methyl-3 -butynyl, 1 -ethyl-3 -butynyl , 2-pentynyl, 1-methyl-2-pentyl, 3-pentyl, 1-methyl-3-pentyl, 2-methyl-3-pentyl, 4-pentyne C 2 of phenyl, 1-methyl-4-pentynyl, 2-methyl-4-pentynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, or 5-hexynyl _ 6 straight or branched alkynyl, preferably C2_3 alkynyl, most preferably 2-propynyl. In the above definition of "D", "Cu12alkylene" is methylene, methylmethylene, ethylidene , Propyl, trimethylene, 1-methyl phenylethyl, tetramethylene, 1-methyltrimethylene, 2-methyltrimethylene, 3-methyltrimethylene, 1-methyl Propylene, 1,1-dimethylethylene, pentamethylene, tetramethylmethylene, 2-methyltetramethylene, 3-methyltetramethylene, 4-methyltetramethylene Methyl, 1,1-dimethyltrimethylene, 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene, hexamethylene, 1-methylpentamethylene, 2-methylpentamethylene, 3-methylpentamethylene, 4-methylpentamethylene, 5- Methylpentamethylene, 1,1-dimethyltetramethylene, 2,2-dimethyltetramethylene, 3,3-dimethyltetramethylene, 4,4-dimethyl Tetramethylene, heptamethylene, 1-methylhexamethylene, 2-methylhexamethylene, 5-methylhexamethylene, 3-ethylpentamethylene, octamethylene , 2-methylheptamethylene, 5-methylheptamethylene, 2-ethylhexamethylene, 2-ethyl-3-methylpentamethylene, 3-ethyl-2-methyl Pentamethylene, unamethylene, 2-methyloctamethylene, 7-methyloctamethylene, 4-ethylheptamethylene, 3-ethyl-2-methylhexamethylene Ci.12 straight or branched alkylene, 2-ethyl-1-methylhexamethylene, decamethylene, undecylethylene, or dodecyl methylene, preferably C4_1Q alkylene , More preferably hexamethylene, heptamethylene or octamethylene, most preferably heptamethylene or octamethylene. -29- 200300349 The "C2_12 alkylene group containing oxygen atom or sulfur atom in the carbon chain" in the definition of the above-mentioned middle and D is the C2_i2 straight or branched alkylene in the "c! _! 2alkylene" Group containing 1 to 4 oxygen or sulfur atoms, such as -CH2-0-CH2-, -ch2-o- (ch2) 2-,-(ch2) 2-o- (ch2) 2-,-(ch2 ) 2-o- (ch2) 2-o- (ch2) 2-,-(ch2) 2-o- (ch2) 2-o- (ch2) 2-o- (ch2) 2-,-(CH2) 2_〇- (CH2) 2_〇- (CH2) 2_〇- (CH2) 2_〇_ (CH2) 2-, _CH2-S-CH2_, _CH2_S- (CH2) 2_,-(CH2) 2_S- (CH2) 2-,

-(ch2) 2-s- (ch2) 2-s- (ch2) 2-,-(CH2) 2-S- (CH2) 2-S- (CH2) 2-S- (CH2) 2- or- (ch2) 2-s- (ch2) 2-s- (ch2) 2-s- (ch2) 2-s- (ch2) 2, preferably C with 1 to 3 oxygen or sulfur atoms in the carbon chain 2 _ i 〇 alkylene, more preferably a C2_6 alkylene group containing 1 to 2 oxygen or sulfur atoms in the carbon chain, most preferably-(CH2) 2-〇_ (CH2) 2-or-(CH2 ) 2 ~ 〇- (CH2) 2-〇_ (CH2) 2.

In the above definitions of "D", "C 2_12 alkylene having an aryl group in the carbon chain" is C 2 _! 2 straight or branched alkylene in the above "C ii 2 alkylene". 1 aryl group, for example,

-30- 200300349

— (H2C) 2

Preferably it is a C 2_6 alkylene group containing an aryl group in the carbon chain, more preferably C 2_4 alkylene group containing an aryl group in the carbon chain, most preferably

In the above definitions of substituents a and b, "halogen" and R1 are "selected from the group consisting of halogen, low-density, halogen-low-density, meridyl, low-oxyl, low-alkylthio, cyano, and The "halogen" part of the "lower alkylamino-substituted aryl group" is fluorine, chlorine, bromine or iodine, preferably fluorine or chlorine, and most preferably fluorine. In the above definition of R1, "Aromatic compounds substituted with 1 to 3 groups selected from halogen, lower alkyl, halogen lower alkyl, ceryl, lower alkyloxy, lower alkylthio, fluorenyl, and -lower amino" The "halo-lower alkyl" part of the "radical" is substituted by the above-mentioned "low-alkyl" and substituted with halogen, for example, trifluoromethyl, trichloromethyl, difluoromethyl-31-200300349, dichloromethyl, dibromomethyl Methyl, fluoromethyl, 2,2,2-trifluoroethyl 2,2,2-trichloroethyl, 2-bromo, ethyl, 2-chloroethyl, 2-fluoroethyl, 2-iodoethyl Cu halo-lower alkyl, 3-chloropropyl, 4-fluorobutyl, 6-iodohexyl or 2,2-dibromoethyl, preferably haloalkyl, more preferably halo C! _2 alkyl, More preferably, it is a Ci_2 or a Ci_2 or a Ci_2 radical, most preferably a di-methyl radical. 0 In the above definitions, R9, R1 () and the substituent a are "low alkoxy", and in the definition of R1, "selected from halogen "Lower alkoxy" in "lower alkyl", "lower alkyl", "halolower alkyl", hydroxy, lower alkoxy, lower alkylthio, cyano and diloweramino groups The above "low alkyl" is bonded to an oxygen atom, for example, methoxy, ethoxy, propoxy, isopropoxy, Oxy, isobutoxy, second butoxy, third butoxy, pentyloxy, isopentyloxy, 2-methylbutoxy, neopentyloxy, hexyloxy, 4-methyl Pentyloxy, 3-methylpentyloxy, 2-methylpentyloxy, 3,3-methylbutoxy, 2,2-__ • methylbutoxy, 1,1 -_ ^ methyl Butyl butoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy or 2,3-dimethylbutoxy% Ci_6 Straight or branched branch oxygen, preferably Ci_4 Cioxy, more preferably Ci_2, and most preferably methoxy. In the above formula, "low alkylthio" in the definition of substituent a, and "selected from the group consisting of halogen, lower alkyl, halogen lower alkyl, hydroxy, lower alkoxy, lower alkylthio, cyano and di The "lower alkylthio" part of the "lower alkylamino-substituted aryl group" is the above-mentioned "lower alkyl" combined with a sulfur atom such as methylthio, ethylthio, propylthio, isopropyl Propylthio, butylthio, isobutylthio, second butylthio, third butylthio, pentylthio, isopentylthio, 2-methylbutylthio, neopentylthio, hexylthio , 4-methylpentylthio-32- 200300349, 3-methylpentylthio, 2-methylpentylthio, 3,3-dimethylpentylthio, 2,2- > methylpentylthio , 1,1--methylpentylthio, 1,2-_ ^ methylpentylthio, 1,3-dimethylpentylthio, or Ci-6 straight or branched lower alkanes of 2, 3-dimethylpentylthio The thio group is preferably a Ci_4 thio group, more preferably a Ci_2 thio group, and most preferably a methylthio group. In the above formula, the "anion" in the definition of X · is, for example, a halogen ion such as fluoride ion, chloride ion, iodide ion, bromide ion; methanesulfonium ion, ethanesulfonium ion, etc. (^ _6 alkylsulfonium ion; Benzylsulfonium ion, p_Tso- (p-toluenesulfonyl) ion, 0Tf-(trifluoromethanesulfonyl) ion, pentafluoroethanesulfonyl ion, etc. selected from the above-mentioned lower alkyl, lower alkoxy, halogen C 6 _ i arylsulfonium ions of 1 to 3 substituents of atom and haloalkyl, preferably halogen ions, most preferably bromide or chloride ions. In the above formula, when η is an integer of 2 The anions in (X_) n are the same or different. In the above formula, in the definition of R1, "is selected from the group consisting of halogen, lower alkyl, halogen lower alkyl, meridian, lower oxygen, lower sulfur, amino, and The "di-lower alkylamino" part of the "aryl group substituted with 1 to 3 groups" is the above-mentioned "low alkyl" combined with 2 amine groups, for example, dimethylamino, diethylamino, Ν -C1-6 alkylamino groups such as -ethyl-N-methylamino, dipropylamino, dibutylamino, dipentylamino, and dihexylamino, preferably di-(^ _ 4 alkylamino, more preferably Di-C i _ 2 alkane Dimethylamine is the most suitable group. In the above definition of R1, "is selected from the group consisting of halogen, lower alkyl, halogen lower alkyl, hydroxyl, lower alkoxy, lower alkylthio, cyano and diloweramine. Specific examples of "aryl groups substituted by 1 to 3 groups" are, for example, 2-, 3- or 4-fluorophenyl, 2-, 3- or 4-chlorophenyl, 2-, 3- or 4-bromobenzene 2-, 3-, or 4-iodobenzene-33- 200300349, 2-, 3- or 4-tolyl, 2-, 3- or 4-ethylphenyl, 2-, 3- or 4-triphenyl Fluorotolyl, 2-, 3-or 4-via phenyl, 2-, 3-or 4- methoxyphenyl, 2-, 3-or 4- ethoxyphenyl, 2-, 3-or 4- Methylthiophenyl, 2-, 3- or 4-ethylthiophenyl, 3,4-difluorophenyl, 3,4-dichlorophenyl, 3,4-dibromophenyl, 3,5-di Fluorophenyl, 3,5-dichlorophenyl, 3,5-dibromophenyl, 2,3-dimethylphenyl, 3,4-dimethylphenyl, 3,5-dimethylbenzene Group, 2,3-diethylphenyl, 3,4-diethylphenyl, 3,5-diethylphenyl, 2,3-dihydroxyphenyl, 3,4-dihydroxyphenyl, 3,5 -Diphenyl, 2,3-dimethoxyphenyl, 3. 4-dimethoxyphenyl, 3,5-dimethoxyphenyl, 2,3-diethoxyphenyl, 3. 4-diethoxyphenyl, 3,5-diethoxyphenyl, 3,5-ditrifluoromethylphenyl, 3-dimethylaminephenyl or 3-cyano-5-methoxyphenyl, It is preferably an aryl group substituted with 1 to 3 groups selected from halogen, lower alkyl, halogen lower alkyl, hydroxy, lower alkoxy, and lower oxygen sulfur group, more preferably selected from halogen, lower alkyl, halogen Cl- 1-to-3 aryl groups substituted with 2-, 4-, 3-, and 2-thio groups of Ci_2, and more preferably 1 to 3 substituted aryl groups selected from halogen, lower alkyl, and lower alkoxy More preferably, it is a phenyl group substituted with 1 to 3 groups selected from fluorine, chlorine, C! _2 alkyl group, and Ci-2 alkoxy group, more preferably a phenyl group substituted with 1 to 3 fluorine or chlorine group, Preferably it is 3-fluorophenyl, 3,5-dichlorophenyl, 3,4-difluorophenyl or 3,5-difluorophenyl, and most preferably 3,5-difluorophenyl. Specific examples of "selected from the substituents b1 to 3 substituted with a square group" in the above-mentioned definitions of the middle and ring Ar are, for example, 2-, 3-or 4-truncated radicals, 2-, 3-or 4-gas benzene Methyl, 2-, 3- or 4-bromophenyl, 2-, 3- or 4-iodophenyl, 2-, 3- or 4-tolyl, 2-, 3- or 4-ethylphenyl, 2 -, 3- or 4-hydroxyphenyl, 2-, 3- or 4-methoxyphenyl, 2-, 3- or 4-ethoxyphenyl, 2-, 3- or 4-cyanophenyl, 2 -, 3-or 4-nitrophenyl, 2-, 3- or 4-aminophenyl, 2-, 3- or 4-methylaminobenzene-34- 200300349, 2-, 3-or 4-dimethyl Aminophenyl, 2-, 3- or 4-carboxyphenyl, 2-, 3- or 4-methoxycarbonylphenyl, 2-, 3- or 4-acetamidophenyl, 2-, 3-or 4-Amine formamyl, 2-, 3-, or 4-dimethylamine formamyl, 2-, 3-, or 4-aminoformyl phenyl, 2-, 3-, or 4-dimethylamine Methoxyphenyl, 3,4-difluorophenyl, 3,4-dichlorophenyl, 3,4-dibromophenyl, 3,5-difluorophenyl, 3,5-dichlorophenyl , 3,5-dibromophenyl, 2,3-xylyl, 3,4-xylyl, 3,5-xylyl, 2. 3-diethylphenyl, 3,4-diethylphenyl, 3,5-diethylphenyl, 2. 3-dihydroxyphenyl, 3,4-dihydroxyphenyl, 3,5-dihydroxyphenyl, 2. 3-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl, 2. 3-diethoxyphenyl, 3,4-diethoxyphenyl, 3,5-diethoxyphenyl or 3-methoxy-5-methoxycarbonylaminophenyl, preferably selected from the formula-OR9 The aryl group substituted with the groups 1 to 3 of the formula-NR9R1 () group is preferably an aryl group substituted with the groups 1 to 3 of the formula-OR9 group, and more preferably the aryl group substituted with the lower alkoxy group 1 to 3. Most preferably, it is 3-methoxyphenyl, 3,5-dimethoxyphenyl, 3,5-diethoxyphenyl or 3-ethoxy-5-propoxyphenyl. In the above, Gn + is defined as containing 1 or 2 cations in the above (i) to (x) groups. The specific examples of "(i) a lower alkyl group substituted with a group of substituent b and an ammonium group substituted with 3 same or different lower alkyl groups" in the above definition of Gn + are, for example, trimethylammonium, triethylammonium , Tripropylammonium, 2-cyanoethyldiethylammonium, 2-nitroethyldiethylammonium, 2-aminoethyldiethylammonium, 2-methylamineethyldiethylammonium, 2- (dimethylamino) ethyl Dimethylammonium, 2- (dimethylamino) ethyldiethylammonium, 2- (dimethylamino) ethyldipropylammonium, 3- (dimethylamino) propyldimethylammonium, 3- (di Methylamino) propanediamine, 3- (dimethylamino) propyldipropylammonium, 2-hydroxyethylenedimethylammonium, 2-hydroxyethylenediethylammonium, 2-hydroxyethylenedipropylammonium, 3-hydroxyamine Propyl-35- 200300349 Dimethylammonium, 3-hydroxypropyldiethylammonium, 3-hydroxypropyldipropylammonium, 2-methoxyethyldiethylammonium, 2-aminoformamylethyldiethylammonium, 2-carboxyethyl Diethylammonium, 2-methoxycarbonylethyldiethylammonium or benzyldimethylammonium, preferably the same or different low alkyl and low alkyl substituted with -OR9 and -NR9R1 () groups Group 3 substituted ammonium group, more preferably is the same or different group selected from the group consisting of hydroxyl or di-lower alkylamine-substituted lower alkyl and lower alkyl 3 substituted ammonium group, more preferably tri-lower alkyl ammonium It is more preferably a tri-Cij alkylammonium group, more preferably a tri-alkylammonium group, and most preferably a triethylammonium group. In the above definition of Gn +, "(ii) an ammonium group in which a nitrogen atom on the ring is bound to E, a lower alkyl group substituted with a group selected from substituent b, and a substituent 1 to 3 selected from substituent b, The 1-pyridinyl, 1-pyridyl, or 1-pyridinyl group which can be fused with a benzene ring is a pyridine ring, a pyridine ring, or an ammonium group in which a nitrogen atom is bound to E on a pyrimidine ring. Nitrogen and ammonium. Specific examples of the aforementioned "1-pyridinyl, 1-pyridinyl, or 1-pyridinyl" are, for example, 1-methylpyridyl, 2-, or 3-methyl-1-pyridyl, 2 -, 3-or 4 -ethyl-1-methylpyridyl, 3-or 4-pyridyl-1-pyridyl mirror group, 2-, 3-or 4-pyridyl-1-D than sharpyl, 2-, 3- or 4-nitro-1-lafyl, 2-, 3- or 4-methoxy-l-fluorenyl, 2-, 3- or 4-amino-1-pyridyl Indyl, 2-, 3-, or 4-methylamino-1-pyridyl, 2-, 3-, or 4-methylamino-1-pyridine, f-radical, 3- or 4-residue- 1-pyridinyl, 3- or 4-methoxycarbonyl-1 -pyridinyl, 3-or 4-aminocarbamyl-1 -pyridinyl, 3-or 4-(2-hydroxyethyl)- 1-pyridinyl, 3-or 4-(3-hydroxypropyl) -1 -pyridinyl, 3-or 4-(2-aminoethyl) -1 -pyridinyl, 3-or 4- ( 3-aminopropyl) -1-pyridyl, 1-pyridyl, 2-, 3- or 4-methyl-1-pyridyl, 2- or 3-hydroxy- [beta] -pyridyl , 2- or 3-methoxy-1 -pyridyl, 2- or 3-amino-1 -pyridyl, 2- or 3-methylamino-1 -pyridyl, -36-200300349 2 -Or 3 -dimethylamino-1 -pyridyl, 2-or 3-(2-hydroxyethyl) -1 -pyridyl, 2- or 3- (3-Ethyl) -1-pyridyl, 2- or 3- (2-limylethyl) -1-pyridyl, 2- or 3- (3-aminopropyl ) -1 -pyridyl, 1-pyrimidinyl, 2-, 3-or 4-methyl-1-pyridinyl, 2-or 4-hydroxy-1-pyridinyl, 2-or 4-formyl Oxy-1-pyrimidinyl, 2- or 4-amino-1-pyridinyl, 2- or 4-methylamino-1-pyrimidinyl, 2- or 4-dimethylamino-1- Pyridinyl, 2- or 4- (2-hydroxyethyl) -1 -pyrimidinyl, 2-or 4-(3-hydroxypropyl) -1 -pyridinyl, 2- or 4-(2- Aminoethyl) -1 -pyrimidinyl, 2-or 4-(3-aminopropyl) -1 -pyrimidinyl or 1-quinolinyl, preferably a lower alkyl substituted with a group selected from substituent b And a 1-pyridinyl group which may be substituted with a group 1 to 3 selected from the substituent b and may be fused with a benzene ring, more preferably a 1-pyridinyl group which may be substituted with a group 1 to 3 selected from a substituent b It is particularly preferably substituted with a low alkyl group, a formula-OR9 group, and a formula -NR 9 R 1. Group, formula -C Ο 2 R 9 group, formula -C NR 9 R 1 G group or aryl group, 1-pyridinyl group, more preferably a low alkyl group, a hydroxyl group, and a low alkoxydi-lower alkyl group 1-pyridinyl, preferably 1-pyridinyl, which can be substituted with methyl, hydroxyl, methoxy or dimethylamino, most preferably 1-pyridinyl. Gn In the definition "(iii) a carbon atom on the secondary meso ring is bonded to E, at least one nitrogen atom on the ring is substituted with a lower alkyl group or an oxy group to form an ammonium group, and a pyridyl group and a pyridine group which can be fused with a benzene ring Specific examples of "methyl or pyrimidinyl" are, for example, 1-methyl-2-, 3- or 4-pyridyl, 1-ethyl-2-, 3-or 4-pyridinyl, 1-propyl -2-, 3-or 4-pyridinyl, 1 -methyl-2-or 3 -pyridinyl, 1 -ethyl-2-or 3 -pyridinyl, 1 -propyl-2 -or 3-pyrrolidinyl, 1-methyl-2- or 4-chrysyl, 1-ethyl-2- or 4-1¾, fluorenyl, 1-propyl-2- or 4-pyrimidinyl, 1 -Methyl-2 -quinolinyl, 1 -ethyl-3 -quinolinyl or 1 -37- 200300349 oxygen-2-, 3-or 4 -pyridyl, preferably a carbon atom on the secondary mesogenic ring and E Bonded, at least one nitrogen atom on the ring is replaced by a lower alkyl or oxy group Groups, but also with a benzene fused pyrazolyl group of the ingot, the agency is the most appropriate ring carbon atom and E, at least one ring nitrogen atom is substituted with a lower alkyl group to form an ammonium group of the ingot pyrazol. In the above definition of G n +, "the nitrogen atom on the ((iv) secondary mesogenic ring is combined with E, and the nitrogen atom is substituted with a lower alkyl group or an oxy group to form an ammonium group, a 1-piperidinyl group, a 1-piperidinyl group, or a 4- "Morpholinyl" means that the nitrogen atom of the ring to which E is bonded is substituted with a lower alkyl group or an oxy group, and other nitrogen atoms may be substituted with a lower alkyl group or an oxy group. This specific example is, for example, 1-methyl-1 -piperidinyl, 1 -ethyl-1 -piperidinyl, 1 -propyl-1 -piperidinyl, 1 -oxo-1 -piperidinyl, 1- Methyl-piperazinyl, 1-ethyl-1-piperazyl, propyl-1-piperazinyl, 1-oxyl-piperazinyl, 4-methyl-4-morpholinyl, 4- Ethyl-4 -morpholinyl, 4-propyl-4 -morpholinyl, 4-oxo-4 -morpholinyl or 1, 4-dimethyl-1 -piperidyl, preferably a ring nitrogen atom The 1-piperidinyl group substituted with a lower alkyl group or an oxy group to form an ammonium group, and most preferably the 1-piperidinyl group substituted with a low alkyl group in the ring to form an ammonium group. In the above definition of Gn +, "(v) may have a 1- (1-azobicyclic ring substituted with a lower alkyl group substituted with a substituent b, a substituent b and an oxy group [2. 2. 2] octyl) yl or 1- (4-acyl-1-azobicyclo [2. 2. 2] octyl) group "means that the nitrogen atom at position 1 on the ring combines with E to form an ammonium group, and other nitrogen atoms on the ring may also be ammonium groups. Thus the above-mentioned "1-U-azobicyclo [2. 2. 2] octyl) group or 1- (4-az-1-azobicyclo [2 · 2 · 2] octyl) group "may have a lower alkyl group substituted with a group selected from substituent b, substituent b and 1 to 3 substituents of oxygen, this group may be, for example, 1-U -azobicyclo [2 · 2 · 2] octyl), 1-(1--38- 200300349 azo-3-oxobicyclo [2. 2. 2] octyl), 1- (MHZ-3-hydroxybicyclo [2. 2. 2] octyl), 1- (1-azobicyclo [2. 2. 2] octyl), 1- (1-azo-2-methylbicyclo [2. 2. 2] octyl), 1- (1-azo-3-methylbicyclo [2. 2. 2] octyl), 1-Π-azo-3-ethanebicyclo [2 · 2 · 2] octyl), 1- (1-azo-3-cyanobicyclo [2. 2. 2] octyl), 1- (1-azo-3-nitrobicyclo [2. 2. 2] octyl), 1-Π-azo-3-methoxybicyclo [2. 2. 2] octyl), 1- (1-azo-3-amine bicyclo [2. 2. 2] octyl), 1- (buzozo-3-methylamine bicyclo [2. 2. 2] octyl), 1- (1-azo-3-dimethylaminobicyclo [2 · 2 · 2] octyl), 1- (1-azo-3-carboxylic acid bicyclo [2 · 2 · 2] octyl) 1- (1-azo-3-methoxycarbonylbicyclo [2. 2. 2] octyl), 1-Π-azo-3-hydroxymethylbicyclo [2 · 2 · 2] octyl), 1- (1-azo-3-aminomethylbicyclo [2. 2. 2] octyl), 1- (4-acid-1-azobicyclo [2. 2. 2] octyl), 1-(4 -acyl-1 -azo-3 -oxobicyclo [2 · 2. 2] octyl), 1-(4 -acyl -1 -azo-3 -hydroxybicyclo [2 · 2. 2] octyl), 1-(4 -acyl-1 -azobicyclo [2 · 2 · 2] octyl), 1- (4 -acyl-buzoazo-2-methylbicyclo [2 · 2 · 2 ] Octyl), 1-(4 -acyl-1 -azo) -3 -methylbicyclo [2 · 2 · 2] octyl), 1-(4 -acyl-1 -azo-3-ethanebicyclo [ 2 · 2 · 2] octyl), 1- (4-acid-1-azo-3-cyanobicyclo [2 · 2 · 2] octyl), 1-(4 -acid-1-azo-3 -Nitrabicyclo [2 · 2 · 2] octyl), 1-(4 -Ac-1 -azo-3 -methoxybicyclo [2 · 2 · 2] octyl), 1-(4 · Acryl-: 1-Azo-3-amine bicyclic [2. 2. 2] octyl), 1- (4-az-1--1-azo-3-methylamine bicyclic [2 · 2 · 2] octyl), 1-(4 -az-1 -azo-3 -dimethyl Amino bicyclic ring [2 · 2. 2] octyl), 1-(1 -azo-4 -acid-3 -carboxamide bicyclic [2 · 2 · 2] octyl), 1-(1 -azo-4 -acid-3 -methoxy Carbonyl bicyclic [2 · 2 · 2] octyl), 1-(1 -azo-4 -az-3-hydroxymethylbicyclic [2. 2. 2] Octyl), 1- (1-Azo-4-acid-3-amine methylbicyclo [2. 2. 2] octyl, 1- (4-methyl-1,4-diazobicyclo [2 · 2 · 2] octyl) or 1- (4-ethyl-I, 4-diazobicyclo [2 . 2. 2] octyl) group, preferably -39- 200300349, may be substituted with a group selected from substituents b and oxy, such as 1-(1-azobicyclo [2 · 2 · 2] octyl) group or 1 -(4 -Ac-1--1-azobicyclo [2. 2. 2] octyl) group, more preferably a group which may be substituted with a lower alkyl group, a formula-OR9 group, a formula-NR9R1 () group or an oxy group, such as 1- (1-azobicyclo [2. 2. 2] octyl) group or 1- (4 -acyl -1 -azobicyclo [2. 2 · 2] octyl) group, particularly preferably a group which can be substituted with a lower alkyl group, a hydroxyl group, a lower alkoxy group, a di-lower alkylamino group or an oxy group, such as 1- (1-azobicyclo [2. 2. 2] octyl) yl or 1- (4-acyl-1-azobicyclo [2. 2. 2] octyl), preferably 1- (1-azobicyclo [2. 2. 2] octyl) yl or 1- (4 -acyl-1-azobicyclo [2. 2. 2] octyl) yl. In the above definition of Gn +, "(vi) the carbon atom on the meso ring is bonded to E, and at least one nitrogen atom on the ring is substituted with a lower alkyl group or an oxy group to form an (1-azobicyclo [2. 2. 2] octyl) group or (4-acyl-buzo azobicyclic ring [2. 2. 2] octyl) specific examples are, for example, 2-, 3- or 4- (1-azo) -bucarpine bicyclic [2. 2J] octyl), 2-, 3--or 4- (1-azo) -1-ethylbicyclo [2. 2. 2] octyl), 2-, 3-, or 4- (1-azo) -1-propylbicyclo [2. 2. 2] octyl), 2-, 3- or 4-azine bicyclic [2. 2. 2] octyl), 2- or 3- (1-azo) -1-ethyl-4-acyl-bicyclo [2. 2. 2] octyl), 2- or 3- (1-azo) -1-propyl-4-acyl-bicyclo [2. 2. 2] octyl), 2-or 3- (1-azo) -oxo-4-acyl-bicyclo [2. 2. 2] octyl), 2- (1,4-diazolyl) -1,4 -dimethylbicyclo [2 · 2 · 2] octyl), 2- (1,4-diazolyl)- 1,4-diethylbicyclo [2. 2. 2] octyl) or 2- (1,4-diazolyl) -1,4-dipropanebicyclo [2 · 2 · 2] octyl), preferably a carbon atom on the secondary meso ring is bound to Ε, At least one of the nitrogen atoms is substituted by a lower alkyl group to form an (1-azo) bicyclic ring of an ammonium group [2. 2. 2] octyl) or (4 -az-1-azo) bicyclic [2. 2. 2] octyl) yl. Specific examples of "(vii) 1 to 3 substituted oxy groups or hydroxyl groups -40- 200300349 1 -tetrahydrothienyl or 1 -tetrahydrothiopyranyl" in the above definition of Gn +, for example, 1 -tetrahydrothiophene Radical, 3-oxo-1-tetrahydrothienyl, 3-hydroxy-1-tetrahydrothienyl, 1-tetrahydrothiopyranyl, 4-oxo-1 -tetrahydrothiopyranyl, or 4-hydroxy- The 1-tetrafluorothiopyranyl group is preferably a 1-tetraaminosulfanyl group which may be substituted with an oxy group or an acyl group, and most preferably a 1-tetrahydrothienyl group. Specific examples of "(viii) a lower alkyl substituted with a group selected from the substituent b and a same or different 2 substituted sulfonyl group of the lower alkyl group" in the above definition of Gn + are, for example, dimethylsulfonyl, Diethylsulfonyl, dipropylsulfonyl, di (2-cyanoethyl) sulfonyl, di (2-nitroethyl) sulfonyl, di- (aminoethyl) sulfonyl, di (2 -Methylaminoethyl) sulfonyl, bis- (2-dimethylaminoethyl) sulfonyl, bis- (2-hydroxyethyl) sulfonyl, bis- (3-hydroxypropyl) sulfonyl Fluorenyl, di- (2-methoxyethyl) sulfofluorenyl, bis- (2-aminomethylfluorenylethyl) sulfofluorenyl, di- (2-aminomethylmethyl) sulfonyl, di- ( 2-Carboxyethyl) sulfofluorenyl or di- (2-methoxycarbonylethyl) sulfofluorenyl, preferably a lower alkyl group and a lower alkyl group selected from the group consisting of formula-OR9 and formula-NR9 R1 () The same or different group 2 substituted sulfofluorenyl group is more preferably a same or different group 2 substituted sulfofluorenyl group selected from hydroxy or di-loweramino group-substituted lower alkyl group and lower alkyl group. Di-lowersulfanyl, more preferably di-C! _4 alkylsulfanyl, more preferably dialkylsulfanyl, most preferably dimethylsulfanyl or diethylsulfonyl . Specific examples of "(U) a lower alkyl substituted with a group selected from the substituent b and a same or different 3 substituted phosphino group of the lower alkyl group in the definition of Gn +" are, for example, trimethylphosphonium group, trimethylphosphonium group, Ethylphosphonium, tripropylphosphonium, 2-cyanoethyldiethylphosphonium, 2-nitroethyldiethylphosphonium, 2-cyanoethyldiethylphosphonium, 2-methylamineethyl Diethylphosphonium, 2- (dimethylamino) ethyldimethylphosphonium, 2- (dimethylamino) ethyldiethylphosphonium, 2- (dimethylamino-41-200300349) Ethyldipropylphosphonium, 3- (dimethylamino) propyldimethylphosphonium, 3- (dimethylamino) propyldiethylphosphonium, 3- (dimethylamino) propyl Dipropylphosphonium, 2-hydroxyethyldimethylphosphonium, 2-hydroxyethyldiethylphosphonium, 2-hydroxyethyldipropylphosphonium, 3-hydroxypropyldimethylphosphonium, 3-hydroxypropyldiethylphosphonium, 3-hydroxypropyldipropylphosphonium, 2-methoxyethyldiethylphosphonium, 2-aminomethylethyldiethylphosphonium, 2-carboxy Ethyldiethylphosphoranyl or 2-methoxycarbonylethyldiethylphosphoranyl is preferably the same as or lower alkyl substituted with a group selected from the group consisting of formula-OR9 and formula-NR9R1 (). Iso-3 substituted phosphino, more preferably is the same or different group selected from hydroxy or di-loweramino substituted low alkyl and lower alkyl 3-substituted phosphino, and more preferably tri-lowalkinophosphonium More preferably, it is tri-alkylphosphonium, more preferably tri-Cn alkylphosphonium, and most preferably triethylphosphonium. In the above definition of Gn +, "1-pyrrolidinyl group in which the nitrogen atom on the (X) secondary mediating ring is bound to E and the nitrogen atom is substituted by a lower alkyl group or an oxy group to form an ammonium group" is a nitrogen atom on the ring bound to E Substituted by a lower alkyl group or an oxy group, and specific examples thereof are, for example, 1-methyl-1 -pyrrolidyl, 1-ethyl-1 -pyrrolidyl, 1-propyl-1 -pyrrolidyl, or 1-oxyl -pyrrol Ingot group, preferably 1-pyrrolidinium group in which a nitrogen atom on a ring is substituted with a low alkyl group or an oxy group to form an ammonium group, most preferably 1-pyrrolidinium group in which a nitrogen atom on a ring is replaced with a low alkyl group to form an ammonium group base. Among the above Gn + groups, (i) to (X) are preferably (i) the same or different 3 substituted ammonium group selected from the group consisting of formula-OR9 group and formula-NR9R1 () lower alkyl group and lower alkyl group. (Ii) an ammonium group in which a nitrogen atom on the ring is bound to E, a lower alkyl group substituted with a group selected from substituent b, and a group 1 ~ 3 selected from substituent b may be -42- 200300349, 1-pyridinyl, 1-pyridinyl, or 1-pyridinyl, which can be fused with a benzene ring (iii) the carbon atom on the secondary mesogenic ring is bound to E, and at least one nitrogen atom on the ring is lower alkyl or oxy Substituted to form an ammonium group, which can be condensed with a benzene ring, pyridinium group, pyridinium group or pyrimidinyl group, (iv) the nitrogen atom on the secondary mediating ring is bound to E, and the nitrogen atom is substituted by a lower alkyl group or an oxy group To form an ammonium group, a 1-piperidinyl group, a 1-piperidinyl group or a 4-morpholinyl group, (v) a lower alkyl group substituted with a group selected from the substituent b, a substituent b and an oxy group substituted Of 1- (Busazobicyclo [2. 2. 2] octyl) yl or 1- (4-acyl-buzozo bicyclo [2. 2. 2] octyl) group, (vi) the carbon atom on the secondary meso ring is bonded to E, and at least one nitrogen atom on the ring is substituted with a lower alkyl group or an oxy group to form an ammonium group (1-azobicyclo [2. 2. 2] octyl) or (4-acyl-diazobicyclo [2 · 2 · 2] octyl), (vii) oxy or hydroxy 1 to 3 substituted 1-tetrahydrothienyl, (viii) selected from the group consisting of formula-OR9 and formula-NR9R1 ()-substituted lower alkyl and lower alkyl groups which are the same or different 2 substituted sulfonyl groups, or (ix) selected from the group containing formula-OR9 and Formula-NR9R1 ()-substituted lower alkyl and lower alkyl groups which are the same or different from each other 3 substituted phosphino, more preferably, (i) selected from the group consisting of hydroxy or di-lower alkylamine-substituted lower alkyl and lower Same or different alkyl 3 substituted ammonium groups, (ii) ammonium groups in which the nitrogen atom on the ring is bound to E, lower alkyl substituted with a group selected from substituent b, and optionally selected from substituent b 1- to 3-substituted 1-pyridinyl, 1-pyridinyl, or 1-pyridinyl-43- 200300349 substituted with a benzene ring (iii) the carbon atom on the meso ring is bonded to E, and the ring is at least 1 nitrogen atom is substituted by a lower alkyl group or an oxy group to form an ammonium group, and can be fused with a benzene ring, such as pyridyl, pyridyl or pyrimidyl, (iv) the nitrogen atom on the secondary mediating ring is bound to E, and This nitrogen atom is substituted with a lower alkyl group or an oxy group to form an ammonium group, a 1-piperidinyl group, a 1-piperidinyl group Group or a 4 - morpholinyl group, (v) may have substituents selected from the substituent group b is a lower alkyl group, a substituted oxy group b, and the group of substituted 1- (1-azo-bicyclo [2. 2. 2] octyl) yl or 1- (4-acyl-buzozo bicyclo [2. 2. 2] octyl) group, (vi) the carbon atom on the secondary meso ring is bonded to E, and at least one nitrogen atom on the ring is substituted with a lower alkyl group or an oxy group to form an ammonium group (1-azobicyclo [2. 2. 2] octyl) group or (4-az-1-azobicyclo [2 · 2 · 2] octyl) group, (vii) tetrahydrothienyl group, (viii) selected from hydroxy or dioligoalkylamino group Substituted lower alkyl and lower alkyl identical or different groups 2 substituted sulfonyl groups, or (i X) selected from the same or different groups selected from hydroxy or diloweramino substituted lower alkyl and lower alkyl groups 3 substituted phosphino, more preferably, (i) a tri-lower ammonium group, (i) an ammonium group in which a nitrogen atom on the ring is bound to E, a lower alkyl group substituted with a group selected from the substituent b, And may have 1 to 3 substituents selected from the substituent b, 1-pyridinyl, 1-pyridyl, or 1-pyridinyl which may be fused with a benzene ring (iii) a carbon atom on the meso ring is bonded to E , At least one nitrogen atom on the ring -44- 200300349 is substituted with a lower alkyl group or an oxy group to form an ammonium group, and pyridyl, pyridyl or pyrimidyl, which can be fused with a benzene ring, (iv) a secondary mediating ring The upper nitrogen atom is combined with E, and the nitrogen atom is substituted by a lower alkyl group or an oxy group to form an ammonium group, a 1-piperidinyl group, a 1-piperidinyl group or a 4-morpholinyl group, (v) may have a substituent selected from B-substituted lower alkyl, substituted b and oxy-substituted 1-Π-azobicyclo [ 2. 2. 2] octyl) group or 1-(4 -acyl-1 -azobicyclo [2. 2 · 2] octyl) group, (vi) the carbon atom on the secondary meso ring is bonded to E, and at least one nitrogen atom on the ring is substituted with a lower alkyl group or an oxy group to form an ammonium group (1-azobicyclo [2. 2. 2] octyl) group or (4-az-1--1-azobicyclo [2 · 2 · 2] octyl) group, (viii) di-oligosanesulfonyl, or (i X) tri-oligosphosphonium Preferably, (ii) an ammonium group in which a nitrogen atom on the ring is bound to E, a lower alkyl group substituted with a group selected from substituent b, and optionally substituted with groups 1 to 3 selected from substituent b, 1-pyridinyl, 1-pyridinyl, or 1-pyridinyl, which can be fused with a benzene ring (iii) the carbon atom on the secondary mesogenic ring is bound to E, and at least one nitrogen atom on the ring is lower alkyl or oxy Substituted to form an ammonium group, which can be fused with a benzene ring, pyridyl, pyridyl or pyrimidyl, (iv) the nitrogen atom on the secondary mediating ring is bound to E, and the nitrogen atom is substituted by a lower alkyl group or an oxy group While forming ammonium, 1-piperidinyl, 1-piperidinyl or 4-morpholinyl, (v) a lower alkyl group which may be substituted with a group selected from substituent b, substituent b-45-200300349 and oxygen 1-U-azobicyclo substituted with a radical [2. 2. 2] octyl) group or 1- (4-acyl-1-azobicyclo [2 · 2 · 2] octyl) group, or (vi) a carbon atom on an intermediate ring is bonded to E, and at least one nitrogen on the ring Atoms are substituted with lower alkyl or oxy groups to form ammonium groups (1-azobicyclo [2. 2. 2] octyl) group or (4-acyl-1 -azobicyclo [2 · 2 · 2] octyl) group, more preferably, (ii) a lower alkyl group substituted with a group selected from substituent b, and There may be a pyridinyl group substituted by a group 1 to 3 substituted by the substituent b, and may be fused with a benzene ring, (iii) a carbon atom on the secondary meso ring is bonded to E, and at least one nitrogen atom on the ring is a low alkyl group Or an oxy group substituted to form an ammonium group, and a pyridinyl group which can be fused with a benzene ring, (iv) a nitrogen atom on the ring substituted with a lower alkyl group or an oxy group to form an ammonium group, (v) There may be selected from the group consisting of a lower alkyl substituted with a substituent b, a substituent substituted with a b and an oxy group substituted with a 1- (1-azo double bond [2. 2. 2] Sheepyl) group or 1-(4-acyl-1 -azobicyclic [2 · 2 · 2] octyl) group, or (vi) the carbon atom on the secondary mediating ring is bound to E, and at least 1 nitrogen on the ring (1 -Azobicyclo [2 · 2 · 2] octyl) or ammonium group substituted by a lower alkyl group Preferably, (i) there may be 1-pyridinyl substituted with the groups 1 to 3 selected from the substituent b, (iii) the carbon atom on the secondary mediate ring is combined with E, and at least one nitrogen atom on the ring is low Pyridinyl group substituted by alkyl group to form ammonium group, 1-piperazinyl group substituted with lower alkyl group to form ammonium group by nitrogen atom on ring (iv), or -46-200300349 (V) may have a substituent selected from b And 1- (1-azobicyclo [2 · 2 · 2] octyl) or 1- (4-azo-1-azobicyclo [2 · 2 · 2] octyl) groups substituted with oxo groups More preferably, (ii) may have a low alkyl group, a 1-pyridinyl group substituted with a formula-OR9 group and a formula -NR9R1 () group, (ii) a formula-C02R9 group and a formula-CONR9R1 () group Substituted aryl 1-pyridinyl, or (v) may have a low alkyl group, a formula -OR9 group, a formula -NR9R1 () group and an oxy-substituted 1- (1-azobicyclic ring [2. 2. 2] octyl) yl or 1- (4-acyl-buzozo bicyclic ring [2. 2. 2] octyl), and again, (i) 1-pyridinyl which may be substituted with lower alkyl, hydroxyl, lower alkoxy and di-lower alkylamino groups, (ii) substituted aryl groups Pyridinyl, or (v) may be substituted with 1- (buzo azobicyclo [2. 2 · 2] octyl) yl or 1- (4 -azine-azobicyclic ring [2. 2. 2] octyl) group, and more preferably, (i) 1-pyridinyl group which may be substituted with hydroxyl group and low alkoxy group, or (v) may have low alkyl group, hydroxyl group, low alkoxy group, di-lower group Alkylamino and oxy substituted 1-(1-azobicyclo [2 · 2 · 2] octyl) groups or 1-(4 -azine-azobicyclo [2. 2. 2] octyl) group, most preferably, 47- 200300349 1-pyridinyl, 1-(1 -azobicyclo [2 · 2 · 2] octyl) group and 1- (4 -az-1- Azobicyclo [2. 2,2] octyl) group, or (iv) 1-piperidyl group in which the nitrogen atom on the ring is substituted with a lower alkyl group to form an ammonium group. The "pharmacologically acceptable salt" in the above is when the compound (I) and ( II) When there is a basic group such as an amine group, it reacts with an acid; if it has an acidic group such as a carboxyl group, it reacts with a base to form a salt. Salts based on basic groups are preferred with hydrohalic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid, and hydroiodic acid; inorganic salts such as nitrate, perchlorate, sulfate, and phosphate; such as methanesulfonic acid Salts, trifluoromethanesulfonate, ethanesulfonate and other low alkane sulfonates; such as benzene sulfonate, p-toluene sulfonate and other aromatic sulfonates; such as acetate, malate, fumarate, Organic acid salts such as succinate, citrate, ascorbate, tartrate, repair salt, maleate; and such as glycine, lysine, spermine, ornithine, Salts of amino acids such as glutamate and aspartate are more preferably a hydrohalide, and most preferably a hydrochloride. Acid-based salts are preferably alkali metal salts such as sodium, potassium, and lithium salts, alkaline earth metal salts such as calcium and magnesium salts, metal salts such as aluminum and iron salts, and inorganic salts such as ammonium; Amine salt, diTamine salt, morpholine salt, glucosamine salt, phenylglycylic acid alkyl ester salt, ethylenediamine salt, N-methyl polyglucosamine salt, guanidine salt, diethylamine salt, triethylamine salt , Dicyclohexylamine salt, N, N'-diT ethylenediamine salt, chloroprocaine salt, procaine salt, diethanolamine salt, NT-based phenylethylamine salt, pipera salt, tetramethylammonium salt, Ginseng (hydroxymethyl) amine salts such as amine salts, and amines such as glycine, lysine, spermine, guanamine, glutamate, aspartate Base acid-48- 200300349. More preferred are alkali metal salts and alkaline earth metal salts, and most preferred are sodium salts and calcium. The compounds of the general formulae (I) and (II) of the present invention can be placed in the atmosphere or recrystallized to absorb moisture, and may become hydrates. In these cases, these hydrates are also included in the salts of the present invention. When the compounds of the general formulae (I) and (II) of the present invention have an asymmetric carbon in the molecule, there are various isomers. These isomers and their mixtures are all represented by a single formula, that is, by the general formulae (I) and (II). Therefore, the isomers thereof are included individually or in any proportion. The aforementioned "esters" refer to the esters of the compounds of the general formulae (I) and (Π) of the present invention as esters, and these esters may be "hydroxy esters" and "carboxyl esters", and each of the ester residues is "general "Protective group" or "protective group in vivo that can be cleaved by biological methods such as hydrolysis". "General protective group" refers to a protective group that can be cleaved by chemical methods such as hydrogenolysis, hydrolysis, electrolysis, and photolysis. The "general protecting group" of the "hydroxy ester" may be, for example, methylamyl, ethylamyl, propylamyl, butylamyl, isobutylamyl, pentamyl, pentamyl, isoamyl, octyl, nonyl , Decanoyl, 3-methylnonyl, 8-methylnonyl, 3-ethyloctyl, 3,7-dimethyloctyl, ^ -methyl, dodecyl, tridecyl Base, tetradecyl, pentadecyl, hexadecyl, 1-methylpentadecyl, 14-methylpentadecyl, 13, 13-dimethyltetradecanyl, heptadecyl Alkyl, 15-methylhexadecyl, octadecyl, 1-methylhexadecyl, nonadecanyl, icosyl, or di ~ 1-'fluorenyl, and other alkyl groups, chloroethenyl Alkyl, dichloroethenyl, trichloroethenyl, trifluoroethenyl and other alkanecarbonyl groups, methoxyethenyl and other alkoxyalkylcarbonyl groups, propyl-49- 200300349 alkenyl, propionyl, methyl "Substitutable low-aliphatic fluorenyl groups" such as propylene fluorenyl, buten fluorenyl, isobutyl fluorenyl, (E) -2-methyl-2-buten fluorenyl, etc. (preferably C 1-6 Low aliphatic fluorenyl); benzylfluorenyl, α-naphthylmethyl, β-naphthylmethyl, and other aromatic carbonyl groups, 2 -Haloarylcarbonyl such as bromobenzyl, 4-chlorobenzylidene, low alkylarylcarbonyl such as 2,4,6-trimethylbenzylidene, 4-methylbenzylidene, and 4-methoxybenzylidene Alkoxyarylcarbonyl, 4-nitrobenzylfluorenyl, nitroarylcarbonyl such as 2-nitrobenzylfluorenyl, lower alkoxycarbonylarylcarbonyl such as 2- (methoxycarbonyl) benzylfluorenyl, 4-phenylbenzylfluorenyl "Substitutable aromatic amidino" such as aryl aryl carbonyl; methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, second butoxycarbonyl, third butoxycarbonyl, isobutoxycarbonyl, etc. "Alkoxycarbonyl" such as alkoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2-trimethylsilylethoxycarbonyl and other halogens or tri-lower alkylsilyl-substituted lower alkoxycarbonyl; tetrahydro Pyran-2-yl, 3-bromotetrahydropyran-2-yl, 4-methoxytetrahydropyran-4-yl, tetrahydrothiopyran-2-yl, 4-methoxytetrahydro "Tetrahydropyranyl or tetrahydrothiopyranyl" such as thiopyran-4-yl; "tetrahydrofuranyl or tetrahydrothiofuranyl" such as tetrahydrofuran-2-yl and tetrahydrothiofuran-2-yl; three Methylsilyl, triethylsilyl, isopropyldimethylsilyl, third butyldi Trialkylsilyl groups such as silyl, methyldiisopropylsilyl, methylditributylsilyl, triisopropylsilyl, diphenylmethylsilyl, diphenylbutylsilyl, Diphenylisopropylsilyl, phenyldiisopropylsilyl, etc. "fluorenyl" such as tri-lower alkylsilyl with 1 to 2 aryl groups; methoxymethyl, 1,1-dimethyl Low-alkoxymethyl such as methyl-1-methoxymethyl, ethoxymethyl, propoxymethyl, isopropoxymethyl, butoxymethyl, third butoxymethyl, 2-methoxyethoxymethyl And other low-alkoxymethyl groups such as low-alkoxymethyl groups, 2,2,2-trichloroethoxymethyl, and bis (2--50- 200300349 chloroethoxy) methyl groups "Hydroxymethyl"; "lower alkoxyethyl such as 1-ethoxyethyl, 1- (isopropoxy) ethyl, etc.", "substituted ethyl" such as haloethyl such as 2,2,2-trichloroethyl ”; Benzyl, α-naphthylmethyl, β-naphthylmethyl, dityl, trityl, α-naphthyldiphenyl, 9-onionyl, etc. have 1 to 3 aryl groups Substituted lower alkyl, 4-methylbenzyl, 2,4,6-trimethylbenzyl, 3,4,5-trimethylbenzyl, 4-methoxybenzyl, 4-methoxyphenyl dibenzoyl Aromatic rings for lower radicals, such as lower alkyl, 2-nitrobenzyl, 4-nitrobenzyl, 4-chlorobenzyl, 4-bromofluorenyl, 4-aminofluorenyl, lower oxygen, nitro, halogen, and amino Substituted "aralkyl" such as 1 to 3 aryl-substituted lower alkyls; "enoxycarbonyl" such as ethyleneoxycarbonyl and allyloxycarbonyl; benzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 3, 4-Dimethoxybenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, etc. may have 1 to 2 lower alkoxy groups or "aralkyloxycarbonyl" substituted with aromatic ring for nitro, preferably A methoxymethyl group, a silyl group or an aralkyl group, more preferably a methoxymethyl group, a third butyl disilyl group or a benzyl group, and most preferably a benzyl group. The "general protecting group" of "carboxyl ester" should be the aforementioned "low alkyl group"; the aforementioned "lower alkyl group"; the "lower fast group"; the "halo low alkyl group"; and the aforementioned "hydroxyl ester" "General protecting group" is "aralkyl", preferably lower alkyl or aralkyl, more preferably ethyl, third butyl or benzyl, most preferably third butyl. "Protection group in vivo that can be cleaved by biological methods such as hydrolysis" refers to a protective group that can be cleaved in the human body by biological methods such as hydrolysis to form a free acid or its salt. After the experimental animals are injected intravenously, the body fluids of the animals are investigated, and it is determined whether the original compounds or their pharmacologically acceptable salts can be detected. -51- 200300349 "Hydroxy esters" "protective groups in vivo that can be cleaved by biological methods such as hydrolysis" may be iformyloxymethyl, ethoxymethyl, dimethylamine ethoxymethyl, propane Oxymethyl, butyryloxymethyl, pivalamyloxymethyl, pentamyloxymethyl, isoamyloxymethyl, hexamethyleneoxymethyl, 1-methylamyloxyethyl, 1-acetamyloxyethyl Ethyl, 1-propanthoxyethyl, 1-butanthoxyethyl, 1-pentamthyloxyethyl, 1-pentamthyloxyethyl, 1-isopentamyloxyethyl, hexamethyleneoxyethyl , 1-methylpyroxypropyl, 1-ethylpyroxypropyl, 1-propylpyroxypropyl, 1-butylpyroxypropyl, 1-tetramethylpyroxypropyl, 1-pentylpyroxypropyl, 1-Isoamyloxypropyl, 1-hexamethyleneoxypropyl, 1-ethylammonyloxybutyl, buprofamyloxybutyl, buamimoxybutyl, 1-tetramethyleneoxybutyl, 1-acetamidine Oxypentyl, 1-propanyloxypentyl, 1-butanyloxypentyl, 1-tetrapentyloxypentyl, 1-tetrapentyloxyhexyl, etc. 1-("low aliphatic fluorenyl" oxy) `` Lower alkyl '', cyclopentylcarbonyloxymethyl, cyclohexylcarbonyloxymethyl, 1-cyclopentylcarbonyloxyethyl, 1-cyclohexanecarbonyloxyethyl, 1-cyclopentylcarbonyloxypropyl, 1-cyclo Hexyloxy Propyl, 1-cyclopentylcarbonyloxybutyl, 1-cyclohexylcarbonyloxybutyl, etc. 1-("cycloalkyl" carbonyloxy) "lower alkyl", benzyloxymethyl, etc. 1-("aryl Group fluorenyl "oxy)" low alkyl "1- (fluorenyl)" low alkyl "; methoxycarbonyloxymethyl, ethoxycarbonyloxymethyl, propoxycarbonyloxymethyl, isopropyl Oxocarbonyloxymethyl, butoxycarbonyloxymethyl, isobutoxycarbonyloxymethyl, pentoxycarbonyloxymethyl, hexyloxycarbonyloxymethyl, cyclohexyloxycarbonyloxymethyl, cyclohexyloxycarbonyloxy (cyclic Hexyl) methyl, 1- (methoxycarbonyloxy) ethyl, 1- (ethoxycarbonyloxy) ethyl, 1- (propoxycarbonyloxy) ethyl, 1- (isopropoxycarbonyloxy ) Ethyl, 1- (butoxycarbonyloxy) ethyl, 1- (isobutoxycarbonyloxy) ethyl, 1- (third butoxycarbonyloxy) ethyl, 1- (pentyloxylan Yl) ethyl, 1- (hexanoyloxy) ethyl, 1- (hexanoyloxy) ethyl, 1- (cyclopentyloxycarbonyloxy) propyl, 1- (cyclohexanyloxy) Ore 200300349 oxy) propyl, ι- (cyclopentyloxycarbonyloxy) butyl, ι- (cyclohexyloxycarbonyloxy) butyl, 1- (cyclohexyloxycarbonyloxy) ethyl, 1- ( Ethoxycarbonyloxy) propyl, 1- (methoxycarbonyloxy Propyl, 1- (ethoxycarbonyloxy) propyl, 1- (propoxycarbonyloxy) propyl, 1- (isopropoxycarbonyloxy) propyl, 1- (butoxycarbonyloxy) propyl Group, 1- (isobutoxycarbonyloxy) propyl, 1- (pentyloxycarbonyloxy) propyl, 1- (hexyloxycarbonyloxy) propyl, 1- (methoxymethoxy) butyl , 1- (ethoxycarbonyloxy) butyl, 1- (propoxycarbonyloxy) butyl, 1- (isopropoxycarbonyloxy) butyl, 1- (butoxycelloxy) butyl, 1- (isobutoxyloxy) butyl, 1- (methoxyloxy) pentyl, 1- (ethoxyloxy) pentyl, 1- (methoxyloxy) hexyl, 1- (Ethoxycarbonyloxy) hexyl and other (lower alkoxycarbonyloxy) alkyl groups; (5-phenyl-2-oxo-1,3-dioxofluoren-4-yl) methyl, [5- (4 -Tolyl) -2-oxo-1,3-oxodimethyl-4-yl] methyl, [5- (4 -methoxyphenyl) -2-oxo-1,3-oxodimethyl-4- Yl] methyl, [5- (4-fluorophenyl) -2-oxo-1,3-oxendhen-4-yl] methyl, [5- (4-chlorophenyl) -2-oxo- 1,3 -methylene-4-methyl] methyl, (2-oxo-1,3 -methylene-4-methyl) methyl, (5-methyl-2-oxo-1,3-methylene Fluorenyl-4-yl) methyl, (5-ethyl-2-oxo-1,3 -extend Dimingo-4-yl) methyl, (5-propyl-2-oxo-1,3-propenylpent-4-yl) methyl, (5-isopropyl-2-oxo-1, 3-Methenyl-4-methyl) methyl, (5-butyl-2-oxo-1,3-methylene-pyridin-4-yl) methyl, etc. "Low alkyl": "phthaloyl" such as phthaloyl, dimethylphthaloyl, dimethoxyphthaloyl: the aforementioned "low aliphatic fluorenyl": the aforementioned "aromatic fluorenyl": "half ester residue of succinic acid "": "Phosphate salt residue": "Ester-forming residues of amino acids": Carbamate: Carbamate with 1 to 2 lower alkyl substitutions: and tamopentamate Oxygen bases such as "1- (oxygen) oxygen radicals" should be simulated oxygen radicals. "Ester of carboxyl group" "protective group in vivo that can be cleaved by biological methods such as hydrolysis-53- 200300349" may suitably be methoxyethyl, 1-ethoxyethyl, ι-methyl-1-methoxyethyl , 1- (isopropoxy) ethyl, 2-methoxyethyl, 2-ethoxyethyl, 1,1-dimethyl-1-methoxyethyl, ethoxymethyl, n-propoxymethyl Base, isopropyloxymethyl, n-butoxymethyl, tertiary butoxymethyl%, low oxygen, low oxygen, 2-methoxyethoxymethyl, low oxygen, low oxygen, low alkyl, phenoxy "Aryl" oxygen such as methyl, "lower alkyl", 2,2,2-trichloroethoxymethyl, bis (2-chloroethoxy) methyl, etc. Halogen low alkoxy low radical% Oxygen base "; Methionite methyl%" "Low-base oxygen" Mine base "Low-base": Oxymethyl, 2-aminoethyl% "Amo-based base" Low-base "; Methylthiomethyl 2. Ethylthiomethyl% "" lower radical "thiomethyl"; phenylthiomethyl, naphthylthiomethyl and other "" aryl "thiomethyl"; 2-methanesulfonylethyl, trifluoromethanesulfonyl Ethyl, etc. "low alkyl" sulfofluorenyl "low alkyl" which may be substituted with halogen; 2-benzenesulfonylethyl, 2-tosylsulfonylethyl, etc. "Aryl" sulfonic group "lower radical"; then "1- (acidoxy)" lower alkyl ": the aforementioned" phthaloyl "; the aforementioned" aryl "; the aforementioned" low alkyl "; "Carboxyalkyl" such as carboxymethyl; and "amidoamine-forming residues of amino acids" such as phenylmethoxybenzene, preferably 1- (fluorenyl) "low alkyl". The "other derivative" refers to a derivative other than the "pharmacologically acceptable salt" and the "its ester" described above when the compound of the formula (I) or (II) of the present invention has an amine group. These derivatives may be amidino derivatives such as amidino. Specific examples of the compounds of general formulae (I) and (π) of the present invention may be the compounds shown in the following table, but the present invention is not limited to these compounds. The compounds in Tables 1 to 2 have the following structural formulae (la) and (Ila), respectively. In Tables 1 and 2, the R1 substituent is selected from the following groups (R-1) to (R-13) -54- 200300349 (R-1)

(R-4)

(R-7) (R-10)

(R-13)

Gn + and N (Me) 2 (x-) n are selected from the following groups (Gl) to (G104)

-55- 200300349

56- 200300349 (G26)

(G27)

OMe (G28)

OMe (G29)

(G32)

(G30) (G33)

(G31)

(G34)

N (Me) 2

(G35) (G38)

(G41)

(G44) (G47)

Me Me Me-57- 200300349

Me Me

Br '(G65) Me〆

(G70)

(G71)

(G72) cr (G73) \

-58- 200300349

Bf

(G75) (G78)

+ SN

(G76), N + cr, N + cr

Bf (G80) (G83)

Br, Me (G81) \ (G84), +

OH (G79) (G82)

cr (G85), Me

Me (G86), S: r Cl · (G87) \ g / Me (G88) \ J, Et (G89)

Br ", Et

Me

Me

Et

Et cr (G90) \ p / Me u / XMe

Br * Cl * (G91) (G92) \ 〇-Et Me Me Et Et (G93)

Br ",: < Et Et Et

-59- 200300349 (G103)

Br " (G100) \

(G101)

Br " (G102)

Me

Ph

Me ΒΓ ″ + Me

The table and the above substituents are abbreviated as follows:

All: Allyl S Bu: Butyl 'E t I, Ethyl Me:. Methyl Ph: Phenyl Ph y: Phenyl Pr: Propyl P rp: 1-Propynyl 2 — P rp: 2 -Propynyl

-60- 200300349 [Table 1] R7 Ο Ο

Compd. R1 No. Substitution No. R2 R -A * ~ D_E--(Gn +) (X_) n R5 Substitution No. R4 R6 R7 1-1 (Rl) Et 5-MeO-o (ch2) 6- (G 4) MeO HHH 1-2 (Rl) Et 5-MeO -0 (CH2) 6- (G 9) MeO HHH 1-3 (Rl) Et 5 ~ MeO _〇 (CH2) 6-(G14) MeO HHH 1 ~ 4 (Rl) Et 5-MeO -〇 (CH2) r (G65) MeO HHH 1-5 (R-1) Et 5-MeO -〇 (CH2) 6- (G74) MeO HHH 1-6 ( Rl) Et 5-MeO -0 (ch2) 6- (G77) MeO HHH 1-7 (R-3) Et 5-MeO -〇 (ch2) 6- (G 4) MeO HHH 1-8 (R-3 ) Et 5-MeO -0 (ch2) 6- (G 9) MeO HHH 1-9 (R-3) Et 5-MeO -0 (ch2) 6-(G14) MeO HHH 1-10 (R-3) Et 5-MeO-〇 (CH2) 6-(G65) MeO HHH 1-11 (R-3) Et 5-MeO -〇 (CH2) 6- (G74) MeO HHH 1-12 (R-3) Et 5 -MeO -o (ch2) 6- (G77) MeO HHH 1-13 (R ~ 4) Et 5-MeO -〇CHr (G49) MeO HHH 1-14 (R-4) Et 5-MeO -〇CH2 ~ (G50) MeO HHH 1-15 (R-4) Et 5-MeO -OCH2- (G53) MeO HHH 1-16 (R ~ 4) Et 5-MeO -OCH2-(G54) MeO HHH

-61 200300349

1-17 (R-4) Et 5-MeO -〇CH2 " (G57) MeO HHH 1 -18 (R ~ 4) Et 5-MeO -〇CHr (G58) MeO HHH 1-19 (R-4) Et 5-MeO -〇 (CH2) 2 ~ (G14) MeO HHH 1Γ20 (R-4) Et 5-MeO -〇 (CH2) 2-(G50) MeO HHH 1-21 (R-4) Et 5-MeO -0 (CH2) 2- (G54) MeO HHH 1-22 (R-4) Et 5-MeO -o (CH2) 2- (G65) MeO HHH 1-23 (R-4) Et 5-MeO -o (ch2) 2- (G74) MeO HHH 1-24 (R-4) Et 5-MeO -o (CH2) r (G77) MeO HHH 1-25 (R-4) Et. 5-MeO-0 (CH2 ) 3-(G14) MeO HHH 1-26 (R-4) Et 5-MeO -〇 (CH2) 3- (G50) MeO HHH 1-27 (R-4) Et 5-MeO -0 (ch2) 3 -(G54) MeO HHH 1-28 (R-4) Et 5-MeO -0 (CH2) 3- (G65) MeO HHH 1-29 (R-4) Et 5-MeO-〇 (CH2) 3- ( G74) MeO HHH 1-30 (R-4) Et 5-MeO -0 (ch2) 3_ (G77) MeO HHH 1-31 (R-4) Et 5-MeO -0 (CH2) 4- (G14) MeO HHH 1-32 (R-4) Et 5-MeO -〇 (ch2) 4- (G50) MeO HHH 1-33 (R_4) Et 5-MeO -〇 (ch2) 4- (G54) MeO HHH 1-34 (R-4) Et 5-MeO-0 (CH2) 4-(G65) MeO HHH 1-35 (R-4) Et 5-MeO -0 (CH2) r (G74) MeO HHH 1-36 (R- 4) Et 5-MeO -0 (CH2) r (G77) MeO HHH 1-37 (R-4) Et 5-MeO -〇 (CH2) r (G14) MeO HHH 1-38 (R-4) Et 5-MeO-〇 (CH2) 5-(G50) MeO HHH 1-39 (R-4) Et 5-MeO -〇 (CH2) r (G54) MeO HHH 1-40 (R-4) Et 5-MeO -0 (ch2) 5- (G65) MeO HHH 1-41 (R-4) Et 5-MeO -〇 ( ch2) 5- (G74) MeO HHH 1-42 (R-4) Et 5-MeO-0 (ch2) 5- (G77) MeO HHH -62 200300349

1-43 (R-4) Me 5-MeO -0 (CH2) 6- (G14) MeO HHH 1-44 (R-4) Me 5-MeO -〇 (ch2) 6- (G50) MeO HHH 1- 45 (R ~ 4) Me 5-MeO -o (ch2) 6- (G54) MeO HHH 1-46 (R-4) Me 5-MeO -〇 (CH2) r (G65) MeO HHH 1-47 (R -4) Me 5-MeO -0 (CH2) 6- (G74) MeO HHH 1-48 (R-4) Me 5-MeO -0 (ch2) 6- (G77) MeO HHH 1-49 (R-4 ) Et 5-MeO-0 (CH2) 「(G 4) MeO HHH 1-50 (R-4) Et 5-MeO -0 (CH2) 6-(G 7) MeO HHH 1-51 (R-4) Et 5-MeO -〇 (CH2) 6- (G 9) MeO HHH 1-52 (R-4) Et 5-MeO-o (ch2) 6- (G12) MeO HHH 1-53 (R-4) Et 5-MeO-0 (ch2) 6-(G14) MeO HHH 1-54 (R-4) Et 5-MeO -o (ch2) 6- (G23) MeO HHH 1-55 (R-4) Et 5- MeO -0 (ch2) 6-(G25) MeO HHH 1-56 (R_4) Et 5-MeO -〇 (ch2) 6- (G28) MeO HHH Bu 57 (R-4) Et 5-MeO -〇 (CH2 ) 6-(G30) MeO HHH 1-58 (R-4) Et 5-MeO -〇 (CH2) r (G35) MeO HHH 1-59 (R-4) Et 5-MeO-0 (ch2) 6- (G50) MeO HHH 1-60 (R-4) Et 5-MeO-0 (ch2) 6-(G54) MeO HHH 1-61 (R-4) Et 5_MeO -〇 (CH2) 6- (G60) MeO HHH 1-62 (R-4) Et 5-MeO -0 (ch2) 6- (G65) MeO HHH 1-63 (R_4) Et 5-MeO -0 (ch2) 6-(G71) MeO HHH 1-64 (R-4) Et 5-MeO -〇 (ch2) 6- (G74) MeO HHH 1-65 (R-4) Et 5- MeO -0 (ch2) 6- (G77) MeO HHH 1-66 (R-4) Et 5-MeO-0 (ch2) 6- (G78) MeO HHH 1-67 (R-4) Et 5-MeO- 0 (ch2) 6-(G80) MeO HHH 1-68 (R-4) Et 5-MeO -〇 (CH2) 6-(G83) MeO HHH -63 200300349

1-69 (R-.4) Pr 5-MeO -〇 (ch2) 6- (G 4) MeO HHH 1-70 (R-4) Pr 5-MeO -〇 (ch2) 6- (G 7) MeO HHH 1-71 (R-4) Pr 5-MeO -〇 (ch2) 6- (G 9) MeO * HHH 1-72 (R-4) Pr 5-MeO -〇 (ch2) r (G12) MeO HHH 1-73 (R-4) Pr 5-MeO -〇 (ch2) 6- (G14) MeO HHH 1-74 (R-4) Pr 5-MeO -〇 (ch2) 6- (G23) MeO HHH 1- 75 (R-4) Pr 5-MeO -〇 (ch2) 6-(G25) MeO HHH 1-76 (R-4) Pr 5-MeO -〇 (ch2) 6- (G28) MeO HHH 1-77 ( R-4) Pr 5-MeO -〇 (ch2) 6-(G30) MeO HHH 1-78 (R-4) Pr 5-MeO -〇 (CH2) 6- (G35) MeO HHH 1-79 (R- 4) Pr 5-MeO -o (ch2) 「(G50) MeO HHH 1-80 (R-4) Pr 5-MeO _〇 (CH2) r (G54) MeO HHH 1-81 (R-4) Pr 5 -MeO -0 (ch2) 6- (G60) MeO HHH 1-82 (R-4) Pr 5-MeO -0 (ch2) 6- (G65) MeO HHH 1-83 (R-4) Pr 5-MeO -0 (ch2) 6- (G71) MeO HHH, 1 -84 (R-4) Pr 5-MeO -o (ch2) 6-(G74) MeO HHH 1-85 (R-4) Pr 5-MeO- 0 (CH2) 6-(G77) MeO HHH 1_86 (R-4) Pr 5-MeO -〇 (CH2) 6- (G80) MeO HHH 1-87 (R- 4) Pr 5-MeO -0 (ch2) 6- (G83) MeO HHH 1-88 (R-4) Bu 5-MeO -0 (ch2) 6- (G 4) MeO HHH 1-89 (R-4) Bu 5-MeO-0 (ch2) 6-(G 7) MeO HHH 1-90 (R-4) Bu 5-MeO -〇 (CH2) 6- (G 9) MeO HHH 1-91 (R-4) Bu 5-MeO -〇 (ch2) 6- (G12) MeO HHH 1-92 (R-4) Bu 5-MeO -0 (ch2) 6- (G14) MeO HHH 1-93 (R-4) Bu 5 -MeO -0 (ch2) 6- (G23) MeO HHH 1-94 (R-4) Bu 5-MeO-0 (ch2) 6-(G25) MeO HHH -64 200300349

1-95 (R-4) Bu 5-MeO -〇 (CH2) 6- (G28) MeO HHH 1-96 (R-4) Bu 5-MeO -0 (CH2) 6- (G30) MeO HHH 1- 97 (R-4) Bu 5-MeO -〇 (ch2) 6- (G35) MeO HHH 1-98 (R-4) Bu 5-MeO -0 (CH2) 6- (G50) MeO HHH 1-99 ( R-4) Bu 5-MeO -0 (CH2) e- (G54) MeO HHH 1-100 (R-4) Bu 5-MeO -0 (CH2) r (G60) MeO HHH 1-101 (R-4 ) Bu 5-MeO -o (ch2) 6- (G65) MeO HHH 1-102 (R-4) Bu 5-MeO -〇 (CH2) 6- (G71) MeO HHH 1-103 (R-4) Bu 5-MeO -0 (CH2) 6 ~ (G74) MeO HHH 1-104 (R-4) Bu 5-Me0 -〇 (CH2) 6- (G77) MeO HHH 1-105 (R-4) Bn 5- MeO -〇 (CH2) r (G80) MeO HHH 1-106 (R_4) Bu 5-MeO -〇 (CH2) r (G83) MeO HHH 1-107 (R-4) Et 5-MeO -ch2o (ch2 ) 6-(G 4) MeO HHH 1_108 (R-4) Et 5-MeO -CH20 (CH2) 6-(G 7) MeO HHH 1-109 (R-4) Et 5-MeO -CH20 (CH2) r (G 9) MeO HHH 1-110 (R-4) Et 5-MeO -ch2o (ch2) 6- (G14) MeO HHH 1-111 (R-4) Et 5-MeO -CH20 (CH2) r (G25 ) MeO HHH 1-112 (R_4) Et 5-MeO -CH20 (CH2) 6- (G35) MeO HHH 1-113 (R-4) Et 5-MeO -CH20 (CH2) 6-(G50) MeO HHH 1 -114 (R-4) Et 5-MeO -CH20 (CH2) 6 & q uot; (G54) MeO HHH 1-115 (R-4) Et 5-MeO -CH20 (CH2) 6- (G65) MeO HHH 1-116 (R-4) Et 5-MeO -CH20 (CH2) 6- (G74) MeO HHH 1-117 (R ~ 4) Et 5-MeO ~ CH20 (CH2) 6 ~ (G77) MeO HHH 1-118 (R-4) Et 5-MeO -CH20 (CH2) 6- (G80 ) MeO HHH 1-119 (R-4) Et 5-MeO -ch2o (ch2) 6- (G83) MeO HHH 1-120 (R_4) Pr 5-MeO -ch2〇 (ch) 6- (G 4) MeO HHH -65- 200300349

1-121 (R-4) Pr 5-MeO -CH20 (CH2) 6-(G 7) MeO HHH 1-122 (R-4) Pr 5-MeO -ch2o (ch2) 6- (G 9) MeO HHH 1-123 (R-4) Pr 5-MeO -CH20 (CH2) 6- (G25) MeO HHH 1-124 (R-4) Pr 5-MeO -CH20 (CH2) 6- (G35) MeO HHH 1- 125 (R_4) Pr 5-MeO -CH20 (CH2) 6- (G50) MeO H. HH 1-126 (R-4) Pr 5-MeO -CH20 (CH2) 6- (G54) MeO HHH 1-127 ( R-4) Pr 5-MeO -CH20 (CH2) 6- (G65) MeO • HHH 1-128 (R-4) Pr 5-MeO _CH20 (CH2) r. (G74) MeO HHH 1-129 (R- 4) Pr 5-MeO -ch2o (ch2) 6- (G77) MeO HHH 1-130 (R-4) Pr 5-MeO -CH20 (CH2) 6-(G80) MeO HHH 1-131 (R-4) Pr 5-MeO -ch2o (ch2) 6- (G83) MeO HHH 1-132 (R-4) Bu 5-MeO -ch2o (ch2) r (G 4) MeO HHH 1-133 (R-4) Bu 5 -MeO-ch2o (ch2) 6- (G 7) MeO HHH 1-134 (R-4) Bu 5-MeO -ch2〇 (ch2). 6- (G 9) MeO HHH 1-135 (R-4) Bu 5-MeO -ch2o (ch2) 6- (G25) MeO HHH 1-136 (R-4) Bu 5-MeO-ch2o (ch2) 6- (G35) MeO HHH 1-137 (R-4) Bu 5 -MeO -ch2o (ch2) 6- (G50) MeO HHH 1-138 (R-4) Bu 5-MeO -ch2o (ch2) 6- (G54) MeO HHH 1-139 (R-4) Bu 5-MeO -CH20 (ch2) 6- (G65) MeO HHH 1-140 (R-4) Bu 5-MeO-CH20 (CH2) 6-(G74) MeO HHH 1-141 (R-4) Bu 5-MeO _CH20 (CH2) 6-(G77) MeO HHH 1- 142 (R-4) Bu 5-MeO -ch2o (ch2) 6- (G80) MeO H • HH 1-143 (R-4) Bu 5-MeO-CH20 (ch2) 6- (G83) MeO HHH 1- 144 (R-4) Et 5-MeO -S (CH2) 6-(G 4) MeO HHH 1-145 (R-4) Et 5-MeO -S (CH2) 6-(G14) MeO HHH 1-146 (R_4) Et 5-MeO-s (ch2) 「(G65) MeO HHH ref-66 200300349

1-147 (R ~ 4) Et 5-MeO-S (CH2) 6- (G74) MeO HHH 1-148 (R-4) Et 5-MeO -S (CH2) 6- (G77) MeO HHH 1- 149 (R-4) Et 5-MeO -S (CH2) r (G80) MeO HHH 1-150 (R-4) Et 5-MeO -s (ch2) 6- (G83) MeO HHH 1-151 (R -7) Et 5-MeO -0 (CH2) 6- (G 4) MeO HHH 1-152 (R-7) Et 5-MeO -〇 (ch2) 6- (G14) MeO HHH 1-153 (R- 7) Et 5-MeO -0 (ch2) 6- (G65) MeO HHH 1-154 (R-7) Et 5-MeO-o (ch2) 6-(G74) MeO HHH 1-155 (R-7) Et 5-MeO -〇 (CH2) 6- (G77) MeO HHH 1-156 (R-7) Et 5-MeO-o (ch2) 6- (G83) MeO HHH 1-157 (Rl) Et 5-MeO -0 (CH2) 7- (G 4) MeO HHH 1-158 (Rl) Et 5-MeO -〇 (ch2) 7- (G14) MeO HHH 1-159 (Rl) Et 5-MeO-0 (CH2) 7- (G65) MeO HHH 1-160 (Rl) Et 5-MeO -0 (CH2) r (G74) MeO HHH 1-161 (R-1) Et 5-MeO -0 (CH2) 7- (G77 ) MeO HHH 1-162 '(Rl) Et 5-MeO -〇 (CH2) r (G83) MeO HHH 1-163 (R-3) Et 5-MeO-0 (CH2) 7- (G 4) MeO HHH 1-164 (R-3) Et 5-MeO-0 (CH2) 7- (G14) MeO HHH 1-165 (R-3) Et 5-MeO-〇 (CH2) 7-(G65) MeO HHH 1- 166 (R-3) Et 5-MeO-0 (CH2) 7_ (G74) MeO HHH 1-167 (R-3) Et 5-MeO -〇 (CH2) r (G77) MeO HHH 1-168 (R-3) Et 5-MeO -〇 (CH2) r (G83) MeO HHH 1- 169 (R-4) Me 5-MeO-0 (CH2) 7- (G 4) MeO HHH 1-170 (R ~ 4) Me 5-MeO -0 (CH2) r (G14) MeO HHH 1-171 ( R-4) Me 5-MeO -〇 (ch2) 7- (G65) MeO HHH 1-172 (R-4) Me 5-MeO -0 (CH〇) 7- (G74) MeO HHH -67 200300349

1-173 (R-4) Me 5-MeO -〇 (CH2) 7- (G77) MeO HHH 1-174 (R-4) Me 5-MeO-0 (CH2) 7- (G83) MeO HHH 1- 175 (R ~ 4) Et 5-MeO -〇 (CH2) r (G 4) MeO HHH 1-176 (R-4) Et 5-MeO -〇 (ch2) 7- (G 7) MeO HHH 1-177 (R-4) Et 5-MeO -〇 (CH2) 7- (G 9) MeO HHH 1-178 (R-4) Et 5-MeO -o (ch2) 7-(G12) MeO HHH 1-179 ( R-4) Et 5-MeO -〇 (ch2) 7- (G14) MeO HHH 1-180 (R-4) Et 5-MeO -〇 (ch2) 7- (G23) MeO HHH 1-181 (R- 4) Et 5-MeO -〇 (CH2) 7- (G25) MeO HHH 1-182 (R-4) Et 5-MeO -0 (CH2) 7- (G28) MeO HHH 1-183 (R-4) Et 5-MeO-o (ch2) 7- (G30) MeO HHH 1-184 (R-4) Et 5-MeO -〇 (ch2) 7- (G35) MeO HHH 1-185 (R-4) Et 5_MeO -o (ch2) 7-(G50) MeO HHH 1 -186 (R ~ 4) Et 5-MeO -〇 (CH2) r (G54) MeO HHH 1-187 (R-4) Et 5-MeO -〇 ( CH2) 7- (G60) MeO HHH 1-188 (R-4) Et 5-MeO -o (ch2) 7- (G65) MeO HHH 1-189 (R-4) Et 5-MeO -〇 (ch2) 7- (G71) MeO HHH 1-190 (R-4) Et 5-MeO. -〇 (ch2) 7- (G74) MeO HHH 1-191 (R ~ 4) Et 5-MeO -〇 (CH2) r (G77) MeO HHH 1-192 (R ~ 4) Et 5-MeO -〇 (CH2) 7- (G80) MeO HHH 1-193 (R-4) Et 5-MeO -0 (CH2) 7- (G83) MeO HHH 1-194 (R-4) Et 5-EtO -0 (CH2) 7- (G 4) MeO HHH 1-195 (R-4) Et 5-EtO -0 (CH2) r (G 7) MeO HHH 1-196 (R-4) Et 5-EtO -〇 (CH2) 7- (G 9 ) MeO HHH 1-197 (R_4) Et 5-EtO -0 (CH2) 7- (G12) MeO HHH 1-198 (R-4) Et 5-EtO -〇 (CH2) 7- (G14) MeO HHH- 68 200300349

1-199 (R-4) Et 5-EtO -〇 (CH2) r (G23) MeO. HHH 1-200 (R ~ 4) Et 5-EtO -〇 (ch2) 7- (G25) MeO HHH 1- 201 (R ~ 4) Et 5-EtO -〇 (CH2) 7_ (G28) MeO HHH 1-202 (R-4) Et 5-EtO -o (ch2) 7- (G30) MeO HHH 1-203 (R -4) Et 5-EtO -〇 (ch2) 7- (G35) MeO HHH 1-204 (R-4) Et 5-EtO -o (ch2) 7-(G50) MeO HHH 1-205 (R-4 ) Et 5-EtO-0 (CH2) 7- (G54) MeO HHH 1-206 (R-4) Et 5-EtO -o (ch2) 7- (G60) MeO H. HH 1-207 (R-4 ) Et 5-EtO -0 (CH2) 7- (G65) MeO HHH 1-208 (R-4) Et 5-EtO -〇 (CH2) 7- (G71) MeO HHH 1-209 (R-4) Et 5-EtO -〇 (ch2) 7- (G74) MeO HHH 1-210 (R-4) Et 5-EtO -〇 (CH2) 7- (G77) MeO HHH 1-211 (R-4) Et 5- EtO -0 (CH2) r (G80) MeO HH Ή 1-212 (R ~ 4) Et 5-EtO-0 (CH2) 7- (G83) MeO HHH 1-213 (R-4) Et 5-MeS- 〇 (CH2) 7- (G 4) MeO HHH 1-214 (R-4) Et 5-MeS -o (ch2) 7-(G 7) MeO HH • H 1-215 (R-4) Et 5- MeS -〇 (CH2) 7- (G 9) MeO HHH 1-216 (R-4) Et 5-MeS -0 (CH2) r (G12) MeO HHH 1-217 (R-4) Et 5-MeS- 〇 (CH2) 7- (G14) MeO HHH 1-218 (R-4) Et 5-MeS -0 (CH2) 7- (G23) MeO HHH 1-219 (R-4) Et 5-MeS -〇 (CH2) 7- (G25) MeO HHH 1-220 (R-4) Et 5-MeS -0 (CH2) 7- (G28) MeO HHH 1-221 (R ~ 4) Et 5-MeS -0 (CH2) 7- (G30) MeO HHH 1-222 (R-4) Et 5-MeS-o (ch2) 7- ( G35) MeO HHH 1-223 OR-4) Et 5-MeS -〇 (CH2) r (G50) MeO HHH 1-224 (R-4) Et 5-MeS-0 (CH2) r (G54) MeO HHH- 69 200300349

1-225 (R-4) Et 5-MeS -0 (CH2) r (G60) MeO HHH 1-226 (R-4) Et 5-MeS -〇 (CH2) 7- (G65) MeO HHH 1-227 (R-4) Et 5-MeS -〇 (CH2) 7- (G71) MeO HHH 1-228 (R-4) Et 5-MeS -〇 (CH2) 7- (G74) MeO HHH 1-229 (R -4) Et 5-MeS-0 (CH2) 7- (G77) MeO HHH 1-230 (R-4) Et 5-MeS -o (ch2) 7-(G80) MeO HHH 1-231 (R-4 ) Et 5-MeS-0 (CH2) 7-(G83) MeO HHH 1-232 (R-4) Et 5-N (Me) 2 -0 (CH2) r (G 4) MeO HHH 1-233 (R -4) Et 5-N (Me) 2 -0 (CH2) 7- (G 7) MeO HHH 1-234 (R-4) Et 5-N (Me) 2-0 (CH2) 7- (G 9 ) MeO HHH 1-235 (R-4) Et 5 -N (Me) 2 -〇 (CH2) 7- (G12) MeO HH H. 1-236 (R-4) Et 5 -N (Me) 2- 〇 (CH2) 7- (G14) MeO HHH 1-237 (R ~ 4) Et 5-N (Me) 2-0 (CH2) 7- (G23) MeO HHH 1-238 (R-4) Et 5- N (Me) 2 -0 (CH2) 7- (G25) MeO HHH 1-239 (R_4) Et 5-N (Me) 2 -〇 (CH2) 7-(G28) MeO HHH 1-240 (R-4 ) Et 5-N (Me) 2-o (ch2) 7- (G30) MeO HHH 1-241 (R-4) Et 5-N (Me) 2 -〇 (ch2) r (G35) MeO HHH 1- 242 (R-4) Et 5-N (Me) 2 -〇 (CH2) r (G50) MeO HHH 1-243 (R-4) Et 5-N (Me) 2 -0 (CH2) 7- (G54 ) MeO HHH 1-244 (R-4) Et 5-N (Me) 2-o (ch2) 7-(G60) MeO HHH 1-245 (R_4) Et 5-N (Me) 2-0 (CH2) 7- ( G65) MeO HHH 1-246 (R-4) Et 5-N (Me) 2--(CH2) 7- (G71) MeO HHH 1-247 (R-4) Et 5-N (Me) 2- -〇 (CH2) 7- (G74) MeO HHH 1-248 (R-4) Et 5-N (Me) 2 -0 (CH2) r (G77) MeO HHH 1-249 (R-4) Et 5-N ( Me) 2 -〇 (CH2) 7 ~ (G80) MeO HHH 1-250 (R-4) Et 5-N (Me)?, -0 (CH2) 7- (G83) MeO HHH -70 200300349

1-251 (R-4) Pr 5-MeO -o (ch2) 7- (G 4) MeO HHH 1-252 (R ~ 4) Pr. 5-MeO-0 (CH2) 7- (G 7) MeO HHH 1-253 (R ~ 4) Pr 5-MeO -〇 (CH2) r (G 9) MeO HHH 1-254 (R ~ 4) Pr 5-MeO -〇 (ch2) r (G12) MeO HHH 1- 255 (R-4) Pr 5-MeO -o (ch2) 7- (G14) MeO HHH 1-256 (R-4) Pr 5-MeO -o (ch2) 7-(G23) MeO HHH 1-257 ( R-4) Pr 5-MeO -〇 (ch2) 7- (G25) MeO HHH 1-258 (R-4) Pr 5-MeO -〇 (ch2) 7- (G28) MeO HHH 1-259 (R- 4) Pr 5-MeO -〇 (ch2) 7- (G30) MeO HHH 1-260 (R-4) Pr 5-MeO-o (ch2) 7_ (G35) MeO HHH 1-261 (R-4) Pr 5-MeO -〇 (ch2) 7- (G50) MeO HHH 1-262 (R ~ 4) Pr 5-MeO -〇 (ch2) r (G54) MeO HH · H 1-263 (R-4) Pr 5 -MeO -〇 (CH2) r (G60) MeO HHH 1-264 (R-4) Pr 5-MeO -0 (CH2) r (G65) MeO HHH 1-265 (R-4) Pr 5-MeO -o (ch2) 7- (G71) MeO HHH 1-266 (R ~ 4) Pr 5-MeO-o (ch2) 7- (G74) MeO HHH 1-267 (R-4) Pr 5-MeO -〇 (ch2 ) r (G77) MeO HHH 1-268 (R-4) Pr 5-MeO -0 (CH2) 7- (G80) MeO HHH 1-269 (R-4) Pr 5-MeO -o (CH2) r ( G83) MeO HHH 1-270 (R-4) Pr 5-EtO -o (ch2) 7- (G 4) MeO H HH 1-271 (R-4) Pr 5-EtO -0 (CH2) r (G 7) MeO HHH 1-272 (R-4) Pr 5-EtO-o (ch2) 7- (G 9) MeO HHH 1-273 (R-4) Pr 5-EtO -0 (CH2) r (G12) MeO HHH 1-274 (R-4) Pr 5-EtO -o (CH2) 7- (G14) MeO HHH 1-275 (R-4) Pr 5-EtO -0 (CH2)?-(G23) MeO HHH 1-276 (R-4) Pr 5-EtO-o (ch2) 7- (G25) MeO HHH -71 200300349

1-277 (R-4) Pr 5-EtO -o (ch2) 7- (G28) MeO HHH 1-278 (R-4) Pr 5-EtO-o (ch2) 7-(G30) MeO HHH 1- 279 (R-4) Pr 5-EtO -o (ch2) 7- (G35) MeO HHH 1-280 (R-4) Pr 5-EtO -〇 (ch2) r (G50) MeO HHH 1-281 (R -4) Pr 5 -E tO -〇 (CH2) r (G54) MeO HHH 1-282 (R-4) Pr 5-EtO -0 (CH2) r (G60) MeO HHH 1-283 (R-4) Pr 5-EtO -0 (CH2) r (G65) MeO HHH 1-284 (R-4) Pr 5-EtO-0 (CH2) 7- (G71) MeO HHH 1-285 (R-4) Pr 5- EtO -0 (CH2) 7- (G74) MeO HHH 1-286 (R-4) .Pr 5-EtO -o (ch2) 7- (G77) MeO HHH 1-287 (R-4) Pr 5-EtO -o (ch2) 7- (G80) MeO HHH 1-288 (R-4) Pr 5-EtO -〇 (ch2) 7- (G83) MeO HHH 1-289 (R-4) Pr 5-M.eS -o (ch2) 7- (G 4) MeO HHH 1-290 (R-4) Pr 5-MeS-o (ch2) 7-(G 7) MeO HHH 1-291 (R-4) Pr 5-MeS -o (ch2) 7-(G 9) MeO HHH 1-292 (R-4) Pr 5-MeS-o (ch2) 7- (G12) MeO HHH 1-293 (R-4) Pr 5-MeS- o (ch2) 7-(G14) MeO HHH 1-294 (R-4) Pr 5-MeS-o (ch2) 7-(G23) .MeO HHH 1-295 (R_4) Pr 5-MeS-o (ch2 ) 7- (G25) MeO HHH 1-296 (R-4) Pr 5-MeS -〇 (ch2) 7- (G28) MeO HHH 1-297 (R-4) Pr 5-MeS -〇 (ch2) 7- (G30) MeO HHH 1-298 (R-4) Pr 5-MeS -〇 (ch2) 7- (G35) MeO HHH 1-299 (R-4) Pr 5 -MeS -〇 (ch2) 7- (G50) MeO HHH 1-300 (R_4) Pr 5-MeS -〇 (ch2) 7- (G54) MeO HHH 1-301 (R-4) Pr 5-MeS -〇 (ch2) r (G60) MeO HHH 1-302 (R-4) Pr 5-MeS -〇 (CH〇) 7- (G65) MeO HHH -72 200300349

1-303 (R-4) Pr 5-MeS -〇 (CH2) r (G71) MeO HHH 1-304 (R-4) Pr 5 ~ MeS -0 (CH2) r (G74) MeO HHH 1-305 ( R-4) Pr 5-MeS-0 (CH2) 7- (G77) MeO HH 1-306 (R-4) Pr 5-MeS-0 (CH2) r (G80) MeO HHH 1-307 (R-4 ) Pr 5-MeS -〇 (CH2) 7- (G83) MeO HHH 1-308 (R-4) Pr 5-N (Me) 2-0 (CH2) 7_ (G 4) MeO HHH 1-309 (R -4) Pr 5-N (Me) 2 -〇 (CH2) 7- (G 7) MeO HHH 1-310 (R-4) Pr 5-N (Me) 2 -o (ch2) 7- (G 9 ) MeO HHH 1-311 (R-4) Pr 5-N (Me) 2 -〇 (ch2) r (G12) MeO HHH 1-312 (R_4) Pr 5-N (Me) 2-o (ch2) 7 -(G14) MeO HHH 1-313 (R-4) Pr 5-N (Me) 2 -〇 (CH2) r (G23) MeO HHH 1-314 (R-4) Pr 5-N (Me) 2- 〇 (ch2) r (G25) MeO HHH 1-315 (R-4) Pr 5-N (Me) 2-0 (CH2) 7- (G28) MeO HHH 1-316 (R-4) Pr 5-N (Me) 2-o (ch2) 7-(G30) MeO HHH 1-317 (R ~ 4) Pr 5-N (Me) 2 -〇 (CH2) 7- (G35) MeO HHH 1-318 (R- 4) Pr 5-N (Me) 2 -0 (CH2) r (G50) MeO HHH 1-319 (R-4) Pr 5-N (Me) 2 -〇 (ch2) r (G54) MeO HHH 1- 320 (R-4) Pr 5-N (Me) 2 -o (ch2) 7-(G60) MeO HHH 1-321 (R-4) Pr 5-N (Me) 2 -〇 (CH2) r (G65 ) MeO HHH 1- 322 (R-4) Pr 5-N (Me) 2 -0 (CH2) r (G71) MeO HHH 1-323 (R-4) Pr 5-N (Me) 2 -0 (CH2) 7- (G74 ) MeO HHH 1-324 (R-4) Pr 5-N (Me) 2 -0 (CH2) r (G77) MeO HHH 1-325 (R-4) Pr 5-N (Me) 2 -〇 (ch2 ) r (G80) MeO HHH 1-326 (R-4) Pr 5-N (Me) 2, -0 (CH2) r (G83) MeO HHH 1-327 (R-4) Bu 5-MeO -〇 ( CH2) 7- (G 4) MeO HHH 1-328 (R-4) Bu 5-MeO -〇 (ch2) r (G 7) MeO HHH -73 200300349 1-329 (R-4) Bu 5-MeO- o (ch2) 7- (G 9) 1-330 (R ~ 4) Bu 5-MeO ~ 0 (CH2) r (G12) 1-331 (R-4) Bu 5-MeO -〇 (CH2) r ( G14) 1-332 (R-4) Bu 5-MeO -o (ch2) 7-(G23) 1-333 (R-4) Bu 5-MeO-0 (CH2) 7- (G25) 1-334 ( R ~ 4) Bu 5-MeO -〇 (CH2) 7- (G28) 1-335 (R-4) Bu 5-MeO-o (ch2) 7-(G30) 1-336 (R-4) Bu 5 -MeO -0 (CH2) r (G35) 1-337 (R-4) Bu 5-MeO-0 (CH2) 7- (G50) 1-338 (R-4) Bu. 5-MeO -o (ch2 ) 7-(G54) 1-339 (R-4) Bu 5-MeO -0 (CH2) r (G60) 1-340 (R-4) Bu 5-MeO-0 (CH2) 7- (G65) 1 -341 (R-4) Bu 5-MeO -〇 (ch2) r (G71) 1-342 (R-4) Bu 5-MeO _o (ch2) 7- (G74) 1-343 (R-4) Bu 5-MeO -〇 (CH2) 7- (G77) 1-344 (R-4) Bu 5-MeO-0 (CH2) 7- (G80) 1-345 (R-4) Bu 5-MeO -0 (CH2) 7- (G83) 1-346 (R ~ 4) All 5-MeO-o (ch2) 7- (G 4) 1-347 (R-4) All 5-MeO-o (ch2) 7-(G 7) 1-348 (R-4) All 5 ~ MeO -o (ch2) 7-(G 9) 1-349 ( R-4) All 5 ~ MeO -o (ch2) 7- (G12) 1-350 (R-4) All 5-MeO -0 (CH2) r (G14) 1-351 (R-4) All 5- MeO -0 (CH2) r (G23) 1-352 (R-4) All 5-MeO-o (ch2) 7- (G25) 1-353 (R-4) All 5-MeO-o (ch2) 7 -(G28) 1-354 (R_4) All 5-MeO -〇 (CH2) (G30)

MeO Η Η Η MeO Η Η Η MeO Η Η Η O MeO Η Η Η MeO Η Η Η O MeO Η Η Η MeO Η Η Η MeO Η Η Η

MeO Η Η Η MeO Η Η O MeO Η Η Η O MeO Η Η Η MeO Η Η Η MeO Η Η Η MeO Η Η Η MeO Η Η Η MeO Η O Η Η

MeO Η Η Η MeO Η Η O MeO Η Η Η O MeO Η Η Η MeO Η Η Η MeO Η Η Η MeO Η Η Η MeO Η Η Η MeO Η O Η Η

-74 200300349

1-355 (R-4) All 5-MeO -0 (CH2) 7- (G35) MeO HHH 1-356 (R-4) All 5-MeO -〇 (CH2) 7- (G50) MeO HHH 1- 357 (R-4) All 5-MeO -〇 (CH2) 7- (G54) MeO HHH 1-358 (R-4) All 5-MeO-0 (CH2) 7- (G60) MeO HHH 1-359 ( R-4) All 5-Me〇-〇 (CH2) 7- (G65) MeO HHH 1-360 (R ~ 4) All 5-MeO -〇 (CH2) 7- (G71) MeO HHH 1-361 (R -4) All 5-MeO -〇 (ch2) 7- (G74) MeO HHH 1-362 (R-4) All 5-MeO -〇 (CH2) r (G77) MeO HHH 1-363 (R-4) All 5-MeO -〇 (ch2) 7- (G80) MeO HHH 1-364 (R-4) All 5-MeO -〇 (CH2) 7- (G83) MeO HHH 1-365 (R-4) Prp 5 -MeO-0 (CH2) 7- (G 4) MeO HHH 1-366 (R-4) Prp 5-MeO -0 (CH2) 7- (G 7) MeO HHH 1-367 (R-4) Prp 5 -MeO -〇 (CH2) 7- (G 9) MeO HHH 1-368 (R-4) Prp 5-MeO -〇 (CH2) 7- (G12) MeO HHH 1-369 (R-4) Prp 5- MeO -〇 (CH2) 7- (G14) MeO HHH 1-370 (R-4) Prp 5-MeO -0 (CH2) 7- (G23) MeO HHH 1-371 (R-4) Prp 5-MeO- 0 (CH2) 7- (G25) MeO HHH 1-372 (R-4) Prp 5-MeO -0 (CH2) 7- (G28) MeO HHH 1-373 (R-4) Prp 5-MeO _o (ch2 ) 7- (G30) MeO HHH 1-374 (R-4) Prp 5-MeO -0 (CH2) r (G35) MeO HHH 1-375 (R ~ 4) Prp 5-MeO -〇 (ch2) r (G50) MeO HHH 1-376 (R_4) Prp 5-MeO -o (ch2) 7 -(G54) MeO HHH 1-377 (R ~ 4) Prp 5-MeO-o (ch2) 7- (G60) MeO HHH 1-378 (R ~ 4) Prp 5-MeO -o (ch2) 7-( G65) MeO HHH 1-379 (R-4) Prp 5-MeO -0 (CH2) 7- (G71) MeO HHH 1-380 (R-4) Prp 5-MeO-0 (CH2) r (G74) MeO HHH -75 200300349

1-381 (R-4) Prp 5-MeO -〇 (CH2) 7_ (G77) MeO HHH 1-382 (R_4) Prp 5-MeO -o (ch2) 7- (G80) MeO HHH 1-383 (R ~ 4) Prp 5-MeO-0 (CH2) 7- (G83) MeO HHH 1-384 (R-4) Et 5-MeO -ch2o (ch2) 7- (G 4) MeO HHH 1-385 (R- 4) Et 5-MeO -CH20 (CH2) r (G 7) MeO HHH 1-386 (R-4) Et 5-MeO -CH20 (CH2) 7-(G 9) MeO HHH 1-387 (R-4 ) Et 5-MeO -CH20 (CH2) r (G14) MeO HHH 1-388 (R-4) Et 5-MeO a ch2o (ch2) 7- (G25) MeO HHH 1-389 (R-4) Et 5 -MeO -ch2o (ch2) 7- (G35) MeO HHH 1-390 (R-4) Et 5-MeO -ch2〇 (ch2) 7- (G50) MeO HHH 1-391 (R-4) Et 5- MeO -CH20 (CH2) 7- (G54) MeO HHH 1-392 (R-4) Et 5-MeO -CH20 (CH2) r (G65) MeO HHH 1-393 (R-4) Et 5-MeO-CH20 (CH2) 7-(G74) MeO HHH 1-394 (R-4) Et. 5-MeO-CH20 (CH2) 7- (G77) MeO HHH 1-395 (R-4) Et 5-MeO -ch2o ( ch2) 7- (G80) MeO HHH 1-396 (R-4) Et 5-MeO -CH20 (CH2) 7- r (G83) MeO HHH 1-397 (R-4) Et 5-MeO -s (ch2 ) 7-(G 4) MeO HHH 1-398 (R_4) Et 5-MeO-S (CH2) r (G 7) MeO HHH 1-399 (R-4) Et 5-MeO -S (CH2) r ( G 9) MeO HHH 1-400 (R-4) Et 5-MeO -s (CH2) r (G14) MeO HHH 1-401 (R-4) Et 5-MeO -S (CH2) r (G25) MeO HHH 1-402 (R-4) Et 5-MeO -S (CH2) r (G35) MeO HHH 1-403 (R_4) Et 5-MeO '-S (CH2) r (G50) MeO HHH 1-404 (R ~ 4) Et 5-MeO -S (CH2) r (G54) MeO HHH 1-405 (R_4) Et 5-MeO -s (ch2) 7- (G65) MeO HHH 1-406 (R-4) Et 5-MeO -s (ch2)?-(G74) MeO HHH -76- 200300349

1-407 (R-4) Et 5-MeO -S (CH2) r (G77) MeO HHH 1-408 (R-4) Et 5-MeO -s (ch2) 7- (G80) MeO HHH 1-409 (R-4) Et 5-MeO -s (ch2) 7- (G83) MeO HHH 1-410 (R-7) Et 5-MeO -〇 (CH2) r (G 4) MeO HHH 1-411 (R -7) Et 5-MeO -〇 (CH2) r (G14) MeO HHH 1-412 (R-7) Et 5-MeO -〇 (CH2) 7- (G65) MeO HHH ί-413 (R-7) Et 5-MeO -〇 (ch2) r (G74) MeO HHH 1-414 (R-7) Et 5-MeO -o (ch2) 7- (G77) MeO HH .H 1-415 (R-7) Et 5-MeO -〇 (ch2) r (G83) MeO HHH 1-416 (Rl) Et 5-MeO -0 (ch2) 8- (G 4) MeO HHH 1-417 (Rl) Et 5-MeO-o ( ch2) 8-(G14) MeO HHH 1-418 (Rl) Et 5-MeO-〇 (CH2) 8-(G65) MeO HHH 1-419 (Rl) Et 5-MeO-〇 (CH2) 8-(G74 ) MeO HHH 1-420 (Rl) Et 5-MeO -〇 (CH2) 8- (G77) MeO HHH 1-421 (R_l) Et 5-MeO -〇 (ch2) 8- (G83) MeO HHH 1-422 (R-3) Et 5-MeO -〇 (CH2) 8- (G 4) MeO HHH 1-423 (R-3) Et 5-MeO-0 (ch2) 8-(G14) MeO HHH 1-424 ( R-3) Et 5-MeO-o (ch2) 8-(G65) MeO HHH 1-425 (R-3) Et. 5-MeO -〇 (CH2) 8- (G74) MeO HHH 1-426 (R -3) Et 5-MeO -o (ch2) 8- (G77) MeO HH H 1-427 (R-3) Et 5-MeO -〇 (ch2) 8- (G83) MeO HHH 1-428 (R-4) Me 5-MeO -〇 (ch2) 8- (G 4) MeO HHH 1-429 (R-4) Me 5-MeO -0 (CH2) 8- (G14) MeO HHH 1-430 (R-4) Me 5-MeO -0 (CH2) 8- (G65) MeO HHH 1- 431 (R-4) Me 5-MeO -0 (ch2) 3- (G74) MeO HHH 1-432 (R-4) Me 5-MeO _o (ch2) 8-(G77) MeO HHH -77 200300349

1-433 (R-4) Me 5-MeO -〇 (ch2) 8- (G83) MeO HHH 1-434 (R-4) Et 5-MeO -〇 (ch2) 8-(G 4) MeO HHH 1 -435 (R_4) Et 5-MeO -o (ch2) 8- (G 7) MeO HHH 1-436 (R-4) Et 5-MeO -o (ch2) 8- (G 9) MeO HHH 1-437 (R-4) Et 5-MeO-o (ch2) 8-(G12) MeO HHH 1-438 (R-4) Et 5-MeO -〇 (ch2) 8- (G14) MeO HHH 1-439 (R_4 ) Et 5-MeO -〇 (ch2) 8- (G23) MeO HHH 1-440 (R-4) Et 5-MeO-〇 (ch2) 8- (G25) MeO HHH 1-441 (R-4) Et 5-MeO -〇 (ch2) 8-(G28) MeO HHH 1-442 (R-4) Et 5-MeO -0 (ch2) 8- (G30) MeO HHH 1-443 (R-4) Et 5- MeO-0 (ch2) 8-(G35) MeO HHH 1-444 (R ~ 4) Et 5-MeO-0 (ch2) 8- (G50) MeO HHH 1-445 (R-4) Et. 5-MeO -0 (CH2) r (G54) MeO HHH 1-446, (R ~ 4) Et 5-MeO -o (ch2) 8- (G60) MeO HHH 1-447 (R-4) Et 5-MeO -o (ch2) 8-(G65) MeO HHH 1-448 (R-4) Et 5-MeO -o (ch2) 8- (G71) MeO HHH 1-449 (R-4) Et 5-MeO-o (ch2 ) 8-(G74) MeO HHH 1-450 (R-4) Et 5-MeO-0 (CH2) 8-(G77) MeO HHH 1-451 (R_4) Et 5-MeO -0 (CH2) 8-( G80) MeO HHH 1-452 (R-4) Et 5-MeO -0 (ch2) 8- (G83) MeO HHH 1- 453 (R-4) .Et 5-MeO -CH20 (CH2) r (G 4) MeO HHH 1-454 (R-4) Et 5-MeO -ch2o (CH2) 8- (G 9) MeO HHH 1- 455 (R-4) Et 5-MeO -ch2o (ch2) 8- (G14) MeO HHH 1-456 (R-4) Et 5-MeO-CH20 (CH2) 8-(G65) MeO HHH 1-457 ( R-4) Et 5-MeO ~ ch2o (ch2) 8- (G74) MeO HHH 1-458 (R-4) Et 5-MeO -ch2〇 (ch2) 8- (G77) MeO HHH -78 200300349

1-459 (R-4) Et 5-MeO -ch2o (ch2) 8- (G80) MeO HHH 1-460 (R-4) Et 5-MeO-CH20 (CH2) 8- (G83) MeO HHH 1- 461 (R-4) Et 5-MeO-s (ch2) 8-(G 4) MeO HHH 1-462 (R-4) Et 5-MeO -s (ch2) 8- (G 9) MeO HHH 1- 463 (R-4) Et 5-MeO -s (ch2) 8- (G14) MeO HHH 1-464 (R-4) Et 5-MeO -s (ch2) 8- (G65) MeO HHH 1-465 ( R-4) Et 5-MeO -s (ch2) 8- (G74) MeO HHH 1-466 (R-4) Et 5-MeO -s (ch2) 8-(G77) MeO HHH 1-467 (R- 4) Et 5-MeO-s (CH2) 8-(G80) MeO HHH 1-468 (R-4) Et 5-MeO -s (ch2) 8- (G83) MeO HHH 1-469 (R-7) Et 5-MeO -0 (ch2) 8- (G 4) MeO HHH 1-470 (R-7) Et 5-MeO -0 (ch2) 8- (G14) MeO HHH 1-471 (R-7) Et 5-MeO -0 (ch2) 8-(G65) MeO HHH 1-472 (R-7) Et 5-MeO-o (ch2) 8-(G74) MeO HHH 1-473 (R-7) Et 5- MeO -〇 (CH2) 8- (G77) MeO HHH 1-474 (R-7) Et 5-MeO -0 (ch2) 8- (G83) MeO HHH 1-475 (R ~ l) Me 5-MeO- OCH2 (l, 2-Phy) CHr (G 3) MeO HHH 1-476 (R ~ l) Me 5-MeO -0CH2 (1,2-Phy) CHr (G 8) MeO HHH 1-477 (R-1 ) Me 5-MeO -0CH2 (1,2-Phy) CHr (G13) MeO HHH 1-478 (R_l) Me 5-MeO -OCH2 (l, 2-Phy) CHr (G24) MeO HHH 1-479 (R -1) Me 5-MeO -0CH2 (1,2-Phy) CHr (G34) MeO HHH 1-480 (R_l) Me 5-MeO -OCH2 (l, 2- Phy) CHr (G64) MeO HHH 1-481 (Rl) Me 5-MeO -0CH2 (1,2-Phy) CHr (G73) MeO HHH 1-482 (Rl) Me 5-MeO -0CH2 (1,2- Phy) CHr (G76) MeO HHH 1-483 (R ~ l) Me. 5-MeO -OCH2 (l, 2-Phy) CHr (G79) MeO HHH 1 -484 (Rl) Me 5-MeO -OCH2 (l , 2-Phy) CHr (G82) MeO H .HH-79- 200300349

1-48.5 (R_l) Et 5-MeO -0CH2 (1,2-Phy) CHr (G 3) MeO HHH 1-486 (R-1) Et 5-MeO -OCH2 (l, 2-Phy) CH2- ( G 6) MeO HHH 1-487 (R-1) Et 5-MeO -〇CH2 (l, 2-Phy) CH2- (G 8) MeO HHH 1-488 (Rl) Et 5-MeO -OCH2 (l, 2-Phy) CHr (G13) MeO HHH 1-489 (R-1) Et 5-MeO -〇CH2 (l, 2-Phy) CHr (G22) MeO HHH 1-490 (Rl) Et 5-MeO-0CH2 (l, 2-Phy) CHr (G24) MeO HHH 1-491 (Rl) Et 5-MeO -〇CH2 (l, 2-Phy) CHr (G27) MeO HHH 1-492. (Rl) Et 5-MeO -〇CH2 (l, 2-Phy) CHr (G29) MeO HHH 1-493 (Rl) Et 5-MeO -〇CH2 (l, 2-Phy) CH2- (G34) MeO HHH 1-494 (R ** l) Et 5-MeO -OCH2 (l, 2-Phy) CHr (G59) MeO HHH 1-495 (Rl) Et 5-MeO -OCH2 (l, 2-Phy) CHr (G64) MeO HHH 1-496 ( Rl) Et 5-MeO -〇CH2 (l, 2-Phy) CHr (G70) MeO HHH 1-497 (Rl) Et 5 ~ M6〇-OCH2 (l, 2-Phy) CHr (G73) MeO HHH 1- 498 (Rl) Et 5-MeO -〇CH2 (l, 2-Phy) CHr (G76) MeO HHH 1-499 (R_l) Et 5-MeO -OCH2 (l, 2-Phy) CHr (G79) MeO HHH 1 -500 (Rl) Et 5-MeO -OCH2 (l, 2-Phy) CHr (G82) MeO HHH 1-501 (R ~ l) Et 5-MeO -OCH2 (l, 2-Phy) CHr (G85) MeO HHH 1-502 (Rl) Et 5-MeO -OCH2 (l, 2_Phy) CHr (G92) MeO HHH 1-503 (R-2) Me 5-MeO -OCH2 (l, 2-Phy) CHr (G 3) MeO HHH 1- 504 (R-2) Me 5-MeO -OCH2 (l, 2-Phy) CHr (G 8) MeO HHH 1-505 (R-2) Me 5-MeO-0CH2 (l, 2HPhy) CHr (G13) MeO HHH 1-506 (R-2) Me 5-MeO -〇CH2 (l, 2-Phy) CHr (G24) MeO HHH 1-507 (R-2) Me 5-MeO -OCH2 (l, 2-Phy) CHr (G34) MeO HHH 1-508 (R-2) Me 5-MeO -0CH2 (1,2-Phy) CHr (G64) MeO HHH 1-509 (R-2) Me 5-MeO -OCH2 (l, 2-Phy) CHr (G73) MeO HHH 1-510 (R-2) Me 5-MeO -0CH2 (1,2-Phy) CHr (G76) MeO HHH -80- 200300349

1-511 (R-2) Me 5-MeO -〇CH2 (l, 2-Phy) CHr (G82) MeO HHH 1-512 (R-2) Et 5-MeO -〇CH2 (l, 2-Phy) CHr (G 3) MeO HHH 1-513 (R-2) Et 5-MeO -〇 CH2 (l, 2-Phy) CHr (G 8) MeO HHH 1-514 (R-2) Et 5-MeO -〇 CH2 (l, 2-Phy) CHr (G13) MeO HHH 1-515 (R-2) Et 5-MeO -OCH2 (l, 2-Phy) CHr (G24) MeO HHH 1-516 (R-2) Et 5-MeO -〇CH2 (l, 2-Phy) CH2- (G34) MeO HHH 1-517 (R-2) Et 5-MeO -〇CH2 (l, 2-Phy) CH2- (G64) MeO HHH 1 -518 (R-2) Et 5-MeO -〇CH2 (l, 2-Phy) CHr (G73) MeO HHH 1-519 (R-2) Et 5-MeO -OCH2 (l, 2-Phy) CHr ( G76) MeO HHH 1-520 (R-2) Et 5-MeO -〇CH2 (l, 2-Phy) CHr (G82) MeO HHH 1-521 (R-3) Me 5-MeO -〇CH2 (l, 2-Phy) CHr (G 3) MeO HHH 1-522 (R-3) Me 5-MeO -〇CH2 (l, 2-Phy) CHr (G 8) MeO HHH 1-523 (R-3) Me 5 -MeO -〇CH2 (l, 2-Phy) CHr (G13) MeO HHH 1-524 (R-3) Me 5-MeO -〇CH2 (l, 2-Phy) CHr (G24) MeO HHH 1-525 ( R-3) Me 5-MeO -〇CH2 (l, 2-Phy) CHr (G34) MeO HHH 1-526 (R-3) Me 5-MeO -〇CH2 (l, 2-Phy) CHr (G64) MeO HHH 1-527 (R-3) Me 5-MeO -〇CH2 (l, 2-Phy) CHr (G73) MeO HHH 1-528 (R-3) Me 5-MeO -〇CH2 (l, 2-Phy) CHr (G76) MeO HHH 1-529 (R-3) Me 5-MeO -〇CH2 (l, 2-Phy) CHr (G82) MeO HHH 1-530 (R-3) Et 5-MeO -〇CH2 (l, 2-Phy) CHr (G 3) MeO HHH 1-531 (R-3) Et 5-MeO -OCH2 ( l, 2-Phy) CHr (G 6) MeO HHH 1-532 (R-3) Et 5-MeO -〇CH2 (l, 2-Phy) CHr (G 8) MeO HHH 1-533 (R-3) Et 5-MeO -〇CH2 (l, 2-Phy) CHr (G13) MeO HHH 1-534 (R-3) Et 5-MeO -〇CH2 (l, 2-Phy) CHr (G22) MeO HHH 1- 535 (R-3) Et 5-MeO -〇CH2 (l, 2-Phy) CHr (G24) MeO HHH 1-536 (R-3) Et 5-MeO -OCH2 (l, 2-Phy) CHr (G27 ) MeO HHH -81- 200300349

1-537 (R-3) Et 5-MeO -0CH2 (1,2-Phy) CHr (G29) MeO HHH 1-538 (R-3) Et 5-MeO -〇CH2 (l, 2-Phy) CHr (G34) MeO HHH 1-539 (R-3) Et 5-MeO -0CH2 (1,2-Phy) CHr (G59) MeO HHH 1-540 (R-3) Et 5-MeO -0CH2 (1,2 -Phy) CHr (G64) MeO HHH 1-541 (R-3) Et 5-MeO -0CH2 (1,2-Phy) CHr (G70) MeO HHH 1-542 (R-3) Et 5-MeO -0CH2 (1,2-Phy) CHr (G73) MeO HHH 1-543 (R-3) Et 5-MeO -0CH2 (1, 2 ~ Phy) CHr (G76) MeO HHH 1-544 (R-3) Et 5 -MeO -0CH2 (1,2-Phy) CHr (G79) MeO HHH 1-545 (R-3) Et 5-MeO-OCH2 (l, 2 -Phy) CH2-(G82) MeO HHH 1-546 (R -3) Et 5-MeO-OCH2 (l, 2-Phy) CHr (G85) MeO HHH 1-547 (R-3) Et 5-MeO -〇CH2 (l, 2-Phy) CHr (G92) MeO HHH 1-548 (R-4) Me 5-MeO -OCH2 (l, 2-Phy) CHr (Gl) MeO HHH 1-549 (R-4) Me 5-MeO -〇CH2 (l, 2-Phy) CH2 -(G 3) MeO HHH 1-550 (R-4) Me 5-MeO -OCH2 (l, 2-Phy) CHr (G 4) MeO HHH 1-551 (R-4) Me 5-MeO -OCH2 ( l, 2-Phy) CHr (G 6) MeO HHH 1-552 (R-4) Me 5-MeO -0CHZ (1,2-Phy) CHr (G 8) MeO HHH 1-553 (R-4) Me 5-MeO -OCH2 (l, 2-Phy) CHr (Gil) MeO HHH 1-554 (R-4 ) Me 5-MeO -OCH2 (l, 2-Phy) CHr (G13) MeO HHH 1-555 (R-4) Me 5-MeO ~ 0CH2 (1,2-Phy) CHr (G22) MeO HHH 1-556 (R-4) Me 5-MeO -OCH2 (l, 2-Phy) CH2- (G24) MeO HHH 1-557 (R-4) Me 5-MeO -0CH2 (1,2-Phy) CHr (G34) MeO HHH 1-558 (R-4) Me 5-MeO -0CH2 (1,2-Phy) CHr (G59) MeO HHH 1-559 (R-4) Me 5-MeO -〇CH2 (l, 2-Phy ) CHr (G62) MeO H. HH 1-560 (R-4) Me 5-MeO ~ OCH2 (l, 2-Phy) CHr (G64) MeO HHH 1-561 (R-4) Me 5-MeO -〇 CH2 (l, 2 ~ Phy) CHr (G67.) MeO HHH 1-562 (R-4) Me 5-MeO -〇CH2 (l, 2-Phy) CHr (G70) MeO HHH

-82- 200300349

1-563 (R-4) Me 5-MeO -〇CH2 (l, 2-Phy) CHr (G73) MeO HHH 1-564 (R-4) Me 5-MeO -0CH2 (1,2-Phy) CHr (G74) MeO HHH 1-565 (R-4) Me 5-MeO -〇CH2 (l, 2-Phy) CH2- (G76) MeO HHH 1-566 (R ~ 4) Me 5-MeO ~ OCH2 (l , 2-Phy) CHr (G79) MeO HHH 1-567 (R-4) Me 5 ~ Me0 -〇CH2 (l, 2-Phy) CHr (G82) MeO HHH 1-568 (R-4) Me 5- MeO -0CH2 (1,2-Phy) CHr (G86) MeO HHH 1-569 (R ~ 4) Et 5-MeO -OCH2 (l, 2-Phy) CHr (Gl) MeO HHH 1-570 (R ~ 4 ) Et 5-MeO -0CH2 (1,2-Phy) CHr (G 3) MeO HHH 1-571 (R-4) Et 5-MeO -0CH2 (1,2-Phy) CHr (G 4) MeO HHH 1 -572 (R-4) Et 5-MeO -OCH2 (l, 2-Phy) CHr (G 6) MeO HHH 1-573 (R-4) Et 5_Me0 -0CH2 (l, 2-Phy) CH2- (G 8) MeO HHH 1-574 (R-4) Et 5-MeO -OCH2 (l, 2-Phy) CH2- (Gil) MeO HHH 1-575 (R-4) Et 5-MeO -OCH2 (l, 2 -Phy) CH2- (G13) MeO HHH 1-576 (R-4) Et 5-MeO -OCH2 (l, 2-Phy) CH2-, (G16) MeO • HHH 1-577 (R-4) Et 5 -MeO -OCH2 (l, 2 -Phy) CH2- (G18) MeO HHH 1-578 (R ~ 4) Et 5-MeO -OCH2 (l, 2-Phy) CH2- (G20) MeO HHH 1-579 ( R-4) Et 5-MeO -OCH2 (l, 2-Phy) CHr (G22) MeO HHH 1-580 (R-4) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G24) MeO HHH 1-581 (R-4) Et 5 ~ MeO -OCH2 (l, 2-Phy) CHr (G27) MeO HHH 1-582 (R-4) Et 5-MeO -0CH2 (1,2-Phy) CHr (G29) MeO HHH 1-583 (R-4) Et 5-MeO -0CH2 (1,2-Phy) CHr (G32) MeO HHH 1-584 (R-4) Et 5-MeO -0CH2 (1,2-Phy) CHr (G34) MeO HHH 1-585 (R-4) Et 5-MeO ~ 0CH2 (1,2 -Phy) CHr (G37) MeO HHH 1-586 (R-4) Et 5-MeO -0CH2 (1,2-Phy) CHr (G39) MeO HHH 1-587 (R-4) Et 5-MeO -0CH2 (1,2-Phy) CHr (G41) MeO HHH 1-588 (R-4) Et 5-MeO -0CH2 (1,2-Phy) CHr (G43) MeO HHH

-83- 200300349

1-589 (R-4) Et 5-MeO -0CH2 (1,2-Phy) CHr (G45) MeO HHH 1-590 (R-4) Et 5-MeO -0CH2 (1,2-Phy) CHr ( G59) MeO HHH 1-591 (R-4) Et 5-MeO-0CH2 (1,2, Phy) CH2- (G62) MeO HHH 1-592 (R-4) Et 5-MeO -0CH2 (l, 2 --Phy) CH2- (G64) MeO HHH 1-593 (R-4) Et 5-MeO -〇CH2 (l, 2-Phy) CHr (G67) MeO HHH 1-594 (R-4) Et 5 ~ Me0 -0CH2 (1,2-Phy) CHr (G70) MeO HHH 1-595 (R-4) Et 5-MeO -0CH2 (1,2-Phy) CHr (G71) MeO HHH 1-596 (R-4) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G73) MeO HHH 1-597 (R-4) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G76) MeO HHH 1-598 ( R-4) Et 5-NH2 -0CH2 (1, 2-Phy) CHr (G76) MeO HHH 1-599 (R-4) Et 5-NHMe -0CH2 (1, 2-Phy) CHr (G76) MeO HHH 1-600 (R-4) Et 5-N (Me): 2 -0CH2 (1,2-Phy) CHr (G76) MeO HHH 1-601 (R-4) Et 5-MeO -0CH2 (1, 2 -Phy) CHr (G76) MeO HFH 1-602 (R-4) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G76) MeO H Me H 1-603 (R-4) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G76) MeO H MeO H 1-604 (R-4) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G77) MeO HHH 1-605 (R- 4) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G79) Me OHHH 1-606 (R-4) Et 5-MeO -0CH2 (1,2-Phy) CHr (G82) MeO HHH 1-607 (R-4) Et 5-MeO ~ 0CH2 (1,2-Phy) CHr (G85) MeO HHH 1-608 (R-4) Et 5-MeO -0CH2 (1,2-Phy) CHr (G86) MeO HHH 1-609 (R-4) Et 5-MeO -0CH2 (1,2 -Phy) CHr (G88) MeO HHH 1-610 (R-4) Et 5-MeO -0CH2 (1,2-Phy) CHr (G90) MeO HHH 1-611 (R-4) Et 5-MeO -0CH2 (1,2-Phy) CHr (G92) MeO HHH 1-612 (R-4) Pr 5-MeO -OCH2 (l, 2-Phy) CHr (Gl) MeO HHH 1-613 (R ~ 4) Pr 5 -MeO -0CH2 (1,2-Phy) CHr (G 3) MeO HHH 1-614 (R-4) Pr 5-MeO -0CH2 (1,2-Phy) CHr (G 6) MeO HHH-84- 200300349

1-615 (R ~ 4) Pr 5-MeO -〇CH2 (l, 2-Phy) CHr (G 8) MeO HHH 1-616 (R-4) Pr 5-MeO -〇CH2 (l, 2-Phy ) CHr (Gil) MeO HH, H 1-617 (R-4) Pr 5-MeO -〇CH2 (l, 2-Phy) CHr (G13) MeO HHH 1-618 (R-4) Pr 5-MeO- 〇CH2 (l, 2-Phy) CHr (G16) MeO HHH 1-619 (R-4) Pr 5-MeO -OCH2 (l, 2-Phy) CH2- (G18) MeO HHH 1-620 (R-4 ) Pr 5-MeO -OCH2 (l, 2-Phy) CH2- (G20) MeO HHH 1-621 (R-4) Pr 5-MeO -OCH2 (l, 2-Phy) CHr (G22) MeO HHH 1- 622 (R-4) Pr 5-MeO -〇CH2 (l, 2 ~ Phy) CHr (G24) MeO HHH 1-623 (R-4) Pr 5-MeO -〇CH2 (l, 2-Phy) CHr ( G27) MeO HHH 1-624 (R-4) Pr 5-MeO-OCH2 (l, 2-Phy) CH2- (G29) MeO HHH 1-625 (R-4) Pr 5-MeO -OCH2 (l, 2 -Phy) CHr (G32) MeO HHH 1-626 (R-4) Pr 5-MeO -OCH2 (l, 2-Phy) CHr (G34) MeO HHH 1-627 (R-4) Pr 5-MeO -〇 CH2 (l, 2-Phy) CH2- (G37) MeO HH Ή 1-628 (R-4) Pr 5-MeO -0CH2 (1,2-Phy) CHr (G39) MeO HHH 1-629 (R-4 ) Pr 5-MeO -OCH2 (l, 2 -Phy) CH2- (G41) MeO HHH 1-630 (R_4) Pr 5-MeO -OCH2 (l, 2-Phy) CHr (G43) MeO HHH 1-631 ( R-4) Pr 5-MeO -OCH2 (l, 2-Phy) CHr (G45) MeO H HH 1-632 (R ~ 4) Pr 5-MeO -〇CH2 (l, 2-Phy) CHr (G59) MeO HHH 1-633. (R-4) Pr 5-MeO -〇CH2 (l, 2- Phy) CHr (G62) MeO HHH 1-634 (R-4) Pr 5-MeO -OCH2 (l, 2-Phy) CHr (G64) MeO HHH 1-635 (R-4) Pr 5-MeO -OCH2 ( l, 2-Phy) CHr (G67) MeO HHH 1-636 (R-4) Pr 5-MeO -OCH2 (l, 2-Phy) CHr (G70) MeO HHH 1-637 (R-4) Pr 5- MeO -〇CH2 (l, 2-Phy) CHr (G73) MeO HHH 1-638 (R-4) Pr 5-MeO -〇CH2 (l, 2-Phy) CHr (G76) MeO HHH 1-639 (R -4) Pr 5-NH2 -OCH2 (l, 2-Phy) CHr (G76) MeO HHH 1-640 (R-4) Pr 5-NHMe -OCH2 (l, 2-Phy) CHr (G76) MeO HHH- 85- 200300349

1-641 (R ~ 4) Pr 5-N (Me) 1-642 (R_4) Pr 5-MeO 1-643 (R_4) Pr 5-MeO 1-644 (R ~ 4) Pr 5-MeO 1-645 (R-4) Pr 5-MeO 1-646 (R-4) Pr 5-MeO 1-647 (R ~ 4) Pr 5-MeO 1-648 (R-4) Pr 5-MeO 1-649 (R -4) Pr 5-MeO 1-650 (R-4) Pr 5-MeO 1-651 (R-4) Pr 5-MeO 1-652 (R_4) Bu 5-MeO 1-653 (R-4) Bu 5-MeO 1-654 (R-4) Bu 5-MeO 1-655 (R-4) Bu 5-MeO 1-656 (R_4) Bu 5-MeO 1-657 (R-4) Bu 5-MeO 1 -658 (R-4) Bu 5-MeO 1-659 (R-4) Bu 5-MeO 1-660 (R-4) Bu 5-MeO 1-661 (R-4) Bu 5-MeO 1-662 (R-4) Bu 5-MeO 1-663 (R-4) Bu 5-MeO 1-664 (R-4) Bu 5-MeO 1-665 (R-4) Bu 5-MeO 1-666 (R -4) Bu 5-MeO -〇CH2 (l, 2-Phy) CHr -0CH2 (1,2-Phy) CHr -OCH2 (l, 2-Phy) CHr -0CH2 (1,2-Phy) CHr -0CH2 (1,2-Phy) CHr -0CH2 (1,2-Phy) CHr -0CH2 (1,2-Phy) CHr -0CH2 (1, 2-Phy) CHr -〇CH2 (l, 2-Phy) CHr- 0CH2 (1, 2-Phy) CHr -0CH2 (1, 2-Phy) CHr -0CH2 (1, 2-Phy) CHr -0CH2 (1, 2-Phy) CHr -0CH2 (1, 2-Phy) CHr- 0CH2 (1, 2-Phy) CHr -0CH2 (1, 2-Phy) CHr -0CH2 (1, 2-Phy) CHr -0CH2 (1, 2-Phy) CHr -0CH2 (1, 2-Phy) CHr- 0CH2 (1, 2-Phy) CHr -0CH2 (1,2-Phy) CHr -0CH2 (1, 2-Phy) CHr -0CH2 (1, 2-Phy) CHr -0CH2 (1, 2-Phy) CHr -0CH2 (1,2-Phy) CHr -0CH2 (1,2-Phy) CHr

(G76) MeO HHH (G76) MeO HFH (G76) MeO H Me H (G76) MeO H MeO H (G77) MeO HHH (G79) MeO HHH (G82) MeO HHH (G85). MeO HHH (G88) MeO HHH (G90) MeO HHH (G92) MeO HHH (Gl) MeO HHH (G 3) MeO HHH (G 6) MeO HHH (G 8) MeO HHH (Gil) MeO H H. H (G13) MeO HHH (G16) MeO HHH (G18) MeO HHH (G20) MeO HHH (G22) MeO HHH (G24) MeO HHH (G27) MeO HHH (G29) MeO HHH (G32) MeO HHH (G34) MeO HHH -86- 200300349

1-667 (R-4) Bu 5-MeO -0CH2 (1,2-Phy) CH2- (G37) MeO HHH 1-668 (R-4) Bu 5-MeO -〇CH2 (l, 2-Phy) CHr (G39) MeO HHH 1-669 (R-4) Bu 5-MeO -OCH2 (l, 2-Phy) CHr (G41) MeO HHH 1-670 (R-4) Bu 5-MeO -〇CH2 (l , 2-Phy) CHr (G43) MeO HHH 1-671 (R-4) Bu 5-MeO -0CH2 (1,2-Phy) CHr (G45) MeO HHH 1-672 (R-4) Bu 5-MeO -OCH2 (l, 2-Phy) CHr (G59) MeO HHH 1-673 (R-4) Bu 5-MeO -0CH2 (1,2-Phy) CHr (G62) MeO HHH 1-674. (R-4 ) Bu 5-MeO -0CH2 (1,2-Phy) CHr (G64) MeO HHH Bu. 675 (R-4) Bu 5-MeO -0CH2 (l, 2-Phy) CHr (G67) MeO HHH 1-676 (R-4) Bu 5-MeO -0CH2 (1,2-Phy) CHr (G70) MeO HHH 1-677 (R-4) Bu 5-MeO -0CH2 (1,2-Phy) CHr (G73) MeO HHH 1-678 (R-4) Bu 5-MeO -0CH2 (1,2-Phy) CHr (G76) MeO HHH 1-679 (R-4) Bu 5-NH2 -OCH2 (l, 2-Phy) CHr (G76) MeO HHH 1-680 (R-4) Bu 5-NHMe -0CH2 (1,2-Phy) CHr (G76) MeO HHH 1-681 (R-4) Bu 5-N (Me): 2- 〇CH2 (l, 2-Phy) CH2- (G76) MeO HHH 1-682 (R-4) Bu 5-MeO -OCH2 (l, 2-Phy) CHr (G76) MeO HFH 1-683 (R-4 ) Bu 5-MeO-OCH2 (l, 2-Phy) CH2- (G76) MeO H Me H 1-684 (R-4) Bu 5-MeO -OCH2 (l, 2-Phy) CHr (G76) MeO H MeO H 1-685 (R-4) Bn 5-MeO -0CH2 (1,2-Phy) CHr (G77) MeO HHH 1-686 (R-4) Bu 5-MeO -OCH2 (l, 2-Phy) CHr (G79) MeO HHH 1-687 (R-4) Bu 5-MeO -0CH2 (1, 2-Phy) CHr (G82) MeO HHH 1-688 (R-4) Bu 5-MeO-OCH2 (l, 2-Phy) CH2- (G85) MeO HHH 1-689 (R-4) Bu 5-MeO -0CH2 (1,2-Phy) CHr (G88) MeO HHH 1-690 (R-4) Bu 5-MeO -OCH2 (l, 2, y) CH2- (G90) MeO HHH 1-691 (R-4 ) Bu 5-MeO -OCH2 (l, 2-Phy) CH2- (G92) MeO HHH 1-692 (R ~ 4) All 5-MeO -0CH2 (1,2-Phy) CHr (Gl) MeO HHH -87 -200300349 1-693 1-694 1-695 1-696 1-697 1-698 1-699 1-700 1-701 1-702 1-703 1-704 1-705 1-706 1-707 Bu 708 1 -709 1-710 1-711 1-712 '1-713 1-714 1-715 1-716 1-717 1-718

(R ~ 4) All 5-MeO -0CH2 (1,2-Phy) CHr (G 3) MeO HHH (R ~ 4) All 5-MeO -0CH2 (1,2-Phy) CHr (G 6) MeO HHH (R-4) All 5-MeO -0CH2 (1,2-Phy) CHr (G 8) MeO HHH (R-4) All 5-MeO -0CH2 (1,2-Phy) CHr (Gil) MeO HHH ( R-4) All 5-MeO -0CH2 (1,2-Phy) CHr (G13) MeO HHH (R-4) All 5-MeO -0CH2 (1, 2-Phy) CHr (G16) MeO HHH (R- 4) All 5-MeO -0CH2 (1,2-Phy) CHr (G18) MeO HHH (R ~ 4) All 5-MeO -0GH2 (1,2-Phy) CHr (G20) MeO HHH (R-4) All 5-MeO -0CH2 (1, 2-Phy) CH2- (G22) MeO HHH (R_4) All 5-MeO -0CH2 (1, 2-Phy) CH2- (G24) MeO HHH (R-4) All 5 -MeO-0CH2 (1, 2-Phy) CH2- (G27) MeO HHH (R-4) All 5-MeO -0CH2 (1, 2-Phy) CHr (G29) MeO HHH (R_4) All 5-MeO- 0CH2 (1,2-Phy) CHr (G32) MeO HHH (R-4) All 5-MeO -0CH2 (1, 2-Phy) CH2- (G34) MeO HHH (R-4) All 5-MeO -0CH2 (1, 2-Phy) CH2- (G37) MeO HHH (R-4) All 5-MeO -0CH2 (1,2-Phy) CH2- (G39) MeO HHH (R-4) All 5-MeO -0CH2 (1, 2-Phy) CHr (G41) MeO HHH (R-4) All 5-MeO -0CH2 (1, 2-Phy) CHr (G43) MeO HHH (R-4) All 5-MeO -0CH2 (1 , 2-Phy) CH2- (G45) MeO HHH (R_4) All 5-MeO -0CH2 (1,2-Phy) CHr (G59) MeO HHH (R-4) All 5-MeO -0CH2 (1, 2-Phy) CHr (G62) MeO HHH (R -4) All 5-MeO -0CH2 (1,2-Phy) CHr (G64) MeO HHH (R-4) All 5-MeO -0CH2 (1,2-Phy) CHr (G67) MeO HHH (R-4 ) All 5-MeO -0CH2 (1,2-Phy) CHr (G70) MeO HHH (R-4) All 5-MeO -0CH2 (1,2-Phy) CHr (G73) MeO HHH (R-4) All 5-MeO -0CH2 (1, 2-Phy) CHr (G76) MeO HHH 耆

-88- 200300349

1-719 (R-4) All 5-NH2 -OCH2 (l, 2-Phy) CHr (G76) MeO HHH 1-720 (R-4) All 5-NHMe -OCH2 (l, 2-Phy) CHr ( G76) MeO HHH 1-721 (R-4) All 5-N (Me).: -0CH2 (l, 2-Phy) CHr (G76) MeO HHH 1-722 (R-4) All 5-MeO -OCH2 (l, 2-Phy) CH2- (G76) MeO HFH 1-723 (R-4) All 5-MeO -OCH2 (l, 2-Phy) CHr (G76) MeO H Me H 1-724 (R-4 ) All 5-MeO-OCH2 (l, 2-Phy) CH2- (G76) MeO H MeO H 1-725 (R-4) All 5-MeO -OCH2 (l, 2-Phy) CH2- (G77) MeO HHH 1-726 (R-4) All 5-MeO -OCH2 (l, 2-Phy) CH2- (G79) MeO HHH 1-727 (R-4) All 5-MeO -OCH2 (l, 2-Phy) CH2- (G82) MeO HHH 1-728 (R-4) All 5-MeO -OCH2 (l, 2-Phy) CHr (G85) MeO HHH 1-729 (R-4) All 5-MeO -OCH2 (l , 2-Phy) CH2- (G88) MeO HHH 1-730 (R-4) All 5 ~ Me0 -OCH2 (l, 2-Phy) CH2- (G90) MeO HHH 1-731 (R-4) All 5 -MeO -OCH2 (l, 2-Phy) CHr (G92) MeO HHH 1-732 (R-4) Prp 5-MeO -OCH2 (l, 2-Phy) CH2- (Gl) MeO HHH 1-733 (R -4) Prp 5-MeO -OCH2 (l, 2-Phy) CHr (G 3) MeO HHH 1-734 (R-4) Prp 5-MeO -〇CH2 (l, 2-Phy) CHr (G 6) MeO HHH 1-735 (R-4) Prp 5-MeO -OCH2 (l, 2-Phy) CH2- (G 8) MeO HHH 1-736 (R-4) Prp 5-MeO -OCH2 (l, 2-Phy) CHr (Gil) MeO HHH 1-737 (R-4) Prp 5-MeO -OCH2 (l, 2-Phy) CHr (G13) MeO HHH 1-738 (R-4) Prp 5-MeO -OCH2 (l, 2-Phy) CHr (G16) MeO HHH 1-739 (R-4) Prp 5-MeO -OCH2 (l, 2-Phy) CH2- (G18) MeO HHH 1-740 (R-4) Prp 5-MeO -OCH2 (l, 2-Phy) CH2- (G20) MeO HHH 1-741 (R-4) Prp 5- MeO -OCH2 (l, 2-Phy) CHr (G22) MeO HHH Bu 742 (R-4) Prp 5-MeO -0CH2 (1,2-Phy) CHr (G24) MeO HHH 1-743 (R-4) Prp 5-MeO -OCH2 (l, 2-Phy) CHr (G27) MeO HHH 1-744 (R-4) Prp 5-MeO -〇CH2 (l, 2-Phy) CHr (G29) MeO HHH 耆

-89- 200300349 1-745 1-746 1-747 1-748 1-749 1-750 1-751 1-752 1-753 1-754 1-755 1-756 1-757 1-758 1-759 1 -760 1-761 1-762 1-763 1-764 1-765 1-766 1-767 1-768 1-769 1-770

(R-4) Prp 5-MeO -0CH2 (1,2 ~ Phy) CH2 ~ (G32) MeO HHH (R-4) Prp 5-MeO -0CH2 (1,2-Phy) CHr (G34) MeO HHH ( R-4) Prp 5-MeO -0CH2 (1,2-Phy) CHr (G37) MeO HHH (R-4) Prp 5-MeO -〇CH2 (l, 2-Phy) CHr (G39) MeO HHH (R -4) Prp 5-MeO -0CH2 (1,2-Phy) CHr (G41) MeO HHH (R_4) Prp 5-MeO -0CH2 (1, 2-Phy) CHr (G43) MeO HHH (R-4) Prp 5-MeO -0CH2 (1,2-Phy) CHr (G45) MeO HHH (R-4) Prp 5-MeO -0CH2 (1, 2-Phy) CHr (G59) MeO HHH (R-4) Prp 5- MeO -0CH2 (1, 2-Phy) CHr (G62) MeO HHH (R-4) Prp 5-MeO -0CH2 (1, 2-Phy) CHr (G64) MeO HHH (R-4) Prp 5-MeO- 0CH2 (1, 2-Phy) CHr. (G67) MeO HHH (R-4) Prp 5-MeO -0CH2 (1, 2-Phy) CHr (G70) MeO HHH (R-4) Prp 5-MeO -0CH2 (1, 2-Phy) CHr (G73) MeO HHH (R-4) Prp 5-MeO -0CH2 (1, 2-Phy) CHr (G76) MeO HHH (R ~ 4) Prp 5-NH2 -0CH2 (1 , 2-Phy) CHr (G76) MeO HHH (R_4) Prp 5-NHMe -0CH2 (1, 2-Phy) CHr (G76) MeO HHH (R-4) Prp 5-N (Me) 2 -0CH2 (1 , 2-Phy) CH2- (G76) MeO HHH (R-4) Prp 5-MeO -0CH2 (1, 2-Phy) CHr (G76) MeO HFH (R-4) Prp 5-MeO -0CH2 (1 , 2-Phy) CHr (G76) MeO H Me H (R-4) Prp 5-MeO -0CH2 (1, 2-Phy) CHr (G76) MeO H MeO H (R_4) Prp 5-MeO -0CH2 (1, 2-Phy) CHr (G77) MeO HHH (R_4) Prp 5-MeO -0CH2 (1? 2-Phy) CHr (G79) MeO HHH (R_4) Prp 5-MeO -0CH2 (1, 2-Phy) CHr (G82) MeO HHH (R_4) Prp 5-MeO -0CH2 (15 2-Phy) CHr (G85) MeO HHH (R-4) Prp 5-MeO -0CH2 (1,2-Phy) CHr (G88) MeO HHH (R-4) Prp 5-MeO -0CH2 (1,2-Phy) CHr (G90) MeO HHH

-90- 200300349

1-771 (R-4) Prp 5-MeO -〇CH2 (l, 2-Phy) CHr (G92) MeO HHH 1-772 (R-4) Et 5-MeO -0CH2 (1,4-Phy) CHr (Gl) MeO HHH 1-773 (R-4) Et 5-MeO -0CH2 (l, 4-PhV) CHr (G 3) MeO HHH 1-774 (R_4) Et 5-MeO -0CH2 (1,4- Phy) CHr (G 6) MeO HHH 1-775 (R-4) Et 5-MeO -0CH2 (1,4-Phy) CHr (G 8) MeO HHH 1-776 (R ~ 4) Et 5-MeO- 0CH2 (1,4-Phy) CHr (Gil) MeO HHH 1-777 (R-4) Et 5-MeO -0CH2 (1,4-Phy) CHr (G13) MeO HHH 1-778 (R-4) Et 5-MeO -0CH2 (l, 4-Phy) CHr (G16) MeO HHH 1-779 (R-4) Et 5-MeO -0CH2 (1,4-Phy) CHr (G18) MeO HHH 1-780 (R -4) Et 5-MeO -0CH2 (1,4-Phy) CHr (G20) MeO HHH 1-781 (R-4) Et 5-MeO-0CH2 (1,4-Phy) CH2- (G22) MeO HHH 1-782 (R-4) Et 5-MeO -0CH2 (1,4-Phy) CHr (G24) MeO HHH 1-783 (R-4) Et 5-MeO -0CH2 (1,4-Phy) CHr ( G27) MeO HHH 1-784 (R-4) Et 5-MeO -0CH2 (1,4-Phy) CH2- (G29) MeO HHH 1-785 (R-4) Et 5-MeO -0CH2 (l, 24Phy ) CHr (G32) MeO HHH 1-786 (R-4) Et 5-MeO -0CH2 (1,4-Phy) CHr (G34) MeO HHH 1-787 (R-4) Et 5-MeO -0CH2 (1 , 4-Phy) CH2- (G37) MeO HHH 1-788 (R-4) E t 5-MeO -0CH2 (l, 4 ~ Phy) CHr (G39) MeO HHH 1-789 (R-4) Et 5-MeO -0CH2 (1,4-Phy) CHr (G41) MeO HHH 1-790 ( R-4) Et 5-MeO -0CH2 (1,4-Phy) CHr (G43) MeO HHH 1-791 (R-4) Et 5-MeO -0CH2 (1,4-Phy) CHr (G45) MeO HHH 1-792 (R ~ 4) Et 5-MeO -0CH2 (l, 4-Phy) CHr (G59) MeO HHH 1-793 (R ~ 4) Et 5-MeO -0CH2 (1,4-Phy) CHr ( G62) MeO HHH 1-794 (R-4) Et 5-MeO -0CH2 (1,4-Phy) CHr (G64) MeO HHH 1-795 (R ~ 4) Et 5-MeO -0CH2 (l, 4- Phy > CHr (G67) MeO HHH 1-796 (R-4) Et 5-MeO -0CH2 (1,4-Phy) CHr (G86) MeO HHH -91- 200300349

1-797 (R-4) Et 5-MeO 1-798 (R-4) Et 5-MeO 1-799 (R-4) Et 5-MeO 1 ~ 8 0 0 (R-4) Et 5-NH2 1-801 (R-4) Et 5-NHMe 1-802 (R-4) Et 5-N (Me) 1-803 (R-4) Et 5-MeO 1-804 (R-4) Et 5- MeO 1-805 (R-4) Et 5-MeO 1-806 (R-4) Et 5-MeO 1-807 (R-4) Et 5-MeO 1-808 (R-4) Et 5-MeO 1 -809 (R-4) Et 5-MeO 1-810 (R-4) Et 5-MeO 1-811 (R-4) Et 5-MeO 1-812 (R-4) Et 5-MeO 1-813 (R-4) Me 5-MeO 1-814 (R-4) Me 5-MeO 1-815 (R-4) Me 5-MeO 1-816 (R-4) Me 5-MeO 1-817 (R -4) Me 5-MeO 1-818 (R-4) Me 5-MeO 1-819 (R ~ 4) Et 5-MeO 1-820 (R-4) Et 5-MeO 1-821 (R ~ 4 ) Et 5-MeO 1-822 (R-4) Et 5-MeO -0CH2 (1,4-Phy) CHr -0CH2 (1,4-Phy) CHr -0CH2 (1,4-Phy) CHr -0CH2 ( 1,4-Phy) CHr -0CH2 (l, 4 ~ Phy) CHr: -0CH2 (l, 4-Phy) CHr -0CH2 (1,4-Phy) CHr -0CH2 (1,4-Phy) CHr -0CH2 (1,4-Phy) CHr -0CH2 (1,4-Phy) CHr -0CH2 (1,4-Phy) CHr -0CH2 (1,4-Phy) CHr -0CH2 (1,4-Phy) CHr -0CH2 (1,4-Phy) CH2--0CH2 (1,4-Phy) CHr -0CH2 (l, 4 ~ Phy) CHr -0 (CH2) 2 (1,2-Phy) CHr -0 (CH2) 2 ( 1,2-Phy) CHr -0 (CH2) 2 (1,2-Phy) CHr -0 (CH2) 2 (l, 2 ~ Phy) CHr -0 (CH2) 2 (1,2-Phy) CH r -0 (CH2) 2 (1,2-Phy) CHr -0 (CH2) 2 (1,2-Phy) CHr -0 (CH2) 2 (1,2-Phy) CHr -0 (CH2) 2 ( 1,2-Phy) CHr -0 (CH2) 2 (1,2-Phy) CHr

(G70) MeO HHH (G73) MeO HHH (G76) MeO HHH (G76) MeO HHH (G76) MeO HHH (G76) MeO HHH (G76) MeO HFH (G76) MeO H Me H (G76) MeO H MeO H ( G77) MeO HHH (G79) MeO HHH (G82) MeO HHH (G85) MeO HHH (G88) MeO HHH (G90) MeO HHH (G92) MeO HHH (G 3) MeO HHH (G13) MeO HHH (G64) MeO HHH (G73) MeO HHH (G76) MeO HHH (G82) MeO HHH (G 3) MeO HHH (G13) MeO HHH (G64) MeO HHH (G73) MeO HHH 200300349

1-823 (R-4) Et 5-MeO -〇 (CH2) 2 (l, 2-Phy) CHr (G76) MeO 1-824 (R-4) Et 5-MeO -0 (CH2) 2 (1 , 2-Phy) CHr (G82) MeO 1-825 (R-4) Et 5-MeO -CH20CH2 (1,2-Phy) CHr (G 3) MeO 1-826 (R-4) Et 5-MeO- CH2OCH2 (l, 2-Phy) CH2- (G 8) MeO 1-827 (R-4) Et 5-MeO -CH20CH2 (1,2-Phy) CHr (G13) MeO 1-828 (R-4) Et 5-MeO -CH2OCH2 (l, 2-Phy) CHr (G24) MeO 1-829 (R-4) Et 5-MeO -CH2OCH2 (l, 2-Phy) CHr (G34) MeO 1-830 (R-4 ) Et 5-MeO -CH20CH2 (1,2-Phy) CH2- (G64) MeO 1-831 (R-4) Et 5-MeO -CH20CH2 (1,2-Phy) CH2- (G73) MeO 1-832 (R-4) Et 5-MeO ~ CH20CH2 (1,2-Phy) CHr (G76) MeO 1-833 (R-4) Et 5-MeO -CH2OCH2 (l, 2-Phy) CHr (G79) MeO 1 -834 (R-4) Et 5-MeO -CH2OCH2 (l, 2-Phy) CHr (G82) MeO 1-835 (R-4) Et 5-MeO -SCH2 (1,2-Phy) CHr (G 3 ) MeO 1-836 (R-4) Et 5-MeO -SCH2 (1,2-Phy) CHr (G 8) MeO 1-837 (R-4) Et 5-MeO -SCH2 (1,2-Phy) CHr (G13) MeO 1-838 (R-4) Et 5-MeO -SCH2 (1,2-Phy) CHr (G24) MeO 1-839 (R-4) Et 5-MeO -SCH2 (1,2- Phy) CHr (G34) MeO 1-840 (R-4) Et 5-MeO -SCH2 (1,2-Phy) CHr (G64) MeO 1-841 (R_4) Et 5-MeO -SCH2 (1,2- Ph y) CHr (G73) MeO 1-842 (R-4) Et 5-MeO -SCH2 (1,2-Phy) CHr (G76) MeO 1-843 (R-4) Et 5-MeO -SCH2 (1, 2-Phy) CHr (G79) MeO 1-844 (R-4) Et 5-MeO -SCH2 (1,2-Phy) CHr (G82) MeO 1-845 (R-5) Me 5-MeO -OCH2 ( l, 2-Phy) CHr (G 3) MeO 1-846 (R-5) Me 5-MeO -OCH2 (l, 2-Phy) CHr (G13) MeO 1-847 (R-5) Me 5-MeO -〇CH2 (l, 2-Phy) CHr (G64) MeO 1-848 (R-5) Me 5-MeO -〇CH2 (l, 2-Phy) CHr (G73) MeO 200300349

1-849 (R-5) Me 5-MeO -〇CH2 (l, 2-Phy) CHr (G76) MeO HHH 1-850 (R-5) Me 5-MeO -0CH2 (1, 2-Phy) CHr (G82) MeO HHH 1-851 (R-5) Et 5-MeO -0CH2 (1,2-Phy) CHr (G 3) MeO HHH 1-852 (R-5) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G 8) MeO HHH 1-853 (R-5) Et 5-MeO -0CH2 (1; 2-Phy) CHr (G13) MeO HHH 1-854 (R-5) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G24) MeO HHH 1-855 (R-5) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G34) MeO HHH 1-856 (R-5) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G64) MeO HHH 1-857 (R-5) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G73) MeO HHH 1-858 ( R-5) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G76) MeO HHH 1-859 (R-5) Et 5-MeO -〇CH2 (l, 2 ~ Phy) CHr (G82) MeO HHH 1-860 (R-6) Me 5-MeO -0CH2 (1, 2-Phy) CHr (G 3) MeO HH tH 1-861 (R-6) Me 5-MeO -0CH2 (1, 2-Phy ) CHr (G13) MeO HHH 1-862 (R-6) Me 5-MeO -0CH2 (1, 2-Phy) CHr (G64) MeO HHH 1-863 (R-6) Me 5-MeO -0CH2 (1 , 2-Phy) CHr (G73) MeO HHH 1-864 (R-6) Me 5-MeO -0CH2 (1, 2-Phy) CHr (G76) MeO HHH 1-865 (R-6) Me 5-MeO -0CH2 (1, 2-Phy) CHr (G82) MeO HHH 1-866 (R-6) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G 3) MeO HHH 1-867 (R-6) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G 8) MeO HHH 1- 868 (R-6) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G13) MeO HHH 1-869 (R-6) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G24) MeO HHH 1-870 (R-6) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G34) MeO HHH 1-871 (R-6) Et 5-MeO -0CH2 (1,2-Phy) CHr (G64) MeO HHH 1-872 (R-6) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G73) MeO HHH 1-873 (R_6) Et 5-MeO -0CH2 (1, 2- Phy) CHr (G76) MeO HHH 1-874 (R-6) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G82) MeO HHH -94- 200300349

1-875 (R-7) Me 5-MeO -〇CH2 (l, 2-Phy) CHr (G 3) MeO HHH 1-876 (R-7) Me 5-MeO -0CH2 (1, 2-Phy) CHr (G13) MeO HHH 1-877 (R-7) Me 5-MeO -〇CH2 (l, 2-Phy) CHr (G64) MeO HHH 1-878 (R-7) Me 5-MeO -0CH2 (1 , 2-Phy) CHr (G73) MeO HHH 1-879 (R-7) Me 5-MeO -0CH2 (1, 2-Phy) CHr (G76) MeO HHH 1-880 (R-7) Me 5-MeO -0CH2 (1,2-Phy) CHr (G82) MeO HHH 1-881 (R-7) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G 3) MeO HHH 1-882 (R-7 ) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G 8) MeO HHH 1-883 (R-7) Et 5-MeO -0CH2 (1,2-Phy) CHr (G13) MeO HHH 1- 884 (R-7) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G24) MeO HHH 1-885 (R-7) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G34) MeO HHH 1-886 (R-7) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G64) MeO HHH 1-887 (R-7) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G73) MeO HHH 1-888 (R-7) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G76) .MeO • HHH 1-889 (R-7) Et 5-MeO -0CH2 ( 1, 2-Phy) CHr (G79) MeO HHH 1-890 (R-7) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G82) MeO HHH 1-891 (R-8) Me 5- MeO -0CH2 (1, 2-Phy) CH2- (G 3) MeO HHH 1-892 (R- 8) Me 5-MeO -0CH2 (1, 2-Phy) CHr (G13) MeO HHH 1-893 (R-8) Me 5-MeO -0CH2 (1,2-Phy) CHr (G64) MeO HHH 1- 894 (R-8) Me 5-MeO -0CH2 (1,2-Phy) CHr (G73) MeO HHH 1-895 (R-8) Me 5-MeO -0CH2 (1,2-Phy) CHr (G76) MeO HHH 1-896 (R-8) Me 5-MeO -0CH2 (1,2-Phy) CHr (G82) MeO HHH 1-897 (R-8) Et 5-MeO -0CH2 (1,2-Phy) CHr (G 3) MeO HHH 1-898 (R-8) Et 5-MeO -0CH2 (1,2-Phy) CHr (G 8) MeO HHH 1-899 (R-8) Et 5-MeO -0CH2 ( 1,2-Phy) CHr (G13) MeO HHH 1-900 (R ~ 8) Et 5-MeO -0CH2 (1,2-Phy) CHr (G24) MeO HHH -95- 200300349

1-901 (R-8) Et 5-MeO -0CH2 (l, 2-Phy) CH2- (G34) MeO HHH 1-902 (R-8) Et 5 ~ Me0 -0CH2 (1,2-Phy) CHr (G64) MeO HHH 1-903 (R-8) Et 5-MeO -〇CH2 (l, 2-Phy) CHr (G73) MeO HHH 1-904 (R-8) Et 5-MeO -〇CH2 (l , 2-Phy) CHr (G76) MeO HHH 1-905 (R-8) Et 5-MeO -〇CH2 (l, 2-Phy) CHr (G82) MeO HHH 1-906 (R- 9) Me 5- MeO -〇CH2 (l, 2-Phy) CHr (G 3) MeO HHH 1-907 (R-9) Me 5-MeO -OCH2 (l, 2-Phy) CHr (G13) MeO HHH 1-908 (R -9) Me 5-MeO -0CH2 (1,2-Phy) CH2- (G64) MeO HHH 1-909 (R-9) Me 5-MeO -〇CH2 (l, 2 ~ Phy) CHr (G73) MeO HHH 1-910 (R-9) Me 5-MeO -0CH2 (1,2-Phy) CHr (G76) MeO HHH 1-911 (R-9) Me 5-MeO -OCH2 (l, 2-Phy) CHr (G82) MeO HHH 1-912 (R-9) Et 5-MeO -0CH2 (1,2-Phy) CHr (G 3) MeO HHH 1-913 (R-9) Et 5-MeO -〇CH2 (l , 2-Phy) CHr (G 8) MeO HHH 1-914 (R-9) Et 5-MeO -OCH2 (l, 2-Phy) CHr (G13) MeO HHH 1-915 (R-9) Et 5- MeO -〇CH2 (l, 2-Phy) CHr (G24) MeO HHH 1-916 (R-9) Et 5-MeO -OCH2 (l, 2-Phy) CHr (G34) MeO HHH 1-917 (R- 9) Et 5-MeO -〇CH2 (l, 2-Phy) CHr (G64) MeO HHH 1 -918 (R-9) Et 5-MeO -0CH2 (1,2-Phy) CHr (G73) MeO HHH 1-919 (R-9) Et 5-MeO -0CH2 (1,2-Phy) CHr (G76) MeO HHH 1-920 (R-9) Et 5-MeO -0CH2 (1,2-Phy) CHr (G82) MeO HHH 1-921 (R-10) Me 5-MeO -〇CH2 (l, 2-Phy) CHr (G 3) MeO HHH 1-922 (R-10) Me 5-MeO -0CH2 (1,2-Phy) CHr (G13) MeO HHH 1-923 (R-10) Me 5-MeO -0CH2 (1 , 2-Phy) CHr (G64) MeO HHH 1-924 (R-10) Me 5-MeO -0CH2 (1,2-Phy) CHr (G73) MeO HHH 1-925 (R-10) Me 5-MeO -〇CH2 (l, 2-Phy) CHr (G76) MeO HHH 926 (R-10) Me 5-MeO -〇CH2 (l, 2-Phy) CHr (G82) MeO HHH -96- 200300349 bu 927 bu 928 1-929 1-930 1-931 1-932 1-933 1-934 1-935 Bu 936

(R-10) Et 5-MeO -0CH2 (1,2-Phy) CHr (G 3) MeO HHH (R-10) Et 5-MeO -0CH2 (l, 2-Phy) CH2- (G 8) MeO HHH (R-10) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G13) MeO HHH (R -10) Et 5-MeO -0CH2 (1,2-Phy) CH2- (G24) MeO HHH (R-10) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G34) MeO HHH (R -10) Et 5-Me0 -0CH2 (1, 2-Phy) CHr (G64) MeO HHH (R -10) Et 5-MeO -0CH2 (-1, 2-Phy) CHr (G73) MeO HHH (R-10) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G76) MeO HHH (R- 10) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G82) MeO HHH (R-4) Et 5-MeO -0CH2 (1, 2-Phy) CHr (G68) MeO HHH -97- 200300349

Compd. R1 R2 Αη-A-D-E--(Gn +) (Γ) n R4 R6 .R7, No. substituent No. substituent No.

2-1 (Rl) Et 3,5-diMeO-Ph-〇 (CH2) r (G14) HHH 2-2 (R-1) Et 3,5-diMeQ-Ph -〇 (ch2) 6- (G50) HHH 2-3 (Rl) Et 3,5-diMeO-Ph -o (ch2) 6- (G54) HHH 2-4 (R-1) Et 3,5-diMeO-Ph -〇 (ch2) 6- ( G65) HHH 2-5 (Rl) Et 3,5-diMeO-Ph -0 (CH2) 6- (G74) HHH 2-6 (R ~ l) Et 3,5-diMeO-Ph -0 (CH2) 6 -(G77) HHH 2-7 (R-3) Et 3,5-diMeO-Ph-0 (CH2) 6- (G14) HHH 2-8 (R-3) Et 3,5-diMeO-Ph -0 (CH2) 6- (G50) HHH 2-9 (R-3) Et 3,5-diMeO-Ph -o (ch2) 6- (G54) HHH 2-10 (R-3) Et 3,5-diMeO -Ph -o (ch2) 6- (G65) HHH 2-11 (R-3) Et 3,5-diMeO-Ph -0 (CH2) 6- (G74) HHH 2-12 (R-3) Et 3 , 5-diMe〇-Ph -0 (CH2) 6- (G77) HHH 2-13 (R-4) Et 3,5-diMeO-Ph -〇CHr (G47) HHH 2-14 (R-4) Et 3,5-diMeO-Ph -〇CH2- (G48) HHH 2-15 (R-4) .Et 3,5-diMeO-Ph -OCHr (G49) HHH 2-16 (R-4) Et 3,5 -diMeO-Ph -〇CHr (G50) HHH 2-17 (R-4) Et 3,5-diMeO-Ph -〇CHr (G53) HHH -98- 200300349

2-18 (R ~ 4) Et 3,5-diMeO-Ph -〇CHr (G54) HHH 2-19 (R-4) Et 3,5-diMeO-Ph -〇CHr (G57) HHH 2-20 ( R-4) Et 3,5 ~ diMe〇-Ph ~ 0CH2_ (G58) HHH 2-21 (R-4) Et 3? 5-diMe〇-Ph -o (CH2) 2- (G14) HHH 2-22 (R-4) Et 3,5-diMeO-Ph -〇 (ch2) 2- (G50) HHH 2-23 (R_4) Et 3,5-diMe〇-Ph -〇 (ch2) 2- (G54) HHH 2-24 (R ~ 4) Et 3,5-diMeO-Ph -o (CH2) 2- (G65) HHH 2-25 (R-4) Et 3,5-diMeO-Ph -〇 (ch2) 2- (G74) HHH 2-26 (R-4) Et 3,5-diMeO-Ph -0 (CH2) 2-(G77) HHH 2-27 (R-4) Et 3,5-diMeO-Ph -0 ( CH2) 3- (G14) HHH 2-28 (R ~ 4) Et 3,5-diMeO-Ph -〇 (CH2) 3- (G50) HHH 2-29 (R-4) Et 3,5-diMeO- Ph-0 (CH2) 3-(G54) HHH 2-30 (R-4) Et 3,5-diMeO-Ph -〇 (CH2) 3- (G65) HHH 2-31 (R_4) Et 3,5- diMeO-Ph-0 (ch2) 3-(G74) HHH 2-32 (R-4) Et 3,5-diMeO-Ph -0 (CH2) 3- (G77) HHH 2-33 (R-4) Et 3,5-diMeO-Ph -o (ch2) 4-(G14) HHH 2-34 (R-4) Et 3,5-diMeO-Ph -〇 (CH2) 4-(G50) HHH 2-35 (R -4) Et 3,5-diMeO-Ph _0 (CH2) 4- (G54) HHH 2-36 (R-4) Et 3,5-diMeO-Ph -o (ch2) 4- (G65) HHH 2- 37 (R ~ 4) Et 3, 5-diMeO-Ph -〇 (CH2) r (G74) HHH 2-38 (R ~ 4) Et 3,5-diMeO-Ph -o (ch2) 4- (G77) HHH 2-39 (R-4) Et 3,5-diMeO-Ph -0 (ch2) 5- (G14) HHH 2-40 (R_4) Et 3,5-diMe〇-Ph-o (ch2) 「(G50) HHH 2-41 (R_4) Et 3,5-diMeO-Ph -0 (CH2) 5- (G54) HHH 2-42 (R-4) Et 3,5-diMeO-Ph -0 (CH2), (G65) HHH 2-43 (R -4) Et 3,5-diMeO-Ph-o (ch2) 「(G74) HHH -99- 200300349

2-44 (R-4) Et 3, 5-diMe〇-Ph -0 (CH2) 5- (G78) HHH 2-45 (R-4) Me 3, 5-diMe〇-Ph -0 (CH2) 6- (G15) HHH 2-46 (R_4) Me 3, 5-diMeO-Ph -〇 (CH2) 6-(G75) HHH 2-47 (R ~ 4) Me 3,5-diMe〇-Ph -〇 (ch2) 6- (G78) HHH 2-48 (R-4) Et 3,5-diMe〇-Ph -〇 (ch2) 6- (G5) HHH 2-49 (R-4) Et 3,5- diMe〇-Ph -〇 (ch2) 6- (G10) HHH 2-50 (R-4) Et 3,5-diMe〇-Ph -〇 (ch2) 6- (G15) HHH 2-51 (R-4 ) Et 3,5-diMeO-Ph -0 (ch2) 6- (G26) HHH 2-52 (R-4) Et 3,5-diMe〇-Ph -〇 (ch2) 6-(G39) HHH 2- 53 (R-4) Et 3,5-diMeO-Ph -〇 (CH2) 6- (G31) HHH 2-54 (R ~ 4) Et 3,5-diMeO-Ph -〇 (CH2) r (G36) HHH 2-55 (R ~ 4) Et 3,5-diMeO-Ph -0 (CH2) 6- (G50) HHH 2-56 (R-4) Et 3,5-diMeO-Ph -〇 (CH2) 6 -(G54) HHH 2-57 (R-4) Et 3,5-diMeO-Ph -0 (ch2) 6- (G58) HHH 2-58 (R-4) Et 3,5-diMeO-Ph -〇 (ch2) 6_ (G61) HHH 2-59 (R-4) Et 3,5-diMeO-Ph -0 (CH2) 6- (G66) HHH 2-60 (R-4) Et 3,5-diMeO- Ph -〇 (CH2) 6-. (G73) HHH 2-61 (R-4) Et 3,5-diMeO-Ph -0 (CH2) 6- (G75) HHH 2-62 (R-4) Et 3 , 5-diMeO-Ph -〇 (CH2) 6- (G76) HHH 2-63 (R-4) Et 3,5-diMeO-Ph -0 (CH2) 6- '(G78) HHH 2-64 (R-4) Et 3,5-diMeO-Ph -0 (CH2) 6- (G81) HHH 2-65 (R-4) Et 3,5-diMeO-Ph -o (ch2) 6- (G84) HHH 2-66 (R_4) Et 、 3,5- diMe〇-Ph -0 (ch2) 6- (G86) HHH 2-67 (R ~ 4) Et 3,5-diMeO-Ph -0 (ch2) 6- (G87) HHH 2-68 (R-4) Pr 3,5-diMeO-Ph -0 (CH2) 6- (G15) HHH 2-69 (R-4) Pr 3,5-diMeO-Ph-〇 (CH2) 6-(G75) HHH -100- 200300349

2-70 (R-4) Pr 3,5-diMeO-Ph -0 (CH2) 6- (G78) HHH 2-71 (R-4) Et 3,5-diMe〇-Ph -ch2o (ch2) r (G5) HHH 2-72 (R-4) Et 3,5-diMe〇-Ph -CH20 (CH2) 6-(G10) HHH 2-73 (R-4) Et 3,5-diMeO-Ph -ch2o (ch2) 6- (G15) HHH 2-74 (R-4) Et 3,5-diMe〇-Ph -ch2o (ch2) 6- (G26) HHH 2-75 (R-4) Et 3,5- diMe〇-Ph -CH20 (CH2) 6-(G36) HHH 2-76 (R_4) Et 3,5-diMeO-Ph -ch2o (CH2) r (G50) HHH 2-77 (R-4) Et 3, 5-diMeO-Ph -ch2o (ch2) 6- (G66) HHH 2-78 (R ~ 4) Et 3,5-diMeO-Ph -ch2o (ch2) 6- (G75) HHH 2-79 (R-4 ) Et 3,5-diMeO-Ph -ch2o (ch2) 6- (G78) HHH 2-80 (R-4) Et 3,5-diMeO-Ph -ch2o (ch2) 6- (G84) HHH 2-81 (R_4) Pr 3,5-diMeO-Ph -ch2o (ch2) 6-(G15) HHH 2-82 (R-4) Pr 3,5-diMeO-Ph -ch2o (ch2) 6- (G75) HHH 2 -83 (R_4) Pr 3,5-diMeO-Ph -ch2o (ch2) 6- (G78) HHH 2-84 (R-4) Et 3,5-diMeO-Ph -S (CH2) 6- (G5) HHH 2-85 (R-4) Et 3,5-diMeO-Ph -S (CH2) 6- (G10) HHH 2-86 (R-4) Et 3, .5-diMeO-Ph -s (ch2) 6- (G15) HHH 2-87 (R-4) Et 3,5-diMeO-Ph -S (CH2) 6- (G26) HHH 2-88 (R-4) Et 3, 5-diMeO-Ph -S (CH2) 6- (G36) HHH 2-89 (R-4) Et 3,5-diMeO-Ph -s (ch2) 6-(G50) HHH 2-90 (R-4 ) Et 3,5-diMeO-Ph-s (ch2) 6- (G66) HHH 2-91 (R-4) Et 3,5-diMeO-Ph -s (ch2) 6- (G75) HHH 2-92 (R-4) Et 3,5-diMeO-Ph -S (CH2) 6- (G78) HHH 2-93 (R-4) Et 3,5-diMeO-Ph -S (CH2) r (G84) HHH 2-94 (R-4) Pr 3,5-diMeO-Ph -s (ch2) 6- (G15) HHH 2-95 (R-4) Pr 3,5-diMeO-Ph -s (CH2) 6- (G75) HHH -101-200300349

2-96 (R-4) Pr 3,5-diMe〇-Ph -s (CH2) 6- (G78) H. HH 2-97 (R-7) Et 3,5-diMe〇-Ph-0 ( CH2) 「(G14) HHH 2-98 (R-7) Et 3, 5-diMeO-Ph-〇 (ch2) 6-(G50) HHH 2-99 (R-7) .Et 3,5-diMeO- Ph -0 (CH2) 6- (G54) HHH 2-100 (R-7) Et 3,5-diMeO-Ph -0 (CH2) 6-(G65) HHH 2-101 (R-7) Et 3, 5-diMeO-Ph -0 (CH2) 6- (G74) HHH 2-102 (R-7) Et 3,5-diMeO-Ph -0 (ch2) 6- (G77) HHH 2-103 (Rl) Et 3,5-diMeO-Ph -〇 (CH2) 7- (G14) HHH 2-104 (Rl) Et 3,5-diMeO ~ Ph -〇 (CH2) 7- (G50) HHH 2-105 (Rl) Et 3,5-diMeO-Ph -0 (CH2) 7- (G54) HHH 2-106 (Rl) Et 3,5-diMeO-Ph -o (CH2) r (G65) HHH 2-107 (Rl) Et 3 , 5-diMeO-Ph _0 (CH2) 7- (G74) HHH 2-108 (Rl) Et 3,5-diMeO-Ph -〇 (CH2) f (G77) HHH 2-109 (R-3) Et 3 , 5-diMeO ~ Ph -0 (CH2) r (G14) HHH 2-110 (R-3) Et 3,5-diMeO ~ Ph -o (CH2) 7- (G50) HHH 2-111 (R-3 ) Et 3,5-diMeO-Ph -0 (CH2) r (G54) HHH 2-112 (R-3) Et 3,5-diMeO-Ph-0 (CH2) 7- (G65) HHH 2-113 ( R-3) Et 3,5-diMeO-Ph -0 (CH2) 7- (G74) HHH 2-114 (R-3) Et 3,5-diMeO-Ph -0 (CH 2) 7- (G77) HHH 2-115 (R-4) Me 3,5-diMeO-Ph -o (ch2) 7- (G14) HHH 2-116 (R-4) Me 3,5-diMeO- Ph-o (ch2) 7- (G50) HHH 2-117 (R-4) Me 3,5-diMeO-Ph -0 (CH2) 7- (G54) HHH 2-118 (R-4) Me 3, 5-diMeO-Ph -0 (CH2) 7- (G65) HHH 2-119 (R-4) Me 3,5-diMeO-Ph -0 (CH2) 7- (G74) HHH 2-120 (R-4 ) Me 3,5-diMeO-Ph -0 (CH2) 7- (G77) HHH 2-121 (R-4) Et 3,5-diMeO-Ph -〇 (CH2) 7- (G4) HHH -102- 200300349 2-122 (R-4) Et 3,5-diMe〇-Ph -0 (CH2) 7- (G9) HHH 2-123 (R-4) Et 3,5-diMeO-Ph -0 (CH2) r (G14) HHH 2-124 (R ~ 4) Et 3,5-diMe〇-Ph -〇 (CH2) r (G25) HHH 2-125 (R-4) Et 3, 5-diMe〇-Ph- 〇 (CH2) r (G28) HHH 2-126 (R-4) Et 3,5-diMe 〇-Ph -〇 (CH2) r (G30) HHH 2-127 (R-4) Et 3, 5-diMeO -Ph -〇 (CH2) r (G35) HHH 2-128 (R-4) Et 3,5-diMeO-Ph -〇 (CH2) 7- (G50) HHH 2-129 (R-4) 'Et 3 , 5-diMe〇-Ph -0 (CH2) r (G51) HHH 2-130 (R-4) Et 3, 5-diMe〇-Ph -〇 (CH2) r (G52) HHH 2-131 (R- 4) Et 3,5-diMe〇-Ph -0 (CH2) r (G53) HHH 2-132 (R-4) Et 3,5-diMe (HPh-0 (CH2) 7- (G54) HHH 2- 133 (R -4) Et 3,5-diMeO-Ph -0 (CH2) r (G55) HHH 2-134 (R_4) Et 3,5-diMe0-Ph -〇 (CH2) 7- (G56) HHH 2-135 ( R-4) Et 3,5-diMeO-Ph -0 (CH2) r (G58) HHH 2-136 (R-4) Et 3, 5-diMeO-Ph -0 (CH2) r (G60) HHH 2- 137 (R-4) Et 3,5-diMeO-Ph -0 (CH2) r (G65) HHH 2-138 (R-4) Et 3, 5-diMeO-Ph -0 (CH2) 7- (G72) HHH 2-139 (R_4) Et 3, 5-diMeO-Ph_0 (CH2) 7- (G73) HHH 2-140 (R-4) Et 3, 5-diMeO-Ph -〇 (CH2) r (G74) HHH 2-141 (R-4) Et 3, 5-diMeO-Ph -0 (CH2) r (G76) HHH 2-142 (R-4) Et 3,5-diMeO-Ph -0 (CH2) r (G77 ) HHH 2-143 (R-4) Et 3, 5-diMeO-Ph -〇 (CH2) r (G80) HHH 2-144 (R-4) Et 3,5-diMeO-Ph -0 (CH2) r (G83) HHH 2-145 (R-4) Et. 3,4-diMeO-Ph -0 (CH2) r (G4) HHH 2-146 (R-4) Et 3,4-diMeO-Ph -〇 ( CH2) r (G9) HHH 2-147 (R-4) Et 3,4-diMe〇-Ph -〇 (CH2) r (G14) HHH '200300349

2-148 (R ~ 4) Et 3,4-diMeO-Ph -〇 (CH2) r (G25) HHH 2-149 (R-4) Et 3,4-diMeO-Ph -0 (CH2) r (G28 ) HHH 2-150 (R-4) Et 3,4-diMeO-Ph -〇 (CH2) 7- (G30) HHH 2-151 (R-4) Et 3,4-diMe〇-Ph -〇 (CH2 ) r (G35) HHH 2-152 (R_4) Et 3,4-diMe〇-Ph -〇 (ch2) 7- (G50) HHH 2-153 (R-4) Et 3,4-diMe〇-Ph- 0 (CH2) 7- (G54) HHH 2-154 (R-4) Et 3,4-diMe〇-Ph -0 (CH2) 7- (G58) HHH 2-155 (R_4) Et 3,4-diMe 〇-Ph -〇 (CH2) 7- (G60) HHH 2-156 (R-4) Et 3,4-diMe〇-Ph -o (ch2) 7- (G65) HHH 2-157 (R-4) Et 3,4-diMe〇-Ph-0 (CH2) 7- (G72) HHH 2-158 (R ~ 4) Et 3,4-diMe〇-Ph-0 (CH2) 7- (G73) HHH 2- 159 (R-4) Et 3,4-diMeO-Ph-0 (CH2) 7- (G74) HHH 2-160 (R-4) Et 3,4-diMe〇-Ph -〇 (CH2) 7- ( G76) HHH 2-161 (R-4) Et 3,4-diMeO-Ph -0 (CH2) 7- (G77) HHH 2-162 (R-4) Et 3,4-diMeO-Ph -0 (CH2 ) r (G80) HHH 2-163 (R-4) Et 3,4-diMeO-Ph -〇 (CH2) 7- (G83) HHH 2-164 (R-4) Et 3-EtO-Ph -o ( ch2) 7-(G4) H H. H 2-165 (R-4) Et 3-Et〇-Ph-0 (CH2) 7- (G9) HHH 2-166 (R_4) Et 3-EtO-Ph- 〇 (C H2) 7- (G14) 1 HHH 2-167 (R-4) Et 3-EtO-Ph -〇 (CH2) 7- (G25) HHH 2-168 (R-4) Et 3-EtO-Ph-0 (CH2) 7- (G28) HHH 2-169 (R-4) Et 3-EtO-Ph -0 (CH2) 7- (G30) HHH 2-170 (R-4) Et 3-EtO-Ph-o (ch2) 7-(G35) HHH 2-171 (R-4) Et 3-EtO-Ph ~ 0 (CH2) r (G50) HHH 2-172 (R-4) Et 3-EtO-Ph-o ( ch2) 7- (G54) HHH 2-173 (R ~ 4) Et 3-EtO-Ph -〇 (CH2) 7- (G58) HHH -104- 200300349

2-174 (R-4) Et 3-Et〇-Ph -〇 (CH2) r (G60) HHH 2-175 (R-4) Et 3-EtO-Ph -〇 (CH2) 7- (G65) HHH 2-176 (R-4) Et 3-Et〇-Ph-0 (CH2) 7- (G72) HHH 2-177 (R-4) Et 3-Et〇-Ph-0 (CH2) r (G73) HHH 2-178 (R-4) Et 3-EtO-Ph-0 (CH2) 7-(G74) HHH 2-179 (R ~ 4) Et 3-Et〇-Ph -〇 (CH2) r (G76) HHH 2-180 (R-4) Et 3-Et〇-Ph-0 (CH2) r (G77) HHH 2-181 (R ~ 4) Et 3-Et〇-Ph-0 (CH2) r (G80) HHH 2-182 (R-4) Et 3-EtO-Ph ~ 0 (CH2) r (G83) HHH 2-183 (R-4) Pr 3,5-diMeO-Ph -o (ch2) 「(G4) HHH 2-184 (R-4) Pr 3,5-diMe〇-Ph -o (ch2) 7- (G9) HHH 2-185 (R ~ 4) Pr 3,5-diMeO-Ph -〇 (CH2) r (G14) HHH 2-186 (R-4) Pr 3,5-diMe〇-Ph -〇 (CH2) r (G25) HHH 2-187 (R-4) Pr 3,5-diMe〇-Ph- o (ch2) 7- (G28) HHH 2-188 (R_4) Pr 3,5-diMe〇-Ph -〇 (ch2) 7- (G30) HHH 2-189 (R ~ 4) Pr 3,5-diMe 〇-Ph -〇 (ch2) 7- (G35) HHH 2-190 (R ~ 4) Pr 3,5-diMeO-Ph-o (ch2) 7-(G50) HHH 2-191 (R-4) Pr 3,5-diMe〇-Ph-0 (CH2) 7- (G54) HHH 2-192 (R-4) Pr 3,5-diMe〇-Ph -0 (CH2) r (G58) HHH 2-193 ( R-4) Pr 3,5-diMe〇-Ph -o (ch2) 7- (G60) HHH 2-194 (R-4) Pr 3,5-diMeO-Ph -〇 (ch2) r (G65) HHH 2-195 ( R-4) Pr 3,5-diMe.0-Ph _0 (CH2) r (G72) HHH 2-196 (R-4) Pr 3,5-diMeO-Ph -〇 (ch2) 7- (G73) HH H. 2-197 (R-4) Pr 3,5-diMe〇-Ph-o (ch2) 7_ (G74) HHH 2-198 (R-4) Pr 3,5-diMeO-Ph-0 (CH2) r (G76) HHH 2-199 (R-4) Pr 3,5-diMeO-Ph-0 (CH2) 7-(G77) HHH -105- 200300349

2-200 (R-4) Pr 3,5-diMeO-Ph -o (ch2) 7-(G80) HHH 2-201 (R-4) Pr 3,5-diMeO-Ph -〇 (CH2) 7- (G83) HHH 2-202 (R-4) Pr 3-EtO-Ph-o (ch2) 7-(G4) HHH 2-203 (R-4) Pr 3-Et〇-Ph -〇 (CH2) 7 -(G9) HHH 2-204 (R_4) Pr 3-Et〇-Ph-0 (CH2) 7- (G14) HHH 2-205 (R-4) Pr 3-Et〇-Ph -〇 (CH2) 7 -(G25) HHH 2-206 (R-4) Pr 3-Et〇-Ph -0 (CH2) 7- (G28) HHH 2-207 (R_4) Pr 3-Et〇-Ph -o (ch2) 7 -(G30) HHH 2-208 (R-4) Pr 3-Et〇-Ph _o (ch2) 7-(G35) HHH 2-209 (R-4) Pr 3-EtO-Ph -0 (CH2) f -(G50) HHH 2-210 (R-4) Pr 3-EtO-Ph -0 (CH2) f- (G54) HHH 2-211 (R-4) Pr 3-EtO-Ph -o (CH2) r (G58) HHH 2-212 (R-4) Pr 3-Et〇-Ph -o (ch2) 7-(G60) HHH 2-213 (R-4) Pr 3-EtO-Ph -o (ch2) 7 -(G65) HHH 2-214 (R-4) Pr 3-Et〇-Ph-o (ch2) 7-(G72) HHH 2-215 (R-4) Pr 3-EtO-Ph -0 (CH2) 7- (G73) HHH 2-216 (R ~ 4) Pr 3-EtO-Ph -o (ch2) 7-(G74) HHH 2-217 (R-4) Pr 3-EtO-Ph-o (ch2) 7-(G76) HHH 2-218 (R-4) Pr 3-EtO-Ph -0 (CH2) 7- (G77) HHH 2-219 (R-4) Pr 3-EtO-Ph -0 (CH2) r (G80) HHH 2-220 (R-4) Pr 3-EtO-Ph-o (ch2) 7- (G83) HHH 2-221 (R-4) Bu 3,5-diMeO-Ph _o (ch2) 7-(G4) HHH 2-222 (R-4) Bu 3,5-diMeO-Ph -〇 (CH2) r (G9) HHH 2-223 (R-4) Bu 3,5-diMeO-Ph -0 (CH2) r ( G14) HHH 2-224 (R-4) Bu 3,5-diMeO-Ph -o (ch2) 7-(G25) HHH 2-225 (R-4) Bu 3,5 ~ diMe〇-Ph -0 ( CH2) r (G28) HHH -106- 200300349

2-226 (R-4) Bu 3,5-diMe〇-Ph -0 (CH2) r (G30) HHH 2-227 (R-4) Bu 3,5-diMeO-Ph -〇 (CH2) 7- (G35) HHH 2-228 (R-4) Bu 3, 5-diMe〇-Ph -〇 (CH2) r (G50) HHH 2-229 (R-4) Bu 3,5-diMe〇-Ph -0 (CH2) 7- (G54) HHH 2-230 (R-4) Bu 3,5-diMe〇-Ph -0 (CH2) r (G58) HHH 2-231 (R-4) Bu 3,5-diMe 〇-Ph -0 (CH2) 7- (G60) HHH 2-232 (R-4) Bu 3,5-diMe〇-Ph -0 (CH2) 7- (G65) HHH 2-233 (R-4) Bu 3,5-diMeO-Ph -0 (CH2) r (G72) HHH 2-234 (R-4) Bu 3, 5-diMe〇-Ph -0 (CH2) r (G73) HHH 2-235 (R -4) Bu 3, 5-diMe〇-Ph -0 (CH2) r (G74) HHH 2-236 (R-4) Bu 3,5-diMeO-Ph -0 (CH2) r (G76) HHH 2- 237 (R-4) Bu 3, 5-diMe〇-Ph -0 (CH2) r (G77) HHH 2-238 (R-4) Bu 3? 5-diMeO-Ph -0 (CH2) r (G80) HHH 2-239 (R-4) Bu 3, 5-diMeO-Ph -0 (CH2) r (G83) HHH 2-240 (R-4) All 3,5 ~ diMe0-Ph -0 (CH2) r ( G4) HHH 2-241 (R-4) All 3, 5-diMeO-Ph -0 (CH2) 7- (G9) HHH 2-242 (R-4) All 3, 5 ~ diMeO ~ Ph -0 (CH2 ) 7-. (G14) HHH 2-243 (R-4) All 3, 5-diMeO-Ph -0 (CH2) r (G25) HHH 2-244 (R-4) All 3, 5-diMeO-Ph -0 (CH2) r (G28) HHH 2-245 (R-4) All 3, 5-diMeO-Ph -0 (CH2) r (G30) HHH 2-246 (R-4) All 3,5-diMeO-Ph -0 (CH2) 7- (G35) HHH 2-247 (R ~ 4) All 3, 5-diMeO-Ph -0 (CH2) r (G50) HHH 2-248 (R-4) All 3,5-diMeO-Ph -0 (CH2) r (G54 ) HHH 2-249 (R-4) All 3,5-diMeO-Ph -0 (CH2) r (G58) HHH 2-250 (R ~ 4) All 3,5-diMeO-Ph -0 (CH2) r (G60) HHH 2-251 (R-4) All 3,5-diMeO-Ph -0 (CH2) 7- (G65) HHH -107 > 200300349

2-252 (R-4) All 3,5-diMe〇-Ph -0 (CH2) r (G72) HHH 2-253 (R-4) All 3,5-diMe〇-Ph -0 (CH2) r (G73) HHH 2-254 (R-4) All 3,5-diMe〇-Ph -〇 (CH2) > 7- (G74) HHH 2-255 (R-4) All 3,5-diMe〇- Ph -0 (CH2) r (G76) HHH '2-256 (R-4) All 3,5-diMe〇-Ph -0 (CH2) r (G77) HHH 2-257 (R ~ 4) All 3, 5-diMe〇-Ph -0 (CH2) r (G80) HHH 2-258 (R-4) All 3,5-diMe〇-Ph -0 (CH2) r (G83) HHH 2-259 (R-4 ) Prp 3,5-diMe〇-Ph -〇 (CH2) r (G4) HHH 2-260 (R-4) Prp 3,5-diMe〇-Ph -0 (CH2) r (G9) HHH 2-261 (R-4) Prp 3,5 ~ diMe〇-Ph -0 (CH2) 7- (G14) HHH 2-262 (R-4) Prp 3,5-diMeO-Ph -0 (CH2) 7- (G25 ) HHH 2-263 (R-4) Prp 3,5-diMeO-Ph -0 (CH2) r (G28) HHH 2-264 (R-4) Prp 3,5-diMe〇-Ph -0 (CH2) r (G30) HHH 2-265 (R-4) Prp 3,5-diMeO-Ph -0 (CH2) 7- (G35) HHH 2-266 (R-4) Prp 3,5-diMe〇-Ph- 0 (CH2) r (G50) HHH 2-267 (R-4) Prp .3,5-diMeO-Ph -0 (CH2) 7- (G54) HHH 2-268 (R-4) Prp 3,5- diMeO-Ph -〇 (CH2) 7- (G58) HHH 2-269 (R-4) Prp 3,5-diMe〇-Ph -〇 (CH2) r (G60) HHH 2-270 (R-4) Prp 3,5-diMeO-Ph -0 ( CH2) r (G65) HHH 2-271 (R-4) Prp 3,5-diMeO-Ph -0 (CH2) r (G72) HHH 2-272 (R-4) Prp 3,5-diMeO-Ph- 0 (CH2) r (G73) HHH 2-273 (R-4) Prp 3,5-diMeO-Ph -〇 (CH2) r (G74) HHH 2-274 (R ~ 4) Prp 3,5-diMeO- Ph -0 (CH2) r (G76) HHH 2-275 (R-4) Prp 3,5-diMeO-Ph -0 (CH2) r. (G77) HHH 2-276 (R-4) Prp 3,5 -diMeO-Ph -〇 (CH2) r (G80) HHH 2-277 (R-4) Prp 3,5-diMeO-Ph -〇 (CH2) r (G83) HHH -108- 200300349 2-278 2-279 2-280 2-281 2-282 2-283 2-284 2-285 2-286 2-287 2-288 2-289 2-290 2-291 2-2.92 2-293 2-294 2-295 2- 296 2-297 2-298 2-299 2-300 2-301 2-302 2-303

(R-4) Et 3,5-diMeO-Ph -CH20 (CH2) 7- (G4) HHH (R ~ 4) Et 3,5-diMeO-Ph -CH20 (CH2) r (G14) HHH (R- 4) Et 3,5-diMe〇-Ph -CH20 (CH2) 7- (G25) HHH (R-4) Et 3,5-diMe〇-Ph -CH20 (CH2) r (G35) HHH (R-4 ) Et 3,5-diMe〇-Ph -CH20 (CH2) r (G60) HHH (R ~ 4) Et 3,5-diMeO-Ph -CH20 (CH2) r (G65) HHH (R ~ 4) Et 3 , 5-diMeO-Ph -CH20 (CH2) r (G71) HHH (R-4) Et 3,5-diMe〇-Ph -CH20 (CH2) 7- (G74) HHH (R_4) Et 3,5-diMe 〇-Ph -CH20 (CH2) r. (G77) HHH (R-4) Et 3,5-diMeO-Ph -CH20 (CH2) r (G80) HHH (R-4) Et 3,5-diMeO-Ph -CH20 (CH2) 7- (G83) HHH (R-4) Et 3,5-diMe〇-Ph -S (CH2) r (G4) HHH (R-4) 'Et 3,5-diMeO-Ph- S (CH2) r (G14) HHH (R-4) Et '3,5-diMe〇-Ph -S (CH2) 7- (G25) HHH (R-4) Et 3,5-diMeO-Ph -S (CH2) 7- (G35) HHH (R-4) Et 3,5-diMeO-Ph ~ S (CH2) 7- (G60) HHH (R-4) Et 3,5-diMeO-Ph -S (CH2 ) 7- (G65) HHH (R-4) Et 3,5-diMeO-Ph -S (CH2) r (G71) HHH (R_4) Et 3,5-diMeO-Ph -S (CH2) 7- (G74 ) HHH (R-4) Et 3,5-diMe〇-Ph -S (CH2) r (G77) HHH (R ~ 4) Et 3,5-diMeO-Ph -S (CH2) 7- (G80) HHH (R ~ 4) Et 3,5-diMeO-Ph -S (CH2) 7- (G83) HHH (R-7) Et 3,5-diMeO-Ph -0 (CH2) r (G4) HHH (R-7) Et 3,5 -diMeO-Ph -〇 (CH2) 7- (G14) HH .H (R-7) Et 3,5-diMeO-Ph -〇 (CH2) 7- (G65) HHH (R-7) Et 3,5 -diMeO-Ph -〇 (CH2) 7- (G74) HHH -109- 200300349 2-304 (R-7) Et 3,5-diMeO-Ph -〇 (CH2) 7- (G77) Η Η Η 2- 305 (R-7) Pr 3,5-diMeO-Ph -o (ch2) 7-(G74) Η Η Η 2-306 (R-1) Et 3,5-diMe〇-Ph-〇 (ch2) 8 -(G4) Η Η Η 2-307 (Rl) Et 3,5-diMeO-Ph _o (ch2) 8-(G14) Η Η 308 2-308 (Rl) Et 3,5-diMeO-Ph -〇 ( CH2) r (G65) Η Η Η 2-309 (Rl) Et 3,5-diMeO-Ph _0 (CH2) 8-(G74) Η Η 310 2-310 (Rl) Et 3,5-diMeO-Ph- 〇 (ch2) 8_ (G77) Η Η Η 2-311 (Rl) Pr 3,5-diMeO-Ph _o (ch2) 8-(G74) Η Η 312 2-312 (R-3) Et 3,5- diMeO-Ph-〇 (CH2) 8-(G4) Η Η Η 2-313 (R-3) Et 3,5-diMeO-Ph-〇 (CH2) 8-(G14) Η Η Η 2-314 (R -3) Et 3,5-diMeO-Ph -〇 (CH2) 8-(G65) Η Η Η 2-315 (R-3) Et 3,5-diMeO-Ph -〇 (CH2) 8- (G74) 316 Η Η 2-316 (R-3) Et 3,5-diMeO-Ph -o (ch2) 8- (G77) Η Η Η 2-317 (R-3) Pr 3,5-diMe〇- Ph-〇 (CH2) 8-(G74) Η Η Η 2-318 (R-3) Bu 3,5-diMeO-Ph -〇 (CH2) 8- (G74) Η Η 319 2-319 (R-4 ) Me 3,5-diMeO-Ph -〇 (ch2) 8- (G4) Η Η 320 2-320 (R-4) Me 3,5-diMeO-Ph -o (ch2) 8- (G14) Η Η Η 2-321 (R ~ 4) Me 3,5-diMeO-Ph -〇 (CH2) 8- (G65) Η Η 322 2-322 (R-4) Me 3,5-diMeO-Ph -0 (ch2 ) 8- (G74) Η Η Η 2-323 (R-4) Me 3,5-diMeO-Ph-0 (ch2) 8- (G77) Η Η 324 2-324 (R-4) Et 3,4 -diMe〇-Ph -0 (ch2) 8-(G4) Η Η Η 2-325 (R-4) Et 3,4-diMeO-Ph -〇 (CH2) 8- (G9) Η Η Η 2-326 (R-4) Et 3,4-diMeO-Ph-0 (ch2) 8- (G14) Η Η Η 2-327 (R-4) Et 3,4-diMeO ~ Ph -〇 (CH2) 8-( G25) Η Η Η 2-328 (R-4) Et 3,4-diMeO-Ph-〇 (CH2) 8-(G28) Η Η Η 2-329 (R-4) Et 3,4-diMe〇- Ph -〇 (CH2) 8-(G30) Η Η Η -110- 200300349

2-330 (R-4) Et 3,4-diMeO-Ph -0 (CH2) 8- (G35) HHH 2-331 (R-4) Et 3, 4 ~ diMe〇-Ph -0 (CH2) 8 -(G50) HHH 2-332 (R-4) Et 3,4-diMe〇-Ph -0 (CH2) 8- (G54) HHH 2-333 (R-4) Et 3,4-diMeO-Ph- 0 (CH2) 8-. (G58) HHH 2-334 (R-4) Et 3, 4 ~ diMe〇-Ph -0 (CH2) 8- (G60) HHH 2-335 (R-4) Et 3, 4-diMeO-Ph -0 (CH2) 8- (G65) HHH 2-336 (R-4) Et 3,4-diMeO-Ph -0 (CH2) 8- (G72) HHH 2-337 (R-4 ) Et 3,4-diMeO-Ph ~ 0 (CH2) 8- (G73) HHH 2-338 (R-4) Et 3,4-diMeO-Ph ~ 0 (CH2) 8-, (G74) HHH 2- 339 (R-4) Et 3,4-diMeO-Ph -0 (CH2) 8- (G76) HHH 2-340 (R-4) Et 3,4-diMeO-Ph ~ 0 (CH2) 8- (G77 ) HHH 2-341 (R-4) Et 3,4-diMeO-Ph -0 (CH2) 8- (G80) HHH 2-342 (R-4) Et 3,4-diMeO-Ph -0 (CH2) 8- (G83) HHH 2-343 (R ~ 4) Et 3, 5-diMe〇-Ph -0 (CH2) 8- (G4) HHH 2-344 (R-4) Et 3,5-diMeO-Ph -0 (CH2) 8- (G9) HHH 2-345 (R-4) Et 3,5-diMeO-Ph -0 (CH2) 8- (G14) HHH 2-346 (R-4) Et 3,5 -diMeO-Ph -0 (CH2) 8- (G25) HHH 2-347 (R-4) Et 3, 5-diMeO-Ph -〇 (CH2) 8- (G28) HHH 2-348 (R-4) Et 3,5-diMeO-Ph -0 (CH2) 8-(G30) HH H 2-349 (R-4) Et 3, 5-diMeO-Ph -0 (CH2) 8- (G35) HHH 2-350 (R-4) Et 3, 5-diMeO-Ph -0 (CH2) 8 -(G50) HHH 2-351 (R-4) Et 3, 5-diMeO-Ph -〇 (CH2) 8- (G54) HHH 2-352 (R-4) Et 3,5-diMeO-Ph -〇 (CH2) 8- (G58) HHH 2-353 (R-4) Et 3, 5-diMeO-Ph -〇 (CH2) 8- (G60) HHH 2-354 (R-4) Et 3,5-diMe 〇-Ph -0 (CH2) r (G65) HHH 2-355 (R-4) Et 3,5-diMeO-Ph -0 (CH2) 8 ~ (G72) HHH 200300349 2-356 2-357 2-358 2-359 2-360 2-361 2-362 2-363 2-364 2-365 2-366 2-367 2-368 2-369 2-370 2-371 2-372 2-373 2-374 2- 375 2-376 2-377 2-378 2-379 2-380 2-381

(R-4) Et 3,5-diMeO-Ph -0 (CH2) 8- (G73) HHH (R-4) Et 3,5-diMe〇-Ph -0 (CH2) 8- (G74) HHH ( R-4) Et 3,5-diMe〇-Ph -0 (CH2) 8- (G76) HHH (R-4) Et 3,5-diMeO-Ph-0 (CH2) 8- * (G77) HHH ( R ~ 4) Et 3,5-diMe〇-Ph-〇 (ch2) 8-(G80) HHH (R-4) Et 3,5-diMeO-Ph-〇 (ch2) 8_ (G83) HHH (R- 4) Et 3-EtO-Ph -o (ch2) 8-(G4) HHH (R-4) Et 3-Et〇-Ph -0 (CH2) 8- (G9) HHH (R-4) Et 3- EtO-Ph -0 (CH2) 8- (G14) HHH (R-4) Et 3-EtO-Ph-0 (ch2) 8- (G25) HHH (R-4) Et 3-Et〇-Ph -0 (CH2) 8_ (G28) HHH (R_4) Et 3-EtO-Ph -〇 (CH2) 8-(G30) HHH (R ~ 4) Et 3-EtO-Ph -0 (CH2) 8- (G35) HHH (R-4) Et 3-E10-Ph -0 (CH2) 8- (G50) HHH (R-4) Et 3-EtO-Ph -〇 (CH2) 8-(G54) HHH (R-4) Et 3-EtO-Ph -〇 (CH2) 8- (G58) HHH (R-4) Et 3-EtO-Ph-o (ch2) 8-(G60) HHH (R ~ 4) Et 3-EtO-Ph- 〇 (CH2) 8- (G65) HHH (R-4) Et 3-EtO-Ph -0 (ch2) 8- (G72) HHH (R-4) Et 3-EtO-Ph -〇 (ch2) 8- (G73) HHH (R-4X Et 3-EtO-Ph _0 (ch2) 8_ (G74) HHH (R_4) Et 3-EtO-Ph -o (ch2) 8- (G76) HHH (R-4) Et 3-EtO-Ph -0 (CH2) 8- (G77) HHH (R-4) Et 3-EtO-Ph -〇 (CH2) 8-(G80) HHH (R-4) Et 3-EtO-Ph _o (ch2) 8- (G83) HHH (R-4) Pr 3,5-diMeO-Ph -o (ch2) 8- (G4) HHH -112- 200300349 2-382 (R ~ 4) Pr 3,5- diMe〇-Ph -〇 (ch2) 8- (G9) Η Η Η 2-383 (R-4) Pr 3,5-diMe〇-Ph -0 (ch2) 8-(G14) Η Η 384 2-384 (R-4) Pr 3,5-diMeO-Ph -〇 (ch2) 8- (G25) Η Η Η 2-385 (R-4) Pr 3,5-diMeO-Ph -〇 (ch2) 8-( G28) Η Η Η 2-386 (R-4) Pr 3,5-diMeO-Ph -〇 (ch2) 8- (G30) Η Η Η 2-387 (R-4) Pr 3,5-diMeO-Ph -o (ch2) 8-(G35) Η Η Η 2-388 (R-4) Pr 3,5-diMeO-Ph-〇 (ch2) 8- (G50) Η Η Η 2-389 (R ~ 4) Pr 3,5-diMeO-Ph-o (ch2) 8-(G54) Η Η Η 2-390 (R-4) Pr 3,5-diMeO-Ph -〇 (ch2) 8- (G58) Η Η Η 2-391 (R-4) Pr 3,5-diMe0 ~ Ph-0 (ch2) 「(G60) Η Η Η 2-392 (R-4) Pr 3,5-diMeO-Ph -0 (ch2) 8 -(G65) Η • Η Η 2-393 (R-4) Pr 3,5-diMeO-Ph -〇 (ch2) 8- (G72) Η Η Η 2-394 (R-4) Pr 3,5- diMeO-Ph -o (ch2) 8- (G73) Η Η Η 2-395 (R-4) Pr • 3,5-diMeO-Ph-o (ch2) 8- (G74) Η Η 396 2-396 ( R-4) Pr 3,5-diM eO-Ph -〇 (CH2) r (G76) Η Η 397 2-397 (R-4) Pr 3,5-diMeO-Ph _〇 (CH2) 8-(G77) Η Η 398 2-398 (R- 4) Pr 3,5-diMeO-Ph -〇 (CH2) 8- (G80) Η Η Η 2-399 (R-4) Pr 3,5-diMe〇-Ph -〇 (ch2) 8- (G83) Η Η Η 2-400 (R-4) Pr 3-Et〇-Ph -0 (ch2) 8- (G4) Η Η 401 2-401 (R-4) Pr 3-Et〇-Ph -0 (ch2 ) 8- (G9) Η Η Η 2-402 (R_4) Pr 3-Et〇-Ph-0 (ch2) 8- (G14) Η Η Η 2-403 (R-4) Pr 3-EtO-Ph- 0 (ch2) 8-(G25) Η Η Η 2-404 (R-4) Pr 3-Et〇-Ph -〇 (ch2) 8- (G28) Η Η 405 2-405 (R-4) Pr 3 -EtO-Ph -0 (ch2) 8- (G30) Η Η Η 2-406 (R-4) Pr 3-EtO-Ph-0 (ch2) 8-(G35) Η Η 2-407 (R- 4) Pr 3-Et〇-Ph-〇 (CH2) 8-(G50) Η Η Η -113- 200300349

2-408 (R-4) Pr 3-EtO-Ph -0 (CH2) 8- (G54) HHH 2-409 (R-4) Pr 3-Et〇-Ph -0 (CH2) 8- (G58) HHH 2-410 (R-4) Pr 3-Et〇-Ph -0 (CH2) 8- (G60) HHH 2-411 (R-4) Pr 3-Et〇-Ph -0 (ch2) 8- ( G65) HHH 2-412 (R-4) Pr 3-Et〇-Ph-o (ch2) 8_ (G72) HHH 2-413 (R-4) Pr 3-Et〇-Ph-o (ch2) 8- (G73) HHH 2-414 (R-4) Pr 3-Et〇-Ph-0 (CH2) 8_ (G74) HHH 2-415 (R-4) Pr 3-Et〇-Ph -〇 (CH2) 8 -(G76) HHH 2-416 (R-4) Pr 3-Et〇-Ph-0 (ch2) 8-(G77) HHH 2-417 (R-4) Pr 3-EtO-Ph-0 (ch2) 8- (G80) HHH 2-418 (R-4) Pr 3-EtO-Ph-o (ch2) 8- (G83) HHH 2-419 (R-4) Bu 3,5-diMeO-Ph -0 ( CH2) 8-(G4) HHH 2-420 (R-4) Bu 3? 5-diMe〇-Ph -〇 (CH2) 8- (G9) HHH 2-421 (R-4) Bu 3,5-diMe 〇-Ph ~ 0 (CH2) 8- (G14) HHH 2-422 (R-4) Bu 3, 5 ~ diMe〇-Ph -0 (CH2) 8- (G25) HHH 2-423 (R-4) Bu 3, 5 ~ diMe〇-Ph -0 (CH2) 8- (G28) HHH 2-424 (R-4) Bu 3,5-diMe0-Ph -0 (CH2) 8- (G30) HHH 2-425 (R-4) Bu 3,5-diMe〇-Ph -0 (CH2) 8- (G35) HHH 2-426 (R-4) Bu 3,5-d iMeO-Ph -0 (CH2) 8- ( G50) HHH 2-427 (R-4) Bu 3, 5-diMeO-Ph -0 (CH2) 8- (G54) HHH 2-428 (R-4) Bu 3,5-d iMeO-Ph _0 (CH2) 8- (G58) HHH 2-429 (R-4) Bu 3,5-d iMeO-Ph _0 (CH2) 8- (G60) HHH 2-430 (R_4) Bu 3,5-diMeO ~ Ph -0 (CH2) 8 ~ ( G65) HHH 2-431 (R-4) Bu 3,5-diMeO-Ph -0 (CH2) r (G72) HHH 2-432 (R-4) Bu 3,5-diMe〇-Ph -0 (CH2 ) 8- (G73) HHH 2-433 (R-4) Bu 3,5-diMeO-Ph -〇 (CH2) 8- (G74) HHH -114- 200300349 2-434 (R-4) Bu 3,5 -diMeO-Ph -0 (CH2) 8-2-435 (R-4) Bu 3,5-diMeO-Ph -〇 (CH2) 8- 2-436 (R-4) Bu 3,5-diMe〇- Ph -〇 (CH2) 8- 2-437 (R-4) Bu 3,5-diMeO-Ph -0 (CH2) 8- 2-438 (R-4) Me 3,5-diMeO-Ph -CH20 ( CH2) 8- 2-439 (R-4) Et 3,5-diMe〇-Ph -CH20 (CH2) 8- 2-440 (R-4) Et 3,5-diMe〇-Ph -CH20 (CH2) 8- 2-441 (R-4) Et 3,5-diMe〇-Ph -CH20 (CH2) 8- 2-442 (R-4) Et 3,5-diMe〇-Ph -CH20 (CH2) 8- 2-443 (R-4) Et 3,5-diMe〇-Ph -CH20 (CH2) 8- 2-444 (R-4) Pr 3, 5-diMeO-Ph -CH20 (CH2) 8_ 2-445 ( R-4) Bu 3,5-diMe〇-Ph -CH20 (CH2) 8- 2-446 (R-4) Me 3,5-diMe〇-Ph -S (CH2) 8- 2-447 (R- 4) Et 3,5-diMe〇-Ph -S (CH2) r 2-448 (R-4) Et 3,5-diMeO-Ph -S (CH 2) 8- 2-449 (R-4) Et 3, 5-diMe〇-Ph -S (CH2) 8- 2-450 (R-4) Et 3,5-diMeO-Ph -S (CH2) 8 -2-451 (R-4) Et 3,5-diMe (HPh -S (CH2) r 2-452 (R-4) Pr 3,5-diMeO-Ph -S (CH2) 8- 2-453 ( R-4) Bu 3,5-diMeO-Ph -S (CH2) 8- 2-454 (R-7) Et 3,5-diMeO-Ph -〇 (CH2) 8- 2-455 (R-7) Et 3,5-diMeO-Ph -0 (CH2) 8- 2-456 (R-7) Et 3,5-diMeO-Ph -〇 (CH2) 8- 2-457 (R-7) Et 3,5 -diMeO-Ph -0 (CH2) 8_ 2-458 (R-7) Et 3,5-diMeO-Ph -〇 (CH2) 8- 2-459 (R-1) Me 3,5-diMeO-Ph- 0CH2 (1,4-Phy) CH2-

(G76) Η Η H (G77) Η Η H (G80) Η Η H (G83) Η Η H (G74) Η Η H (G4) Η Η H (G14) Η Η H (G65) Η Η H (G74) ) Η Η H (G77) Η Η H (G74) Η Η H (G74) Η Η H (G74) Η Η H (G4) Η Η H (G14) Η Η H (G65) Η Η H (G74) Η Η H (G77) Η Η H (G74) Η Η H (G74) Η Η H (G4) Η Η H (G14) Η Η H (G65) Η Η H (G74) Η Η H (G77) Η Η H (G3) Η Η H

-115- 200300349 2-460 2-461 2-462 2-463 2-464 2-465 2-466 2-467 2-468 2-469 2-470 2-471 2-472 2-473 2-474 2 -475 2-476 2-477 2-478 2-479 2-480 2-481 2-482 2-483 2-484 2-485

(Rl) Me 3,5-diMeO-Ph -0CH2 (1,4-Phy) CHr (G8) HHH (Rl) Me 3,5-diMe〇-Ph -0CH2 (1,4-Phy) CHr (G13) HHH (Rl) Me 3,5-diMe〇-Ph -0CH2 (13 4-Phy) CHr (G24) HHH (Rl) Me 3,5 ~ diM6〇-Ph -〇CH2 (1,4-Phy) CH2- (G34) HHH (Rl) Me 3,5-diMeO-Ph -〇CH2 (l, 4-Phy) CHr (G59) HHH (Rl) Me 3,5-diMe〇-Ph -0CH2 (1,4-Phy ) CHr (G64) HHH (R_l) Me 3,5-diMeO-Ph -0CH2 (1,4-Phy) CHr (G70) HHH (Rl) Me 3,5-diMeO-Ph -〇CH2 (1,4- Phy) CHr (G72) HHH (Rl) Me 3,5-diMeO-Ph -0CH2 (1,4-Phy) CHr (G73) HHH (Rl) Me 3, 5-diMeO-Ph -0CH2 (1,4- Phy) CHr (G76) HHH (Rl) Me 3,5-diMeO-Ph -0CH2 (1,4-Phy) CHr (G79) HHH (Rl) Me 3,5-diMeO-Ph -0CH2 (1,4 ~ Phy) CHr (G82) HHH (Rl) Et 3,5-diMeO-Ph -〇CH2 (l, 4-Phy) CHr (G3) HHH (Rl) Et 3,5-diMeO-Ph -0CH2 (1,4 -Phy) CHr (G8) HHH (Rl) Et 3,5-diMeO-Ph -0CH2 (1,4-Phy) CHr (G13) HHH (Rl) Et 3,5-diMeO-Ph -0CH2 (1,4 -Phy) CHr (G24) HHH (Rl) Et 3,5-diMeO-Ph -0CH2 (1, 4-Phy) CHr (G34) HHH (Rl) Et 3,5-diMeO-Ph -0CH2 (1, 4 -Phy) CHr (G59) HHH (Rl ) Et 3,5-diMe〇-Ph -0CH2 (1,4-Phy) CH2 ~ (G64) HHH (Rl) Et 3,5 ~ diMeO-Ph -OCH2 (1,4-Phy) CH2 ~ (G70) HHH (Rl) Et 3,5-diMeO-Ph -〇CH2 (1, 4-Phy) CHr (G73) HHH (R ~ l) Et 3,5-diMeO-Ph -OCH2 (1,4-Phy) CHr (G76) HHH (Rl) Et 3,5-diMeO-Ph -0CH2 (1,4-Phy) CHr (G79) HHH (Rl) Et 3,5-diMeO-Ph -〇CH2 (1,4-Phy) CHr (G82) HHH (R-2) Me 3,5-diMeO-Ph -OCH2 (1,4-Phy) CHr (G3) HHH (R-2) Me 3,5-diMeO-Ph -〇CH2 (1 , 4-Phy) CHr (G13) HHH

-116- 200300349 2-486 2-487 2-488 2-489 2-490 2-491 2-492 2-493 2-494 2-495 2-496 2-497 2-498 2-499 2-500 2 -501 2-502 2-503 2-504 2-505 2-506 2-507 2-508 2-509 2-510 2-511

(R-2) Me 3,5-diMe〇-Ph -〇CH2 (l, 4-Phy) CHr (G24) HHH (R-2) Me 3,5-diMe〇-Ph -〇CH2 (l, 4 -Phy) CHr (G59) HHH (R-2) Me 3,5-diMe〇-Ph -〇CH2 (l, 4-Phy) CHr (G64) HHH (R-2) Me 3,5-diMe〇- Ph -0CH2 (1, 4-Phy) CHr (G73) HHH (R-2) Me 3,5-d iMeO-Ph -〇CH2 (1,4-Phy) CHr (G76) HHH (R-2) Me 3,5-diMe〇-Ph -0CH2 (1,4-Phy) CHr (G79) HHH (R-2) Me 3,5-d iMeO-Ph -0CH2 (1,4-Phy) CHr (G82) HHH (R-2) Et 3,5-d iMeO-Ph -〇CH2 (1,4-Phy) CHr (G3) HHH (R-2) Et 3,5-diMe〇-Ph -0CH2 (1,4- Phy) CHr (G13) HHH (R-2) Et 3,5 ~ diMeO-Ph ~ OCH2 (1, 4-Phy) CH2- (G24) HHH (R-2) Et 3,5-diMe〇-Ph- 0CH2 (1, 4-Phy) CHr (G59) HHH (R-2) Et 3,5-d iMeO-Ph -OCH2 (1, 4-Phy) CHr (G64) HHH (R-2) Et 3,5 -diMe〇-Ph -0CH2 (1, 4-Phy) CHr (G73) HHH (R-2) Et 3,5-diMeO-Ph -〇CH2 (l, 4-Phy) CHr (G76) HHH (R- 2) Et 3,5-diMeO-Ph -0CH2 (1, 4-Phy) CH2- (G79) HHH (R-2) Et 3,5_diMeO-Ph _0CH2 (1, 4-Phy) CH2- (G82) HHH (R-3) Me 3,5 ~ diM6〇 ~ Ph -OCH2 (1, 4-Phy) CH2 ~ (G3) HHH (R-3) Me 3,5-diMe〇-Ph -0CH2 (1,4-Phy) CHr (G13) HHH (R-3) Me 3,5-diMeO-Ph -0CH2 (1,4-Phy) CHr (G24) HHH (R-3) Me 3,5 -diMeO-Ph -0CH2 (l, 4-Phy) CH2- (G59) HHH (R-3) Me 3,5-d iMeO ~ Ph -OCH2 (1,4-Phy) CHr (G64) HHH (R- 3) Me 3,5-d iMeO-Ph -0CH2 (1,4-Phy) CH2- (G73) HHH (R-3) Me 3,5-d iMeO-Ph -OCH2 (1,4-Phy) CHr (G76) HHH (R-3) Me 3,5-diMeO-Ph -OCH2 (1,4-Phy) CH2- (G79) HHH (R-3) Me 3,5 * ~ diMeO-Ph _OCH2 (1, 4-Phy) CH2- (G82) HHH (R-3) Et 3,5-d iMeO-Ph-() (¾ (1,4-Phy) CH2- (G3) HHH -117- 200300349 2-512 2 -513 2-514 2-515 2-516 2-517 2-518 2-519 2-520 2-521 2-522 2-523 2-524 2-525 2-526 2-527 2-528 2-529 2-530 2-531 2-532 2-533 2-534 2-535 2-536 2-537

(R-3) Et 3,5-diMeO-Ph -〇CH2 (1,4-Phy) CHr (G13) HHH (R-3) Et 3,5-diMeO-Ph -〇CH2 (1,4-Phy ) CHr (G24) HHH (R-3) Et 3,5-d iMeO-Ph -〇CH2 (1,4-Phy) CHr (G59) HHH (R-3) Et 3,5-d iMeO-Ph- 〇CH2 (1,4-Phy) CHr (G64) HHH (R-3) Et 3,5-d iMeO-Ph -〇CH2 (1,4-Phy) CHr (G73) HHH (R-3) Et 3 , 5 ~ d iMeO-Ph -〇CH2 (1,4-Phy) CHr (G76) HHH (R-3) Et 3,5-d iMeO-Ph -〇CH2 (1,4-Phy) CHr (G79) HHH (R-3) Et 3,5-d iMeO-Ph -〇CH2 (1,4-Phy) CHr (G82) HHH (R-4) Me 3, 5 ~ diMeO-Ph -〇CH2 (1,4 -Phy) CHr (G3) HHH (R-4) Me 3, 5-d iMeO-Ph -OCH2 (1,4-Phy) CHr (G13) HHH (R-4) Me 3,5-d iMeO-Ph -0CH2 (1,4-Phy) CHr (G24) HHH (R-4) Me 3,5-d iMeO-Ph -OCH2 (1,4-Phy) CHr (G59) HHH (R-4) Me 3, 5-d iMeO-Ph -〇CH2 (1, 4-Phy) CHr (G64) HHH (R-4) Me 3,5-d iMeO-Ph > OCH2 (1,4-Phy) CH2- (G73) HHH (R-4) Me 3,5-d iMeO-Ph -OCH2 (1, 4-Phy) CHr (G76) HHH (R-4) Me 3,5-d iMeO-Ph -OCH2 (1, 4- Phy) CHr (G79) HHH (R-4) Me 3,5-d iMeO-Ph -OCH2 (1,4-Phy) CHr (G82) HHH (R-4) Et 3,5-d iMeO- Ph -〇CH2 (1,4-Phy) CH2- (G3) HHH (R-4) Et 3, 5-d iMeO-Ph -OCH2 (1,4-Phy) CHr (G6) HHH (R-4) Et 3,5-d iMeO-Ph -OCH2 (1,4-Phy) CHr (G8) HHH (R-4) Et 3,5-diMeO-Ph -0CH2 (1,4-Phy) CH2- (Gil) HHH (R-4) Et 3,5-diMeO-Ph -OCH2 (1,4_Phy) CHr (G13) HHH (R-4) Et 3,5-d iMeO-Ph -OCH2 (1,4-Phy) CHr (G16) HHH (R-4) Et 3,5 ~ diM6〇 ~ Ph -OCH2 (1,4-Phy) CH2 ~ (G17) HHH (R-4) Et 3,5-d iMeO-Ph -OCH2 ( 1,4-Phy) CHr (G18) HHH (R-4) Et 3,5-diMeO-Ph -0CH2 (1,4-Phy) CH2- (G19) HHH -118- 200300349 2-538 2-539 2 -540 2-541 2-542 2-543 2-544 2-545 2-546 2-547 2-548 2-549 2-550 2-551 2-552 2-553 2-554 2-555 2-556 2-557 2-558 2-559 2-560 2-561 2-562 2-563

(R-4) Et 3,5-diMe〇-Ph -〇CH2 (l, 4-Phy) CHr (G20) HHH (R-4) Et 3,5-diMe〇-Ph -0CH2 (1,4- Phy) CH2- (G21) HHH (R-4) Et 3, 5-diMeO-Ph -〇CH2 (1,4-Phy) CHr (G22) HHH (R-4) Et 3,5-diMe〇-Ph -0CH2 (1,4-Phy) CHr (G24) HHH (R-4) Et 3, 5-d iMeO-Ph -〇CH2 (1,4-Phy) CHr (G27) HHH (R-4) Et 3 , 5-d iMeO-Ph -0CH2 (1,4-Phy) CH2- (G29) HHH (R-4) Et 3, 5-d iMeO-Ph -0CH2 (1, 4-Phy) CHr (G32) HHH (R-4) Et 3, 5-d iMeO-Ph -〇CH2 (l, 4-Phy) CHr (G33) HHH (R-4) Et 3,5-d iMeO-Ph -OCH2 (1,4- Phy) CHr (G34) HHH, (R-4) Et 3, 5-d iMeO-Ph -0CH2 (1,4-Phy) CH2- (G37) HHH (R-4) Et 3,5-diMe〇- Ph -0CH2 (1,4-Phy) CH2- (G38) HHH (R ~ 4) Et 3,5-d iMeO-Ph -〇CH2 (1,4-Phy) CHr (G39) HHH (R-4) Et 3, 5-diMe〇-Ph -0CH2 (1,4-Phy) CHr (G40) HHH (R-4) Et 3,5-d iMeO-Ph -0CH2 (1,4-Phy) CHr (G41) HHH (R-4) Et 3,5-d iMeO-Ph -0CH2 (1,4-Phy) CH2- (G42) HHH (R-4) Et 3,5-d iMeO-Ph -0CH2 (1,4 -Phy) CHr (G43) HHH (R-4) Et 3,5-diMe〇-Ph -0GH2 (1,4-Phy) CH2- (G44) HHH (R-4) Et 3, 5-d iMeO- Ph- CH2 (1,4-Phy) CHr (G45) HHH (R-4) Et 3, 5-d iMeO-Ph -0CH2 (1,4-Phy) CH2- (G59) HHH (R-4) Et 3, 5-d iMeO-Ph -0CH2 (1,4-Phy) CHr (G62) HHH (R_4) Et 3,5 ~ diMeO-Ph -0CH2 (1,4-Phy) CH2- (G63) HHH (R-4 ) Et 3,5-d iMeO-Ph -0CH2 (1,4-Phy) CHr (G64) HHH (R-4) Et 3,5-d iMeO-Ph -〇CH2 (l, 4-Phy) CHr ( G66) HHH (R ~ 4) Et 3,5-diMeO-Ph -OCH2 (1,4-Phy) CHr (G70) HHH (R-4) Et 3,5-d iMeO-Ph -0CH2 (1,4 -Phy) CHr (G73) HHH (R_4) Et 3,5-diMeO-Ph -〇CH2 (1,4-Phy) CH2- (G76) HHH -119- 200300349

2-564 (R ~ 4) Et 3,5-diMeO-Ph -0CH2 (1,4-Phy) CHr (G79) HHH 2-565 (R-4) Et 3,5-diMeO-Ph -0CH2 (1 , 4-Phy) CHr (G82) HHH 2-566 (R ~ 4) Et 3,5-diMeO-Ph -0CH2 (1,4-Phy) CHr (G85) HHH 2-567 (R-4) Et 3 , 5-diMeO-Ph -0CH2 (1,4-Phy) CHr (G86) HHH 2-568 (R-4). Et 3, 5-diMe〇-Ph -0CH2 (1,4-Phy) CHr (G106 ) HHH 2-569 (R_4) Et 3, 5-diMeO-Ph -0CH2 (1,4-Phy) CHr (G90) HHH 2-570 (R-4) Et 3,5-diMeO-Ph -0CH2 (1 , 4-Phy) CHr (G91) HHH 2-571 (R-4) Et 3, 5-diMeO-Ph -0CH2 (1,4-Phy) CHr (G92) HHH 2-572 (R-4) Et 3 , 5-diMeO-Ph -0CH2 (1,4-Phy) CHr (G93) HHH 2-573 (R-4) Et 3-MeO-Ph -0CH2 (1,4-Phy) CHr (G3) HHH 2- 574 (R ~ 4) Et 3-MeO-Ph -0CH2 (1,4-Phy) CHr (G13) HHH 2-575 (R-4) Et 3-MeO-Ph -0CH2 (1,4-Phy) CHr (G24) HHH 2-576 (R-4) Et 3-MeO-Ph -0CH2 (1,4-Phy) CHr (G59) HH .H 2-577 (R-4) Et 3-MeO-Ph -0CH2 (1,4-Phy) CHr (G64) HHH 2-578 (R-4) Et 3-MeO-Ph -0CH2 (1,4-Phy) CHr (G73) HHH 2-579 (R-4) Et 3 -MeO-Ph -0CH2 (1,4-Phy) CHr (G76) HHH 2-580 (R ~ 4) Et 3-MeO-Ph-0CH2 (1,4-Phy) CH2- (G79) HHH 2-581 (R-4) Et 3-MeO-Ph -0CH2 (1,4-Phy) CHr (G82) HHH 2-582 (R-4) Et 3,4-diMe〇-Ph -0CH2 (1 , 4-Phy) CHr (G3) HHH 2-583 (R_4) Et 3,4-diMeO-Ph -0CH2 (1,4-Phy) CHr (G13) HHH 2-584 (R ~ 4) Et 3,4 -diMeO-Ph -0CH2 (1,4-Phy) CHr (G24) HHH 2-585 (R-4) Et 3,4-diMeO-Ph -0CH2 (1,4-Phy) CHr (G59) HHH 2- 586 (R-4) Et 3,4-diMeO ~ Ph -0CH2 (1,4-Phy) CHr (G64) HHH 2-587 (R ~ 4) Et 3,4-diMeO-Ph-0CH2 (1,4 -Phy) CHr (G73) HHH 2-588 (R-4) Et 3,4-diMeO-Ph-0CH2 (l, 4-Phy) CH2- (G76) HHH 2-589 (R ~ 4) Et 3, 4-diMeO-Ph -0CH2 (1,4-Phy) CHr (G79) HHH -120- 200300349

2-590 (R-4) Et 3,4-diMeO-Ph -0CH2 (1,4-Phy) CHr (G82) HHH 2-591 (R-4) Et 3,5-diEtO-Ph -0CH2 (1 , 4-Phy) CHr (G3) HHH 2-592 (R-4) Et 3,5-diEt〇-Ph -0CH2 (1, 4-Phy) CHr (G13) HHH 2-593 (R-4) Et 3,5 ~ diEt〇-Ph -0CH2 (l, 4-Phy) CHr (G24) HHH 2-594 (R-4) Et 3,5-diEt〇-Ph -0CH2 (1,4-Phy) CHr ( G59) 'HHH 2-595 (R-4) Et 3,5-diEtO-Ph -0CH2 (l, 4-Phy) CHr (G64) HHH 2-596 (R-4) Et 3, 5-diEt〇- Ph -〇CH2 (l, 4-Phy) CHr (G73) HHH 2-597 (R-4) Et 3,5-diEtO-Ph -0CH2 (1, 4-Phy) CHr (G76) HHH 2-598 ( R-4) Et 3, 5-diEt〇-Ph -0CH2 (l, 4-Phy) CHr (G79) HHH 2-599 (R-4) Et 3,5-diEt〇-Ph ~ 0CH2 (1,4 -Phy) CHr (G82) HHH 2-600 (R_4) Pr 3,5-diMeO-Ph -0CH2 (1, 4-Phy) CHr (G3) HHH 2-601 (R-4) Pr 3, 5-d iMeO-Ph -0CH2 (1,4-Phy) CHr (G13) HHH 2-602 (R-4) Pr 3, 5-diMeO-Ph -0CH2 (1, 4-Phy) CHr (G24) HHH 2-603 (R-4) Pr 3, 5-diMeO-Ph -0CH2 (1,4-Phy) CHr (G59) HHH 2-604 (R-4) Pr 3, 5-diMeO-Ph -OCH2 (1, 4- Phy) CHr (G64) HHH 2-605 (R-4) Pr 3, 5-diMeO-Ph -0CH2 (1,4-Phy) CHr (G73) HHH 2-606 (R-4 ) Pr 3, 5-diMeO-Ph -0CH2 (1,4-Phy) CHr (G76) HHH 2-607 (R-4) Pr 3, 5-d iMeO-Ph -OCH2 (1,4-Phy) CHr (G79) HHH 2-608 (R-4) Pr 3, 5-diMe〇-Ph -〇CH2 (1,4-Phy) CHr (G82) HHH 2-609 (R-4) Bu 3, 5-diMe 〇-Ph -0CH2 (1,4-Phy) CHr (G3) HHH 2-610 (R_4) Bu 3, 5-diMeO-Ph -OCH2 (1,4 ~ Phy) CHr (G13) HHH 2-61.1 (R -4) Bu 3,5-d iMeO-Ph -OCH2 (1,4-Phy) CHr (G24) HHH 2-612 (R-4) Bu 3,5-d iMeO-Ph -OCH2 (1,4- Phy) CHr (G59) HHH 2-613 (R-4) Bu 3, 5 ~ diMe〇-Ph -0CH2 (1,4-Phy) CHr (G64) HHH 2-614 (R_4) Bu 3, 5-diMe 〇-Ph -0CH2 (1,4-Phy) CHr (G73) HHH 2-615 (R-4) Bu 3, 5 ~ d iMeO-Ph -〇CH2 (1,4-Phy) CHr (G76) HHH- 121- 200300349 2-616 2-617 2-618 2-619 2-620 2-621 2-622 2-623 2-624. 2-625 2-626 2-627 2-628 2-629 2-630 2 -631 2-632 2-633 2-634 2-635 2-636 2-637 2-638 2-639 2-640 2-641 (R-4) Bu 3,5-diMe〇-Ph -0CH2 (1 , 4-Phy) CHr (R-4) Bu 3,5-diMe〇-Ph -0CH2 (1,4-Phy) CHr (R-4) Me 3,5-diMeO-Ph -0 (CH2) 2 ( 1,4-Phy) CH2- (R-4) Me 3,5-diMeO-Ph -〇 (CH2) 2 (l, 4-Phy) CH2- (R-4) Me 3,5-d iMeO-Ph ~ 0 (CH2) 2 (1,4-Phy) CH2- (R ~ 4) Me 3,5-diMeO-Ph -0 (CH2) 2 (1,4-Phy) CHr (R-4) Me 3,5-diMeO-Ph -0 (CH2) 2 (1,4-Phy) CH2- (R-4) Me 3,5-d iMeO-Ph -0 (CH2) 2 (1,4-Phy) CHr (R-4) Et 3 , 5-diMeO ~ Ph -0 (CH2) 2 (1,4-Phy) CHr (R-4) Et 3,5-d iMeO-Ph -0 (CH2) 2 (1,4-Phy) CHr (R -4) Et 3,5-d iMeO-Ph -0 (CH2) 2 (1,4-Phy) CHr (R-4) Et 3,5-d iMeO-Ph -0 (CH2) 2 (1,4 -Phy) CHr (R-4) Et 3, 5-d iMeO-Ph -0 (CH2) 2 (1,4-Phy) CHr (R-4) Et 3, 5-d iMeO-Ph -0 (CH2 ) 2 (1,4-Phy) CHr (R-4) Et 3,5-diMeO-Ph -0 (CH2) 2 (1,4-Phy) CH2- (R-4) Et 3,5-diMeO- Ph -0 (CH2) 2 (1,4-Phy) CH2- (R-4) Et 3,5-d iMeO-Ph -0 (CH2) 2 (1,4-Phy) CH2- (R-4) Pr 3,5-diMeO-Ph -0 (CH2) 2 (1,4-Phy) CH2- (R-4) Pr 3,5-d iMeO-Ph Ό (CH2) 2 (1,4-Phy) CHr (R-4) Pr 3,5-d iMeO-Ph -0 (CH2) 2 (1,4-Phy) CHr (R-4) Pr 3,5-d iMeO-Ph -0 (CH2) 2 (1 , 4-Phy) CH2- (R-4) Pr 3,5-d iMeO-Ph -0 (CH2) 2 (1,4-Phy) CH2- (R-4) Pr 3,5-diMeO-Ph- 0 (CH2) 2 (1,4 ~ Phy) CH2- (R-4) Pr 3,5-diMeO-Ph -0 (CH2) 2 (1,4-Phy) CHr (R-4) Pr 3,5 -diMeO-Ph -0 (CH2) 2 (1,4-Phy) CHr (R-4) Pr 3,5-d iMeO-Ph -0 (CH2) 2 (1,4-Phy) CH2-

(G79) Η Η H (G82) Η Η H (G3) Η Η H (G13) Η Η H (G64) Η 'Η H (G70) Η Η H (G73) Η Η H (G76) Η Η H ( G3) Η Η H (G13) Η Η H (G24) Η Η H (G59) Η Η H (G64) Η Η H (G73) Η Η H (G76) Η Η H (G79) Η Η H (G82) Η Η H (G3) Η Η H (G13) Η Η H (G24) Η Η H (G59) Η Η H (G64) Η Η H (G73) Η Η H (G76) Η Η H (G79) Η Η Η H (G82) Η Η H -1222003200349

2-642 (R-4) Bu 3,5-diMe〇-Ph -0 (CH2) 2 (1,4-Phy) CHr (G3) Η Η H

2-643 (R-4) Bu 3,5-diMe〇-Ph -0 (CH2) 2 (1,4-Phy) CHr (G13) Η Η H

2-644 (R-4) Bu 3,5-diMe〇-Ph -0 (CH2) 2 (1,4-Phy) CHr (G24) Η Η H

2-645 (R-4) Bu 3,5-diMeO-Ph -0 (CH2) 2 (l, 4-Phy) CH2- (G59) Η Η H

2-646 (R-4) Bu 3,5-diMe〇-Ph -0 (CH2) 2 (l, 4-Phy) CHr (G64) Η Η H

2-647 (R-4) Bu 3,5-diMe〇-Ph -0 (CH2) 2 (1,4-Phy) CHr (G73) Η Η H

2-648 (R-4) Bu 3,5-diMe〇-Ph -〇 (CH2) 2 (l, 4-Phy) CHr (G76) Η Η H

2-649 (R-4) Bu 3,5-diMeO-Ph -0 (CH2) 2 (l, 4-Phy) CH2- (G79) Η Η H

2-650 (R-4) Bu 3,5-diMe〇-Ph -〇 (CH2) 2 (l, 4-Phy) CHr (G82) Η Η H

2-651 (R-4) All 3,5-diMe〇-Ph -〇 (CH2) 2 (l, 4-Phy) CHr (G3) Η Η H

2-652 (R-4) All 3,5-diMeO-Ph -0 (CH2) 2 (1,4-Phy) CHr (G13) Η Η H

2-653 (R-4) All 3,5-diMe〇-Ph -0 (CH2) 2 (1,4-Phy) CHr (G2'4) Η Η H

2-654 (R-4) All 3,5-diMeO ~ Ph -0 (CH2) 2 (1,4-Phy) CHr (G59) Η Η H

2-655 (R-4) All 3,5-diMe〇-Ph -0 (CH2) 2 (1,4-Phy) CHr (G64) Η Η H

2-656 (R-4) All 3,5-diMe〇-Ph ~ 0 (CH2) 2 (1,4-Phy) CHr (G73) Η Η H

2-657 (R-4) All 3,5-diMeO-Ph -0 (CH2) 2 (1,4-Phy) CHr (G76) Η Η H

2-658 (R-4) All 3,5-diMeO-Ph -0 (CH2) 2 (1,4-Phy) CHr (G79) Η Η H

2-659 (R-4) All 3,5-diMeO-Ph -0 (CH2) 2 (1,4-Phy) CHr (G82) Η Η H

2-660 (R-4) Me 3,5-diMeO-Ph-0 (CH2) "1,4-Phy) CH" (G3) Η Η H

2-661 (R-4) Me 3,5-diMe〇-Ph -0 (CH2) 3 (l, 4_Phy) CH2- (G13) Η Η H

2-662 (R-4) Me 3,5-diMe〇-Ph -〇 (CH2) 3 (l, 4-Phy) CHr (G64) Η Η H

2-663 (R-4) Me 3,5-diMe〇-Ph -0 (CH2) 3 (1,4-Phy) CHr (G70) Η Η H

2-664 (R-4) Me 3,5-diMeO-Ph -0 (CH2) 3 (1,4-Phy) CH Factory (G73) Η Η H

2-665 (R-4) Me 3,5-diMeO-Ph -0 (CH2) 3 (1,4-Phy) CHr (G76) Η Η H

2-666 (R-4) Et 3,5-diMe〇-Ph -0 (CH2) 3 (1,4-Phy) CHr (G3) Η Η H

2-667 (R-4) Et 3,5-diMeO-Ph -0 (CH2) 3 (1,4-Phy) CHr (G13) Η Η H -123- 200300349

2-668 (R-4) Et 3,5 ~ diMe〇-Ph ~ 0 (CH2) 3 (1,4-Phy) CHr (G24) Η Η H

2-669 (R-4) Et 3,5-diMeO-Ph -0 (CH2) 3 (1,4-Phy) CHr (G59) Η Η H

2-670 (R-4) Et 3,5-diMeO-Ph -0 (CH2) 3 (1,4-Phy) CHr (G64) Η Η H

2-671 (R-4) Et 3,5-diMeO-Ph -〇 (CH2) 3 (l, 4-Phy) CHr (G73) Η Η H

2-672. (R-4) Et 3,5-diMeO-Ph -0 (CH2) 3 (1,4-Phy) CHr (G76) Η Η H

2-673 (R-4) Et 3,5-diMe〇-Ph -0 (CH2) 3 (1,4-Phy) CHr (G79) Η Η H

2-674 (R-4) Et 3,5 ~ diMe〇-Ph -0 (CH2) 3 (1,4-Phy) CHr (G82) Η Η H

2-675 (R-4) Pr 3,5-diMe〇-Ph -0 (CH2) 3 (1,4 ~ Phy) CHr (G3) Η Η H

2-676 (R-4) Pr 3,5-diMeO-Ph -0 (CH2) 3 (1,4-Phy) CH2- (G13) Η Η H

2-677 (R-4) Pr 3,5 ~ diMe〇-Ph -0 (CH2) 3 (1,4-Phy) CHr (G24) Η Η H

2-678 (R-4) Pr 3,5-diMeO-Ph -0 (CH2) 3 (l, 4-Phy) CH2- (G59) Η Η H

2-679 (R-4) Pr 3,5-diMe〇-Ph -0 (CH2) 3 (1,4-Phy) CHr (G64) Η Η H

2-680 (R-4) Pr 3,5-diMe〇-Ph -0 (CH2) 3 (1,4-Phy) CHr (G73) Η Η H

2-681 (R-4) Pr 3,5-diMeO-Ph -0 (CH2) 3 (1,4-Phy) CH2- (G76) Η Η H

2-682 (R ~ 4) Pr 3,5-diMe〇-Ph -0 (CH2) 3 (1,4-Phy) CHr (G79) Η Η H

2-683 (R-4) Pr 3,5-diMeO-Ph -0 (CH2) 3 (1,4-Phy) CHr (G82) Η Η H

2-684 (R-4) Me 3,5-diMeO-Ph -0 (CH2) 2 (1,4-Phy) (CH2) 2- (G3) Η Η H

2-685 (R-4) Me 3,5-diMe〇-Ph -0 (CH2) 2 (1,4-Phy) (CH2) r (G13) Η Η H

2-686 (R-4) Me 3,5-diMeO-Ph -0 (CH2) 2 (1,4-Phy) (CH2) 2- (G64) Η Η H

2-687 (R-4) Me 3,5-diMe〇-Ph -〇 (CH2) 2 (l, 4-Phy) (CH2) r (G70) Η Η H

2-688 (R-4) Me 3,5-diMe〇-Ph -0 (CH2) 2 (1,4-Phy) (CH2) r (G73) Η Η H

2-689 (R-4) Me 3,5-diMe〇-Ph -0 (CH2) 2 (1,4-Phy) (CH2) r (G76) Η Η H

2-690 (R-4) Et 3,5-diMeO-Ph -0 (CH2) 2 (1,4-Phy) (CH2) 2- (G3) Η Η H

2-691 (R ~ 4) Et 3, 5-diMe〇-Ph -〇 (CH2) 2 (l, 4-Phy) (CH2) r (G13) Η Η H

2-692 (R-4) Et 3,5-diMe〇-Ph -〇 (CH2) 2 (l, 4-Phy) (CH2) r (G24) Η Η H

2-693 (R-4) Et 3,5-diMe〇-Ph -0 (CH2) 2 (1,4-Phy) (CH2) r (G59) Η Η H -124- 200300349

2-694 (R-4) Et 3,5-diMeO-Ph -0 (CH2) 2 (1,4-Phy) (CH2) r (G64) HHH 2-695 (R-4) Et 3,5- diMeO-Ph -〇 (CH2) 2 (l, 4-Phy) (CH2) r (G73) HHH 2-696 (R-4) Et 3,5-diMeO-Ph -0 (CH2) 2 (1,4 -Phy) (CH2) r (G76) HHH 2-697 (R-4) Et 3,5 ~ diMeO-Ph -〇 (CH2) 2 (l, 4-Phy) (CH2) r (G79) HHH 2- 698 (R-4) Et 3,5-diMeO-Ph -〇 (CH2) 2 (l, 4-Phy) (CH2) r (G82) HHH 2-699 (R-4) Pr 3,5-diMeO- Ph -0 (CH2) 2 (1, 4-Phy) (CH2) r (G3) HHH 2-700 (R-4) Pr 3, 5-diMeO-Ph -0 (CH2) 2 (i, 4-Phy ) (CH2) 2- (G13) HHH 2-701 (R-4) Pr 3, 5-diMeO-Ph -〇. (CH2) 2 (l, 4-Phy) (CH2) 2- (G24) HHH 2 -702 (R-4) Pr 3,5-diMe〇-Ph -0 (CH2) 2 (1, 4-Phy) (CH2) r (G59) HHH 2-703 (R-4) Pr 3,5- diMe〇-Ph -0 (CH2) 2 (1,4-Phy) (CH2) 2- (G64) HHH 2-704 (R-4) Pr 3, 5-diMe〇-Ph -0 (CH2) 2 ( 1, 4-Phy) (CH2) r (G73) HHH 2-705 (R-4) Pr 3, 5-diMe〇-Ph -0 (CH2) 2 (1, 4-Phy) (CH2) r (G76 ) HHH 2-706 (R-4) Pr 3, 5-diMeO-Ph -0 (CH2) 2 (1,4-Phy) (CH2) r (G79) HHH 2-707 (R-4) Pr 3, 5-diMeO-Ph -0 (CH2) 2 (1,4-Phy) (CH2) r (G82) HHH 2-708 (R-4) Et 3, 5-diMe〇-Ph -CH2OCH2 (l, 4 ~ Phy) CHr (G3) HHH 2-709 (R-4) Et 3, 5-diMe〇-Ph -CH20CH2 (1, 4-Phy) CHr (G8) HHH 2-710 (R -4) Et 3, 5-diMeO-Ph -CH2OCH2 (l, 4 ~ Phy) CHr (G13) HHH 2-711 (R-4) Et 3,5-diMeO-Ph -CH2OCH2 (l, 4-Phy) CHr (G24) HHH 2-712 (R-4) Et 3, 5-diMeO ~ Ph -CH2OCH2 (l, 4-Phy) CHr (G34) HHH 2-713 (R-4) Et 3, 5-diMeO ~ Ph -CH2OCH2 (l, 4 ~ Phy) CHr (G59) HHH 2-714 (R-4) Et 3, 5-diMe〇-Ph -CH20CH2 (1,4-Phy) CHr (G64) HHH 2-715 ( R-4) Et 3, 5-diMeO-Ph -CH20CH2 (1,4-Phy) CH2- (G70) HHH 2-716 (R_4) Et 3, 5-diMeO ~ Ph -CH20CH2 (1,4-Phy) CHr (G73) HHH 2-717 (R-4) Et 3, 5-diMeO-Ph -CH20CH2 (1,4-Phy) CHr (G76) HHH 2-718 (R-4) Et 3, 5-diMeO- Ph -CH2OCH2 (l, 4-Phy) CHr (G79) HHH 2-719 (R-4) Et 3, 5-diMeO-Ph -CH20CH2 (1,4-Phy) CH2- (G82) HHH -125- 200300349 2-720 (R-4) Et 3,5-diMe〇-Ph -SCH2 (1,4-Phy) CHr (G3) Η Η Η 2-721 (R ~ 4) Et 3,5-diMeO-Ph- SCH2 (1,4-Phy) CHr (G8) Η Η Η 2-722 (R-4) Et 3,5-diMe〇-Ph -SCH2 (1,4-Phy) CH2- (G13) Η Η Η 2 -723 (R ~ 4) Et 3,5-diMeO-Ph -SCH2 (1 4-Phy) CHr (G24) Η Η Η 2-724 (R-4) Et 3,5-diMeO-Ph -SCH2 (1,4-Phy) CHr (G34) Η Η Η 2-725 (R-4 ) Et 3,5-diMe0-Ph -SCH2 (1,4-Phy) CHr (G59) Η Η Η 2-726 (R-4) Et 3,5-diMeO-Ph -SCH2 (1,4-Phy) CHr (G64) Η Η Η 2-727 (R-4) Et 3,5-diMeO-Ph -SCH2 (1,4-Phy) CHr (G70) Η Η 728 2-728 (R-4) Et 3, 5-diMeO-Ph ~ SCH2 (1,4-Phy) CHr (G73) Η Η Η 2-729 (R ~ 4) Et 3,5-diMeO-Ph-SCH2 (1,4 -Phy) CHr (G76) 730 Η Η 2-730 (R-4) Et 3,5-diMeO-Ph-SCH2 (l, 4-Phy) CHr (G79) Η Η Η 2-731 (R-4) Et 3,5-diMeO- Ph-SCH2 (l, 4_Phy) CH2- (G82) Η Η Η 2-732 (R-4) Et 3,5-diEt〇-Ph-0 (CH2) 6- (G63) Η Η 733 2-733 ( R-4) Et 3,5-diEtO-Ph-0 (CH2) 6-(G77) Η Η Η 2-734 (R-4) Et 3-Me0-5-Pr0-Ph -0 (CH2) r ( G63) Η Η Η 2-735 (R-4) Et 3-Me〇-5-PrO-Ph -0 (CH2) 6- (G77) Η Η Η 2-736 (R-2) Et 3,5- diMeO-Ph-o (ch2) 7-(G77) Η Η 737 2-737 (R-4) Et 3,5-diMeO-Ph-o (ch2) 7-(G7) Η Η Η 2-738 (R -4) Et 3,5-diMeO-Ph-o (ch2) 7- (G46) Η Η 739 2-739 (R-4) Et 3,5-diMeO-Ph -0 (CH2) r (G63) Η Η Η 2-740 (R-4) Et 3,5-diMeO ~ Ph -o (ch2) 「(G71) Η Η Η 2-741 (R-4) Et 3,5-diMeO-Ph-o (ch2) 7 -(G94) Η Η Η 2-742 (R-4) Et 3,5-diMeO-Ph -〇 (ch2) r (G95) Η Η 743 2-743 (R-4) Et 3,5-diMeO- Ph-0 (CH2) r (G96) Η Η Η 2-744 (R-4) Et 3,5-diMeO-Ph-o (ch2) 7-(G97) Η Η 745 2-745 (R-4) Et 3,5-diMeO-Ph-o (ch2) 7-(G98) Η Η Η 200300349 2-746 (R-4) Et 3,5-diMe〇-Ph ~ 0 (CH2) r (G99) Η Η Η 2-747 (R-4) iPr 3,5-diMeO-Ph -〇 (CH2) 7- (G77) Η Η 748 2-748 (R-4) Et 3, 4-diMeO_Ph -o (ch2) 7 -(G63) Η Η Η 2-749 (R-4) Me 3,5-diEtO-Ph -0 (CH2) 7- (G63) Η Η 750 2-750 (R-4) Et 3,5-diEt 〇-Ph-〇 (CH2) 7-(G14) Η Η Η 2-751 (R-4) Et 3,5-diEtO-Ph-0 (CH2) 7- (G63) Η Η Η 2-752 (R -4) Et 3,5-diEtO-Ph -〇 (CH2) r (G65) Η Η 753 2-753 (R-4) Et 3,5-diEt〇-Ph -〇 (CH2) r (G74) Η Η Η 2-754 (R-4) Et 3,5-diEt〇-Ph-0 (CH2) 7- (G77) Η Η Η 2-755 (R-4) Et 3,5-diEt〇-Ph- o (ch2) 7- (G100) 丨 Η Η Η 2-756 (R-4) Et 3,5-diEtO-Ph-o (ch2) 7-(G101) 丨 Η Η Η 2-757 (R -4) Et 3,5-diEtO-Ph-o (ch2) 7-(G63) Η O MeO 2-758 (R-4) Et 3,5-diEtO-Ph-0 (CH2) r (G77) Η Η MeO 2-759 (R-4) iPr 3,5-diEt〇-Ph-0 (CH2) 7-(G63) Η Η Η 2-760 (R-4) 2-Prp 3,5-diEtO-Ph -o (ch2) 7_ (G63) Η Η Η 2-761 (R-4) 2-Prp 3,5-diEtO-Ph-0 (ch2) 7-(G74) Η Η Η 2-762 (R-4 ) 2-Prp 3,5-diEtO-Ph -o (ch2) 7- (G77) Η Η 763 2-763 (R-8) Et 3,5-diEtO-Ph-o (ch2) 7- (G63) 764 Η Η 2-764 (R-8) Et 3,5-diEtO-Ph-o (ch2) 「(G77) Η Η 765 2-765 (R-10) Et 3,5-diEtO-Ph-0 ( CH2) 7- (G63) Η Η Η 2-766 (R-10) Et 3,5-diEt〇-Ph-o (ch2) 7- (G77) Η Η 767 2-767 (R-11) Et 3 , 5-diEtO ~ Ph -0 (CH2) r (G63) Η Η Η 2-768 0M1) Et 3,5-diEtO-Ph -o (ch2) 7- (G77) Η Η Η 2-769 (R- 4) Et 3-MeO-5-PrO-Ph -0 (CH2) 7- (G14) Η Η Η 2-770 (R-4) Et 3-MeO-5-PrO-Ph -〇 (CH2) 7- (G63) Η Η Η 2-771 (R-4) Et 3-Me〇-5-Pr〇-Ph-0 (CH2) r (G74) Η Η Η -127- 200300349

2-772 (R-4) Et 3-Me〇-5-PrO-Ph -0 (CH2) 7-(G77) HHH 2-773. (R_4) Et 3-MeO-5-PrO-Ph -0 ( CH2) r (G100) HHH 2-774 (R-4) Et 3-MeOUrO-Ph-0 (CH2) 7- (G101) HHH 2-775 (R-4) 2-Prp 3-Me〇-5- Pr〇-Ph -〇 (CH2) r (G14) HHH 2-776 (R-4) 2-Prp 3-MeO-5-Pr〇-Ph -0 (CH2) r (G63) HHH 2-777 (R_4 ) 2-Pi * p 3-MeO-5-PrO-Ph -0 (CH2) r (G77) HHH 2-778 (R-4) Et 3-MeO-5-CF3-Ph -0 (CH2) r ( G63) HHH 2-779 (R-4) Et 3-Me0-5_CF3—Ph-0 (CH2) 「(G77) HHH 2-780 (R-4) Et 3-Me〇-5-C02Me ~ Ph -0 (CH2) 7- (G63) HHH 2-781 (R-4) Et 3-MeO-5-NOrPh -0 (CH2) r (G63) HHH 2-782 (R-4) Et 3 -EtO-5- MeO-Ph -0 (CH2) 7-(G14) HHH 2-783 (R-4) Et 3-EtO-5_Me (HPh -0 (CH2) 7-(G74) HHH 2-784 (R-4) Et 3-EtO-5-Me〇-Ph -〇 (CH2) 7- (G77) HHH 2-785 (R-4) Et 3_E t〇-5_Pr〇-Ph -〇 (CH2) 7- (G14) HHH 2 -786 (R-4) Et 3-EtO-5-Pr (HPh -0 (CH2) 7-(G63) HHH 2-787 (R-4) Et 3-EtO-5-PrO-Ph -0 (CH2 ) 7-(G74) HHH 2-788 (R-4) Et 3-EtO-5 -PrO-Ph -0 (CH2) Factory (G77) HHH 2-789 (R-4) Et 3-EtO-5- i PrO-Ph -0 (CH2) 7- (G63) HHH 2-790 (R-4) Et 3-Et〇-5-iPr (HPh-〇 (CH2) 7- (G77) HHH 2-791 (R- 4) Et 3,5-diPr〇-Ph -〇 (CH2) r (G63) HHH 2-792 (R-4) Et 3,5-diPrO-Ph -0 (CH2) r (G74) HHH 2-793 (R-4) Et 3,5-diPrO-Ph -0 (CH2) r (G77) HHH 2-794 (R-4) Et 3-iPrO-5-Me〇-Ph -0 (CH2) r (G63 ) HHH 2-795 (R-4) Et 3-iPr〇-5-MeO-Ph -0 (CH2) r (G74) HHH 2-796 (R-4) Et 3-iPr0-5-MeCHPh_0 (CH2) 7- (G77) HHH 2-797 (R-4) Et 3-Bu〇-5-Me〇-Ph -0 (CH2) 7- (G14) HHH

-128- 200300349

2-798 (R-4) Et 3-Bu0-5 ~ * Me0-Ph-0 (CH2) 7-(G74) HHH 2-799 (R-4) Et 3-Bu0 ~ 5-Me0-Ph -0 (CH2) 7- (G77) HHH 2-800 (R-4) Et 3,5-diMe ~ Ph -〇 (CH2) r (G63) HHH 2-801 (R-4) Et 3,5-diEt- Ph -0 (CH2) r (G63) HHH 2-802 (R_4) Et 3,5-diF-Ph -〇 (CH2) 7 ~ (G63) HHH 2-803 (R-4) Et 3,5-diF -Ph -〇 (CH2) f (G74) HHH 2-804 (R-4) Et 3-F-4-Me〇-Ph -0 (CH2) 7- (G63) HHH 2-805 (R-4) Et 3-F-4-MeO-Ph-0 (CH2) 7- (G77) HHH 2-806 (R ~ 4) Et 3-Pr〇-Ph -0 (CH2) 7- (G14) HHH 2-807 (R-4) Et 3-Pr〇-Ph ~ 0 (CH2) 7- (G74) HHH 2-808 (R-4) Et 3-Pr〇-Ph -0 (CH2) 7- (G77) HHH 2 -809 (R-4) Et 3-Bu〇-Ph -0 (CH2) r (G14) HHH 2-810 (R_4) Et 3-BuCHPh-o (ch2) 7- (G63) HHH 2-811 (R -4) Et 3-BuO-Ph -0 (CH2) 7- (G74) HHH 2-812 (R-4) Et 3-BuO-Ph -0 (CH2) 7- (G77) HHH 2-813 (R -4) Et 3-CONHr5-MeO-Ph -〇 (CH2) 7- (G63) HHH 2-814 (R-4) Et 3-OCON (Me) 2-5 -MeO-Ph -0 (CH2) r (G63) HHH 2-815 (R-4) Et 3 ~ OCON (Me) r5-MeO-Ph -0 (CH2) r (G77) HHH 2-816 (R-4) Et 3-NHAc + MeO-Ph -〇 (CH2 ) 7- (G63) HHH 2-817 (R-4) Et 3-N (Me) 2-5-MeO-Ph -0 (CH2) r (G63) HHH 2-818 (R-4) Et 3- CN-5-Me〇-Ph -〇 (CH2) 7- (G63) HHH 2-819 (R-4) Et 3,4-diMeO-Ph -〇 (CH2) 8-(G63) HHH 2-820 ( R-4) Et 3,5-diEtO-Ph -〇 (CH2) 8-(G14) HHH 2-821 (R-4) Et 3,5-diEt〇-Ph -〇 (CH2) 8-(G63) HHH 2-822 (R-4) Et 3,5-diEtO-Ph -o (ch2) 8-(G65) HHH 2-823 (R-4) Et 3,5-diEtO-Ph-o (ch2) 8 -(G74) HHH -129- 200300349

2-824 (R-4) Et 3,5-diEt〇-Ph _〇 (CH2) r (G77) HHH 2-825 (R-4) Et 3,5-diEt (HPh-〇 (CH2) r ( G102) HHH 2-826 (R-4) Et 3,5-diEtO-Ph ~ 〇 (ch2) 8- (G63) HH MeO 2-827 (R ~ 4) Et 3,5-diEtO-Ph ~ 〇 ( ch2) 8- (G77) HH MeO 2-828 (R-4) Et 3-Me〇-5-Pr (HPh -〇 (ch2) 8- (G14) HHH 2-829 (R-4) Et 3- Me〇-5-PrO-Ph -o (ch2) 「(G63) HHH 2-830 (R-4) Et 3-Me〇-5-PrO-Ph -o (ch2) 8-(G74) HHH 2- 831 (R_4) Et 3-Me〇-5-PrO-Ph -〇 (ch2) 8- (G77) HHH 2-832 (R-4) 2 ~ Prp 3-Me0-5-PrCHPh _〇 (ch2) 8 -(G14) HHH 2-833 (R-4) 2-Prp 3-MeO-5-PrO-Ph-〇 (CH2) 8-(G63) HHH 2-834 (R_4) 2-Prp 3-MeO-5 -PrO-Ph-o (ch2) 8-(G74) HHH 2-835 (R-4) Pi * p 3-MeO-5-PrCHPh-〇 (CH2) 8-(G77) HHH 2-836 (R- 4) Et 3-EtO-5-MeO-Ph -0 (CHZ) 8- (G14) HHH 2-837 (R-4) Et 3-EtO-5-MeO-Ph -0 (CH2) 8- (G74 ) HHH 2-838 (R-4) Et 3 -EtO-5 -MeiHPh -〇 (CH2) f (G77) HHH 2-839 (R-4) Et 3-EtO-5 ~ Pr〇-Ph _〇 ( CH2) r (G63) HHH 2-840 (R-4) Et 3-EtO-5-PrO-Ph -0 (CH2) 8- (G74) HHH 2-841 (R-4) Et 3 ~ EtO-5 -Pr〇 -Ph -〇 (CH2) 8- (G77) HHH 2-842 (R-4) Et 3,5-diPrO-Ph -0 (ch2) 8- (G77) HHH 2-843 (R-4) Et 3 -BuO-5-Me〇-Ph-0 (ch2) 8- (G14) HHH 2-844 (R-4) Et 3-BuO-5 *-* MeO-Ph -o (ch2) 8-(G74) HHH 2-845 (R-4) Et 3-Bu〇-5-Me〇-Ph _0 (ch2) 「(G77) HHH 2-846 (R-4) Et 3-Pr〇-Ph-0 (ch2) 8-(G14) HHH 2-847 (R-4) Et 3-PrO-Ph-0 (CH2) r (G74) HHH 2-848 (R-4) Et 3-PrO-Ph-0 (CH2) r (G77) HHH 2-849 (R-4) Et 3-iPrO-5-Me (HPh -0 (ch2) 8- (G63) HHH -130- 200300349

2-850 (R-4) Et 3 ~ Bu〇-Ph ~ 〇 (ch2) 8- (G14) HHH 2-851 (R ~ 4) Et 3 ~ Bu〇-Ph -〇 (ch2) 8- (G63 ) HHH 2-852 (R-4) Et 3-BuO-Ph -o (ch2) 8- (G74) HHH 2-853 (R-4) Et 3-Bn〇-Ph -〇 (ch2) 「(G77 ) HHH 2-854 (R-4) Et 3,5-diEtO-Ph-S (CH2) 7- (G63) HHH 2-855 (R-4) Et 3,5-diEtO-Ph-S (CH2) 7-(G65) HHH 2-856 (R-4) Et 3,5-diEtO-Ph-S (CH2) 7- (G102:) HHH 2-857 (R-4) Et 3,5-diMeO-Ph _o (ch2) 3nhco- (G50) HHH 2-858 (R-4) Et 3,5-diMeO-Ph -0 (CH2) 3NHC0- (G54) HHH 2-859 (R-4) Et 3,5- diEt〇-Ph -o (ch2) 3nhco- (G96) HHH 2-860 (R-4) Et 3,5 ~ diEtO_Ph -o (ch2) 3conh-(G96) HHH 2-861 (R-4) Et 3 , 5-diMeOHPh -0CH2 (1,4-Phy) (CH2) 2- (G77) HHH 2-862 (R-4) Et 3,5-diMeO-Ph -0CH2 (1,4-Phy) (CH2> 3- (G77) HHH 2-863 (R-4) Et 3,5-diMeO-Ph--0 (CH2) 2 (l, 4HPhy) CHr (G77) HHH 2-864 (R ~ 4) Et 3, 5-diMe〇-Ph--0 (CH2) 2 (1,4-Phy) (CH2) r (G77) HHH 2-865 '(R-4) Et 3,5-diMeO-Ph--0 (CH2 ) 3 (l, 4 ~ Phy) CHr (G77) HHH 2-866 (R-4) 2-Prp 3-Me0-5-Pr0-Ph -0 (CH2) 7- (G77) HHH 2-867 (R -4) Et 3,5-diMeO-Ph-〇 (ch2) 8-(G63) HHH 2-868 (R-4) Et 3,5-diF-Ph -〇 (CH2) 7-(G77) HHH 2-869 ( R-4) Et 3,5-diEtO-Ph-o (ch2) 7- (G102) H: HH 2-870 (R-4) Et 3,5-diEtO-Ph-s (ch2) 7-(G77 ) HHH 2-871 (R-4) 2 ~ Prp 3,5-diMeO-Ph -0 (CH2) 7- (G77) HHH 2-872 (R-4) Et 3,5-diPrO-Ph-〇 ( ch2) 8- (G74) HHH 2-873 (R_4) Et 3,5-diPrO-Ph-o (ch2) 8- (G63) HHH 2-874 (R -13) Et 3,5-diEtO-Ph- o (ch2) 7-(G77) HHH 2-875 (R-13) Et 3,5-diEtO-Ph -0 (CH2) r (G63) HHH -131- 200300349

2-876 (R-12) Et 3,5-diEtO-Ph -0 (CH2) 7-(G63) HHH '2-877 (R ~ 4) Et 3-MeO-5-NHC02Me-Ph -〇 (CH2 ) 7- (G63) HHH 2-878 (R-4) Et 3,5-diEtO-Ph-0 (CH2) 7- (G76) HHH 2-879 (R-4) Et 3,5-diMeO-Ph -〇 (CH2) r (G62) HHH 2-880 (R-4) Et • 3,5-diEtO-Ph-0 (CH2) 8-(G62) HHH 2-881 (R-4) Et 3,5 -diEtO-Ph-o (ch2) 7-(G62) HH MeO 2-882 (R-4) Et 3, 5-diEtO,-0 (CH2) 7_ (G76) HH MeO 2-883 (R-4) Et 3,5-diEtO-Ph -〇 (CH2) 8- (G76) HH MeO 2-884 (R-4) Et 3,5-diEt〇-Ph -0 (CH2) 7- (G62) HHH 2- 885 (R-4) Et 3-Et〇-5-PrO-Ph -0 (CH2) r (G76) HHH 2-886 (R-4) Et 3,5-diEtO-Ph -0 (CH2) 7- (G62) H tt H 2-887 (R-4) Et 3,5-diEtO-Ph -0 (CH2) r (G103) HHH 2-888 (R-4) Et 3,5-diEtO-Ph -〇 (CH2) r (G104) HHH 2-889 (R-4) Et 3-Bu〇-5-MeCHPh -0 (CH2) r (G63) HHH Particularly preferred among the above is the compound number: Bu 14, 1-2.6, 1-27, Bu 32, Bu 33, Bu 66, Bu 173, Bu 175, 1-179, Bu 188, 1-190, 1-191, 1-192, 1-550, 1-561, 1-564, 1-568, 1-570, 1-573, 1-575, 1-579, 1-580, 1-581, 1-584, 1-592, 1-595, 1- 596, 1-597, 1-604, 1-605, 1-606, 1-608, 1- 611, 1-799, 2-28, 2-29, 2-34, 2-35, 2-44, 2-47, 2-50, 2-63, 2-121, 2-122, 2- 123, 2-124, 2-125, 2-127, 2-137, 2-158, 2-159, 2- 160, 2-161, 2-162, 2-163, 2-178, 2-180, 2-185, 2-196, 2-197, 2-198, 2-199, 2-242, 2-254, 2-256, 2-290, 2-296, 2-297, 2-298, 2-299, 2-324, 2-326, 2-335, 2-337, 2-338, 2-339, 2- 340, 2-341, 2-529, 2-533, 2-563, 2-624, 2-625, 2-628, 2-629, 2-630, 2-631, 2-691, 2-695, 2-696, 2-739, 2-751, 2-754, 2-757, 2-758, 2-788, 2-821, 2-827, 2-878, 2-879, 2-880, 2- 881, 2-882, 2-883, 2-884, and 2-885, more preferably, -132- 200300349, preferably the exemplified compound number: 1-2 6, 1-2 7, 1-3 2, 1-3 3, 1-1 7 5, 1 -1 7 9, 1-188, 1-190, 1-191, 1-192, 1-570, 1-573, 1-575, 1-579, 1-580, 1-581, 1-584,1-592 ^ 1-596, 1-597

, 1-604, 1-605, 1-606, 2-28, 2-29, 2-34, 2-35, 2-121, 2-122, 2-123, 2-124, 2-125 ^ 2 -127, 2-137, 2-158, 2-159, 2-160, 2-16, 2-162, 2-163, 2-178, 2-180, 2-185, 2-196, 2-197 , 2-198, 2-199, 2-242, 2-254, 2-256, 2-290, 2-2 9 6, 2-2 9 7, 2-2 9 8, 2-2 9 952-3 2 4, 2-3 2 6, 2-3 3 5, 2-337, 2-338, 2-339, 2-340, 2-34, 2-624, 2-625, 2-628, 2-629 , 2-630, 2-631, 2-691, 2- 695, 2-696, 2-793, 2-751, 2-754, 2-757, 2-758, 2-788, 2-821, 2 -827, 2-878, 2-879, 2-880, 2-881, 2-882, 2-883, 2-884 and 2-8 8 5 and more preferably,

Exemplary compound numbers: 1-32, 1-33, 1-175, 188, 1-179, 1-190, 1-191, 1-192, 1-570, 1-575, 1-575, 1-580 , 1-581, 1-584, 1-592, 1-596, 1-597, 1-604, 1-605, 2-34, 2-35, 2-121, 2-123, 2-124, 2 -125, 2-127, 2-137, 2-158, 2-159, 2-160, 2-161,2-162 ^ 2-178, 2-1 80, 2-290, 2-296, 2- 2 97, 2 -29 8, 2-299, 2 -3 24, 2-326, 2-3 3 5, 2-3 3 7 ^ 2-3 3 8, 2-3 3 9, 2-3 40, 2-34 1, 2-625, 2-629, 2-630, 2-739, 2-751, 2-754, 2-757, 2-758, 2-788, 2-821, 2-827, 2 -878, 2-879, 2-880, 2-881, 2-882, 2-883, 2-884 and 2-8 8 5, more preferably, exemplified compound number: 1-1 7 9, 1-1 9 0, 1-1 9 1, 1-5 7 0, 1-5 7 5-133- 200300349, 1-592, 1-596, 1-597, 1-604, 1-605, 2-121, 2 -123, 2-137, 2-158, 2-159, 2-160, 2-161,2-162 ^ 2-178, 2-180, 2-290, 2-296, 2-297, 2-326 , 2-337, 2-338, 2-339, 2-340, 2-739, 2-751, 2-754, 2-757, 2-758, 2-788, 2-821, 2-827, 2 -878, 2-879, 2-880, 2-881, 2-882, 2-8 83,2-884 and 2-885, most preferably selected from any of the following compounds, exemplified compound No. 5 7 5: Chlorinated 1-{2-{3-{3-[N-(3,5 -2 Fluorophenyl) -N-ethylaminomethylmethyl] -7-methoxy-4-oxo-4H-quinolin-1-yl} -5 -methoxyphenoxymethyl} benzyl} pyridine, exemplified Compound No. 1-5 9 6 ·· 1- {2- {3- {3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -7-methoxy 4-oxo-4H-quinolin-1-yl} -5-methoxyphenoxymethyl} benzyl} azobicyclo [2.2.2] octane, exemplified compound numbers 1-5 9 7: chloride 1 -{2- {3- {3-[> ^-(3,5-difluorophenyl) -N-ethylaminemethylmethyl] -7-methoxy-4-oxo-4H-quinoline- Alkyl} -5-methoxyphenoxymethyl} benzyl} -4-acyl-1-azobicyclo [2.2.2] octane exemplified compound number 1-6 0 4: brominated 1- {2- { 3- {3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -7-methoxy-4-oxo-4H-quinoline-bubbill 5-methoxy Phenoxymethyl} benzyl 4 -acyl-1 -azobicyclo [2.2 · 2] octane Λ Exemplified compound number 2-1 2 3: Brominated 1-{7-[3-[N-(3, 5 -difluorophenyl) -N-ethylaminomethylmethyl] -1- (3,5-dimethoxyphenyl) -4 -oxy-1,4- Hydroquinoline-7-yloxy] heptyl} pyridine, Exemplified Compound Number 2-158: 1- {7- [3- [N- (3,5-difluorophenyl 200300349) -N- Ethylaminomethyl] -1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] heptylbu 1-azobicyclo [2.2 .2] Octane, Exemplified Compound Number 2-1 5 9: Brominated 1-{7-[3-[N-(3,5-difluorophenyl) -N-ethylaminomethylmethyl]]-1- (3,5 -dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7-yloxy] heptylazobicyclo [2.2.2] octane, Exemplified Compound Number 2-1 6 0: 1-{7-[3-[N-(3,5-difluorophenyl) -N-ethylaminomethylmethyl]]-1- (3,5-dimethoxyphenyl)- 4-oxo-1,4-dihydroquinoline-7-yloxy] heptyl} -4 -azol-1-azobicyclo [2 · 2 · 2] octane, exemplified compound number 2-1 6 6 ·· Bromide 1-{7-[3-[Ν-(3,5-difluorophenyl) -N-ethylaminomethylmethyl]]-1- (3,5-dimethoxyphenyl) -4 -Oxo-1,4-dihydroquinoline-7-yloxy] heptylbu 4-acyl-1-azobicyclo [2.2.2] octane, exemplified compound number 2-2 9 0: brominated 1 -{7-[3-[Ν-(3,5-difluorophenyl) -N-ethylaminomethylmethyl]]-1- (3,5 -Dimethoxyphenyl) -4 -oxo-1,4-dihydroquinolin-7-ylsulfanyl] heptyl} pyridine, Exemplified Compound No. 2-2 9 6: Brominated 1-{7- [3-[Ν-(3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3,5-dimethoxyphenyl) -4 -oxy-1,4-dihydro Quinoline-7-ylsulfanyl] heptyl}-1-azobicyclo [2 · 2 · 2] octane, and exemplified compound number 2-2 9 7: Brominated 1-{7-[3-[ Ν-(3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7 -Alkylsulfanyl] heptylb 4 -Acryl-1 -azobicyclo [2.2 · 2] octane or selected from any of the following compounds Exemplified compound number 2-7 3 9: Brominated 1-{7-[3 -[Ν-(3,5-difluorophenyl) -N-ethylaminomethylmethyl] · -1- (3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquine Phenolin-7-yloxy] heptylb-methylpiperidine, exemplified compound number 2-7 5 1: bromide 1-(7-{1-(3,5-diethoxyphenyl 200 300 349)-3 -[N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -4 -oxo-1,4-dihydroquinoline-7-yloxy} heptyl) -1 -methyl Piperidine, Exemplified Compound Numbers 2-7 5 4: 1- (7-{1-(3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -4 -oxy- 1,4 -dihydroquinoline-7-yloxy} heptyl) -4 -acyl-1 -azobicyclo [2.2 · 2] octane, Exemplified compound number 2-7 5 7: Brominated 1-( 7-{1-(3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -5-methoxy-4- Oxy-1,4-dihydroquinoline-7-yloxy} heptyl) -diphendipine, Exemplified compound number 2-7 5 8: Brominated 1-(7-{1-(3,5- Diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -5-methoxy-4-oxo-1,4-dihydroquinoline -7-yloxy} heptyl) -4-acyl-1-azobicyclo [2 · 2 · 2] octane, exemplified compound number 2-7 8 8: brominated 1-{7-[3-[ N-(3,5-difluorophenyl) -N -ethylaminomethylmethyl] -1- (3-ethoxy-5-propoxyphenyl) -4 -oxo-1,4-dihydroquine Phenolin-7-yloxy] heptylb 4-az-1-azobicyclo [2 · 2 · 2] octane, exemplified compound number 2-8 2 1: brominated 1-(8-{1-( 3,5-diethoxyphenyl) -3- [1 (3,5-difluorophenyl)-^ ethylaminomethylmethyl] -4-oxo-1,4-dihydroquinolin-7-yl Yl} octyl) -1-methylpiperidine, exemplified compound number 2-8 2 7: bromide 1-(8-{1-(3,5-diethoxyphenyl) -3- [N- (3 , 5 -difluorophenyl) -N-ethylamine formamidine 5-methoxy-4 -oxo-1,4-dihydroquinoline-7-yloxy} octyl) -4 -acyl- Pyrazinebicyclo [2 · 2 · 2] octane, Exemplified Compound Numbers 2-8 7 8: Chlorinated 1-(7-{1-(3,5 -diethoxyphenyl) -3- [Ν- (3,5-difluorophenyl) -1 ethylaminomethylmethyl] -4-oxo-1,4- -136- 200300349 dihydroquinoline-7 -yloxy} heptyl) -4 -acyl- 1-Azobicyclo [2 · 2 · 2] octane, Exemplified Compound Number 2-8 7 9: Chlorinated 1-{7-[3-[N-(3, 5 -difluorophenyl) -N- Ethylaminomethylmethyl] -1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] heptylbuprofen 1-methylpiperidine, exemplified Compound Number 2-8 8 0: Chloride 1-(8-{1-(3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -1 ^ -ethyl Carbamidyl] -4-oxo-1,4-dihydroquinolin-7-yloxy} octyl) -propranolol, Exemplified Compound No. 2-8 8 1: Chloride 1-(7- {1-(3,5-diethoxyphenyl) -3- [1 ^-(3,5-difluorophenyl)] 1 -Ethylaminomethyl}}-5-methoxy-4-oxo-1,4-dihydroquinoline-7-yloxy) heptyl) -1-methylpiperidine, Exemplified Compound Number 2-882: 1- (7- {1- (3,5-diethoxyphenyl) -3- [1 (3,5-difluorophenyl) -1 ethylamine formamidine 5-methoxy- 4-oxo-1,4-dihydroquinoline-7-yloxy} heptyl) -4-acid-1-azobicyclo [2 · 2 · 2] octane, exemplified compound number 2-8 8 3 : 1-(8 · {1-(3,5-diethoxyphenyl) -3- [1 (3,5-difluorophenyl) -1 ^ -ethylaminomethyl)]-5- Methoxy-4-oxo-1,4-dihydroquinoline-7-yloxy} octyl) -4-acyl-1-azobicyclo [2.2 · 2] octane, exemplified compound numbers 2-8 8 4: 1-{7-[1-(3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N -ethylaminomethyl]] 4-oxo-1,4-dihydroquinoline-7-yloxy] heptylb-methylpiperidine and exemplified compound number 2-8 8 5 ·· chloride 1-{7-{3-[N -(3,5-difluorophenyl) -N-ethylaminomethyl] -1- (3-ethoxy-5-propoxyphenyl) -4-oxo-1,4-dihydroquinoline -7-yloxy} heptylb 4-az-1-azobicyclo-137- 200300349 [2.2.2] octane. The compounds having the formulae (I) and (Π) of the present invention can be produced by the following method. Method A is to prepare the compound (I) of the present invention in which Gn + is (i), (ii), (iv), (v), (vii), (viii), (ix) or (X) group (lb ) And a method in which Gn + is a compound (I c) of (iii), (iv) or (vi) group. Method A

In the formula, Ri, R2, R4, R5, R6, R7, A, D, E, (χ-) η and ring Ar are as defined above, Rla, R4a, R5a, 1163 and 1173 are R1, R4, R5, R6 And R7 group except for the amino group, hydroxyl group, and / or carboxyl group contained in the substituent, which can be protected, the same groups as R1, R4, R5, R6, and R7,

The definition of Gln + is as described above for Gn + group, (i) a lower alkyl group substituted with a group selected from substituent b and the same 200300349 or an isopropyl 3 substituted ammonium group, (ii) a nitrogen atom on the ring and E A combined ammonium group, a lower alkyl group substituted with a group selected from the substituent b, and a 1-pyridinyl group, which may be substituted with a group 1 to 3 selected from the substituent b and fused with a benzene ring Pyridyl or 1-pyridinyl> (iv) The nitrogen atom on the secondary median ring is bound to E, and the nitrogen atom is replaced by a lower alkyl or oxy group to form an ammonium group, a 1-piperidinyl group, a 1-piperidine Or 4-morpholinyl, (v) may have a 1- (1-azobicyclo [2.2.2] octyl substituted with a lower alkyl substituted with a substituent b, a substituent b and an oxo group Or a 1- (4-acyl-1 -azobicyclo [2 · 2 · 2] octyl) group, (vii) may have an oxy group or 1 to 3 substituted 1-tetrahydrothienyl groups or 1-tetrahydrothiopyranyl, (viii) has a lower alkyl group substituted with a substituent b and the same or different group of a lower alkyl group 2 substituted sulfonyl groups, (i X) has a substituent selected from b-substituted lower alkyl and lower alkyl are the same or different 3 substituted phosphino, or (X) nitrogen atom on the secondary mesogenic ring and E is bonded, and the nitrogen atom is substituted by a lower alkyl group or an oxy group to form an ammonium 1-pyrrolidinyl group, and G1 indicates that the above-mentioned Gln + group is represented by (i), (ii), ( iw), (v), (vii), (viii), (ix) or (x), ie: (i-1) a lower alkyl group and a lower alkyl group substituted with a group selected from the substituent b Identical or different 3 substituted amine compounds, (ϋ-1) lower alkyl substituted with a group selected from substituent b, and optionally substituted with 1 to 3 selected from group b, and may be fused with a benzene ring Pyridine ring compound -139- 200300349, pyridine ring compound or pyrimidine ring compound, piperidine ring compound, piperidine ring compound or morpholine in which the nitrogen atom on the (i V-1) ring is substituted with lower alkyl or oxy group A ring compound, (v-1) may have a 1- (1-azobicyclo [2.2.2] octyl) ring selected from the group consisting of a lower alkyl substituted with a substituent b, a substituent b and an oxy group. Compound or 1- (4-acyl-1-azobicyclo [2.2 · 2] octyl) ring compound, (vii-1) tetrahydrothiophene ring compound or tetrahydro Thiopyran compound, (viii-1) has a substituent b The same or different group substituted with lower alkyl and lower alkyl group 2 substituted sulfofluorenyl compounds, (i X-1) the same or different group substituted with lower alkyl and lower alkyl selected from substituent b A heterocyclic 3 substituted phosphino compound, or a pyridine D-fixed ring compound in which the nitrogen atom on the (X-1) ring is substituted with a lower alkyl group or an oxy group, ... G 2 n + is the aforementioned definition of Gn + group: (iii) A pyridinyl group, a pyridyl group, or a pyrimidine group which is bonded to the carbon atom on the secondary meso ring, and at least one nitrogen atom on the ring is substituted with a lower alkyl group or an oxy group to form an ammonium group, and which can be fused with a benzene ring An ammonium group, (iv) a nitrogen atom on the secondary median ring is bonded to E, and the nitrogen atom is substituted by a lower alkyl group or an oxy group to form an ammonium group, piperidin-1-yl, piperin-1-yl, or morpholine-4 -Group, or (vi) a carbon atom on the secondary mesial ring is bonded to E, and at least one nitrogen atom on the ring is substituted with a lower alkyl group or an oxy group to form an ammonium group (1-azobicyclo [2.2.2] octyl) Group or (4 -acryl-1-azobicyclo [2.2.2] octyl) group, G2 is shown in the above definition of G2n + group by the positive charge of fluorene (iii), -140- 200300349 (iv) or ( vi), ie: (iii-1) carbon atoms on the meso ring Pyridinyl, pyridyl, or pyrimidyl, which can be fused with benzene ring, and piperidine-1 -yl, piperidin-1 -yl, which is bound to the nitrogen atom on the secondary median ring with E Or a morpholin-4-yl or (vi-1) secondary mesogenic ring with a carbon atom bound to E (1-azobicyclo [2.2 · 2] octyl) yl or (1,4-diazobicyclo [2.2 .2] octyl) group, X is a group which is an anion in the definition of X · by negative charge of 帯, that is, a halogen atom selected from fluorine atom, chlorine atom, iodine atom, bromine atom, etc .; Ci-6 alkylsulfonyloxy, such as ethanesulfonyloxy; benzenesulfonyloxy, p-TsO_ (p-toluenesulfonyloxy), OTf — (trifluoromethanesulfonyloxy), pentafluoroethanesulfonyloxy C6_1G arylsulfonyloxy, such as the above-mentioned lower alkyl, lower alkoxy, halogen atom and halogen lower alkyl having 1 to 3 substituents. The "protecting group" of the "protectable amine group" in the above definitions of R4a, R5a, R6a and R7a is not specific as long as it is an amine protecting group used in organic synthetic chemistry, and may be as described in "General protection of hydroxyl esters" "Aliphatic fluorenyl"; "aromatic fluorenyl"; "co-oxyfluorenyl"; "enoxyfluorenyl"; "aralkoxycarbonyl"; "silyl"; or "aralkyl" Or N, N-dimethylamine methylene, benzylidene, 4-methoxybenzylidene, 4-nitrobenzylidene, sulfenyl, 5-chlorosulfenyl, diphenylmethylene, "Substituted methylene forming a Schiff base" such as (5-chloro-2 -hydroxyphenyl) benzylidene, preferably an aliphatic fluorenyl, alkoxycarbonyl or aralkyloxycarbonyl group, more preferably a methylfluorenyl group , A third butoxycarbonyl group or a benzyloxycarbonyl group, most preferably a benzyloxycarbonyl group. In the above, the "protecting group" of the "protectable hydroxyl group" in the definitions of Rla, R4a, R5a, R6a, and R7a2 is not specific as long as it is a hydroxyl protecting group used in organic synthetic chemistry -141-200300349. As the aforementioned "general protecting group in the reaction of hydroxyl esters", it is preferably an alkoxymethyl group, a silyl group or an aralkyl group, more preferably a methoxymethyl group, a third succinic group or a benzyl group, and most preferably Is methoxymethyl or benzyl. In the above, Rla, R4a, R5a, R6a, and R7a, the "protecting group" of the "protectable carboxyl group" is not specific as long as it is a carboxyl protecting group used in organic synthetic chemistry, and may be the same as the "carboxyl ester" The general protecting group in the reaction "is preferably low or square, more preferably ethyl, third butyl or benzyl, and most preferably third butyl. It is called that the project A1 is a process for manufacturing the compound (lb), and the compound (III) is reacted with the compound (IV) in an inert solvent for execution. (a) In order to convert the nitrogen atom on the ring of the G1 + group into an ammonium group, the compound obtained after the above reaction in an inert solvent is reacted with the following compound of general formula (V): X-R1 1 (V) [wherein, X is the same as In the foregoing meaning, R11 is a lower alkyl group substituted with a group selected from the substituent group b and a group substituted with the group b. ], And / or, Lu (b) Removal and protection of amine, hydroxy, and or carboxyl groups in Rla, R4a, R5a, feet 63 and R7a. The inert solvent used in the reaction between compound (III) and compound (IV) is not specific as long as it does not affect the reaction, such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, third butanol, isopropyl alcohol Alcohols such as pentanol, diethylene glycol, glycerol, octanol, cyclohexanol, or methoxyethanol; nitriles such as acetonitrile, isopropionitrile; or formamidine, dimethylformamide, and dimethylacetamide And amines such as trimethylamine hexamethylphosphate, preferably nitriles or amines (most preferably ethyl-142-200300349 nitrile or dimethylformamide). The reaction temperature of the reaction between the compound (III) and the compound (IV) varies depending on the raw material compound, the solvent, etc., and is usually -2 (TC ~ 20 (TC (preferably ot ~ 100V)). The compound (III) and the compound ( IV) The reaction time varies depending on the raw material compound, solvent, reaction temperature, etc., and it is usually 30 minutes to 48 hours (preferably 1 to 24 hours). The G 1 + radical in the ring The inert solvent used in the ammonium conversion reaction is a solvent inert to the reaction, as long as it does not affect the reaction, for example, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, third Alcohols such as butanol, isoamyl alcohol, diethylene glycol, glycerol, octanol, cyclohexanol, or methoxyethanol; nitriles such as acetonitrile, isopropionitrile; or formamidine, dimethylformamide, and dimethylformamide The ammonium amines such as acetylacetamide and hexamethylphosphonium triamine are preferably nitriles (most preferably acetonitrile). The reaction temperature used for the conversion of the ammonium group of the nitrogen atom on the ring in the G 1 + group should be expected. It varies with raw material compounds, solvents, etc., usually 0 ° C ~ 150 ... (preferably 20 ~ 100 ° c). The reaction time required for the conversion of the ammonium group of the nitrogen atom on the G 1 + group to be carried out depends on the raw material compound, solvent, reaction temperature, etc., and is usually 30 minutes to 24 hours (preferably 1 hour to 12 hours) ). The removal of the protective groups of amine, hydroxyl and carboxyl groups varies according to their types, and can generally be based on the methods of organic synthetic chemistry technology last week, for example, T.W.Green. (Proteqtive Groups in Organic Synthesis), John Wiley & Sons: J. FW McOmis. (Protective Groups in Organic Chemistry), Plenum Press The method -143- 200300349 is carried out as follows. When the protective group of the amino group is a silyl group, it can usually be treated with tetrabutylammonium fluoride. , Hydrofluoric acid, hydrofluoric acid-pyridine, potassium fluoride and other compounds that generate fluoride anions to remove. The solvent used in the above reaction is not limited, but in order to suppress side reactions, such as diethyl ether, diisopropyl ether, tetrahydrofuran should be used. , Dioxane, dimethoxyethane, or diethylene glycol dimethyl ether, etc. The reaction temperature and reaction time are not limited. Usually, the reaction temperature is 0 to 50 ° C, and the reaction time is 1 to 1 8 hours. Amine When the protecting group of the group is an aliphatic fluorenyl group, an aromatic fluorenyl group, an alkanecarbonyl group, or a substituted methylene group forming a Schiff base, it is removed by treatment with an acid or a base in the presence of an aqueous solvent. The acid used in the above reaction As long as the acid used in the removal of the protective group of the above amine group is not specific, for example, inorganic acids such as hydrobromic acid, hydrochloric acid, sulfuric acid, perchloric acid, phosphoric acid, or nitric acid, and hydrochloric acid are preferred. The alkali acid used when removing the protective group of the above-mentioned amine group is not specific. For example, alkali metal carbonates such as lithium carbonate, sodium lithium carbonate, and potassium carbonate; alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide Species; metal alkoxides such as lithium methoxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide; or ammonia such as ammonia, concentrated ammonia-methanol. The solvent used in the above reaction may be, for example, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tertiary butanol, isoamyl alcohol, diethylene glycol, glycerol, octanol, cyclohexanol or Alcohols such as methoxyethanol; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, or diethylene glycol dimethyl ether; water; or a mixture of water and the above organic solvent, preferably an alcohol Class (especially 200 300 349 ethanol). The reaction temperature and reaction time vary depending on the starting compound, the solvent, and the acid or base used, and are not specific. However, in order to suppress side reactions, the reaction temperature is usually 0 to 150 ° C and the reaction time is 1 to 10 hours. When the protective group of the amine group is an aralkyl group or an aralkyloxycarbonyl group, it is usually removed by contacting a reducing agent in an inert solvent (catalyst reduction, catalyst reduction at normal temperature) or using an oxidizing agent. The inert solvent used in the catalyst reduction is not specific as long as it does not affect the reaction. Aliphatic hydrocarbons such as hexane, heptane, petroleum spirit or petroleum ether can be used; aromatic hydrocarbons such as toluene, benzene, or xylene; ethyl acetate, Esters such as propyl acetate and diethyl carbonate; ethers such as diethyl ether, isopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; ethanol, n-propanol, isopropyl alcohol , N-butanol, isobutanol, tertiary butanol, isoamyl alcohol, diethylene glycol, glycerol, octanol, cyclohexanol, methoxyethanol and other alcohols; organic acids such as acetic acid; water; or the above solvents and Mixtures of water, preferably alcohols, ethers, organic acids or water (most preferably alcohols or organic acids). The catalyst used in the catalyst reduction is preferably Pd / C, Ruanlai nickel, platinum oxide, platinum black, rhodium-alumina, triphenylphosphine-rhodium oxide, palladium-barium sulfate. The pressure is not specified, and is usually applied at 1 to 10 atmospheres. The reaction temperature and reaction time vary depending on the starting compounds, catalysts, inert solvents, etc. Generally, the reaction temperature is 0 ° C to 100 ° C, and the reaction time is 5 minutes to 24 hours. The inert solvent used for the oxidative removal is not specific as long as it does not affect the reaction. An organic solvent containing water is preferred. This organic solvent can be halogenated hydrocarbons such as chloroform, dichloromethane, -145- 200300349 1, 2-dichloroethane, carbon tetrachloride; nitriles such as acetonitrile, ether, isopropyl ether, tetrahydrofuran, and dioxane , Dimethoxyethane or diethylene glycol dimethyl ether; ketones such as acetone; formamidine, dimethylformamide, dimethylacetamide or hexamethylphosphonium triamine Amines; or dimethylene, cyclobutane, and other fluorenes, preferably halogenated hydrocarbons, ethers, or fluorenes (most preferably halogenated hydrocarbons or fluorenes). The oxidant used in the above reaction can remove the amine protecting group. The oxidant used is not specific. It is preferably potassium persulfate, sodium persulfate, ammonium nitride (CAN), 2,3-dichloro-5, 6-di Cyano-p-quinone (DDQ). The reaction temperature and reaction time vary depending on the starting compound, oxidant, solvent, etc. Generally, the reaction temperature is from 0 ° C to 150 ° C, and the reaction time is from 10 minutes to 24 hours. When the protecting group of the amine group is an aralkyl group, the protecting group may be removed by an acid. The acid used in the above reaction can remove the aralkyl group of the amine protecting group. The acid used is not specific, and it is preferably an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, perchloric acid, phosphoric acid; Acid, p-toluenesulfonic acid, sulfonic acid, trifluoroacetic acid, trifluoromethanesulfonic acid, and other organic acids such as Bululin deacidification; zinc chloride, tin tetrachloride, boron trichloride, boron trifluoride, Lewis acid such as boron tribromide; acidic ion exchange resin; inorganic or organic acid (preferably hydrochloric acid, acetic acid or trifluoroacetic acid). The inert solvent used in the above reaction is not specific as long as it does not affect the reaction. Aliphatic hydrocarbons such as hexane, heptane, petroleum spirit or petroleum ether can be used; aromatic hydrocarbons such as benzene, toluene, or xylene; chloroform, dichloride Methane, 1,2-dichloroethane, carbon tetrachloride and other halogenated hydrocarbons; methyl acetate, ethyl acetate, propyl acetate, butyl acetate, diethyl carbonate and other esters; ethyl-146- 200300349 ether , Isopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether and other ethers; methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, third Alcohols such as butanol, isoamyl alcohol, diethylene glycol, glycerol, octanol, cyclohexanol, methoxyethanol; formamidine, dimethylformamide, dimethylacetamide, hexamethylphosphorus Hydrazones such as hydrazine triamine; water; or a mixed solvent of water and the above solvents; preferably ethers, alcohols or water (preferably tetrahydrofuran, dioxane, ethanol or water). The reaction temperature varies depending on the raw material compound, the acid used, the solvent, and the like. Generally, the reaction temperature is -20 ° C to the boiling point (preferably 0 ° C to 100 ° C). _ The reaction time varies depending on the raw material compound, the acid used, the inert solvent, the reaction temperature, etc., and is usually 15 minutes to 48 hours (preferably 30 minutes to 20 hours). When the protective group of the amine group is an alkenyloxycarbonyl group, the conditions for removing the reaction when the protective group of the imine amine group is the aforementioned aliphatic fluorenyl group, aromatic fluorenyl group, alkenyloxycarbonyl group, or substituted methylene group forming a Schiff base Perform with alkali treatment. In the case of an allyloxycarbonyl group, the removal method using palladium and triphenylphosphine or nickel tetracarbonyl is particularly simple and has few side reactions. · If the protective group of the hydroxy group is a silane group, it is usually treated with tetrabutylammonium fluoride, hydrofluoric acid, hydrofluoric acid-pyridine, potassium fluoride and other compounds that form fluoride anions, or it is removed with hydrochloric acid, hydrogen, etc. Inorganic acids such as bromic acid, sulfuric acid, perchloric acid, and phosphoric acid, or organic acids such as acetic acid, formic acid, oxalic acid, methanesulfonic acid, p-toluenesulfonic acid, sulfonic acid, trifluoroacetic acid, and trifluoromethanesulfonic acid Remove. When the fluoride anion is removed, the reaction may be promoted by adding organic acids such as formic acid, acetic acid, and propionic acid. -147 · 200300349 The inert solvent used in the above reaction is not specific as long as it can dissolve the raw materials and reagents without affecting the reaction, such as diethyl ether, isopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol di Ethers such as methyl ether; nitriles such as acetonitrile and isobutyronitrile; organic acids such as acetic acid; water; a mixed solvent of the above solvents. The reaction temperature and reaction time vary depending on the starting compounds, catalysts, inert solvents, etc. Generally, the reaction temperature is 0 ° C to 100 ° C (preferably lot to 50 ° C), and the reaction time is 1 to 24 hours. When the protective group of the hydroxy group is an aralkyl group or an aralkyloxycarbonyl group, it is usually removed by contacting with a reducing agent in an inert solvent (preferably under a catalyst, reduction at room temperature) or by using an oxidizing agent. Catalytic reduction is used to remove the inert solvents used as long as it does not affect the reaction. Aliphatic hydrocarbons such as hexane, heptane, petroleum spirit, petroleum ether can be used; aromatic hydrocarbons such as benzene, toluene, xylene; acetic acid Ester such as ethyl acetate, propyl acetate; ethers such as diethyl ether, isopropyl ether, tetrahydrofuran, dihumane, dimethoxyethane, diethylene glycol dimethyl ether; methanol, ethanol, n-propanol, isopropyl alcohol , N-butanol, isobutanol, tertiary butanol, isoamyl alcohol, diethylene glycol, glycerol, octanol, cyclohexanol, methoxyethanol and other alcohols; formamidine, dimethylformamide , Dimethylacetamide, N-methyl-2 2-pyrrolidone, hexamethylphosphonium triamine, and other amines; fatty acids such as formic acid, acetic acid; water; or a mixed solvent of the above solvents; preferably alcohols (Preferably methanol or ethanol). The catalyst used for removal by catalyst reduction may be a user who conventionally removes the above-mentioned hydroxy protecting group for catalytic reduction reaction, but it is not specific, and may be, for example, palladium-carbon, palladium black, Ruanlai nickel, platinum oxide, platinum hafnium, rhodium-alumina, Triphenylphosphine monochloride-148- 200300349 Germanium, palladium-barium sulfate, preferably palladium-carbon. The pressure is not specified, and is usually 1 to 10 atmospheres. The reaction temperature and reaction time vary depending on the raw material compound, catalyst, inert solvent, etc. Generally, the reaction temperature is 0 ° C to 100 ° C (preferably 20 ° c to 70 ° C), and the reaction time is 5 minutes to 4 8 Hours (preferably 1 ~ 2 4 hours). The solvent used for removal by oxidation is not limited as long as it does not participate in the reaction, and is preferably an aqueous organic solvent. For example, ketones such as acetone; halogenated hydrocarbons such as chloroform, dichloromethane, and carbon tetrachloride; nitriles such as acetonitrile; ethers such as diethyl ether, tetrahydrofuran, and dioxane; dimethylformamide, dimethylacetamidine Amines, such as amines, hexamethylphosphonium triamine, and boron, such as dimethylphosphine. The oxidant used in the above reaction is not limited to the oxidized oxygen used to remove the above-mentioned hydroxyl protecting group, and is preferably not limited to potassium persulfate, sodium persulfate, ammonium nitride (CAN), 2,3-dichloro-5,6 -Dicyano-p-quinone (DDQ). The reaction temperature and reaction time vary depending on the starting compounds, oxidizing agents, inert solvents, etc. Generally, the reaction temperature is 0 ° C to 150 ° C, and the reaction time is 10 minutes to 24 hours. Liquid ammonia or methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tertiary butanol, isoamyl alcohol, diethylene glycol, glycerol, octanol, cyclohexanol, methoxy Alcohols such as ethyl alcohol can also be removed from alkali metals such as lithium and sodium at -7 ° C ~ 0 t. It can also be removed in an inert solvent with an alkylsilyl halide such as aluminum chloride-sodium iodide or trimethylsilane iodide. The inert solvent used is not limited as long as it does not participate in the reaction, and halogenated hydrocarbons such as chloroform, methylene chloride, and carbon tetrachloride; nitriles such as acetonitrile; and a mixed solvent of the above solvents can be used. -149- 200300349 The reaction temperature and reaction time vary depending on the starting compounds, inert solvents, etc. Usually, the reaction temperature is 0 to 50 ° C, and the reaction time is 5 minutes to 72 hours. If the reaction substrate has sulfur atoms, aluminum chloride-sodium iodide is suitable. If the protective group of the hydroxyl group is an aliphatic fluorenyl group, an aromatic fluorenyl group or an alkoxycarbonyl group, it is removed by treatment with a base in an inert solvent. The base used in the above reaction is a base used to remove the above-mentioned hydroxy protecting group, and is not particularly limited. It is preferably an alkali metal carbonate such as lithium carbonate, sodium carbonate, potassium carbonate, etc .; lithium hydrogen carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, etc. Alkali metal hydrogen carbonates; Lithium hydroxide, sodium hydroxide, potassium hydroxide and other alkali metal hydroxides; lithium methoxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide and other metal alkoxides; ammonia, concentrated Ammonia such as ammonia-methanol, preferably alkali metal hydroxides, metal alkoxides or ammonia (preferably alkali metal hydroxides or metal alkoxides). The inert solvent used in the above reaction is not specific as long as it is used by ordinary hydrolysis reaction users, and ethers such as diethyl ether, isopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, and diethylene glycol dimethyl ether can be used; methanol , Alcohol, n-propanol, isopropanol, n-butanol, isobutanol, tertiary butanol, isoamyl alcohol, diethylene glycol, glycerol, octanol, cyclohexanol, methoxyethanol and other alcohols; Water; a mixed solvent of the above solvents. The reaction temperature and reaction time vary depending on the starting compound, the base used, the inert solvent, etc. In order to suppress side reactions, the reaction temperature is usually -20 to 150 ° C and the reaction time is 1 to 10 hours. When the protective group of the hydroxy group is an alkoxymethyl group, a tetrahydropyranyl group, a tetrahydrothiopyranyl group, a tetrahydrofuryl group, a tetrahydrothiofuranyl group or a substituted acetylene-150- 200300349 group, it is usually inert. The solvent was removed by treatment with an acid. The acid used in the above reaction is an acid used to remove the above-mentioned hydroxy-protecting group, and is not particularly limited. Generally, those who are used as Brienzide acid or Lewis acid can be inorganic acids such as hydrogen chloride, hydrochloric acid, sulfuric acid, nitric acid; Or bleach deacidification of organic acids such as acetic acid, trifluoroacetic acid, methanesulfonic acid, p-toluenesulfonic acid, etc .; Lewis acids such as boron trifluoride; also strong acidic cation exchange resins such as D owe X 50 W. The inert solvent used in the above reaction is not specific as long as it does not affect the reaction, and aliphatic hydrocarbons such as hexane, heptane, petroleum spirit, and petroleum ether can be used; aromatic hydrocarbons such as benzene, toluene, and xylene; chloroform and dichloromethane Institute, carbon tetrachloride, dichloroethane, chlorobenzene, dichlorobenzene and other halogenated hydrocarbons; ethyl formate, ethyl acetate, propyl acetate, butyl acetate, diethyl carbonate and other esters; ether, isopropyl Ethers such as propyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tertiary butanol , Isoamyl alcohol, diethylene glycol, glycerol, octanol, cyclohexanol, methoxyethanol and other alcohols; acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone, cyclohexanone, etc. Ketones; water; or mixed solvents of the above solvents; preferably ethers or alcohols (preferably tetrahydrofuran or methanol). The reaction temperature and reaction time vary depending on the raw material compound, the acid used, the inert solvent, etc., usually the reaction temperature is -10 to 200 ° c (preferably 0 to 150 ° c), and the reaction time is 5 minutes to 48 hours (preferably (30 minutes to 10 hours) 〇 When the protective group of the hydroxyl group is an alkenyloxycarbonyl group, the protective group of the imitation hydroxyl group is usually -151- 200300349 when the aforementioned aliphatic ethyl group, aromatic ethyl group or alkoxycarbonyl group is used. The reaction conditions were the same except that the reaction was performed by alkali treatment. In the case of an allyloxycarbonyl group, it is particularly suitable to remove it with palladium, triphenylphosphine or bis (methyldiphenylphosphine) (1,5-cyclooctadiene) iridium (I) · hexafluorophosphate. Simple and few side reactions. When the protective group of a carboxyl group is a lower alkyl group, a lower alkynyl group, or a lower alkenyl group, the removal reaction conditions are generally the same when the protective group mimicking a hydroxyl group is the aforementioned aliphatic fluorenyl group, aromatic fluorenyl group, or alkoxycarbonyl group. This is achieved by alkali treatment. The acid used in the above reaction is an acid used to remove the carboxy protecting group, and is not particularly limited, such as hydrochloric acid, sulfuric acid, phosphoric acid or hydrobromic acid. The bases used in the above reactions are bases that can be used to remove the carboxyl protecting group, such as alkali metal carbonates such as sodium carbonate and potassium carbonate; alkali metal hydrogens such as sodium hydroxide and potassium hydroxide Oxides; concentrated atmosphere-methanol solution, preferably sodium hydroxide. It may be isomerized by hydrolysis of alkali. The solvent used in the above reaction may be water or alcohols such as methanol, ethanol, n-propanol; ethers such as dioxane; or a mixed solvent of the above organic solvent and water, preferably an alcohol (most preferably methanol). The reaction temperature and reaction time vary depending on the starting compounds, solvents, and reagents used. They are not specific, but in order to suppress side reactions, the reaction temperature is usually 0 to 2 2 Ot and the reaction time is 0.5 to 10 hours. When the protective group of the carboxyl group is an aralkyl group or a halogenoalkyl group, it is usually removed by reduction in a solvent. Reduction method If the protective group of the carboxyl group is a halo-lower alkyl group, a chemical reduction method such as zinc-acetic acid is suitable; if it is an aralkyl group, a catalyst reduction method such as palladium-carbon or platinum catalyst is suitable, or Potassium sulfide, sodium sulfide and other alkali gold-152- 200300349 are chemical reduction methods to remove sulfides. The solvent used is not specific as long as it does not affect the reaction. Alcohols such as methanol and ethanol; ethers such as tetrahydrofuran and dioxane; fatty acids such as acetic acid; or mixed solvents of the above organic solvents and water. The reaction temperature and reaction time vary depending on the starting materials, the solvent, and the reduction method. Usually, the reaction temperature is from 01 to room temperature, and the reaction time is from 5 minutes to 12 hours. Removal of the protective groups of the amine group, the hydroxyl group and / or the carboxyl group can be carried out in a different order, and the desired removal reaction can be performed sequentially. After the reaction was completed, the target compound (lb) was recovered according to the usual method. For example, it can be obtained by distilling off the solvent. The obtained target compound is obtained by conventional methods, such as recrystallization, reprecipitation, and the like, which are conventionally used for separation and purification of organic compounds, and are purified by appropriately dissolving out a dissolving agent using chromatography. Process A2 is a process for producing compound (Ic). (C) In order to convert a nitrogen atom on a ring in the G 2 group into an ammonium group, a compound of general formula (VI) is reacted with the following general formula (V ') in an inert solvent. X-R1 la (V ') φ [wherein X has the same meaning as above, and Rlla is a lower alkyl group. ], Or, (d) In an inert solvent, react the compound (VI) with an oxidizing agent, and replace the nitrogen atom with an oxy group on the nitrogen atom of the G2 ring to convert the nitrogen atom to an ammonium group. If necessary, Rla, R4a, R5a Removal reaction of amine, hydroxy and / or carbonyl protecting groups in R7a and R7a. The inert solvent used in the reaction of compound (VI) and compound (V ') in (c) above is not specific as long as it does not affect the reaction and can be used Such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tertiary butanol, isoamyl alcohol-153- 200300349, diethylene glycol, glycerol, octanol, cyclohexanol or methoxy Alcohols such as ethanol; nitriles such as acetonitrile and isopropionitrile; or amidines such as formamidine, dimethylformamide, dimethylacetamide, and hexamethylphosphonium triamine, preferably nitriles (most (Acetonitrile is preferred). The reaction temperature of the reaction between the compound (VI) and the compound (ν ') in the above (C) may vary depending on the raw material compound, solvent, etc., and is usually 0 t ~ 2 50 ° C (preferably 20 ° C ~ 200 ° C). The reaction time of the above (c) compound (VI) and compound (VJ reaction can be determined by the starting compound, solvent, reaction The temperature varies depending on the temperature, and is usually 30 minutes to 24 hours (preferably 1 hour to 12 hours). The inert solvent used in the reaction between the compound (VI) and the oxidizing agent in the above (d) is not affected as long as it does not affect the reaction. Specific, for example, halogenated hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane, and carbon tetrachloride; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, or diethylene glycol Ethers such as dimethyl ether; nitriles such as acetonitrile, isopropionitrile; or amidines such as formamidine, dimethylformamide, dimethylacetamide, and hexamethylphosphonium triamine; preferably Halogenated hydrocarbons (most preferably dichloromethane). The oxidants used in (d) above are potassium persulfate, sodium persulfate, cerium ammonium nitride (CAN), 2,3-dichloro-5, 6- Dicyano-p-quinone (DDQ)) or m-chloroperbenzoic acid (mCPBA), preferably m-chloroperbenzoic acid. The reaction temperature of the reaction between the compound (VI) and the oxidant in (d) above may vary depending on the raw material compound, the solvent, etc. Normally, it is -2 0 t: ~ 100 ° C (preferably (TC ~ 50 ° C). The reaction time of the reaction between the compound (VI) and the oxidant in the above (d) can be determined by the combination of raw materials. Depending on the substance, solvent, reaction temperature, etc., it is usually 15-154- 200300349 minutes to 12 hours (preferably 30 minutes to 6 hours). If necessary, amines in Rla, R4a, R5a, R6a, and R7a The removal reaction of the protecting group of a hydroxyl group, a hydroxyl group, and / or a carbonyl group can be performed according to the above-mentioned A1 process of method A. After the reaction is completed, the target compound (1C) of the reaction can be obtained from the reaction mixture by a conventional method. For example, the reaction mixture The solvent is obtained by distillation. If necessary, the obtained target compound is obtained by combining conventional methods such as recrystallization, reprecipitation and other methods used for conventional separation and purification of organic compounds, and using chromatography to dissolve the elution agent appropriately. The method B is a method for producing the raw material compound (III) of the method A. Method B R7a no R7a 〇 〇

R7a Ο 0

In the formula, Rla, R2, R4a, R5a, R6a, R7a, rings Ar, D, E, and X are as defined above, and R 1 2 is a hydroxyl group or a protected hydroxyl group (the definition of the protecting group is the same as the protecting group for the above-mentioned hydroxyl group), m is an integer of 0 or 1, Y is an oxygen atom or a sulfur atom, Q is a leaving group of a general nucleophilic residue, and it is preferably a halogen such as chlorine, bromine, or iodine; trihalomethyl such as trichloromethoxy Oxy-155-200300349; lower alkanesulfonyloxy groups such as methanesulfonyloxy group and ethanesulfonyloxy group; haloalkanesulfonyloxy groups such as trifluoromethanesulfonyloxy group and pentafluoroethanesulfonyloxy group; Or arylsulfonyloxy, such as benzenesulfonyloxy, p-methanesulfonyloxy, and p-nitrobenzenesulfonyloxy, is most preferably a halogen atom. Process B 1 is a process for producing a compound of general formula (IX), which is obtained by reacting a compound of general formula (VII) with a compound of general formula (VIII) in the presence of an inert solvent and a base. The inert solvent used in the above reaction is not specific as long as it does not affect the reaction, for example, ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, and diethylene glycol dimethyl ether; or formazan Amines, such as amines, dimethylformamide, dimethylacetamide, and hexamethylphosphoniumtriamine; preferably amidines (most preferably N, N-dimethylformamide). The bases used in the above reactions are alkali metal carbonates such as sodium carbonate, potassium carbonate, and lithium carbonate; alkali metal hydrogen carbonates such as sodium hydrogen carbonate, potassium hydrogen carbonate, and lithium hydrogen carbonate; lithium hydride, sodium hydride, lithium hydride, etc. Alkali metal hydrides; alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, palladium hydroxide, and lithium hydroxide; inorganic salts such as alkali metal fluorides such as sodium fluoride and potassium fluoride; sodium methoxide , Alkali alkoxides such as sodium ethoxide, potassium methoxide, potassium ethoxide, potassium tert-butoxide, lithium methoxide, etc .; alkali metal sulfides such as sodium methyl sulfide, sodium ethane sulfide; ammonia water, concentrated ammonia -Ammonia such as methanol; or N-methylmorpholine, triethylamine, tripropylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinepyridine , Picolin, 4- (N, N-dimethylamino) pyridine, 2,6-bis (third butyl) -4-methylpyridine, quinoline, N, N-xylylamine, N, N -Diethylaniline, 1,5-diazinebicyclo [4.3.0] non-5-ene (DBN), 1,4-diazinebicyclo200300349 [2 · 2 · 2] octane (DABCO), 1,8 -Two acryl Bicyclic [5.4.0] deca-7-ene (D B U) and other organic bases, preferably alkali metal hydrides or alkali metal carbonates (most preferably sodium hydride or potassium carbonate). The reaction temperature varies depending on the starting compound, base, solvent, etc., and is usually -20 ° C to 120 ° C (preferably, 0 ° C to 7 (TC). The reaction time depends on the starting compound, base, solvent, and reaction temperature. It varies from 30 minutes to 24 hours (preferably 1 to 12 hours). The second step B2 is a process for producing the compound (III) and when the hydroxyl group of the R 1 2 group is protected in the compound (IX). 2. After removing the protecting group, in an inert solvent, in the presence or absence of Lewis acid (preferably in the absence of), convert the hydroxyl group to X. The compound (IX) has a protected hydroxyl group of the R12 group. In this case, the method for removing the protecting group can be performed according to the method for removing the protecting group of the hydroxyl group in the A1 process of Method A. The reagent for converting the hydroxyl group to X is a sulfonium halide such as methanesulfonyl chloride and p-toluenesulfonyl chloride. ; Sulfenyl chloride, sulfenyl bromide, sulfenyl iodine, and other sulfinyl halides; sulfenyl chloride, sulfinyl iodine bromide, sulfinyl iodine and other sulfinyl halides; phosphorus trichloride, tribromo Phosphorous trihalides such as phosphorus ions, phosphorus triiodide; phosphorus pentahalides such as phosphorus pentachloride, phosphorus pentabromide, and phosphorus pentaiodide; or oxygen chloride Phosphorus halides such as phosphorus, oxybromide, and iodide iodide are preferably sulfonium halides. The Lewis acid used in the above reaction may be zinc halides such as zinc iodide and zinc chloride; tin tetrachloride Boron halides such as boron trichloride, boron trifluoride, and boron tribromide, preferably boron halides (most preferably boron trichloride). The inert solvents used in the reaction are, for example, methylene chloride, chloroform, Halogenated hydrocarbons such as carbon tetrachloride, dichloroethane, chlorobenzene, dichlorobenzene; ether, isopropyl-157- 200300349 ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether And other ethers; or ammonium amines such as formamidine, dimethylformamide, dimethylacetamide, and hexamethylphosphonium triamine, preferably halogenated hydrocarbons (most preferably dichloromethane). The temperature may vary depending on the raw material compound, the reagents used, the solvent, etc., and is usually _5 (TC to 100 ° C (preferably -20 ° C to 50 ° C). The reaction time may depend on the raw material compound, the reagents, the solvent, And reaction temperature, etc., it is usually 30 minutes to 24 hours (preferably 1 to 12 hours). The first step B1 is to change the compound (VIII) Compound, formula XDEX (X) [In the above formula, D, E, and X are as defined above.] Reaction with compound (VII) to directly produce compound (III). After the completion of each engineering reaction in method B above, the compounds for each engineering purpose may be Obtained from the reaction mixture according to a conventional method. For example, the reaction mixture is neutralized as necessary, and when insolubles are filtered off, a mixed organic solvent of water and ethyl acetate is added, and the organic layer containing the target compound is separated. It is obtained by washing with water, drying with anhydrous magnesium sulfate, anhydrous sodium sulfate, or anhydrous sodium bicarbonate, etc., and then distilling off the solvent. The obtained target compound can be isolated and purified by conventional methods such as recrystallization, reprecipitation, etc. The compound is obtained by a combination of methods, which is purified by appropriately dissolving the eluting agent using chromatography. Method C is a method for producing the raw material compound (V I) in the aforementioned method A 200300349 Method c R7a 〇 〇

(VII) where R 1 a, R2, R4a, R5a, R

R7a Ο O

(VI), R7a, ring Ar, D, E, G2, m, Y and Q are as defined above.

The first project C1 is a process for producing compound (VI). In the presence of an inert solvent and a base, the compound (VII) is reacted with a compound of general formula (XI). . The method D is a method for producing the starting compound (VII) in the methods B and C described above. Method D

(XV) (XVI)

-159 200300349 R7a Π Ο R7a Ο Ο

Ja Ν〆

(CH2) m-YH R7a Ο

Project D 8 (XXIII) R15-C〇2R13 (XXIV)

D9, R16R17NCH (R14) 2 (XXV)

R7a 0 R6a, Λ human OR13 R5] T, 1 !, nr16r17 (XXVI) R7a 〇 0 R6a \ Λ λ R5a, R2 Rla Section D 1 1 project, wcsnr16r17 (XXVII) R5a (CH2) m-〇H (XIX)

D10th project R7a O O — ΛΛ r ^ OR13 ΎΒ18 R5a ^ I (CH2) m—YR

(XXI) 18

(Vila)

R7a Ο O

(CH2) m-〇CSNR16R17 R7a O 〇

(CH2) m-SH R7a O 〇

Project D 1 2 r6, Everyone N / R1a Project D 1 3 "r63, (CH2) m-SCONR16R17 (XXIX) (Vllb) where R13, R2, R4 R5a, R", R7a, ring Ar , M, γ and Q are as defined above, W is a halogen atom, R13 and R13a are the same or the same phase -160- 200300349 isopropyl group, each is a carboxy protecting group (the definition is as above), R14 is a hydroxyl group or a lower alkoxy group, R15 is a halogen atom, a lower alkoxy group or a cyano group, R16 and R17 are the same or different groups, may be a lower alkyl group, R 18 is hydrogen, a hydroxyl protecting group (as defined above), or a hydrogen thio protecting group ( Its definition is as shown in the aforementioned "general protecting group of hydroxyl ester", "aliphatic fluorenyl", "aromatic fluorenyl" or "aralkyl", preferably aralkyl, most preferably benzyl. ). Project D 1 is a process for manufacturing a compound of general formula (X 111), in an inert solvent (preferably halogenated hydrocarbons, aromatic hydrocarbons or ethers, halogenated hydrocarbons), and compound of general formula (XII) and a halogenating agent (Suitable for halogenating agents such as sulfenyl chloride, sulfenyl bromide, sulfinyl iodine, etc. or organic acid salts such as chloramphenicol), at -20 ° C ~ 100 ° C ( It should be 0 ° C ~ 50 ° C), and the reaction time is 15 minutes ~ 12 hours (preferably 30 minutes ~ 6 hours). To promote the reaction, catalysts such as formamidine, Ν, Ν-dimethylformamide, dimethylacetamide, hexamethylphosphonium triamine, and other amines can be added. Process D 2 is a process for manufacturing compounds of general formula (XV), in an inert solvent (preferably halogenated hydrocarbons, amidines or nitriles, most preferably dichloromethane, dimethylformamide or acetonitrile) In the presence of a base (preferably organic amines, most preferably triethylamine), in the presence of typical metal salts such as magnesium chloride, the compound (XIII) and the general formula (XIV) compound, at -20 ° C ~ 100 ° C (preferably 0 ° C to 50 ° C), and the reaction is performed from 5 minutes to 24 hours (preferably 30 minutes to 12 hours). Project D3 is a process for manufacturing compounds of general formula (XVI), in an inert solvent (preferably halogenated hydrocarbons, most preferably dichloromethane), in the presence of an acid catalyst (preferably acetic acid, formic acid, oxalic acid, formic acid Bronsted acid-161-200300349 (most preferably trifluoroacetic acid), organic acids such as sulfonic acid, p-toluenesulfonic acid, Izsulfonic acid, trifluoroacetic acid, trifluoromethanesulfonic acid, etc.), the compound (xv), and 0 ° c to 1 2 0 ° c (preferably 1 (TC to 8 (TC), heating for 10 minutes to 24 hours (preferably 15 minutes to 12 hours) for decarbonation reaction. Section D 4 Project is the process of manufacturing compounds of general formula (XV 111), in an inert solvent (preferably esters, most preferably anhydrous acetic acid), in the presence or absence of an acid catalyst (preferably an organic acid), the compound (XVI) and compound of general formula (XV 11), at 50 ° C ~ 2 0 0 ° C (preferably 80 ° C ~ 16 0 ° C), reaction for 15 minutes ~ 2 4 hours (preferably 30 minutes to 12 hours) to perform. The D 5th process is a process for manufacturing a compound of general formula (XX), in an inert solvent (preferably alcohols, most preferably ethanol), and combining (XVIII) and a compound of general formula (XIX), at -7 0 ° C to 100 ° C (preferably -50 ° C to 50 ° C), and reaction for 15 minutes to 50 hours (preferably 30 minutes to 24 hours). The D 6th process is a process for manufacturing a compound of general formula (XXI). The compound (XX) is performed by U 11 ma η reaction, in an inert solvent (preferably amidine, Most preferably Ν, Ν -dimethylformamide), compound (XX) and base (preferably alkali metal carbonates, most preferably potassium carbonate), at 20t ~ 240 ° C (preferably 40 ° C ~ 18 0 ° C), 15 minutes to 50 hours (preferably 30 minutes to 24 hours) for the reaction. The D7 process is a process for producing the compound (VII) and R13 for the compound (XXI). The protective group of the carboxyl group in the group is removed, and the compound (XXI) or a reactive derivative thereof (fluorene halide, activated ester or mixed acid anhydride) is reacted with a compound of general formula (XX Π) in a inert solvent (halogen halide method) , Activated ester method or mixed acid anhydride method), the hydroxyl group or the sulfhydryl group in the R 1 8 group may be removed to remove the protecting group for implementation as needed. The compound (XXI) has a carboxyl group in the R13 group. The method of removing the protecting group can be carried out according to the method of removing the carboxy protecting group in the A1 process of the aforementioned method A. Compound (XXI) or its reactive derivative (halogen halide, activated ester or mixed acid anhydride) and- (XXII) The reaction of compounds can be carried out according to the following method. (E) Halogenation method The halogenation method is a compound in an inert solvent (preferably halogenated hydrocarbons, ethers or amidines) to remove the carboxy protecting group ( XXI) and halogenating agents (defined above. ), At -2 0 t: ~ 150 ° C (preferably 0 ° C ~ 50 ° C), reaction for 15 minutes to 80 hours (preferably 30 minutes to 48 hours) This halogenated compound and compound (XXII), in an inert solvent (preferably halogenated hydrocarbons, ethers or amidines), in the presence or absence of a base (preferably organic amines, most preferably Triethylamine), at -20 ° C to 150 ° C (preferably 0 ° C to 50 ° C), reaction time 15 minutes to 80 hours (preferably 30 minutes to 48 hours) Execute. (f) Activated ester method The activated ester method is performed in an inert solvent (preferably a halogenated method as described above). Compound (XXI) and an activated ester agent (preferably N-hydroxybutanediamine, 1-hydroxyl N-hydroxy compounds such as benzotriazole, N-hydroxy-5-norbornene-2,3-dicarboxymethyleneimide; disulfinyl fluorenyl compounds such as dipyridine disulfinyl fluorenyl; dicyclohexyl carbodicarbonate Carbodiimide and other carbodiimide; carbonyldiimidazole; triphenylphosphine; diphenylphosphine and other condensing agents.), At -7 0 ° C ~ 150 ° C (preferably -1 0 ° C ~ 100 ° C), reaction for 30 minutes to 80 hours (preferably 1 hour to 48 hours) to produce an active ester, and then in an inert solvent (preferably using 200300349 as the aforementioned halogen halogen method.), In In the presence or absence of a base (preferably using the aforementioned halogen halogen method), the compound (XXII), at -2 (TC ~ 100t (preferably 01: ~ 5 01 :), reaction for 30 minutes ~ 80 hours (preferably 1 hour ~ 48 hours) to implement. (G) Mixed acid anhydride method The mixed acid anhydride method is in an inert solvent (preferably using the aforementioned halogen halogen method.), In the presence or absence of a base Down (preferably use The aforementioned halogen halide method.), Compound (XXI) and a mixed acid anhydride physicochemical (preferably a low-alkane carbonate such as ethyl chlorocarbonate and isobutyl chlorocarbonate, and most preferably isobutyl chlorocarbonate.), In- 50T: ~ 100 ° C (preferably Ot ~ 6 (TC), reaction 30 minutes ~ 72 hours (preferably 1 hour ~ 24 hours) to produce mixed acid anhydride, and then in an inert solvent (preferably such as The aforementioned halogen halogen method.), In the presence or absence of a base (preferably using the aforementioned halogen halogen method.), The mixed acid anhydride and the compound (XX 11), at -3 0 ° C ~ 100 ° C (preferably 0 ° C to 80 ° C) for 5 minutes to 24 hours (preferably 30 minutes to 16 hours) to perform the reaction. The hydroxyl protecting group in R 1 8 can be removed if necessary, and the A The method of removing the carboxyl protecting group in the A1 project of the method is implemented. The method of removing the sulfhydryl protecting group may be different according to the type, and is generally performed according to the method known in organic synthetic chemistry technology. For example, TWGreen, (Protective Groups in Organic Synthesis) j John Wiley & Sons · JFW McOmis, (Protective Groups in Organic Chemistry), P 1 e The method described in num P ress is used. Project D 8 is another way of the above method to produce compound (XVI), in an inert solvent (preferably ethers), in the presence of a base (using method B as described above) For Project B 1 ), The compound of the general formula (XX 111) 200300349 and the compound of the general formula (XXIV), at 0 ° c ~ 220 ° c (preferably 50 t: ~ 18 0 ° C), and reaction for 15 minutes to 24 hours ( It should be carried out from 30 minutes to 12 hours J. Project D 9 is a process for manufacturing a compound of general formula (XXVI), in an inert solvent, in the presence or absence of an acid catalyst (preferably in the presence), The compound (XVI) is carried out by reacting with a compound of the general formula (XXV). This process can be carried out in accordance with the method of the D method of the D4 project. The D10 project is another way of the above method to produce the compound (XXI). Engineering, in an inert solvent (preferably amidoamines, most preferably dimethylformamide), in the presence of a base (preferably alkali metal carbonates, most preferably potassium carbonate), the compound (XX VI) And compound (XIX) at 0 ° C ~ 220 ° C (preferably 501: ~ 180 ° C) and react for 15 minutes to 24 hours (preferably 30 minutes to 12 hours). The D11 project is manufacturing Engineering of compounds of general formula (XXVIII), in an inert solvent (preferably amidoamines, most preferably dimethylformamide), in the presence of a base It is preferably an alkali metal hydroxide, most preferably sodium hydroxide), a compound (V 11 a) in which -YR 1 8 group of compound (V 11) is a hydroxyl group, and a compound of general formula (乂 乂 ¥ 11) 2. Perform at -2 0 ° (: ~ 70 ° 〇 (preferably 0 < ^ ~ 50 0 > (:) reaction time 30 minutes ~ 24 hours (preferably 1 hour hour ~ 20 hours).) D12 process is the process of manufacturing the compound of general formula (XXIX), in an inert solvent (preferably ethers, most preferably phenyl ether), compound (XX VIII), at 50 ° C ~ 3 00 ° C (preferably 1 00 ° C ~ 2 50 t) Likou thermal reaction for 15 minutes to 12 hours (preferably 30 minutes to 8 hours) to perform -165- 200300349 The D13 project is a process for manufacturing compounds (Vllb), In an inert solvent (preferably ethers, most preferably ethanol), compound (XXIX) and base (preferably alkali metal hydroxides, most preferably sodium hydroxide), at -2 0 ° C ~ 7 〇 ° C (preferably 0 ° C ~ 50 ° C) reaction time is 15 minutes ~ 12 hours (preferably 30 minutes ~ 8 hours).

After the reaction of each process of the aforementioned D method is completed, the target compounds of each project can be obtained from the reaction mixture according to a conventional method. For example, after neutralizing the reaction mixture as needed, filtering off insoluble matters, adding a mixture of organic solvents such as water and ethyl acetate, separating the organic layer containing the target compound, washing with water, and then using anhydrous magnesium sulfate. , Anhydrous sodium sulfate, or anhydrous sodium bicarbonate, etc., after drying, the solvent is obtained. The obtained target compound can be obtained by combining conventional methods, such as recrystallization, reprecipitation, and other methods commonly used in the separation and purification of organic compounds, if necessary, by chromatography, and dissolving the elution agent appropriately. Process E is the production of the compound (II) of the present invention, wherein Gn + is a compound of the group (i), (ii), (iv), (v), (vii), (viii), (U) or (x) ( lib) and Gn + are compounds (lie) based on (iii), (iv) or (vi).

E method

El Project R2 G1 (IV)

R2

Fi1a E 2 Project R2

R2 -166-200300349 where R1, Rla, R2, R4, R4a, R5, R5a, R6, R6a, R7, R7a, ring Ar, A, ϋ, E, Gl, G2, Gln +, G2n +, x and ( X) n_ is as defined above. Process El is a process for manufacturing a compound (lib). The compound of general formula (XXX) is in an inert solvent, and after reacting with compound (IV), if necessary, the nitrogen atom in the ring of (h) Gl + group is converted into an ammonium group. In an inert solvent, the compound obtained by the above reaction and the following compound of general formula (V): X-R11 (V) [wherein, X is as defined above, and R11 is substituted by a group selected from the group of substituents. Lower alkyl and a group selected from the substituent group b. ] Reaction, and / or, (j) Removal of amine, hydroxyl and / or carboxyl protecting groups in Rla, R4a, R5a, ruler and R7a, this project can be carried out according to the method of the above-mentioned A, A1 project. The E2 process is a process for manufacturing a compound (lie), (k) ammonium conversion of a nitrogen atom on a ring in the G2 group, in an inert solvent, reacting a compound of the general formula (XXXI) with the compound (V '), or, ( m) In an inert solvent, replace the compound (XXXI) with an oxidizing agent, and replace the nitrogen atom of the nitrogen atom on the G 2 ring with the nitrogen atom into an ammonium group. If necessary, Rla, R4a, R5a, R6a, and R7a Removal of the amine group, hydroxyl group and / or carboxyl protecting group, this process can be carried out according to the method of the above-mentioned method A and A2. Method F is a method of manufacturing the aforementioned starting material compound (XXX) of method E. Method F-167- 200300349 F law

A, D, E, m, Q, X and Y are as defined above. The F1 project is a process for manufacturing a compound of the general formula (XX XIII). The compound of the general formula (XX × Π) is reacted with the compound (VIII) in an inert solvent and in the presence of a base. B1 project method. The F2 process is a process for manufacturing the compound (XXX). If the R12 group of the compound (XXXIII) is a protected base, after removing the protective group, in an inert solvent, in the presence or absence of Lewis acid, The hydroxyl group is converted to X for implementation. This process can be performed according to the method of the B process B 2 process described above. In the F1 process, the compound (VIII) is replaced by the following formula X-D-E-X (X) [In the above formula, D, E, and X are as defined above. ] Compound (XXX) is reacted to produce compound (XXX) directly. The G method is a method for producing the starting compound (XXIX) of the aforementioned E method. -168-200300349 G

G2, m, Q, Y are as defined above. The G1 project is a process for producing the compound (XXXI). The compound (XXXII) is reacted with the compound (X) in an inert solvent and in the presence of a base. This process can be performed according to the method of the C1 process of the aforementioned method C. The hydrazone method is a method for producing the starting compound (XXXII) of the above-mentioned methods F and G. Method

R7a Ο R7a Ο

Phase 2 R1302CT ^ C02R13a (XIV)

-169- 200300349

OR 13 R7a 0 R18Y—m (H2C)

11a Project H8 R15-C02R13 (XXIV)

R7a Ο O

OR 13 R18Y-m (H2C), Ah, Q (XXXVII) (XLII) H9 project, R6a \ R7a 0 0 cbcV ^ ° R13 ^ NR16R17 Η1 0 project R16R = (R14) 2 ~ H H2N- ^^-R5a (XXV) R4a (XXXIX) (XLIII) R7a O 0

R18Y—m (H2C), Ya 1V_ > R5a (XLI) R7a O 0 H〇-m (H2C)

Hll Project N ----- ^ wcsnr16r17 (XXVII) R7a 〇 O 16R17RNSC〇-m (H2C)

-170- 200300349

In the formula, Rla, R2, R4a, R5a, R6a, R7a, R13, R14, R,

R16, R17, R18, rings Ar, m, Q, W and Y are defined as above. The HI process is a process of manufacturing a compound of the general formula (XXXV). The compound of the general formula (XXXIV) is reacted with a halogenating agent in an inert solvent. This process can be performed according to the method of the D1 process of the aforementioned D method.

Process H2 is the process of manufacturing the compound of general formula (XXXVI). In the presence of inert solvents and bases, in the presence of typical metal salts such as magnesium chloride, the reaction of compound (XXXV) with compound (XIV) can be carried out according to the foregoing. Method D method D 2 works. The H3 project is a process for manufacturing a compound of the general formula (XXXVII). The compound (XXXVI) is heated and decarbonated in an inert solvent and in the presence of an acid catalyst. Method. The H4 project is a process for manufacturing a compound of the general formula (XXXVIII). The compound (XX XV II) is reacted with the compound (XVII) in an inert solvent and in the presence of an acid catalyst. D4 -171- 200300349 engineering method. Process H5 is a process for manufacturing a compound of general formula (XL). The compound (XXXVIII) is reacted with a compound of general formula (XXXIX) in an inert solvent. This process can be carried out according to the method of process D 5 of the aforementioned method D. get on. The H6 process is a process for manufacturing a compound of the general formula (XLI), and the compound (XL) is performed by Ull man reaction. This process can be performed according to the method of the D6 process of the aforementioned D method. Process H7 is a process for producing compound (XXXII). After removing the carboxyl protecting group in the R13 group of compound (XLI), in an inert solvent, after reacting compound (XLI) or its reactive derivative with compound (XXII) 3. If necessary, the protective group of R 1 8 hydroxyl group or sulfhydryl group is removed for implementation. This project can be carried out according to the method of the D project No. D 7 above. The H8 project is another process for producing the compound (XXXVII), which is performed in an inert solvent and in the presence of a base by reacting a compound of the general formula (XLII) with a compound (XXIV). This process can be performed according to the aforementioned D method. Method D 8 is carried out. The H9 project is a process for manufacturing a compound of the general formula (XLIII). The compound (XXXV 11) is reacted with the compound (XXV) in an inert solvent and in the presence or absence of an acid catalyst to perform the project. Method D of Section D 4 of the method. The tenth project is another process for producing the compound (XLI) in the above method. The compound (XLIII) is reacted with the compound (XXXIX) to perform in an inert solvent and in the presence of a base. 10 engineering methods. -172- 200300349 The H11 process is a process for producing a compound of general formula (XLIV). In an inert solvent and in the presence of a base, a compound (XXXIIa) 'in which -YR18 group is a hydroxyl group in compound (XXXII) is reacted with compound (XXVII). For the future implementation, this project can be carried out in accordance with the method of Article D 1 1 of the aforementioned D method. The H12 process is a process for manufacturing a compound of the general formula (XLV), and the compound (X L I V) is heated in an inert solvent to carry out the process. This process can be carried out according to the method of the D12 process of the aforementioned D method. The H13 project is a process for manufacturing a compound (XXXI lb). The compound (X LV) is reacted with an alkali in an inert solvent. This process can be performed according to the method of the D 13th process of the aforementioned D method. Method I is a method for producing the starting compound (XIX) in the aforementioned method D. I method R1302C ~ Q ~ (CH2) m—YR18 U 1 project, H02C ^^ (CH2) m-YR18 The first 2 workers-XLVI (XLVII) OCN-^^-(CH2) m-YR18 —R1602CHN -^^ (CH2) m—YR18 (XLVIII) (IL) (L), Φ I 4_. 工. 宁》 H2N-^) ~ (CH2) m-YR18 (XIX) where r13, R16, R18 The meanings of ring, Ar, m, and Y are as above. The second project is a process for manufacturing a compound of general formula (XLVII). The R13 group of the carboxyl protecting group of a compound of general formula (XLVI) is removed for implementation. In the A1 project, the method of removing the end-protective group is performed. The twelfth project is the process of manufacturing compounds of general formula (XLV III), derived from -173- 200300349 inert solvents (preferably aromatic hydrocarbons, most preferably toluene), and the presence of arylphosphonium amines such as diphenylphosphonium azide The reaction is carried out at a temperature of 0 ° C ~ 22 (TC (preferably 50 ° C ~ 18 0 t :) for 15 minutes to 12 hours (preferably 30 minutes to 8 hours)). The 13th project is manufacturing Engineering of compounds of general formula (L), in an inert solvent (preferably aromatic hydrocarbons, most preferably toluene), compound (XLVII) and compound of general formula (IL), at 0 ° C ~ 2 2 0 ° C (preferably 50 t: ~ 180 ° C) for 15 minutes to 48 hours (preferably 30 minutes to 24 hours) to perform. The 14th process is a process for producing a compound (XIX), In an inert solvent (preferably an ester, most preferably ethyl acetate), a compound (L) and an acid catalyst (preferably an inorganic acid, most preferably hydrochloric acid), at -2 (TC ~ 150 ° C (preferably 0) ° C ~ 80 ° C) Inverse 15 minutes to 48 hours (preferably 30 minutes to 24 hours) to perform. After the completion of the reaction of each process of the above method I, the target compounds of each project can be obtained from the reaction mixture according to the usual method. For example, neutralize the reaction mixture as necessary, and filter off insoluble matters, add water and ethyl acetate to the mixture of organic solvents, separate the organic layer containing the target compound, wash with water, and then use anhydrous sulfuric acid. Magnesium, anhydrous sodium sulfate, or anhydrous sodium bicarbonate are dried and evaporated to obtain the solvent. The target compound obtained can be combined with conventional methods, such as recrystallization, reprecipitation and other methods used for conventional separation and purification of organic compounds, if necessary, using chromatography. It is obtained by refining and dissolving the dissolving agent appropriately. J method is a method for producing the above-mentioned D method and Η method starting material compound (XXII), wherein R2 is a low alkyl compound (XXIIa). J method-174- 200300349 R1a— NH2 (LI) J1 Project (r19c〇) 2〇 (LII) R1a—NHCOR19 J2 Project-(LIII) R1aNHCH2R19 (XXIIa) R1a—NH2 (LI) J3 Project r19c (or16) 3 (LIV) R1a—n = c ~ r19 OR16 (LV) J4 Project <-^ R1aNHCH2R19 (XXIIa) where R1a and R16 are as defined above, and R19 is a Ci-5 alkyl group.

Project J1 is a process for manufacturing a compound of general formula (LIII), in the presence or absence of an inert solvent (preferably pyridine), in the presence of a base (preferably an organic base, most preferably pyridine), and general formula ( LI) The compound is reacted with a compound of general formula (LII) at -2 ° C to 100 ° C (preferably 0 ° C to 50 ° C) for 5 minutes to 12 hours (preferably 15 minutes to 6 hours).

Project J2 is a process for producing compound (XXII a), in an inert solvent (preferably ethers, most preferably tetrahydrofuran), compound (LIII) and a reducing agent such as borane-dimethylsulfide complex, etc. ° C ~ 2 2 (TC (preferably 50 ° C ~ 1 8 01 :) reaction 5 minutes ~ 12 hours (preferably 15 minutes ~ 6 hours) to implement. The third J3 project is manufacturing-general formula (LV ) Compound engineering, in the presence of an acid catalyst (preferably an organic acid, most preferably trifluoroacetic acid), the compound (LI) and-general formula (LIV) compound, at 0 ° C ~ 220 ° C (preferably (50 ° C ~ 180 ° C) for 5 minutes to 12 hours (preferably 15 minutes to 6 hours) to carry out. The J4 project is another way of manufacturing compound (XXIIa), in an inert solvent (preferably Alcohols, most preferably ethanol), compound (LV) and base (preferably sodium borohydride), at 0 ° C ~ 2 2 0 ° C (preferably 50 ° C ~ 18 0 ° C) -175 -200300349 The reaction is carried out for 5 minutes to 12 hours (preferably 15 minutes to 6 hours). After the completion of each reaction of the aforementioned J method, the target compounds of each project can be obtained from the reaction mixture according to the usual method. For example, Neutralize the reaction mixture as necessary, and filter off insoluble matters, add water and ethyl acetate to the mixture of organic solvents, separate the organic layer containing the target compound, wash with water, etc., and then use anhydrous magnesium sulfate and anhydrous. It is obtained by drying the sodium sulfate, anhydrous sodium bicarbonate, etc., and then distilling off the solvent. The obtained target compound can be combined with conventional methods, such as recrystallization, reprecipitation and other methods used for conventional separation and purification of organic compounds, if necessary, using chromatography, and appropriately It is obtained by refining a dissolving and dissolving agent. The K method is another method of the mash method, and can be used to prepare the starting material compounds (XXXII) of the F method and the G method.

In the formula, Rla, R2, R4a, R5a, R6a, R7a, R13, R18, rings Ar, m, W and Y are as defined above. Process K1 is a process for manufacturing a compound of general formula (LVII). After removing the carboxyl protecting group in the R13 group of compound (XLI) (-176- 200300349 of the carboxyl protecting group), the carboxyl group can be removed according to the above method A, A1. Protective group method.), In an inert solvent (preferably halogenated hydrocarbons), in the presence or absence of a base (preferably an organic amine.), The compound (XLI) and a mixed anhydride (preferably chloroformic acid) Isobutyl esters and other chloroformates.), At -50 ° C ~ 100 ° C (preferably 0 ° C ~ 60 ° C), reaction time 10 minutes ~ 7 2 hours (preferably 15 minutes ~ 24 hours) to carry out the production of mixed acid anhydride, in an inert solvent (preferably using the aforementioned halide method), in the presence or absence of a base (preferably using the foregoing.), Mixing the mixed acid anhydride with the compound (LVI) The reaction is carried out at a temperature of -30 ° C to 100 ° C (preferably 0 ° C to 80 ° C) for 5 minutes to 24 hours (preferably 30 minutes to 16 hours). Project K2 is a process for producing compound (XXXII), in an inert solvent (preferably amidoamines), in the presence of a base (preferably an alkali metal hydride such as sodium hydride.), Compound (LVII) and the general formula (LVIII) Compound, react at -3 ° C ~ 100 ° C (preferably 0 ° C ~ 80 ° C) for 5 minutes or 24 hours (preferably 30 minutes ~ 16 hours, if necessary) Remove the hydroxyl or sulfhydryl protecting group in the R 1 8 group (if necessary, the project of removing the hydroxyl or sulfhydryl protecting group in the R 1 8 group can be removed in accordance with the aforementioned D method D7 project After the reaction of each process of the aforementioned K method is completed, the target compounds of each project can be obtained from the reaction mixture according to the usual method. For example, after neutralizing the reaction mixture as necessary, and filtering off insoluble matters 2. Adding a mixed organic solvent of water and ethyl acetate, separating the organic layer containing the target compound, washing with water, drying with anhydrous magnesium sulfate, anhydrous sodium sulfate, or anhydrous sodium bicarbonate, etc., and obtaining the solvent by distillation. If necessary, the obtained target compound can be subjected to ordinary methods, such as recalculation. Conventional separation and purification of organic compounds, such as reprecipitation and re-precipitation, etc. -177- 200300349 It is obtained by combining methods and using chromatography to dissolve the eluent appropriately. L method is the starting material compound (XXXI) in the E method, and E is the formula -CONR8. -A method for producing a base compound (XXXIa).

R7a Ο Ο

R2

In the formula, Rla, R2, R4a, R5a, R6a, R7a, R8, R13, ring Ar, D, m, Q, Y and G2 are as defined above. The LI project is a process for manufacturing a compound of general formula (LX), in an inert solvent (preferably amidoamines), in the presence of a base (preferably an alkali metal carbonate such as potassium carbonate.), Compound (XXXII) and -Compound of general formula (LIX), reacted at -3 0 ° C to 100 ° C (preferably 0 ° C to 80 ° C) for 5 minutes to 24 hours (preferably 30 minutes to 16 hours) Come on. The L2 process is a process for producing a compound (XXXIa). After removing the protective group of the carboxyl group in the R13 group of the LX (the method of removing the carboxyl protective group can be performed as the method of removing the carboxyl protective group in the A1 process of the above method A) .), In an inert solvent, the compound (LX) and its reaction derivative ((halogen halide, activated ester or mixed acid anhydride) with the general formula (LXI) -178- 200300349 compound (halogen halide method, Activated ester method or mixed acid anhydride method), this project can be carried out in accordance with the method of the aforementioned D method D7 project. After the completion of the reaction of each process of the aforementioned L method, the target compound of each project can be obtained from the reaction mixture according to the usual method. For example, The reaction mixture is neutralized as necessary, and after insoluble matter is filtered off, a mixed organic solvent of water and ethyl acetate is added, an organic layer containing the target compound is separated, washed with water, etc., and then anhydrous magnesium sulfate and anhydrous sulfuric acid are used. Sodium or anhydrous sodium bicarbonate is obtained by drying, and the solvent is distilled off. The obtained target compound can be isolated and purified by conventional methods, such as recrystallization, reprecipitation and the like, if necessary. Together, using chromatography, eluting fittingly eluted from refining agent. [Mu] Method E Method as starting materials in compound (XXXI), E is -CONH- group of the compound of formula (XXXIb) of the manufacturing method.

(XXXII) R7a 〇 〇 (LXIII)

(XXXIb)

-179- 200300349

γ, W and G2 are as defined above, Pht is phthalocyanine A r, D, m,

amine. The process of manufacturing a compound of general formula (LXIII) by the train pass, in the inert M1 project as a # solvent, in the presence test, the compound (XXIX) is reacted with the compound of general formula (LXII) to carry out, this project can be Carry out according to the method of the B1 project of the above-mentioned B method. The M2 project is a process of manufacturing a compound of general formula (LXIV), in an inert solvent (preferably alcohols such as ethanol.), The compound (LXI11) and hydrazone, and 0 ° C ~ 200 ° C (preferably 20 ° C ~ 100 ° C) for 5 minutes to 24 hours (preferably 30 minutes to 12 hours). Project M 3 is a process for producing compound (XXXI b). The compound of general formula (LXV) or its reactive derivative (halogen halide, -180- 200300349 activated ester or mixed acid anhydride) and compound are prepared in an inert solvent. (LXIV) compound reaction (halogenation method, activated ester method, or mixed acid anhydride method), this project can be carried out according to the method of the D method D7 above. Compound (LXV) is replaced by compound of formula (LXVI), in an inert solvent (preferably halogenated hydrocarbons), in the presence of a base (preferably organic amines), compound (LX IV) and compound ( l XVI), perform at -3 0 t: ~ 100 0 t: (preferably 0 ° C to 80 ° C) for 5 minutes to 24 hours (preferably 30 minutes to 16 hours). The M4 project is a process for manufacturing a compound of the general formula (LX VIII). The compound (XXX II) is reacted with a compound of the general formula (LX VII) to be carried out in an inert solvent and in the presence of a base. Method B 1 is carried out. The M5 project is a process for manufacturing a compound of general formula (LX IX), in an inert solvent (preferably amidoamines), compound (LXVII.I) and an alkali metal azide (preferably azide) Sodium.), At -30 ° C to 100 ° C (preferably 0 ° C to 80 ° C) for 5 minutes to 48 hours (preferably 30 minutes to 30 hours) to perform. The M6 project is a process for manufacturing a compound (LXIV). The azide group of the compound (LX IX) is reduced to an amine group in an inert solvent. The project is to compound (LX IX) and a reducing agent (preferably palladium- Catalysts such as carbon for catalyst reduction), reaction at -2 ° C ~ 100 ° C (preferably 0 ° C ~ 50 ° C) for 5 minutes to 24 hours (preferably 30 minutes to 1 2 hours). After the reaction of each process of the aforementioned M method is completed, the target compound of each project can be obtained from the reaction mixture according to a conventional method. For example, after neutralizing the reaction mixture as necessary, and filtering off insoluble matters, adding water-ethyl acetate-181-200300349 to mix the organic solvent, separating the organic layer containing the target compound, washing with water, etc. It is obtained by drying with anhydrous magnesium sulfate, anhydrous sodium sulfate, or anhydrous sodium bicarbonate, and then evaporating the solvent. The obtained target compound can be obtained by combining conventional methods, such as recrystallization, reprecipitation, and other methods commonly used in the separation and purification of organic compounds, if necessary, by chromatography, and dissolving the elution agent appropriately. Raw material compounds (IV), (ν), (ν '), (νπι), (X), (XΙ), (XΙΙ), (XIV), (XVII), (XXII), (XXIX), (XXIV) , (XXV), (XXVII), (XXXIV), (XXXIX), (XLII), (XLVI), (IL), (LI), (LII), (LIV), (LVI), (LVIII), (( LIX), (LXI), (LXII), (LXV), (LXVI) and (LXVII) are known or can be easily manufactured by known methods or similar methods. Effect of the Invention The aforementioned general formula (I) or (II) compound of the present invention, its pharmacologically acceptable salt, its ester or other derivatives have excellent ileal-type cholic acid carrier inhibitory effect, have low side effects, and can be used for hyperlipidemia and Preventive or therapeutic agent for arteriosclerosis. Industrial application When the compound of the general formula (I) or (II), its pharmacologically acceptable salt, its ester or other derivative of the present invention is used as the above-mentioned therapeutic or preventive agent, it can be used alone or in combination with appropriate pharmacologically acceptable excipients, Diluents and the like are administered orally, such as lozenges, capsules, granules, powders, or syrups, or parenterally, such as injections or suppositories. These preparations can be prepared by conventional methods, such as excipients (such as sugar derivatives such as lactose, white sugar, glucose, mannose, and sorbose; corn starch, potato starch, α-starch, dextrin and other starch derivatives; crystalline cellulose, etc. Cellulose 182- 200300349 Vitamin derivatives; gum arabic; polydextrose; polytriglucose and other organic excipients: and silicate derivatives such as silicic anhydride, synthetic aluminum silicate, calcium silicate, magnesium aluminum silicate, etc. Substances; phosphates such as calcium hydrogen phosphate; carbonates such as calcium carbonate; inorganic excipients such as calcium sulfate; and lubricants (such as stearic acid, calcium stearate, magnesium stearate, etc.) Salt; talc; colloidal silica; waxes such as propolis and cetyl wax; boric acid; adipic acid; sulfates such as sodium sulfate; ethylene glycol; fumaric acid; sodium benzyl acid; DL leucine; fatty acid sodium salt; ten Dodecyl sulfates such as sodium dibasic sodium sulfate and dodecyl magnesium sulfate; silicic acids such as silicic anhydride and silicic acid hydrate; and the above starch derivatives.), Binding agents (for example, hydroxypropyl cellulose, hydroxymethyl Cellulose, polyvinylpyrrolidone, polyethylene glycol and the aforementioned additives Agents, etc.), disintegrating agents (such as low-substituted hydroxypropyl cellulose, carboxymethyl cellulose, calcium carboxymethyl cellulose, cellulose derivatives such as internally bridged carboxymethyl cellulose; carboxymethyl starch, Chemically modified starch celluloses such as sodium carboxymethyl starch, bridged polyvinylpyrrolidone, etc.), stabilizers (parabens such as methylparaben, propylparaben, etc .; neoprene Alcohols such as alcohol, benzyl alcohol, phenethyl alcohol; benzane ammonium chloride; phenols such as phenol and cresol; thimerosal; dehydroacetic acid: and sorbic acid.), Flavoring agents (such as conventional sweeteners, sour ingredients, Spices, etc.), thinners and other additives. Dosage varies depending on symptoms, age, etc. For example, the daily lower limit is 0.1 mg (preferably 1.0 mg), the upper limit is 100 mg (preferably 50 mg), and the lower daily limit is 0.1 mg when administered intravenously. (Preferably 1.0 mg), the upper limit is 500 mg (preferably 300 mg), and if necessary, it is administered 1 to 6 times daily depending on the symptoms. Best Mode for Carrying Out the Invention The present invention is described in detail by the following examples, reference examples, and test examples -183- 200300349, but the scope of the present invention is not limited thereto. Example 1 Desertification 1- {2- {3 · {3_ [n_ (3,5- = fluorophenyl) · ethylaminomethylmethyl] -7-methoxy-4 · oxy "fluorene · quinoline-丨 _ Jibuhong methoxyphenoxymethyl} benzyl 4-4-yal-1-azobicyclo [2.2 2] octane (exemplified compound number: Bu "4) (la) 2- (2,4- Dimethoxybenzyl) butyl malonate

Dissolve 20.2 g of 2,4-dimethoxybenzoic acid in 2000 ml of a dichloromethane solution, add 15.3 ml of chlorammonium chloride and a catalyst amount of N, N-dimethylformamide, and stir at room temperature for 1 · 5 hours. The reaction solution was evaporated under reduced pressure to remove the solvent, and 5 ml of acetonitrile was added to dissolve. To 25.0 g of an acetonitrile solution containing 25.0 g of ethyl acetate of third butyl malonate was added triethylamine 4 6.0 m 1 and 15.7 g of magnesium chloride under ice cooling, and the mixture was stirred for 10 minutes.醯 Chlorine solution and stir at room temperature for 1.5 hours. The reaction solution was diluted with dilute hydrochloric acid to neutralize, and the solvent was distilled off under reduced pressure. The residue was extracted with ethyl acetate, and the ethyl acetate layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: Jiyuan / ethyl acetate = 1/1) to obtain the title compound as a yellow oily substance. NMR (CDC13) (5ppm: 1.27 (3H, t, J = 7.2Hz), 1.55 (9H, s), 3.85 (3H, s), 3.87 (3H, s), 4.25 (2H, q, J = 7.1Hz ), 5.13 (1H, s), 6.42 (1H, d, J = 2.2 Hz), 6. 58 (1H, dd, J = 2.3, 8.9Hz), 8.02 (1H, d, J = 8.9Hz ). (Lb) 3- (2,4-dimethoxyphenyl) -3-oxopropanoic acid acetamidine The 2- (2,4-dimethoxybenzyl) malonic acid obtained in Example (la) To 30 ml of a solution of 34.9 g of ethyl butyl acetate in dichloromethane was added 30 ml of trifluoroacetic acid, and the mixture was stirred at 401: for 1 hour. The reaction solution was depressurized -184- 200300349, the solvent was distilled off, and a saturated sodium hydrogen carbonate aqueous solution was added to Neutralize and extract with ethyl acetate. The ethyl acetate layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane / acetic acid Ethyl ester = 1/1), the title compound was obtained as a yellow oily substance 2 2.4 g. NMR (CDC13) δρριη: 1.24 (3H, t, J = 7.1Hz), 3.867 (3H, s), 3.872 (3H, s), 3.93 (2H, s), 4.19 (2H, q, J = 7.2Hz), 6.44 (1H, d, J = 2.3Hz), 6.56 (1H, dd, J = 2.3, 8 · 8Ηζ), 7.95 (1H, d, J = 8.8 Hz). (Lc) 3- (3-Benyl-5-methoxyaniline ) Ethyl 2- (2,4-dimethoxybenzyl) acrylate. 2.24 g of ethyl 3- (2,4-dimethoxyphenyl) -3 -oxopropionate obtained in Example (lb), A mixture of 8.8 ml of ethyl orthoformate and 2.5 ml of anhydrous acetic acid was stirred at 140 ° C for 2 hours. After the reaction was completed, the volatiles were distilled off under reduced pressure. The residue was dissolved in ethanol 30 m 1 at -4. 3.00 g of 3-benzyloxy-5-methoxyaniline obtained in Reference Example 1 was added at 0 ° C, and the mixture was warmed to room temperature and stirred for 2 hours. The reaction solution was concentrated under reduced pressure, water was added, and extracted with ethyl acetate. The ethyl acetate layer was washed with dilute hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate). = 1/1), the yellow oily substance of the title compound was obtained. 4.06 g ° NMR. (CDC13) 5ppm: 1.05 and 1. 26 (total 3H, each t, J = 7.2 Hz), 3.74, 3 . 76, 3. 80 and 3. 85 (total 9H, each s), 4. 04 and 4.12 (total 2H, each q, J = 7.1Hz), 5.00 and 5. 05 (total 2H, each s) ,, 5. 86-6. 01 (2H, m), 6. 32-6. 57 (3H, m), 7. 31-7. 42 (6H, m), 8.34 and 8. 38 (total 1H, each s) 〇 (ld) l- (3-benzyloxy-5-methoxyphenyl) -7-methoxy-4-oxo-1,4- 200300349 dihydroquinoline Ethyl carboxylate Ethyl 3- (3-benzyloxy-5-methoxyaniline) -2- (2,4-dimethoxybenzyl) acrylic acid ethyl ester obtained in Example (1c) 4.05 g of N, N-dimethylformamide solution 30 ml, 2.28 g of potassium carbonate was added, and stirred at 140 ° C for 2.5 hours. The reaction solution was added with dilute hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol = 1 0/1) to obtain 1.58 g of the title compound as a pale yellow solid. NMR (CDC13) (5ppm: 1.40 (3H, t, 1 = 7.1Hz), 3.75 (3H, s), 3.83C3H, s), 4.39 (2H, q, J = 7.1Hz), 5.08 (2H, d, J = 2.6Hz), 6.44 (1H, d, J = 2.3Hz), 6.56 (1H, t, 1 = 2.0Hz), 6.63 (1H, t, J = 2.0Hz), 6.72 (1H, t, J = 2.2Hz), 7.00 (1H, dd, J = 2.3, 8.9Hz), 7.38-7.44 (5H, m), 8.44 (lH, s), 8.47 (lH, d, J = 9.0Hz). (le) l- (3-Ethoxymethoxyphenylmethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid The 1- (3-benzyl) obtained in Example (1d) Oxy-5 -methoxyphenyl) -7-methoxy-4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid ethyl ester 1. 5 6 g of a methanol solution of 20 ml, added with hydroxide 544 mg of sodium and 5 ml of water were heated under reflux for 1 hour. The reaction solution was added with dilute hydrochloric acid to oxidize, the solvent was concentrated under reduced pressure, and extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate. Then, the solvent was concentrated under reduced pressure. The precipitated solid was washed with hexane to obtain 1.4 1 g of the title compound as a yellow solid. NMR (DMS0-d6) δ ppm: 3.78 (3H, s), 3.84 (3H, s) , 5.09 (2H, d, J = 3.2Hz), 6.55-6.56 (2H, in), 6.62 (1H, t, J = 1.9Hz), 6.75 (1H, t, J = 1.8Hz), 7.14 (1H, dd, J = 2.3, 9.1Hz), 7.38-7.43 C5H, m), 8.47 (1H, d, J = 9.1Hz), 8.73 (1Η, s). -186- 200300349 (lf) l- (3-benzyloxy-5-methoxyphenyl) -7-methoxyoxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5 -Difluorophenyl) -N-acetamidine The 1- (3-benzyloxy-5-methoxyphenyl) -7-methoxy-4-oxo-1,4 obtained in Example (1e) -Dihydroquinoline-3 -carboxylic acid 445mg in 15ml of dichloromethane solution, 0.2ml of chlorammonium chloride and N, N-dimethylformamide as catalyst, and stirred at room temperature for 1.5 hours. After reducing the pressure of the reaction solution, the residue was dissolved in 5 ml of methylene chloride. The dichloromethane solution containing N-ethyl-3, 5-difluoroaniline 3 30 mg and triethylamine 0.4 m 1 obtained in Reference Example 2 was added to the above-mentioned chloroform solution under ice cooling, and the mixture was stirred at room temperature. 1 hour. The reaction solution was added to water, and dichloromethane was concentrated under reduced pressure, and the residue was extracted with ethyl acetate. The ethyl acetate layer was washed successively with dilute hydrochloric acid, a saturated sodium bicarbonate solution and a saturated sodium chloride solution, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol = 20/1) to obtain the title compound as a light yellow foamy substance 4 7 4 mg. Li R (DMS0-d6) δρριη: 1.08 (3H, t, J = 7.1 Hz), 3.66 (3H, s), 3.8K3H, s), 3. 81-3. 85 (2H, m), 5.16 ( 2H, s), 6.37 (1H, d, J = 2.2Hz), 6.66 (1H, s), 6.77 (1H, s), 6.83 (1H, t, J = 2.1Hz), 7.00 (1H, dd, J = 2.2, 8.9Hz), 7.04-7.12 (3H, m), 7.33-7.47 (5H, m), 8.01 (1H, d, J = 9.1Hz), 8.09 (1H, s) 〇 (lg) l- ( 3 -Hydroxy-5-methoxyphenyl) -7-methoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl N -ethyl Example 1 (1- (3-benzyloxy-5-methoxyphenyl) -7-methoxy-4-oxo-1,4-dihydroquinoline, 3-carboxylic acid N -(3,5 · Difluorophenyl N-acetamide 4 40 mg in ethanol solution 15 m 1 10% P d-C 105 mg was added, and stirred at room temperature under atmospheric pressure of 1 atmosphere of hydrogen 3 hours. The reaction solution was filtered, the catalyst was washed with ethyl acetate, the filtrate was combined, and concentrated under reduced pressure. The residue -187- 200300349 residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol = 10/1 The precipitated solid was collected and washed with hexane to obtain the title compound as a white solid 2 7.6 mg ° NMR (DMS0-d6) (5ppm: 1.08 (3H, t, J = 7.0Hz), 3.69 (3H, s) , 3.77 (3H, s), 3.82 (2H, q, J-7.1Hz), 6.40 (2H, t, J-2.0Hz), 6.48 (1H, s), .6.55 (1H, t, J = 2.1Hz) , 7.00 (1H, dd, J = 2.2, 8.9Hz), 7. 04-7. 12 (3H, m), 8.01 (1H, d, J = 8.9Hz), 8.07 (1H, s) 〇 ( lh) l- [3- (2-Bromomethylbenzyloxy) -5 -methoxyphenyl] -7-methoxy-4-oxo-1,4 -monoamidine-3 -unsaturated acid N- (3,5-^^ phenyl) -N-acetamide. The 1- (3-hydroxy-5 -methoxyphenyl) -7-methoxy-4 -oxo obtained in Example (1 g) was used. 1,4-Dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 9 7 mg of N, N -dimethylformamide solution 1 0 Under ice-cooling, 20.3 mg of 55% sodium hydride was added and stirred for 15 minutes, α, α'-dibromo-o-xylene was added at 264 mg, and stirred at room temperature for 1.5 hours. The reaction solution was added with dilute hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and then the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol = 15/1) to obtain 1 2 3 mg of the title compound as a pale yellow foam. Li R (CDC13) 5ppm: 1.2K3H, t, J = 7.1Hz), 3.73 (3H, s), 3.83 (3H, s), 3.91- 3.95 (2H, m), 4.62 (2H, s), 5.22 ( 2H, s), 6.43 (1H, d, J = 2.3Hz), 6.52 (1H, t, J = 2.0Hz), 6.58-6.65 (2H, m), 6.72 (1H, t, J = 2.2Hz), 6.82-6. 86 (2H, m), 6.91- 6.94 (1H, m), 7.36-7.48 (4H, m), 7.87 (1H, s), 8.22 (1H, d, J-9.0Hz) 〇 (1 i) Brominated 1-{2-{3-{3-[N-(3,5-difluorophenyl) -N -ethylaminomethylmethyl] -7-methoxy-4-oxo-4H- Quinoline-1-ylbu 5 -methoxy-benzene-188 · 200300349 oxymethylbubenzyl 4- 4-acyl-1 -azobicyclo [2.2.2] octane Example 1 (1 h) to obtain 1-[ 3-(2 -bromomethylbenzyloxy) -5 -methoxyphenyl] -7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5- 4 ml of an acetonitrile solution of 120 mg of difluorophenyl) -N-acetamidamine, added with 4.3 mg of 1,4-diazilbicyclo [2.2.2] octane, and stirred at room temperature for 3 hours. The reaction solution was concentrated under reduced pressure, and ether was added to precipitate a solid. The solid was collected and washed with ether to give 105 mg of the title compound as a pale yellow solid. NMR (DMS0-d6) (5ppm: 1.08 (3H, t, J = 7.0Hz), 2. 95-3. 05 (6H, m), 3.27-3. 38 (6H, m), 3.70 (3H, s ), 3.83 (3H, s), 3.78-3.85 (2H, m), 4.66 (2H, s), 5.3K2H, s), 6.4K1H, d, J = 2.2Hz), 6.73 (1H, s), 6.85 (1H, s), 6.92 (1H, t, J = 2.0Hz), 6.98-7.14 (4H, m), 7. 51-7.60 (3H, m), 7.74 (1H, d, J = 7.6Hz), 8.02 (1H, d, J = 9.0Hz), 8.10 (1H, s). • Melting point: 163 ° C ~ Example 2 Chloride 1- {4- {3- {3- [N- (3,5-difluorophenyl) -N-ethylaminemethylmethyl] -7-methoxy 4-oxo-4H-quinolin-1-ylbu 5-methoxy-phenoxymethyl} benzylbu 4 -az-1 -azobicyclo [2 · 2 · 2] octane (exemplified compounds Number: 1 -7 9 9) (2a) K [3- (4-chloromethylbenzyloxy) -5-methoxyphenyl] -7-methoxy-4 -oxo-1,4-dihydroquine Porphyrin-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 1- (3-hydroxy-5-methoxyphenyl) -7-formaldehyde obtained in Example (1 g) Oxy-4-oxo-1,4-dihydroquinoline · 3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 115 11 ^, potassium carbonate 5.0.11 ^ And 0, "'-dichloro-p-xylene, 168 mg, were reacted and purified according to the method of Example (1 h) to obtain 4 6.2 mg of the titled -189- 200300349 compound as a pale yellow foamy substance. NMR (CDC13) δρρπι: 1.2Κ3Η, t, J = 7.1Hz), 3.72 (3H, s), 3.82 (3H, s), 3.93 (2H, q, J = 7.2Hz), 4.6K2H, s), 5.07 (2H, s), 6.40 (1H, d, J = 2.4Hz), 6.50 (1H, t, J = 2.0Hz), 6.55 (1H, t, J = 1.9Hz), 6.62-6.65 (1H, m) , 6.68 (1H, t, J = 2.2Hz), 6.83 (2H, dd, J-2.4, 5.4Hz), 6.92 (1H, dd, J = 2. 3, 9. 0 Hz); 7. 43 (4H, s), 7.85 (1H, s), 8.22 (1H, d, J = 8.9Hz). (2b) chloride l- {4- {3 -{3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -7-methoxy-4-oxo-4H-quinolin-1-yl} -5-methyl Oxy-phenoxymethylbenzyl 4-benzyl-1 -azobicyclo [2.2 · 2] octane The 1- [3- (4-chloromethylbenzyloxy) -5-methyl obtained in Example (2a) 7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -acetamide 44.0 mg and 1,4- Diazepine [2.2.2] octane 9.6 mg, reacted according to the method of Example (li) to obtain the title compound as a pale yellow solid 4 2.0 mg. R (DMS0-d6) δρριη: 1.08 (3H, t, J = 7.2Hz), 3. 00-3. 04 (6H, m), 3.28-3. 37 (6H, m), 3.68 (3H, s), 3.82 (3H, s), 3. 81-3. 86 (2H, m), 4.52 (2H, s), 5.22 (2H, s), 6.38 (1H, d, J-2.2Hz), 6.70 (1H, s), 6.79 (1H, s), 6.84 (1H , t, J = 2.1Hz), 7.00-7.12 (4H, m), 7.54 (2H, d, J = 8.0Hz), 7.6K2H, d, J = 8.0Hz), 8.02 (1H, d, J = 8.9 Hz), 8.09 (1H, s). Melting point: 167 ° C ~. Example 3 4- {3- {3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -7-methoxy-4-oxo-4H -quinoline-1 -Kib 5 -methoxy-phenoxymethyl b 1-methylpyridine mesylate (exemplified compound number: 1-1 4) (3a) l- [3-methoxy-5- (pyridine- 4-ylmethoxy) phenyl]--190- 200300349 7 -methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3, 5-difluorophenyl) -N-Ethylamine To neutralize and extract 4-pyridylformamidine chloride 1 hydrochloride 9 3,5 mg with ethyl ether. The ether layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain a free body of 4-pyridinecarboxamidine chloride. The 1- (3-hydroxy-5-methoxyphenyl) -7-methoxy-4_oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3, 9-Difluorophenyl) -N-acetamidine 93.0mg, 55% sodium hydride 23.3mg and the above 4-pyridinemethylchloride were reacted according to the method of Example (1 h) to obtain the title compound Light yellow foamy substance 36. 4 mg oli R. (CDC13) δ ppm: 1.2K3H, t, J = 7.1 Hz), 3.73 (3H, s), 3.84 (3H, s), 3.93 (2H , Q, J = 7.1Hz), 5.10C2H, s), 6.38 (1H, d, J = 2.3Hz), 6.53 (1Η, t, J = 2.0Hz), 6.56 (1H, t, J-2.0 Hz), 6.59-6.66 (1H, m), 6.68 (1H, t, J = 2.3Hz), 6.84 (2H, dd, J = 2.2, 8.0Hz), 6.92 (1H, dd, J = 2.4, 9.0Hz ), 7.36 (2H, d, J = 5.6Hz), 7.86 (1H, s), 8.22 (1H, d, J = 9.0Hz), 8.65 (2H, br). (3b) 4- {3- {3- [N- (3,5-difluorophenyl) -N-ethylaminemethylmethyl] -7-methoxy-4-oxo-4H-quinoline-bu Benzyl 5 methoxy-phenoxymethyl} -methylpyridine methanesulfonic acid The 1- [3-methoxy-5-(pyridin-4-ylmethoxy) benzene obtained in Example (3 a) Group] -methoxy_4-oxo-I, 4-dihydroquinolinecarboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 36.0 mg in acetonitrile solution 8 ml, add methanesulfonic acid Methyl ester 13.9 mg 'Heat reflux 24 hours. The solvent was concentrated under reduced pressure, and the residue was washed with diethyl ether and filtered to obtain the title compound as a white foamy substance (2.8 mg). 200300349 Rei R (DMS0-d6) (5ppm: 1.08 (3H, t, J = 7.2Hz), 2.29 (3H, s), 3.69 (3H, s), 3.75-3.87 (2H, m), 3.84 (3H, s), 4.34 (3H, s), 5.56 (2H, s), 6.38 (1H, d, J = 2.3Hz), 6.76 (1H, s), 6.85 (1H, s), 6.9K1H, t, J = 2.1Hz), 6.99-7.12 (4H, m), 8.02 (1H, d, J = 8.9Hz), 8.09 (1H, s), 8.13 (2H, d, J = 6.5Hz), 8.97 (2H, d, J = 6.5Hz) Example 4 1- {2- {3- {3- [N- (3,5-difluorophenyl) -N-methylaminemethylmethyl] -7-methoxy 4-oxo-4H-quinolin-1-ylb 5-methoxyphenoxymethyl} benzyl}-1-azobicyclo [2.2 · 2] octane (Exemplary compound number: 1-5 6 4) (4a) l- (3-benzyloxy-5--methoxyphenyl) -7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N-(3, 5 Difluorophenyl) -N-formamidine The 1- (3-benzyloxy-5-methoxyphenyl) -7-methoxy-4-oxo-1,4-obtained in Example (1e) 3.63 g of dihydroquinoline-3 carboxylic acid, 1.2 ml of scopolamine, 2.40 g of N-methyl-3,5-difluoroaniline, and 3.5 ml of triethylamine were purified by the method of Example (1 f) 2. The title compound was obtained as a pale yellow foamy substance of 2.76 g. Circle R (DMS0-d6) (5ppm: 3.34 (3H, s), 3.67 (3H, s), 3. 81 (3H, s), 5.16 (2H, s), 6.39C1H, d, 1 = 2.2 Hz ), 6.70 (1H, s), 6. 81-6. 83 (2H, m), 7.01-7. 05 (2H, m), 7.15 (2H, dd, J = 2.2, 8.6Hz), 7.35-7.47 (5H, m), 8.04 (1H, d, J = 8.9Hz), 8.09 (1H, s) 〇 (4b) l- (3-hydroxy-5-methoxyphenyl) -7-methoxy-4 -Oxygen-1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl) -N -formamidine The 1-(3 -benzyloxy) obtained in Example (4 a) -5 --methoxyphenyl) -7-methoxy-4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N-(3, 5difluorophenyl) -N -formamidine 2.75 g and 10% Pd-C700 mg were reacted according to the method of Example (lg) to obtain the title compound as a white solid, 1.96 g. 200300349 NMR (DMS0-d3) δρριη: 3.33 (3H, s), 3.70 (3H, s), 3. 77 (3H, s), 6. 42 (1H, d, J-2.3Hz), 6.43 (1H, d, J = lr9Hz), 6.52 (1H, d, J = 1.7Hz), 6.55 (1H, t, J = 2. 1Hz), 7.01-7.07 (2H, m), 7.14 (2H, dd, J = 2.3 , 8.5Hz), 8.03 (1H, d, J-9.1Hz), 8.07 (1H, s) 〇 (4c) l- [3- (2-Bromomethylbenzyloxy) -5 -methoxyphenyl]- 7-Methoxy-4 -oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -formamidine The obtained product from Example (4 b) 1-( 3 -Hydroxy-5 -methoxyphenyl) -7 -methoxy-4_oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N- Formamidine 32211 ^, 55% sodium hydride 60.211 ^, and 0.0: -dibromo-o-xylene 1.46 g. Purified by the method of Example (1 h) to obtain the title compound. White foamy substance 3 17 mg. NMR (CDC13) < 5ppm: 3.46 (3Η, s), 3.74 (3Η, s), 3.84 (3Η, s), 4.62 (2H, s), 5.23 (2H, s), 6.45 (1H, d , J = 2.3Hz), 6.54 (1H, t, 1 = 2.0Hz), 6.60-6.65 (1H, m), 6.73 (1H, t, J-2.2Hz), 6.90 (2H, dd, J = 2.2, 8.1Hz), 6.95 (2H, dd, J = 2.3, 9.0Hz), 7. 36-7. 40 (2H, m), 7. 41-7. 47 (2H, m), 7.94 (1H, s) , 8. 25 (1H, d, J = 9.0Hz) 〇 (4d) Brominated 1- {2- {3- {3- [N- (3,5-difluorophenyl) -N-methylamine methyl Fluorenyl] -7-methoxy-4-oxo-4H-quinolin-1-ylbu 5-methoxy-phenoxymethyl} benzyl 丨 -buzobicyclo [2.2.2] octane will [3-(2-Bromomethylbenzyloxy) -5 -methoxyphenyl] -7-methoxy-4-oxo-1,4-dihydroquinoline-3- obtained in Example (4c) The carboxylic acid N- (3,5-difluorophenyl) -N-formamidine 119 mg quinidine 24.4 mg was reacted according to the method of Example (li) to obtain the title compound as a white solid 113 mg. -193- 200300349 Li R (DMS0-d6) δρριη: 1.84 (6H, br), 2. 02-2. 04 (1H, m), 3.35 (3H, s), 3.44 (6H, t, J = 7.4Hz ), 3.7K3H, s), 3.83 (3H, s), 4.55 (2H, s), 5.30 (2H, s), 6.43 (1H, d, J = 2.2Hz), 6.77 (1H, s), 6.87 ( 1H, t, J = 1.8Hz), 6.9K1H, t, J = 2.1Hz), 7. 03-7. 07 (2H, m), 7.16 (2H, dd, J = 2.2, 8.7Hz), 7. 49-7. 61 (3H, m), 7.72 (1H, d, J = 7.6Hz), 8.05 (1H, d, J = 9.0Hz), 8.1K1H, s). Melting point · 165 ° C ~ . Example 5 {2- {3- {3- [N- (3,5-difluorophenyl) -N-methylaminomethylmethyl] -7-methoxy-4-oxo-4H-quine Phenyl-1-yl} -5 -methoxy-phenoxymethyl} benzyl} triethylammonium (exemplified compound number: 1-5 5 0) 1-[3-(2 -Bromomethylbenzyloxy) -5 -methoxyphenyl] -7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3, 5-difluorophenyl ) -N-formamidine 117 mg and triethylamine 54.6 mg were reacted according to the method of Example (li) to obtain 101 mg of the title compound as a white solid. NMR (DMS0-d6) (5ppm: 1.22 (9H, t, 1 = 7.1Hz), 3.26-3. 32 (6H, m), 3.35 (3H, s), 3.7K3H, s), 3.83 (3H, s ), 4.62 (2H, s), 5.34 (2H, s), 6.40 (1H, d, J = 2.2Hz), 6.78 (1H, s), 6. 89-6. 90 (2H, m), 7. 02-7. 07 (2H, m), 7.16 (2H, dd, J = 2.1, 8.7Hz), 7. 51-7. 61 (3H, m), 7.70 (1H, d, J = 7.8Hz), 8.05 (1H, d, J = 9.0Hz), 8.1K1H, s). Melting point: 130 ° C ~. Example 6 {2- {3- {3- [N- (3,5-difluorophenyl) -N-methylaminemethylmethyl] -7-methoxy-4-oxo-4H-quinoline- 1-Gib 5 -methoxyphenoxymethyl} benzyl} dimethylsulfonium bromide (exemplified compound number: 1-5 6 8) 1- [3- (2-bromomethylbenzyl) obtained in Example (4c) (Oxy) -5-methoxybenzene-194- 200300349 group] -7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl ) -N-formamidine 48.2mg and dimethylsulfide 48.3mg. According to the method of Example (li), the title compound was obtained as white solid 30.Omg. MR (DMS〇-d6) δ ppm: 2.87 (6H, s), 3.35 (3H, s), 3.71 (3H, s), 3. 84 (3H, s), 4.79C2H, s), 5.28 (2H, s), 6.44 (1H, d, J = 2.4Hz), 6.78 (1H, s), 6.88 (1H, d, J = 1.6Hz), 6.90 (1H, t, J = 2.1Hz), 7. 02- 7.07 (2H, m), 7.16 (2H, dd, J = 2.2, 8.5Hz), 7.48-7.57 (3H, m), 7.66-7.68 (1H, m), 8.05 (1H, d, J = 8.9 Hz), 8.10 (1H, s). Melting point: 138 ° C ~. Example 7Iodide 1- {6- {3- {3- [N- (3,5-difluorophenyl) -1 ethylaminomethylmethyl] -7-methoxy-4-oxo-4H -Quinoline-1-ylbu 5 -methoxyphenoxy 丨 hexylbu 4 -acyl-1 -azobicyclo [2.2 · 2] octane (Exemplified compound number: 1-66) (7 &) 1- [ 3- (6-iodohexyloxy) -5-methoxyphenylb 7-methoxy-4-oxo-1,4-dihydroquinoline: 3-carboxylic acid N-(3,5-difluoro Phenyl) -N-acetamidinium 1- (3-hydroxy-5-methoxyphenyl) -7-methoxy-4-oxo-1,4-dihydroquinoline obtained in Example (〗 g) -3 -carboxylic acid N- (3,5-difluorophenyl) -N- acetamidine 1001 ^, 55% sodium hydride 18.211 ^, and 1,6-diiodohexanoate 5 6 7 mg, Purification was carried out according to the method of Example (1 h) to obtain the title compound as a light yellow foamy substance (118 mg). Surface, (CDC13) 5PPm: 1.21 (3H, t, Ι = 7 · ΙΗζ), 1.48-1 · 54 (4Η, in), 1.78-1.92 (4Η, m), 3.2K2H, t, J = 7.0 Hz), 3.74 (3H, s), 3.83 (3H, s), 3. 89-3. 97 (4H, m), 6.43 (1H, d, J = 2.3Hz), 6.46 (2H, d, J = 2.1Hz), .6.60-6. 65 (2H, m), 6.84 (2H, dd, J = 2.0, 8.0Hz), 6.92 (1H, dd, J-2.3, 8.9Hz), 7.86 (1H, s) , 8.22 (1H, d, J = 9.0Hz). -195- 200300349 (7b) Iodide {6- {3- {3- [N- (3,5-difluorophenyl) -N-ethylamine [Methylfluorenyl] -7-methoxy-4-oxo-4H-quinolin-1-ylbumethoxyphenoxy} hexylbu 4-acyl-1azobicyclo [2.2 · 2] octane Example (7 a) The obtained 1- [3- (6-iodohexyloxy) -5-methoxyphenyl] -7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 117 mg of N- (3,5-difluorophenyl) -N-acetamidine and 2 2.8 mg of 1,4-diazinebicyclo [2.2.2] octane, reacted according to the method of Example (1 i), 115 mg of the title compound was obtained as a white solid. NMR (DMS0-d6) δρριι: 1.08 (3H, t, J = 7.0Hz), 1.32-1.38 (2H, m), 9 1.44-1.51 (2H, m), 1.64-1 79 (4H, m), 3.02 (6H, t, 1 = 7.4Hz), 3.17 (2H, dd, J = 5.1, 8.4Hz), 3.25 (6H, t, J = 7.8Hz), 3.69 (3H, s), 3.8K3H, s ), 3.81-3.84 (2H, m), 4.03 (2Η, t, J = 6.0Hz), 6.39 (1H, d, J = 2.2Hz), 6.65 (2H, d, J = 7.9Hz), 6 71 (1Η, t, J-2.0Hz), 7.0K1H, dd, J = 2.2, 8.9Hz), 7.04-7.10 (3H, m), 8.0K1H, d, J = 8.9Hz), 8.08 (1H, s). Melting point: U7 ° C ~. Example 8 Chloride {2- {3- {3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -7-φ Methoxy-4-oxo- 4Η-quinolin-1-yl 丨 -5 -methoxyphenoxymethyl} benzyl} triethylammonium (exemplified compound number: 1-5 7 0) (8a) l- [ 3- (2-chloromethylbenzyloxy) -5-methoxyphenyl-7-methoxy- 4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-di Fluorophenyl-N-acetamidinium 1- (3-hydroxy-5-methoxyphenyl) -7-methoxy-4-oxo-1,4-dihydroquinoline obtained in Example (1 g) -3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 4 5 2 mg, 55% sodium hydride 8 2 mg and α, α, dichloro-o-dimethyl-196- 200300349 1. 2 g of benzene was reacted according to the method of Example (1 h) to obtain 472 mg of the title compound as a white foamy substance. NMR. (CDC13) δρριη: 1.2Κ3Η, t, J = 7.1Hz), 3.77 (3H, s), 3.83 (3H, s), 3.93 (2H, q, J = 7.1Hz), 4.72 (2H, s) , 5.22 (2H, s), 6.42 (1H, d, J = 2.3Hz), 6.5K1H, t, J = 1.9Hz), 6.60 (1H, t, J = 2.0Hz), 6.61-6.65 (1H, m ), 6.71 (1H, t, J = 2.2Hz), 6.84 (2H, dd, J = 2.2, 8.0Hz), 6.92 (1H, dd, J = 2.3, 9.0Hz), 7.38-7.41 (2H, m) , 7.43-7.49 (2H, m), 7.87 (1H, s), 8.23 (1H, d, J = 9.0Hz) 〇 (8b) chloride {2- {3- {3- [N- (3,5 -Diphenyl) -N-ethylaminomethyl] -7-methoxy-4-oxo-4H-quinolin-1-yl} -5 -methoxyphenoxymethyl} benzyl} diethylene The 1- [3-(2-chloromethylbenzyloxy) -5 -methoxyphenyl-7 -methoxy-4-oxo-1,4-dihydroquinoline-3 obtained in Example (8 a) was obtained. -Carboxylic acid N- (3,5-difluorophenyl-N-acetamidine 102 mg and triethylamine 180 mg, reacted according to the method of Example (1 i), to obtain the title compound as a white solid 9 0 · 3 mg NMR. (DMS0-d6) δρριη: 1.08 (3H, t, J = 7.1Hz), 1.22 (9H, t, J = 7.0Hz), 3.28-3. 33 (6H, m), 3.70 (3H, s ), 3.83 (3H, s), 3. 81-3. 88 (2H, m), 4.62 (2H, s), 5.34 (2H, s), 6.38 (1H, d, J = 2.3Hz), 6.73 ( 1H, s), 6.86 (1H, s), 6.90 (1H, t, J = 2.1Hz ), 7.02 (1H, dd, J = 2.2, 8.9Hz), 7.05-7.13 (3H, m) „7.51-7.61 (3H, m), 7.70 (1H, d, J = 7.7Hz), 8.02 (1H, d, J = 8.9Hz), 8.10 (1H, s). Melting point: 143 ° C ~. Example 9 Chloride 1- {2- {3- {3- [N- (3,5-monochlorophenyl) ) -N-Ethylaminomethyl] -7-methoxy-4-oxo-4H-quinoline-bukib 5-b-methoxyphenoxymethyl} benzyl azobicyclo [2.2.2] octyl Alkane (exemplified compound number: 1-5 9 6) The 1- [3- (2-chloromethylbenzyloxy) -5 -methoxyphenyl_7_ -197- 200300349 methoxy- 140 mg of 4-oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl-N-acetamidine and 37.7 mg of quinidine were reacted according to the method of Example (li) 147 mg of the title compound was obtained as a white solid. _R (DMS0-d6) δρρπι: 1.08 (3Η, t, J = 7. ΟΗζ), 1.84 (6H, br), 2 .. 03 (1H, br), 3.45 (6H, t, J = 7. 7Hz) , 3.70 (3H, s), 3. 79-3. 86 (2H, m), 3.83 (3H, s), 4.57 (2H, s), 5.3K2H, s), 6.4K1H, d, J = 2.3Hz ), 6.72 (1H, s), 6.85 (1H, s), 6.9K1H, t, 1-2.0Hz), 7.02 (1H, dd, J = 2.3, 9.0Hz), 7. 06-7.14 (3H, m ), 7.52 (1H, d, J-7.0Hz), 7.57-7.61 (2H, m), 7.72 (1H? D, J = 7.5Hz), 8.02 (1H, d, J = 9.0Hz), 8.11 (1H , s). Melting point: 175 ° C ~. φ Example 1 〇 {2- {3- {3-[^ (3,5-difluorophenyl) -1 ethylamine formamidine 7-methoxy-4-oxo-4H-quinoline-1 -Yl}-5 -methoxyphenoxymethyl} benzyl} triethylphosphonium chloride (exemplified compound number: 1-6 11) [3- (2-chloromethylbenzyloxy) obtained in Example (8a) ) -5-methoxyphenyl-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl-N-acetamidine l 〇3mg and triphenylphosphine 23.8 mg, reacted according to the method of Example (1i) to obtain the title compound as a white foamy substance · 8 9.0 mg 〇 ^ R (DMSO-d6) 0ppni: 0.99-1.10 (12H, m ), 2.2H.30 (6H, in), 3.70 (3H, s), 3.83 (3H, s), 3.78-3.92 (2Η, m), 3.92 (2Η, d, J = 15.6Hz), 5.23 (2H , s), 6.39 (1H, d, J = 2.2Hz), 6.73 (1H, s), 6. 85 (1H, s), 6.91 (1H, t, J-1.9Hz), 7.04-7.12 (4H, m), 7.43-7.46 (3H? m), 7.61 (1H, dd, J-2.5, 7.5Hz), 8.02 (1H, d, J = 9.0Hz), 8.HK1H, s). Example n L- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylamidino] -1- -198- 200300349 (3,5-dimethoxy Phenyl) -4 -oxo-1,4-dihydroquinoline-7 -yloxy] heptylbu 4 -acyl-1 -azobicyclo [2 · 2.2] octane (Exemplified compound number: 2-142 ) (lla) l- (4-benzyloxy-2-hydroxyphenyl) ethanol A solution of 2 ', 4'-diacetophenone in acetone 100 m 1 was added under ice-cooling potassium carbonate 1 3.6 g, stir for 10 minutes, add benzyl bromide 8.60 m 1 and stir at 60 ° C for 1 hour. The reaction solution was added with dilute hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The solidified residue was recrystallized from ethyl acetate to obtain 1 2.9 g of the title compound as a light-colored solid. Li R * (CDC13) δρριη: 2.55 (3H, s), 5.09 (2H, s), 6. 48-6. 55 (2H, m), 7.32-7 · 45 (5Η, m), 7.64 ( 1H, d, J = 8.1Hz). (llb) l- (4-benzyloxy-2-methoxyphenyl) ethanone The N, N-of 1- (4-benzyloxy-2-hydroxyphenyl) ethanol 6.83 obtained in Example (11a) 70 ml of a dimethylformamide solution was added at room temperature to 5.84 g of potassium carbonate, and after stirring for 15 minutes, methyl iodide was added at 2.63 ml, and the mixture was stirred at 40 ° C for 2 hours. The reaction solution was added with dilute hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained solid was collected by filtration and washed with diisopropyl ether to obtain 7.06 g of the title compound as a pale yellow solid. NMR (rac13) 5ppm: 2.47 (3H, s), 3.76 (3H, s), 5.00 (2H, s), 6.44 (lH, d, J = 2.2Hz), 6.49 (1H, dd, J = 2.2, 8.8 Hz), 7.21-7.38 (5H, in), 7.72 (1H, d, J = 8.8Hz) 〇 (llc) 3- (4-benzyloxy-2-methoxymethoxy) -3-oxopropanoic acid ethyl Ester-199- 200300349 Diethyl carbonate solution of 1- (4-benzyloxy-2-methoxyphenyl) ethanol 1.0.0 (^) obtained in Example (1 1 b) 7: 111, 55% hydrogenation was added Sodium 2 7 2 1 ^, heated under reflux for 1 hour. The reaction solution was added with dilute hydrochloric acid and extracted with ether. The ether layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was evaporated. Purified by silica gel column chromatography (eluent: ethyl acetate / hexane = 1/3) to obtain the title compound as a yellow oily substance 966 mg 〇 r (CDC13) δ ppm: 1.24 (3H, t, 1 = 7. 3Hz), 3.85 (3H, s), 3.92 (2H, s), 4. 18 (2H, q, J = 7.3Hz), 5.12 (2H, s), 6.52 (1H3 d, 1 = 2.2 Hz), 6.63 (1H, dd, J = 2.9, 8.8Hz), 7. 32-7. 46 (5H, m), 7.94 (1H, d, I = 8.8Hz) 〇 (lld) 2- (4 -Benzyloxy-2-methoxybenzylfluorenyl) -3 -dimethylamine ethyl acrylate The 3-(4-benzyloxy) obtained in Example (1 1 c) 50 ml of a tetrahydrofuran solution of 4.77 g of ethyl 2-methoxyphenyl) -3 -oxopropionate was added with N, N-dimethylacetamide 2. 8 9 m 1, and heated under reflux for 5 hours. The reaction solution was decompressed. The residue was concentrated and purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/3) to obtain 5.0 1 g of the title compound as a yellow oily substance. NMR. (CDC13) δ ppm: 0.91 (3H , t, 1 = 6.6 Hz), 3.00 (6H, bs), 3.75 (3H, s), 3.93 (2H, q, 1 = 6.6Hz), 5.09 (2H, s), 6.48 (1H, d, J -2.2Hz), 6.56 (1H, dd, 1 = 2.2, 8.8Hz), 7.30-7 · 46 (5Η, m), 7.63 (2Η, bs). (Lle) 7-benzyloxy- l- (3,5-Dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid ethyl ester The 2- (4-benzyloxy) obtained in Example (1 1 d) -2 -Methoxybenzyl)-5.0-g of dimethylamine ethyl acrylate N, N -dimethylformamide solution 100 m 1. Add 3,5 -dimethoxyaniline 3.0 0 0 g and potassium carbonate 3.61 g, and stirred at -200- 200300349 1 4 0 ° C for 5 hours. The reaction solution was concentrated under reduced pressure, diluted hydrochloric acid and ethyl acetate were added, and the insoluble matter was washed with water and ethyl acetate, and collected by filtration to obtain 3.70 g of the title compound as a yellow solid. NMR (CDC13) (5ppm: 1.39 (3H, t, J = 6.6Hz), 3.82 (6H, s), f4.38 (2H, q? J = 6.6Hz), 5.0K2H, s), 6.45-6. 52 (3H, m), 6.64 (1H, t, J = 2.2Hz), 7.06 (1H, dd, J 2.2, 8.8Hz), 7.27-7.38 (5H, m), 8.42 (1H, s), 8 45 (1Η, d, J = 8.8Hz). (llf) 7-benzyloxy-1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid. The result obtained in Example (1 1 e) is 7 -Benzyloxy-1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester 4.23 g of ethanol solution 200 ml, Add 10% sodium hydroxide aqueous solution 50 m 1, according to the method of Example (1e) to obtain the title compound as a yellow solid 3.67 g. Li R. ⑽S0-d6) 5ppnK 3.80 (6H, s), 5.06 (2H, s), 6.45 (1H, d, J = 2.2Hz), 6.64-6.70 (2H, m), 6.74 (1H, t, J = 2.2Hz), 7.08 (1H, dd, J = 2.2, 8.8Hz), 7.26-7.40 (5H, m), 8.20 (1H, d, J = 8.8Hz), 8. 26-8.38 (1H, m) 〇 (llg) 7-benzyloxy-1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N-(3, 5 -difluoro Phenyl) -N-acetamidine The 7-benzyloxy-1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline obtained in Example (1 1 f) -3 -carboxylic acid 3.67 g, grasshopper chlorine 1.48 ml, catalyst amount N, N -dimethylformamide, 2.67 g of N-ethyl-3,5-difluoroaniline obtained in Reference Example 2 and triethyl Amine 4.74m: 1. According to the method of Example (If), 4.3 2 g of the yellow foamy substance of the title compound was obtained. -201- 200300349 Orbit (CDC13) (5ppm: 1.20 (3H, t, J = 6.6Hz), 3.80 (6H, s), 3.92 (2H, q, J-6.6Hz), 4.97 (2H, s), 6.40 (2H, d, J = 2.2Hz), 6.43 (1H, d, J = 2.9Hz), 6.56-6.66 (2H, m), 6.83 (2H, dd, 1 = 2.2, 8.1Hz), 6.98 (1H, dd, J = 2.2, 8.8Hz), 7.23-7 · 36 (5Η, in), 7.83 (1Η, s), 8.21 (1Η, d, J = 9.5Hz). (llh) l- ( 3,5-dimethoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenylacetamidine) Examples ( 1 1 g) of the obtained 7-benzyloxy-1-(3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-di 3.54 g of fluorophenyl) -N-acetamidamine and 800 mg of 10% Pd-C, reacted according to the method of Example (lg), and the title compound was obtained as a white solid 2 · 7 4 g. R (CDC13) 0ppm: 1 · 17 (3Η, t, J = 7.1Hz), 3.77 (6H, s), 3.89 (2H, Q, 1 = 7.1 Hz), 6.40 (2Η, d, J = 2.1Hz), 6.48 (1H, d , J = 2.0Hz), 6.54 (1H, t, J = 2.2Hz), 6.53-6.57 (1H, m), 6. 75-6. 85 (2H, m), 6. 89 (1H, dd, J = 2.1, 9.0Hz) r 7.80 (1H, s), 7.89 (1Η, d, .b 8.9Hz), 9.64 (1Η, bs). (Lli) 7- (7-bromoheptyloxy) -1- (3, 5-dimethoxyphenyl) -4 -oxy-1,4 -di Quinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 1- (3,5-dimethoxyphenyl) -7- obtained in Example (1 1 h) Hydroxy-4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl-N-acetamidamine 198mg N, N-dimethylformamide solution 6ml 85.3 mg of potassium carbonate was added, and after stirring for 20 minutes, 0.21 ml of 1,7-dibromoheptane was added and stirred at room temperature for 3 hours. The reaction solution was added with dilute hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was rinsed The organic layer was dried over anhydrous sodium sulfate with water and saturated brine, and then the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate / hexane = 2/1) to obtain the title compound as a white foamy substance of 261 mg. -202- 200300349 NMR (CDC13) δρριη: 1.2K3H, t, J = 6.6Hz), 1. 30-1.50 (6H, m), 1.67-1.90 (4H, m), 3.39 (2H, t, J = 6.6 Hz), 3.84 (6H, s), 3.87 (2H, t, J = 6.6Hz), 3.93 (2H, q, J-6.6Hz), 6.40 (1H, d, J = 2.2Hz), 6.50 (2H, d, J = 2.2Hz), 6.59-6.67 (2H, in), 6.85 (2H, dd, J = 2.2, 8.1Hz), 6.91 (1H, dd, J = 2.2, 8.8Hz), 7.85 (1H, s ), 8.21 (1Η, d, J = 8.8Hz). (llj) bromide 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3, 5-dimethoxyphenyl)- 4-oxo-1,4-dihydroquinoline-7-yloxy] heptyl} -4-acyl-1-azobicyclo [2.2.2] octane will be obtained from Example (1 Π) 7-( 7-bromoheptyloxy) -1-(3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl ) -N-acetamidine 261 mg of N, N-dimethylformamide solution 2m in 1, 4-diazinecyclo [2.2.2] octane 4 4.5 mg, and stirred at room temperature for 12 hours. The reaction was concentrated under reduced pressure, and ether was added to solidify the product. The solid was collected by filtration, and washed with diethyl ether to obtain the title compound as a white solid, 24 8 mg NMR; (CDC13) δ ppm: 1.20 (3H, t, J = 6.6Hz), 1. 32-1.43 (6H, bs), 1.65-1.80 (4H, m), 3.24 (6H, t, J-7.3Hz), 3.50-3.57 (2H, m), 3.65 (6H, t, J = 7.3Hz), 3.83 (6H, s), 3.82 -3.87 (2H, m), 3.9K2H, q, J-6.6Hz), 6.39 (1H, d, J = 2.2Hz), 6.44 (2H, d, 1 = 2.2Hz), 6.6K1H, t, J- 2.2Hz), 6.62-6.67 (1H, m), 6.83 (2H, dd, J = 2.2, 8.1Hz), 6.9K1H, dd, J = 2.2, 8.8Hz), 7.78 (1H, s), 8.19 (1H, d, J-8. 8Hz). Melting point: 130-1 32 ° C. Example 1 2 1- {4- [3- [N- (3,5-difluorophenyl) 1-ethylaminomethyl]]-1- (3,5-dimethoxyphenyl)- 4-oxo-1,4-dihydroquinoline-7-yloxymethyl 200300349] benzylbu 4_acryl-Mazinebicyclo [2 · 2 · 2] octane (exemplified compound number: 2-563) (12a) 7- (4-chloromethylbenzyloxy) -1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3 1,5-difluorophenyl) -N-acetamidine The 1- (3,5-dimethoxyphenyl) -7-hydroxy-4-oxy-1,4-diamine obtained in Example (1 1 h) Hydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 152nig N, N-dimethylformamide solution 2ml, 65.5mg potassium carbonate was added, and stirred for 15 minutes 1. Add 166 mg of α, α'-dichloro-p-xylene and stir at 5 ° C for 3 hours. Add the reaction solution to dilute hydrochloric acid and extract with ethyl acetate. Wash the ethyl acetate layer with water and saturate. The solution was dried with anhydrous sodium sulfate, and the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate / hexane = 2/1) to obtain the title compound as a transparent oily substance 1 6 0 mg. Li (CDC13) δ ppm: 1.19 (3H, t, J = 7.3Hz), 3.80 (6H, s) , 3.91 (2H, q, 1 = 7.3 Hz), 4.56 (2H, s), 4.96 (2H, s), 6. 38-6.45 (3H, m), 6.57-6.65 (2H, m), 6.82 ( 2H, dd, 1 = 2.2, 8.1Hz), 6.96 (1H, dd, J = 2.2, 8.8Hz), 7.26 (2H, d, J = 8. 1Hz), 7.34 (2H, d, J = 8.1Hz) , 7.83 (1Η, s), 8.20 (1H, d, J = 8.8Hz). (12b) l- {4- [3- [N- (3,5-difluorophenyl) -N -Ethylaminomethyl] -l- (3,5-dimethoxyphenyl) -4-oxy-1,4-dihydroquinoline-7-yloxymethyl] benzyl}-4-卩 γ -1-Aromatic Shuangyun [2 · 2 · 2] The semi-academy will take 7-(4-chloromethylbenzyloxy) -1-(3,5-dimethoxyphenyl) obtained in Example (1 2 a). -4 -Oxygen-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 1 5 9 mg of N, N -dimethylformamidine An amine solution of 3 ml 1 was added with 1,4-diazinebicyclo [2 · 2 · 2] octane 28.8 mg, and the mixture was stirred at room temperature overnight. The reaction solution was concentrated under reduced pressure, and ether was added to solidify the product. 200300349 The solid was collected by filtration and washed with diethyl ether to obtain the title compound as a white solid 152 mg. NMR (CDC13) δρριη: 1.19 (3H, t, J = 7.3Hz)? 3.15 (6H, t, J = 7.3Hz) , 3.70 (6H, t, J = 7.3Hz), 3.84 (6H, s), 3.9K2H, q, J = 7.3Hz), 4.98 (2H, s), 5.08 (2H, s), 6.39 (2H, d , J = 2.0Hz), 6.45 (1H, d, J = 2.0Hz), 6.58-6.68 (2H, m), 6.83 (2H, dd, 1 = 2.2, 8.6Hz), 6.94 (1H, dd, J = 2.2, 9.4Hz), 7.39 (2H, d, J = 8.0Hz), 7.63 (2H, d, J = 8.0Hz), 7.82 (1H, s), 8.20 (1H, d, J = 8.6Hz). Melting point : 1 8 0-1 8 2 ° C. Example 1 3 1- {4- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethyl]-1- (3,5-dimethoxyphenyl ) -4 -oxy-1,4-dihydroquinoline-7-yloxymethyl] benzyl} pyridine (exemplified compound number · 2-5 2 9) 7- (obtained in Example (12a) 4-chloromethylbenzyloxy) -1- (3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 5-difluorobenzene ) -N-acetamidine 195 mg and pyridine 1 m 1 were reacted according to the method of Example (1 2 b) to obtain the title compound as a white solid 98.8 mg. Ship R (DMS0-d6) δρρίϋ: 1.08 (3H, t, J = 6.8Hz), 3.80 (6H, s), 3.82 (2H, # q, 1 = 6.8Hz), 5.06 (2H, s), 5.88 ( 2H, s), 6.41 (1H, d, J-2.9Hz), 6.57 (2H, s), 6.75 (1H, s), 7.03-7.14 (4H, m), 7.40 (2H, d, J = 7.8Hz ), 7.52 (2H, d, J-7.8Hz), 8.00 (1H, d, 1 = 8.8Hz), 8.07 (1H, s), 8.18 (2H, t, J = 7.8Hz), 8.63 (1H, t , J = 7.8Hz), 9.18-9. 26 (2H, m). Melting point: 1 8 1-1 8 4 ° C. Example 1 4 {4- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl]-1- (3,5-dimethoxyphenyl) -4 -Yl-1,4-dihydroquinoline-7-yloxymethyl]-205-200300349 benzyl} diethylammonium (example compound number: 2-5 3 3) 7 obtained in Example (12a) -(4-chloromethylbenzyloxy) -1- (3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-di 137 mg of fluorophenyl) -N-acetamidine and 0.5 ml of triethylamine were reacted according to the method of Example (12b) to obtain the title compound as a white solid 107 mg. NMR (CDC13) δ ppm: 1.19 (3H, t, J = 7.3Hz), 1.45 (9H, t, J = 7.3Hz), 3.44 (6H, q, J = 7.3Hz), 3.84 (6H, s), 3.9K2H, q, J = 7.3Hz), 4.84 (2H, d, J = 10.3Hz), 4.99 (2H, s), 6.4K2H, d, J = 2.2Hz), 6.46 (1H, d, J = 2.2Hz), 6.48-6. 66 (2H, m), _ 6.82 (2H, dd, J = 2.2, 8.1Hz), 6.94 (1H, dd, J = 2.2, 8.8Hz), 7.40 (2H, d, J = 8.1Hz), 7.58 (2H, d, J = 8.1Hz), 7.82 (1H, d, J = 2.2Hz), 8.20 (1H, d, 1 = 9.5Hz). Melting point: 1 6 7-1 7 0 ° C. Example 1 5 Iodine 1-5-[3-[N-(3,5-difluorophenyl) -N -ethylaminomethylmethyl]]-1- (3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7-yloxy] benzylbenzene 4-az-1-azobicyclo [2.2.2] octane (exemplified compound number: 2-44) φ ( 15a) l- (3,5-dimethoxyphenyl) -7- (5-iodopentyloxy) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5 -Difluorophenyl) -N-acetamidinium Example U 1 h) The obtained 1-(3,5-dimethoxyphenyl) -7 -hydroxy-4 -oxo-1,4-dihydroquinoline -3 -carboxylic acid N- (3,5-difluorophenyl-N-acetamidamine 2 0 5 mg, potassium carbonate 8 8 · 5 mg, and 1,5-diiodopentane 0.1 9 6 m] The reaction was purified according to the method of Example (2i) to obtain 197 mg of the title compound as a yellow oily substance.-206- 200300349 Orbital (CDC13) όρρπκ 1.19 (3Η, t, Ι = 7 · 3Ηζ ), 1.46-1.56 (2Η, m), 1.69-1.89 (4Η, m), 3.17 (2Η, t, J = 6.6Hz), 3.82 (6Η, s), 3.86 (2Η, t, J = 6.6Hz), 3.9K2H, q, J = 7.3Hz), 6.38 (1H, d, J = 2.2Hz), 6.46 (2H, d, J = 2.2Hz), 6.58-6.66 (2H, m), 6.83 (2H, dd, J = 2.2, 8.1Hz), 6.89 0H, dd, J = 2.2, 8.8Hz), 7.84 (1H, s), 8.2 (1H, d, J = 8.8Hz). (15b) Iodine 1- {5- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3,5-dimethoxyphenyl)- 4-oxo-1,4-dihydroquinoline-7-yloxy] pentyl}-4 -acyl-1 -azobicyclo [2 · 2 · 2] octane (3,5-Dimethoxyphenyl) -7- (5-iodopentanoyloxy) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 5-difluoro 197 mg of phenyl) -N-acetamidamine and 32.7 mg of 1,4-diazinebicyclo [2 · 2 · 2] octane. The reaction was carried out according to the method of Example (1 1 j) to obtain the title compound as a white solid. 179mg. NMR, (CDC13) δ ppm: 1.20 (3H, t, J = 7.3Hz), 1.45-1. 56 (2H, m), 1.65-1.92 (4H, m), 3.23 (6H, t, J = 7.3Hz ), 3.48-3.57 (2H, m), 3.63 (6H, i, J = 7.3Hz), 3.83 (6H, s), 3.80-3.87 (2H? M), 3.9K2H, q, J = 7.3Hz), 6.37 (1H, d, J = 2.2Hz), 6.42 (2H, d, J-2.2Hz), 6.62 (1H, t, J = 2.2Hz), 6.63-6.68 (1H, e), '6.82 (2H , dd, J = 2.2, 7.3Hz), 6.90 (1H, dd, 1 = 2.2, 8.8Hz), 7.76 (1H, s), 8.18 (1H, d, 1 = 8.8 Hz). Melting point: 1 3 7 -1 4 0 ° C. Example 1 6 Iodide 1- {6- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3,5-dimethoxyphenyl) -4 -oxo-1,4 -dihydroquinoline-7 -yloxy] hexylbu 4 -acryl-1-azobicyclo [2.2.2] octane (exemplified compound number ·· 2 _ 6 3)- 207-200300349 (16a) l- (3,5-dimethoxyphenyl) -7- (6-iodohexyloxy) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 1- (3,5-dimethoxyphenyl) -7-hydroxy-4,4-oxy-1,4-obtained in Example (11h) Dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl-N-acetamidamine 203mg, potassium carbonate 87.5mg and 1,6-diiodohexane 0.215ml, according to the example (1 1 The reaction was purified by the method of i), and the title compound was obtained as a transparent oily substance of 2.1 mg. NMR. (CDC13) δ ppm: 1.2K3H, t, J-7.3Hz), 1. 38-1.48 (4H, m ), 1.70-1.86 (4H, m), 3.18 (2H, t, J = 7.3Hz), 3.84 (6H, s), 3.87 (2H, t, J = 6.6Hz), 3.93 (2H, q, J = 7.3Hz), 6.39 (1H, d, J = 2.2Hz), 6.47 (2H, d, J = 2.2Hz), 6.58-6.66 (2H, m), 6.84 (2H, dd, J = 2.2, 8.1Hz) , 6.9K1H, dd, J = 2.2, 8.8Hz), 7.85 (1H, s), 8.21 (1Η, d, J = 8.8Hz). (16b) l- {6- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3,5-dimethoxyphenyl)- 4-oxo-1,4-dihydroquinolin-7-yl'oxy] hexylb 4-azyl-Mazinebicyclo [2.2.2] octane Example 1 (16a) to obtain 1-(3 , 5-dimethoxyphenyl) -7- (6-iodohexyloxy) -4-oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-Acetylamine 2010 ^ and 1,4-diazinebicyclo [2.2.2] octane 32.511 ^, the reaction was carried out according to the method of Example (11j) to obtain 123 mg of the title compound as a white solid. NMR (CDC13) (5ppm: 1.20 (3H, t, J = 7.3Hz), 1. 36-1.46 (4H, πι), 1.68-1.86 (4H, m), 3.24 (6H, t, J = 7.3Hz) , 3.48-3.56 (2H, m), 3.62 (6H, t, 1-7.3Hz), 3.84 (6H, s), 3. 82-3. 87 (2H, m), 3.91 (2H, q, J = 7.3Hz), 6.38 (1H, d, 1 = 2.2Hz), 6.44 (2H, d, J = 2.2Hz), 6.62 (1H, t, 1 = 2.2Hz), 6.63-6.67 (1H, m), 6.82 (2H, dd, J-2.2, 8.1Hz), 6.9K1H, dd, J-2.2, 9.5z), 7.79 (1H, s), 8. 19 (1H, d, J-8.8Hz).-208- 200300349 Melting point: 1 3 0-1 3 3 ° C. Example 17 1- {6- [3- [N- (3,5-— ^ chlorophenyl) -N-ethynylmethyl] -1_ (3, 5-dimethoxyphenyl)- 4-oxo-1,4-chlorochloroquinolin-7-yloxy] hexyl 丨 pyridine (exemplified compound number: 2-5 0) 1-(3, 5- Dimethoxyphenyl) -7- (6-iodohexyloxy) -4-oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N- Acetylamine 196 mg and pyridine 1 m 1 were reacted according to the method of Example (1 1 j) to obtain the title compound as a white solid 1 6 1 mg ° NMR (CDC13) (5ppm: 1.20 (3H , t, J = 7.3Hz), 1.42-1. 58 (4H, m), 1. 67-1. 75 (2H, m), 2. 06-2. 13 (2H, m), 3.83 (6H, s), 3. 84-3. 87 (2H, m), 3.92 (2H, q, J = 7.3Hz), 4.96 (2H, t, 1 = 7.8Hz), 6.37 (1H, s), 6.43 (2H , s), 6.60-6.67 (2H, m), 6.83 (2H, d, J = 6.7Hz), 6.90 (1H, d, J = 8.1 Hz), 7.78 (1H, s), 8. 10 (2H , t, J = 6.7Hz), 8.16 (1H, d, J = 8.8Hz), 8.49 (1H, t, J = 7.7Hz), 9.40 (2H, s). Melting point: 1 1 8-1 2 0 ° C. Example 1 8 1- {8- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] _1_ (3,5-dimethoxyphenyl bromide) ) -4 -oxy-1,4-dihydro Phenyl-7-yloxy) octyl] -4 -acyl-pyrazobicyclo [2.2 · 2] octane (Exemplified compound number: 2-340) (18 &) 7- (8-bromooctyloxy) -1- (3,5-Dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -unsaturated acid N- (3,5-difluorophenyl) -N acetamidine 1- (3,5-dimethoxyphenyl) -7-hydroxy-4-oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5) obtained in Example (1 1 h) -Difluorophenyl-N-acetamidamine- 209-200300349 200mg, potassium carbonate 88.9mg and 1,8-dibromooctane 0.235ml, and the reaction was purified according to the method of Example (1 1 i) to obtain the title Compound 2 1 1 mg of pale yellow oily substance. NMR (CDC13) δρριη: 1.20 (3H, t, J = 7.3Hz), 1. 28-1. 50 (8H, m), 1.67-1.76 (2H, m), 1.82-1.90 (2H, m), 3.40 (2H, t, J = 7.3Hz), 3.83 (6H, s), 3.86 (2H, t, J = 7.3Hz), 3.93 (2H, q, 1 = 7.3 Hz), 6.40 (1H, s), 6.48 (2H, d, J = 2.0Hz), 6.60-6.66 (2H, m), 6.85 (2H, dd, J = 2.0, 7.8Hz), 6.9K1H, dd, J = 2.0, 8.8Hz), 7.85 ( 1H, s), 8.21 (1H, d, J = 8.8Hz). (18b) 1- {8- [3- [1 (3,5-difluorophenyl) -1 ethylaminomethyl] -1- (3,5-dimethoxyphenyl) -4-bromide Oxy-1,4-dihydroquinoline-7-yloxy] octyl} -4-acyl-1-azobicyclo [2.2 · 2] octane (Illustrated compound number :)

7- (8-Bromooctyloxy) -1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline · 3-carboxylic acid N obtained in Example (18a) -(3,5-difluorophenyl) -N acetamide 240 mg and 1,4-diazinebicyclo [2 · 2 · 2] octane 40.1 mg. The reaction was carried out according to the method of Example (1 lj), but 166 mg of the title compound was obtained as a white solid. NMR (CDC13) δρριη: 1.20 (3H, t, J = 7.3Hz), 1. 25-1.44 (8H, m), 1.65-1.83 (4H, m), 3.25 (6H, t, J = 7.3Hz), 3.48-3.55 (2H, m), 3.64 (6H, t, J = 7.3Hz), 3.83 (6H, s), 3.83-3.88 (2H, m), 3.9K2H, q, J = 7.3Hz), 6.39 ( 1H, d, J = 2.2Hz), 6.45 (2H, d, J = 2.2Hz), 6.6K1H, t, J = 2.2Hz), 6.63-6.68 (1H, m), 6.83 (2H, dd, J = 2.2, 8.1Hz), 6.92 (1H, dd, J = 2.2, 8.8Hz), 7.79 (1H, s), 8.19 (1H, d, J = 9.5Hz). Melting point: 12 8 -130 ° C. Example 1 9 Iodide 1- {6- [3- [N- (3,5-difluorophenyl) -N-methylaminemethylmethyl 200300349] -1- (3,5-dimethoxyphenyl ) -4-oxo-1,4-dihydroquinoline-7-yloxy] hexylbu 4 _acyl-i_azobicyclo [2 · 2 · 2] octane (Exemplified compound number: 2-47) (19a) 7-benzyloxy-1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorobenzene -N-formamidine The 7-benzyloxy-1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3- obtained in Example (Ilf) 5.00 g of carboxylic acid, 2.02 ml of chloracetin, catalytic amount of N, N-dimethylformamide, 3.3 2 g of N-methyl-3,5-difluoroaniline obtained in Reference Example 3, and triethylamine 6.4 6 m 1, according to the method of Example (1 f), the reaction was purified to obtain the yellow foamy substance of the title compound 3.4 3 g NMR (CDC13) δρριη: 3.45 (3H, s), 3. 81 (6H, s ), 4. 99 (2H, s), 6.44 (2H, d ,. J = 2.2Hz), 6.46 (1H, d, J = 2.2Hz), 6.58-6.66 (2H, m), 6.89 (2H, dd , J = 2.2, 8.1Hz), 7.0K1H, dd, J = 2.2, 8.8Hz), 7.25-7.38 (5H, m), 7.9K1H, s), 8.24 (1H, d, J = 8.8Hz). (19b) l- (3,5-dimethoxyphenyl) -7-hydroxy-4-oxo-1,4 · dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-formamidine The benzyloxy-1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid obtained in Example (19a) N- (3,5-difluorophenyl) -N-formamidine 3.43 g and 10% Pd-C700 mg were reacted according to the method of Example (lg) to obtain the title compound as a light yellow solid 7 8 9 mg . NMR (DMS0-d6) δρριη: 3.33 (3H, s), 3.81 (6H, s), 6.39 (1H, d, J = 2.2Hz), 6.67 (2H, d, J = 2.2Hz), 6.74 (1H, t, J = 2.2Hz), 6.8K1H, dd, J = 2.2, 8.8Hz), 7.00-7.20 (3H, m), 7.95 (1H, d, 1 = 8.8Hz), 8.02 (1H, s), 10.4 (1H, s) 〇 (19c) l- (3,5-dimethoxyphenyl) -7- (6-iodohexyloxy) -4-oxo-1,4- 200300349 dihydroquinoline-3- Carboxylic acid N- (3,5-difluorophenyl) -N-methanamine The 1- (3,5-dimethoxyphenyl) -7-hydroxy-4-oxo obtained in Example (1 9 b) 1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-formamidine 189 mg, potassium carbonate 83.9 mg, and 1,6-diiodohexane 0.21 ml. Purification was carried out by the method of Example (1 1 i) to obtain 20.5 mg of the title compound as a white foamy substance. NMR (CDC13) δ ppm: 1.40-1.50 (4H, m), 1. 70-1.88 (4H, m), 3.18 (2H, t, J = 7.3Hz), 3.46C3H, s), 3.84 (6H, s ), 3.88 (2H, t, J = 6.6Hz), 6.42 (1H, d, J = 2.2Hz), 6.50C2H, d, J = 2.2Hz), 6.58-6. 66 (2H, m), 6.89 ( 2H, dd, J = 2.2, 8.1Hz), 6.93 (1H, dd, J = 2.2, 8 · 8Ηζ), 7.91 (1H, s), 8 · 24 (1Η, d, J = 8.8Hz). (19d) Iodine 1- {6- [3- [N- (3,5-difluorophenyl) -N-methylaminemethylmethyl] -1- (3,5-dimethoxyphenyl)- 4-oxo-1,4-dihydroquinoline-7-yloxy] hexyl}-4 -acyl-1 -azobicyclo [2 · 2 · 2] octane Example 1 (1 9 c) is obtained as 1 -(3,5-dimethoxyphenyl) -7-(6-iodohexyloxy) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluoro 204 mg of phenyl) -N-methylformamide and 33.8 mg of 1,4-diazinebicyclo [2 · 2 · 2] octane were reacted according to the method of Example (1 lj) to obtain the title compound as a pale orange solid 1 9 9 mg. NMR (CDC13) δρριη: 1. 36-1. 56 (4Η, m), 1.68-1.86 (4H, m), 3.26 (6H, t, J = 7.3Hz), 3.45 (3H, s), 3.47-3.56 (2H, m), 3.64 (6H, t, J = 7.3Hz), 3.84 (6H, s), 3.87 (2H, t, J = 5.9Hz), 6.40 (1H, d, J = 2.2Hz), 6.47 (2H, d, J = 2.2Hz), 6.60-6.67 C2H, m), 6.88 (2H, dd, 1 = 2.2, 7.3Hz), 6.94 (1H, dd, J = 2.2, 8.8Hz), 7.84 (1H , s), 8.22 (1H, d, 1 = 8.8Hz)., Melting point: 1 3 4-1 3 6 ° C. Example 2 0 200300349 7 -methoxy-l- {3-methoxy- 5- [2- (l-oxoperidine-1-yloxy) benzyloxy] phenylbenzene 4-oxo-1 , 4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-formamidine (Exemplified compound number: 1-5 6 1) (20a) 7 -methoxy- l- [3-Methoxy-5- (2-piperidin-1-ylmethylbenzyloxy) benzyl] -4-oxo-1,4- — ^ Aqueous quinolin-3-conc (3,5-monophenyl) -N-formamide The 1- [3- (2-bromomethylbenzyloxy) -5-methoxyphenyl] -7-methoxy group obtained in Example (4c) 4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-formamidine 2 4 6 mg in methanol solution 8 ml 1 and piperidine was added 64 mg, stirred at room temperature overnight. The solvent was concentrated under reduced pressure, a saturated sodium bicarbonate solution was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and then the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol = 15/1) to obtain the title compound as a white foamy substance (226 mg). NMR. (CDC13) δ ppm: 1. 28-1.43 (6H, m), 2.32 (4H, br), 3.46 (3H, s), 3.47 (2H, s), 3.71 (3H, s), 3.83 (3H , s), 5.33 (2H, s), 6.42 (1H, d, J = 2.3Hz), 6.49 (1H, t, J = 1.9Hz), 6. 59-6. 64 (2H, m), 6.72 ( 1H, t, J = 2.2Hz), 6. 85 ~ 6. 95 (3H, m), 7.25-7.29 (3H, m), 7.43-7.45 (lH, in), 7.92 (m, s), 8.24 ( lH, d ,; f = 9.0Hz). (20b) 7-methoxy-l- {3-methoxy- 5- [2- (l-oxoperidine-1-ylmethyl) benzyloxy] phenyl} -4 -oxo-1, 4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-formamidine The 7-methoxy-l- [3-methoxy group obtained in Example (20a) -5 · (2-piperidin-1-ylmethylbenzyloxy) phenyl] -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-formamidine 164mg in dichloromethane solution 8 ml 1, and 67% m-chloroperbenzoic acid 7 1 · 0 mg was added at -3 ° C, and stirred at room temperature 200300349 for 1 hour. Add 15% The sodium thiosulfate solution was extracted with ethyl acetate. The ethyl acetate layer was washed with water, a saturated aqueous sodium hydrogen carbonate solution and a saturated saline solution, dried over anhydrous sodium sulfate, and the solvent was concentrated under reduced pressure. The residue was concentrated under reduced pressure. Purified by silica gel column chromatography (eluent: dichloromethane / methanol = 5/1), the white foamy substance of the title compound 1 65 mg ° ⑽ SO-d6) 6 ppm: 1.12-1 · 51 (4H, in ), 1.85-2. 02 (2H, π), 2. 70-2. 85 (2H, br), 3.14 ~ 3.26 (2H, m), 3. 33 (3H, s), 3.64 (3H, s) , 3.80 (3H, s), 4.39 (2H, s), 5.76 (1H, d, J = 8.8Hz), 5.92 (1H, d, J = 8.4Hz), 6.35 (1H, d, J = 2.2Hz), 6.63 (1H, s), 6.92 (1H, t, J = 2.1Hz), 6.98-7.09 (3H, m), 7.15 (2H, dd, J = 2.0, 8.6Hz), 7. 30 -7.40 (2H, m), 7.46-7.48 (2H, m), 8.02 (1H, d, J = 9.0Hz), 8.07 (1H, s). Example 2 1 Bromide 1- {7- {3- {3- [N- (3,5-difluorophenyl) -cardioethylaminemethyl] -7-methoxy-4_oxo-4H-quinolin-1-ylbuthyl 5-methoxyphenoxy Yl} heptyl} -4 -acyl-1 -azobicyclo [2.2 · 2] octane (Exemplified compound number: 1 -173) (21a) [[(3- (7-bromoheptyloxy) -5-methyl] Oxyphenyl-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -acetamidine Example (1 g) Resulting 1- (3-hydroxy-5-methoxyphenyl) -7-methoxy-4-oxy-1,4-dihydroquinoline-3-carboxylic acid 1 ^-(3,5-difluorobenzene Base) ·] ^-acetamidine 109 mg, 55% sodium hydride 19.8 mg and 7-dibromoheptane 475 mg, the reaction was carried out according to the method of Example (7 a), and the title compound was obtained as a pale yellow foam. 121 mg. -214- 200300349 NMR. (CDC13) δρριη: 1.2K3Η, t, 1 = 7.1Hz), 1. 38-1. 58 (6H, m), 1.78-1.93 (4H, m), 3.42 (2H, t, J = 6.8Hz), 3.73 (3H, s), 3.83 (3H, s), 3. 91-3. 97 (4H, m), 6.42 (1H, d, J = 2.4Hz), 6.46C2H, d, J = 2.2Hz), 6.59-6. 63 (2H, m), 6.84 (2H, dd, J = 2.2, 8.0Hz), 6.92 (1H, dd, J = 2.3, 9.0Hz), 7.86 (1H, s ), 8.22 (1H, d, J = 8.8Hz). (21b) Bromide 1- {7- {3- {3- [N- (3,5-difluorophenyl) -1 ethylaminomethylmethyl] -7-methoxy-4-oxo-4H -Quinolin-1-yl} -5 -methoxyphenoxy} heptylbu 4 -acyl-1 -azobicyclo [2 · 2 · 2] octane Example 1 (2 la) obtained 1- [3 -(7-Bromoheptyloxy) -5-methoxyphenyl-7-methoxy-4-oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorobenzene Group) -N-acetamidine 118mg and 1,4-diazinebicyclo [2.2.2] octane 24 Jmg, the reaction was carried out according to the method of Example (7b) to obtain the title compound as a white foamy 109 mg. NMR. (DMS0-d6) δ ppm: 1.08 (3H, t, J = 6.9Hz), 1. 30-1. 51 (6H, m), 1.63-1.78 (4H, m), 3.0K6H, t, J = 7.2Hz), 3.14-3.19 (2H, m), 3.25 (6H, t, J = 6.9Hz), 3.69 (3H, s), 3.8K3H, s), 3.81-3.85 (2H, m), 4.02 ( 2H, t, J = 7.2Hz), 6.39 (1H, d, J = 2.2Hz), 6.64 (1H, t, J = 1.3Hz), 6.65 (1H, s), 6.71 (1H, t, J = 2.1 Hz), 7.0K1H, dd, 1 = 2.2, 8.9Hz), 7.03-7.10 (1H, m), 7.1K2H, dd, J = 2.0, 8.2Hz), 8.0K1H, d, J = 8.9Hz), 8.08 (1H, s) Example 2 2 {2- {3- {3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -7-methoxy- 4-oxo-4H-quinolin-1-ylb 5-methoxyphenoxymethyl} benzyl} dimethylsulfamidine (exemplified compound number: 1-608) The 1-[3 h -(2-bromomethylbenzyloxy) -5 -methoxyphenyl] -7-methoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-di 200300349 Fluorophenyl) -N-acetamidine 127mg and dimethylsulfide 120mg. The reaction was carried out in accordance with the method of Example (1i) to obtain the title compound as a white solid 9 3.0 mg. NMR (DMS0-d6) δρριη: 1.08 (3H, t, J = 7.1Hz), 2.87 (6H, s), 3.70 (3H, s), 3.82-3.87 (2H, in), 3.84 (3H, s), 4.79 (2H, s), 5 .28 (2H, s), 6.42 (1H, d, J = 2.3Hz >, 6.73 (1H, s), 6.84 (1H, s), 6.9K1H, t, J = 2.0Hz), 7.01-7.10 (2H , m), 7.1K2H, dd, J = 2.1, 8.6Hz), 7. 50-7.57 (3H, m), 7.66-7. 68 (1H, m), 8.02 (1H, d, J = 9.0Hz) , 8.10 (1H, s). R Melting point: 1 4 4 ° C ~. Example 2 3 1- [2- {3- {3- [N- (3,5-difluorophenyl) -1 ^ -ethylaminomethylmethyl] -7-methoxy-4-oxy -4H -quinoline-l-yl} -5 -methoxyphenoxymethyl} benzyl] tetrahydrothiophene (exemplified compound number: 1-5 9 5) 1-[3- (2-Bromomethylbenzyloxy) -5-methoxyphenyl] -7-methoxy-4-oxo-1,4-dihydroquinoline 3-carboxylic acid N- (3,5-difluoro 104 mg of phenyl) -N-acetamidine and 44.2 mg of tetrahydrothiophene were reacted according to the method of Example (1 i) to obtain the title compound as a white solid 5 7 · 2 mg. NMR (DMS0-d6) δ ppm : 1.08 (3H, t, J = 7.1 Hz), 2. 07-2. 16 (2H, m), 2.25 ~ 2. 32 (2H, in), 3. 23 ~ 3. 42 (4H, in) , 3.71 (3H, s), 3. 82-3. 85 (2H, in), 3.84 (3H, s), 4.67 (2H, s), 5.30 (2H, s), 6.42 (1H, d, J = 2.2Hz), 6.73 (1H, s), 6.86-6. 92 (2H, m), 6. 98-7.12 (4H, m), 7.50-7. 55 (3H, m), 7. 62- 7. 67 (1H, m), 8.02 (1H, d, J = 8.9Hz), 8.10 (1H, s). Melting point: 8 3 ° C ~. Example 24 -216- 200300349 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine 1- (3,5-dimethoxybenzene) bromide Radical) -4 -oxo-1,4-dihydroquinolin-7-ylsulfanyl] heptylb 4-az-1-azobicyclo [2.2,2] octane (Exemplified compound number: 2-297 ) (24a) Dimethionine carboxylic acid 0- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3, 5-dimethoxyphenyl) -4-O-l, 4-dihydroquinolin-7-yl] ethyl ester The 1- [3- (2-bromomethylbenzyloxy) -5-methoxyphenyl group of Example (1 1 h) ] -7-methoxy-4-oxo-1,4-dihydroquinoline 3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 591 mg of N, N-di 10 ml of methylformamide solution, 64.4 mg of sodium hydride was added under ice-cooling, and after stirring for 10 minutes, 228 mg of N, N-dimethylthiamine formamidine chloride was added and stirred at room temperature overnight. Dilute hydrochloric acid was added and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and then the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate / hexane = 3/1) to obtain 488 mg of the title compound as a white solid. NMR (CDC13) δρριη: 1.2K3Η, t, J = 7.3Hz), 3.31 (3H, s), 3.4K3H, s), 3.83 (6H, s), 3.93 (2H, q, 1 = 7.3 Hz), 6. 51-6. 73 (4H, m), 6. 81-6. 93 (3H, m), 7.07 (1H, dd, J = 2.2, 8 · 8Ηζ), 7.97 (1Η, s), 8.32 (1H, d, J = 8.8Hz). (24b) Dimethionine S- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3, 5-dimethoxyphenyl)- 4-Oxy-1,4-dihydroquinolin-7-yl] ethyl ester The dimethyl thiamine formate obtained in Example (24a) was 0- [3- [N- (3,5-difluorophenyl)- N-ethylamine formamidine 1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinolin-7-yl] ethyl ester 3 9 5 mg of phenyl ether solution 3ml , And stirred at 200 300 349 200 ° C for 3 hours. The residue was purified by silica gel column chromatography (eluent: ethyl acetate / hexane = 3/1) to obtain the title compound as an orange foamy substance 3 1 8 mg NMR (CDC13) δρριη: 1.2K3H, t, J = 7.3Hz), 2.99 (3H, bs) ,. 3.04 (3H, bs), 3.84 (6H, s), 3.93 (2H, q, J = 7.3Hz), 6.5K2H, d, J = 2.2Hz), 6.6K1H, t, J = 2.2Hz), r 6.62-6. 68 (1H, m), 6.83 (2H, dd, J = 2.2, 8.1Hz), 7.25 (1H, d, J = 2.5Hz), 7.42 (1H, dd, J = 1.5, 8.8Hz), 7.95 (1H, s), 8.27 (1H, d, J = 8.1Hz). (24c) l- (3,5-dimethoxyphenyl) -7-hydrothio-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorobenzene ) -N-acetamidine The dimethyl thiaminecarboxylic acid s-[3-[N-(3,5-difluorophenyl) -N-ethylaminemethane]] obtained in Example (2 4 b)- 1 · (3, 5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinolin-7-yl] ethyl ester in a solution of 105 mg of ethanol in 5 m, 30 mg of sodium hydroxide and 2 ml of water were added, and at room temperature Stir for 3 hours. Dilute hydrochloric acid was added and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and then the solvent was concentrated under reduced pressure. The solid residue was recrystallized from ethyl acetate to obtain 53.3 mg of the title compound as a pale yellow needle-like substance. NMR (CDC13) δρρπι: 1.2〇 (3H, t, J = 7.3Hz), 3.84 (6H, s), 3.92 (2H, q, J = 7.3Hz), 6.45 (2H, d, J = 2.2Hz), 6. 60-6. 88 (5H, m), 7.15 (1H, dd, J = 1.5, 8.8Hz), 7.86 (1Η, s), 8.13 (1Η, d, J = 8, 8Hz) . (24d) 7- (7-bromoheptylsulfonyl-dimethoxyphenyl-b 4-oxo-1,4-dihydro-line-3-residual acid ^ (3,5-difluorophenyl) 4 Acetylamine W3,5_dimethoxyphenylhydrothio-4-oxo-1,4-dihydroteroline, 3-carboxylic acid N- (3,5-difluoro) obtained in Example (24c) Phenyl) -N-acetamidine, 33.3 mg, potassium carbonate I3.9 mg, and 1,7-dibromoheptene compound 0.034 ml, 200300349 The reaction was purified according to the method of Example (1 π) to obtain the title compound. 26.3mg of transparent oily substance. NMR. (CDC13) 0ppm: 1.2K3H, t, J = 7.3Hz), 1. 24-1.46 (6H, m), 1.56-1.88 (4H, m), 2.83 (2H, t, J = 7.3Hz), 3.39 (2H, t, J = 6.6Hz), 3.84 (6H, s), 3.93 (2H, q, J = 7.3Hz), 6.47 (2H, d, J = 2.2Hz) , 6.60-6.67 (2H, m), 6.81 (1H, d, J = 1.5Hz), 6.84 (2H, dd, J = 2.2, 8.1Hz), 7.17 (1H, dd, J = 2.2, 8.1Hz), 7.87 (1H, s), 8.16 (1H, d, J = 8.8Hz). (24e) L- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3,5-dimethoxyphenyl)- 4-oxo-1,4-dihydroquinoline-7-ylsulfanyl] heptyl} -4 4-acyl-; 1-azobicyclo [2.2,2] octane 7- obtained in Example (24d) (7-Bromoheptylsulfonyl) -1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluoro Phenyl) -N-acetamidamine 26.3 mg and 1,4-diazinebicyclo [2 · 2 · 2] octane 4. 3 8 mg. The reaction was carried out according to the method of Example (1 1 j) to obtain the title. The compound was 18.7 mg as a white solid. NMR (CDC13) 6ppm: 1.20 (3H, t, J = 7.3Hz), 1.33 (6H, bs), 1.55-1.80 (4H, m), 2.85 (2H, t, J = 7.3Hz), 3.25 (6H, t, J = 7.3Hz), 3.50-3.57 (2H, m), 3.64 (6H, t, J = 7.3Hz), 3.84 (6H, s), 3.9K2H, q, J = 7.3Hz), 6.44 (2H , d, J = 2.2Hz), 6.62-6.70 (2H, m), 6. 80-6.86 (3H, m), 7.20 (1H, dd, J = 2.2, 8.8Hz), 7.81 (1H, s), 8.16 0H, d, 1 = 8.8Hz). Melting point: 1 2 2-1 2 4 t:. Example 2 5 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -l- (3,5 -monomethoxyphenyl) -4 -oxo-1,4-dichloroquinolin-7-yloxy] heptyl} pyridine (exemplified compound number: 2-1 2 3) -219- 200300349 The result obtained in Example (1 1 i) 7- (7-Bromoheptyloxy) -1-(3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorobenzene ) -N-acetamidine 297 mg and pyridoxine 1 ml 1 were reacted according to the method of Example 17 to obtain 241 mg of the title compound as a white solid. NMR (CDC13) δρριη: 1.20 (3H, t, J = 7.3Hz), 1.38 (6H, bs), 1. 63-1.75 (2H, m), 1.98-2.10 (2H, m), 3.83 (6H, s ), 3.78-3.86 (2H, m), 3.92 (2H, q, J = 7.3Hz), 4.99 (2H, t, J = 7.3Hz), 6.37 (1H, d, J = 2.2Hz), 6.44 (2H , d, J = 2.2Hz), 6.6K1H, t, J = 2.2Hz), 6. 63-6. 67 (1H, m), 6.83 (2H, dd, J = 2.2, 8.1Hz), 6.90 (1H, dd, J = 2.2, 8.8Hz), 7.79 (lH, s), 8.11 (2H, t, J = 7.3Hz), 8.17 (1H, d, J = 8.8Hz), 8.48 (1H, t, J = 8.1Hz), 9.48 (2H, d, J = 5.9Hz). Melting point: 9 8-1 Ο 1 ° C. Example 2 6 Bromine {7- [3- [N- (3,5-difluorophenyl) -N · ethylaminomethylmethyl]-1- (3,5-dimethoxyphenyl) -4 -Oxy · 1,4-dihydroquinoline-7-yloxy] heptyl} triethylammonium (exemplified compound number: 2-121) Example 7 ((1 1 i)) (Oxy) -1-(3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N- 144 mg of acetamide and 2 mL of triethylamine were reacted according to the method of Example (llj) to obtain 99.5 mg of the title compound as a pale orange solid. NMR (CDC13) δρριη: 1.20 (3H, t, J = 7.4Hz), 1.38 (9H, t, J = 7.4Hz), 1.4K4H, ffl), 1.74 (6H, bs), 3.3K2H, m), 3.49 (6H, q, J = 7.4Hz), 3.84 (6H, s), 3.83-3.88 (2H, m), 3.92 (2H, q, 1 = 7.2Hz), 6.38 (1H, d, J = 2.3Hz), 6.46 (2H, d, J = 2.2Hz), 6.60-6.66 (2H , in), 6.84 (2H, dd, J = 2.3, 8.0Hz), 6.90 (1H, dd, J = 2.3, 8.8Hz), 7.82 (1H, s), 8.20 (1H, d, J = 9.2 Hz).

Melting point: 8 8 -90 ° C -220- 200300349 Example 2 7 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethyl] -1] bromide -(3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7-yloxy] heptyl}-1 -azobicyclo. [2 · 2 · 2] octyl Alkane (exemplified compound number: 2-140) The 7-(7-bromoheptyloxy) -1-(3,5-dimethoxyphenyl) -4 -oxo-1 obtained in Example (1 1 i), 4-Dihydroquinoline-3-carboxylic acid N- (3, 5-difluorophenyl) -N-acetamidine 1 5 7 mg and panquinidine 2 7 · 3 mg, according to the example (1 1 j ), And 169 mg of the title compound was obtained as a white solid. NMR. (CDC13) δ ppm: 1.20 (3H, t, J = 7.3Hz), 1.38 (6H, bs), 1.68 (4H, m), 2.05 (6H, m), 2.23 (1H, m), 3.49 ( 2H, m), 3.69 (6H, t, J = 7.3Hz), 3.84 (6H, s), 3.82-3.87 (2H, m), 3.92 (2H, q, J = 7.3Hz), 6.38 (1H, d , 1 = 2.3Hz), 6.46 (2H, d, J = 2.0Hz), 6.60-6.67 (2H, m), 6.84 (2H, dd, 1 = 1.8, 7.3Hz), 6.90 (1H, dd, J = 2.0, 8.8Hz), 7.82 (1H, bs), 8.20 (1H, d, J = 8.8Hz).

Melting point · 1 2 2-1 2 5 ° C Example 2 8 Bromide 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine 5- Dimethoxyphenyl) _4_oxy-1,4-dihydroquinolin-7-yloxy] heptylbu 3 -hydroxy-1 -azobicyclo [2 · 2 · 2] octane (exemplified compound numbers : 2-144) The 7-(7-bromoheptyloxy) -1-(3, 5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquine obtained in Example (1 1 i) was used. Porphyrin-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 16 3 mg and 3-[] quinidine 3 1.4 mg, according to the example (1 1 j) The reaction was carried out by the method to obtain 178 mg of the title compound as a white solid. -221-200300349 NMR (CDC13) (5ppm: 1.19 (3H, t, J = 7.4Hz), 1. 37 (6H, m), 1. 59-1.85 (6H, m), 2.00 (2H, bs), 2.34 (1H, s), 2.46 (1H, t, J = ll.〇Hz), 3.26-3.69 (6H, m), 3.82 (6H, s), 3.86 (2H, t, J = 6.3Hz), 3.91 (2H, q, J = 7.0Hz), 4.00 (1H, t, J = 8.9Hz), 4.39 (1H, s), 5.18 (1H, d, J = 17.9Hz), 6.38 (1H, d, J = 2.4Hz), 6.45 (1H, d, J = 1.3Hz), 6.6K1H, t, J-2.1Hz), 6.64 (1H, dt, J = 2.1, 8.7Hz), 6.83 (2H, dd, J = 2.4 , 8.2Hz), 6.93 (1H, dd, J = 2.1, 9.2Hz), 7.80 (1H, s), 8.19 (1H, d, J = 9.2Hz).

Melting point · 1 1 7-1 2 0 ° C Example 2 9 1- {7- [3- [N- (3,5-difluorophenyl) -1 ethylamine formamidine 1- ( 3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] heptylbuproxil (exemplified compound number: 2-124) Examples (1 1 i) The obtained 7-(7-bromoheptyloxy) -1-(3,5-dimethoxyphenyl) -4 -oxo-1,4 · dihydroquinoline-3-carboxylic acid N- 160 mg of (3,5-difluorophenyl) -N-acetamidine and 23.1 mg of 3-hydroxypyridine were reacted according to the method of Example (llj) to obtain the title compound as a light yellow solid 1 1 3 mg R (CDCI3) δρριη: 1.20 (3Η, t, 1 = 6.6 Hz), 1.38 (6Η, bs), 1.70 (2Η, t, J = 6.6Hz), 2.0Κ2Η, t, J-6.6Hz), 2.68 (1H, s), 3.83 (6H, s), 3.81-3.88 (2H, m), 3.92 (2H, q, J = 7.3Hz), 4.61 (2H, t, J = 7.2Hz), 6.38 (1H, d, J = 2.2Hz), 6.44 (2H, d, J = 2.1Hz), 6.62 (1H, t, J = 2.1Hz), 6.65 (1H, dt, 1 = 2.2, 8.8Hz), 6.83 (2H, dd, J = 2.2, 8.0Hz), 6.92 (1H, dd, J = 2.2, 8.8Hz), 7.75 (lHdd, J = 5.9, 8.8Hz), 7.80 (1H, s), 8.03 (1H, dd , 1 = 2.0, 8.7Hz), 8.18 (1H, d, J = 8.7Hz), 8.29 (1H, d, J = 6.0Hz), 9.0K1H, s).

Melting point: 8 7-9 0 ° C Example 3 0 200300349 3-Aminomethylbromide-l- {7- [3- [N- (3,5-difluorophenyl) -1 ethylamine formamidine Group] -1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] heptyl 丨 pyridine (Exemplified compound number: 2-7 4 1) The 7-(7-bromoheptyloxy) -1-(3, 5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 obtained in Example (1 1 i) -Carboxylic acid N- (3,5-difluorophenyl) -N-acetamide 1 51 mg and nicotinamide 2 8 · 1 ng, the reaction was carried out according to the method of Example (1 1 j), but 27.0 mg of the title compound was obtained as a white solid. NMR (CDC13) (5ppm: 1.19 (3H, t, J = 7.3Hz), 1.39 (6H, bs), 1.68 (2H, s), # 2.10 (2H, s), 3.82 (6H, s), 3.80-3.87 (2H, m), 3.9K2H, q, J = 7.3Hz), 4.88 (2H, t, J = 7.3Hz), 6.36 (1H, d, J = 2.2Hz) , 6.41-6.47 (2H, m), 6.60 (1H, t, J = 2.2Hz), 6.64 (1H, dt, J = 2.2, 8.8Hz), 6.82 (2H, dd, J = 2.2, 7.3Hz), 6.90 (1H, dd, J = 2.2, 8.8Hz), 7.76 (1H, s), 8.12 (1H, d,] = 8 · 0Ηζ), 8.14 (1Η, t, J = 9.5Hz), 9 · 08-9 · 15 (3Η, m). Melting point: 1 0 2-1 0 4 t: Example 3 1 Bromide 1- {7- [3- [N- (3,5 -2 Phenyl) -N-ethylaminomethylmethyl] -1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinolin-7-yloxy] heptyl} Tetrahydrothiophene (exemplified compound number: 2-7 4 0) The 7-(7 -bromoheptyloxy) -1-(3,5-dimethoxyphenyl)-4-obtained in Example (1 1 i) Oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 148 mg and tetrahydrothiophene 1 ml were reacted according to the method of Example (llj) 24.0 mg of the title compound was obtained as a white solid. -223-200300349 NMR. (CDC13) (5ppm: 1.20 (3H, t, J-7.3Hz), 1.40 (4H, bs) 5 1.5K2H, quintet, J = 7.3Hz), L 66-1.85 (4H, in ), 2.45 (4H, quintet, J = 3.7Hz), 3.52-3.63 (4H, m), 3.83 (6H, s), 3.81-3,87 (2H, m), 3.88 (4H, m), 6.38 ( 1H, d, J = 2.2Hz), 6.46 (2H, d, J = 2.2Hz), 6.62 (1H, t, J = 2.2Hz), 6.64 (1H, dt, J = 2.2, 8.8Hz), 6.84 ( 2H, dd, J = 2.2, 7.3Hz), 6.9K1H, dd, J = 2.2, 8.8Hz), 7.82 (1H, s), 8.20 (1H, d, J = 9.5Hz). Example 3 2 Bromination l- {7- [3- [N- (3,5-difluorophenyl) -1 ethylaminomethylmethyl] -1-(3, 5-dimethoxyphenyl) -4-oxo-1, 4-dihydroquinoline-7-yloxy] ® heptylbu 3 -oxo-1-azobicyclo [2 · 2 · 2] octane (exemplified compound number: 2-143) Example (1 1 i) The obtained 7- (7-bromoheptyloxy) -1- (3,5-dimethoxyphenyl) -4-oxo-I, 4-dihydroquinoline-3-carboxylic acid N- (3, 5-Difluorophenyl) -N-acetamidamine 150 mg and 3-eyepyridine hydrochloride 2000 mg, added with sodium hydroxide solution to neutralize, extracted with ether, dried, according to Example (1 1 j) and 147 mg of the title compound was obtained as a white solid. NMR. (CDC13) δρριη: 1.2K3Η, t, J = 7.3Hz), 1.38 (6H, s), 1. 63-1. 85 (4H, m), 2.30 (2H, bs), 2.44 (2H, bs ), 2.80 (1H, t, J = 2.9Hz), 3.73-3.80 (2H, m), 3.83 (6H, s), 3.83-3.87 (2H, m), 3.9K2H, q, J = 7.3Hz), 3.95-4.01 (4H, m), 4.54 (2H, s), 6.39 (1H, d, 1 = 2.2Hz), 6.44 (2H, d, J = 2.2Hz), 6.6K1H, t, J = 2.2Hz) , 6.65 (1H, dt, J = 2.2, 8.8Hz), 6.82 (2H, dd, J = 2.2, 8.0Hz), 6.92 (1H, dd, J = 2.2, 8.8Hz), 7.77 (1H, s), 8.18 (1H, d, J = 8.8Hz).

Melting point: 1 2 8-1 3 0 ° C Example 3 3 1- {7- [3- [N_ (3,5-difluorophenyl) -N-ethylaminomethyl]] 224-200300349 (3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7-yloxy] heptyl}-3-methoxycarbonylpyridine (exemplified compound number: 2-7 4 2) The 7-(7-bromoheptyloxy) -1-(3, 5-dimethoxyphenyl) -4 -oxy-1,4-dihydro obtained in Example (1 1 i) Quinoline-3-carboxylic acid N- (3, 5-difluorophenyl) -N-acetamidine 15 1 mg and nicotinic acid methyl ester 3 1 · 4 mg, according to Example (1 1 j) The reaction was carried out by the method to obtain 41.0 mg of the title compound as a yellow solid. NMR (CDC13) (5ppm: 1.20 (3H, t, J = 7.3Hz), 1.40 (4H, s), 1.70 (2H, bs), 2.08 (2H , bs), 2.66 (2H, s), 3.83 (6H, s), 3. 81-3. 88 (2H, m), 3.92 (2H, q, J = 6.6Hz), 4.05 (3H, s), 5.07 (2H, t, J = 8.1 Hz), 6.37 (1H, d, J = 2.2Hz), 6.44 (2H, d, J = 2.2Hz), 6.60- 6.67 (2H, m), 6.83 (2H, dd, J = 2.2, 8.1Hz), 6.90 (1H, dd, J = 2.2, 9.5Hz), 7.79 (1H, s), 8.18 (1H, d, J = 8.8Hz), 8.37 (1H, t, J = 6.6Hz), 8: 93 (1H, d, 1 = 8.1 Hz), 9. 33-9. 45 (2H, m). Example 3 4 4- {7- [3- [1 (3, 5-difluorophenyl) -1 Ethylamine formyl] -1- (3,5-dimethoxyphenyl) -4 -oxo-1,4 · dihydroquinoline-7-yloxy] heptylb 4-methylmorpholine -4 -yl bromide (exemplified compound number: 2-1 3 7) 7 _ (7 -bromoheptyloxy) -1-(3,5-dimethoxyphenyl) -4 obtained in Example (1 Π) -4 -Oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3, 5-difluorophenyl) -N-acetamidine 208 mg and N-methomorph 1 m 1 according to implementation The reaction of Example (Π j) was carried out to obtain the title compound as a pale orange solid 191 1 mg ο NMR (CDCI3) δρριη: 1.20 (3H, t, J = 7.3Hz), 1.4K6H, s), 1.65-L82 (4H, m), 3.54 (3H, s), 3.56-3.65 (2H, m), 3.84 (6H, s), 3. 78-3. 87 (6H, m), 3. 92 (2H, q, J = 7.3Hz), 3.96-4.09 (4H, m), 6.39 (1H, d, J = 2.2Hz), 6.45 (2H, d, J-2.2Hz), 6.60- 6.67 (2H, m), 6.83 ( 2H, dd, J = 2.2, 8.1Hz), 6.92 (1H, dd, J = 2.2, 8.8Hz), 7.80 (1H, s), 8.20 (1H, d, J = 8.8Hz). 200300349

Melting point: 1 1 3-1 1 5 ° C Example 3 5 Brominated {7- [3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine bb (3,5 -Dimethoxyphenyl) -4 -oxo-1,4 -dihydroquinoline-7 -yloxy] heptyl}-(2 -dimethylaminoethyl)-dimethylammonium (Exemplary compound number: 2 -7 3 7) The 7-(7-bromoheptyloxy) -1-(3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquine obtained in Example (1 1 i) Porphyrin-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 182mg and N, N, N ', N'-tetramethylethylenediamine 1ml, according to the example (1 1 j), the reaction was carried out to obtain 176 mg of the title compound as a white solid. NMR (CDC13) δ ppm: 1.20 (3H, t, J = 7.3Hz), 1.38 (6H, bs), 1.7K4H, bs), 2.27 (6H, s), 2.73 (2H, t, J = 5.1Hz) , 3.38 (6H, s), 3.56-3.64 (2H, m), 3.73 (2H, t, 1 = 4.4 Hz), 3.83 (6H, s), 3. 81-3. 88 (2H, m), 3.92 (2H, q, J = 7.3 Hz), 6.38 (1H, d, J = 2.2Hz), 6.45 (2H, s), 6.59-6.67 (2H, m), 6.84 (2H? Dd, J = 2.2, 8.1Hz), 6.9K1H, dd, J = 2.2, 9.5Hz), 7.82 (1H, s), 8.19 (1H, d, J = 9.5Hz).

Melting point: 5 8-6 0 ° C Example 3 6 Bromine {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylamidino] -ΙΟ, 5-dimethyl Oxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] heptyl}-(2-hydroxyethyl) -dimethylammonium (exemplified compound number: 2-1 2 2) The 7-(7-bromoheptyloxy) -1-(3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3-carboxylate obtained in Example (1 1 i) was used. The acid N- (3,5-difluorophenyl) -N-acetamidine 196 mg and N, N -dimethylethanolamine 1 m 1 were reacted according to the method of Example 200300349 (1 1 j). 1 28 mg of the title compound was obtained as a pale yellow solid. NMR (CDC13) δρριη: 1.19 (3H, t, J = 7.3Hz), 1.38 (6H, bs), 1.71 (4H, bs), 3.30 (6H, s) , 3.48-3.55 (2H, m), 3.64-3.69 (2H, m), 3.82 (6H, s), 3.87 (2H, t, J = 6.6Hz), 3.91 (2H, q, J = 7.3Hz), 4.07 (2H, bs), 6.39 (1H, d, J = 2.2Hz), 6.44 (2H, d, J = 2.2Hz), 6.6K1H, t, J = 2.2Hz), 6.65 (1H, dt, J = 2.2, 8.8Hz), 6.84 (2H, dd, J = 2.2, 8.1Hz), 6.95 (1H, dd, J = 2.2, 8.8Hz), 7.80 (1H, s), 8.19 (1H, d, J = 8.8 Hz). Example 3 7 Bromide 1- {8- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -l- ( 3,5 -dipropoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7 -yloxy] octyl}--mepidol (Exemplary compound number: 2-8 7 3) will 7- (8-Bromooctyloxy)-obtained in Example (2 Ο 1 a); 1- (3,5-dipropoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3- Carboxylic acid N- (3,5-difluorophenyl) · N-acetamidine 175 mg and N-methylpiperidine 191 mg. The reaction was carried out according to the method of Example (1 i) to obtain the title. Light yellow solid of the compound 170 mg NMR (DMS0-d6) δρριη: 0.98 (6H, t, J = 7.5 Hz), 1.08 (3H, t, J = 7.2Hz), 1.23-1.37 (8H, m ), 1.49-1. 78 (14H, m), 2.97 (3H, s), 3. 24-3. 31 (6H, m), 3.82 (2H, q, J = 7.1Hz), 3.89 (2H, t , J-6.3Hz), 3.98 (4H, t, J = 6.3Hz), 6.36 (1H, d, J = 2.1Hz), 6.6K2H, s), 6.7K1H, t, 1 = 2.1 Hz), 6.99 (1H, dd, J = 2.2, 8.9Hz), 7.03-7.09 (1H, m), 7.11. (2H, dd, J = 2.2, 8.7Hz), 8.00 (1H, d, J = 9.0Hz), 8.08 (1H, s). Melting point: ~ 1 1 1 t: Example 3 8 3-chloro-1-bromide {7- [3- [N- (3,5-difluorophenyl) -N-ethyl Carbamate 1- (3,5-dimethoxyphenylb 4- 4-oxy-1,4-dihydroquinoline-7-yloxy] 200300349 heptyl}-1-azo Bicyclic [2 · 2 · 2] octane (exemplified compound number: 2-744) 7-(7 -bromoheptyloxy) -1- (3,5-dimethoxyphenyl) obtained in Example (1 Π) ) -4 -oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3, 5-difluorophenyl) -N-acetamidine 1 5 7 mg and 3-chloropyridine 4 4 · 4 m 1, the reaction was carried out according to the method of Example (1 1 j) to obtain the title compound as a white solid 1 6 4 mg ο NMR (CDC13) δρρηι: 1.2K3H, t, J = 7.3 Hz)? 1. 38 (6H, bs)? 1.70 (4H, bs), 1.99-2.13 (1H, m), 2.16-2. 34 (2H, m), 2.44 (2H, bs), 3.29-3.56 (4H, m), 3 62-3. 78 (2H, m), 3.83 (6H, s), 3. 81-3. 88 (2H, m), 3.92 (2H, q, J-7.3Hz), 4.18 (1H, bs) , 4.63-4.70 (lH, m), 4.85-4.96 (1H, m), 6.38 (1H, d, J = 2.2Hz), 6.45 (2H, d, J = 1.5Hz), 6.62 (1H, t, J = 2.2Hz), 6.64 (1H, dt, J = 2.2, 8.8Hz), 6.83 (2H, dd, J = 2.2, 8.1Hz), 6.90 (1H, dd, J = 2.2, 8.8Hz), 7.8 K1H, s), 8.20 (1H, d, J = 8.8Hz).

Melting point: 1 1 9-1 2 2 ° C Example 3 9 Bromide 1- {7- [3- [1 ^-(3,5-difluorophenyl)-: ^-ethylaminemethyl] 1- (3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7-yloxy] heptyl 丨 -3-(R) -hydroxy-1 -azobicyclo [2 · 2.2] Octane (Exemplified Compounds: 5-2-1 4 4) The 7-(7 -bromoheptyloxy) -1-(3,5 -dimethoxy) obtained in Example (1 1 i) Phenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 1 5 3 mg and (R)-3- [] Quinidine 3 2 · 6 mg. The reaction was carried out according to the method of Example (1 1 j) to obtain the title compound as a white solid, 138 mg. -228-200300349 LiR (CDC13) (5ppm: 1.19 (3H, t, J = 7.4Hz), 1.37 (6Η, π), 1.59Ί.85 (6Η, m), 2.00C2H, bs), 2.34 (1H , s), 2.46 (1H, t, J = ll. 0Hz), 3.26-3.69 (6H, m), 3.82 (6H, s), 3.86 (2H, t, J = 6.3Hz), 3.9K2H, q, J = 7.0Hz), 4.00 (1H, t, J = 8.9Hz), 4.38 (1H, s), 6.38 (1H, d, J = 2.4Hz), 6.45 (1H, d, J = 1.3Hz), 6.6 K1H, t, J = 2.1Hz), 6.64 (1H, dt, J = 2.1, 8.7Hz), 6.83 (2H, dd, J = 2.4, 8.2Hz), 6.93 (1H, dd, J = 2.1, 9.2Hz ), 7.80 (1H, s), 8.19 (1H, d, J = 9.2Hz).

Melting point: 1 1 7-1 2 0 ° C Example 4 0 1- {7- [3-N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- ( 3,5 -dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7-yloxy} heptyl} quinoline (exemplified compound number: 2-7 3 8) Examples 1 1 i) 7- (7-bromoheptyloxy) -1-(3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- ( 14.6 mg of 3,5-difluorophenyl) -N-acetamidine and 2 8.7 mg of quinoline were reacted according to the method of Example (1 1 j) to obtain 24.0 mg of the title compound as a green solid. NMR (CDC13) (5ppm: 1.19 (3H, t, J = 7.3Hz), 1.39 (4H, s), 1.52 (2H, s), .1.65-1.82 (2H, m), 2. 03-2.13 (2H , m), 3.82 (6H, s), 3. 79 -3. 86 (2H, m), 3.9K2H, q, 1 = 7.3 Hz), 5.37 (2H, t, 1 = 8.1Hz), 6.35 ( 1H, d, J = 2.2Hz), 6.43 (2H, d, J = 2.2Hz), 6.60 (1H, t, J = 2.2Hz), 6.63 (1H, dt, J = 2.2, 8.8Hz), 6.83 (2H, dd, J = 2.2, 8.1Hz), 6.86 (1H, dd, J-2.2, 9.5Hz), 7. 81 (1H, s), 7.95 (1H, t, J = 7.3Hz), 8.10 -8. 21 (3H, m), 8.29C2H, t, J = 8.1Hz), 8.97 (1H, d, 1 = 8.1Hz), 10.5 (1H, d, 1-5.9Hz). Example 4 1 Bromine 1- {8- {3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3,5-dipropoxyphenyl) -4 -oxo- 1,4 -dihydroquinoline-7-yloxy} octyl}-1-azobicyclo [2 · 2 · 2] octane (Exemplified Compound No. 200300349: 2-872) Example (2 0 1 a) The obtained 7- (8-bromooctyloxy) -1- (3,5-dipropoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3, 150 mg of 5-difluorophenyl) -N-acetamidine and 25. 2 mg of pyridine were reacted according to the method of Example (1 i) to obtain 14 2 mg of the title compound as a white solid. NMR (DMS0-d6) δρριη: 0.98 (6H, t, J = 7.4Hz), 1.08 (3H, t, J = 7.1Hz), 1.21-1.36 (8H, m), 1.56-1. 78 (8H, m ), 1. 81-1. 86 (6H, m), 2. 03-2. 07 (1H, m), 3. 03-3. 07 (2H, m), 3. 30-3. 37 (6H , m), 3.82 (2H, q, J = 7.1 Hz), 3.89 (2H, t, J = 6.3Hz), 3.98 (4H, t, J = 6.4Hz), 6.36 (1H, d, J = 2.3 Hz), 6.6K2H, s), 6.7K1H, t, J-2.1Hz), 6.99 (1H, dd, J-2.2, 8.9Hz), 7. 04-7. 09 (1H, m), 7.11 (2H , dd, J-2.2, 8.6Hz), 8.00 (1H, d, J = 8.9z), 8.08 (1H, s). Melting point: ~ 1 2 0 ° C Example 42 3_ {4- [3- [N -(3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7- Oxy] butyl} -l-methylpyridine mesylate (exemplified compound number: 2-35) (42a) l- (3,5-dimethoxyphenyl) -4-oxo-7- ( 4- (pyridin-3-yl) butoxy) -1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine Example (1 1 h) 1- (3,5-dimethoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 205mg, potassium carbonate 295mg and 3- (4-bromobutyl) pyridine hydrogen obtained in Reference Example 15 3 78 mg of the acid salt was reacted according to the method of Example (1 h) to obtain the title compound as a yellow oily substance 2 09 mg.-230- 200300349 NMR (CDC13) 6ppm: 1.2K3H, t, J = 7.3 Hz), 1. 72-1. 80 (4H, m), 2.60-2.68 (2H, m), 3.83 (6H, s), 3.88 (2H, t, 1 = 6.6Hz), 3.93 (2H, q, J-7.3Hz), 6.38 (1H, d, J = 2.2Hz), 6.47 (2H, d, J = 2.2Hz), 6.59 * -6.66 (2H, m), 6.84 (2H, dd, J = 2.2, 8.1Hz), 6.89 (1H, dd, 1 = 2.2, 8.8Hz), 7.20 (1H, dd, J = 4.4, 6.6Hz), 7.48 (1H, d, J = 7.3Hz), 7.84 (1H, d, J = 1.5Hz), 8.20 (1H, d, J = 8.8Hz), 8.43 (2H, d, J = 2.9Hz). (42b) 3- {4- [3- [N- (3,5 -two Fluorophenyl) -N-ethylamine formamidine 1- (3, 5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] butyl}- 1-methylpyridine mesylate sulfamidine The 1- (3,5-dimethoxyphenyl) -4-oxo-7- (4 φ-(pyridine-3 -yl) butoxy) obtained in Example (42a) ) -1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 209mg, methyl methanesulfonate 113mg, according to Example (3b) The reaction was carried out by the method to obtain 188 mg of the title compound as a pale yellow solid. NMR. (CDC13) δρρίϋ: 1.20 (3Η, t, J: 7.3Hz), 1.75-1.90 (4H, m), 2.69 (3Η, s), 2.9K2H, t, J = 7.3Hz ), 3.83 (6H, s), 3. 86-3. 96 (4H? M), 4.54 (3H, s), 6.37 (1H, d, J = 2.2Hz), 6.44 (2H, d, J = 2.2 Hz), 6.60-6.66 (2H, m), 6.83 (2H, dd, 1 = 2.2, 8.1Hz), 6.89C1H, dd, J = 2.2, 8.8Hz), 7.80 (1H, s), 7.90 (1H, dd, J = 1.5, 6.6Hz), φ 8.14-8.21 (2H, m), 8. 91 (1H, d, J-6.6Hz), 9.07 (1H, s). Melting point: 8 0-8 1 ° C Example 4 3 4- {4- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3,5-dimethoxyphenyl) -4 -Oxy-1,4-dihydroquinoline-7-yloxy] butyl}-1-methylpyridine mesylate (exemplified compound number: 2-3 4) (43a) l- (3,5 -Dimethoxyphenyl) -4 -oxo-7- (4- (pyridin-4-yl) -butoxy) -1,4_-pyridinequinine-3-residue N- (3,5 -Monophenyl) -N-Ethyl-231-200300349 Amidine. The 1- (3,5-dimethoxyphenyl) -7-hydroxy-4-oxy-1,4-obtained in Example (1 1 h) Dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl-N-acetamidamine 199 mg, potassium carbonate 286 mg and 4- (4-bromobutyl) pyridine hydrobromic acid obtained in Reference Example 14 Salt 3 6 7 mg The reaction was carried out according to the method of Example (1 h) to obtain 204 mg of the title compound as a yellow oily substance. NMR (CDC13) (5ppm: 1.21 (3H, t, J = 7.3Hz), 1. 73-1.80 ( 4H, in), 2.60-2.68 (2H, m), 3.83 (6H, s), 3.88 (2H, t, J = 5.9Hz), 3.93 (2H, q, J = 7.3Hz), 6.38 (1H, d , J = 2.2Hz), 6. 47 (2H, d, J = 2.2Hz), 6.59-6.66 (2H, m), 6.84 (2H, dd, J = 2.2, 8.1Hz), 6.90 (1H, dd, J = 2.2, 8.8Hz), 7.09 (2H, d, J = 5.9Hz), 7.84 (1H, s), 8.2K1H, d, J = 8.8Hz), 8.48 (2H, dd, J = 1.5, 4.4Hz). (43b) 4- {4- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3,5-dimethoxyphenyl ) -4-oxo-1,4-dihydroquinoline-7-yloxy] butyl} -1 -methylpyridine mesysulfame The 1- (3,5-dimethyl) obtained in Example (42a) Oxyphenyl) -4-oxo-7- (4- (pyridin-3 -yl) butoxy) -1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl ) -N-acetamidine 2 04 mg, methyl methanesulfonate 1 10 mg. The reaction was carried out according to the method of Example (3b) to obtain 1 31 mg of the title compound as a washed yellow solid. NMR (CDC13) δρριη: 1.20 (3H, t, J = 7.3Hz), 1. 75-1. 92 (4H, m), 2.71 (3H, s), 2.9K2H, t, J = 7.3Hz), 3.83 (6H, s), 3.88 (2H, t, J-5.9Hz), 3.92 (2H, q, J-7.3Hz), 4.5K3H, s), 6.37 (1H, d, J = 2.2Hz), 6.45 ( 2H, d, J-2.2Hz), 6.59-6.66 (2H, m), 6.83 (2H, dd, J-2.2, 8.1Hz), 6.89 (1H, dd, J = 2.2, 9.6Hz), 7.8K3H, t, 1 = 2.8Hz), 8.19 (1H, d, J = 8.8Hz), 9.03 (2H, d, J = 6.6Hz).

Melting point: 9 5-9 8 ° C-232-200300349 Example 4 4 1- (7- {1- (3,5-diethoxyphenyl) -3- [N- (3,5-di Fluorophenyl) -N-ethylaminomethylmethyl] -4 -oxo-1,4-dihydroquinoline-7-yloxy} heptyl) _ 4 -acyl-1 -azobicyclo [2 · 2 · 2] Octane (exemplified compound number: 2-7 5 4) (44a) 3- (4-benzyloxy-2-methoxyphenyl) -3 -oxopropanoic acid methyl ester obtained in Example (lib) 11- (4-benzyloxy-2-methoxyphenyl) ethanone 1 4 9 g, 5 5% sodium hydride 4 1 g, and dimethyl carbonate 8 0 0 m 1, according to the example (1 1 c ), And 183 g of the title compound was obtained as a pale yellow solid. Φ NMR (CDC13) δ ppm: 3.71 (3H, s), 3.85 (3H, s), 3.93 (2H, s), 5.12 (2H, s), 6.52 0H, d, J = 2.2Hz) , 6.63 (1H, dd, J = 2.2, 8.8Hz), 7.33-7.45 (5H, m), 7.94 (1H, d, 1 = 8.8Hz). (44b) 2- (4-benzyloxy-2- Methoxybenzyl) -3 -dimethylamino-methyl acrylate The methyl 3- (4-benzyloxy-2-methoxyphenyl) -3-oxopropanoate obtained in Example (44a) 30.5 g and N, N-dimethylformamide dimethyl acetal 1.9.3 m 1, the reaction was carried out according to the method of Example (1 1 d) to obtain the title φ compound as a yellow oily substance 2 9.3 g. NMR (CDC13) δρριη: 3.00 (6H, br), 3.49 (3H, s), 3.76 (3H, s), 5.09 (2H, s), 6.49 (1H, d, J = 2.2Hz), 6.58 (1H, dd, J = 2.2, 8.8Hz), 7.31-7.45 (5H, m), 7.63 (2H, s). (44c) 7-benzyloxy-1- (3,5-diethoxyphenyl) -4 -Oxy-1,4-dihydroquinoline-3 -carboxylic acid methyl ester The 2- (4-benzyloxy-2-methoxybenzyl) -3-dimethylamino group obtained in Example (44b)- 2.50 g of methyl acrylate and 3,5-233-200300349-diethoxyaniline hydrochloride 2.2 1 g and potassium carbonate 2.81 g obtained in Reference Example 6 can be reacted according to the method of Example (11 e) to obtain The title compound was a pale yellow solid 2.43 g ° NMR (CDC13) δρρη: 1.44 (6H, t, J-7.3Hz), 3.91 (3H, s), 3. 96-4. 06 (4H, m), 5.0K2H, s), 6.45 (2H, d, J = 2.2Hz), 6.50 (1H, d, J-2.2Hz), 6.62 (1H, t, 1 = 2.2Hz), 7.06 (1H, dd, J = 2.2, 8.8 Hz), 7.27-7. 38 (5H, in), 8.45 (1H, d, J = 9.5 Hz), 8.46 (1H, s). (44d) 7-benzyloxy-1- (3,5- Diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid The 7-benzyloxy-1- (3,5-diethoxyphenyl) obtained in Example (44c) -2.4-oxy-1,4-dihydroquinoline-3 -carboxylic acid methyl ester 2.4 2 g and sodium hydroxide 6 13 mg The reaction of Example (le) was carried out to obtain the title compound as a white solid, 2.24 g of R. (CDCl3) 5 ppm: 1.45 (6Η, t, J = 7.3Hz), 3.96-4 · 06 (4Η, m), 5.04 (2Η, s), 6.43 (2H, d, J = 2.2Hz), 6.6K1H, d, J = 2.2Hz), 6.65 (1H, t, 1 = 2.2Hz), 7.19 (1H , dd, J = 2.2, 8.8Hz), 7.26-7.36 (5H, m), 8.45 (1H, d, J = 8.8Hz), 8.70 (1H, s). (44e) 7_benzyloxy-1- (3,5-Diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl) -N -acetamide (44d) 2.24 g of 7-benzyloxy-1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-residue, chloracetin 0.848 ml The amount of catalyst N, N-dimethylformamide, 1.5-g of N-ethyl-3,5-difluoroaniline and 2.72ml of triethylamine. The reaction can be carried out according to the method of Example (If). The title compound was obtained as a yellow foamy substance 1.3 g. -234- 200300349 Wake-up R (CDC13) δρριιι: 1.20 (3Η, t, J = 7.3Hz), 1.44 (6Η, t, J = 7.3Hz), 3.92 (2H, q, J = 7.3Hz), 3.95-4.05 (4H, m), 4.97 (2H, s), 6.38 (2H, d, 1 = 2.2Hz), 6.46 (1H, d, J = 2.2Hz), 6.60 (1H, t, J = 2.2Hz), 6.62 (1H, tt, J = 2.2, 8.8Hz), 6.84 (2H, dd, J = 2.2, 8.1Hz), 6.98 (1H, dd, J = 2.2, 9.5Hz), 7.26-7.37 (5H, m), 7.84 (1H, s), 8.2K1H, d, J = 8.8Hz). R (44f) l- (3,5-diethoxyphenyl) -7-hydroxy_4 · oxy-I, 4-dihydro Quinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidinium 7-benzyloxy-1- (3,5-diethoxyphenyl) obtained in Example (44e) ) -4 -oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -ethinamide 134g and 10% Pd-C130mg, according to the example (lg ) To carry out the reaction to obtain 1.14 g of the title compound as a yellow solid. NMR (CDC13) δρριη: 1.17 (3H, t, J = 7.3Hz), 1.40 (6H, t, J = 7.3Hz), 3.89 (2H, q, J = 7.3Hz), 3.97 (4H, q, J = 7.3Hz), 6.38 (2H, d, J-2.2Hz), 6.47 (1H, d, J = 1.5Hz), 6.52-6.65 (2H, m), 6.8K2H, dd, 1 = 2.2, 7.3Hz), 6.88 (1H, dd, J = 2.2, 8.8Hz), 7.79 (1H, s), 7.99 (1H, d, 1 = 8.8Hz). (44g) 7- (7-bromoheptyloxy) -1- ( 3,5-Diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidin (44f) 1- (3,5-diethoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) ) -N-Acetylamine 570mg, potassium carbonate 232mg and 1,7-dibromoheptane 0.575ml. The reaction was carried out according to the method of Example (1i) to obtain 592mg of the title compound as a yellow oily substance. NMR. (CDC13) 6ppm: 1.20 (3H, t, J = 7.3Hz), 1. 31-1.46 (6H, m), 1.43 (6H, t, J = 7.3Hz), 1.69-1.78 (2H, m) , .1.85 (2H, quintet, J = 7.3Hz), 3.39 (2H, t, J = 7.3Hz), 3.86 (2H, t, 1-6.6Hz), 3.93 (2H, q, J = 7.3Hz), 4.04 (4H, q, J-7.3Hz),-235-200300349 6.40 (1H, d, J = 2.2Hz), 6.44 (2H, d, J = 2.2Hz), 6.60 (1H, t, J = 2.2Hz ), 6.62 (1H, dd, J = 2.2, 8.1Hz), 6.83 (2H, dd, J = 2.2, 8.1Hz), 6.90 (1H, dd, 1 = 2.2, 8.8Hz), 7.84 (1H, s) , 8.20 (1H, d, J = 9.5Hz). (44h) Bromide 1- (7- {1- (3,5-diethoxyphenyl) -3- [1 ^-(3,5-di Fluorophenyl) -N-ethylaminomethylmethyl] -4-oxy-1,4-dihydroquinoline-7-yloxy} heptyl) -4 -fluorene f-1-azobicyclo [2.2. 2] Half-fired Example (44 g) 7- (7-bromoheptyloxy) -1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquine 104 mg of N- (3,5-difluorophenyl) -N-acetamidine-3-carboxylic acid and 20.8 mg of 1,4-diazepinebicyclo [2 · 2 · 2] octane, according to the example (1 1 j), 97.9 mg of the title compound was obtained as a pale yellow solid. NMR. (CDC13) (5ppm: 1.20 (3H, t, J = 7.3Hz), 1.38 (6H, br), 1.43 (6H, t, J = 7.3Hz), 1.64-1.80 (4H, m), 3.24 (6H, t, J-7.3Hz), 3. 52-3. 60 (2H, m), 3.65 (6H, t, J = 7.3Hz), 3.85 (2H, t, J = 5.9Hz), 3.9 K2H, q, J = 7.3Hz), 4. 03 (4H, q, J = 6.6Hz), 6.40 (1H, d, J = 1.5Hz), 6.42 (2H, d, J = 2.2Hz), 6.58- 6.66 (2H, m), 6.82 (2H, dd, J = 1.5, 5.9Hz), 6.90 (1H, dd, J = 2.2, 8.8Hz), 7.79 (1H, s), 8.19 (1H, d, J- 9.5Hz). Melting point: 1 1 4-1 1 7 ° C Example 4 5 Bromide 1. (8- {l- (3,5-diethoxyphenyl) -3- [N- (3,5 -Difluorophenyl) -N-ethylaminomethyl] -4_oxy-1,4-dihydroquinoline-7-yloxy} octyl) -4 -acyl-1 -azobicyclo [2 · 2 · 2] octane (exemplified compound number: 2-824) (45a) 7- (8_bromooctyloxy) -1- (3,5_diethoxyphenyl) _4_oxy-1,4- Dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 1- (3,5-diethoxyphenyl) -7-hydroxyl obtained in Example (44f) _4_ 200300349 Oxy-1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl) -N -acetamide 570 mg, potassium carbonate 232 mg and 1,8-dibromooctane 0.62ml, the reaction was carried out according to the method of Example (1 1 i) As a result, the title compound was obtained as a yellow oily substance (658 mg). NMR. '(CDCl3) Sppm: 1.19 (3H, t, J = 6.8Hz), 1. 28-1.43 (8H, m), 1.42 (6H, t, J = 6.8Hz), 1.70 (2H, quintet, 1 = 6.8 Hz), 1.83 (2H, quintet, J = 6.8Hz), 3.38 (2H, t, 1 = 6.8 Hz), 3.85 (2H, t, J = 6.8Hz), 3.92 (2H, q, J -6.8Hz), 4.03 (4H, q, J = 6.8Hz), 6.40 (1H, d, J = 2.9Hz), 6.43 (2H, d, J-2.0Hz), 6.57-6.64 (2H, m), 6.83 (2H, dd, J = 2.0, 7.8Hz), 6.89 (1H, dd, J = 2.0, 6.8Hz), 7.83 (1H, s), 8.19 (1H, d, J = 8.8Hz). 45b) Bromide 1- (8- {l- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine 4- Oxy-1,4-dihydroquinoline-7-yloxy} Halfyl group ^-卩 卩 -1-Coupling bis-5a [2 · 2 · 2] Yang Yuan will obtain 7 of Example (45a) -(8-Bromooctyloxy) -1- (3,5-diethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluoro Phenyl) -1 acetamide 1540 ^ and 1,4-diazinebicyclo [2.2.2] octane 30.11 ^. The reaction was carried out according to the method of Example (llj) to obtain the title compound as a white solid 1 5 1 mg. (CDC13) δρριη: 1.20 (3H, t, J = 6.6Hz), 1. 24-l \ 42 (8H, m), 1.43 (6H, t, J = 7.3Hz), 1.64-1.76 (4H, m), 3.25 (6H, t, J = 7.3Hz), 3.50-3.56 (2H, m), 3. 65 (6H, t, J = 7.3Hz), 3.86 (2H, t, J-6.6Hz), 3.9K2H, q, J-6.6Hz), 4.03 (4H, q, J = 7.3Hz), 6.40 (1H , d, J-2.9Hz), 6.42 (2H, d, J = 2.2Hz), 6.59 (1H, t, J = 2.2Hz), .60 ~ 6.66 (1H, m), 6.83 (2H, dd, J -2.2, 8.1Hz), 6.9K1H, dd, J = 2.2, 8.8Hz), 7.80 (1H, s), 8.20 (1H, d, J = 8.8Hz). Melting point: 1 1 4-1 1 6 t Implementation Example 4 6 1- (8- {1- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl 200300349) -N-ethylaminomethylmethyl] -4 -oxo-1,4-dihydroquinoline-7-yloxy} octyl) -1 -azobicyclo [2 · 2 · 2] octane (exemplified compound number: 2 _ 8 2 3) will 7- (8-Bromooctyloxy) -1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxyl obtained in Example (4 5a) The acid N- (3,5-difluorophenyl) -N-acetamidine 156 mg and panquinidine 30. 7 mg were reacted according to the method of Example (1 1 j) to obtain the title compound. 11 4 mg of a pale yellow solid. NMR. (CDC13) δρριη: 1.20 (3Η, t, J = 7.3Hz), 1.23-1.43 (8Η, m), 1.43 (6Η, t, 1 = 7.3Hz), 1.65- 1.76 (4H, m), 2.05 (6H, br), 2.17-2.23 (1H, m), 3. 40-3. 47 (2H, m), 3.70 (6H, t, J-7.3Hz), 3.85 ( 2H, t, J = 6.6Hz), 3.9K2H, q, J = 7.3Hz), 4.03 (4H, q, J = 7.3Hz), 6.39-6.44 (3H, m), 6.60 (1H, t, J = 2.2Hz), 6.60-6.67 (1H, m), 6.83 (2H, dd, J = 2.2, 7.4Hz), 6.9K1H, dd, J = 2.2, 9.5Hz), 7.79 (1H, s), 8.18 (1H , d, J = 8.8Hz). Melting point: 8 6-8 9 ° C! Example 4 7 Brominated l- (8- {l- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminomethyl] -4-oxy-1,4-dihydroquinoline-7-yloxy} octyl) 2-8 2 0) The 7-(8-bromooctyloxy) -1-(3,5-diethoxyphenyl) -4 -oxy-1,4 -di obtained in Example (4 5 a) Hydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 174 mg and pyridine 1 ml were reacted according to the method of Example (llj) to obtain the title compound as a pale yellow solid. 104 mg. NMR (CDCr3) δ ppm: 1.20 (3H, t, J = 7.3Hz), 1.25-1.43 (8H, m), 1.42 (6H, t, J = 7.3Hz), 1.64-1.73 (2H, m), 2.00 -2.10 (2H, m), 3.84 (2H, t, J = 5.9Hz), 3.9K2H, q, 1-7.3Hz), 4.03 (4H, q, J-7.3Hz), 5.00 (2H, t, J = 7.3Hz), 6.40 (3H, d, J-2.2Hz), 6.59 (1H, t, J = 2.2Hz), 6.60-6.68 (1H, m), 6.83 (2H, dd, J = 2.2, 8.1Hz ), 6.90 (1H, dd, J-2.2, 8.8Hz), 7.77 (1H, s), 8. 11-8.21 (3H, m), 8.52 (1H, t, J = 8.1Hz), 9.57 (2H, d, J = 5.9Hz) .- 238-200300349

Melting point: 8 3-8 5 ° C Example 4 8 1- (7- {1- (3,5-diethoxyphenyl) -3-[^ (3,5-difluorophenyl)- N-ethylamine formamyl] -4 -oxy-1,4-dihydroquinoline-7-yloxy} heptyl) D ratio ingot (exemplified compound number: 2-7 5 0) Example (4 4 g) of the obtained 7- (7-bromoheptyloxy) -1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- ( 3,5-difluorophenyl) -N-acetamidine 203 mg and pyridine 1 m L. The reaction was carried out according to the method of Example (1 1 j) to obtain the title compound as a pale orange solid 1 3 8 mg . NMR. (CDCl3) 5ppm: 1.20 (3H, t, J = 7.3Hz), 1.34-1.44 (6H, m), 1.43 (6H, t, J = 7.3Hz), 1.62-1.72 (2H, m), 1.99 -2.10 (2H, m), 3.84 (2H, t, J = 6.6Hz), 3.92 (2H, q, J = 7.3Hz), 4.03 (4H, q, J = 7..3Hz), 4.99 (2H, t, J = 7.3Hz), 6.39 (1H, d, J = 2.2Hz), 6.4K2H, d, J = 2.2Hz), 6.59 (1H, t, J = 2.2Hz), 6.60-6.66 (1H, m ), 6.83 (2H, dd, 1-2.2, 5.9Hz), 6.89 (1H, dd, 1 = 2.2, 8.8Hz), 7.80 (1H, s), 8.09 (2H, t, J = 7.3Hz), 8.17 (1H, d, 1-9.5Hz), 8.45 (1H, t, J = 7.4Hz), 9.43 (2H, d, J = 5.1Hz). Melting point: 9 4-9 7 ° C Example 4 9 Bromination 1- (7- {1- (3,5-diethoxyphenyl) -3- [1 (3,5-difluorophenyl) -N-ethylaminocarboxylate] -4 -oxy-1,4 -__ ^ Aspirin-7-yloxy} heptyl) -1-azobicyclo [2.2.2] octane (exemplified compound number: 2-7 5 3) The result obtained in Example (4 4 g) 7-(7 -bromoheptyloxy) -1-(3,5-diethoxyphenyl 4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorobenzene (Base) -N-acetamidine 2 02 mg and pyridine 44.0 mg, the reaction was performed according to the method of Example 20011349 to obtain 212 mg of the title compound as a white solid. NMR. (CDC13) δρριι: 1.20 (3H, t , J = 7.1Hz), 1.38 (6H, bs), 1.43 (6H, t, J-7.1Hz), 1.65-1. 85 (4H, m), 2.05 (6H, bs), 2. 20-2. 25 (1H, m), 3. 45-3.55 (2H, m), 3.70 (6H, t, J = 8.0Hz), 3.85 (2H, t, J = 6.2Hz)? 3.92 (2H, q, 1- 7.1Hz), 4.03 (4H, q, J-7.1Hz), 6.40 (1H, d, J = 2.1Hz), 6.42 (2H, d, Ι = 2.1Ηζ), 6.60 (1H, t, J-2. 1Hz), 6.60- 6.66 (1H, m), 6.83 (2H, dd, J = 2.1, 7.9Hz), 6.90 (1H, dd, J = 2.2, 9.0Hz), 7.8K1H, s), 8.19 (1H, d, 1-9.0Hz).

Melting point: 1 1 2-1 1 5 ° C Example 5 Ο φ bromide 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -l -(3,5-monomethoxyphenyl) -4-oxo-1,4 -monoquinine · 7-yloxy] heptylb-methylpyridine (Exemplary compound number: 2-7 3 9) The 7-(7-bromoheptyloxy) -1-(3, 5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3-carboxylate obtained in Example (1 1 i) was used. The acid N- (3,5-difluorophenyl) -N-acetamidine 150 mg and 1-methylpiperidine 1 m 1 were reacted according to the method of Example (1 1 j) to obtain the title compound. 150 mg of a pale yellow solid. NMR (CDC13) όρρϋκ 1.20 (3Η, t, Ι = 7 · 2Ηζ), 1.4U6H, bs), φ 1.65-2. 00 (10Η, m), 3.32 (3Η, s), 3. 60-3 80 (6Η, m), 3.84 (6H, s), 3. 80-3. 90 (2H, m), 3.92 (2H, q, J = 7.1Hz), 6.38 (1H, d, J = 2.1Hz ), 6.46 (2H, d, J = 2.1Hz), 6.60- 6.66 (2H, m), 6.84 (2H, dd, J = 2.1, 8.0Hz), 6.90 (1H, dd, J-2.2, 9.1Hz) , 7.83 (1H, s), 8. 20 (1H, d, 1 = 8.9Hz).

Melting point: 1 0 7-1 10 ° C Example 5 1 Bromide l- {7- [3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine 1- ( 3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy]-240-200300349 heptyl}-1-methylpyrrolidium (Exemplary compound number: 2- 1 3 6) The 7-(7-bromoheptyloxy) -1-(3, 5-dimethoxyphenyl) -4 -oxo-1, 4-dihydroquine obtained in Example (1 1 i) Porphyrin-3 -carboxylic acid N-(3,5-difluorophenyl) -N -acetamidinium 15 2 mg and 1-methylpyrrolidine 1 m 1, carried out according to the method of Example (1 1 j) The reaction gave the title compound as a white solid, 150 mg NMR (CDC13) δρριι: 1.20 (3Η, t, J 2 7.2 · ζ), 1.41 (6Η, bs), 1.65-1 · 85 (4Η, m), 2.20-2. 38 (4Η, m), 3.27 (3Η, s), 3. 63-3. 75 (2Η, m), 3.84 (6H, s),

3.76 ~ 3.88 (6H, m), 3.92 (2H, q, J = 7.1Hz), 6.39 (1H, d, J = 2.2Hz), 6.46 (2H, d, J = 2.1Hz), 6.62 (1H, t , J = 2.2Hz), 6. 62-6. 66 (1H, m), 6.84 (2H, dd, 1 = 2.1, 7.8Hz), 6.9K1H, dd, J = 2.2, 8.9Hz), 7.27 (1H , s), 8.20 (1H, d, J = 9.0Hz).

Melting point: 1 0 1-1 0 4 ° C Example 5 2 Bromide 1-{7-[3-[N-(3, 5 -difluorophenyl) -N -ethylaminomethylmethyl]]-1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] heptylb 4-phenylpyridine (exemplified compound number: 2-7 4 5) The 7-(7-bromoheptyloxy) -1-(3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3-carboxylate obtained in Example (1 1 i) was used. Acid N- (3,5-difluorophenyl) -N-acetamidine 149 mg and 4-phenylhydrazine ratio D 45.7 mg. According to the method of Example (1 1 j), the reaction can be obtained. The title compound was a white solid 101 mg (R) (CDC13) (5 ppm: 1.20 (3Η, t, J: 7.2Hz), 1.39 (6Η, bs), 1.65-1.75 (2Η, m), 2.00-2 · 13 (2Η, m), 3.83 (6Η, s), 3.78-3.88 (2Η, m), 3.92 (2H, q, J = 7.2Hz), 4.96 (2H, t, J = 7.2Hz), 6.37 (1H, d, J-2.0Hz), 6.44 (2H, d, 1 = 2.0Hz), 6.60-6.66 (2H, m), 6.83 (2H, dd, J-2.0 , 7.9Hz), 6.89 (1H, dd, J = 2.0, 8.2Hz), 7.55-7.65 (3H, m), 7.75-7. 85 (3H, m), 8.15-8.25 (3H, m), 9.48 (2H, d, J-6.2Hz). -241-200300349

Melting point: 1 1 2 -1 1 5 ° C Example 5 3 Brominated b {7- [3- [N- (3,5-difluorophenyl) -1 ^ ethylamine formamidine 1- (3 , 5 -dimethoxyphenyl) _4_oxy-1,4-dihydroquinoline-7-yloxy] heptyl}-3-phenylpyridine (exemplified compound number: 2-7 4 6) will be implemented Example (1 1 i) 7-(7 -bromoheptyloxy) -1-(3,5-dimethoxyphenyl) -cardio-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 150 mg and 3-phenylpyridine D 0. 3 m 1 were reacted according to the method of Example (1 1 j) to obtain the title compound. 1 3 3 mg ο NMR (CDC13) δρριη: 1.20 (3H, t, J = 7.2Hz), 1. 35-1.47 (6H, m), 1.68 (2H, t, J = 5.6Hz), 2.00-2.12 (2H, m), 3.82 (6H, s), 3.80-3.88 (2H, m), 3.93 (2H, q, 1 = 7.2Hz), 5.16 (2H, t, 1 = 7.4Hz), 6.36 (1H, d, J = 2.1Hz), 6.44 (2H, d, J ^ 2.1Hz), 6.6K1H, t, J = 2.1Hz), 6. 61-6. 66 (1H, in), 6.83 (2H , dd, J = 2.1, 7.7Hz), 6.88 (1H, dd, 1-2.1, 8.9Hz), 7.48-7. 60 (3H, m), 7.8K1H, s), 7.86 (2H, dd, J = 1.5, 7.7Hz), 8.1K1H, dd, J = 6.1, 8.0Hz), 8.18 (1H, d, J = 9.0Hz), 8.56 (1H, d, J = 8.2Hz), 9.4K1H, d, J = 5.9Hz), 9.66 (1H, s). Melting point: 1 1 0-1 1 3 ° c Example 5 4 Bromide 1- {7-[3-[N-(3,5-difluorophenyl) -N-(2 -propargyl ) Aminomethyl] -l- (3-methoxy-5-propoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] heptylbu 4 1-Azobicyclo [2 · 2.2] octane (Exemplified compound number: 2-8 6 6) (54a) 7-methoxymethoxy-1- (3-methoxy-5-propoxyphenyl) -4--242-200300349 Oxy-1,4-dihydroquinoline-3 -carboxylic acid methyl ester The 3-dimethylamino-2- (2-methoxy-) obtained in Example (104d) 3.methoxyg 4-methoxymethoxy-benzyl) acrylate, 3.83g of 3-methoxy-5-propoxyaniline and 3.27g of potassium carbonate obtained in Reference Example 4, according to Example (1 1 e) The reaction was carried out in this manner to obtain 5.06 g of the title compound as a pale yellow solid. NMR. (CDC13) δρρπι: 1.05 (3H, t, J = 7.3Hz), 1.83 (2H, sextet, 1 = 7.3 Hz), 3.43 (3H, s), 3.84 (3H, s), 3.92 (3H, s), 3.91-3.98 (2H, m), 5.14 (2H, s), 6.53-6.55 (2H, di) ^ 6.63 (1H, t, J-2.2Hz), 6.68 (1H, d, J = 2.2Hz ), 7. 13 (1H, dd, J = 2.2, 8.8Hz), 8.47 (1H, d, J = 8.8Hz), 8.50 (1H, s). '(54b) 7-methoxymethoxy-1 -(3-methoxy-5-propoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid 5.0 6 g obtained in Example (5 4 a) and sodium hydroxide 1.42 g. The reaction was carried out according to the method of Example (1e) to obtain 4.20 g of the title compound as a pale yellow solid. Brain R. (CDC13) δ ppm: 1.05 (3H, t, J = 6.8Hz), 1.83 (2H, sextet, J = 6.8Hz), 3.44 (3H, s), 3.84 (3H, s), 3.93 (2H , q, 1 = 6.8Hz), 5.18 (2H, s), 6.53 (2H, s), 6.660H, s), 6.82 (1H, s), 7.24-7.29 (1H; s), 8. 47 (1H , d, J = 8.8Hz), 8.75 (1H, s) ... (54c) 7-methoxymethoxy-1- (3-methoxy-5-propoxyphenyl) _4_oxy-1,4 -Dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -amidine The 7-methoxymethoxy-1-(3-methoxy group obtained in Example (5 4 b) Methyl-5 -propoxyphenyl) -4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid in a solution of dichloromethane 8.20 m 1. Triethylamine 3. 5 4 m 1 and Isobutyl chloroformate (1.98 ml) was stirred at room temperature for 20 minutes, and then 3,5-difluoroaniline 1.92 g 200300349 was added, followed by stirring at room temperature for 3 hours. The reaction solution was added with dilute hydrochloric acid and extracted with dichloromethane. The methylene chloride layer was washed with saturated sodium bicarbonate water and saturated brine, and dried over anhydrous sodium sulfate, and then the solvent was concentrated under reduced pressure. The obtained solid was washed with diisopropyl ether to obtain the title compound as a pale yellow solid, 4.81 g, ω R (CDC13) δ ppm: 1.05 (3H, t, J = 7.3Hz), 1.83 (2H, sextet, J = 7.3Hz), 3.44 (3H, s), 3.84 (3H, s), 3.94 (2H, dt, J-3.7, 6.6Hz), 5.17 (2H, s), 6.50-6.57 (3H, m), 6.65 (1H, t, J-2.2Hz), 6.79 (1H, d, J = 2.2Hz), 7.23 (1H, dd, J = 2.2, 8.8Hz), 7.39 (2H, dd, J = 2.2, 8.8Hz ), 8.48 (1H, d, J-8.8Hz), 8.82 (1H, s). (54d) 7-methoxymethoxy-1- (3-methoxy-5-propoxyphenyl) -4 -Oxy-1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl) -N-(2-propargyl) sulfonamide The obtained from Example (5 4 c) 7-methoxymethoxy-1-(3-methoxy-5 -propoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-di Fluorophenyl) -ammonium 2.00g of N, N-dimethylformamide solution 20m 加入 At 0 ° C, add 55% sodium hydride 200 mg, stir for 10 minutes, add propargyl bromide 0.4 3 ml 1, and stirred at room temperature for 3 hours. Methanol was added, and after stirring, the reaction solution solvent was concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated sodium bicarbonate water and saturated brine, dried over anhydrous sodium sulfate, and then the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate / hexane = 2/1) to obtain 1.64 g of the title compound as a yellow solid. NMR (⑶Cl3) δρρπι: 1.05 (3Η, t, J = 7.3Ηζ), 1.83 (2Η, sextet, J = 7.3Hz), 2.24 (1Η, t, J = 2.2Hz), 3.4K3H , s), 3.83 (3H, s), 3.92 (2H, dt, J = 1.5, 6.6Hz), 4.64 (2H, d, J = 2.2Hz), 5.12 (2H, s), 6.48 (2H, t, J = 1.5Hz), 6.61 (1H, t, J = 2.2Hz), -244-200300349 6.63-6 · 69 (2Η, m), 6.96 (2Η, dd, J 2.2, 8 · 1Ηζ ), 7.06 (1H, dd, J = 2.2, 8 · 8Ηζ), 7.98 (1H, s), 8.23 (1H, d, J = 9.5Hz) .. (54e) 7-hydroxy-1- (3- Oxy-5-propoxyphenyl) -4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N- (2-propargyl) The amidamine is the 7-methoxymethoxy-1-(3-methoxy-5 -propoxyphenyl) _4-oxy-I, 4-dihydroquinoline-carboxyl obtained in Example (5 4 d). Acid N- (3,5-difluorophenyl) _N-(2-propargyl) amidine 1 · 2 7 g of ethyl acetate solution 2 0 m 1 and 4 NHC 1 / ethyl acetate solution 1 0 m 1, and stirred at room temperature for 5 hours. The white precipitate obtained was collected by filtration and washed with ethyl acetate to obtain 1.1 g of the title compound as a white solid. NMR (CDC13) (5ppm: 1.04 (3H, t, J = 7.3Hz), 1.8K2H, sextet, J = 7.3Hz), 2.23 (1H, t, J = 2.2Hz), 3.82 (3H, s), 3.90 (2H, t, J = 6.6Hz), 4. 72 (2H, d, 1 = 2.2Hz), 6.35 (1H, s), 6.40 (1H, s), 6.6K1H, t, J = 2.2Hz), 6.73 (1H, d, J = 2.2Hz), 6.80 (1H, tt, 1 = 2.2, 8.8Hz), 7.1K2H, dd, J = 2.2, 6.6Hz), 7.51 (1H, dd, J = 2.2, 9.5 Hz), 7.95 (1H, s), 8.17 (1H, d, J = 9.5Hz). (54f) 7- (7-bromoheptyloxy) -1- (3-methoxy-5-propoxybenzene Group) -4- ^ oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N- (2-propargyl) fluorenamine will be described in Example (5 4 e) 7-hydroxy-1-(3-methoxy-5 -propoxyphenyl) 4-oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 5- 540 mg of difluorophenyl) -N- (2-propargyl) phosphonium amine, 216 mg of potassium carbonate, and 1,7-dibromoheptane 0.5 3 4 m 1, according to the method of Example (1 1 i) By reaction, 610 mg of the title compound was obtained as a transparent oily substance. -245-200300349 NMR ^ (CDC13) 6 ppm: 1.05 (3H, t, J = 7.3Hz), 1.30-1.48 (6H, m), 1.69-1.89 (6H, m), 2.24 (1H, t, J = 2.2Hz), 3.39 (2H, t, J = 6.6Hz), 3.83 (3H, s), 3.87 (2H, t, J = 6.6Hz), 3.93 (2H, dt, J = 2.2, 6.6Hz), 4.64 (2H, d, J = 1.5Hz), 6.43 (1H, d, J = 2.2Hz), 6.48 (2H, d, J = 2.2Hz), 6.62 (1H, t, J = 2.2Hz), 6.66 (1H , tt, 1 = 2.2, 8.8Hz), 6.92 (1H, dd, J = 2.2, 8.8Hz), 6.97 (2H, dd, J = 2.2, 7.3Hz), 7.94 (1H, s), 8.22 (1H, d, J = 9.5Hz). (54g) bromide l- [7- [3- [N- (3,5-difluorophenyl) -N- (2-propargyl) aminocarbamyl]- 1- (3-methoxy-5-propoxyphenyl) -4-oxy-1,4-dihydro

Quinoline-7-yloxy] heptyl] -4 -az-1-azobicyclo [2 · 2 · 2] octane The 7- (7-bromoheptyloxy) obtained in Example (54f)- 1- (3-methoxy-5 -propoxyphenyl) -4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 5-difluorophenyl) -N- ( 155 mg of 2-propargyl) phosphonium amine and 1,4-diazepine bicyclo [2 · 2 · 2] octane 3 3.1 mg. The reaction was carried out according to the method of Example (1 1 j) to obtain the title compound. Light yellow solid i43mg. NMR (CDCI3) δρριη: 1.05 (3H, t, J-7.8Hz), 1.39 (6H, bs), 1. 67-1. 78 (4H,

m), 1.83 (2H, sextet, J = 7.8Hz), 2.26 (1H, t, J = 2.3Hz), 3.25 (6H, t, J = 7.8Hz), 3.53-3.58 (2H, m), 3.65 ( 6H, t, J = 7.8Hz), 3.84 (3H, s), 3.84-3.96 (4H, m), 4.63 (2H, d, J = 2.0Hz), 6.42 (1H, d, J = 2.9Hz), 6.45 (2H? D, J = 2.0Hz), 6.61-6.70 (2H, m), 6.91-6.97 (3H, m), 7.89 (1H, s), 8.20 (1H, d? J = 9.8Hz).

Melting point: 1 1 5-1 1 8 ° C Example 5 5 Brominated 1-{7-[3-[N-(3,5-difluorophenyl) -N-(2 -propargyl) amine methylamine Fluorenyl] -1- (3-methoxy-5-propoxyphenyl) · 4-oxo-I, 4-dihydroquinoline-yloxy] heptylbazobicyclo [2 · 2.2] Octane (exemplified compound number: 2-777) -246- 200300349 The 7- (7-bromoheptyloxy) -1- (3-methoxy-5 -propoxyphenyl) obtained in Example (54f) -4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 5-difluorophenyl) -N-(2-propargyl) amidamine 1 6 4 mg and eye pyridine 3 5.1 mg was reacted in the same manner as in Example (1 1 j) to obtain the title compound as a white solid, 161 mg.

Ml. (CDC13) δρριη: 1.06 (3H, t, J = 7.3Hz), 1.40 (6H, bs), 1. 67-1. 77 (4H, m), 1.85 (2H, sextet, J = 7.3Hz) , 2. 02-2.11 (6H, m), 2.21 ~ 2. 26 (2H, m), 3.46-3.53 (2H, m), 3.69 (6H, t, J = 8.1Hz), 3.85 (3H, s) , 3.84-3.87 (2H, m), 3.95 (2H, q, J = 6.8Hz), 4.65 (2H, s), 6.42 (1H, d, J = 2.0Hz), 6.48 (2H, bs), 6.63 ( 1H, bs), 6.68 (1H, t, J = 8.8Hz), 6.92 (1H, dd, 1 = 2.0, 8.8Hz), 6.96 (2H, d, J = 8.0Hz), 7.93 (1H, s), 8.22 0H, d, J-9.8Hz).

Melting point: 1 1 4-1 1 6 ° C Example 5 6 Bromide 1-{7-[3-[N-(3,5-difluorophenyl) -N-(2 -propargyl) amine methylamine Fluorenyl] -1_ (3-methoxy > 5-propoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] heptylpyridine (exemplified compound number · 2 _ 7 7 5)

The 7 _ (7 _ bromoheptyloxy) _ 1 _ (3 _methoxy-5-propoxyphenyl) -4-oxo-14-dihydroquinoline-3 obtained in Example (5 4 f) _Carboxylic acid ν- (3,5 · difluorobenzyl) -N- (2-propargyl) fluorenamine 1 4 7 mg and pyridoxine 1 m 1 were reacted according to the method of Example (1 1 j) 1. The title compound was obtained as a pale orange solid 1 0 3 mg NMR (CDCI3) δρριι: 1.05 (3H, t, J = 7.3Hz), 1.40 (6H, bs), 1. 66-1. 74 (2H, m ), L83 (2H, sextet, J-7.3Hz), 2.00-2.10 (2H, m), 2.25 (1H, t, 1 = 2.2Hz), 3.83 (3H, s), 3.82-3.87 (2H, m) , 3.93 (2H, dt, J = 2.2, 6.6Hz), 4.64 (2H, d, J = 2.2Hz), 5.04 (2H, t, I = 7.3Hz); 6.40 (1H, d, J = 2.2Hz) , 6.45 (2H, d, 1 = 2.2Hz),-247 · 200300349 6.62 (1H, t, J = 2.2Hz), 6.67 (1H, tt, J = 2.2, 8.8Hz), 6.9K1H, dd, J = 2. 2, 8.8Hz), 6.95 (2H, dd, J = 2.2, 8.1Hz), 7.90 (1H, s), 8.09 (2H, t, J = 7.3Hz), 8.19 (1H, d, J = 9.5 Hz), 8.47 (1H, t, J = 8.1Hz), 9.51 (2H, d, J = 5.9Hz). Melting point: 9 1-9 4 t: Example 5 7 Bromide 1- {7-[3- [N-(3,5-difluorophenyl) -N · (2-propargyl) aminomethyl] -1- (3-methoxy-5-propoxyphenyl) -4-oxo- 1, 4- • Aspirin-7-yloxy] heptylb-methylpiperidine (exemplified compound number: 2-7 7 6) 7- (7-bromoheptyloxy) -1 obtained in Example (54f) -(3-Methoxy-5 -propoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-(2 -Propargyl) amine 1 40 mg and 1-methylpiperidine 1 m 1. The reaction was carried out according to the method of Example (1 1 j) to obtain the title compound as a yellow solid 1 110 mg 0 NMR; (CDC13) (5ppm: 1.04 (3H, t, J = 7.3Hz), 1.42 (6H, bs),

1.66-1.94 C12H, m), 2.24 (1H, t, J = 2.2Hz), 3.32 (3H, s), 3.62-3.76 (6H, m), 3.83 (3H, s), 3.82-3.88 (2H, m ), 3.93 (2H, dt, J = 2.2, 6.6Hz), 4.64 (2H, d, J = 2.2Hz), 6.4K1H, d, J = 2.2Hz), 6.46 (2H, d, J = 2.2Hz) , 6.62 (1H, t, J = 2.2Hz), 6.66 (1H, tt, J = 2.2, 8.8Hz), 6.9K1H, dd, J = 2.2, 8.8Hz), 6.95 (2H, dd, J = 2.2, 7.3Hz), 7.92 (1H, s), 8.21 (1H, d, J = 8.8Hz).

Melting point: 9 4-9 7 ° C Example 5 8 1- {8- [3- [N- (3,5-difluorophenyl) -N- (2-propargyl) aminocarbamyl bromide ] _1_ (3-Methoxy-5-propoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] octylb 4-azine-1-azobicyclo [2.2 · 2] Octane (Exemplified compound number: 2-8 3 5)-248-200300349 (58a) 7- (8-bromooctyloxy)-(3 -methoxy-5-propoxyphenyl) -4 -Oxy-1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl) -N-(2-propargyl) fluorenamine The obtained from Example (5 4 e) 7-Hydroxy-1-(3-methoxy-5 -propoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 5-difluorophenyl) -N- (2-propargyl) sulfonamide 600 mg, potassium carbonate 240 mg, and 1,8-dibromooctane 0.64 m 1, the reaction was carried out according to the method of Example (1 1 i) to obtain the title compound 720 mg of transparent oily substance. NMR .. (CDC13) δPPΠΐ: 1.05 (3H, t,] = 7.3Ηζ), 1. 29-1.47 (8Η, m), 1.68-1.89 (6Η, m), 2.24 (1Η, t, J = 2.2Hz), 3.39 (2Η, t, J = 6.6Hz), 3.83 (3H, s), 3.87 (2H, t, J = 6.6Hz), 3.93 (2H, dt, J = 1.5, 6.6Hz), 4.65 (2H, d, J = 2.2Hz), 6.43 (1H , d, J = 2.2Hz), 6.48 (2H, d, J = 2.2Hz), 6.62 (1H, t, J = 2.2Hz), 6.66 (1H, tt, 1 = 2.2, 8.8Hz), 6.92 (1H , dd, J = 2.2, 8.8Hz), 6.97 (2H, dd, J = 2.2, 7.3Hz), 7.94 (1H, s), 8.22 (1H, d, J = 8.8Hz). (5 8 b) bromine 1-{8-[3-[N-(3 5 5 -difluorophenyl) -N-(2-propargyl) aminomethylamidino] -1- (3-methoxy-5-propane Oxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] octylb 4-azr-1-azobicyclo [2.2.2] octane obtained from Example (58a) 7- (8-Bromooctyloxy)-(3-methoxy-5-propoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5 -Difluorophenyl) -N- (2-propargyl) phosphonium amine 1 4 3 mg and 1,4-diazinebicyclo [2 · 2 · 2] octane 3 0.0 mg, according to Example (1 1 j ), And 114 mg of the title compound was obtained as a white solid. NMR. (CDC13) δρριπ: 1.05 (3H, t, J = 6.8Hz), 1.28-1.43 (6H, id), 1.67-1.78 (4H, m), 1.83 (2H, sextet, J-6.8Hz)? 2.25 (1H, t, J-2.0Hz), 3.25 (6H, 200300349 t, 1 = 6.8Hz), 3.52-3.57 (2H, m), 3.65 (6H, t, J = 6.8Hz), 3.72 (2H, t , J = 6.8Hz), 3.84 (3H, s), 3.87 (2H, t, J = 6.8Hz), 3.91-3.96 (2H, m), 4.63 (2H, .d, J = 1.9Hz), 6.42C1H , d, J-2.0Hz), 6.46 (2H, d, J-2.0Hz), 6.62 (1H, t, J = 2.0Hz), 6.67 (1H, tt, J = 2.0, 8.8Hz), 6.93 (1H , dd, J = 2.0, 8.8Hz), 6.95 (2H, dd, J = 2.0, 7.8Hz), 7.90 (1H, s), 8.2K1H, d, J = 8.8Hz). Melting point: 1 1 5-1 1 8 t: 'Example 5 9 Bromide 1- {8-[3-[N-(3,5-difluorophenyl) -N-(2-propargyl) aminomethylamidino] -1- (3-Methoxy-5 -propoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7-yloxy] octylbazobicyclo [2.2 · 2] octane (exemplified Compound No. 2-834) The 7- (8-bromooctyloxy)-(3-methoxy-5-5-propoxyphenyl) -4-oxy-1,4-obtained in Example (5 8a) Dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N- (2-propargyl) phosphonium amine 1 26 mg and pyridine 2.6 · 5 mg, according to the examples ( 1 1 j) The reaction was carried out according to the method to obtain the title compound as a white solid 1 18 mg 0 Li R. (CDC13) δ ppm: 1.05 (3H, t, 1 = 7.8 Hz), 1. 26-1.42 (6H, m), 1.65-1.74 (4H, m), 1.83 (2H, sextet, J = 6.8Hz), 2. 00-2.10 (6H, m), 2.23-2. 27 (2H, m), 3.46-3.52 ( 2H, m), 3.7K6H, t, J = 7.8Hz), 3.76 (2H, t, J-7.8Hz), 3.84 (3H, s), 3.86 (2H, t, J = 6.8Hz), 3. 91 -3. 96 (2H, m), 4.64 (2H, s), 6.42 (1H, d, J = 2.0Hz), 6.47 (2H, s), 6.62 (1H, t, J = 2.0Hz), 6.67 (1H, tt, J = 2.0, 8.8Hz), 6.92 (1H, dd, J = 2.0, 8.8Hz), 6.96 (2H, dd, J = 2.0, 7.8Hz), 7.92 (1H, s), 8.21 (1H, d, J-8.8Hz).

Melting point: 1 0 7-1 1 0 ° C Example 6 0 Bromide 1-{8-[3-[N-(3,5-difluorophenyl) -N-(2 -propargyl) amine methylamine Fluorenyl; l- (3-methoxy-5-propoxyphenyl) -4-oxo-1,4-dihydroquinoline-250- 200300349 -7-yloxy] octylpyridine (Exemplified compound number: 2-8 3 2) The 7-(8-bromooctyloxy)-(3-methoxy-5 -propoxyphenyl) -4 -oxo obtained in Example (5 8 a) -1,4 -dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-(2-propargyl) fluorenamine 1 5 5 mg and pyridine D 1 m 1, The reaction was carried out in accordance with the method of Example (1 1 j) to obtain the title compound as a pale orange solid 108 mg R · (CDC13) δρρι: 1.05 (3H, t, 1-7.3Hz), 1. 25- 1.44 ('8H, m), 1.69 (2H, t, J = 7.3Hz), 1.83 (2H, sextet, J = 7.3Hz), 2.04 (2H, quintet, J = 7.3Hz), 2.25 (1H, t, J = 2.0Hz), 3.83 (3H, s), 3.85 (2H, t, J = 5.9Hz), 3.92 (2H, dt, J = 2.2, 6.6Hz), 4.64 (2H, d, J = 2.2Hz) , 5.03 (2H, t, J = 7.3Hz), 6.41 (1H, d, J = 2.2Hz), 6.45 (2H, d, J = 2.2Hz), 6.6K1H, t, J = 2.2Hz), 6.67 ( 1H, tt, 1 = 2.2, 8.8Hz), 6.92 (1H, dd, J = 2.2, 8.8Hz), 6.95 (2H, dd, J = 2.2, 8. 1Hz), 7.90 (1H, s), 8.10 (2H, t, J = 6.6Hz), 8.20 (1H, d, J = 8.8Hz), 8.47 (1H, t, J = 8.1 Hz), 9.5K2H, d, J = 6.6Hz). Example 6 1 1- {8- [3- [N- (3,5-difluorophenyl) term-(2-propargyl) aminomethyl]- 1- (3-Methoxy-5-propoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] octylb-methylpiperidine (exemplified compound number: 2 -8 3 3) The 7-(8-bromooctyloxy)-(3-methoxy-5 -propoxyphenyl) -4 -oxo-1,4 -di obtained in Example (5 8 a) Hydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-(2-propargyl) fluorenamine 1 40 mg and 1-methylpiperidine 1 m 1, according to the example ( 1 1 j) to obtain the title compound as a yellow solid 1 2 1 mg NMR (CDC13) δρριι: 1.05 (3H, t, J-6.8Hz), 1.29-1.46 (8H, m) , 1.67-1. 98 (1 2H, m), 2.24 (1H, t, J-2.0Hz), 3.33 (3H, s), 3.64-3.70 (4H, m), 3.71-3.79 (2H, m), 3.84 (3H, s), 3.86 (2H, t, J-6.8Hz), 3.91-3. 96 (2H, m), 200300349 4.64 (2H, s), 6.42 (1H, d, J = 2.0Hz), 6.47 (2H, d, J = 2.0Hz), 6.62 (1H, t, J = 2.0Hz), 6.67 (1H, t, J = 8.8Hz), 6.92 (1H, dd, J = 2.0, 8.8Hz), 6.96 (2H, d, J = 6.8Hz), 7.92 (1H, s), 8.2K1H, d, J = 8.8Hz).

Melting point: 9 7-9 9 ° C Example 6 2 1- {8- [3- [N- (3,5-difluorophenyl) -N-ethylaminemethylmethyl] -1- (3 , 5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] octyl}-1-methylpiperidine (exemplified compound number: 2-8 6 7) will 7- (8-Bromooctyloxy) -1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxyl obtained in Example (18a) The acid N- (3, 5-difluorophenyl) -N-acetamidine 189 mg and norpiperidine 1 m 1 were reacted according to the method of Example (1 1 j) to obtain the title compound. Light yellow solid 1 6 8 m § NMR (CDC13) δρριι: 1.21 (3Η, t, J: 7.3Hz), 1.28-1.45 (8Η, m), 1.65-1.95 (10Η, m), 3.32 (3Η, s), 3. 62-3. 77 (6Η, m), 3.84 (6H, s), 3. 81-3. 87 (2H, m), 3.93 (2H, q, J-7.3Hz) , 6.38 (1H, d, 1 = 2.2Hz), 6.46 (2H, d, J = 2.2Hz), 6.58-6.65 (2H, m), 6.84 (2H, dd, J = 2.2, 8.1Hz), 6. 90 (1H, dd, J = 2.2, 8.8Hz),

I 7.83 (1H, s), 8.20 (1H, d, J = 8.8Hz).

Melting point: 1 0 2-1 0 5 ° C Example 6 3 1- {8- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethyl]] bromide-1- (3,5 -dimethoxyphenyl) -4 -oxo-1,4-dihydro Aquinoline-7 -yloxy] octylbazobicyclo [2 · 2.2] octane (Exemplified compound number : 2 -3 5 7) The 7-(8-bromooctyloxy) -1-(3,5-di- 252-200300349 methoxyphenyl) -4 -oxo obtained in Example (1 8 a) 1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 187 mg and panquinidine 4 1.4 mg, according to the example (1 1 j) and 192 mg of the title compound was obtained as a white solid. NMR. (CDC13) (5ppm: 1.20 (3H, t, J = 7.3Hz), 1. 25-1.42 (8H, m), 1. 60-1. 75 (4H, m), 2.05 (6H, bs) , 2.23 (1H, bs), 3.45-3. 52 (2H, m), 3.70 (6H, t, J = 8.1Hz), 3.84 (6H, s), 3.81-3.87 (2H, m), 3.92 ( 2H, q, J = 7.3Hz), 6.38 (1H, d, J = 2.2Hz), 6.46 (2H, d, 1 = 2.2 Hz), 6. 60-6.66 (2H, m), 6.84 (2H? dd, J = 2.2, 8.1Hz), 6.90C1H, dd, J = 2.2, 8.8Hz), 7.82 (1H, s), 8.20 (1H, d, J = 8.8Hz).

Melting point · 1 1 6-1 1 9 ° C Example 6 4 1- {7- [3- [N- (3, 5-difluorophenyl) -N-ethylamine formamidine 3-methoxy-5-propoxyphenyl) 4-oxo-1,4-dihydroquinoline-7-yloxy] heptylbupipidol (exemplified compound number: 2-7 7 0) (64a) 7-methoxymethoxy-1- (3-methoxy-5-propoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- ( 3,5-difluorophenyl) -N-acetamidine The 7-methoxymethoxy-1-(3-methoxy-5 -propoxyphenyl) obtained in Example (5 4 c)- 4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -amidamine 2 60 mg, 55% sodium hydride 3 2 · 4 mg, ethyl bromide The alkane 0 · 1 1 m 1 was reacted in the same manner as in Example (5 4 d) to obtain 2 74 mg of the title compound as a yellow oily substance. NMR, (CDC13) δρριη: 1.05 (3H, t, J-7. 3Hz), 1. 21 (3H, t, J = 7.3Hz), 1.83 (2H, sextet, 1 = 7.3Hz), 3.4K3H, s ), 3.82 (3H, s), 3.89-3.97 (4H, m), 5.1K2H, s), 6.46 (2H, d, J-2.2Hz), 6.60 (1H, t, J-2.2Hz), 6. 61-6.66 (2H, m), 6.84 (2H, dd, J-2.2, 8.1Hz), 7.04 (1H, dd,] = 2.2, 9.5Hz), 7.88 (1H, s), 8.22 (1H, d, J-8.8Hz). 200300349 (64b) 7-Hydroxy-1- (3-methoxy-5-propoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-Difluorophenyl) -N-acetamidine The 7-methoxymethoxy-1- (3-methoxy-5-propoxyphenyl) -4 obtained in Example (64a) -Oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl-acetamidamine 274mg and 4NHC1 / ethyl acetate solution 3ml, according to the example (5 4 e) The method was carried out to obtain 2 5 2 mg of the title compound as a white solid. R (CDCl3) 5 ppm: 1.0K3H, t, 1 = 7.3Hz), 1.16 (3H, t, J = 7.3Hz), 1. 79 (2H, sextet, J = 7.3Hz), 3.76 (3H, s), 3.84-3.93 (4H, m), 6.40 (2H, br), 6.55 (2H, d, J = 8.8Hz), 6.63 (1H, t, J = 8.8Hz), 6.82 (2H, d, J = 5.9Hz), 7.02 (1H, d, J = 8.8Hz), 7.82 (1H, s), 8.00 (1H, d, J = 8.8Hz) (64c) 7- ( 7-bromoheptyloxy) -1- (3-methoxy-5-propoxyphenyl) -4-oxo-1,4-dihydroquinoline 3-carboxylic acid N- (3,5-di Fluorophenyl) -N-acetamidine The 7-hydroxy-1- (3-methoxy-5-propoxyphenyl) -4-oxo-1,4-dihydroquinoline obtained in Example (64b) -3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 252mg, potassium carbonate 103mg, and 1,7-dibromoheptane 0.254ml, according to Example (1 1 i) The method was reacted to obtain 247 mg of the title compound as a transparent oily substance. Li R (CDC13) δρριη: 1.05 (3H, t, J = 7.3Hz), 1.20 (3H, t, J = 7.3Hz), 1.29-1.49 (6H, m), 1.67-1. 77 (2H, m) , 1. 78-1. 89 (4H, m), 3.40 (2H, t, J = 6.6Hz), 3.83 (3H, s), 3.87 (2H, t, J = 6.6Hz), 3.89-3.97 (4H , m), 6.40 (1H, d, J = 2.2Hz), 6.46 (2H, d, J = 2.2Hz), 6. 58-6.66 (2H, m), 6.84 (2H, dd, J = 2.2, 8.1 Hz), 6.90 (1H, dd, J-2.2, 8.8Hz), 7.85 (1H, s), 8.20 (1H, d, J = 8.8Hz). (64d) bromide l- {7- [3- [ N- (3,5-difluorophenyl) -N-ethylamine formamidine 200300349 group] -1- (3-methoxy-5-propoxyphenyl) -4 -oxo-1,4-dihydro Quinoline-7-yloxy] heptyl} -1-methylpiperidine The 7- (7-bromoheptyloxy) -1- (3-methoxy-5 -propoxy) obtained in Example (64c) Phenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 1 5 2 mg and 1-methylpiperidine 1 m 1, the reaction was carried out according to the method of Example (1 1 j), and the title compound was obtained as a yellow solid 120 mg oli R _ (CDC13) < 5ppm: 1.05 (3H, t, J = 7.8Hz), 1.2K3H, t, J = 7.8Hz), 1.42 (6H, bs), 1.68-1. 96 (12H, m), 3.33 (3H, s), 3. 62-3. 78 (6H, m), 3.83 (3H, s), 3.86 (2H, t, J = 6.8Hz), 3.89-3.96 (4 H, m), 6.40 (1H, s), 6.45 (2H, s), 6.62 (2H, s), 6.84 (2H, d, J = 6.8Hz), 6.90 (1H, d, J = 8.8Hz), 7.82 (1H, s), 8.20 (1H, d, J = 8.8Hz).

Melting point: 94-9 7 ° C Example 6 5 (7- {1- (3,5-difluorophenyl) -3- [N- (3,5-difluorophenyl) -N- Ethylaminocarbamyl 4-oxo-1,4-dihydroquinoline-7-yloxy] heptyl 丨 4- 4-acyl-1-azobicyclo [2.2 · 2] octane (Illustrated compound number: 2-8 6 8) (65a) 7-benzyloxy-1-(3,5-difluorophenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid methyl ester (4 4 b) 2-(4-benzyloxy-2 -methoxybenzylfluorenyl) -3 -dimethylamino-methyl acrylate 1.9 9 g, 3, 5-difluoroaniline 8 3 5 mg and potassium carbonate 1.12 g were reacted according to the method of Example (1 1 e) to obtain the title compound as a pale yellow solid 1. 6 4 g. NMR. (CDCl3) (5ppm: 3.89 ( 3Η, s), 5.04 (2H, s), 6.36 (1Η, d, J: 2.2Hz), 6.93-7.00 (2H, m), 7. 05-7.12 (2H, m), 7.25-7. 39 (5H, m), 8.37 (1H, s), 8.43 (1H, d, J = 8.8Hz) .- 255-200300349 (65b) 7-benzyloxy-1- (3,5-difluorophenyl) ) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid will be used as the 7-methoxy-1- (3,5--phenylphenyl) -4-oxo obtained in Example (65a). 1-4,4-dihydroquinoline-3 -carboxylic acid methyl ester 1.6 4 g and hydroxide Sodium 33 1 mg ^ The reaction was carried out according to the method of Example (1 e) to obtain the title compound as a light yellow solid 1.4 8 g. R (CDC13) δρριη: 5.08 (2H, s), 6.45 (1H, s) ), 6.95 (2H, d, J = 4.4Hz), 7. 10-7.40 (7H, m), 8.45 (1H, br), 8.63 (1H, s). (65c) 7-benzyloxy-1- (3,5-Difluorophenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 6 5 b) The obtained 7-benzyloxy-1-(3,5-difluorophenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid 1.48g, oxadiazine 0.632ml 1. The amount of catalyst N, N-dimethylformamide, N-ethyl-3,5-difluoroaniline 1.14g and triethylamine 2.03ml, the reaction was carried out according to the method of Example (If), and the title was obtained. The compound is a yellow foamy substance of 1. 19 g. NMR... (CDC13) δρριη: 1.19 (3H, t, J = 7.3Hz), 3.9K2H, q, 1 = 7.3 Hz), 5.0K2H, s), 6.33 (1H, d, J = 1.5Hz) , 6.63 (1H, t, J = 8.8Hz), 6.83 (2H, dd, J = 2.2, 7.3Hz), 6.89 (2H, dd, 1 = 2.2, 6.6Hz), 7.00 (1H, d, J = 9.5 Hz), 7.06 (1H, t, 1-8.1Hz), 7.25-7.37 (5H, m), 7.81 (1H, s), 8.19 (1H, d, 1 = 8.8Hz). (65d) l- (3 , 5-difluorophenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine will be implemented 7-benzyloxy-1-(3, 5-difluorophenyl)-4 -oxo-1, 4-dihydroquinoline-3 -carboxylic acid N-(3, 5 -Difluorophenyl) -N-acetamidamine 660 mg and 10% P d -C 60 mg according to the method of Example (1 g)-256-200300349 5 2 6 mg as a yellow solid. NMR. (CDC13) δρρπι: 1.16 (3Η, t, J = 7.3Hz), 3.38 (2H, q, J = 7.3Hz), 6.33 (1H, s), 6. 60-6.68 (1H, m), 6 75-6. 92 (5H, m), 6.97 (1H, tt, J = 2.2, 8.8Hz), 7.74 (1H, s), 7.93 (1H, d, J = 8.8Hz). (65 ^) 7 -(7-bromobutoxy) -1- (3,5-difluorophenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorobenzene Group) -N-acetamidinium 1- (3,5-difluorophenyl) -7-hydroxy-4-oxy-1,4-dihydroquinoline-3-obtained in Example (65d) Carboxylic acid N- (3,5-difluorophenyl) -acetamidine 526 mg, potassium carbonate 239 mg and 1,7-dibromoheptane 0.591 ml. The reaction was carried out according to the method of Example (1 Π), and the title was obtained. 5 1 2 mg of compound as a yellow oil. Li R (CDC13) 5ppm: 1.20 (3H, t, J = 7.3Hz), 1. 30-1.49 (6H, m), 1.74 (2H, quintet, J = 6.6Hz), 1.84 (2H, quintet, J = 6.6Hz), 3.39 (2H, t, 1 = 6.6Hz), 3.85-3.96 (4H, m), 6.3K1H, d, J = 2.2Hz), 6.63 (1H, t, J = 8.8Hz), 6.84 ( 2H, dd,] = 2.2, 8.1Hz), 6.92 (1H, dd, 1 = 2.2, 8.8Hz), 7.00 (2H, dd, J = 2.2, 6.6Hz), 7.07 (1H? Tt, J = 2.2, 8.8Hz), 7.83 (1H, s), 8.2K1H, d, J = 8.8Hz). (65f) brominated l- (7- {l- (3,5-difluorophenyl) -3- [N -(3,5-difluorophenyl) -N-ethylaminomethylmethyl] -4 -oxy-1,4-dihydroquinoline-7-yloxy} heptyl) -4 -acyl-1- The azobicyclo [2 · 2 · 2] octane will be 7-(7 -bromoheptyloxy) -1-(3, 5 -difluorophenyl) -4 -oxy- 1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 180 mg, 1,4-diazinebicyclo- [2.2.2] -octane 39.0 mg. The reaction was carried out according to the method of Example (1 lj) to obtain 163 mg of the title compound as a white solid. -257-200300349 NMR ... (CDC13) όρριι: 1.19 (3H, t, J = 7.3Hz), 1.39 (6H, bs), 1. 50-1. 85 (4H, m), 3.24C6H, t, J = 7.3Hz), 3.50-3.60 (2H, m), 3.65 (6H, t, J-7.3Hz), 3.84-3.95 (4H, m), 6.29 (1H, d3 1-2.2Hz), 6.64 (1H, tt, 1 = 2.2, 8.8Hz), 6.82 (2H, dd, J-2.2, 8.1Hz), 6.92 (1H, dd, J = 2.2, 8.8Hz), 6.97 (2H, d, J = 4.4Hz), 7.07 (1H, tt, J-2.2, 8.8Hz), 7.78 (1H, s), 8.18 (1H, d, J = 8.8Hz).

Melting point: 1 3 2-1 3 5 ° C Example 6 6 1- (7-Π- (3,5-difluorophenyl) -3- [N- (3,5-difluorophenyl) bromide -N- Ethylaminomethyl] -4-oxo-1,4-dihydroquinolin-7-yloxy} heptyl) -l-azobicyclo [2.2 · 2] octane (Exemplary compound number: 2-8 Ο 3) The 7-(7-bromoheptyloxy) -1-(3, 5 -difluorophenyl) -4 -oxy-1,4 -dihydro obtained in Example (6 5 g) Quinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 1 8 mg, panquinidine 4 0 · 8 mg, the reaction was carried out according to the method of Example (11 j) 18.5 mg of the title compound was obtained as a white solid. NMR. (CDCI3) δρρπι: 1.20 (3H, t, J = 7.3Hz), 1.38 (6H, bs), 1. 66-1. 77 (4H, m), 2. 00-2. 09 (6H, m ), 2.20-2. 25 (1H, m), 3. 45-3.54 (2H, m), 3.70 (6H, t, J = 7.3Hz), 3.83-3.95 (4H, m), 6.29 (1H, d , J-1.5Hz), 6.63 (1H, tt, J-2.2, 8.8Hz), 6.82 (2H, dd, 1 = 2.2, 7.3Hz), 6.92 (1H, dd, J = 2.2, 8.8Hz), 6.97 (2H, dd, J = 2.2, 6.6Hz), 7.07 (1H, tt, J-2.2, 8.8Hz), 7.79 (1H, s), 8.19 (1H, d, J = 8.8Hz). Melting point: 1 2 3-1 2 6 ° C Example 6 7 Desertification 1- (7_ {1_ (3,5-monochlorophenyl) -3- [N- (3,5-one ^ truncated) -N-ethyl Carboxamidine] -4 -oxo-I, 4-dihydroquinoline-7-yloxy} heptyl) -propaphenidium (exemplified compound number: 2-8 0 2) Examples (65g) The obtained 7- (7-bromoheptyloxy) -1- (3,5 -200200349phenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5- Difluorophenyl) -N-acetamidine 2 15 mg and 1-methylpiperidine 1 m 1 were reacted according to the method of Example (1 1 j) to obtain 170 mg of the title compound as a yellow solid. NMR: (CDC13) δρριι: 1.20 (3H, t, J = 7.3Hz), 1.42 (6H, bs), 1. 67-1. 99 (1H, m), 3.3K3H, s), 3.59-3.75 ( 6H, m), 3.86-3.96 (4H, m), 6.30 (1H, d, J = 2.2Hz), 6.64 (1H, tt, J = 2.2, 8.8Hz), 6.83 (2H, dd, J = 2.2, 8.1Hz), 6.93 (1H, dd, J = 2.2, 9.5Hz), 6.98 (2H, dd, J = 2.2, 6.6Hz), 7.08 (1H, tt, J = 2.2, 8.1Hz), 7.80 (1H, s), 8.20 (1H, d, J = 8.8Hz). Melting point: 1 1 5 · 1 1 7 ° C Example 6 8 Bromide 1-Π- {1- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -4 -oxo-1,4-dihydroquinoline-7-yloxy} heptyl) _ 4 -Phenyl-1 -azobicyclo [2.2 · 2] octane (exemplified compound number: 2-755) The 7-(7 -bromobutoxy) -1-(3 , 5-Diethoxyphenyl) -4-oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 1 5 3 mg and 4-Benzoquinidine 5 1 · 2 mg, reacted according to the method of Example (1 1 j) to obtain the title compound as a white solid 1 7 5 mg ο R R (CDC13) (5ppm: 1.19 (3H, t , J = 7.3Hz), 1.39 (6H, bs), 1.42 (6H, t, J = 7.3Hz), 1.67-1.80 (4H, m), 2.3K6H, t, J = 7.3 Hz), 3.57-3.65 (2H, m), 3.80-3.95 (10H, m), 4.02 (4H, q, 1-7.3Hz), 6.39 (1H, d, J = 2.2Hz), 6.42 (2H, d, J = 2.2Hz), 6.59 (1H, t, J = 2.2Hz), 6. 58-6. 65 (1H, m), 6.82 (2H, dd, J = 2.2, 8.1Hz), ΐ .88 (1Η, dd, J-2.2, 8.8Hz), 7. 23-7. 30 (3H, m), 7. 32-7. 38 (2H, m), 7. 81 (1H, s), 8.19 (1H, d, J = 8.8Hz). 200300349 Melting point: 1 1 5-1 1 7 ° C Example 69 Desertification 1- (8- {l- (3,5-^ ethoxyphenyl)- 3_ [N- (3,5-monogas / benzyl) -N-ethylaminomethylmethyl] -4 -oxo-1,4-dihydroquinoline-7 -yloxy} octyl) -1 -methyl Piperidine (Exemplary compound number: 2-8 2 1) The 7-(8-bromooctyloxy) -1-(3,5-diethoxyphenyl)-4-obtained in Example (4 5 a) Oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 166 mg and 1-methylpiperidine 1 m 1, according to the examples The reaction was carried out by the method of (1 1 j) to obtain 152 mg of the title compound as a yellow solid. Li R (CDC13) (5ppm: 1.20 (3H, t, J = 7.3Hz), 1. 30-1.45 (8H, m), 1.43 (6H, t, J = 7.3Hz), 1.65-2. 00 (10H , m), 3.34 (3H, s), 3. 62-3. 70 (4H, m), 3. 72-3. 82 (2H, in), 3.85 (2H, t, J = 6.6Hz), 3.92 (2H, q, J = 7.3Hz), 4.03 (4H, q, J = 7.3Hz), 6.40 (1H, d, J = 2.2Hz), 6.43 (2H, d, J = 2.2Hz), 6.59 (1H , t, J = 2.2Hz), 6.58-6.67 (1H, m), 6.83 (2H, dd, J = 2.2, 8.1Hz), 6.90 (1H, dd, J = 2.2, 8.8Hz), 7.81 ( 1H, s), 8.20 (1H, d, J = 8.8Hz).

Melting point: 1 0 0-1 0 2 ° C Example 7 0 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine 1- ( 3-methoxy-5-propoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] heptylbu 4-phenyl-; 1-azobicyclo [2 · 2 · 2] octane (exemplified compound number: 2- 773) 7-(7-bromobutoxy) -1-(3-methoxy-5 -propoxybenzene) obtained in Example (6 4 c) N- (3,5-difluorophenyl) -N-acetamidine 1 6 5 mg and 4-Benzoquinidine 5 5.2 mg was reacted according to the method of Example (1 1 j) to obtain the title compound as a white solid 200300349 1 78 mg oli R, (CDC13) (5 ppm: 1.05 (3H, t, 1-7. 3Hz), 1.20 (3H, t, J = 7.3Hz), 1.40 (6H, bs), 1.66-1.88 (4H, m), 2.32 (6H, t, .J = 7.3Hz), 3.57-3.65 (2H, m), 3.83 (3H, s), 3.84-3.96 (12H, m), 6.40 (1H, d, J = 2.2Hz), 6.45 (2H, d, J = 2.2Hz), 6.6K1H, t, J = 2.2Hz), 6.58-6.65 (1H, m), 6.84 (2H, dd, J = 2.2, 8.1Hz), 6.90 (1H, dd, J = 2.2, 8.8Hz), 7.24-7. 31 (3H, m ), 7. 33-7. 39 (2H, m), 7.82 (1H, s), 8.20 (1H, d, J = 8.8Hz).

Melting point: 1 1 2-1 1 5 ° C Example 7 1 φ bromide 1- {7- [3- (3,5-difluorophenyl) 1-ethylaminomethylmethyl] -1- (3- Isopropoxy-5-methoxyphenyl) -4 -oxo-1,4-dihydroquinolin-7 -yloxy} heptylbu 4 -acyl-1 -azobicyclo [2 · 2 · 2 ] Octane (Exemplified compound number: 2-7 9 6) (71a) 7-benzyloxy-1- (3-isopropoxy-5-methoxyphenyl) -4-oxo-1,4-di Hydroquinoline-3 -carboxylic acid methyl ester The methyl 2- (4-benzyloxy-2-methoxybenzyl) -3-dimethylamine acrylate obtained in Example (44b) 7. 3 8 g, Reference Example 21 3.6 g of 3-isopropyloxy-5-methoxyaniline and 2.76 g of potassium carbonate were reacted according to the method of Example (lie) to obtain the title compound as a white solid 4.1 5 g . NMR (DMS0-d6) δ ppm: 1.28 (6H, t, J: 6.5Hz), 3.72 (3H, s), 3.78 (3H, s), 4.68 (1H, quint, J-6.1Hz), 5.08 (2H, s), 6.45 (1H, d, J = 2.2Hz); 6. 71 (1H, m), 6.75 (1H, m), 6.80 (1H, m), 7.17 (1H, dd, J-9.1 , 2.2Hz), 7.28-7.37 (5H, m), 8.18 (1H, d, J = 9.1Hz), 8.37 (1H, s). (71b) 7-benzyloxy-1- (3-isopropoxy Methyl-5-methoxyphenyl) -4-oxo-1,4-dihydroBquinoline-3-unsaturated acid-261- 200300349 The 7-benzyloxy-1- (1) obtained in Example (7a) 3-isopropoxy ... 5-methoxyphenyl) 4-oxy 1,4-dihydroquinoline-3-carboxylic acid methyl ester 2.07 g and sodium hydroxide 5 2 5 mg, according to the example (1 e ), And 1.98 g of the title compound was obtained as a white solid. NMR (CDC13) (5ppm: 1.37 (6H, t, J = 6.6Hz), 3.8K3H, s), 4.54 (1H, quintet, J = 6.6Hz), 5.02 (1H, d, J = 11.7Hz), 5.07 (1H, d, J = 11.7Hz), 6.42 (1H, t, J = 2.2Hz), 6.46 (1H, t, J = 2.2Hz), 6.63 (1H, d5 J = 2.2Hz), 6.65 (1H, t, J = 2.2Hz), 7.19 (1H, dd, J = 2.2, 8.8Hz), 7. 26-7. 38 (5H, m), 8.44 (1H, d, J = 8.8Hz), 8.70 (1H (s). (71c) 7-Benzyloxy-1- (3-isopropoxy-5-methoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N -(3,5-difluorophenyl) -acetamidine The 7-benzyloxy-1-(3-isopropoxy-5 -methoxyphenyl) -4 obtained in Example (7 1 b) -Oxygen-1,4-dihydroquinoline-3-carboxylic acid 1.98g, grasshopper chlorine 0.750ml, catalyst amount N, N-dimethylformamide, N-ethyl-3,5-difluoro Aniline 1.02 g and triethylamine 1,80 m 1 were reacted according to the method of Example (1 f) to obtain 2.49 g of the title compound as a yellow solid. NMR (CDC13) δ ppm: 1.20 (3H, t, J-7. 3Hz), i. 33-1.40 (6H, m), 3.7H3H, # s), 3.92 (2H, q, J = 7.3Hz), 4.52 (1H, quintet, J = 5.9Hz), 4.97 (2H, d, J = 2.9Hz), 6.36 (1H, t, J = 2.2Hz), 6.40 (1H, t, J = 2.2Hz), 6.47 ( 1H, d, J = 2.2Hz), 6.59 (1H, t, J = 2.2Hz), 6.62 (1H, tt, J = 2.2, 8.8Hz), 6.83 (2H, dd, 1 = 2.2, 8.1Hz) , 6.98 (1H, dd, J = 2.2, 8.8Hz), 7.25-7.37 (5H, m), 7.84 (1H, s), 8.21 (1H, d, J-9.5Hz). (71d) 7 -hydroxy- 1- (3-isopropoxy-5-methoxyphenyl) -4-oxo-I, 4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N ethyl The amidine was obtained from the 7-benzyloxy-1-(3-isopropoxy-5 -methoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 obtained in Example (7 1 c). -Carboxylic acid N- (3, 5-difluorophenyl- 262-200300349) -N-acetamidine 2.49 g and 10% Pd-C 250 mg. The reaction was carried out according to the method of Example (lg) to obtain the title compound. Pale green solid 2.1 g. Li R (CDC13) δρριη: 1.16 (3H, t, J = 7.3Hz), 1. 29-1. 34 (6H, m), 3.76 (3H, s), 3.88 (2H, q, J = 7.3Hz) , 4.49 (1H, quintet, J = 5.9Hz), 6.39 (1H, t, J = 2.2Hz), 6.42 (1H, t, J = 2.2Hz), 6.53 (2H, t, J = 2.2Hz), 6.61 (1H, tt, J = 2.2, 8.8Hz), 6.80 (2H, dd, 1 = 2.2, 8.1Hz), 6.97 (1H, dd, 1 = 2.2, 8.8Hz), 7.82 (1H, s), 8.01 ( 1H, d, J = 8.8 Hz). (71e) 7- (7-bromoheptyloxy) -1- (3-isopropoxy-5-methoxyphenylbuth 4-oxo-I, 4- Dihydroquinoline-3 · carboxylic acid N- (3,5-difluorophenyl IN-ethoxyamine) The 7-hydroxy-1-(3-isopropoxy- 5-methoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N acetamide 700 mg, potassium carbonate 285 mg, and 1 , 7-dibromoheptane 0.76 ml, reacted according to the method of Example (1 1 i) to obtain the title compound as a transparent oily substance 6 50 mg. NMR. (CDC13) (5ppm: 1.2K3Η , t, 1-7. 3Hz), 1. 28-1. 48 (1 2H, m), 1. 67-1. 76 (2H, m), 1.84 (2H, quintet, J = 7.3Hz), 3.39 (2H, t, 1-7. 3Hz), 3.82 (3H, Φ s), 3.86 (2H, t, J = 6.6Hz), 3.93 (2H, q, J = 7.3Hz), 4.54 (1H, quintet, J = 5.9 Hz), 6.4 K1H, d, J = 2.2Hz), 6.44 (2H, t, J = 2.2Hz), 6.59 (1H, t, J-2.2Hz), 6.62 (1H, tt, J-2.2, 8.8Hz), 6.83 ( 2H, dd, J = 2.2, 8.1Hz), 6.90 (1H, dd, J-2.2, 8.8Hz), 7.84 (1H, s), 8.21 (1Η, d, J = 8.8Hz) · (71f) 1- {7- [3- (3,5-difluorophenyl) -N-ethylamine formamidine 1- (3-isopropoxy ... 5-methoxyphenyl) -4-oxy -1,4-dihydroquinoline-7-yloxybuheptylbu 4 -acyl-1 -azobicyclo [2 · 2 · 2] octane The 7-(7- Bromoheptyloxy) -1-(3-isopropyl- 263-200300349 oxy-5-methoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 135 mg of 5-difluorophenyl) -N-acetamidamine and 2 7.0 mg of 1,4-diazinebicyclo- [2 · 2 · 2] -octane. 129 mg of the title compound was obtained as a white solid. NMR- (CDC13) δρρπι: 1.20 (3H, t, J-7.3Hz), 1. 33-1.44 (12H, m), 1.67-1.78 (4H, m), 3.25 (6H, t, J = 7.3Hz) , 3.53-3.59 (2H, m), 3.64 (6H, t, J = 7.3Hz)? 3.82 (3H, s), 3.85 (2H, t, J = 6.6Hz), 3.92 (2H, q, J ^ 7.3 Hz), 4.54 (1H, quintet, J = 5.9Hz), 6.40 (1H, d, J = 2.2Hz), 6.42 (2H, br), 6.59 (1H, t, J = 2.2Hz), 6.63 (1H, tt, J = 2.2, 8.8Hz), 6.83 (2H, dd, J = 2.2, 7.3Hz), 6.90 (1H, d, J = 8.8Hz), 7.32 (1H, s), 8.20 (1H , d, J = 8.8Hz).

Melting point: 1 2 1-1 2 3 ° C Example 7 2 Bromide 1- {7- [3- (3, 5-difluorophenyl) -N-ethylamine formamidine ΙΟ-isopropoxy -5-methoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy 丨 heptyl}-1-azobicyclo [2 · 2 · 2] octane (exemplified compound numbers : 2-7 9 5) The 7-(7-bromoheptyloxy) -1-(3 -isopropoxy-5-methoxyphenyl) -4 -oxo obtained in Example (7 1 e) 1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 16 3 mg, and pyridine 3 2 · 7 mg, according to Example (1 1 j) The reaction was carried out to obtain 146 mg of the title compound as a white solid. NMR. (CDC13) δρρη: 1.20 (3H, t, J = 7.3Hz), 1.32- 1.45 (12H, in), 1. 66-1. 76 (4H, m), 2. 00-2.10 (6H, m), 2.23 (1H, t, J = 2.9Hz), 3. 44-3.53 (2H, m), 3.70 (6H, t , J = 7.3Hz), 3.82 (3H, s), 3.85 (2H, t, 1 = 5.9 Hz), 3.92 (2H, q, 1 = 7.3 Hz), 4.54 (1H, quintet, 1 = 5.9Hz ), 6.40 (1H, d, J = 2.2Hz), 6.43 (2H, br), 6.59 (1Η, t, 200300349 J = 2.2Hz), 6.63 (1H, tt, 1 = 2.2, 8.8Hz), 6.83 ( 2H, dd, J = 2.2, 8.1Hz), 6.90 (1H, dd, 1 = 2, 2, 8.8Hz), 7.82 (1H, s ), 8.20 (1H, d, J = 8.8Hz).

Melting point: 1 1 6-1 1 8 ° C Example 7 3 L- {7- [3- (3,5-difluorophenyl) -N-ethylaminemethylmethyl] -1- (3- Isopropoxy-5_methoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7-yloxy} heptylbuproxyl-1-methylpyridine (exemplified compound number: 2-7 9 4 ) The 7-(7-bromobutoxy) -1-(3-isopropoxy-5-methoxyphenyl) -4 -oxo-1,4-dihydro obtained in Example (7 1 e) The reaction of quinoline-3 carboxylic acid N- (3,5-difluorophenyl) -acetamidine and 1-methylpiperidine 1ml 'was carried out according to the method of Example (1 1 j) to obtain the title compound. 160 mg of light yellow solid NMR-(CDC13) (5ppm: 1.20 (3H, t, J = 7.3Hz), 1.36 (6H, t, J = 5.9Hz), 1.4K6H, bs), 1.68-1.96 ( 10H, m), 3. 31 (3H, s), 3.59-3. 75 (6H, m), 3.83 (3H, s), 3.86 (2H, t, 1 = 6.6Hz), 3.92 (2H, q, J = 7.3Hz), 4.54 (1H, quintet, 1 = 6.6Hz), 6.40 (1H, d, J = 2.2Hz), 6.43 (2H, d, J = 1.5Hz), 6.60 (1H, t, J = 2.2Hz), 6.63 (1H, tt, J = 2.2, 8.8Hz), 6.83 (2H, dd, J = 2.2, 8.1Hz), 6.90 (1H, dd, J = 2.2, 9.5Hz), 7.82 (1H, s), 8.20 (1H, d, J = 8.8Hz).

Melting point: 105-107 ° C Example 7 4 L- {8- [3- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3- Isopropoxy--5-methoxyphenyl) -4-oxy-1,4-dihydro Dquinoline-7-yloxy} octylbupropane-methyl piperidine (exemplified compound number: 2-8 4 9) (74a) 7- (8-bromooctyloxy) -1- (3-isopropoxy-5-methoxyphenyl) -4-oxo-1,4-dihydrosialine-3- Residual acid N- (3,5-difluorophenyl) -N-ethyl-265-200300349 fluorenamine 7-Hydroxy-1- (3-isopropoxy-5-methoxy) obtained in Example (71d) Phenyl) _4-oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 353 mg, potassium carbonate 144 mg, and 1,8-dibromo Octane 0.3 8 4 m 1 was reacted according to the method of Example (1 1 i) to obtain the title compound as a transparent oily substance 3 5 7 mg. NMR, (CDC13) δρριη: 1.2K3Η, t, 1 = 7.3 Hz), 1.28-1.46 (14H, m), 1.67-1.76 (2H, m), 1.84 (2H, quintet, J = 7.3Hz) , 3.40C2H, t, J = 7.3Hz), 3.82 (3H, s), 3.86 (2H, t, 1 = 6.6Hz), 3.93 (2H, q, J = 7.3Hz), 4.54 (1H, quintet, 1 = 5.9Hz), 6.4K1H, d, 1 = 2.2Hz), 6.44 (2H, t, J = 2.2Hz), 6.59 (1H, t, J = 2.2Hz), 6.62 (1H, tt, J = 2.2, 8.8Hz), 6.84 (2H, dd, J = 2.2, 8.1Hz), 6.90 (1H, dd, J = 2.2, 8.8Hz), 7.84 (1H, s), 8.2K1H, d, J = 8.8Hz). (74b) Desertification of 1- {8- [3- (3,5 -monochlorophenyl) -N-ethylaminemethyl] -1- (3-isopropoxy-5-methoxyphenyl) 4-oxy-1,4-dihydroquinoline-7-yloxy 丨 octylb-methylpyridine The 7- (8-bromooctyloxy) -1 obtained in Example (7 4 a) -(3 -isopropoxy-5_methoxyphenyl) -4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N -ethyl Ammonium 192 mg and 1-methylpiperidine 1 m 1 were reacted according to the method of Example (1 1 j) to obtain the title compound as a pale yellow solid 1 3 5 mg NMR (CDC13) (5 ppm: 1.20 (3H? T, J-7.3Hz), 1. 28-1. 44 (14H, m), 1. 65-1.97 (1 0H, m), 3. 31 (3H, s), 3.58-3.67 (4H , m), 3. 68-3. 77 ( 2H, m), 3.82 (3H, s), 3.85 (2H, t, J = 6.6Hz), 3.92 (2H, q, J = 7.3Hz), 4.54 (1H, quintet, J = 5.9Hz), 6. 40-6. 44 (3H, m), 6.59 (1H, t, J = 2.2Hz), 6.63 (1H, tt, 1 = 2.2, 8.8Hz), 6.83 (2H, dd, J-1.5, 7.3Hz) , 6.9K1H, dd, J = 2.2, 8.8Hz), 7.8K1H, s), · 8.20 (1H, d, J = 8.8Hz). 200300349 Melting point: 1 ο 1-1 ο 3 ° c Example 7 5 Bromine Benzyl- (7- {l- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -4 -oxo -1,4-dihydroquinoline-7-yloxy} heptyl) -dimethylammonium (exemplified compound number: 2-7 5 6) The 7-(7 -bromo) obtained in Example (4 4 g) Heptyloxy) -1-(3,5-diethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N -Ethylamine 186mg and N-benzyldimethylamine 1ml, the reaction was carried out according to the method of Example (llj), to obtain the title compound as a white solid 124mg oli R / (CDC13) (5ppm: 1.20 (3H, t, J = 7.3Hz), 1.37 (6H, bs), 1.43 (6H, t, J = 7.3Hz), 1.64-1. 73 (2H, m), 1. 76-1. 87 (2H, m), 3.28 ( 6H, s), 3. 55-3. 63 (2H, m), 3.83 (2H, t, J = 5.9Hz), 3.92 (2H, q, J-7.3Hz), 4.03 (4H, q, J = 7.3Hz), 5.06 (2H, s), 6.39 (1H, d, J = 2.2Hz), 6.42 (2H, d, 1 = 2.2Hz), 6.59 (1H, t, J = 2.2Hz), 6.62 (1H, tt, J = 2.2, 8.8Hz), 6.83 (2H, dd, J = 2.2, 8.1Hz), 6.90 (1H, dd, J = 2.2, 8.8Hz), 7.39 ~ 7.49 (3H, m), 7.63-7.68 (2H, m), 7.81 (1H, s), 8.19 (1H, d, J-8.8Hz). Melting point: 9 6-9 9 ° C Example 7 6 Benzyl bromide- {7- [3- [N- ( 3,5 -difluorophenyl) -N-ethylaminomethylmethyl] -1- (3-methoxy-5-propoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7 -Yloxy] heptylbium dimethylammonium (exemplified compound number: 2-7 7 4) The 7-(7 -bromoheptyloxy) -1-(3 -methoxy) obtained in Example (6 4 c) Propyl-5 -propoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N-(3, 5 -difluorophenyl) -N-acetamidamine 174 mg and N- The reaction of benzyldimethylamine lm bu I -267-200300349 example (1 1 j) was carried out to obtain 174 mg of the title compound as a white solid. Li R. (CDC13) (5ppm: 1.05 (3H, t, J = 7.3Hz), 1.20 (3H, t, J = 7.3Hz), 1.35-L45 (6H, m), 1. 67-1. 75 ( 2H, m), 1. 77 ~ 1. 86 (4H, m), 3.27 (6H, s), 3.57-3. 64 (2H, m), 3.83 (3H, s), 3.83-3.97 (6H, m ), 5.02 (2H, s), 6.40 (1H, d, J = 2.2Hz), 6. 44 (2H, d, J = 2.2Hz), 6. 59-6. 65 (2H, m)? 6.83 ( 2H, dd, J = 2.2, 8.8Hz), 6.90 (1H, dd, J = 2.2, 8.1Hz), 7. 42-7. 49 (3H, m), 7. 61-7.66 (2H, in), 7.83 (1H, s), 8.20 (1Η, d, J = 8.8Hz). Melting point: 9 4-9 6 ° C Example 7 7 Bromide 1- {8- [3- [N- (3, 5-difluorophenyl) -N-ethylaminomethyl] -IO-methoxy-5-propoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] Octyl}-1-Methylpiperidine (Exemplified compound number: 2-8 2 9) (7 7 a) 7-(8-Bromooctyloxy) -1-(3 -methoxy-5 -propoxy · Phenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) acetamidine The 7-hydroxy group obtained in Example (6 4 b) 1-(3-methoxy-5 -propoxyphenyl) -4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N -ethyl Ammonium 16 6 mg, potassium carbonate 6 7 .7 mg, and 1,8-dibromooctane 0.1 8 0 m 1 Reaction was carried out according to the method of Example (1 1 i), the substance can be obtained as a clear oil of the title compound 1 6 4 m g. NMR (CDC13) δρρίϋ: 1.05 (3Η, t, J-7.3Hz), 1.20 (3H, t, J-7.3Hz), 1.29-1. 49 (8H, m), 1.67-1.77 (2H, m), 1. 78-1. 89 (4H, m), 3.40 (2H, t, J = 6.6Hz), 3.83 (3H, s), 3.87 (2H, t, J = 6.6Hz), 3.89-3.97 (4H, m), 6.40 (1H, d, J = 2.2Hz), 6.46 (2H, d, J = 2.2Hz), 6. 58-6.66 (2H, m), 6.84 (2H, dd, J = 2.2, 8.1Hz ), 6.90 (1H, dd, J-2.2, 8.8Hz), 7.85 (1H, s), 8.20 (1H, d, J-8.8Hz) .- 268-200300349 (77b) bromide 1- {8- [ 3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3-methoxy-5-propoxyphenyl) -4-yl-1,4- Dihydroquinoline-7-yloxy] octylb-methylpiperidine The 7- (8-bromooctyloxy) -1-(3-methoxy-5) obtained in Example (7 7a) -Propoxyphenyl) -4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 164mg and 1-methidine 1 ml, the reaction was carried out according to the method of Example (1 1 j), and the title compound was obtained as a yellow solid 1 4 5 mg NMR (CDC13) (5ppm: 1.05 (3H, t, J = 7.3Hz), 1.20 (3H , t, J = 7.3Hz), 1.28-1.46 (8H, m), 1.66-1. 75 (4H, m), 1. 76-1. 98 (8H, m), 3.33 (3H, s), 3 61-3. 70 (4H, m), 3. 72-3. 80 (2H, m), 3.83 (3H, s), 3.86 (2H, t, J = 6.6Hz), 3.89-3.98 (4H, m), 6.40 (1H, d, J = 2.2Hz), 6.44 (2H, d, J = 2.2Hz), 6.61 (1H, t, J = 2.2Hz), 6.60-6.66 (1H, m), 6.84 (2H, dd, J = 2.2, 8.1Hz), 6.90 (1H, dd, J = 2.2, 9.5Hz), 7.82 (1H, s), 8.20 (1H, d, 1 = 8.8Hz).

Melting point: 9 8-100 ° C Example 7 8 Bromide 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -l- ( 3,4 -dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7 -yloxy] heptyl}-4 -acyl-1 -azobicyclo [2 · 2.2] octane (Exemplified compound number: 2-161) (78a) 7-Benzyloxy-1- (3,4-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid methyl ester The ester was 5.19 g of 2- (cardibenzyloxy-2-methoxybenzylfluorenyl) -3 -dimethylamino-methacrylate, 2.58 g of 3,4-dimethoxyaniline obtained in Example (44b), and Potassium carbonate, 3.8 g, was reacted according to the method of Example (1 1 e) to obtain-269-200300349, a titled compound, as a gray solid, 5.8 3 g. Bandit R (CDC13) δ ppm: 3.86 (3H, s), 3.91 (3H, s), 4.01 (3H, s), 4.90-5 · 05 (2H, m), 6.40 ( 1H, d, J (2 · 9Ηζ), 6.79 (1H, d, J = 2, 2Hz), 6.93 (1H, dd, J-2.2, 8.1Hz), 7.0K1H, d, J = 8.1Hz), 7.07 (1H, dd, J = 2.2, 8.8Hz), 7.24-7. 30 (2H, m), 7.30-7.37 (3H, m), 8.45 (1H, d, J = 8.8Hz), 8.47 (1H (s). (7813) 7-Benzyloxy-1- (3,4-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid. Examples (7 8 a) The obtained 7-benzyloxy-1-(3,4-dimethoxyphenyl) -4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid methyl ester 5.8 3 g and hydrogen 1.57 g of sodium oxide was reacted according to the method of Example (1e) to obtain 5.0 6 g of the title compound as a pale yellow solid. NMR (CDC13) δρριη: 3.85 (3H, s), 4.02 (3H, s), 5.00 (1H, d, J = 12.0Hz), 5.06 (1H, d, J = 12.0Hz), 6.51 (1H, d, J = 2.9Hz), 6.76 (1H, d, J = 2.9Hz), 6.93 (1H, dd? J-2.2, 8.8Hz), 7.02 (1H, d, J = 8.8Hz), 7.20 (1H, dd, J = 2.2, 8.8Hz), 7.23-7.28 (2H, m), 7.31-7. 37 (3H, m), 8.45 (1H, d, J = 8.8Hz), 8.71 (1H, s). (78〇 7-benzyloxy-1- (3,4-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl)- The ammonium amine obtained the 7-benzyloxy-1-(3,4-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid obtained in Example (7 8 b) 5.06 g, 4.09 ml of triethylamine, 2.28 ml of isobutyl chloroformate, and 1.82 g of 3,5-difluoroaniline. The reaction was carried out according to the method of Example (5 4 c) to obtain the title compound as a gray solid. 6.36 g NMR , (CDC13) δρριη: 3.85 (3Η, s), 4.01 (3H, s), 4.97 (1Η, d, J = 12.5Hz), 5.03 (1H, d, J = 12.5Hz), 6.47 ( 1H, d, 1 = 2.9Hz), 6.52 (1H, tt, J-2.2, 8.8Hz), 6.79 (1H, d, J-2.2Hz), 6.93 (1H, dd, J-2.9, 8.1Hz), 7.02 (1H, d, J-8.8Hz), 200300349 7.15C1H, dd, J = 2.2, 9.5Hz), 7. 26-7.40 (7H, m), 8.45 (1H, d, J = 8.8 Hz ), 8.77 (1H, s). (78d) 7-benzyloxy-1- (3,4-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N -(3, 5-difluorophenyl) -N-acetamidine The 7-benzyloxy-1-(3,4-dimethoxyphenyl) -4-oxo obtained in Example (7 8 c) -1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -fluorenamine 1.99 g, 55% sodium hydride 240 mg, and iodoethane 0.88 ml, according to the example (5 4 d) to obtain the title compound as a yellow solid 1.81 1 g ° R (CDC13) δρρη: 1.20 (3H, t, J = 7.3Hz), 3.84 (3H, s), 3.92 (2H , q, J = 7.3Hz), 4.00 (3H, s), 4.92 (1H, d, J = 12.0Hz), 4.97 (1H, d, J = 12.0Hz), 6.35 (2H, d, J = 2.2Hz ), 6.62 (1H, tt, J = 2.2, 8.8Hz), 6.72 (1H, d, J = 2.2Hz), 6. 81-6,89 (3H, m), 6.99 (2H, d, J = 8 8Hz), 7.23-7. 36 (5H, m), 7.85 (1H, s), 8.2K1H, d, J = 9.5Hz). (78e) l- (3,4-dimethoxyphenyl)- 7-Hydroxy-4_oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 7- obtained in Example (78d) Benzyloxy-1- (3,4-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -acetamidine Amine 1.8 g and 10% P d-C 180 mg, reacted according to the method of Example (1 g) to obtain the title compound as a pale green solid 1.4 g g NMR (CDC13) (5ppm: 1.19 (3H, t, J = 6.8Hz), 3.84 (3H, s), 3. 85-3. 94 (2H, m), 3.95 (3H, s), 6.38 (1H, s), 6.63 (1H, t, J-8.8Hz), 6.76-6.86 (4H, m), 6.86-6.96 (2H, m), 7.8K1H, s), 8.03 (1H, d, J = 8.8Hz). (78f) 7- (7-bromoheptyloxy)- 1- (3,4-Dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl) · N -acetamidine 1- (3,4-dimethoxyphenyl) -7-hydroxy-271- 200300349 -4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3 obtained in Example (78e) 1,5-difluorophenyl) -N-acetamidamine 1.OOg, potassium carbonate 431mg and 1,7-dibromoheptane 1.07ml, which can be reacted according to the method of Example (1 1 i) to obtain 1.09 g of the white foamy substance of the title compound. NMR (CDC13) (5ppm: L21 (3H, t, J = 7.3Hz), 1. 29-1.49 (6H, m), 1.72 (2H, quintet, J = 6.6Hz), 2.05 (2H, quintet, J = 6.6Hz), 3.39 (2H, t, J = 7.3Hz), 3.83 (2H, t, J = 6.6Hz), 3.90 (3H, s), 3. 90-3. 97 (2H, m), 3.99 ( 3H, s), 6.29 (1H, d, J = 2.2Hz), 6.62 (1H5 tt, J = 2.2, 8.8Hz), 6.80 (1H, d5 J = 2.9Hz), 6.84 (2H, dd, 1 = 2.2 , 8.1Hz), 6.87- 6.95 (2H, m), 7.0K1H, d, J = 8.8Hz), 7.86 (1H, s), 8.2K1H, d, J = 9.5Hz). (78g) Desertification l- {7- [3- [N- (3,5-monofluorophenyl) -N-ethylaminomethylmethyl] -1- (3,4-dimethoxyphenyl) -4 -oxy-1,4 -Dihydroquinoline-7-yloxy] heptylbu 4 -acyl-1 -azobicyclo [2 · 2 · 2] octane The 7- (7-bromoheptyloxy) obtained in Example (78f) ) -1- (3,4-dimethoxyphenyl) -4 -oxy-1,4-dihydroquinoline · 3-carboxylic acid N- (3,5-difluorophenyl) -1 ^ -ethyl Amidamine 1650 ^ and 1,4-di-diabicyclo [2.2.2] Xinyuan 3 4.5 mg were reacted according to the method of Example (1 1 j) to obtain 150 mg of the title compound as a white solid. NMR. (CDC13) δρριη: 1.2K3Η, t, J = 7.3Hz), 1.38 (6H, bs), 1. 66-1. 80 (4H, m), 3.24C6H, t, J = 7.3Hz), 3.52 -3.59 (2H, m), 3.65 (6H, t, J = 7.3Hz), 3.82 (2H, t, J = 6.6Hz), 3.89 (3H, s), 3. 90-3. 96 (2H, m ), 3.99 (3H, s), 6.29 (1H, d, J = 2.2Hz), 6.63 (1H, tt, J = 2.2, 8.8Hz), 6.79 (1H, d, J = 2.2Hz), 6.83 (2H , dd, J = 2.2, 8.1Hz), 6.87- 6.94 (2H, m), 7.03 (1H, d, 1 = 8.1Hz), 7.8K1H, s), 8.20 (1H, d, J = 8.8Hz). Melting point: 1 3 4-1 3 6 ° C Example 7 9 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl- 272- 200300349 -Dimethoxyphenyl) -4 -oxo-I, 4-dihydroquinoline-7-yloxy] heptyl}-1 -azazobicyclo [2 · 2 · 2] octane (exemplified compound numbers : 2-159) The 7- (7-bromoheptyloxy) -1- (3,4-dimethoxyphenyl) -4-oxo-1,4-dihydroquine obtained in Example (78 f) was used. N- (3,5-difluorophenyl) -N-acetamidine-3, carboxylic acid 177 mg and D-quinidine 37. 0 mg, the reaction was carried out according to the method of Example (1 1 j) 172 mg of the title compound was obtained as a white solid. NMR ^ CDC13) δρριη: 1.2K3Η, t, J = 7.3 Hz), 1.38 (6H, bs), 1.64-1. 76 (4H, m), 2.05 (6H, br), 2.24 (1H, br), 3.45-3.54 (2H, m), 3.70 (6H, t, J = 8.1Hz), 3.82 (2H, i, J = 5.9Hz), 3.89 (3H, s), 3.90-3.96 (2H, m), 3.99 (3H, s), 6.29 (1H, s), 6.58-6. 67 (1H, m), 6.80 (1H, bs), 6.81-6.96 (4H, m), 7.03 (1H, d, J = 8.8Hz ), 7.83 (1H, s), 8.20 (1H, d, J = 8.8Hz).

Melting point: 1 3 2-1 3 5 ° C Example 8 0 Bromide 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine 1- ( 3,4-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] heptylb-methylpiperidine (exemplified compound number: 2-7 4 8) will 7-(7 -bromoheptyloxy) -1-(3,4-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylate obtained in Example (7 8 f) The acid N- (3,5-difluorophenyl) -N-acetamidine 193 mg and 1-methylpiperidine 1 m 1 were reacted according to the method of Example (1 1 j) to obtain the title compound. 1 7 3 mg ο NMR. (CDC13) δρριη: 1.20 (3H, t, .I = 7.3Hz), 1.40 (6H, bs), 1.65-1.95 (10H, m), 3.3K3H, s) , 3.62-3.77 (6H, m), 3.82 (2H, t, J = 6.6Hz), 200300349 3.89 (3H, s), 3.89-3 · 96 (2H, m), 3.99 (3Η, s), 6.28 (1Η, d, J = 2.2Hz), 6.62 (1Η, tt, J = 2.2, 8.8Hz)? 6.79 (1H, d, J = 2.2Hz), 6.83 (2H, dd, J- 2.2, 8.1Hz), 6.89 (1H, dd, J = 2.2, 8.8Hz), 6.920H, dd, J = 2.2, 8.8Hz), 7.03 (1H, d, J = 8.8Hz), 7.83 (1H, s ), 8.20 (1H, d, J = 8.8Hz).

Melting point: 1 2 8-1 3 0 ° C Example 8 1 Desertification 1- {8- [3- [N- (3,5-— ^ winphenyl) -N-ethylaminomethyl] -1 -(3,4-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7-yloxy] octylbupropane-1 (exemplified compound number: 2-8 1 9 ) (81a) 7- (8-Bromooctyloxy) -1- (3,4-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3 1,5-difluorophenyl) -N-acetamidine The 1- (3,4-dimethoxyphenyl) -7-hydroxy-4-oxy-1,4-obtained in Example (7 8 e) Dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 398mg, potassium carbonate 172mg and 1,8-dibromooctane 0.458ml, according to the example (1 1 The reaction was carried out according to the method of i) to obtain 465 mg of the title compound as a transparent oily substance. R. (CDC13) δρρπι: 1.2Κ3Κ, t, J = 7.3Hz), 1. 28-1.46 (8H, in), 1.7K2H, quintet, 1 = 6.6Hz), 1.84C2H, quintet, J = 7.3Hz ), 3.39 (2H, t, J = 6.6Hz), 3.83 (2H, t, 1 = 6.6 Hz), 3.90 (3H, s), 3. 90-3. 97 (2H, m), 3.99 (3H , s), 6.29 (1H, d, J = 2.2Hz), 6.62 (1H, tt, J = 2.2, 8.8Hz), 6.80 (1H, d, J = 2.9Hz), 6.84 (2H, dd, J = 2.2, 8.1 Hz), 6.87-6 · 95 (2Η, m), 7.01 (1Η, d, J = 8.8Hz), 7.86 (1H, s), 8.21 (1Η, d, J = 9.5Hz). (81b) bromide l- [8- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylamidino] -1- (3,4-dimethoxy Phenyl) -4 -oxo-1,4-dihydroquinolin-7-yloxy] amyl] -methyl group 7-(8 -bromooctyloxy) obtained in Example (8 1 a)- 1-(3,4-di- 274- 200300349 methoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 5-difluorophenyl) -N- 195 mg of acetamidine and 1 ml of 1-methylpiperidine were reacted according to the method of Example (1 1 j) to obtain the title compound as a pale yellow solid 188 mg. (CDC13) (5ppm: 1.2K3H , t, J = 7.3Hz), 1.27-1.44 (8H, m), 1.65-1.95 (10H, m), 3.3K3H, s), 3.61-3.77 (6H, m), 3.82 (2H, t, J = 6.6Hz), 3.89 (3H, s) , 3.90-3.97 (2H, m), 3.99 (3H, s), 6.29 (1H, d, J = 2.2Hz), 6.63 (1H, tt, J = 2.2, 8.8Hz), 6.80 (1H, d, J = 2.2Hz), 6.84 (2H, dd, J = 2.2, 8.1Hz), 6.88-6.95 (2H, m), 7.03 (1H, d, J = 8.8Hz), 7.84 (1H, s), 8.20 (1H , d, J = 8.8Hz). Melting point: 1 1 8-1 2 1 ° C Example 8 2 Bromide 1- (7- {l- (3,5-diethylphenyl) -3- [N- (3,5 -difluorophenyl) -N-ethylaminomethylmethyl] -4 -oxo-1,4-dihydroquinoline-7-yloxy} heptyl) -1 -methylpiperidine (exemplified Compound number: 2-8 0 1) (82a) 7 benzyloxy-1- (3,5-diethylphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid methyl ester 714 mg of 2- (4-benzyloxy-2-methoxybenzyl) -3-methylamino-methyl acrylate obtained in Example (44b) and 346 mg of 3,5-diethylaniline obtained in Reference Example 5 And 401 mg of potassium carbonate were reacted according to the method of Example (lie) to obtain 420 mg of the title compound as a yellow solid. NMR (CDC13) δ ΡΡΠΐ: 1.28 (6H, t, J = 7.3Hz), 2.72 (4H, q, J = 7.3Hz), 3.92C3H, s), 4.98 (2H, s), 6.45 (1H, d, J = 2.2Hz), 7.00 (2H, s), 7.07 (1H, dd, J = 2.2, 9.5Hz), 7.23 (1H, s), 7.25-7.35 (5H, m), 8.47 (2H, d, J = 4.4Hz). (82b) 7-Benzyloxy-1- (3,5-diethylphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid-275-200300349 will be implemented 417mg of 7-benzyloxy-1- (3,5-diethylphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid and sodium hydroxide 1 obtained in Example (82a) 20 mg was reacted according to the method of Example (1e) to obtain 354 mg of the title compound as a yellow solid. Li R (CDC13) (5ppm: 1.29 (6H, t, J = 7.8Hz), 2. 68-2. 77 (4H, m), 5.0K2H, s), 6.53-6.57 (lH, m), 6.99 (2H, s), 7.17-7. 22 (1H, m), 7.23-7.28 (4H, m), 7.29-7. 37 (2H, m), 8.47 (1H, d, 1 = 8.8 Hz), 8.72 (1H, s). (82〇7-benzyloxy-1- (3,5-diethylphenyl) -4-oxo-1,4-dihydro_line-3-carboxylic acid N- (3 , 5-difluorophenyl) -N-acetamidinium 7-benzyloxy-1- (3,5-diethylphenyl) -4-oxo-1,4-diamine obtained in Example (82b) 462mg of hydroquinoline-3 carboxylic acid, 0.140ml of chloramidine, catalyst amount N, N-dimethylformamide, N-ethyl-3, 5-difluoroaniline 256 mg, and triethylamine 0.0454 ml, the reaction was carried out according to the method of Example (If), and the title compound was obtained as a yellow oily substance 288 mg. NMR. (CDC13) δρριη: 1.20 (3H, t, J = 7.3Hz), 1.27 ( 6H, t, J = 7.3Hz), 2.70 (4H, q, J = 7.3Hz), 3.93 (2H, q, J = 7.3Hz), 4.94 (2H, s), 6.40 (1H, d, J = 2.2 Hz), 6.63 (1H, tt, J = 2.2, 8.8Hz), 6.84 (2H, dd, J = 2.2, 8.1Hz), 6.93 (2H, s), 6.99 (1H, dd, 1 = 2.2, 9.5Hz ), 7.2K1H, s), 7.24-7.35 (5H, m), 7.86 (1H, s), 8.22 (1H, d, J 9.5Hz) (82d) l- (3,5-diethylphenyl) ) -7-hydroxy-4-oxy -1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 7-benzyloxy-1-obtained in Example (8 2 c) (3, 5 -diethylphenyl) -4 -oxo-1,4-dihydroquinoline-3 -residual acid N- (3,5-diphenylphenyl) -N-acetamidamine 186mg and 10 % Pd-C20.0mg. The reaction was carried out according to the method of Example (lg) to obtain 156 mg of the title compound as a green solid. -276- 200300349 NMR (CDC13) δρριη: 1.18 (3H, t, J = 7.3Hz), 1.24 (6H, t, J = 7.3Hz), 2.67 (4H, q, J = 7.3Hz), 3.90 (2H, q, 1 = 7.3Hz), 6.44 (1H, d, J = 1.5Hz), 6.63 (1H, tt, J = 1.5, 8.8Hz), 6.8K2H, dd, 1 = 1.5, 8.1Hz), 6.9K2H, s), 6.96 (1H, d, J = 8.8Hz), 7.18 (1H, s), 7.81 (1H, s), 8.03 (1H, d, J = 8.8Hz). (826) 7- (7-Br Heptyloxy) -1- (3,5-diethylphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N- Acetylamine was used to obtain the 1- (3,5-diethylphenyl) -7-hydroxy-4-oxy-1,4-dihydroquinoline-3-carboxylic acid N- ( 156 mg of 3, 5-difluorophenyl) -N-acetamidamine, 68.0 mg of potassium carbonate and 0.168 ml of 1,7-dibromoheptane. The reaction was carried out according to the method of Example (1 1 i) to obtain the title compound. Yellow oily substance 1 6 6 mg NMR (CDCI3) δρριη: 1.2K3H, t, 1 = 7.3Hz), 1.28 (6H, t, J = 7.3Hz), 1.30-1.47 (6H, m), 1.66-1.76 (2H, m), 1.83 (2H, quintet, J = 7.3Hz), 2.7K4H, q, J = 7.3Hz), 3.39 (2H, t, J = 7.3Hz), 3.83 (2H, t, J = 7.3 Hz), 3.93 (2H, q, J = 7.3Hz), 6.33 (1H, d, J = 2.2Hz), 6.63 (1H, tt, J = 2.2, 8.8Hz), 6.84 (2H, dd, J = 2 . 2, 8.1Hz), 6.90 (1H, dd, J = 2.2, 8.8Hz), 6.97 (2H, s), 7.21 (1H, s), 7.86 (1H, s), 8.2K1H, d, J = 8.8 Hz) (82f) bromide l- (7- {l- (3,5-diethylphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine 4 -O-l, 4-dihydroquinoline-7-yloxy} heptyl) -1 -methylpiperidine. The 7- (7-bromoheptyloxy) 1- ( 3, 5-diethylphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N -acetamidine 16 6 mg and 1-methylpiperidine 1 m was reacted according to the method of Example (1 1 j) to obtain 157 mg of the title compound as a yellow solid. -277-200300349 NMR (CDC13) δρριη: 1.20 (3H, t, J = 7.3Hz), 1.28 (6H, t, J = 7.3Hz), 1.39 (6H, bs), 1.65-1.95 (10H, m), 2.72 (4H, q, J = 7.3Hz), 3.30 (3H, s), 3.58-3.74 (6H, m), 3.82 (2H, t, J-6.6Hz), 3.92 (2H, q, J = 7.3Hz ), 6.33 (1H, d, 1 = 2.2Hz), 6.64 (1H, tt, 1-2.2, 8.8Hz), 6.84 (2H, dd, J = 2.2, 8.1Hz), 6.90 (1H, dd, J = 2.2, 8.8Hz), 6.96 (2H, s), 7.2K1H, s), 7.83 (1H, s), 8.20 (1H, d, 1 = 8.8 Hz). Example 8 3 4- (7- {1 -(3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -4 -oxo-1,4-dihydroquinoline -7-yloxy} heptyl) 4-methylmorpholin-4 -yl bromide (exemplified compound number: 2-7 5 2) The 7- (7-moheptyloxy) obtained in Example (44g) 1 ^ ethoxyphenyl) _ 4-oxo-1,4-dihydroquinoline · 3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 170mg and N-methylmorpholine 1ml, the reaction was carried out according to the method (1 1 j), 82.0mg of the title compound was obtained as a white solid. Leg (CDC13) δρριη: 1.20 (3H, t, J = 7.3Hz), 1.37-1.47 (6H, m), 1.43 (6H, t, J = 7.3Hz), 1.68-1.80 (4H, m), 3.50 ( 3H, s), 3.54-3. 63 (2H, m), 3. 75-3. 82 (4H, m), 3.85 (2H, t, J = 5.9Hz), 3.9K2H, q, J = 7.3Hz ), 3.95-4.09 (8H, m), 6. 38-6.44 (3H, m), 6.59C1H, t, J = 2.2Hz), 6.63 (1H, tt, J = 2.2, 8.8Hz), 6.83 (2H , dd, 1 = 2.2, 8.1Hz), 6.92 (1H, dd, 1 = 2.2, 8.8Hz), 7.79 (1H, s), 8.19 (1H, d, J = 9.5Hz). Example 8 4 1_ ( 7_ {1 · (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -4 -oxy-1,4-di Hydroquinoline-7-yloxy 丨 heptyl) -1,4-dimethylpiperazine-: 1-yl bromide (exemplified compound number: 2-8 6 9) 7 obtained in Example (4 4 g) -(7 -Bromoheptyloxy) -1-(3,5-diethyl • 278- 200300349 oxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N_ (3,5 -Difluorophenyl) -N-acetamidine 168 mg and N, N'-dimethylpiperidine 1 m1. The reaction was carried out according to the method of Example (1 1 j) to obtain the title compound as a white solid. 1 6 3 mg NMR (CDC13) δρριη: 1.20 (3H, t, J = 6.8Hz), 1.41 (6H, bs), 1.43 (6H, t, J = 6.8Hz), 1.6 8-1.77 (4H, m), 2.39 (3H, s), 2.70-2.82 (4H, m), 3.40 (3H, s), 3.49-3.57 (2H, m), 3.71-3.78 (4H, m), 3.85 (2H, t, J = 6.8Hz), 3.92 (2H, q, J = 6.8Hz), 4.03 (4H, q, J = 6.8Hz), 6.38-6.44 (3H, m), 6.60 (1H, t , J = 2.0Hz), 6.63 (1H, tt, 1 = 2.0, 8.8Hz), 6.83 (2H, dd, J = 2.0, 7.3Hz), 6.90 (1H, dd, J = 2.0, 8.8Hz), 7.82 (1H, s), 8.20 (1H, d, J = 8.8Hz). Example 8 5 4- (8- {1- (3,5-diethoxyphenyl) -3- [1 ^ (3, 5-difluorophenyl) -1 ethylaminomethylmethyl] -4 -oxo-1,4-dihydroquinoline-7 -yloxy} octyl) -4 -morpholine-4-yl bromide ( Exemplary compound number: 2-8 2 2) The 7-(8-bromooctyloxy) -1-(3,5-diethoxyphenyl) -4 -oxy-1 obtained in Example (4 5 a) , 4-Dihydroquinoline-3 -carboxylic acid N- (3, 5-difluorophenyl) -N-acetamidine 1 72 mg and 1-methylmorpholine 1 m. Examples (1 1 j ), And the title compound was obtained as a yellow solid (128 mg). NMR (CDC13) δρριη: 1.20 (3H, t, J = 7.3Hz), 1.27-1.46 (8H, m), 1.43 (6H, t, J = 7.3Hz), 1.66-1.82 (4H, m), 3.50 ( 3H, s), 3.54-3.62 (2H, m), 3.73-3. 83 (4H, m), 3.86 (2H, t, 1 = 6.6Hz), 3.9K2H, q, J-7.3Hz), 3.95-4.10 (8H, m), 6.38-6.44 (3H, m), 6.59 (1H, t, J = 2.2Hz), 6.63 (1H, tt, J = 2.2, 8.8Hz), 6.83 (2H, dd, J = 2.2, 7.3Hz), 6.92 (1H, dd, J = 2.2, 8.8Hz), 7.80 (1H, s), 8.19 (1H, d, J = 9.5Hz). Example 8 6-279- 200300349 1- (8- {1- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -1 ethylaminomethylmethyl] -4 -oxy-1 , 4-dihydroquinoline-7-yloxy} octyl) -1,4-dimethylpiperazine-1-yl bromide (exemplified compound number: 2-8 6 5) The compound obtained in Example (45a) 7- (8-Bromoepoxy) -1- (3,5-monoethoxyphenyl) -4-oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3, 5-di Fluorophenyl) -N-acetamidine 174 mg and N, N'-dimethylpiperidine 1 m 1 were reacted according to the method of Example (1 1 j) to obtain the title compound as a white solid 1 8 7 mg 〇 (CDei3) (5ppm: 1.20 (3H, t, J = 6.8Hz), 1.28-1.46 (8H, m), 1.43 (6H, t, J = 6.8Hz), 1.66-1.80 (4H, m) , 2.39 (3H, s), 2.70-2.82 (4H, m), 3.42 (3H, s), 3.50-3.58 (2H, m), 3. 71-3. 80 (4H, m), 3.85 (2H? t, J = 6.8 Hz), 3.92 (2H, q, J = 6.8Hz), 4.03 (4H, q, J = 6.8Hz), 6.38-6.44 (3H, m), 6.59 (1H, t, J = 2.2Hz), 6.63 ( 1H, tt, J = 2.2, 8.8Hz), 6.83 (2H, d, J = 6.8Hz), 6.90 (1H, dd, J = 2, 9, 8. 8Hz), 7.82 (1H, s), 8.20 ( 1H, d, J = 8.8Hz). Example 8 7 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -l- ( 3,5 -xylyl) -4 -oxo-1,4-dihydroquinolin-7-yloxy] heptyl} -1-mepidol (Exemplary compound number: 2-8 0 0) (87a ) 7-benzyloxy-1- (3,5-xylyl) -4-oxo-1,4-dihydroquinoline-3-, methyl carboxylate The 2- (2) obtained in Example (44b) 4-benzyloxy-2-methoxymethoxy) 3 -dimethylamino-methyl acrylate 2.1 1 g, 3, 5-xylylamine 8 3 1 mg and potassium carbonate 1. 18 g The reaction was carried out according to the method of Example (1 1 e) to obtain 2.15 g of the title compound as a pale yellow solid. -280- 200300349 NMR (CDC13) (5ppm: 2.40 (6H, s), 3.91 (3H, s), 5.00 (2H, s), 6.43 (1H, d, J = 2.9Hz), 6.96 (2H, s) , 7.07 (1H, dd, J = 2.2, 9.5Hz), 7.20 (1H, s), 7.27-7.38 (5H, m), 8.44 (1H, s), 8.47 (1H, d, J = 9.5Hz). (87b) 7-Benzyloxy-1- (3,5-xylyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid. 7- Benzyloxy-1-(3; 5-xylyl) -4 -oxo-1, 4 -dihydroquinoline-3 -carboxylic acid methyl ester 2. 15 g and sodium hydroxide 600 mg, according to the examples (The reaction was carried out in the method of 10 to obtain 2.15 g of the title compound as a pale orange solid. RCD. (CDCI3) (5ppm: 2.4K6H, s), 5.03 (2H, s), 6.55 (1H, d, J = 2.2Hz), 6.95 (2H, s), 7.20 (1H, dd, J = 2.2, 8.8Hz), 7.24 (1H, s), 7.26-7.30 (2H, m), 7.32-7.38 (3H , m), 8.46 (1H, d, J = 8.8Hz), 8.69 (1H, s). (87c) 7-benzyloxy-1- (3, 5-xylyl) -4-oxo-1, 4-Gas D-Querin-3- Junic acid N- (3,5-_Dynyl) -N-amine acetate The 7-benzyloxy-1- (3,5- Monomethylbenzyl) 2.08 g of 4-oxy-1,4-dihydroquinoline-3-carboxylic acid, 0.906 ml of chloramidine, catalyst amount 1 ^, 1 dimethylformamide, ^ Ethyl-3,5-difluoroaniline 1.64§ and triethylamine 2.90 m 1. The reaction was carried out according to the method of Example (1 f) to obtain the title compound as a pale yellow foamy substance 2. 4 0 g. Li R. (CDC13) δρριη: 1.20 (3H, t, J = 7.3Hz), 2.39 (6H, s), 3.92 (2H, q5 J = 7.3Hz), 4.96 (2H, s), 6.39 (1H , d, J = 2.2Hz), 6.63 (1H, tt, J = 2.2, 8.8Hz), 6.83 (2H, dd, J = 2.2, 8.1Hz), 6.89 (2H, s), 6.98 (1H, dd, J = 2.2, 9.5Hz), 7.17 (1H, s), 7.26-7.36 (5H, m), 7.83 (1H, s), 8.22 (1H, d, J = 9.5Hz). (8 7 d) 1- (3,5 -Xylyl) -7 -hydroxy-4 -oxy-1, 4 -dihydroquinoline-281- 200300349 -3 -carboxylic acid N- (3,5-difluorophenyl) -N- The 7-benzyloxy-1-(3,5-xylyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -acetamidine 2.40 g and 10% Pd-C500 mg were reacted according to the method of Example (lg) to obtain 2.00 g of the title compound as a pale green solid. NMR (CDC13) δρρπι: 1.17 (3H, t, J = 6.6Hz), 2.34 (6Η, s), 3.89 (2H, q, J-6.6Hz), 6.45 (1H, s), 6.63 (1H, t, J = 8.1Hz), 6.81 (2H, d, J = 6.6Hz), 6.85 (2H, s), 6.94 (1H, d, J = 8.8Hz), 7.12 (1H, s), 7.78 (1H, s) , 7.98 (1H, d, J = 8.8Hz). (87 ^) 7- (7-bromoheptyloxy) -1- (3,5-xylyl) -4-oxo-1,4-dihydro Quinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N acetamidine The 1- (3,5-xylyl) -7-hydroxy- obtained in Example (87d) 4-Oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 500 mg, potassium carbonate 231 mg, and 1,7-dibromoheptane 0.572 ml, the reaction was carried out according to the method of Example (1 1 i), to obtain 560 mg of the title compound as a transparent oily substance. R. (CDC13) δρρπι: 1.20 (3H, t, J = 7.3Hz), 1. 30-1.49 (6H, m), 1.64-1.76 (2H, m), 1.84 (2H, quintet, J = 6.6Hz ), 2.4K6H, s), 3.30 (2H, t, J = 6.6Hz), 3.85 (2H, t, J = 6.6Hz), 3.93 (2H, q, J = 7.3Hz), 6.33 (1H, d5 J = 2.2Hz), 6.63 (1H, tt, J = 2.2, 8.8Hz), 6.83 (2H, dd, J-2.2, 8.1Hz), 6.90 (1H, dd, J-2.2, 8.8Hz), 6.94 (2H , s), 7.17 (1H, s), 7.83 (1H, s), 8.2K1H, d, J = 8.8Hz). (87f) Brominated l- {7- [3- [N- (3,5- Difluorophenyl) -N-ethylaminomethylmethyl] -1- (3,5 -xylyloxy-l, 4-dihydroquinolin-7-yloxy] heptyl 丨 -1-methylpiperyl The 7- (7-bromoheptyloxy) -1-(3,5 -dimethyl) obtained in Example (8 7 e)

Phenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-282-200300349 Acetamide 2 0 0 mg and 1 -formyl Piperidine 1 m 1 was reacted according to the method of Example f 1 1 j) to obtain 200 mg of the title compound as a yellow solid. Li R .. (CDC13) (5ppm: 1.20 (3H, t, J = 7.3Hz), 1.40 (6H, bs), 1.63-1.95 (10H, m), 2.4K6H, s), 3.32 (3H, s) , 3.60-3.76 (6H, m), 3.83 (2H, t, J = 6.6Hz), 3.92 (2H, q, J = 7.3Hz), 6.32 (1H, d, J = 2.2Hz), 6.63 (1H, tt, J = 2.2, 8.8Hz), 6.83 (2H, dd, 1 = 2.2, 8.1Hz), 6.89 (1H, dd, J = 2.2, 8.8Hz), 6.93 (2H, s), 7.18 (1H, s ), 7.8K1H, s), 8.20 (1H, d, J-9.5Hz). Example 8 8 Brominated (3,5-diethoxyphenyl) -3- [1 (3,5-difluorobenzene ) -N-ethylaminomethylmethyl] -4-oxo-1,4-dihydroquinolin-7-ylsulfanyl} heptyl) -4-acyl-1-azobicyclo [2.2 · 2] Octane (Exemplified compound number: 2-8 7 0) (88a) Dimethionine O- {1- (3,5-diethoxyphenyl) -3- [N- (3,5-difluoro Phenyl) -N-ethylaminomethylmethyl] -4-oxo-I, 4-dihydroquinolin-7-yl} ester The 1- (3,5-diethoxybenzene) obtained in Example (44f) ) -7-hydroxy-4 -oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 2.0 0 g, 55% hydrogenation Sodium 2 5 7 mg and N, N-dimethyl thiamine formamidine chloride 9 7 2 mg were reacted according to the method of Example (2 4 a) to obtain the title compound as a yellow foamy substance 2.3 3 g_R (CDC13) (5ppm: 1.20 (3H, t, J = 7.3Hz), 1.42 (6H, t, J = 7.3Hz), 3.29 (3H, s), 3.4K3H, s), 3.92 (2H, q, J-7.3Hz), 4.03 (4H, q, J = 7.3Hz), 6.49 (2H, d, J-2.2Hz), 6.59 (1H, t, J = 2.2Hz), 6.66 (1H, tt, J = 2.2, 8.8Hz), 6.80 (1H, d, J = 2.2Hz), 6.85 (2H, dd, J = 2.2, 8.1Hz), 7.05 (1H, dd, J = 2.2, 8.8Hz), 7.94 (1H, s), 8.3K1H, d, 1 = 8.8Hz). 200300349 (88b) Dimethionine S- {l- (3,5-diethoxyphenyl) -3- [N- (3,5- Difluorophenyl) -N-ethylaminomethylmethyl] -4-oxo-1,4-dihydroquinolin-7-yl} ester The dimethyl thiamine formic acid obtained in Example (8 8 a) {1-(3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -4-oxo-1,4-dihydro Quinoline-7-yl} ester 2.23§ was reacted according to the method of Example (2413) to obtain the title compound as a pale orange solid 1.95 g. Rei R. (CDC13) (5ppm: 1.2K3H, t, 1 = 7.3 Hz), 1.43 (6H, t, J = 7.3Hz), 2.99 (3H, br), 3.04 (3H, br), 3.92 (2H , q, J = 7.3Hz), 3. 99-4. 08 (4H, m), 6.48C2H, d, J = 2.2Hz), 6.59 (1H, t, 1 = 2.2Hz), 6.64 (1H, tt , J = 2.2, 8.8Hz), 6.83 (2H, dd, J = 2.2, 8.1Hz), 7.25 (1H, s), 7.41 (1H, dd, 1 = 1.5, 8.1Hz), 7.95 (1H, s) , 8.27 (1H, s) · (88c) l- (3,5-diethoxyphenyl) -7-hydrothio-4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 5 -Difluorophenyl) -N-acetamidine The dimethyl thiaminecarboxylic acid S-{1- (3,5-diethoxyphenyl) -3- obtained in Example (8 8 b) [N- (3,5-difluorophenyl) -ethylaminomethyl] 4-oxo-1, 4-dihydroquinolin-7-yl} ester 1.20 g and sodium hydroxide 9 7.0 mg, which was reacted according to the method of Example (2 4 c) to obtain 1.06 g of the title compound as a pale yellow solid. NMR (CDC13) δ ppm: 1.20 (3H, t, J = 7.3Hz), 1.44 (6H, t, J = 7.3Hz), 3.92 (2H, q, 1-7.3Hz), 4.04 (4H, q, J = 7.3Hz), 6.4K2H, d, J = 2.2Hz), 6.60 (1H, t, J = 2.2Hz), 6.62 (1H, tt, J = 2.2, 9.5Hz), 6.82 (2H, dd, J = 2.2, 8.1Hz), 6.86 (1H, d, J = 2.2Hz), 7.14 (1H, dd, J = 2.2, 8.8Hz), 7.84 (1H, s), 8.12 (1H, d, J = 8.8Hz) (88 (1) 7- (7-bromoheptylsulfanyl) -1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N -(3,5-difluorophenyl) -N-acetamidamine- 284-200300349 The 1- (3,5-diethoxyphenyl) -7-hydrothio group obtained in Example (8 8 c) 1.06-g of 4-4-oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamide, 419 mg of potassium carbonate and 1,7-dibromoheptan The alkane 1.04m was reacted according to the method of Example (lli) to obtain 1.10 g of the title compound as a white solid. R, (CDC13) δ ppm: 1.21 (3H, t, J = 7.3 Hz), 1 25-1.45 (6H, m), 1.44 (6H, t, J = 7.3Hz), 1.60C2H, quintet, J-7.3Hz), 1.83 (2H, quintet, J-7.3Hz), 2.83 (2H, t , J = 7.3Hz), 3.39 (2H, t, J = 7.3Hz), 3.92 (2H, q, J-7.3Hz), 4.04 (4H, q, J = 7.3 Hz), 6.44 (2H, d, J = 2.2Hz), 6 .60 (1H, t, J = 2.2Hz), 6.63 (1H, tt, 1 = 2.2, 8.8Hz), _ 6.80-6.86 (3H, m), 7.17 (1H, dd, J = 2.2, 8.8Hz) , 7.86 (1H, s), 8.15 (1H, d, b 8.1Hz), (88e) bromide l- (7- {l- (3,5-diethoxyphenyl) -3- [N- ( 3,5-difluorophenyl) -N-ethylamine formamidine 4-oxo-1,4-dihydroquinolin-7-ylsulfanylbuheptyl) -4 -acyl-1 -azobicyclo [ 2 · 2.2] Xin Yuan will use the 7- (7-bromoheptylsulfanyl) -1-(3,5-diethoxyphenyl) -4 -oxy-1,4-obtained in Example (8 8 d) Dihydroquinoline-3 -carboxylic acid N- (3, 5-difluorophenyl) -N-acetamidine 169mg and 1,4-diazinebicyclo [2 · 2 · 2] octaneru 33.1 mg, according to The reaction of Example (11j) was performed to obtain 162 mg of the title compound as a white solid. R / (CDC13) (5ppm: 1.20 (3H, t, J = 7.3Hz), 1.33 (6H, bs), 1.44 (6H, t, 1 = 7.3Hz), 1.57-1.75 (4H, m), 2.86 C2H, t, J = 7.3Hz), 3.25 (6H, t, J = 7.3Hz), 3.49-3.57 (2H, m), 3.64 (6H, t, 1 = 7.3Hz), 3.9K2H, q, J- 7.3Hz), 4.04 (4H, q, J = 7.3Hz), 6.4K2H, d, J = 2.2Hz), 6.58-6.67 (2H, m), 6.82 (2H, dd, J-2.2, 8.1Hz), 6.87 (1H, s), 7.19 (1H, dd, J = 2.2, 9.5Hz), 7.82 (1H, s) 5 8.16 (1H, d, J-9.5Hz). Melting point: 1 1 5 t ~-285- 200300349 Example 8 9 1- (7- {1- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminemethylbromide ] -4 -oxo-1,4-dihydroquinoline-7-ylsulfanyl} heptyl) -1-piperidine (exemplified compound number: 2-8 5 4); Example (8 8 d The obtained 7- (7-bromoheptylsulfanyl) -1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3 1,5-difluorophenyl) -N-acetamidine 175 mg and 1-methylpiperidine 1 ml 1, the reaction was carried out according to the method of Example (1 1 j), and 162 mg of the title compound was obtained as a yellow solid. NMR (CDC13) (5ppm: 1.20 (3H, t, J = 7.3Hz), 1.37 (6H, bs), 1.44 (6H, t, J = 7.3Hz), 1.55-1. 97 (10H, m) , 2. 86 (2H, t, J = 7.3Hz), 3.32 (3H, s), 3. 60-3. 78 (6H, m), 3.92 (2H, q, J = 7.3Hz), 4.04 (4H , q, J = 7.3 Hz), 6.42 (2H, d, J = 2.2Hz), 6.60 (1H, t, J = 2.2Hz), 6.64 (1H, tt, J = 2.2, 8.8Hz), 6.82 (2H, dd, J = 2.2, 7.3Hz), 6.86 (1H, d, J = 1.5Hz), 7.18 (1H, dd, J = 1.5, 8.8Hz), 7.84 (1H, s), 8 16 (lH, 'd, J = 8.8Hz). Example 9 0 4- (7- {l- (3,5-diethoxyphenyl) -3- [1 (3,5-difluorobenzene )-. Ethylaminomethyl] -4 -oxo-1,4-dihydroquinolin-7-ylsulfanyl} heptyl) __ 4-morpholine-4 -yl bromide (exemplified compound number: 2- 8 5 5) The 7-(7-bromoheptylsulfanyl) -1-(3,5-diethoxyphenyl) -4 -oxy-1,4-dihydro obtained in Example (8 8 d) Quinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 185 mg and N-methylmorpholine were reacted according to the method of Example (1 1 j). There was obtained 6 8 · 9 mg of the title compound as a pale yellow solid. Brain 1 (CDCI3) δ ppm: 1.20 (3H, t, J = 6.8Hz), 1.36 (6H, bs), 1.43 (6H, t, J = 6.8Hz), 1.56-1.80 (4H, m), 2.87 ( 2H, t, J = 6.8Hz), 3.5K3H, s), 3. 55-3. 63 (2H, m), 3. 76-3. 84 (4H, m), 3.91. (2H, q, J = 6.8Hz), 3.95-4.09 (8H, m), 6.41 (2H, d, 200300349 J = 2.0Hz), 6.60 (1H, t, J-2.0Hz), 6.64 (1H, tt, J-2.0 , 8.0Hz), 6.82 (2H, dd, J = 2.0, 7.3Hz), 6.87 (1H, s), 7.20 (1H, dd, J = 2.0, 8.0Hz), 7.82 (1H, s), 8.15 (1H , d, J = 7.8Hz). Example 9 1 l- (7- {l- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N -Ethylaminomethylammonyl] oxy-1,4-dihydroxanthenyl-7-ylsulfanyl-1-heptyl) * 1, 4-dimethylpiperazine-1 -yl bromide (exemplified compound number: 2- 8 5 6) The 7-(7-bromoheptylsulfanyl) -1-(3,5-diethoxyphenyl) -4 -oxo-1,4 -dihydro obtained in Example (8 8 d) Quinoline-3 -carboxylic acid N · (3,5-difluorophenyl) -acetamidine 177mg and N, N'-dimethylpipeline 1ml, the reaction was carried out according to the method of Example (1 1 j), but Obtained the title compound as a pale yellow solid 1 31 mg 〇MR (CDCl3) 6ppm: 1.20 (3H, t, J = 7.3Hz), 1.36 (6H, bs), 1.44 (6H, t, J = 7.3Hz), 1.55 -1. 65 (2H, m), 1. 69-1. 80 (2H, m), 2.39 (3H, s), 2. 70-2. 83 (4H, in), 2.86 (2H, t, J = 7.3Hz) , 3.40 (3H, s), 3. 50-3. 59 (2H, m), 3. 68 ~ 3.80 (4H, m), 3.9K2H, q, J = 7.3Hz), 4.04 (4H, q, 1 = 7.3Hz), 6.42 (2H, d, J = 2.2Hz), 6.60 (1H, t, J = 2.2Hz), 6.64 (1H, it, 1 = 2.2, 8.8Hz), 6.83 (2H, dd, J = 1.5, 8.1Hz), 6.85 (1H, s), 7.19 (1H, dd, J = 1.5, 8.8Hz), 7.83 (1H, s), 8.16 (1H, d, J-8.8Hz). Embodiment 9 2 bromide l- (7- {l- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N -methylamine formamyl] -4- Oxygen 1,4-dihydroquinoline-7-yloxy 丨 heptyl) _ 1-mesotriamidine (example compound number: 2-7 4 9) (92a) 7-benzyloxy-1- ( 3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -amidamine Example (4 4 d ) The obtained 7-benzyloxy-1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid 1.15g, triethylamine 0.872ml -287 -200300349, 0.47 ml of isobutyl chloroformate and 387 mg of 3,5-difluoroaniline. The reaction was carried out according to the method of Example (5 4 c) to obtain 1.36 g of the title compound as a white solid. NMR (CDC13) δ ppm: 1.45 (6H, t, J = 6.6Hz), 3. 96-4. 06 (4H, m), 5.03 (2H, s), 6.45 (2H, d, J = 2.2Hz) , 6.53 (1H, tt, J = 2.2, 8.8Hz), 6.59 (1H, d, J = 2.2Hz), 6.65 (1H, t, J = 2.2Hz), 7. 16 (1H, dd, 1 = 2.2 , 8.8Hz), 7.27-7.41 (7H, m), 8.46 (1H, d, J = 9.5Hz), 8.78 (1H, s). (92b) 7-benzyloxy-1- (3,5 -di Ethoxyphenyl) -4-yl-1,4-dihydroquinoline-3-carboxylic acid N- (3,5difluorophenyl) -N-formamidine The obtained from Example (9 2 a) 7-benzyloxy-1-(3,5-diethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) 醯300 mg of amine, 34.4 mg of 55% sodium hydride and 0.065 ml of iodoformin were reacted according to the method of Example (54 d) to obtain 307 mg of the title compound as a yellow oily substance. NMR: (CDCI3) (5 ppm: J.44 (6H, t, J = 7.3Hz), 3.45 (3H, s), 3. 96-4. 04 (4H, m), 4.98 (2H, s), 6.40 (2H, d, J = 2.2Hz), 6.47 (1H, d, J = 2 * 2Hz), 6.57-6.65 (2H, m), 6.88 (2H, dd, J = 2.2, 8.1Hz), 7.00 ( 1H, dd, 1 = 2.2, 8.8Hz), 7. 27-7. 36 (5H, m), 7.89 (1H, s), 8.23 (1H, d, J-8.8Hz). (92c) l- ( 3,5-diethoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl) -N -formamidine The 7-benzyloxy-1-(3,5-diethoxyphenyl) -4 -oxyl, 4-dihydroquinoline-3 -carboxylic acid N- (3 obtained in Example (9 2 b) , 5-difluorophenyl) · N-formamidine 3 07 mg and 10% P d-C 30 mg, the reaction was carried out according to the method of Example (1 g) to obtain the title compound as a white solid 261 mg-288-200300349 NMR (CDC13) δ ppm: 1.40 (6H, t, 1 = 5.9 Hz), 3.43 (3H, s), 3. 94-4. 04 (4H, m), 6.37 (2H, br ), '6.52-6. 59 (2H, m), 6. 60-6. 67 (1H, m), 6.87 (2H, br), 7.08 (1H, br), 7.82 (1H, br), 8.03 ( 1H, br). (92 (1) 7- (7-bromoheptyloxy) -1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3- Carboxylic acid N- (3,5-difluorophenyl) -N-formamide will be implemented (9 2 c) 1- (3,5-diethoxyphenyl) -7-hydroxy-4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 5 -di Fluorophenyl) -N-formamidine 261mg, potassium carbonate 109mg and 1,7-dibromoheptane 0.27ml, the reaction was carried out according to the method of Example (1 Π) to obtain the title compound as a transparent oily substance 2 3 3 mg. Awake R '(CDCl3) (5ppm: 1.32-1.42 (6Η, m), 1.44 (6Η, t, J = 7.3Hz), 1. 69-1. 80 (2H, m ), 1.85 (2H, quintet, J = 7.3Hz), 3.40 (2H, t, J = 6.6Hz), 3.46 (3H, s), 3.87C2H, t, J = 6.6Hz), 4.04 (4H, q, J = 7.3Hz), 6.42 (1H, d, J = 2.2Hz), 6.47 (2H, d, J = 1.5Hz), 6.58-6.65 (2H, m), 6.86-6.95 (3H, m), 7.91 ( 1H, s), 8.23 (1H, d, J = 8.8Hz). (92e) bromide l- (7- {l- (3,5-diethoxyphenyl) -3- [N- (3, 5-Difluorophenyl) -N-methylaminemethylamidino] -4 -oxo-1,4-dihydroquinoline-7-yloxy} heptyl) -1-piperidine Example (9 2 d) 7- (7-Bromoheptyloxy) -1-(3, 5 -diethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- ( 3,5-difluorophenyl) -N-formamidine 1 54 mg and 1-mperididine 1 m. The method according to Example (1 1 j) was performed. Should be, can be obtained as a pale yellow solid of the title compound 1 2 2 m g. NMR, (CDCI3) (5ppm: 1.40-1.46 (12H, m), 1. 67-1. 95 (10H, m), 3.32 (3H, s), 3.45 (3H, s), 3.65-3. 77 ( 6H, m), 3.86 (2H, t, J = 5.9Hz), 4.04 (4H, q, J = 7.3 Hz), 6.42 (1H, d, J = 1.5Hz), 6.46 (2H, d, J = l. 5Hz), 6.58-6.65 (2H, m), 6.86-6. 94 (3H, m), 7.89 (1H, s), 8.23 (1H, d, J = 8.8Hz). 200300349 Example 9 3 1- (7- {1- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -5- Methoxy-4-oxo-1,4-dihydroquinoline-7-yloxy} heptyl) -1 -mesamin (example compound number: 2-7 5 7) (93 &) 1 ^ -(3,5-Dimethoxyphenyl) acetamide. 3,5-Dimethoxyaniline 11.7 g of pyridine solution 100 m 1 was added under ice cooling and 50 m 1 of acetic anhydride was stirred. 30 minutes. The solvent of the reaction solution was concentrated under reduced pressure, dilute hydrochloric acid was added, and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated sodium bicarbonate water and saturated brine, dried over anhydrous sodium sulfate, and then decompressed. The solvent was concentrated. The obtained solid was washed with hexane and dried to obtain 1 1.4 g of the title compound as a pale yellow solid. NMR. (CDC13) δ ppm: 2.16 (3H, s), 3.77 (6 H, s), 6.23 (1H, s), 6.75 (2H, s), 7.23UH, br), (93b) N- (4-ethylamido-3,5-dimethoxyphenyl) ethyl Ammonium Chloride A solution of 11.4 g of N-(3,5-dimethoxyphenyl) acetamide in 60 ml of carbon disulfide obtained in Example (9 3 a) was added in succession 6.88 g of acetamidine chloride and 2 3.0 g of aluminum chloride. Stir at 50 ° C for 1 hour. The reaction solution was poured into ice water and extracted with dichloromethane. The methylene chloride layer was washed with saturated sodium bicarbonate water and saturated brine, dried over anhydrous sodium sulfate, and then the solvent was concentrated under reduced pressure. The residue was recrystallized from ethyl acetate to obtain 5.90 g of the title compound as a yellow solid. NMR (CDC13) δρρπι: 2. 17 (3H, s), 2.46 (3Η, s), 3.76 (6H, s), 6.79 (2Η, s), 7.45 (1H, br). 200300349 (93 〇) 1- (4-Amino-2,6-dimethoxyphenyl) ethanone The N- (4-ethylamido-3,5-dimethoxyphenyl) ethanyl obtained in Example (93b) Put a solution of 5.90 g of ethanol in 30m of ethanol, force into 15ml of 12NHC1, and heat to reflux for 3 hours. The reaction solution was added with a sodium hydroxide solution under ice-cooling to make it alkaline and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated sodium bicarbonate water and saturated brine, dried over anhydrous sodium sulfate, and the solvent was concentrated under reduced pressure. The obtained solid was washed with diethyl ether to obtain 2.31 g of a pale yellow solid as a standard compound. NMR (CDC13) 5ppm: 2.45 (3H, s), 3.76 (6H, s), 3.87 (2H, br), 5.85 (2H, s). (93d) 1- (4-hydroxy-2,6-dimethyl Oxyphenyl) ethyl ketone 20 ml of an aqueous solution of 2.3-lg of 1- (4-amino-2,6-dimethoxyphenyl) ethyl ketone obtained in Example (9 3c) was added under ice cooling. Slowly add an aqueous solution of osmium sodium nitrate 9 3 6 m 2 m 1. After stirring at 0 ° C for 10 minutes, slowly add 30 mg of copper (1) oxide, warm to room temperature and stir for 3 hours. The mixture was extracted with ethyl acetate, the ethyl acetate layer was washed with water, dried over anhydrous sodium sulfate, and the solvent was concentrated under reduced pressure. The obtained solid was washed with diethyl ether to obtain 2.0 2 g of the title compound as a yellow solid. Round R (CDCl3) 5ppm: 2.47 (3H, s), 3.71 (6Η, s), 6.02 (2H, s). (936) 1- (4-benzyloxy-2,6-dimethoxybenzene Methyl) ethyl ketone 30 ml of an acetone solution of 1.08 g of 1- (4-hydroxy-2,6-dimethoxyphenyl) ethyl ketone obtained in Example (9 3 d) was added 913 mg of carbonic acid and benzyl bromide in this order. 7 9 m 1. Stir at 5 ° C for 3 hours. The solvent of the reaction solution was concentrated under reduced pressure, diluted hydrochloric acid was added, and extracted with ethyl acetate. The ethyl acetate-291- 200300349 ethyl acetate layer was washed with saturated sodium bicarbonate. Water and saturated brine, dried over anhydrous sodium sulfate, and concentrated the solvent under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate / hexane = 1/2) to obtain the title compound as a transparent oil. Substance 1.6 1 g. NMR (CDC13) 6ppm: 2.44 (3H, s), 3.75 (3H, s), 3.76 (3H, s), 5.06 (2H, s), 6.17 (2H, s), 7. 30- 7.45 (5H, m). (93〇3- (4-benzyloxy-2,6-dimethoxyphenyl) -3-oxo-propionic acid ethyl ester The obtained from Example (9 3e) 1-(4-benzyloxy-2,6 -dimethoxyphenyl) ethyl ketone 1. 5 8. G of diethyl carbonate solution 10 m 1, add 5 5% sodium hydride 3 6 1 mg, heat Reflux for 2 hours. Methanol was added under stirring, and the solvent of the reaction solution was concentrated under reduced pressure. Dilute hydrochloric acid was added, followed by extraction with ethyl acetate. The ethyl acetate layer was washed with saturated sodium bicarbonate water and saturated brine, dried over anhydrous sodium sulfate, The solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate / hexane = 1/2) to obtain the title compound as a yellow oily substance (1.98 g). NMR. (CDC13) δ ppm : 1.2K3H, t, J = 6.8Hz), 3. 74-3. 80 (8H, m), 4.14 (2H, q, J-6.8Hz), 5.07 (2H, s), 6. 17 (2H, s), 7.31-7.45 (5H, m). (93g) 2- (4-benzyloxy-2,6-dimethoxybenzylfluorenyl) -3 -dimethylamino-ethyl acrylate. Examples ( 93f) 1.98 g of 3- (4-benzyloxy-2,6-dimethoxyphenyl) 3-oxo-propionic acid ethyl ester and Ν, Ν-dimethylformamide dimethyl acetal The aldehyde 5 m 1 was reacted according to the method of Example (1 1 d) to obtain the title compound as a yellow oily substance 2.20 g. NMR.. (CDC13) δρριπ: 0.92 (3H, t, J = 6.8Hz) , 3. 00-3. 40 (6H, br), 3.72 (6H, s), 3.90 (2H, q, J = 6.8Hz), 5.07 (2H, s), 6.17 (2H, s), 7. 26 -7. 45 (5H, m), 7.74 (1H, br).-292-200300349 (93h) 7-benzyloxy-l- (3,5-diethoxyphenyl) -5-methoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid ethyl ester will be implemented Example (93g) 490 mg of 2- (4-benzyloxy-2,6-dimethoxybenzylfluorenyl) -3 -dimethylamino-ethyl acrylate, 3,5-diethyl obtained in Reference Example 6 Oxyaniline 258% and potassium carbonate 246.1% were reacted in accordance with the method of Example (116) to obtain the title compound as a pale yellow solid, 409 mg of R, (CDC13) δρρπι: 1.36 (3H, t, J = 6.8Hz), 1.44 (6H, t, J = 6.8Hz), 3.93 (3H, s), 3.95-4.05 (4H, m), 4.34 (2H, q, J = 6.8Hz), 4.93 (2H, s ), 6.00 (1H, d, J = 2.0Hz), 6.40 (2H, d, J = 2.0Hz), 6.43 (1H, d, J = 2.0Hz), 6.60 (1H, bs), 7.23-7. 36 (5H, m), 8.2K1H, s). (93i) 7-benzyloxy-l- (3,5-diethoxyphenyl) -5-methoxy_4-oxy-1,4-di Hydroquinoline-3 -carboxylic acid The 7-benzyloxy-1-(3,5-diethoxyphenyl) -5 -methoxy-4-oxo-1 obtained in Example (9 3 h), 409 mg of ethyl 4-dihydroquinoline-3-carboxylic acid and 4 7.0 mg of sodium hydroxide were reacted according to the method of Example (1e) to obtain 339 mg of the title compound as a pale yellow solid. NMR. (CDC13) (5ppm: 1.45 (6H, t, 1 = 7.3 Hz), 3. 95-4. 05 (7H, m), 4. 97 (2H, s) 3 6.14C1H, d, J- 2.2Hz), 6.39 (2H, d, J = 2.2Hz), 6.55 (1H, d, J = 2.2Hz), 6.64 (1H, t, J-2.2Hz), 7.21-7.25 (2H, m), 7.30 -7.37 (3H, m), 8.6K1H, s). (93j) 7-benzyloxy-1- (3,5-diethoxyphenyl) -5-methoxy-4-oxo-1,4 -Dihydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl) fluorenamine The 7 -benzyloxy-1-(3, 5 -diethoxy) obtained in Example (9 3 i) Phenyl) -5-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 339mg, triethylamine-293-200300349 0.241m isobutyl chloroformate 0.135ml and 3,5 -107 mg of difluoroaniline, reacted according to the method of Example (54c) to obtain 325 mg of the title compound as a pale yellow solid. Li R (CDC13) (5 ppm: 1.45 (6H, t, 1 = 7.3Hz), 3. 93-4. 05 (7H, m), 4.96 (2H, s), 6.12 (1H, d, 1 = 2.2 Hz), 6.42 (2H, d, J = 2.2Hz), 6.47-6.55 (2H, m), 6.64 (1H, t, J = 2.2Hz), 7.21-7.27 (2H, m), 7.30-7.41 (5H , m), 8.67 (1H, s). (931〇7-benzyloxy-1- (3,5-diethoxyphenyl) -5-methoxy-4-oxo-1,4-dihydro Quinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 7-benzyloxy-1-(3,5-diethyl) obtained in Example (9 3 j) (Oxyphenyl) -5-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 1 ^-(3,5-difluorophenyl) -amidamine 325 mg, 55% sodium hydride 35.4 mg and 0.130 ml of iodoethane were reacted according to the method of Example (54d) to obtain 210mg of the title compound as a light yellow solid. R. (CDCl3) 5ppm: 1.19 (3Η, t, J = 7.3Hz), 1.43. (6Η, t, J = 7.3Hz), 3. 84-3.91 (5H, m), 3.93-4.04 (4H, m), 4.90 (2H, s), 5.95 (1H, d, J = 1.5Hz), 6.30 (2H, d, J = 1.5Hz), 6.36 (1H, d, J-2.2Hz), 6.58 (1H, t, J = 2.2Hz), 6.65 (1H, tt, J = 2.2, 8.8Hz), 6.87 (2H, dd, 1 = 2.2, 7.3Hz), 7.22-7.25 (2H, m), 7. 29-7. 36 (3H, m), 7.54 (1H, s) (931) 1- (3,5-diethoxyphenyl) -7- 5-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine Example (9 3k) The obtained 7-benzyloxy-1- (3,5-diethoxyphenyl) -5 -methoxy-4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 5-Difluorophenyl) -N-acetamidamine 200 mg and 10% P d-C 20 mg. The reaction was carried out according to the method of Example (1 g) to obtain the title compound as a pale yellow solid 1 90 mg-294-200300349 NMR (CDC13) (5ppm: Ί. 16 (3H, t, J = 7.3Hz), 1.4K6H, t, J = 7.3Hz), 3.64 (3H, br), 3.80-4.00 ( 6H, m), 5.9K1H, d, J = 1.5Hz), 6.15 (1H, d, J = 1.5Hz), 6.3K2H, d, J = 1.5Hz), 6.51 (1H, t, J = 2.2Hz) , 6.58 ~ 6.66 (1H, m), 6.85 (2H, d, J-6.6Hz), 7.47 (1H, s). (93m) 7- (7-bromoheptyloxy) -1- (3,5- Diethoxyphenyl) -5 -methoxy-4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine Example 1-(3,5 -diethoxyphenyl) -7-hydroxy-5 -methoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N obtained from (9 3 1) -(3, 5-difluorophenyl) -N-acetamidamine 170 mg, potassium carbonate 65.4 mg, and 1,7-dibromoheptane 0.2 1 6 m 1, according to the examples 1 1 i) of the method of the reaction, to give a pale yellow solid 176mg of the title compound. NMR (CDCI3) (5ppm: 1.19 (3H, t, J = 7.3Hz), 1. 30-1.47 (6H, m), 1.43 (6H, t, J = 7.3Hz), 1.70 (2H, quintet, J = 7.3Hz), 1.85 (2H, quintet, J = 7.3Hz), 3.40 (2H, t, J = 6.6Hz), 3.78 (2H, t, J = 6.6Hz), 3.84-3.91 (5H, m), 4.02 (4H, q, J = 7.3Hz), 5.9K1H, d, 1 = 2.2Hz), 6.29 (1H, d, J = 2.2Hz), 6.37 (2H, d, J = 2.2Hz), 6.57 (1H, t, J = 2.2Hz), 6.65 (1H, tt, J = 2.2, 8.8Hz), 6.88 (2H, dd, J = 2.2, 7.3Hz), 7.55 (1H, s). (93n) bromination l- (7- {l- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminemethylmethyl] -5 -methoxy 4-oxo-l, 4-dihydroquinoline-7-yloxy} heptyl) -1-formamidine than red 7- (7-bromoheptyloxy) obtained in Example (9 3 m) -1-(3, 5 -diethoxyphenyl) _5_methoxy-4-oxo- I, 4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl)- 170 mg of N-acetoxamine and 1 ml of mepyridine were reacted according to the method of Example (1 1 j) to obtain the title compound as a pale solid-295-200300349 138 mg as a yellow solid.

Ml-(CDC13) δρριη: 1.18 (3H, t, J = 7.3Hz), 1.39 (6H, bs), 1.42 (6H, t, J = 7.3Hz), 1.65-1.95 (10H, m), 3.30 (3H , s), 3.59-3.74 (6H, m), 3.78 (2H, t, J = 6.6Hz), 3.87C2H, q, J = 7.3Hz), 3.90 (3H, s), 4.02 (4H, q, J = 7.3Hz), 5.9K1H, d, J = 2.2Hz), 6.3K1H, d, J = 1.5Hz), 6.36 (2H, d, J = 1.5Hz), 6.57 (1H, t, J = 2.2Hz) , 6.66 (1H, tt, J = 2.2, 8.8Hz), 6.87 (2H, dd, J = 2.2, 7.3Hz), 7.51 (1H, s). Example 94 3- (4- {1- (3, 5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine 4-oxo-1,4-dihydroquinoline-7-yloxy Butylamino) -1 -methyl-1 -azobicyclo [2 · 2 · 2] Octanemethanesulfonamide (exemplified compound number: 2-8 6 0) (94a) 4- {l- ( 3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine 4-oxo-1,4-dihydroquinoline-7- Methyloxy} methyl butyrate The 1- (3,5-diethoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3 -carboxylate obtained in Example (44f) Acid N- (3,5-difluorophenyl) -N-acetamidine. Amine 506mg N, N-dimethylformamide solution 5ml, potassium carbonate 206mg and 4-bromobutyric acid methyl ester 540mg , Stir at 60 ° C for 3 Time. The reaction solution was added with dilute hydrochloric acid and extracted with ether. The ether layer was washed with saturated sodium bicarbonate water and saturated brine, dried over anhydrous sodium sulfate, and then the solvent was concentrated under reduced pressure. The obtained solid was washed with diisopropyl ether to obtain 505 mg of the title compound as a white solid. NMR, (CDC13) δρρπι: 1.20 (3H, t, J = 7.3Hz), 1.44 (6H, t, 1-7.3Hz), 2.05 (2H, quintet, J = 6.6Hz), 2.47 (2H, t, J = 6.6Hz), 3.65 (3H, s), 3. 89-3.97 (4H, in), 4.03 (4H, q, J = 7.3Hz), 6.39 (1H, d, J-2.2Hz), 6.43 (2H , d, J = 2.2Hz), 200300349 6.58-6.66 (2H, m), 6.83 (2H, dd, J = 2.2, 8.1Hz), 6.89 (1H, dd, 1 = 2.2, 8.8Hz), 7.84 (1H , s), 8.20 (1H, d, J = 9.5Hz). (94b) 4- {l- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl ) -N-Ethylaminomethsacyl] -4 -oxy-1,4-_ hydrazone -7-yloxy} butanoic acid will be 4-{1-(3, 5 -diethoxyphenyl) -3-[N- (3, 5-difluorophenyl) -N -ethylaminomethylmethyl] -4 -oxo-1,4 -dihydroquinolin-7 -yl 337 mg of methyloxybutyrate and 33.2 mg of sodium hydroxide were reacted in accordance with the method of Example (10) to obtain the title compound as a white solid, 268 mg. · R (CDC13) δρριη: 1.20 (3H, t, J = 6.6Hz), 1.43 (6H, t, J = 6.6Hz), 2.06 (2H, quintet, J = 6.6Hz), 2.52 (2H, t, J = 6.6Hz), 3. 87-3. 97 (4H, m), 4.04 (4H, q, J = 6.6Hz), 6. 38-6. 47 (3H, m), 6. 58-6. 66 (2H, m), 6.80-6.92 (3H , m), 7.86 (1H, s), 8.2 0 (1H, d, J = 8.8Hz). (9 4 c) 7-[3-(N-(1 -acyl-bicyclo [2.2 · 2] octane-3 -yl) aminomethylamidino) -propyl Oxy] -1- (3,5-diethoxyphenyl) -4-oxo-1,4 · dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N- Acetylamine uses the 4- (1-(3,5-diethoxyphenyl))-3- [N- (3,5-difluorophenyl) -N-ethyl obtained in Example (9 4 b). Carboxamidine] -4-oxo-1,4-dihydroquinoline-7-yloxy} 200 ml of N, N-dimethylformamidine solution of 200 mg of butyric acid, triethylamine 0.094 ml, diamine 0.094 ml of phenylphosphonium azide and 8 0.4 mg of 3-aminoquinidine dihydrochloride were stirred at room temperature for 24 hours. The reaction solution was added to water and extracted with dichloromethane. The dichloromethane layer was washed with saturated sodium bicarbonate water and saturated brine, dried over anhydrous sodium sulfate, and then the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: acetone / dichloromethane = 1/2) to obtain the title compound as a transparent oily substance-297-200300349 2 2 5 mg 〇CR (CDC13) (5ppm: 1.2 〇 (3H, t, J = 7.3Hz), 1.41 (6H, t, J = 7.3Hz), 1.43-1.52 (1H3 m), 1. 68-1. 77 (2H, m), 1.93 (2H, quintet , J = 6.6Hz), 2. 00-2.10 (2H, m), 2.2K2H, t, J = 7.3Hz), 2. 52-2. 80 (3H, m), 3. 03-3.12 (1H, m), 3. 23-3. 32 (1H, m), 3.47-3.55 (1H, m), 3.76 (2H, t, J = 6.6Hz), 3.92 (2H, q, J = 7.3Hz), 4.0 K4H, q, J = 7.3Hz), 4.09-4.18 (lH, m), 6.35 (1H, d, J = 2.2Hz), 6.40 (2H, d, J = 2.2Hz), 6.57 (1H, t, J = 2.2Hz), 6.6K1H, tt, J = 2.2, 8.8Hz), 6.79-6.87 (3H, m), 7.8K1H, s), 8.15C1H, d, J = 8.8Hz). (94d) 3 -(4- {1- (3,5-diethoxyphenyl) -3- [1 < [-(3,5-monophenyl) -N_ethylaminomethylmethyl] -4 -oxy- 1,4-dihydroquinoline-7-yloxy} butanylamino) _bumesan-1-azobiscyclo [2 · 2 · 2] Xinyuan mesylate obtained in Example (94c) 7- [3- (N- (Bu-Ya-bicyclo [2 · 2 · 2] Xinyuan-3-yl) aminomethyl) -propoxy]-丨-(3,5_diethoxy (Phenyl) _4_oxy-1,4-dihydroquinoline-3-carboxy 204 mg of N- (3,5-difluorophenyl) acetamide and 95.9 mg of methyl methanesulfonate were reacted according to the method of Example (3b) to obtain the title compound as a white solid 158 mg ° NMR (CDC13) (5ppm: 1.20 (3H, t, J = 7.3Hz), 1.43 (6H, t, J = 7.3Hz), 1.75-1.82 (1H, m), 2. 00 ^ 2.12 (4H, m), 2. 30-2. 40 (2H, in), 2.43 (2H, t, J = 7.3Hz), 2.74 (3H, s), 3.10 (3H, s), 3. 24-3. 44 (3H, m ), 3. 49-3. 57 (1H, m), 3. 87-3. 95 (4H, m), 4.00-4.10 (5H, m), 4.18-4. 27 (1H, in), 4. 35-4.43 (1H, m), 6.30 (1H, d, J = 2.2Hz), 6.42 (2H, d, J = 2.2Hz), 6.59 (1H, t, J = 2.2Hz), 6.63 (1H, tt , J = 2.2, 8.8Hz), 6.82 (2H, dd, 1 = 2.2, 8.1Hz), 6.92 (1H, dd, J = 2.2, 8.8Hz), 7.79 (1H, s), 8.18 (1H, d, J = 8.8Hz), 8.60 (1H, d, J = 6.6Hz). Melting point: 1 2 0-1 2 2 t: Example 9 5-298- 200300349 Bromide 1- (7- {1- (3, 5-diethoxyphenyl) -3- [1 (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -5 -methoxy-4-oxo-1,4-dihydroquine Porphyrin-7-yloxy} heptyl) -4-acyl-1-azobicyclo [2 · 2 · 2] octane (exemplified compound number: 2-7 5 8) Obtained from Example (9 3 m) Of 7-(7 -Bromoheptyloxy) -1 -(3,5-diethoxyphenyl) -5 -methoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N -166 mg of acetamidine and 1,4-diazinebicyclo [2.2.2] octane 27.9. The reaction was carried out according to the method of Example (11 ") to obtain 160 mg of the title compound as a white solid. NMR (CDC13) δρρηι: 1.18 (3H, t, J = 7.3Hz), 1.35 (6H, bs), 1.42 (6H, t, J = 7.3Hz), 1.62-1.79 (4H, m), 3.24 (6H, t, J = 7.3Hz), 3.50-3.57 (2H, m), 3.64 (6H, t, J = 7.3Hz), 3.77 (2H, t, J = 6.6Hz), 3.87 (2H, q, J = 7.3 Hz), 3.90 (3H, s), 4.02 (4H, q, J = 7.3Hz), 5.9K1H, d, J = 2.2Hz), 6.3K1H, d, J = 2.2Hz), 6.34 (2H, d, J = 1.5Hz), 6.57C1H, t, J = 2.2Hz), 6.66 (1H, tt, 1 = 2.2, 8.8Hz), 6.86 (2H, dd, J = 2.2, 8.1Hz), 7.49 (1H, s ).

Melting point: 1 2 7-1 3 0 ° C Example 9 6 1- (8- {1- (3,5-diethoxyphenyl) -3- [1 ^ (3,5-difluorobenzene) bromide } -N -ethylaminomethyl] -5 -methoxy-4 -oxo-1,4-dihydroquinoline-7 -yloxy) octyl) -4 -acyl-1 -azobicyclo [2. 2. 2] octane (exemplified compound number: 2-8 2 7) (96a) 7- (8-bromooctyloxy) -1- (3,5-diethoxyphenyl) -5 -methoxy-4 -Oxygen-1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl) -N -acetamidine 1-(3, 5 -Diethoxyphenyl) -7 -hydroxyl 200 300349 -5 -methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N -340 mg of acetamide, 131 mg of potassium carbonate, and 515 mg of 1,8-dibromooctane. The reaction was carried out according to the method of Example (1 1 i) to obtain 357 mg of the title compound as a white solid. Li R (CDC13) (5ppm: 1.  19 (3H, t, J = 7. 3Hz), 1.  29-1. 42 (8H, m), 1. 43 (6H, t, J = 7. 3Hz)? 1. 69 (2H, quintet, J = 7. 3Hz), 1. 84 (2H, quintet, J = 7. 3Hz), 3. 40 (2H, t, J = 6. 6Hz), 3. 79 (2H, t, J = 6. 6Hz), 3. 84-3. 92 (5H, m), 4. 02 (4H, q, 1 = 7. 3Hz), 5. 92 (1H, d, 1 = 2. 2Hz), 6. 30 (1H, d, J = 2. 2Hz), 6. 38 (2H, d, J-1. 5Hz), 6. 57 (1H, t, J = 2. 2Hz), 6. 65 (1H, tt, J = 2. 2, 8. 8Hz), 6. 88 (2H, dd, 1 = 2. 2, 8. 1Hz), 7. 55 (1H, s).  (96b) 1- (8- {1- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine 5 -Methoxy-4-oxo-1,4-dihydroquinoline-7-yloxy} octyl) -4 -acyl-1 -azobicyclo [2. 2. 2] Octane 7- (8-bromooctyloxy) -1-(3,5-diethoxyphenyl) -5-methoxy-4-oxo-1 obtained in Example (9 6 a) 163 mg of 4,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine and 1,4-diazine bicyclic [2. 2. 2] octane 2 6. 9 mg, was reacted according to the method of Example (1 1 j) to obtain the title compound as a white solid, 168 mg. NMR (CDC13) δρριη: 1. 19 (3H, t, J = 7.  3Hz), 1. 26-1. 40 (8Η, m), 1. 42 (6Η, t, J = 7. 3Hz), 1. 64-1. 78 (4Η, m), 3. 25 (6Η, t, J = 7. 3Hz), 3. 50-3. 55 (2H, m), 3. 65 (6H, t, 1 = 7. 3Hz), 3. 80 (2H, t, J = 6. 6Hz), 3. 87 (2H, q, J = 7. 3Hz), 3. 90 (3H, s), 4. 02 (4H, q, J = 7. 3Hz), 5. 92 (1H, d, J = 2. 2Hz), 6. 31 (1H, d, J = 2. 2Hz), 6. 35 (2H, d, J = 1. . 5Hz), 6. 59 (1H, t, J-2. 2Hz), 6. 66 (1H, tt, J = 2. 2, 8. 8Hz), 6. 86 (2H, dd, J = 2. 2, 8. 1Hz), 7. 49 (1H, s).  Melting point: 1 2 0-1 2 3 t:-300- 200300349 Example 9 7 Bromide 1- (8- {1- (3,5-diethoxyphenyl) -3- [1 (3,5- Difluorophenyl) -N-ethylaminemethylmethyl] -5 -methoxy-4-oxo-1,4-dihydroquinoline-7-yloxy} octyl) -1-methylpiperidine ( Exemplary compound number: 2-8 2 6) The 7-(8-bromooctyloxy) -1-(3,5-diethoxyphenyl) -5 -methoxy group obtained in Example (9 6 a) -176-oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 176mg and 1-formamidine Dml 1ml, according to the examples ( 1 lj) to carry out the reaction to obtain the title compound as a yellow solid 1 0 1 mg NMR (CDC13) δρριη: 1. 19 (3H, t, J = 7. 3Hz), 1.  26-1. 42 (8H, m), 1. 42 (6H, t, J = 7. 3Hz), 1. 64-1. 96 (10H, m), 3. 32 (3H, s), 3. 61-3. 75 (6H, m), 3. 78 (2H, t, J = 6. 6Hz), 3. 87 (2H, q, J = 7. 3Hz), 3. 90 (3H, s), 4. 02 (4H, q, J = 7. 3Hz), 5. 92 (1H, d, J = 2. 2Hz), 6. 31C1H, d, J = 2. 2Hz), 6. 36 (2H, d, J = 2. 2Hz), 6. 57 (1H, t, J = 2. 2Hz), 6. 65 (1H, tt, J = 2. 2, 8. 8Hz), 6. 86 (2H, dd, J = 2. 2, 8. 1Hz), 7. 51 (1H, s).  Example '9 8 3- (3- {1- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine 4 -Oxy-1,4-dihydroquinoline-7-yloxy} propylaminomethyl) -1 -methyl-1 -azobicyclo [2 · 2. 2] Octanemethanesulfonamide (Exemplified compound number: 2-8 5 9) (98a) 7- (3-bromopropoxy) -1- (3,5-diethoxyphenyl) -4 -oxy -1,4-Dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 1- (3,5-diethoxy) obtained in Example (44f) Phenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 400 mg, potassium carbonate 163 mg, and 1 476 mg of 3-dibromopropane was reacted according to the method of Example (1 Π) to obtain the title compound as a white solid-301- 200300349 3 8 6 mg NMR (CDC13) (5 ppm: 1. 21 (3H, t, J = 7. 3Hz), 1. 44 (6H, t, J = 7. 3Hz), 2. 26 (2H, quintet, J = 5. 9Hz), 3. 53 (2H, t, J = 5. 9Hz), 3. 93 (2H, q, J = 7. 3Hz), 4.  00-4.  08 (6H, m), 6. 44 (3H, d, J = 2. 2Hz), 6. 58-6.  66 (2H, m), 6. 84 (2H, dd, J = 2. 2, 8. 1Hz), 6. 9K1H, dd, J = 2. 2, 8. 8Hz), 7. 85 (1H, s), 8. 22 (1H, d, J = 8. 8Hz).  (98b) 7- (3-azido-propoxy) -1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 5-difluorophenyl) -N-acetamidine The 7- (3-bromopropoxy) -1-(3,5-diethoxyphenyl) obtained in Example (9 8 a) -4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 386mg N, N-dimethylformamide solution 4ml Add 120 mg of sodium azide and stir at room temperature for 24 hours. The reaction solution was added with dilute hydrochloric acid and extracted with ethyl acetate. The ethyl acetate was washed with saturated sodium bicarbonate water and saturated brine, dried over anhydrous sodium sulfate, and the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate / hexane = 1/1) to obtain the title compound as a transparent oily substance 3 6 3 m g οR.R.  (CDC13) δρριη: 1. 2Κ3Η, t, J = 7. 3Hz), 1. 44 (6H, t, J = 7. 3Hz), 1. 99 (2H, quintet, 1 = 6.  6Hz), 3. 47 (2H, t, 1 = 6.  6Hz), 3.  88-3.  98 (4H, m), 4. 04 (4H, q, J = 7. 3Hz), 6.  4〇-6.  46 (3H, in), 6.  58-6.  66 (2H, m), 6. 84 (2H, dd, J = 2. 2, 8. 1Hz), 6. 9K1H, dd, J = 2. 2, 9. 5Hz), 7. 84 (1H, s), 8. 21 (1H, d, J = 8. 8Hz).  (98〇) 7- (3-Aminopropoxy)]-(3,5-diethoxyphenylbenzene 4-oxo-1,4-dihydroquinoline-3 -carboxylic acid -Difluorophenyl) -acetamidine 7- (3-azido-propoxy) -1-(3,5-diethoxyphenyl) -4-obtained in Example (9 8 b) Oxy-I, 4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 3 6 3 mg and 10% Pd-C60 mg, according to the example (lg) -302-200300349, the reaction was carried out to obtain the title compound as a white solid, 279 mg ο NMR (CDC13) (5ppm: 1. 17 (3H, t, J = 7. 3Hz), 1. 39 (6H, t, J = 7. 3Hz), 2. 24 (2H, br), 3. 17 (2H, br), 3.  83-4.  04 (8H, m), 6. 28-6.  39 (3H, m), 6. 56 (1H, s), 6. 6K1H,. t, J = 8. 8Hz), 6. 8K2H, d, J = 6. 6Hz), 6. 89 (1H, d, J = 7. 3Hz), 7. 72 (1H, s), 8. 09 (1H, d, J = 8. 8Hz), 8. 36 (2H, br).  (9 8 d) 7-{3-[(1 -azine-bicyclo [2 · 2 · 2] octane-3 -carbonyl) -amino] -propoxy} -l- (3,5 -a ^ Ethoxybenzyl) -4 -oxy-1,4--^ azepine quinine-3_ carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine Example (9 8 c) The obtained 7- (3-aminopropoxy) -1- (3,5-diethoxyphenyl) -4-oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5 -Difluorophenyl) -N-acetamidamine 178 mg, triethylamine 0.1 113 mg of azido diphenylphosphine and 1-acyl-bicyclo [2 · 2 · 2] octane-3-carboxylic acid-hydrochloride 7 2 · 4 mg of 088 m. The title compound was obtained as a white solid 186 mg ° NMR (CDCI3) δρριη: 1. 20 (3H, t, J = 6. 8Hz), 1. 44 (6H, t, J = 6. 8Hz), 1. 26-1.  34 (1H, m), 1. 49-1.  62 (2H, m), 1.  67-1. 75 (1H, m), 1.  86-1.  91 (1H, m), 1. 94 (2H, quintet, J = 6. 8Hz), 2.  27-2.  33 (1H, m), 2.  69-2.  80 (2H, m), 2.  81-2.  99 (3H, m), 3. 28-3. 48 (3H, m), 3. 88-3. 95 (4H, m), 4. 04 (4H, q, J = 6. 8Hz), 6. 39 (1H, d, J = 2. 0Hz), 6. 42 (2H, d, J = 2. 0Hz), 6. 58-6.  66 (2H, m), 6.  81-6.  88 (3H, m), 7. 82 (1H, s), 8. 19 (1H, d, J = 8. 8Hz).  (98e) 3- (3- {1- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N -ethylamine formamidine 4-oxy -1,4-dihydroquinoline-7-yloxy 丨 propylaminemethylmethyl) -1-methyl-1 -azobicyclo [2. 2. 2] Octanemethanesulfonamide The 7-{3-[(1 -acyl-bicyclo [2. 2. 2] Octane-3-200300349 carbonyl) -aminobupropoxy} -l- (3,5-diethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl) -N -acetamidine 16 8 mg and methyl methanesulfonate 79. 0 mg, reacted according to the method of Example (3b) to obtain 124 mg of the title compound as a white solid. Bandit R (CDC13) δρρπι: M9 (3H, t, J = 7. 3Hz), 1. 43 (6H, t, J = 7. 3Hz), 1. 75-1. 87 (1H, m), L91-2. 0K3H, m), 2.  03-2.  14 (1H, m), 2. 25-2.  37 (1H, m), 2.  48-2.  54 (1H, m), 2. 67 (3H, s), 3. 07 (3H, s), 3.  31-3.  49 (6H, m), 3.  69-3.  84 (3H, m), 3. 90 (2H, q, J = 7. 3Hz), 3. 95 (2H, t, 1 = 5. 9Hz), 4. 03 (4H, q, J = 7. 3Hz), 6. 38-6. 42 (3H, m), 6. 59 (1H, t, J = 2. 2Hz), 6. 63 (1H, tt, J = 2. 2, 8. 8Hz), 6. 82 (2H, dd, 1 = 2. 2, 8. 1Hz), 6. 97 (1H, dd, 1 = 2. 2, 8. 8Hz), 7. 77 (1H, s), 8. 18 (1H, d, J = 8. 8Hz), 8. 24 (1H, t, J = 5. 1Hz).  Example 9 9 Brominated 1-{7-[3-(N-(3,5-difluorophenyl) -N -methylaminomethylmethyl)-1- (3,5-dimethoxyphenyl) -4 -oxo-1,4 -dihydroquinoline-7 -yloxy] heptylbu 4 -acyl-1 -azobicyclo [2 · 2 · 2] octane (Exemplified compound number: 2- 120) (99a) 7-benzyloxy-1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorobenzene -N-formamidine The 7-benzyloxy-1-(3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline obtained in Example (1 1 Π) 200 mg of 3-carboxylic acid and 0. 08ml, (3,5-difluorophenyl) -methylamine 7 3 mg and triethylamine 0 · 1 3 m 1, the reaction was carried out according to the method of Example (1 f), and the title compound was obtained as a colorless foam. 1 5 5 mg NMR (CDC13) δρρη: 3.45 (3Η, s), 3.81 (6Η, s), 4.99 (2Η, s), 6.43 (2Η, d, J = 2. 2Hz), 6. 46 (1Η, d, J = 2. 4Hz), 6. 65 (2Η, m), 6. 89 (2Η, dd, J = 2. 0, 8. 0Hz), 200300349 7. 0K1H, dd, J = 2. 2, 8. 9Hz), 7. 27-7. 37 (5H, m), 7. 91 (1H, s), 8. 24 (1H, d, J = 8. 9Hz).  (99b) l- (3,5 -monomethoxybenzyl) -7-acyl-4-oxo-1,4 -mono > pyridinoline-3 -carboxylic acid N- (3,5-difluoro Phenyl) -N-formamidine The 7-benzyloxy-1-(3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquine obtained in Example (9 9 a) N- (3,5-difluorophenyl) -N-formamidine 145 mg and 10% Pd-C30 mg of phthaloline-3 carboxylic acid were reacted according to the method of Example (11h) to obtain a yellow foam of the title compound. 1 2 2 mg. Li R (CDC13) δρριη: 3. 44 (3H, s), 3. 79 (6H, s), 6. 44 (2H, d, J = 2. 2Hz), 6. 5K1H, d, J = 2. 1Hz), 6. 56 (1H, m), 6. 60-6. 65 (1H, m), 6. 87 (2H, dd, J = 1. 8, 5. 9Hz), 6. 95 (1H, dd, J = 2. 0, 8. 9Hz), 7. 87 (1H, s), 8. 03 (1H5 d, J = 9. 0Hz).  (99〇7- (7-Bromoheptyloxy) -1- (3,5-dimethoxyphenyl) -4-oxy-1,4-dihydroquinoline-3 5-difluorophenyl) -N-formamide The 1- (3,5-dimethoxyphenyl) -7-hydroxy-4-oxy-1,4-diamine obtained in Example (9 9 b) Hydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-formamidine 115mg, 1,7-dibromoheptane 0. 13 ml and 51 mg of potassium carbonate were reacted and purified according to the method of Example (1 1 i) to obtain 101 mg of the title compound as a yellow foam. Li R (CDC13) (5ppm: 1.  32-1. 46 (6H, m), 1.  70-1. 77 (2H, m), 1.  81-1.  84 (2Η, m), 3. 40 (2H, t, J = 6. 7Hz), 3. 46 (3H, s), 3. 84 (6H, s), 3. 87 (2H, t, J = 6. 3Hz), 6. 4K1H, d, J-2. 2Hz), 6. 50 (2H, d, J = 2. 2Hz), 6.  60-6.  65 (2H, m), 6.  88-6.  94 (3H, m), 7. 92 (1H, s), 8. 25 (1H, d, J = 9. 1Hz).  (99d) 1- {7- [3- (N- (3,5-difluorophenyl) -N-methylaminemethylmethyl)-: 1- (3,5-dimethoxyphenyl) bromide -4 -oxo-1,4-dihydroquinoline-7 -yloxy] heptylbu 4_acryl-1 j-azabicyclo [2. 2 · 2] octane 200300349 The 7-(7-bromoheptyloxy) -1-(3, 5 -dimethoxyphenyl) -4-yl-1,4- obtained from Example (9 9 c) Dihydroquinoline-3-carboxylic acid N- (3, 5-difluorophenyl) -N-formamidine 95 mg and 1,4-diazine-bicyclo [2 · 2 · 2] octane 20 mg, according to implementation The reaction of Example (1 1 j) was carried out to obtain 101 mg of a light brown powder of the title compound. NMR, (CDC13) δρριπ: 1. 39 (6H, br), 1.  70-1.  77 (2H, br), 2. 02 (2H, br), 3. 36 (6H, br), 3. 48 (3H, s), 3. 53-3. 58 (2H, dd, m), 3. 72 (6H, br), 3. 83 (6H, s), 3. 86 (2H, t, J-6. 2Hz), 6. 4K1H, d, J = 2. 1Hz), 6. 47 (2H, d, J = 2. 1Hz), 6. 60-6. 65 (2H, m), 6. 88 (2H, dd, J = 1. 9, 7. 9Hz), 6. 94 (1H, dd, J = 2. 1, 8. 9Hz), 7. 85 (1H, s), 8. 22 (1H, d, J = 9. 0Hz).  Melting point: 1 2 8 to 1 3 0 ° C. Example 1 1- {7- [3- (N- (3,5-difluorophenyl) -N-propylaminomethylmethyl) -1- (3,5-dimethoxyphenyl) bromide -4 -oxo-1,4 -dihydroquinoline-7 -yloxy] heptylbu 4 -acyl-1 -azobicyclo [2 · 2 · 2] octane (Exemplified compound number: 2-199) (100 &) 7-benzyloxy-1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluoro Phenyl) -fluorenamine 7-benzyloxy-1-(3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline obtained in Example (1 1 f) · 3 -Carboxylic acid 3. 0 g, isobutyl chloroformate 1. 1ml, triethylamine 1. 94ml and 986mg of 3,5-difluoroaniline were reacted and purified according to the method of Example (5 4 c) to obtain the title compound as colorless crystals 2. 06g. Circle R-(CDC13) δ ppm: 3. 83 (6H, s), 5. 03 (2H, s), 6. 49 (2H, d, J = 2. 2Hz), 6. 5 Bu 6. 56 (1H, m), 6.57 (1Η, d, J = 2. 2Hz), 6. 67UH, t, J: 2. 2Hz), 7.16 (1Η, dd, J = 2. 3, 8. 9Hz), 7. 28-7. 43 (7H, m), 8. 46 (1H, d, J-9. 2Hz), 8. 78 (1H, s).  200300349 (100b) 7-benzyloxy-1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluoro Phenyl) -N-propanamidin The 7-benzyloxy-1-'(3,5-dimethoxyphenyl) -4-oxo-1,4-diphenyl obtained in Example (100a) Hydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) amidamine 200 mg, 55% sodium hydride 24 mg and bromopropane 0.13 m 1, according to the example ( 5 4 d) The reaction was carried out and purified to obtain 97 mg of the title compound as a colorless foam. Li R (CDC13) δ ppm: 0.93 (3H, t, J = 7.  4Hz), 1.  57-1 · 66 (2H, m), 3. 79-3. 85 (8H, m), 4. 97 (2H, s), 6. 40 (2H, d, J = 2. 2Hz), 6. 43 (1H, d, J = 2. 4Hz), 6. 59-6. 64 (2H, m), 6. 84 (2H, dd, J = 2. 1, 8. 1Hz), 6. 99 (1H, dd, J = 2. 3, 9. 1Hz), 7. 26-7. 36 (5H, m), 7. 82 (1H, s), 8. 22 (1H, d, J = 8. 9Hz).  (100c) l- (3,5-dimethoxyphenyl) -7-hydroxy-4-oxo 1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl)- N-propylammonium will be the 7-benzyloxy-1-(3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3-obtained in Example (100b). Carboxylic acid N- (3,5-difluorophenyl) -N-propanamide 90 mg and 10% Pd-C20 mg were reacted according to the method of Example (11h) to obtain the title compound as a yellow foam 7 5 mg. Circle R (CDC13) δ ppm: 0. 90 (3H, t, J = 7. 3Hz), 1. 59 (2H, m), 3.  75-3.  84 (8H, m), 6. 40 (2H, d, J = 2. 0Hz), 6. 48 (1H, d, J = 2. 0Hz), 6. 55 (1H, s), 6. 63 (1H, m), 6. 82 (2H, dd, J = 1. 8, 7. 8Hz), 6. 93 (1H, dd, 1 = 1. 9, 9. 0Hz), 7. 77 (1H, s), 7. 99 (1H, d, J = 8. 9Hz).  (100 (1) 7- (7-bromoheptyloxy) -1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid 3,5-difluorophenyl) -N-propanamidin The 1- (3,5-dimethoxyphenyl) -7-hydroxy200300349-4-oxo-1 obtained in Example (100c), 4-Dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-propanamide 70mg, 1,7-dibromoheptane 0. 07 ml and 29 mg of potassium carbonate were reacted and purified according to the method of Example U 1 i) to obtain 67 mg of the title compound as a colorless foam. NMR (CDC13) δρρπι: 0. 93 (3H, t, J-7.  4Hz), 1.  30-L 48 (6H, m), 1. 57-1. 67 (2H, m), 1.  69-1.  76 (2H, m), 1.  81-1.  88 (2H, m), 3. 40 (2H, t, J = 7. 0Hz), 3. 82-3. 88 (10H, m), 6. 38 (1H, d, J = 2. 2Hz), 6. 47 (2H, d, J = 2. 2Hz), 6. 59-6.  64 (2H, m), 6. 84 (2H, dd, J = 2. 1, 8. 1Hz), 6. 90 (1H, dd, 1 = 2. 2, 8. 9Hz), 7. 83 (1H, s), 8. 2K1H, d, J = 9. 0Hz).  (lOOe) bromide 1- {7- [3- (N- (3,5-difluorophenyl) -1propylaminemethyl) -1- (3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7-yloxy] -heptylb 4-az-1-azobicyclo [2 · 2 · 2] octane Example (100d ) The obtained 7-(7 -bromoheptyloxy) -1-(3,5-dimethoxyphenyl) -4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 64-Difluorophenyl) -Propanamide 64mg and 1,4-Diazine-Bicyclic [2. 2. 21 mg of 13 octane was reacted in the same manner as in Example (1 1 j) to obtain the title compound as a white solid 62 mg. NMR (CDC13) δ ppm: 0. 93 (3H, t, J = 7. 4Hz), 1. 38 (6H, br), 1. 56-1.  66 (2H, m), 1. 69-1. 77 (4H, br), 3. 40 (6H, br), 3. 51-3. 58 (2H, m), 3. 74 (6H, br), 3. 80-3. 87 (10H, m), 6. 38 (1H, d, J = 2. 1Hz), 6. 43 (2H, d, J = 2. 1Hz), 6.  61-6.  65 (2H, m), 6. 83 (2H, dd, 1 = 2. 1, 7. 8Hz), 6. 92 (1H, dd, J = 2. 1, 9. 0Hz), 7. 76 (1H, s), 8. 19 (1H, d, J = 9. 1Hz).  Melting point: ~ 1 2 5 ° C Example 1 〇1 bromide 1- [7- [3- (N- (3,5-difluorophenyl) -N-isopropylamine formamidine 200300349) -1- ( 3,5-mono ^ methoxybenzyl) -4 -oxo-1,4-monopyridine -7-yloxy] heptyl] -4 -acyl-1 -azobicyclo [2. 2 · 2] octane (exemplified compound number: 2-747) (101a) 7-benzyloxy-1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline 3-carboxylic acid N- (3,5-difluorophenyl) -N-isopropylamidine The 7-benzyloxy-1- (3,5-dimethylformaldehyde) obtained in Example (100a) Oxyphenyl) -4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) amidamine 200mg, 55% sodium hydride 24mg and 2-bromopropane 0 14 ml was reacted and purified according to the method of Example (54d) to obtain 34 mg of the title compound as an orange foam. Area R, (CDC13) δ ppm: 1. 20 (6H, d, J = 6. 8Hz), 3. 80 (6H, s), 4.  90-5.  05 (1H, m), 4. 96 (2H, s), 6. 34 (2H, br), 6. 39 (1H, br), 6. 6K1H, s), 6. 69 (1H, m), 6. 82 (2H, d, J = 10. 0Hz), 6. 98 (1H, dd, J = 2. 6, 9. 2Hz), 7. 26-7.  28 (2H, m), 7.  30-7.  36 (3H, m), 7. 59 (1H, br), 8. 24 (1H, d, 1 = 9. 0Hz).  (101b) l- (3,5-dimethoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-isopropylamidine The 7-benzyloxy-1-(3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline obtained in Example (101a) 32 mg of 3-carboxylic acid N- (3,5-difluorophenyl) -isopropylamidamine and 10% Pd-C10 mg were reacted according to the method of Example (11h) to obtain the title compound as a pale yellow foam Compound 2 7 mg. R (CDC13) δρριη: 1. 20 (6H, d, J = 6. 4Hz), 3. 78 (6H, s), 4. 96 (1H, m), 6. 37 (2H, br), 6. 43 (1H, s), 6. 56 (1H, s), 6. 73 (1H, m), 6. 82 (2H, d, J = 7. 3Hz), 6. 93 (1H, d, J = 7. 9Hz), 7. 56 (1H, br), 8. 04 (1H, d, J-8. 4Hz).  (101007- (7-bromoheptyloxy) -1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3 1,5-difluorophenyl) -isopropylhydrazone-309-200300349 amine The 1- (3,5-dimethoxyphenyl) -7-hydroxy-4-oxy- obtained in Example (101b) 1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-isopropylamidine 26mg, 1,7-dibromoheptane 0. 027 ml and 11 mg of potassium carbonate were reacted and purified according to the method of Example (1), and 30 mg of the title compound was obtained as a white solid. Li R (CDC13) (5ppm: 1. 2Κ6Η, d, J = 6. 6Hz), 1.  33-1. 48 (6H, m), 1. 69-1. 48 (2H, m), 1.  81-1.  88 (2H, m), 3. 39 (2H, t, 1 = 6.  8Hz), 3.  83-3.  87 (8H, m), 4. 90-5. 10 (lH, m), 6. 35, (1H, s), 6. 40 (2H, br), 6.  61 (1H, s), 6.  68-6.  69 (1H, m), 6.  83 (2H, m), 6. 93 (1H, d, J = 7. 9Hz) ,.  7. 64 (1H, br), 8. 32 (1H, d, J = 9. 0Hz).  (1 〇1 d) bromide 1-[7-[3-(N-(3,5-difluorophenyl) -N -isopropylaminemethylmethyl) -1--1- (3,5-dimethoxybenzene ) -4 -oxo-1,4-dihydroquinoline-7-yloxy] heptyl] _4_acryl-diazobicyclo [2 · 2 · 2] octane ) The obtained 7-(7.bromoheptyloxy) -1-(3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 29 mg of 5-difluorophenyl) -N-isopropylamidamine and 6 mg of 1,4-diazinebicyclo [2 · 2 · 2] octane were reacted and purified according to the method of Example (1 1 j), but 17 mg of the title compound was obtained as a white solid. Wake upR (CDC13) δppm: 1. 12 (6H, d, J = 6. 6Hz), 1. 39 (6H, br), 1. 50-1 · 95 (4H, br), 3.  57-3. 90 (22H, m), 4. 99 (1H, m), 6. 33 (1H, s), 6. 38 (2H, s), 6. 59 (1H, s), 6. 70 (1H, m), 6. 8K2H, d, J = 8. 1Hz), 6. 92 (1H, d, J = 7. 7Hz), 7. 57 (1H, s), 8. 22 0H, d, J = 8.  1Hz). , Melting point: 1 3 1 ～ 1 3 4 ° C ′ Example 1 〇2 1- {7- [3- (N -allyl- N- (3,5-difluorophenyl) amine formamidine -310- 200300349) -1- (3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7 -yloxy] Nitrobicyclo [2 · 2 · 2] octane (Exemplified compound number: 2-256) (102a) l- (3,5-dimethoxyphenyl) -7-hydroxy-4-oxo-1,4 -di Hydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl) -amidine The 7 -benzyloxy-1-(3,5-dimethoxyl) obtained in Example (1000a) Phenyl) -4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid "(3,5-difluorophenyl) -amidamine 1. 0 g and 10% Pd-C 200 mg were reacted according to the method of Example (11h) to obtain 460 mg of the title compound as a pale yellow solid. Rei ^ (DMSO-dG) δ ppm: 3. 82 (6H, s), 6. 49 (1H, d, J = 2. 1Hz), 6. 79 (1H, t, J = 2. 2Hz), 6. 9K2H, d ,.  J = 2. 2Hz), 6. 95 (1H, m), 7. 02 (1H, dd, J = 2. 2, 8. 8Hz), 7. 5K2H, dd, J = 1. 9, 9. 2Hz), 8. 26 (1H, d, J = 8. 9Hz), 8. 59 (1H, s).  (102b) l- (3,5-dimethoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N-(3, 5 -di Fluorophenyl) -amidine. The 1- (3,5-dimethoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3 obtained in Example (1002a) was used. -A solution of 460 mg of anhydrous carboxylic acid N- (3,5-difluorophenyl) -amidine in 5 ml of anhydrous N, N-dimethylformamide, 211 mg of potassium carbonate was added, and the mixture was stirred at room temperature for 15 minutes. Chloromethyl methyl ether was added dropwise. 23 ml, and stirred at room temperature for 24 hours. Dilute with dichloromethane, and then rinse with dilute hydrochloric acid, water, saturated sodium bicarbonate water, and saturated brine. After drying over anhydrous magnesium sulfate, the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol = 100%; hexane / ethyl acetate = 3/1 to 2/1). The title compound was obtained in a white solid of 37 1 mg. NMR (CDC13) δρριη: 3. 44 (3H, s), 3. 85 (6H, s), 5. 17 (2H, s), 6. 51-6. 56 (3H, m), 6. 66 (1H, t, J = 2. 1Hz), 6. 78 (1H, d, J = 2. 2Hz), 7. 23 (1H, dd, J-2. 2, 8. 9Hz), 7. 39 (2H, dd, J = 2. 0, 8. 8Hz), 8. 48 (1H, d, J = 9. 1Hz), 8. 82 (1H, s).  -311-200300349 (102〇1- (3,5-dimethoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N-ene Propyl · N-3,5-difluorophenyl) -fluorenamine The 1- (3,5-dimethoxyphenyl) -7-methoxymethoxy-4 obtained in Example (102b) -Oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) sulfonamide 16 5 mg, 55% sodium hydride 2 2 mg and 3-bromopropane. 1 1 m 1 was reacted and purified according to the method of Example (5 4 d) to obtain 160 mg of the title compound as a colorless foam. NMR (CDC13) (5ppm: 3. 42 (3H, s), 3. 83 (6H, s), 4. 49 (2H, d, J = 5. 3Hz), 5. 12 (2H, s), 5. 20 (1H, d, J = 10. 2Hz), 5. 32 (1H, d, J = 16. 9Hz), 5.  89-5.  99 (1H, m), 6. 49 (2H, d, J = 2. 2Hz), 6.  57 ~ 6.  64 (3H, m), 6. 85 (2H, dd, J = 2. 1, 8. 1Hz), 7. 05 (1H, dd, J = 2. 2, 8.  8Hz), 7. 94 (1H, s), 8. 22 (1H, d, J = 8. 9Hz).  (1 0 2 d) 1- (3,5-dimethoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N-allyl-N- ( 3,5-difluorophenyl) -fluorenamine 1- (3,5-dimethoxyphenyl) -7-methoxymethoxy-4-oxo-1 obtained in Example (102c) 5ml of 4N-HC1 / ethyl acetate was added to 145ng of 4,4-dihydroquinoline-3-carboxylic acid N-allyl-N-3,5-difluorophenyl) -amidine and stirred at room temperature for 1 hour . The reaction solution was diluted with ether and the solids were collected by filtration and dried to obtain 135 mg of the title compound as a white solid. NMR (DMS0-d6) δ ppm: 3. 82 (6H, s), 4. 43 (2H, d, J = 5. 4Hz), 5. 12 (1H, dd, J = 1. 2, 10. 2Hz), 5. 30 (1H, dd, J = 1. 2, 17. 1Hz), 5. 80-5. 90 (1H, m), 6. 38 (1H, d, J = 2. 1Hz), 6. 65 (2H, d, J = 1. 8Hz), 6. 75 (1H, t, J = 2. 2Hz), 6. 80 (1H, dd, J = 2. 1, 8. 8Hz), 7. 00-7. 11 (3H, m), 7. 9K1H, d, J = 8. 9Hz), 8. 06 (1H, s).  (1026) 7- (7-bromoheptyloxy) -1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid -N- (3,5-difluorophenyl-312- 200300349) -amidamine 1- (3,5-dimethoxyphenyl) -7 -hydroxy-4 obtained in Example (102 d) -Oxy-1,4-dihydroquinoline-3 -carboxylic acid N-allyl-N- (3,5-difluorophenyl) -amidamine 128mg, 1,7-dibromoheptane 0. 13 ml and 59 mg of potassium carbonate were reacted and purified according to the method of Example (1 1 i) to obtain 69 mg of the title compound as a colorless foam. NMR, (CDC13) δ ppm: 1.  31-1. 48 (6H, m), 1.  69-1.  78 (2H, m), 1.  81-1.  88 (2H, m), 3. 40 (2H, t, J-6. 9Hz), 3. 84 (6H, s), 3. 87 (2H, t, J = 6. 4Hz), 4. 49 (2H, d, J = 5. 7Hz), 5. 19 (1H, dd, J = l. l, 10. 3Hz), 5. 32 (1H, d, J = 17. 0Hz), 5. 89-5. 99 (1H, m), 6. 40 (1H, d, J = 2. 2Hz), 6. 48 (2H, d, J = 2. 2Hz), 6. 57-6. 63 (2H, m), 6. 85 (2H, dd, J = 2. 1, 8. 1Hz), 6. 9K1H, dd, J = 2. 2, 8. 9Hz), 7. 90 (1H, s), 8. 21 (1H, d, J = 9. 1Hz).  (102f) bromide 4-oxo-1,4-dihydroquinoline-7-yloxy] heptylbu 4-acyl-1-azobicyclo [2 · 2 · 2] octane obtained in Example (1 02 e) 7- (7-bromoheptyloxy) -1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N-allyl-N -(3,5-difluorophenyl) -amidamine 66mg and 1,4-diazine-bicyclo [2. 2 · 2] octane 14 mg, reacted according to the method of Example (1 1 j) to obtain the title compound as a white powder 43 mg NMR / (CDCI3) δρρη: 1. 39 (6H, br), 1.  69-1.  77 (4H, m), 3. 38 (6H, br), 3. 55-3.  59 (2H, m), 3. 74 (6H, br), 3.  83-3. 89 (8H, m), 4. 47 (2H, d, J = 5. 4Hz), 5. 19 (1H, d, 1 = 10. 3Hz), 5. 30 (1H, d, 1 = 17. 3Hz), 5. 88-5.  97 (1H, m), 6. 39 (1H, d? J = 2. 1Hz), 6. 46 (2H, d, J = 2. 1Hz), 6.  58-6.  64 (2H, m), 6. 84 (2H, dd, J = 2. 0, 8. 0Hz), 6. 92 (1H, dd, J-2. 1, 9. 0Hz), 7. 84 (1H, s), 8.  19 (1H, d, J-9. 0Hz).  200300349 Melting point: ~ 1 15 ° C, Example 1 〇3 bromide 1-{7-[3-(N-(3,5-difluorophenyl) -N-(2-propargylpropylamine Fluorenyl) -1- (3,5-dimethoxyphenylb 4-oxo-1,4-dihydroquinoline-7-yloxy) heptyl) -4 -acyl-1 -azobicyclo [ 2 · 2 · 2] octane (Exemplified compound number · 2-8 7 1) (103a) l- (3,5-_methoxymethoxy) -7-methoxymethoxy-4-oxo-1 4,4-Dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N- (2-propargyl) amidine The 1- (obtained in Example (1 02b)) 3,5-dimethoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -fluorene Ammonium 16 5 mg, 55% sodium hydride 22 mg and 3-bromopropane 0.  10 m 1 was reacted and purified according to the method of Example (5 4 d) to obtain 150 m g of the title compound as a yellow foam. NMR (CDC13) (5 ppm: 2. 24 (1H, t, J = 2.  4Hz), 3.  42. (3H, s), 3. 84 (6H, s), 4. 65 (2H? D, J = 2. 4Hz), 5. 12 (2H, s), 6. 49 (2H, d, 1 = 2. 2Hz), 6. 61-6. 70 (3H, m); 6. 96 (2H, dd, J = 2. 1, 7. 6Hz), 7. 06 (1H, dd, 1 = 2. 2, 8. 9Hz), 7. 98 (1H, s), 8. 24 (1H, d, J = 9. 0Hz).  (103b) l- (3,5-dimethoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl) -N-(2-propargyl) -amidamine The 1- (3,5-dimethoxyphenyl) -7-methoxymethoxy--4-oxo obtained in Example (103a) -1,4-dihydroquinoline-3 -carboxylic acid N- (3, 5-difluorophenyl) -N-(2-propargyl) -amidamine 1 40 mg, according to the example (1 0 2 d) to carry out the reaction and purification, to obtain the title compound as a light brown solid 1 2 1 mg -314- 200300349 face R (DMS0-d6) δρρπι: 3. 21 (1H, t, J = 2. 5Hz), 3. 82 (6H, s), 4.  67 (2H, d, J = 2. 5Hz), 6. 38 (1H, d, J = 2. 2Hz), 6. 65 (2H, d, J = 2. 1Hz), 6. 74 (1H, t, J = 2. 2Hz), 6. 80 (1H, dd, J = 2. 2, 8. 9Hz), 7. 06-7. 14 (1H, m), 7. 16 (2H, dd, J = 2. 2, 8. 2Hz), 7. 90 (1H, d, J = 8. 9Hz), 8. 06 (1H, s).  (103 (〇7- (7-Bromoheptyloxy) -1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 1,5-difluorophenyl) -N- (2-propargyl) -fluorenamine The 1- (3,5-dimethoxyphenyl) -7-hydroxy- obtained in Example (103b) 4-Oxy-1,4-dihydroquinoline_3-carboxylic acid N- (3,5-difluorophenyl) -N- (2-propargyl) -fluorenamine 114 mg, 1,7-dibromo Heptane 0. 12 ml and potassium carbonate 48 mg were reacted and purified according to the method of Example (1 1 i) to obtain 91 1 mg of the title compound as a pale yellow foam. NMR (CDC13) (5ppm: 1. 31-1. 48 (6H, m), 1. 70-1.  78 (2H, m), 1.  80-1.  88 (2H, m), 2. 24 (1H, t, J = 2. 4Hz), 3. 40 (2H, t, J = 6. 7Hz), 3. 84 (6H, s), 3. 87 (2H, t, J = 6. 4Hz), 4. 65 (2H, d, J = 2. 4Hz), 6. 4K1H, d, J = 2. 2Hz), 6. 49 (2H, d, J = 2. 2Hz), 6. 63 (1H, t, J = 2. 2Hz), 6.  64-6.  70 (1H, m), 6.  91-6.  97 (3H, m), 7.  95 (1H, s), 8.  22 (1H, d, J = 9. 0Hz).  (103) bromide 1- {7- [3- (N- (3,5-difluorophenyl) -N- (2-propargyl) aminomethyl) -1- (3,5 -Dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7 -yloxy] heptyl}-4 -azine-pyrazinebicyclo [2 · 2 · 2] octane Example 7- (7-bromobutoxy) -1- (3,5-dimethoxyphenyl) -4-oxo-I, 4-dihydroquinoline-3-carboxyl obtained from (103) Acid N- (3, 5-difluorophenyl) -N-(2-propargyl) -amidine 8 7 mg and 1,4-diazine-bicyclo [2 · 2 · 2] octane 1 8 mg The reaction was performed and purified according to the method of Example (1 1 j) to obtain 6 2 mg of the title compound as a pale yellow powder. 200300349 Li R (CDC13) άρριι: 1. 39 (6Η, br), 1. 69-1.  77 (4Η, m), 2. 28 (1H, t, 1 = 2.  3Hz), 3. 33 (6H, br), 3. 54-3.  58 (2H, m), 3. 7K6H, br), 3.  80-3.  86 (8H, m), 4. 63 (2H, d, J = 2. 2Hz), 6. 40 (1H, d, J = 2. 0Hz), 6. 46 (2H, d, J = 2. 1Hz), 6. 62 (1H, t, J = 2. 1Hz), 6.  65-6.  70 (1H, m), 6.  92-6.  96 (3H, m), 7. 88 (1H, s), 8. 20 (1H, d, J = 8. 9Hz).  Melting point: 1 2 4 ~ 1 2 7 ° C Example 1 〇4 bromide 1- {7- [3- (N- (3,5-difluorophenyl) 1-ethylaminomethylmethyl) -1- (3 -Ethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7 -yloxy] heptylb 4-acyl-Mazepine bicyclo [2 · 2 · 2] octane Compound number: 2-180) (104a) 1- (2-hydroxy-4-methoxymethoxy-phenyl) -ethanone Anhydrous 50 g of 1- (2,4-dihydroxyphenyl) ethanone Tetrahydrofuran 3 50 m 1 solution, 55% sodium hydride 15 was added under ice-cooling and stirring.  8 g. After stirring for 2 hours under ice cooling, chloromethyl methyl ether 27 was added dropwise. 2 m 1. Stir at room temperature for 20 hours. The solvent of the reaction solution was distilled off. The residue was neutralized with dilute hydrochloric acid. Extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine. After drying over anhydrous magnesium sulfate. The solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1 0/1 to 5/1). The title compound was obtained as a colorless oily substance 3 5. 6 g. NMR (CDC13) (5ppm: 2. 57 (3H, s), 3. 48 (3H, s), 5. 21 (2H, s), 6. 55 (1H, dd,] = 2A, 8. 8Hz), 6. 60 (1H, d, J = 2. 4Hz), 7. 65 (1H, d, J = 8. 9Hz).  (104b) l- (2-methoxy-4-methoxymethoxy-phenyl) -ethanone The 1- (2-hydroxy-4-methoxymethoxyphenyl) obtained in Example (104a) ) -Ethyl ketone 89. 8g, methyl iodide 42. 7ml and potassium carbonate 94. 9g, reacted according to the method of Example (1 1 b) to obtain the title compound as a colorless oily substance 200300349 8 5 · 6 g 〇 NMR (CDC13) δ ppm: 2. 58 (3H, s), 3.  49 (3H, s), 3.  90 (3H, s), 5.22 (2H, s), 6. 6K1H, d, J = 2. 2Hz), 6. 66 (1H, dd, J = 2. 1, 8. 7Hz), 7. 80 (1H, d, J = 8. 8Hz).  (104c) 3- (2-methoxy-4-methoxymethoxy-phenyl) -3-oxy-propionic acid methyl ester 4-methoxymethoxyphenyl-)-ethanone 85. 6g, 55% sodium hydride 20. 0 g and dimethyl carbonate 4 0 m 1 were reacted according to the method of Example (1 1 c) to obtain the title compound as a yellow oil 54. 9 g. NMR.  (CDC13) (5ppm: 3. 49 (3H, s), 3. 72 (3H, s), 3. 87 (3H, s), 3. 94 (2H, s), 5. 22 (2H, s), 6. 60 (1H, d, J = 2. 1Hz), 6. 69 (1H, dd, J = 2. 2, 8. 8Hz), 7. 92 (1H, d, J = 8. 8Hz).  (104d) 3-Dimethylamino-2- (2-methoxy-4-methoxymethoxy-benzylfluorenyl) -methyl acrylate ... 3-(obtained in Example (104 c)) 2-methoxy-4 -methoxymethoxy-phenyl) -3-oxo-propionic acid methyl ester 54. 9g and N, N-dimethylformamide methylal 5 4. 8 m 1, the reaction was carried out according to the method of Example (1 1 d) to obtain the title compound as a yellow oil 6 3.  7 g. R (CDC13) (5ppm: 2.  80-3.  20 (6H, br), 3. 49 (3H, s), 3. 50 (3H, s), 3. 78 (3H, s), 5. 20 (2H, s), 6. 54 (1H, d, J = 2. 2Hz), 6. 64 (1H, dd, J = 2. 2, 8. 7Hz), 7. 56 (1H, d, J-8. 6Hz), 7. 64 (1H, s).  (104e) L- (3-benzyloxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid methyl ester Example (104d) The resulting 3-dimethylamino-2-(2-methoxy-4 -methoxymethoxy-benzylfluorenyl) -methyl acrylate 5. 04g, 3-benzyloxyaniline 200300349 4. 7 5 g and potassium carbonate 4. 31 g was reacted according to the method of Example (1 1 e) to obtain the title compound as a pale yellow solid 6.06 g. NMR.  (CDCl3) 5ppm: 3. 42 (3H, s), 3. 92 (3H, s), 5. 12 (4H, s), 6. 60 (1H, d, J = 2. 2Hz), 7. 00-7. 03 (2H, m), 7. 14 (1H, dd, J = 2. 2, 9. 0Hz), 7. 17-7. 20 (1H, m), 7. 34-7. 46 (5H, m), 7. 5K1H, t, J = 8. 2Hz), 8. 48 (1H, d, J = 8. 9Hz), 8. 51 (1H, s).  (104 f) 1- (3-benzyloxyphenyl) -7-methoxymethoxy-4-oxo-1,4-diamine D-quidose-3-Junacic acid The 1- (3-benzyloxyphenyl) -7-methoxymethoxy--4-oxy-1,4-dihydroquinoline-3-carboxylate 96g and sodium hydroxide 2. 7 g, the reaction was carried out according to the method of Example (1e) to obtain the title compound as a white solid 4. 97g. Li R (CDC13) δ ppm: 3. 43 (3H, s), 5. 13, 5. 15, 5. 16, 5. 17 (total 4H, each s), 6. 73 (1H, d, J = 2. 2Hz), 7. 0K1H, d, J = 3. 3Hz), 7. 02 (1H, d, 1 = 1. 3Hz), 7. 21-7.  24 (1H, m), 7. 25-7.  28 (1H, m), 7.  34-7. .  45 (5H, m), 7.  53 (1H, t, J = 8. 5Hz), 8. 48 (1H, d, J = 9. 2Hz), 8. 75 (1H, s).  (104g) 1- (3-benzyloxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline 3-carboxylic acid N-(3,5-difluorophenyl ) -Amine The 1- (3-benzyloxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid obtained in Example (104f) 4. 86g, isobutyl chloroformate 1. 63ml, triethylamine 3. 14ml and 3,5-difluoroaniline 1. 6g, reacted according to the method of Example (5 4 c) to obtain the title compound as a pale yellow solid 4. 58g. .  NMR (CDC13) δρριη: 3. 43 (3H, s), 5. 12, 5. 13, 5. 148, 5. 15 (total 4H, eachs), 6. 52-6. 57 (lH, m), 6. 71 (1H, d, J-2. 2Hz), 7. 02 (1H, d, J = 1. 9Hz), 7. 04 (1H, d, J = 1. 2Hz), 7. 20-7. 27 (2H, m), 7. 34-7. 46 (7H, m), 7. 53 (1H, t, J = 8. 4Hz), 8. 49 (1H, d, J-8. 9Hz), 8. 83 (1H, s).  -318- 200300349 (104 h) (3-benzyloxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5 -Difluorophenyl) -N-acetamidine 1- (3-benzyloxyphenyl) -7-methoxymethoxy-4-oxo-1,4-obtained in Example (104 g) Dihydroquinoline-3 -carboxylic acid 55g, 549mg of 55% sodium hydride and iodonium 2. 66 ml was reacted in the same manner as in Example (54d) to obtain the title compound as a light yellow foam (3.93 g). NMR (CDC13) δρριη: 1. 2Κ3Η, t, J = 7. 0Hz), 3. 40 (3H, s), 3. 93 (2H, q, J = 7. 0Hz), 5. 09 (2H, s), 5. 10 (2H, s), 6. 56 (1H, d, J = 2. 2Hz), 6. 60-6.  66 (1H, m), 6. 84 (2H, dd, J = 2. 1, 8. 0Hz), 6. 95 (1H, d, J = 3. 7Hz), 6. 96 (1H, d, J = 1. 3Hz), 7. 05 (1H, dd, J = 2. 3, 9. 2Hz), 7. 15-7. 17 (1H, m), 7.  34-7.  52 (6H, m), 7. 89 (1H, s), 8. 23C1H, d, J = 9. 〇Hz).  (104i) l- (3-hydroxyphenyl) -7-methoxymethoxy-4 -oxo-1,4-dihydroquinoline · 3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidinium 1- (3-oxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroBquinoline obtained in Example (104 h) 3-N-acid N- (3,5-monofluorophenyl) -N-acetamidine 3. 9 g of ethanol in 50 ml of a solution, 10% P d-C was added, and the mixture was stirred under hydrogen for 1 hour. The catalyst was filtered off and washed with dichloromethane. The solvent combined with the filtrate was concentrated under reduced pressure. The precipitated solid was dissolved in diisopropyl ether and filtered to obtain 3.1 g of the title compound as a white solid. NMR (CDC13) 6ppm: 1. 15 (3H, t, J = 7. 0Hz), 3. 37 (3H, s), 3.  70-3.  93 (2H, m), 5. 056, 5.  060 (total 2H, each s), 6.  54 ~ 6.  63 (3H, m), 6.  78-6.  83 (3H, in), 6. 99 (1H, dd? J = 2. 0, 9. 0Hz), 7. 09 (1H, dd, J = 2. 1, 8. 2Hz), 7. 37 (1H, t, J = 8.  0Hz), 8. 15 (1H, d, J = 8. 9Hz), 8. 22 (1H, s).  200300349 (104j) 1- (3-ethoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluorobenzene ) -N-acetamidinium 1- (3-Transphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3 -Carboxylic acid N- (3,5-difluorophenyl) -N-acetamide 1. 5g, Iodine II Academy 0. 49 ml and 863 mg of potassium carbonate were mixed in anhydrous Ν, Ν-dimethylformamide 20 m 1 and stirred at room temperature for two days. The reaction solution was diluted with water. Extract with dichloromethane. The extract was washed with dilute hydrochloric acid and water in this order. Saturated sodium bicarbonate water, saturated brine. Dry over anhydrous magnesium sulfate. The solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/1 to 1/3) to obtain the title compound as a pale ochre oily substance 2.  1 g. NMR (CDC13) δρρπι: 1. 2Κ3Η, t, J = 7. 2Hz), 1. 45 (3H, t, J = 7. 1Hz), 3. 40 (3H, s), 3. 93 (2H, q, J = 7. 2Hz), 4. 07 (2H, q, J = 7. 0Hz), 5. 10 (2H, s), 6. 57 (1H, d, J = 2. 2Hz), 6.  60-6.  66 (1H, m), 6. 83-6. 85 (3H, m), 6. 9K1H, d, 1 = 7. 9Hz), 7. 04-7. 09 (2H, m), 7. 46 (1H, t, J = 8. 1Hz), 7. 90 (1H, s), 8. 25 (1H, d, J = 8. 9Hz).  (104k) l- (3-ethoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N- Acetylamine was used to obtain the 1- (3-ethoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid obtained in Example (104j). N- (3,5-difluorophenyl) -N-acetamidamine 2.  lg, according to the method of Example (1 0 2 d), the title compound was obtained as a white solid 1. 36g. N Europe.  (CDC13) δρρπι: 1. 17 (3H, t, J = 7. 1Hz), 1. 42 (3H, t, J = 7. 0Hz), 3. 89 (2H, q, J = 7. 1Hz), 4. 0K2H, q, J = 7. 0Hz), 6. 42 (1H, s), 6. 63C1H, t, J = 8. 6Hz), 6. 77-6. 82 (4H, m), 6. 90 (1H, d, J = 8. 5Hz), 7. 02OH, dd, J = 1. 7, 8. 5Hz), 7. 37 (1H, t, J = 8. 0Hz), 7. 79 (1H, s), 7. 99 (1H, d, J = 8. 8Hz).  -320-200300349 (1041) 7- (7-bromoheptyloxy) -1- (3-ethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N-(3 1,5-difluorophenyl) -N-acetamidine The 1- (3-ethoxyphenyl) -7-hydroxy-4-oxy-1,4-dihydro obtained in Example (104 k) Quinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamide 650mg, 1,7-dibromoheptane. 71 ml and 290 mg of potassium carbonate were reacted and purified according to the method of Example (1 1 i) to obtain 717 mg of the title compound as a colorless foam. NMR.  (CDC13) (5ppm: 1. 2K3H, t, J = 7. 1Hz), 1.  34-1. 47 (9H, m), 1. 68-1. 88 (2H, m), 1. 81-1. 88 (2H, m), 3. 39 (2H, t, J = 6. 7Hz), 3. 84 (2H, t, J = 6. 4Hz), 3. 93 (2H, q, J = 7. 1Hz), 4. 07 (2H, q, J = 7. 2Hz), 6. 34 (1H, d, J = 2. 2Hz), 6. 60-6.  65 (1H, m), 6.  83-6.  85 (3H, m), 6.  89-6.  92 (2H, m), 7. 08 (1H, dd, J = 2. 3, 8. 5Hz), 7. 47 (1H, t, J = 8. 2Hz), 7. 8. 6 (1H, s), 8. 22 (m, d, J = 9. 0Hz).  (104m) bromide l- {7- [3- (N- (3,5-difluorophenyl) -1 ethylaminomethyl) -bu (3-ethoxyphenyl) -4-oxy-1 , 4-dihydroquinoline-7-yloxy] heptylbu 4 -acyl-1 -azobicyclo [2 · 2 · 2] octane (Oxy) -1- (3-ethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 200mg and 1,4-diazine bicyclo [2. 2. 2] 43 mg of octane was reacted in the same manner as in Example (1 1 j) to obtain the title compound as a white powder 227 mg. NMR, (CDC13) δρρπι: 1. 20 (3H, t, J = 7. 1Hz), 1. 36 (6H, br), 1. 45 (3H, t, 1 = 6.  8Hz), 1.  65-1.  80 (4H, m), 3. 25-3. 29 (6H, m), 3. 50-3.  55 (2H, m), 3.  65-3.  69 (6H, e), 3. 82 (2H, t, J = 6. 1Hz), 3. 9K2H, q, J = 7. 1Hz), 4. 07 (2H, q, J = 6. 8Hz), 6. 33 (1H, d, J = 2. 1Hz), 6. 61-6. 67 (1H, m), 6.  81-6.  84 (3H, e), 6.  88 ~ 6.  93 (2H, 'm), 7. 08 (1H, dd, 1 = 2. 3, 8. 4Hz), 7. 48 (1H, t, J = 8. 2Hz), 7. 79 (1H? S), 8. 19 (1H, d, J = 8. 9Hz).  200300349 Melting point: ~ 1 1 2 t: Example 1 〇5 bromide 1- {7- [3- (N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl) -1- ( 3 -ethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7-yloxy] heptylpyridine (exemplified compound number: 2-1 6 6) obtained in Example (1041) 7- (7-bromoheptyloxy) -1- (3-ethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorobenzene Group) -N-acetamidamine 2 0 mg and pyridine 0. 0 3 m 1 was reacted according to the method of Example (1 1 j) to obtain 105 mg of the title compound as a white powder. NMR.  (CDC13) (5ppm: 1. 20 (3H, t, J = 7. 2Hz), 1. 38 (6H, br), 1. 45 (3H, t, J = 6. 9H2), 1. . 67 (2H, br), 2. 00-2. 10 (2H, br), 3. 8K2H, t, J = 6. 2Hz), 3. 92 (2H, q, J = 7. 2Hz), 4. 07 (2H, q, J = 6. 7Hz), 5. 02 (2H, t, J = 7. 4Hz), 6. 32 (1H, d, J = 2. 0Hz), 6. 61-6. 66 (1H, m), 6. 81-6.  85 (3H, m), 6.  88-6. 91 (2H, m), 7. 08 (1H, dd, J = 2. 2, 8. 4Hz), 7. 48 (1H, t, J = 8. 1Hz), 7. 81 (1H, s), 8. 07-8.  11 (2H, m), 8. 18 (1H, d, J = 9. 1Hz), 8. 46 (1H, t, J = 7. 7Hz), 9. 50 (2H, d, J = 5. 8Hz).  Melting point: ~ 7 6 ° C Example 1 〇6 bromide 1- {7- [3- (N- (3,5-difluorophenyl) -N-ethylaminemethylamidino) -1- (3- Ethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7 -yloxy] heptyl} -1 -azobicyclo [2 · 2 · 2] octane (Exemplified compound number: 2- 1 7 8) The 7- (7-bromoheptyloxy) -1-(3-ethoxyphenyl)-> 4-oxo-1,4-dihydroquinoline obtained in Example (104) was used. -3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 200 mg and pyridine 4 3 mg. The reaction was carried out according to the method of Example (1 1 j) to obtain the title. Compound white powder 193 mg. 200300349 NMR (CDC13) δρριη: 1. 20 (3H, t, J = 7. 1Hz), 1. 37 (6H, br), 1. 45 (3H, t, J = 7. 1Hz), 1. 65-1. 85 (4H, br), 2. 01 (6H, br), 2. 22 (1H, br), 3. 46-3. 51 (2H, m), 3. 68-3. 71 (6H, m), 3. 82 (2H, t, J = 6. 1Hz), 3. 92 (2H, q, J = 7. 1Hz), 4. 07 (2H, q, J-7. 0Hz), 6. 33 (1H, d, J = 1. 8Hz), 6.  61-6.  66 (1H, m), 6.  83-6.  85 (3H, m), 6. 90-6. 92 (2H, m), 7. 09 (1H, dd, 1 = 2. 1, 8. 4Hz), 7. 49 (1H, t, 1 = 8. 1Hz), 7. 83 (1H, s), 8. 2K1H, d, J = 9. 0Hz).  Melting point: ~ 1 1 3 ° C Example 1 〇7 bromide l- {8- [3- (N- (3,5-difluorophenyl) -N-ethylamine formamyl) -1- (3 -Ethoxyphenyl) -4-oxo-1,4-dihydroquino-7-yloxy] octyl}-4 -acyl-1 -azobicyclo [2 · 2 · 2] octane (exemplified Compound Number: 2-3 7 8) (107a) 7- (8-Bromooctyloxy) -1- (3-ethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxyl Acid N- (3,5-difluorophenyl) -N-acetamidine The 1- (3-ethoxyphenyl) -7-hydroxy-4-oxo 1,4 obtained in Example (104k) -Dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 650mg, 1,8-dibromooctane 0. 78 ml and 290 mg of potassium carbonate were reacted and purified according to the method of Example (1 1 i) to obtain the title compound as a colorless foamy substance of 7 5 9 mg. Circle R, (CDC13) δρρπι: 1. 20 (3H, t, J = 7. 2Hz), 1.  30-1. 47 (11H, m), 1. 67-1. 74 (2H, m), 1. 80-1. 87 (2H, m), 3. 40 (2H, t, J = 7. 0Hz), 3. 84 (2H, t, 1 = 6. 4Hz), 3. 93 (2H, q, J = 7. 2Hz), 4. 07 (2H, q, J-7. 1Hz), 6. 34 (1H, d, Ι = 2. 2Ηζ), 6.  60-6.  65 (1H? M), 6.  83-6.  85 (3H, m), 6.  89-6.  92 (2H, m), 7. 08 (1H, dd, 1 = 2. 2, 8. 4Hz), 7. 47 (1H, t, J = 8.  1Hz), 7. 86 (1H, s), 8. 22 (1H, d, J = 9. 0Hz).  (107b) bromide 1- {8- [3- (N- (3,5-difluorophenyl) -N-ethylamine formamidine 200300349) -1- (3-ethoxyphenyl)- 4-oxyl, 4-dihydroquinoline-7-yloxy] octylbu 4 -acyl-1 -azobicyclo [2 · 2 · 2] octane The obtained product from Example (107a) 7-(8 -bromooctyloxy) -1-(3 -ethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl ) 1-acetamido 2010 ^ and 1,4-diazine bicyclic [2. 2. 2] Octane 421 ^, which was reacted in the same manner as in Example (1 1 j) to obtain the title compound as white powder 2 17 mg. NMR.  (CDC13) δρρπι: 1. 20 (3H, t, 1 = 7. 1Hz), 1.  25-1. 40 (8H, br), 1. 45 (3H, t, J = 6. 9Hz), 1. 65-1. 74 (4H, m), 3.  27-3.  31 (6H, m), 3.  47-3. 54 (2H, m), 3. 67-3. 7K6H, m), 3. 84 (2H, t, J = 6. 3Hz), 3. 9K2H, q, J = 7. 1Hz), 4. 07 (2H, q, J = 6. 9Hz), 6. 34 (1H, d, J = 2. 2Hz), 6.  61-6.  67 (1H, m), 6.  81-6.  84 (3H, m), 6. 88-6. 93 (2H, m), 7. 08 (1H, dd, J = 2. 1, 8. 2Hz), 7. 48 (1H, t, J = 8. 1Hz), 7. 79 (1H, s), 8. 20 (1H, d, 1 = 8. 9Hz).  Melting point: ~ 8 0 t: 'Example 1 〇8 bromide l- [8- [3- (N- (3,5-difluorophenyl N-ethylamine formamyl) -1- (3- Ethoxybenzyl) -4 -oxyl-1, Xinyiqi quelin-7 -yloxy] amyl] -pyroscope (Exemplified compound number: 2-3 6 4) Example (1 07a ) The obtained 7-(8 -bromooctyloxy) -1-(3 -ethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 5 -di Fluorophenyl) -N-acetamidamine 2 0 mg and pyridine 0 · 0 3 m 1, the reaction was carried out according to the method of Example (1 1 j), to obtain 94 mg of the title compound as a pale yellow powder. NMR.  (CDC13) δρρπι: 1. 20 (3H, t, J = 7.  1Ηζ)? 1. 27-1.  36 (8H, m), 1. 45 (3H, t, J = 6. 9Hz), 1. 65-1. 71 (2H, m), 2. 00-2. 07 (2H, m), 3. 82 (2H, t, J = 6. 3Hz), 3. 92 (2H, q, J-7. 1Hz), 4. 07 (2H, q, 1 = 6. 8Hz), 5. 01 (2H, t, J = 7. 4Hz), 6. 33 (1H, 200300349 d, J = 2. 1Hz), 6. 61-6. 66 (1H, m), 6.  82-6.  85 (3H, m), 6.  88-6.  91 (2H, m), 7. 08 (1H, dd, J = 2. 2, 8. 4Hz), 7. 48 (1H, t, J = 8. 1Hz), 7. 82 (1H, s), 8. 08-8.  11 (2H, m), 8. 19 (1H, d, J = 9. 0Hz), 8. 47 (1H.  t, J = 7. 8Hz), 9. 49 (2H, d, J = 5. 9Hz).

Melting point: ~ 8 1 ° C Example 1 〇9 bromide l- [8- [3- (N- (3,5-difluorophenyl) -ethylaminomethyl) -1- (3-ethoxy Phenyl) -4 -oxo-1,4-dihydroquinolin-7 -yloxy] -octyl] -pyrazinebicyclo [2 · 2 · 2] octane (Exemplified compound number: 2-3 7 6) The 7- (8-bromooctyloxy) -1- (3-ethoxyphenyl) -4-oxy-1,4-dihydroquinoline-3-carboxylic acid obtained in Example (107a) N- (3,5-difluorophenyl) -N-acetamidine 200 mg and ophthalidine 42 mg were reacted according to the method of Example (1 1 j) to obtain the title compound as a white powder 190 mg . NMR. (CDC13) δρριη: 1.20 (3H, t, J = 7.1Hz), 1. 30-1.40 (8H, br), 1.45 (3H, i, J = 7.1 Hz), 1.67 (4H, br), 2.05 (6H, br), 2. 22-2.25 (1H, m), 3. 45-3. 51 (2H, m), 3.67-3.71 (6H, m), 3.83 (2H, t, J = 6.3Hz ), 3.93 (2H, q, J = 7.1Hz), 4.07 (2H, q, J-7.2Hz), 6.34 (1H, d, J = 2.1Hz), 6. 61-6. 66 (1H, m) , 6. 83-6. 85 (3H, m), 6.9K2H, dd? J = 1.9, 9.2Hz), 7.09 (1H, dd, J = 2.4, 8.3Hz), 7.48 (1H, t, J-8.2 Hz), 7.84 (1H, s)? 8.22 (1H, d, J = 8.9Hz). Melting point: ~ 7 5 t: ΐ: Example 1 1 〇. Stinking 1- {7- [3-(^ ( 3,5-difluorophenyl)-> ^ Ethylaminomethyl)-ί- (3-propoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7-yloxy] Heptylbu 4 -acyl-1 -azobicyclo [2 · 2 · 2] octane (Exemplified compound number: 2-; 3 8) (110a) 7 -methoxymethoxy ... 4 -oxy-1- ( 3-propoxyphenyl) -1,4-di-325-200300349 hydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine Example (104i ) The obtained 1- (3-hydroxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 1.5g, 1-bromopropane 0.57ml and potassium carbonate 863mg The reaction was carried out according to the method of Example (104j) to obtain the title compound as a yellow oily substance, 1.9 g circle R (CDC13) δρριι: 1.06 (3H, t, J = 7.5Hz), 1.2K3H, t, J = 7.2Hz), 1.80-1.89 (2H, m), 3.40 (3H, s), 3.91-3.96 (4H, m), 5.10 (2H, s), 6.57 (1H, d, J = 2.2Hz), 6. 60-6. 66 (1H, m), 6. 83-6. 85 (3H, m), 6.9K1H, d, J = 7.9Hz), 7.04-7.09 (2H, m), 7.46 (1H, t, J = 8.2Hz), 7.90 (1H, s), 8.25 (1H, d, J = 8.9Hz). (110b) 7-hydroxy-4-oxo-1- (3-propoxyphenyl) -1 1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidinium 7-methoxymethoxy-4- obtained in Example (lla) Oxy-1- (3-propoxyphenyl) -1,4-dihydroquinoline-3-carboxylic acid 1 ^-(3,5-difluorophenyl) -1 acetamidine 1.9 g, according to The reaction was carried out according to the method of Example (102 d) to obtain 1. 41 g of a yellow foam of the title compound. NMR ^ (CDC13) δρριη: 1.04 (3H, t, J = 7.4Hz), 1.18 (3H, t, J = 7.0Hz), 1.77-1.86 (2H, m), 3.87-3.92 (4H, m), 6.44 (1H, s), 6.63 (1H, t, J = 8.6Hz), '6.78-6.85 (4H, m), 6.93 (1H, d, J = 8.5Hz), 7.03 (1H, d, 1 = 7.7Hz ), 7.38 (1H, t, J = 8.0Hz), 7.80 (1H, s), 8.00 (1H, d5 J = 8.5Hz). (110c) 7- (7-bromoheptyloxy) -4 -oxy- 1- (3-propoxyphenyl) -l, 4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine Example (1 1 〇b ) 7-Hydroxy-4-oxy-1-(3-propoxyphenyl) -1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -acetamidine 680 mg of amine, 0.72 ml of 1,7-dibromoheptane and 295 mg of potassium carbonate were reacted and purified according to the method of Example 200300349 (1π) to obtain 582 mg of the title compound as a colorless foam. NMR. (CDCI3) (5ppm: 1.06 (3H, t, J = 7.4Hz), 1.2K3H, t, J = 6.9Hz), 1.30-1 · 47 (6Η, m), 1.68-1.75 (2H, m), 1.80- 1.89 (4H, m), 3.39 (2Η, t, J = 6.7Hz), 3.84 (2H, t, J = 6.5Hz), 3. 91-3. 97 (4H, m) , 6.34 (1H, d, J = 2.2Hz), 6. 60-6. 65 (1H, m), 6. 83-6. 85 (3H, m), 6. 89-6. 92 (2H, m ), 7.09 (1H, dd, J = 2.4? 8.5Hz), 7.47 (1H, t, J = 8. 1Hz), 7.86 (1H, s), 8.22 (1H, d, J = 8.9Hz). (Ll 〇d) L- {7- [3- (N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl) -4-oxo-1- (3-propoxyphenyl) -1,4-dihydroquinoline-7-yloxy] heptylbu 4-acyl-1-azobicyclo [2.2.2] octane The 7- (7) obtained in Example (1 1 0c) -Bromoheptyloxy) -4 -oxo-1-(3-propoxyphenyl) -1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N- Acetylamine 180 〇 ^ and 1,4-diazinebicyclo [2.2.2] octane 3811 ^ were reacted according to the method of Example (1 1 j) to obtain 169 mg of the title compound as a pale red powder. R. ^ (CDC13) δρριη: 1.06 (3H, t, J = 7.4Hz), 1.20 (3H, t, J = 7.0Hz), 1.37 (6H, br), 1. 65-1. 90 (6H, m), 3.33 (6H, br), 3. 52-3. 56 (2H, m), 3.70 (6H, br), 3.83 (2H, t7 J = 6.1Hz), 3. 89-3. 97 (4H , m), 6.34 (1H, d, J = 2.0Hz), 6. 61-6. 67 (1H, m), 6.81-6.84 (3Η, m), 6. 88-6. 93 (2H, m), 7.09 (1H, dd, J = 2.2, 8.4Hz), 7.48 (1H, t, J-8. 1Hz), 7.79 (1H, s), 8.20 (1H, d, J-9.0Hz). Melting point : ~ 1 0 5 ° C Example 1 1 1 1- {7- [3- (N- (3,5-difluorophenyl) -N-ethylaminomethyl) -4-yl-1 bromide -(3-propoxyphenyl) -1,4-dihydroquinoline-7-yloxy] heptyl propidium (exemplified compound number: 2-8 0 6)-327-200300349 Examples (1 10-C) 7- (7-bromoheptyloxy) -4-oxo-1- (3-propoxyphenyl) -1,4-dihydroquinoline-3-carboxylic acid N- (3, 180 mg of 5-difluorophenyl) -N-acetamidine and 0.027 mg of pyridine were reacted in the same manner as in Example (1 1 j) to obtain 99 mg of the title compound as a pale yellow powder. Li R (CDC13) (5ppm: 1.06 (3H, t, J = 7.4Hz), 1.20 (3H, t, J = 7.2Hz), 1.38 (6H, br), 1.65-1. 75 (2H, m), 1. 80-1. 88 (2H, m), 2. 01-2. 06 (2H, m), 3.82 (2H, t, 1 = 6.0Hz), 3.90-3.97 (4H, m), 5.02 (2H , t, J = 7.5Hz), 6.33 (1H, d, J = 2.1Hz), 6.61-6.67 (1H, m), 6.81-6.85 (3H, m), 6.89-6.92 (2H, m), 7.09 ( 1H, dd, J = 2.1, 8.1Hz), 7.48 (1H, t, J = 8.1Hz), 7.82 (1H, s), 8.07-8.10 (2H, m), 8.20 (1H, d, 1 = 9. 0Hz), 8. 44-8.48 (1H, m), 9.5K2H, d, J = 5.9Hz). Melting point: ~ 8 1 ° C Example 1 1 2 Bromide 1- {7- [3- (N- (3,5-difluorophenyl) -N-ethylaminomethyl) -4-oxo-1-(3-propoxyphenyl) -1,4- ] Heptyl} -1_ azobicyclo [2.2 · 2] octane (exemplified compound number: 2-8 0 7) 7-(7 -bromoheptyloxy) -4 obtained in Example (1 1 〇c) -Oxy-1-(3 -propoxyphenyl) -1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N -acetamidine 180 mg and Pyridine 38 mg was reacted in the same manner as in Example (1 1 j) to obtain 160 mg of the title compound as a white powder. NMR (CDCl3) 6ppm: 1.06 (3H, t, J = 7.4Hz), 1.20 (3H, t, J = 7.2Hz), 1.37 (6H, br), 1.65-1. 89 (6H, m), 2.05 ( 6H, br), 2. 21-2. 23 (1H, m), 3. 46-3. 51 (2H, in), 3.67-3.71 (6H, ra), 3.83 (2H, t, J = 6.1Hz ), 3.90-3.98 (4H, m), 6.34 (1H, d, J-2.1Hz), 6.61-6. 66 (1H, m), 6. 83-6. 85 (3H, m), 6.9K2H, dd, J-1.9, 8. 9Hz), 7.09 (1H, dd, J-2.2, 8.3Hz), 7.48 (1H, t, J-8.2Hz), 7.83 (1H, s), 8.2K1H, d, J = 8.9Hz).-328-200300349 Melting point: ~ 1 0 0 ° C Example 1 1 3 1- {8- [3- (N- (3,5-difluorophenyl) -N-ethylamine bromide (Methylamidino) -4 -oxo-1- (3-propoxyphenyl) -1,4-dihydroquinoline-7-yloxy] octylb 4-azyl-1 -azobicyclo [2 · 2 · 2] octane (exemplified compound number: 2-8 4 8) (113a) 7- (8-bromooctyloxy) -4-oxo-1- (3-propoxyphenyl) -1,4- Dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 7-hydroxy-4 -oxo-1-(3 -Propoxyphenyl) -1,4-dihydro Dquinoline-3 -residual acid N- (3,5-difluorophenyl) -1 ^ -acetamidamine 680 mg, 1,8-dibromooctane 0.079 ml and potassium carbonate 295 mg, according to the example (1 1 The reaction of i) was carried out and purified to obtain the title compound as a colorless foam of 5 8 8 g. Lai (CDC13) (5ppm: 1.06 (3H, t, J = 7.4Hz), 1.2K3H, t, J = 7.0Hz), 1. 30-1.43 (8H, m), 1. 65-1. 74 (2H, m), 1. 80-1. 89 (4H, m), 3.39 (2H, t, J = 6.7Hz), 3.84 (2H, t, J-6.4Hz), 3. 91-3. 97 (4H, m), 6.35 (1H, d, J = 2.2Hz), 6. 60-6. 65 (1H, m), 6. 83-6. 85 (3H, m), 6. 89-6. 92 (2H, in), 7.08 (1H, dd, 1 = 2.2, 8.2Hz), 7.47 (1H, t, J = 8.2Hz), 7.86 (1H, s), 8.22 (1H, d, J = 9.1Hz ). (113b) Bromide 1- {8- [3- (N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl) -4-oxo-1- (3-propoxybenzene Group) -1,4-difluoroquinoline-7-yloxy] octylb 4-az-1-azobicyclo [2 · 2 · 2] octane The obtained from Example (1 1 3 a) 7-(8 -bromooctyloxy) -4 -oxo-1- (3-propoxyphenyl) -1,4-dihydroquinoline-3-carboxylic acid 1 ^-(3,5-difluorobenzene Group) -N-acetamidine 180 mg and 1,4-diazinebicyclo [2.2.2] octane 37 mg 'The reaction was carried out according to the method of Example (1 1 j) to obtain the title compound as a white powder 158 mg . -329-200300349 NMR- (CDCl3) 5ppm: 1.06 (3H, t, J = 7.4Hz), 1.20 (3H, t, J = 7.0Hz), 1.25-1.40 (8H, br), 1.65-1. 89 ( 6H, m), 3. 29-3. 33 (6H, m), 3. 47-3.54 (2H, m), 3.68-3. 71 (6H, m), 3.84 (2H, t, 1 = 6. 2Hz), 3. 89-3. 97 (4H, i), 6.34 (1H, d, J-2.1Hz), 6. 61-6. 67 (1H, m), 6. 82-6. 84 (3H , m), 6. 88-6. 93 (2H, m), 7.09 (1H, dd, J = 2.1, 8.3Hz), 7.48 (1H, t, J = 8.1Hz), 7.79 (1H, s), 8.20 (1H, d, J = 9.1Hz). Melting point: ~ 1 1 0 Example 1 1 4 1- {8- [3-(^ (3,5-difluorophenyl) -1 ethylamine methyl bromide Fluorenyl) -4-oxo-1- (3-propoxyphenyl) -1,4-dihydroquinoline-7-yloxy] octyl} -pyridine (exemplified compound number: 2-8 4 6 ) The 7- (8-bromooctyloxy) -4-oxo-1- (3-propoxyphenyl) -1,4-dihydroquinoline-3-carboxyl obtained in Example (1 1 3a) The acid N- (3, 5-difluorophenylb N-acetamidine 180 mg and pyridine 0 · 0 2 7 m 1 were reacted according to the method of Example (1 1 j) to obtain the title compound. White powder 1 1 5 mg. Bandit R (CDCl3) (5ppni: 1.06 (3Η, t, J = 7.4Hz), 1.2U3H, t, J = 7.2Hz), 1.27-1 .. 43 (8H, m ), 1. 64-1. 71 (2H, m), 1 80-1. 89 (2H, m), 2. 00-2. 05 (2H, m), 3.83 (2H, t, 1 = 6.2Hz), 3.90-3.97 (4H, m), 5.0K2H, t , J = 7.4Hz), 6.34 (1H, d, J-2.1Hz), -6.61-6.67 (lH, m), 6. 82-6. 85 (3H, m), 6. 89-6. 92 ( 2H, m), 7.09 (1H, dd, J-2.3, 8.4Hz), 7.48 (1H, t, J = 8.2Hz), 7.83 (1H, s), 8. 08-8.11 (2H, m), 8.2 K1H, d, J-8.9Hz), 8.47 (1H, t, J = 7.7Hz), 9.50 (2H, d, J = 5.8Hz). Melting point: ~ 7 7 ° C Example 1 1 5 Bromide 1- {8- [3- (N- (3,5-difluorophenyl) -N-ethylaminomethyl) -4-oxo-1- (3-propoxyphenyl) -1,4-dihydro Quinoline-7-yloxy] octylbu 1-azobicyclo [2 · 2 · 2] octane (Exemplified compound number: 2-8 4 7) 200300349 7- (8 obtained in Example (113a) -Bromooctyloxy) -4-oxo-1- (3-propoxyphenyl) -1,4-dihydroquinoline-3_carboxylic acid N- (3,5_di.fluorophenyl) -N -180 mg of acetamide and 37 mg of D-quinidine were reacted according to the method of Example (1 1 j) to obtain 1.25 mg of the title compound as a white powder. NMR (CDC13) δρριη: 1.06 (3H, t, J = 7.4Hz), 1.20 (3H, t, J = 7.1Hz), 1.27-1.41 (8H, m), 1. 65-1. 75 (4H, m), 1. 80-1. 89 (2H, m), 2.05 (6H, br), 2. 22-2.25 (1H, m), 3. 45-3. 49 (2H, m), 3. 67 -3. 71 (6H, m), 3.83 (2H, t, J = 6.2Hz), 3. 90-3. 98 (4H, m), 6.34 (1H, d, J = 2.1Hz), 6.61-6 66 (1H, m), 6. 83-6. 85 (3H, m), 6. 90-6. 92 (2H, m), 7.09 (1H, dd, J = 2.2, 8.4Hz), 7.48 ( 1H, t, J = 8.1Hz), 7.84 (1H, s), 8.2K1H, d, J = 8.9Hz). Melting point: ~ 9 7 ° C Example 1 1 6 Brominated l- {7- [l- (3,5-dimethoxyphenyl) -3- (N-ethyl-N-anilinemethyl) -4-oxo-1,4-dihydroquinolin-7-yloxy] heptyl} -4 -Acridine-1-azobicyclo [2 · 2 · 2] Xin Yuan (example compound number · 2-1 0 8) (116a) 7-benzyloxy-1- (3,5-dimethoxy) Phenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N-ethyl-N-phenylhydrazine The 7-benzyloxy-1- (3, 5-Dimethoxyphenyl) · 300 mg of 4-oxo-1,4-dihydrotetraline-3 -residue, 0.12 ml of chloramphenicol, 0.13 ml of N-ethylaniline and 0.29 ml of triethylamine, according to the examples (1 f) The reaction was carried out and purified. 1 40 mg of the title compound was obtained as a pale yellow solid. NMR. (CDC13) δρρπι: 1.2Κ3Η, t, J = 7.0Hz), 3.79 (6H, s), 3.94-3. 97 (2H, m), 4.94 (2H, s), 6.29 (2H, br ), 6.38 (1H, br), 6.59 (1H, s), 6.96 (1H, d, J = 8.7Hz), 7.10-7.35 (10H, m), 7.61 (1H, br), 8.26 (1H, d, J = 8.0Hz). 200300349 (116b) l- (3,5-dimethoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N -ethyl- N-Benzamidine The 7-benzyloxy-1-(3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3-obtained in Example (Π 6 a) 130 mg of carboxylic acid N-ethyl-N-benzidine and 30 mg of 10% Pd-C were reacted according to the method of Example (11h) to obtain 91 1 mg of the title compound as a pale yellow solid. Li R (CDC13) (5ppm: 1.19 (3H, t, J = 7.1 Hz), 3.75 (6H, s), 3. 90-4. 00 (2H, br), 6.26 (2H, br), 6.43 ( 1H, s), 6.52 (1H, t, 1 = 1.9Hz), 6.92 (1H, d, 1 = 8.8Hz), 7.10- 7.30 (5H, m), 7.52 (1H, br), 7.96 (1H, d , J = 8.0Hz). (116 (〇7- (7-Bromoheptyloxy) -1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -Carboxylic acid N-ethyl-N-phenylhydrazine 1- (3,5-dimethoxyphenyl) -7-hydroxy-4-oxy-1,4-obtained in Example (1 1 6 b) 87 mg of dihydroquinoline-3 carboxylic acid N-ethyl-N-phenylamidine, 0.1 ml of 1,7-dibromoheptane and 41 mg of potassium carbonate were reacted and purified according to the method of Example (lli). 88 mg of the title compound was obtained as a white solid. NMR (CDC13) δρριι: 1.2K3Η, t, J = 7.0Hz), 1. 3.0-1.47 (6H, m), 1.67-1.78 (2H, m), 1. 80-1. 87 (2H, m), 3.39 (2H, t, J = 6.8Hz), 3. 81-3. 85 (8H, in), 3. 95-3. 99 (2H, m), 6.25 -6. 40 (3H, m), 6.59 (1H, s), 6.88 (1H, d, J = 8.4Hz), 7.10- 7.30 (5H, m), 7.60 (1H, br), 8.24 (1H, d , 1 = 8.1Hz). (116d) bromide l- {7- [1- (3,5-dimethoxyphenyl) -3- (1ethyl-N-anilinemethyl) -4-oxo -1,4-dihydroquinoline-7-yloxy ] Heptyl Bu 4 -Acryl-Bazo Azo [2 · 2 · 2] Octane The 7-(7 -bromoheptyloxy) -1-(3,5- Dimethoxyphenyl) -4 -oxo-1,4 -monopyridine quinine -3 -n-acid N-ethylbenzamide 8 4 mg and 1,4-diazine-bicyclo [2 · 2.2] octyl 19 mg of alkane was reacted according to the method of Example (1 1 j)-332-200300349 to obtain the title compound as a white powder 8 8 mg. NMR. (CDC13) δρριι: 1.22 (3H, t, J = 7.0Hz ), 1.36 (6H, br), 1.65-1. 85 (4H, m), 3.35 (6H, br), 3.52-3. 56 (2H, m), 3.73 (6H, br), 3. 78-3 .87 (8H, m), 3.93 (2H, q, J = 7.0Hz), 6.25-6.40 (3H, m), 6.58 (1H, t, J = 2.0Hz), 6.89 (1H, d, J-δ 8Hz), 7.15-7. 30 (5H, m) ,. 7. 49 (1H, br), 8. 20 (1H, d, J = 8.5Hz). Melting point: 1 4 9 ~ 1 5 4 ° C Example 1 1 7 1- {7- [l- (3,5-dimethoxyphenyl) -3- [N -ethyl-N- (3-fluorophenyl) -carbamyl] -4 -oxo-1,4-dihydroquinoline-7-yloxy] heptylbu 4 -acryl-1 -azobicyclo [2 · 2 · 2] octane (Exemplary compound number: 2-736) {117 &} 7-benzyloxy-1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline -3 -carboxylic acid N-(3-fluorophenyl) -fluorenamine 7-benzyloxy-1- (3,5-dimethoxyphenyl) -4 -oxy-1 obtained in Example (Ilf) 300 mg of 4-dihydroquinoline 3-carboxylic acid, 0.11 ml of isobutyl chloroformate, 0.29 ml of triethylamine and 0.1 ml of 3-fluoroaniline, the reaction was carried out according to the method of Example (5 4 c), 3 37 mg of the title compound was obtained as NMR (CDC13) (5ppm: 3.83 (6H, s), 5.04 (2H, s), 6.49 (2H, d, 1 = 2.2Hz), 6.58 ( 1H, d, J = 2.2Hz), 6.67 (1H, t, J-2.2Hz), 6.77-6.82 (1H, m), 7.16 (1H, dd, J-2.3, 9.0Hz), 7.25-7.39 (7H , m), 7.75-7.79 (1H, m), 8.47 (1H, d, J = 8.9Hz), 8.80 (1H, s). (117b) 7-benzyloxy-1- (3,5-dimethylformate Oxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N -ethyl -N-(3-fluorophenyl) -amidine 7 obtained in Example (Π 7 a) -Benzyloxy-1-(3, 5 -dimethoxyphenyl 200 300 349)-4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N-(3 -fluorophenyl) -amidamine 3 20 mg, 55% sodium hydride 40 mg, and iodine ethyl compound 0.19 m 1 were reacted in accordance with the method of Example (54 d) to obtain the title compound as a pale yellow solid 3 03 mg NMR (CDC13) δρ πι: 1.20 (3Η, t, J = 6.9Hz), 3.80 (6H, s), 3.93 (2H, q, J = 7.0Hz), 4.96 (2H, s), 6.35 (2H, d, J-1.3Hz ), 6.40 (1H, d, J = 2.0Hz), 6.6K1H, t, J = 2.2Hz), 6.85-6.89 (1H, m), 6.97 (2H, dd, J = 2.0, 9.0Hz), 7.09 ( 1H, d, J = 2.2Hz), 7. 19-7.36 (6H, m), 7.73 (1H, s), 8.22 (1H, d, J = 8.9Hz). (117c) l- (3,5- Dimethoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N-ethyl-N- (3-fluorophenyl) -amidamine Example (1 1 7 b) the obtained 7-benzyloxy-1-(3,5-dimethoxyphenyl) -4-oxy-1, .4 -dihydroquinoline-3 -carboxylic acid N -ethyl -N -(3-Fluorophenyl) -amidamine 290 mg and 10% Pd-C60 mg were reacted according to the method of Example (11h) to obtain the title compound as a pale yellow solid, 231 mg. NMR '(CDC13) δ ppm: 1.18 (3H, t, J = 7.1Hz), 3.77 (6H, s), 3.9K2H, q, 1 = 7.0Hz), 6.34 (2H, s), 6.46 (1H, d , J-1.8Hz), 6.53 (1H, t, J = 2.1Hz), 6.87 ~ 7.00 (3H, m), 7.04 (1H, d, J = 7.8Hz), 7.18-7.24 (1H, m), 7.67 (1H, s), 7.97 (1H, d, J = 8.8Hz). (117 (1) 7- (7-bromoheptyloxy) -1- (3,5-dimethoxyphenyl) -4- Oxy-1,4-dihydroquinoline-3-carboxylic acid N-ethyl-N- (3-fluorophenyl) -amidine The 1- (3, 5-) obtained in Example (1 1 7 c) Dimethoxyphenyl) -7-hydroxy ~ 4-oxy-1,4-dihydroquinoline-3-carboxylic acid N-ethyl-N- (3-fluorophenylbutanamide 220mg, 1,7- 0.24 ml of dibromoheptane and 99 mg of potassium carbonate were reacted and purified according to the method of Example (1Π) to obtain the title compound as a light yellow solid 2 10 mg.-334-200300349 LiR (CDC13) (5ppm: 1.2K3H, t, J = 7.2Hz), 1. 31-1. 47 (6H, m), 1.69-1. 75 (2H, m), 1. 81-1. 88 (2H, m), 3.40 ( 2H, t, J = 6.8Hz), 3. 83-3. 86 (8H, m) / 3.94 (2H, q, J = 7.1Hz), 6.35 (1H, d, J = 1.8Hz), 6.4K2H, d, 1 = 1.1Hz), 6.60 (1H, t, J = 2.2Hz), 6.69-6.90 (2H, m), 6.97-7.00 (1H, m), 7.09 (1H, d, J = 8.1Hz), 7.19-7.24 (1H, m), 7. 73 (1H, s), 8.22 (1H, d, J = 8.9Hz).

(117e) bromide 1- {7- [l- (3,5-dimethoxyphenyl) -3- [N -ethyl-N-(3-fluorophenyl) -carbamoyl] -4 -Oxo-1,4-dihydroquinoline-7-yloxy] heptylbu 4 -acyl-1 -azobicyclo [2 · 2 · 2] octane The obtained from Example (1 1 7 d) 7-(7 -bromoheptyloxy) -1-(3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N -ethyl-N- ( 195 mg of 3-fluorophenyl) -fluorenamine and 70 mg of 1,4-diazine · bicyclo [2 · 2 · 2] octane 'were reacted according to the method of Example (1 lj) to obtain 211 mg of the title compound as a white powder. . NMR.  (CDC13) δρρπι: 1. 20 (3H, t, J = 7. 1Hz), 1. 37 (6H, br), 1.  65-1.  80 (4H, m), 3.  30-3.  40 (6H, in), 3. 52-3. 57 (2H, m), 3.  71-3.  75 (6H, m), 3.  82-3.  85 (8H, m), 3. 92 (2H, q, J = 7. 0Hz), 6.  35-6.  37 (3H, m), 6. 60 (1H, t, J = 2. 1Hz), 6.  86-6.  92 (2H, m), 6. 97 (1H, d, J = 9. 7Hz), 7. 05 (1H, d, J = 8. 0Hz), 7. 19-7. 25 (1H, m), 7. 64 (1H, s), 8. 19 (1H, d, J = 8. 9Hz).  Melting point: ~ 1 2 0 ° C Example 1 1 8 Bromine l- {7- [l- (3-butoxy-5-methoxyphenyl) -3- [N- (3,5-difluoro Phenyl) -N-ethylamine formamyl: l · 4-oxo-I, 4-dihydroquinoline-7-yloxy] heptyl}-4 -acyl-1 -azobicyclo [2 · 2 · 2] Octane (Exemplified compound number: 2-799) (1183) 1- (3-butoxy-5-methoxyphenyl) -7-methoxymethoxy-4--335-200300349 oxygen- 1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -acetamidine The 1- (3-hydroxy-5 -formaldehyde) obtained in Example (1 8 5e) Oxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 1. 52g, l-bromobutane 64ml and 823mg of potassium carbonate were reacted according to the method of Example (104) to obtain the title compound as a colorless foam 1.  5 3 g. Li R ~ (CDCl3) (5ppJH: 0 · 99 (3Η, t, J = 7. 4Hz), 1. 21 (3H, t, J = 7. 0Hz), 1. 45-1.  56 (2H, m), 1.  77-1.  82 (2H, m), 3. 4K3H, s), 3. 82 (3H, s), 3.  90-3.  98 (4H, m), 5. 1K2H, s), 6. 46 (2H, d, J = 1. 8Hz), 6.  59 ~ 6.  67 (3H, m), 6. 84 (2H, dd, J = 2. 1, 8. 0Hz), 7. 04 (1H, dd, J = 2. 2, 8. 9Hz), 7. 89 (1H, s), 8. 23 (1H, d, J = 9. 1Hz).  (118b) 1- (3-butoxy-5-methoxyphenyl) bromide-7-hydroxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5- Difluorophenyl) -N-acetamidinium 1- (3-butoxy-5-methoxyphenyl) _7_methoxymethoxy_4_oxy- obtained in Example (1 1 8 a) 1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidoamine 1.  5 1 g, the reaction was carried out according to the method of Example (1 0 2 d) to obtain the title compound as a white solid 1. 47g. Li R.  (CDC13) δρριη: 0. 98 (3H, t, J = 7. 3Hz), 1. 29 (3H, t, J = 7. 2Hz), 1. 44-1. 54 (2H, m), 1. 73-1. 80 (2H, m), 3,80 (3H, s), 3. 93 (2H, t, J = 6. 4Hz), 4. 0K2H, q, J-7. 1Hz), 6. 28 (1H, s), 6. 35 (1H, s), 6. 59 (1H, s), 6. 69 (1H, d, J = 1. 9Hz), 6. 79 (1H, t, J = 8. 5Hz), 7. 06 (2H, d, J = 4. 8Hz), 7. 58 (1H, dd, J = 1. 6, 9. 0Hz), 7. 74 (1H, s), 8. 20 (1H, d, J = 9. 1Hz).  (118c) 7- (7-bromoheptyloxy) -1- (3-butoxy-5-methoxyphenyl) -4-oxo-I, 4-dihydroquinoline-3-carboxylic acid 1 ( 3,5-Difluorophenyl) -N-acetamidine The 1- (3-butoxy-5-methoxyphenyl) -7-200300349 hydroxy-4- obtained in Example (1 1 8 b) Oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 700 mg, 1,7-dibromoheptane 0. 68 ml and 278 mg of potassium carbonate were reacted and purified according to the method of Example (1 1 i) to obtain 590 mg of the title compound as a colorless foam. Rei R.  (CDC13) δρριη: 0. 99 (3H, t, J = 7. 4Hz), 1. 2K3H, t, J = 7. 2Hz), 1. 31-1. 55 (8H, m), 1. 69-1. 88 (6H, m), 3. 40 (2H, t, J = 6. 9Hz), 3. 83 (3H, s), 3. 86 (2H, t, J = 6. 4Hz), 3. 90-3. 98 (4H, m), 6. 40 (1H, d, J = 2. 2Hz), 6. 46 (2H, d, J = 2. 1Hz), 6. 60-6. 65 (2H, m), 6. 84 (2H, dd, J = 2. 2, 8. 0Hz), 6. 90 (1H, dd, J = 2. 3, 9. 2Hz), 7. 85 (1H, s), 8. 22 (1H, d, J = 8. 9Hz).  (1 1 8 d) bromide 1-{7-[1-(3 -butoxy-5 -methoxyphenyl) -3-[N- (3,5-difluorophenyl) -N -ethyl Carboxamido] -4 -oxo-1,4-dihydroquinoline-7-yloxy] heptyl} -4-acyl-pyrazobicyclo [2; 2. 2] Octane 7-(7 -bromoheptyloxy) -1-(3 -butoxy-5-methoxyphenyl) -4 -oxo-1,4 obtained in Example (1 1 8 c) -Dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 160mg and 1,4-diazine bicyclo [2. 2. 2] 31 mg of octane was reacted according to the method of Example (1 1 j) to obtain 136 mg of the title compound as a white powder. NMR (CDC13) δρριη: 0. 98 (3H, t, J = 7. 4Hz), 1. 20 (3H, t, J = 7. 0Hz), 1. 38 (6H, br), 1. 45-1. 54 (2H, m), 1. 69-1.  82 (6H, m), 3. 3K6H, br), 3.  52-3.  56 (2H, m), 3. 68-3. 71 (6H, m), 3. 83 (3H, s), 3. 85 (2H, t, J = 6. 2Hz), 3. 89-3. 98 (4H, m), 6. 40 (1H, d, J = 2. 1Hz), 6. 42 (2H, dJ = 1. 8Hz), 6. 6K1H, t, J = 2. 1Hz), 6.  62-6.  66 (1H, m), 6. 83 (2H, dd, J = 2. 0, 7. 7Hz), 6. 92 (1H, dd, J = 2. 1, 8. 9Hz), 7. 78 (1H, s), 8. 19 (1H, d, J = 9. 1Hz).  Melting point: ~ 1 1 5 ° C Example 1 1 9-337-200300349 Bromide 1- {7- [l- (3-butoxy-5-methoxyphenyl) -3- [N- (3, 5 -difluorophenyl) -N-ethylaminomethylmethyl] -4 -oxo-1,4-dihydroquinoline-7 -yloxy] heptylpyridine (Exemplified compound number: 2-7 9 7) The 7-(7-bromoheptyloxy) -1-(3 -butoxy-5-methoxyphenyl) -4 -oxo-1,4 -di obtained in Example (1 1 8 c) Hydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamide 200mg and pyridine 5 ml was reacted in the same manner as in Example (1 1 j) to obtain 172 mg of the title compound as a white solid. Rei R.  (CDC13) δρριη: 0. 98 (3H, t, J = 7. 3Hz), 1. 20 (3H, t, J = 7. 0Hz), 1. 39 (6H, br), 1. 45-1.  54 (2H, m), 1.  68-1.  82 (4H, m), 2.  00-2. 10 (2H, br), 3.  83-3.  86 (5H, m), 3.  90-3.  98 (4H, m), 5. 03 (2H, t, J = 7. 5Hz), 6. 39 (1H, d, J = 2. 1Hz), 6. 43 (2H, d, J = 2. 1Hz), 6. 6K1H, t, J = 2. 1Hz), 6. 63-6. 66 (1H, m), 6. 84 (2H, dd, J = 2. 2, 7. 8Hz), 6. 9K1H, dd, J = 2. 2, 8. 9Hz), 7. 8K1H, s), 8. 07-8.  11 (2H, m), 8. 20 (1H, d, J = 8. 9Hz), 8. 46 (1H, t, J = 7. 6Hz), 9. 53 (2H, d, J = 5. 9Hz).  Melting point: 1 Ο 1 ~ 1 0 4 ° C Example 1 2 0 1- {7- [1- (3-butoxy-5-methoxyphenyl) -3- [1 ^-(3, 5-Difluorophenyl) -N-ethylaminomethylmethyl] -4 -oxo-1,4-dihydroquinoline-7 -yloxy] heptyl 丨 -buzozobicyclo [2 · 2 · 2 ] Octane (exemplified compound number: 2 -7 9 8) 7-(7 -bromoheptyloxy) -1-(3 -butoxy-5 -methoxybenzene) obtained in Example (1 1 8 C) N- (3,5-difluorophenyl) -N-acetamidine and 0,3,1 1 mg of p-oxo-1,4-dihydroquinoline-3, carboxylic acid, The reaction was carried out according to the method of Example (1 lj) to obtain the white powder of the title compound 200300349 1 6 8 mg. NMR ', (CDC13) δρριη: 0. 99 (3H, t, J = 7. 4Hz), 1. 20 (3H, t, J = 7. 1Hz), 1. 38 (6H, br), 1. 45-1.  55 (2H, m), 1.  71-1.  86 (6H, m), 2. 05 (6H, br), 2.  21-2. 24 (1H, m), 3.  46-3. 51 (2H, m), 3.  68-3.  72 (6H, m), 3.  83-3.  87 (5H, m), 3.  90 ~ 4.  01 (4H, m), 6. 40 (1H, d, J = 2. 1Hz), 6. 44 (2H, d, J = 2. 1Hz), 6.61 (1Η, t, J = 2. 0Hz), 6.  63-6. 66 (lH, m), 6. 84 (2H, dd, J = 2. 0, 7. 9Hz), 6. 9K1H, dd, J = 2. 1, 8. 9Hz), 7. 83 (1H, s), 8. 2K1H, d, J = 9. 0Hz).  Melting point: ~ 1 1 5 t Example 1 2 1 Bromide 1- {8- [l- (3-butoxy-5-methoxyphenyl) -3- [N- (3,5-difluorobenzene ) -N-ethylaminomethylmethyl] -4-yl · 1,4-dihydroquinoline-7-yloxy] octylbu 4 -acyl-1 -azobicyclo [2 · 2 · 2] Octane (Exemplified compound number: 2-845) (121a) 7- (8-bromooctyloxy) -1- (3-butoxy-5-methoxyphenyl) -4-oxo-1,4- Dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 1- (3 -butoxy-5 -formaldehyde) obtained in Example (1 1 8 b) (Oxyphenyl) -7-yalyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 1 ^-(3,5-difluorophenyl) -N-acetamidine 700mg 8-Dibromooctane 74 ml and 278 mg of potassium carbonate were reacted and purified according to the method of Example (1 1 i) to obtain 593 mg of the titled colorless foam. (CDCI3) (5ppm: 0. 99 (3H, t, J = 7. 4Hz), 1. 2K3H, t, J = 7. 0Hz),: 31-1. 55 (10H, m), 1. 68-1. 88 (6H, m), 3. 40 (2H, t, J = 6. 9Hz), 3. 83 (3H, s), 36 (2H, t, J = 6. 4Hz), 3.  90-3.  3.  98 (4H, m), 6. 40 (1H, d, J = 2. 2Hz), 6. 45 (2H, d,. 1Hz), 6. 6K1H, t, J = 2. 1Hz), 6. 62-6. 65 (lH, m), 6. 84 (2H, dd, J = 2. 1, 8. 0Hz), SI (1H, dd, J-2. 2, 8. 9Hz), 7. 85 (1H, s), 8. 21 (1H, d, J-9. 0Hz).  -339-200300349 (121b) Bromide 1- {8- [1- (3-butoxy-5-methoxyphenyl) -3- [N- (3,5-difluorophenyl) -N- Ethylaminomethyl] -4-yl-1,4-dihydroquinoline-7-yloxy] octylb 4-azyl-1 -azobicyclo [2 · 2. 2] Octane uses the 7- (8-bromooctyloxy) -1-(3-butoxy-5-methoxyphenyl) -4-oxy-1,4-obtained in Example (12 1 a) Dihydroquinoline-3 -carboxylic acid N- (3, 5-difluorophenyl)-[acetamidoamine 16〇11 ^ and 1,4-diazine_bicyclo [2. 2. 2] 31 mg of octane. The reaction was carried out according to the method of Example (11j) to obtain 136 mg of the title compound as a white powder. NMR.  (DMS0-d6) δ ppm: 0. 94 (3H, t, J = 7. 4Hz), 1. 0K3H, t, J = 7. 1Hz), 1. 29 (8H, m), ί.  39-1. 48 (2H, m), 1.  59-1.  74 (6H, m), 2.  99-3.  03 (6H, m), 3. 13-3.  17 (2H, m), 3.  23-3. 26 (6H, m), 3.  81-3.  85 (5H, m), 3. 89 (2H, t, J = 6. 3Hz), 4.  02 (2H, t, J = 6. 5Hz), 6. 36 (1H, d, J = 2. 2Hz), 6. 63 (2H, s), 6. 73 (1H, t, J = 2. 1Hz), 6. 99 (1H, dd, 1 = 2. 1, 8. 9Hz), 7. 04-7.  13 (3H, m), 8. 00 (1H, d, J = 8. 9Hz), 8. 08 (1H, s).  Melting point: ~ 1 1 5 ° C Example 1 2 2 Bromide 1- {8- [l- (3-butoxy-5-methoxyphenyl) -3- [N- (3,5-difluoro Phenyl) -N-ethylamine formamidine 4-oxo-1,4-dihydroquinoline-7-yloxy] amyl} -pyrene ratio table (ex. Compound number · 2-8 4 3) The 7-(8-bromooctyloxy) -1-(3 -butoxy-5 -methoxyphenyl) -4 -oxo-1,4-dihydroquine obtained in Example (1 2 1 a) N- (3,5-difluorophenyl) -N-acetamidine 2 10 mg and pyridine 0.5 m 1 were reacted according to the method of Example (1 1 j). The title compound was obtained as a colorless foam 140 mg-340- 200300349 R R (CDC13) δ ppm: 0. 98 (3H, t, J = 7. 3Hz), 1. 21 (3H, t, 1 = 7.  0Hz), L 25-1. 45 (8H, br), J.  47-1.  54 (2H, m), 1.  67-1.  81 (4H, m), 2. 04 (2H, br), 3.  83-3. 87 (5H, m), 3.  90-4. 01 (4H, m), 5. 01 (2H, br), 6. 40 (1H, d, J = 1. 8Hz), 6. 43 (2H, d, J = 1. 9Hz), 6.  60-6.  66 (2H, m), 6. 84 (2H, dd, J = 2. 0, 7. 8Hz), 6. 9K1H, dd, J = 1. 6, 8. 9Hz), 7. 82 (1H, s), 8. 10 (2H, br), 8. 20 (1H, d, J = 8. 9Hz), 8. 47 (1H, t, J = 7. 4Hz), 9. 5K2H, br).  Example 1 2 3 1- {8- [1- (3-butoxy-5-methoxyphenyl) -3- [1 ^-(3,5-dichlorophenyl) -N-ethyl bromide Aminemethyl] -4 -oxy-1,4 -dichloro D quelin-7 -yloxy] octyl} -1_azobicyclo [2 · 2 · 2] octane (Exemplified compound number: 2 -844) 7-(8-bromooctyloxy) -1-(3 -butoxy-5 -methoxyphenyl) -4 -oxo-1,4-obtained in Example (1 2 1 a) Dihydroquinoline-3 -carboxylic acid N- (3, 5-difluorophenyl) -N-acetamidine 2 10 mg and panquinidine 40 mg were carried out according to the method of Example (1 1 j) By reaction, 167 mg of the title compound was obtained as a white powder. NMR (CDC13) δρριη: 0. 99 (3H, t, J = 7.  4Hz), * 1.  20 (3H, t, 1 = 7. 2Hz), 1. 34 (8H, br), 1. 45-1.  55 (2H, m), 1.  67-1.  82 (6H, m), 2. 06 (6H, br), 2.  22-2.  25 (1H, br), 3. 46-3. 51 (2H, m), 3.  68 ~ 3.  72 (6H, m), 3, 83-3.  87 (5H, m), 3.  90 ~ 3.  98 (4H, m), 6. 40 (1H, d, J = 2. 2Hz), 6. 44 (2H, d, J = 2. 1Hz), 6. 6K1H, t, J = 2. 1Hz), 6. 62-6. 66 (lH, m), 6. 84 (2H, dd, J = 2. 1, 8. 0Hz), 6. 9K1H, dd, 1 = 2. 2, 8. 9Hz), 7. 83C1H, s), 8. 2K1H, d, 1 = 8. 9Hz).  Melting point: ~ 100 ° C Example 1 2 4 (3,5-diethoxyphenyl) bromide 3- [1 ^-(3,5-difluorophenyl 200300349) -N- (2- Propargyl) -carbamoyl 4-oxo-1,4-dihydroquinolin-7-yloxy] heptylbu 4-az-1-azobicyclo [2 · 2 · 2] octane (Exemplified compound number: 2-7 6 2) (124a) 7-benzyloxy-1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxyl Acid N- (3,5-difluorophenyl) -fluorenamine The 7-benzyloxy-4- (3,5-diethoxyphenyl) -1-oxo 1,4 obtained in Example (44d) -Dihydroquinoline-3 -carboxylic acid 3. 0g, isobutyl chloroformate 0. 94ml, triethylamine 1. 82ml and 3,5-difluoroaniline 1. 26g, the reaction was carried out according to the method of Example (54c) to obtain the title compound as a white solid 3. 56g ° Li R (CDC13) δρριη: 1. 45 (6H, t, J = 7. 1Hz), 3.  98-4.  06 (4H, m), 5. 03 (2H, s), 6. 45 (2H, d, J = 2. 2Hz), 6. 51-6. 56 (1H, m), 6. 59 (1H, d, J = 2. 4Hz), 6. 65 (1H, t, J = 2. 2Hz), 7.  16 (1H, dd, J = 2. 3, 9. 0Hz), 7. 28-7. 41 (7H, m), 8. 45 (1H, d, J = 9. 2Hz), 8. 78 (1H, s).  (124b) l- (3,5-diethoxyphenyl) -7-hydroxy-4 · oxy-1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl) -Amidine The 7-benzyloxy-1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxyl obtained in Example (1 2 4a) Acid N- (3,5-difluorophenyl) -amidine 5 g and 10% P d-C, the reaction was carried out according to the method of Example (1 1 h) to obtain the title compound as colorless crystals 2. 2 0 g. ISiMR (DMS0-d6) δ ppm: 1. 34 (6H, t, J = 7. 1Hz), 4.  08 (4H, q, J = 7. 1Hz), 6. 50 (1H, d, J = 2. 1Hz), 6. 74 (1H, t, J = 2. 1Hz), 6. 86 (2H, d, J = 2. 2Hz), 6.  91-6.  97 (1H, m), 7. 02 (1H, dd, J = 2. 2, 8.  8Hz), 7.  46-7. 53 (2H, m), 8. 25 (1H3 d, J = 8. 8Hz), 8. 58 (1H, s).  200300349 (124c) l- (3,5-monoethoxybenzyl) -7 ~ methoxymethoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5- Difluorophenyl) -amidine The 1- (3,5_diethoxyphenyl) -7_hydroxy-4-oxo-1,4-dihydroquinoline obtained in Example (1 2 4 b) 3 -carboxylic acid (3, 5-difluorophenyl) -amidamine 2. 0g, chloromethyl methyl ether 0. 94ml and potassium carbonate i. 15g, the reaction was carried out according to the method of Example (102b), and the title compound was obtained as a white solid 1. 83g  (CDC13) (5 ppm: 1. 44 (6H, t, J =: 6. 7Hz), 3. 44 (3H, s), 4.  02-4.  08 (4H, m), 5. 17 (2H, s), 6.  51-6.  57 (3H, m), 6. 63 (1H, t, J = 2. 2Hz), 6. 78 (1H, d, J = 2. 2Hz), 7. 23 (1H, dd, J = 2. 2, 8. 9Hz), 7. 39 (2H, dd, 1 ^ = 2. 9, 9. 0Hz), 8. 48 (1H, d, 1 = 8. 9Hz), 8. 82 (1H, s).  1- (3,5-diethoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid , 5-Difluorophenyl) _N · (2 · _propargyl) -amidamine Example 1 ((3,5-diethoxyphenyl) -7-methoxymethoxy obtained from Example 124 -4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid- (3, 5-difluorophenyl) -amidamine 1. 8 g, 55% sodium hydride 2 2 5 mg and 3-bromo Propyne 1.  0 3 m 1, according to the method of Example (5 4 d) for reaction and purification, the title compound was obtained as a yellow foam 1. 66g. NMF (CDC13) δρριη: 1. 44 (6H, t, J = 7. 2Hz), 2. 25 (1H, t, J = 2. 5Hz), 3. 4K3H, s), 4. 04 (4H, q, J = 7. 3Hz), 4. 64 (2H, d, J = 2. 4Hz), 5. 12 (2H, s), 6. 46 (2H, d, J = 2. 1Hz), 6. 59 (1H, t, J = 2. 2Hz), 6. 64-6. 70 (2H, m), 6. 96 (2H, dd, J = 2. 1, 7. 9Hz), 7. 06 (1H, dd, J = 2. 2, 8. 9Hz), 7. 98 (1H, s), 8. 230H, d, J = 8. 9Hz).  (124e) 1- (3,5-diethoxyphenyl) 7-hydroxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl) -N- (2-propargyl) -amidamine-343-200300349 The 1- (3,5-diethoxyphenyl) -7-methoxymethoxy ... obtained from Example (124d) -1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N- (2-propargyl) -amidamine 1.  60 g, according to the method of Example (102 d), the reaction was carried out to obtain the title compound as a light brown solid 1.  6 2 g. NMR.  (DMS0-d6) δρριη: 1. 34 (6H, t, J = 7.  1Hz), 3. 20 (1H, t, J = 2. 2Hz), 4. 07 (4H, q, J = 7. 1Hz), 4. 67 (2H, d, J = 2. 4Hz), 6. 39 (1H, d, J = 2. 2Hz), 6. 6K2H, d, J = 2. 1Hz), 6. 70 (1H, t, J = 2. 1Hz), 6. 80 (1H, dd, J = 2. 2, 8. 8Hz), 7. 05-7. 12 (1H, m), 7. 16 (2H, dd, J = 2. 1, 8. 2Hz), 7. 89 (1H, d, I = 8. 8Hz), 8. 06 (1H, s).  (l24f) 7- (7-bromoheptyloxy) -1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N-(3, 5-Difluorophenyl) -N- (2-propargyl) -fluorenamine The 1- (3,5-diethoxyphenyl) -7-hydroxy-4 obtained in Example (1 2 4 e) -Oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N- (2-propargyl) -amidamine 1.  60 g, 1,7-dibromoheptane 1.  4 5 m 1 and potassium carbonate 590 mg were reacted and purified according to the method of Example (1 1 i) to obtain the title compound as a light yellow foam 1.  3 0 g. NMR (CDC13) (5ppm: 1.  31-1. 48 (12H, m), 1. 70-1.  78 (2H, m), 1. 80-1. 88 (2H, e), 2. 24 (1H, t, J = 2. 4Hz), 3. 40 (2H, t, J = 6. 8Hz), 3. 87 (2H, t, J = 6. 4Hz), 4. 04 (4H, q, 1 = 7.  1Hz), 4. 64 (2H, d, J = 2. 2Hz), 6. 42 (1H, d, J = 2. 1Hz), 6. 46 (2H, d, J = 2. 0Hz), 6. 60 (1H, t, J = 2. 0Hz), 6.  64-6.  69 (1H, m), 6, 91-6.  97 (3H, m), 7. 94 (1H, s), 8. 22 (1H, d, J = 9. 3Hz).  (124g) l- {7- [l- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N- (2-fastpropyl)> Aminomethyl] -4 -oxy-1,4-_ chloropirin-7-yloxy] heptylbu 4 -acyl-1 -azobicyclo [2 · 2; 2] octane bromide will 7- (7-Bromoheptyloxy) -1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N obtained in Example (124f) -(3,5 -difluorobenzene 200300349) -N-(2 -propargyl) -amidamine 2 50 mg and 1,4-diazine-bicyclo [2. 2. 2] 82 mg of octane. The reaction was carried out according to the method of Example (llj), and the title compound was obtained as light brown powder 255 mg. NMR (DMS0-d6) (5ppm: 1. 26-1.  39 (12H, m), 1. 59-1.  69 (4H, m), 2. 99-3. 03 (6H, m), 3. 13-3. 17 (2H, m), 3.  21-3. 26 (7H, m), 3. 90 (2H, t, J = 6. 2Hz), 4. 08 (4H, q, J = 6. 9Hz), 4. 68 (2H, d, J = 2. 2Hz), 6. 37 (1H, d, J = 2. 2Hz), 6. 64 (2H, d, J = 1. 9Hz), 6. 70 (1H, t, J = 2. 1Hz), 6. 99 (1H, dd, J-2.  2, 9. 0Hz), 7. 06-7. 12 (1H, m), 7. 17 (2H, dd, J-2. 1, 8. 5Hz), 7. 98 (1H, d, J = 8. 9Hz), 8. 12 (1H, s).  Example 1 2 5 1- {7- [l- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N- (2-propargyl ) -Aminomethylamidino] -4 -oxo-1,4-dihydroquinoline-7 -yloxy] heptyl}-1 -azobicyclo [2 · 2 · 2] octane (exemplified compound numbers : 2-761) The 7-(7-bromoheptyloxy) -1-(3,5-diethoxyphenyl) -4 -oxy-1,4 -di obtained in Example (1 2 4 f) Hydroquinoline-3 -carboxylic acid N- (3, 5-difluorobenzene) -N-(2 -propargylbutanamine 250 mg and eye pyridine 8 2 mg, according to the method of Example (llj) The reaction was conducted to obtain the title compound as a light brown solid 255 mg ° NMR (DMS0-d6) δρρπι: 1. 20-1. 40 (12Η, m), 1.  57-1.  67 (4H, m), L 82-1. 86 (6H, br), 2.  04-2.  07 (1H, m), 3.  04-3.  08 (2H, m), 3. 2K1H, t, J = 2. 3Hz), 3 32-3. 37 (6H, m), 3. 89 (2H, t, J = 6. 3Hz), 4. 07 (4H, q, J = 7. 0Hz), 4. 68 (2H, d,; -2. 3Hz), 6. 37 (1H, d, J = 2. 1Hz), 6. 63 (2H, d, 1 = 1. 9Hz), 6. 70 (1H, t, J = 2. 0Hz), 6. 99 (1H, dd, J = 2. 2, 9. 0Hz), 7. 06-7.  11 〇H, m), 7.  17 (2H, dd, J = 2. 1, 8. 4Hz), 98 (1H, d, J = 9. 0Hz), 8. 12 (1H, s).  200300349 Example 1 2 6 1- {7- [1- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N- (2-alkyne (Propyl) -aminomethylmethyl] -4-oxo-1,4-dihydroquinoline-7-yloxy] heptylb-methyl-piperium (Exemplary compound number: 2-7 6 0) Examples (1 2 4 f) The obtained 7-(7 -bromoheptyloxy) -1-(3,5-diethoxyphenyl) -4-oxo-1,4-dihydro Hquinoline-3-carboxyl Acid N- (3, 5-difluorophenyl) -N-(2-propargyl) -amidamine 2 50 mg and 1-methanilidine 0. The reaction was carried out at 5 m in accordance with the method of Example (1 1 j) to obtain the title compound as a yellow solid 2 2 4 m g NMR (DMS0-d6) δρρπι: 1.  27-1. 40 (12Η, m), 1. 46-1. 58 (2H, m), 1. 59-1. 67 (4H, m), 1. 76 (4H, br), 2. 97 (3H, s), 3. 21 (1H, t, J = 2. 4Hz), 3. 23-3. 30 (6H, m), 3. 90 (2H, t, J = 6. 3Hz), 4. 08 (4H, q, J = 6. 9Hz), 4. 68 (2H, d, J = 2. 3Hz), 6. 37 (1H, d, J = 2. 2Hz), 6. 64 (2H, d, J = 2. 0Hz), 6. 70 (1H, t, J = 2. 1Hz), 7. 04 (1H, dd, J = 2. 2, 9. 2Hz), 7. 06-7.  12 (1H, m), 7.  17 (2H, dd, J = 2. 1, 8. 4Hz), 7. 98 (1H, d, J = 8. 9Hz), 8. 12 (1H, s).  Melting point · 1 2 8 ~ 1 3 0 ° C Example 1 2 7 Bromide l- {7- [1- (3,5-diethoxyphenyl) -3- [1 ^-(3,5- Difluorophenyl) -N-ethylamine formamidine 4-oxo-1,4-dihydroquinoline-7-yloxy] heptyl} -bumethyl-piperidine (Exemplified compound numbers: 2-7 5 1) 7- (7-bromoheptyloxy) · 1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline obtained in Example (4 4 g)- A solution of 3-carboxylic acid N- (3, 5-difluorophenyl) -N-acetamidamine 1 13 g and 1-methylpiperidine 7 5 m 1 in acetonitrile 50 0 m 1, heated under reflux for 15 hours . The solvent and excess 1-methylpiperidine 'were distilled off, and the precipitated solid was washed with diethyl ether to obtain a crude product of the title compound. The obtained crude product-346-200300349 was recrystallized from ethanol. 1 1 g of the title compound was obtained as yellow crystals. Bandit R.  (CDC13) δρρπι: 1. 20 (3H, t, J = 7. 0Hz), 1. 42-1. 45 (12H, m), 1. 72-1. 9K10H, m), 3. 32 (3H, s), 3. 51-3. 76 (6H, m), 3. 85 (2H, t, J = 6. 1Hz), 3. 92 (2H, q, J = 7. 1Hz), 4. 01-4. 06 (4H, m), 6. 40 (1H, d, J = 2. 0Hz), 6. 43 (2H, d, J = 2. 1Hz), 6. 60 (1H, t, J = 2. 2Hz), 6.  61-6.  66 (1H, m), 6. 84 (2H, dd, J = 2. 1, 8. 0Hz), 6. 9K1H, dd, J = 2. 2, 9. 1Hz), 7. 83 (1H, s), 8. 2K1H, d, J-8. 9Hz).  Melting point: 1 3 2 ~ 1 3 5 ° C Example 1 2 8 1- {6- [l- (3,5-diethoxyphenyl) -3- [N- (3,5-difluoro Phenyl) -N-ethylaminomethylmethyl] -4 -oxo-1,4-dihydroquinoline-7 -yloxy] -hexylbu 4 -acyl-1 -azobicyclo [2 · 2 · 2 ] Octane (exemplified compound number: 2-7 3 3) (128 &) 7- (6-bromohexyloxy) -1- (3,5-diethoxyphenyl) -4-yl-1,4 -Dihydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl) -N -acetamidin The 1- (3,5-diethoxyphenyl) obtained in Example (44f)- 7-Hydroxy-4-oxy-1,4-dihydroquinoline-3-carboxylic acid N · (3,5-difluorophenyl) -N-acetamidamine 252mg, 1,6-dibromohexane 0 . 23 ml and 137 mg of potassium carbonate were reacted and purified according to the method of Example (1 1 i) to obtain 280 mg of the title compound as a white wax. Li R (CDC13) δρριη: 1. 20 (3H, t, J = 7. 1Hz), 1. 42-1. 46 (10H, m), 1. 72-1. 76 (2H, m), 1. 83-1. 88 (2H, m), 3. 40 (2H, t, J = 6. 8Hz), 3. 87 (2H, t, J = 6. 2Hz), 3. 93 (2H, q, 1 = 7. 1Hz), 4. 03 (4H, q, J = 6. 9Hz), 6. 40 (1H, d, J = 2. 1Hz), 6. 44 (2H, d, J = 2. 0Hz), 6. 59-6. 65 (2H, m), 6. 84 (2H, dd, J = 2. 0, 8. 0Hz), 6. 9K1H, dd, J = 2. 1, 8. 9Hz), 7. 85 (1H, s), 8. 23 (1H, d, J = 9. 1Hz).  200300349 (128b) 1- {6- [1- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminemethyl] -4 -oxo-1,4 -dihydroquinoline-7 -yloxybhexylb 4 -acyl-1 -azobicyclo [2. 2 · 2] Octane 7-(6 -bromohexyloxy) -1-(3; 5 -diethoxyphenyl) -4 -oxy-1,4-obtained in Example (1 2 8 a) Dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 130mg and 1,4-diazine-bicyclo [2. 2. 2] Octane 4 4 g, which was reacted in the same manner as in Example (1 1 j) to obtain the title compound as a white powder 127 mg. NMR.  (CDC13) δρρηι: 1. 20 (3H, t, J-7. 1Hz), L 41-1. 52 (10H, m), 1. 69- 1.  82 (4H, m), 3.  24-3. 28 (6H, m), 3.  53-3.  58 (2H, m), 3.  65-3.  68 (6H, m), 3. 84 (2H, t, J = 6. 0Hz), 3. 9K2H, q, J = 7. 2Hz), 4. 03 (4H, q, 1 = 6. 9Hz), 6. 39 (1H, d, J = 2. 1Hz), 6. 4K2H, d, J = 2. 0Hz), 6. 60 (1H, t, J = 2. 1Hz), 6. 61-6. 66 (1H, m), 6. 82 (2H, dd, J = 2. 0, 7. 9Hz), 6. 90 (1H, dd, J = 2. 1, 9. 1Hz), 7. 80 (1H, s), 8. 19 (1H, d, J = 8. 9Hz).  Melting point: 1 2 3 ~ 1 2 6 t: Example 1 2 9 1- {6- [1- (3,5-diethoxyphenyl) -3- [1 (3,5-difluorobenzene) bromide ) -N-ethylamine formamyl] -4 -oxo-1,4-dihydroquinoline-7 -yloxy] -hexylb-methylpiperidine (Exemplary compound number: 2-7 3 2) The 7- (6-bromohexyloxy) -1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 obtained in Example (1 2 8a) -Carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 140 mg and 1-methylpiperidine 0.1%.  1 3 m 1, the reaction was carried out according to the method of Example (1 1 j), and the title compound was obtained as a light yellow solid 153 NMR.  (CDCl3) 5ppm: 1. 20 (3H, t, J = 7. 1Hz), 1. 42-1. 55 (10H, m), 1. 70- 1. 95 (10H, m), 3. 33 (3H, s), 3. 63-3. 75 (6H, m), 3. 86 (2H, t, J = 6. 1Hz), 200300349 3. 92 (2H, q, J = 7. 0Hz), 4. 01-4. 07 (4H, m), 6. 39 (1H, d, J = 2. 1Hz), 6. 43 (2H, d, J = 2. 0Hz), 6. 60 (1H, t, J = 2. 1Hz), 6.  62-6.  65 (1H, m), 6. 83 (2H, dd, J = 2. . 0, 7. 9Hz), 6. 89 (1H, dd, J = 2. 1, 8. 9Hz), 7. 82 (1H, s), 8. 20 (1H, d, J = 9. 0Hz).  Melting point: 1 3 0 ~ 1 3 3 ° C Example 1 3 0 Bromide l- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1 -(3-Dimethylamine formamyloxy-5-methoxyphenyl) -4 -oxo 1,4-dihydroquinoline-7 -yloxy] heptylbu 4 -acyl-1 -azobicyclo [twenty two. 2] Octane (Exemplified compound number: 2-8 1 5) (130a) l- (3-dimethylaminemethaneoxy-5-methoxyphenyl) -7-methoxymethoxy-4-oxy -1,4-Dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 1- (3-hydroxy- 5 -methoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 670mg of amine, triethylamine 27ml and N, N-monomethylamine formamidine chloride. 15ml of anhydrous N, N-dimethylformamide 20ml solution ' (: Stir for 1 hour. Dilute with ethyl acetate. Rinse with citric acid aqueous solution 'water' saturated sodium bicarbonate water, saturated brine. After drying over anhydrous magnesium sulfate. Concentrate the solvent under reduced pressure. Use a silica gel column Purification by chromatography (eluent: ethyl acetate) gave the title compound as a colorless foam 6 7 4 mg ° R (CDC13) δρρπι: 1. 20 (3H? T, J = 7. 0Hz) 5 3. 02 (3H, s), 3. 11 (3H, s), 3. 4K3H, s), 3. 85 (3H, s), 3.  89-3.  96 (2H, m), 5. 12 and 5. 15 (total 2H, each s), 6. 60 ~ 6. 64 (1H, m), 6. 65 (1. H, d, J = 2. 2Hz), 6. 72 (1H, t, J-2. 1Hz), 6.  77 ~ 6.  78 (1H, m), 6. 84 (2H, dd, 1 = 2. 2, 8. 0Hz), 6. 89 (1H, t, J = 2. 1Hz), 7. 04 (1H, dd, J = 2. 2, 9. 0Hz), 7. 90 (1H, s), 8. 22 (1H, d, J = 9. 0Hz).  200300349 (130b) l- (3-Dimethylaminemethylmethoxy-5 -methoxyphenyl) -7-hydroxy-4 -oxo-1,4 -dihydroquinolinoline-3 -unsaturated acid N- ( 3,5-monofluorophenyl) -N-acetamidine The 1- (3-dimethylamine formamyloxy-5 -methoxyphenyl) -7-formaldehyde obtained in Example (130) Oxymethoxy-4-oxo-1,4-monoamylline-3 -residue N- (3,5-difluorophenyl) -N-acetamidine 635 mg, according to Example (102d) The reaction was carried out in the same manner to obtain 606 mg of the title compound as a white solid. NMR.  (CDC13) δ ppm: 1.  28 (3H, t, J = 7.2 Hz), 3.0 04 (3H, s), 3.1 (3H, s), 3. 84 (3H, s), 3. 99 (2H, q, J-7. 2Hz), 6. 6K1H, s), 6. 65 (1H, s), 6. 77 (1H, d, J = 1. 8Hz >, 6. 79-6. 84 (lH, m), 6. 90 (1H, s), 7. 0K2H, d, J = 5. 0Hz), 7. 41 (1H, dd, J = 1. 9, 9. 2Hz), 7. 80 (1H, s), 8. 25 (1H, d, 1 = 9. 3Hz).  (130c) 7- (7-bromoheptyloxy) -1- (3-dimethylaminemethylmethoxy-5-methoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3- Carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 1- (3-dimethylaminemethanyloxy-5-methoxyphenyl) obtained in Example (1 3 0 b) ) _7_Hydroxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 0. 56 ml and potassium carbonate 302 mg were reacted and purified according to the method of Example (1 1 i) to obtain the title compound as colorless foam 570 mg. Leg (CDC13) δ ppm: 1. 2K3H, t, J = 7. 1Hz), 1.  31-1.  48 (6H, m), 1. 69-1. 78 (2H, m), 1. 81-1. 88 (2H, m), 3. 02 (3H, s), 3. 1K3H, s), 3. 39 (2H, t, J = 6. 7Hz), 3. 84-3. 96 (7H, m), 6. 46 (1H, d, J-2. 15Hz), 6. 60-6.  65 (1H, m), 6. 72 (1H, t, J = 2. 0Hz), 6. 77 (1H, d, J = 1. 9Hz), 6; 84 (2H, dd, J = 2. 1, 8. 0Hz), 6. 55-6. 91 (2H, m), 7. 87 (1H, s), 8. 20 (1H, d, J = 9. 0Hz).  -350-200300349 (1 3 0 d) bromide 1-{7-[3-[N-(3,5-difluorophenyl) -N -ethylaminomethylmethyl]]-1- (3-dimethyl Aminomethyloxy-5-methoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] heptylbu 4 -acyl-1 -azobicyclo [2 · 2 · 2] octane will be 7-(7 -bromoheptyloxy)-1-(3-dimethylamine formamyloxy-5-methoxyphenyl)-4-oxygen obtained in Example (1 3 0 c) 190 mg of -1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine and 1,4-diazine bicyclo [2. 2. 2] Octane 61 m g. The reaction was carried out according to the method of Example (1 1 j) to obtain the title compound as a white powder 188 m g. NMR.  (CDC13) (5ppm: 1. 19 (3H, t, J = 7. 1Hz), 1. 38 (6H, br), 1.  68-1.  85 (4H, m), 3. 02 (3H, s), 3. 1K3H, s), 3.  26-3. 29 (6H, m), 3.  51-3. 55 (2H, in), 3.  65-3. 69 (6H, m), 3.  83-3.  94 (7H, m), 6. 46 (1H, d, J = 2. 1Hz), 6.  61-6. 66 (1H, m), 6.  69-6.  70 (1H, m), 6.  75-6.  76 (1H, m), 6. 83 (2H, dd, J = 2. 0, 7. 9Hz), 6.  88-6.  92 (2H, in), 7. 8K1H, s), 8.  18 (IK, d, J = 8. 9Hz).  Melting point: ~ 1 3 0 ° C Example 1 3 1 Bromide l- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -l- (3 -Dimethylamine formamyloxy-5-methoxyphenyl) -4 -oxo-1,4 -dihydroquinoline-7 -yloxy] heptylb-methyl piperidine (exemplified compound number : 2-814) The 7-(7-bromoheptyloxy) -1-(3 -dimethylaminemethaneoxy-5-methoxyphenyl) -4-obtained in Example (1 3 0 c) -4- Oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 190mg and 1-methylpiperidine 16 ml was reacted according to the method of Example (1 1 j) to obtain 1 89 mg of the title compound as a yellow solid. -351-200300349 calendar R-^ (CDC13) (5ppm: 1. 20 (3H, t, J = 7.  1Hz), 1. 41 (6H, br), 1. 65-1.  95 (10H, m), 3. 02 (3H, s), 3. 11 (3H, s), 3. 32 (3H, s), 3.  62-6. 68 (4H, m), 3.  71-3.  77 (2H, m), 3.  81-3.  95 (7H, m), 6. 46 (1H, d, J = 2.  1Hz), 6.  60-6. 65 (1H, m), 6. 7K1H, t, J = 1. 7Hz), 6. 76-6. 77 (1H, in), 6. 84 (2H, dd, J = 2. 0, 7. 9Hz), 6. 88-6. 91 (2H, m), 7. 85 (1H, s), 8.  19 (1H, d, J = 8. 9Hz).  Melting point: 1 3 2 to 1 3 5 DC Example 1 3 2 1- {7- [1- (3,5-diethoxyphenyl) -3- [1 (3,5-xylyl) bromide ) -N-Ethylaminomethyl] -4 -oxo-1,4-dihydroquinoline-7-yloxy] heptylbu 4 -acyl-1 -azobicyclo [2. 2. 2] octane (exemplified compound number: 2-764) (132a) 7-benzyloxy-1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -Carboxylic acid N-(3,5-xylyl) -fluorenamine 7-benzyloxy-1- (3,5-diethoxyphenyl) -4 -oxy-1 obtained in Example (44d) , 4-dihydroquinoline-3 -carboxylic acid 1. Og, isobutyl chloroformate 31ml, triethylamine 91ml, and 3,5-dimethyltoluidine 41ml, the reaction was carried out according to the method of Example (5 4 c) to obtain the title compound as a white solid 1. 20g. Li R (CDC13) δρρπι: 1. 44 (6H, t, J = 6. 9Hz), 2. 32 (6H, s), 3.  96-4.  07 (4H, m), 5. 03 (2H, s), 6. 46 (2H, d, J = 2. 2Hz), 6. 59 (1H, d, J = 2. 2Hz), 6. 64 (1H, t, J = 2. 1Hz), 6. 75 (1H, s), 7. 14 (1H, dd, J = 2. 2, 8. 9Hz)? 7. 28-7.  37 (5H, m), 7. 43 (2H, s), 8. 47 (1H? D, J = 9. 2Hz), 8. 80 (1H, s).  (132b) 7-benzyloxy-1- (3, 5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-xylyl ) -N-Acetylamine The 7-benzyloxy-1-(3,5 · diethoxyphenyl-352-200300349) -4 -oxy-1,4-obtained in Example (1 2 2 a) Dihydroquinoline-3 -carboxylic acid N-(3,5-xylyl) -amidamine 1. 18 g, 55% sodium hydride 1 37 mg, and iodoethane 0. 6 6 m 1, the reaction was carried out according to the method of Example (5 4d) to obtain the title compound as a white solid l. llg. NMR (CDC13) δ ppm: 1. 20 (3H, br), 1. 43 (6H, t, J = 7. 0Hz), 2. 2K6H, br), 3. 80- 4. 05 (6H, m), 4. 95 (2H, s), 6. 2K2H, br), 6. 40 (1H, br), 6.  56 (1H, s), 6.  75-7.  00 (4H, m), 7.  26-7.  36 (5H, m), 7. 47 (1H, s), 8.  25-8.  35 (1H, br).  (132c) l- (3,5-diethoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-xylyl)- N-acetamidine The 7-benzyloxy-1-(3,5-diethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 obtained in Example (1 3 2 b) -Carboxylic acid N- (3,5-xylyl) -N-acetamidine 1. 07g and 200% Pd-C200mg were reacted according to the method of Example (11h) to obtain the title compound as a white solid, 807mg. NMR; ^ CDC13) 5ppm: 1. 19 (3H, br), 1. 40 (6H, t, J = 7. 0Hz), 2. 16 (6H, br), 3. 80- 4. 05 (6H, m), 6. 2K2H, br), 6. 4K1H, d, J = 2. 0Hz), 6. 5K1H, t, J = 2. 1Hz), 6. 70-7. 00 (4H, m), 7. 45 (1H, br), 8. 00 (1H, d, J = 8. 6Hz).  (1320) 7- (7-bromoheptyloxy) -1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid 3,5-xylyl)-. Acetylamine 1- (3,5-diethoxyphenyl) -7-hydroxy-4-oxy-1,4-dihydroquinoline-3-carboxylic acid N obtained in Example (1 3 2 c) -(3,5 -Xylyl) -N-acetamidamine 600mg, 1,7-dibromoheptane 0. 61 ml and 331 mg of potassium carbonate were reacted and purified according to the method of Example (1), to obtain 470 mg of the title compound as a white solid. NMR (CDC13) (5ppm: 1. 18-1. 47 (15H, m), 1.  68-1.  88 (4H, m), 2. 2K6H, br), 3. 39 (2H, d, J-6. 6Hz), 3. 80-3. 95 (4H, m), 4. 01 (4H, q, J = 7. 3Hz), 200300349 6. 20-6.  40 (3H, br), 6. 56 (1H, s), 6.  80-6.  95 (4H, m), 7. 47 (1H, br), 8.  25 ~ 8.  35 (1H, br).  (1326) 1- {7- [1- (3,5-diethoxyphenyl) -3- [N- (3,5-xylyl) -N-ethylamine formamidine 4- Oxy · 1,4-dihydroquinoline-7-yloxy] heptylbu 4 -acyl-1 -azobicyclo [2 · 2 · 2] octane 7 obtained in Example (1 3 2 d) -(7 -bromoheptyloxy) -1- (3,5-diethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5 -xylene 200 mg of -N-acetamidamine and 68 mg of 1,4-diazepine-bicyclo [2 · 2 · 2] octane. The reaction was carried out according to the method of Example (llj) to obtain 238 mg of the title compound as a white solid. NMR.  (CDC13) (5ppm: 1.  10-1. 20 (3H, br), 1. 34 (6H, br), 1. 42 (6H, t, J = 6. 6Hz), 1. 65-1. 85 (4H, m), 2. 20 (6H, br), 3. 27-3.  30 (6H, m), 3.  51-3.  55 (2H, m), 3. 68-3.  72 (6H, m), 3. 75-3.  90 (4H, m), 4. 0K4H, q, J = 6. 6Hz), 6. 19 (2H, br), 6/34 (lH, br), 6. 56 (1H, s), 6. 8K3H, br), 6. 90 (1H, d, J = 8. 1Hz), 7. 39 (1H, br), 8. 23 (1H, d, J = 8. 2Hz).  Melting point: 1 3 4 ~ 1 3 7 ° C Example 1 3 3 Brominated l- {7- Π- (3,5-diethoxyphenyl) -3- [N- (3,5 -xylyl) ) -N-Ethylaminomethyl] -4-oxy-1,4-dihydroquinoline-7-yloxy] heptylb-methyl piperidine (Exemplary compound number: 2-7 6 3 ) The 7-(7-bromoheptyloxy) -1-(3, 5 -diethoxyphenyl) -4 -oxo-1,4 -dihydroquinoline obtained in Example (1 2 2 d)- 3-carboxylic acid N- (3,5-xylyl) -N-acetamidamine 200 mg and 1-methylpiperidine 0 · 1 8 τη 1, the reaction was carried out according to the method of Example (1 1 j) The title compound was obtained as a light yellow solid 200 mg 200300349 NMR (CDC13) δρριη ·· 20 (3Η, br), 1. 35-1 · 50 (12H, m), 1. 65-1.  95 (10H, m), 2. 2K6H, br), 3. 3K3H, s), 3.  63-3.  73 (6H, m), 3.  80-3.  95 (4H, m), 4. 01 (4H, q, J = 6. 8Hz), 6. 15-6.  40 (3H, m), 6. 57 (1H, s), 6.  75-6.  95 (4H, m), 7. 43 (1H, br), 8. 20-8.  30 (1H, br).  Melting point: 1 2 7 ~ 1 2 9 ° C γ Example 1 3 4 Bromide l- {7- [l- (3,5-diethoxyphenyl) -3- [N- (3,5 -di Methoxyphenyl) -N-ethylaminomethylmethyl] -4-oxo-1,4-dihydroquinoline-7-yloxy] heptylb 4-az-1-azobicyclo [2 · 2 . 2] Octane (Exemplified compound number: 2-766) (134 &) 3-carboxylic acid N- (3,5-dimethoxyphenyl) -fluorenamine The 7-benzyloxy-1-(3,5-diethoxyphenyl)-obtained in Example (4 4 d)- 4-oxo-1,4-dihydroquinoline-3 -carboxylic acid 1. Og, isopropyl chloroformate 31ml, triethylamine 0. 91ml and 510mg of 3,5-dimethoxyaniline were reacted according to the method of Example (54c) to obtain the title compound as a white solid 1. 26g. Rei R.  (CDC13) (5ppm: 1. 44 (6H, t, J = 7. 1Hz), 3.  81 (6H, s), 3.  96-4.  06 (4H, m), 5. 03 (2H, s), 6. 25 (1H, t, J = 2. 1Hz), 6. 45 (2H, d, J-2. 1Hz), 6. 59 (1H, d, 1 = 2. 2Hz), 6. 64 (1H, t, J = 2. 0Hz), 7. 06 (2H, d, J = 2. 1Hz), 7. 15 (1H, dd, J = 2. 3, 9. 0Hz), 7. 29-7.  38 (5H, m), 8. 47 (1H, d, J = 8. 9Hz), 8.  81 (1H, s).  (134b) 7-benzyloxy-1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-dimethoxy Phenyl) -N-acetamidine The 7-benzyloxy-1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline obtained in Example (134a) 3-carboxylic acid N- (3,5-dimethoxyphenyl) -fluorene-355-200300349 amine 1.  2 4 g, 55% sodium hydride 1 3 6 mg and Iodine B 0. 66 m 1 was reacted in the same manner as in Example (5 4 d) to obtain the title compound as a colorless foam 1 · 1 1 g. NMR (CDC13) δρριη: 1. 22 (3H, t, J = 7. 0Hz), 1. 43 (6H, t, J = 6. 8Hz), 3. 68 (6H, s), 3.  86-4.  00 (6H, m), 4. 96 (2H, s), 6.  20-6.  30 (3H, m), 6. 41 (1H, br), 6. 44 (2H, d, J = 1. 8Hz), 6. 56 (1H, t, J = 2. 1Hz), 6. 98 (1H, dd, J = 1. 6, 8. 9Hz), 7. 27-7. 36 (5H, m), 7. 51 (1H, br), 8. 30 (1H, d, J = 8. 9Hz).  (134c) l- (3,5-diethoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-dimethoxyphenyl ) -N-acetamidine The 7-benzyloxy-1-(3,5-diethoxyphenyl) -4 -oxo-1,4-dihydroquinoline obtained in Example (1 3 4 b) -3 -carboxylic acid N- (3,5-dimethoxyphenyl) -N-acetamidine 1. 08g and 200% Pd-C200mg were reacted according to the method of Example (11h) to obtain 850mg of the title compound as a white solid. NMR.  (CDC13) δρριη: 1. 18-1.  25 (3Η, m), 1. 40 (6Η, t, 1 = 6.  8Hz), 3.  63 (6Η, br), 3.80-4 · 00 (6Η, m), 6. 26 (3Η, br), 6.35-6 · 45 (3Η, m), 6.52 (1Η, t, J = 2. 1Hz), 6. 97 (1Η, dd, 1 = 2A, 8. 9Hz), 7. 50 (1Η, br), 8. 03 (1Η, d, J = 8. 8Hz).  (134d) 7- (7-Bromoheptyloxy) -bu (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5 -Dimethoxyphenyl) -N-acetamidin The 1- (3,5-diethoxyphenyl) -7-hydroxy-4 -oxy-1,4-obtained in Example (1 3 4 c) Dihydroquinoline-3 -carboxylic acid N- (3,5-dimethoxyphenyl-acetamidamine 600mg, 1,7-dibromoheptyl 57 ml and 311 mg of potassium carbonate were reacted and purified according to the method of Example (1 Π) to obtain 5 10 mg of the title compound as a colorless foam. -356-200300349 NMR.  (CDCl3) 6ppm: 1.  23 (3H, t, J = 7. 3Hz), 1.  28-1. 48 (12H, m), 1. 68-1. 75 (2H, m), 1. 81-L88 (2H, m), 3. 40 (2H, t, J = 6. 6Hz), 3. 68 (6H, s), 3. 83-4.  92 (4H, m), 4. 00 (4H, q, J = 7. 3Hz), 6. 25-6. 40 (4H, in), 6. 44 (2H, d, J = 1. 5Hz), 6. 55-6. 56 (lH, m), 6. 88 ~ 6. 90 (1H, m), 7. 50 (1H, br), 8. 30 (1H, d, J = 8.  8Hz).  (134e) L- {7- [l- (3,5-diethoxyphenyl) -3- [N- (3,5-dimethoxyphenyl) -N-ethylamine formamidine] 4-oxo-l, 4-dihydroquinoline-7-yloxy] heptylbu 4 -acyl-buzo azobicyclo [2. 2. 2] Octane 7-(7-bromoheptyloxy) -1-(3,5-diethoxyphenyl) -4 -oxo-1,4 -dihydro obtained in Example (1 3 4 d) 200 mg of quinoline-3-carboxylic acid N- (3,5-dimethoxyphenyl) -N-acetamidine and 65 mg of 1,4-diazine-bicyclo [2 · 2 · 2] octane, according to the examples (1 lj) The reaction was carried out to obtain 199 mg of the title compound as a white solid. Rei R.  (CDC13) 5ppm: 1. 2K3H, t, J = 6. 6Hz), 1. 35 (6H, br), 1. 42 (6H, t, J = 7. 3Hz), 1. 65-1. 80 (4H, m), 3.  28 ~ 3.  32 (6H, m), 3.  51-3. 55 (2H, m), 3.  67-3.  73 (12H, m), 3.  80-3.  91 (4H, m), 4. 00 (4H, q, J = 7. 3Hz), 6.  20-6.  30 (3H, m), 6. 35 (1H, br), 6. 39 (2H, d, J = 1. 5Hz), 6. 56-6.  57 (1H, m), 6.  90 ~ 6.  92 (1H, m), 7. 45 (1H, br), 8. 24 (1H, d, J = 8. 8Hz).  Melting point: 1 2 3 ~ 1 2 6 ° C. Example 1 3 5 1- {7- [l- (3,5-diethoxyphenyl) -3- [N- (3,5-dimethoxyphenyl) -N-ethylamine formamidine Group] -4 -oxo-1,4-dihydroquinoline-7 -yloxy] heptyl}-1-methylpiperidine (exemplified compound number: 2-7 6 5) Example (1 3 4 d ) The obtained 7-(7-bromobutoxy) -1-(3, 5 -diethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3, 5-Dimethoxy200300349 phenyl) -N-acetamidamine 2 0 0 mg and dimepiridine 0.17 m 1, the reaction was carried out according to the method of Example (1 1 j) to obtain the title compound. Yellow solid 2 2 5 mg 〇R (CDC13) δρριι: 1. 22 (3H, t, J = 6. 6Hz), 1. 41-1. 44 (12H, m), 1.  70-2.  00 (10H, m), 3. 3K3H, s), 3.  60 ~ 3.  80 (12H, m), 3.  82-3.  93 (4H, m), 4. 0K4H, q, J = 7. 3Hz), 6. 28 (3H, br), 6. 35 (1H, br), 6. 43 (2H, d, J = 1. 5Hz), 6.  56-6. 57 (1H, m), 6. 90 (1H, dd „J = 1. 5, 8. 8Hz), 7. 49 (1H, br), 8. 27 (1H, d, J = 9. 5Hz).  Melting point: 1 3 8 ~ 1 4 0 ° C Example 1 3 6 Bromide 1-{7-[1-(3,5-diethoxyphenyl) -3-[N -ethyl-N-(3 -Hydroxyphenyl) -carbamoyl] -4 -oxo-1,4-dihydroquinoline-7 -yloxy] heptyl}-4 -acyl-1 -azobicyclo [2 · 2 · 2 ] Octane (Exemplified compound number: 2-7 6 8) (136a) l- (3,5-diethoxyphenyl) -7-methoxymethoxy-4_oxo-1,4-dihydroquine Methyl phthaloline-3 -carboxylate The 3-dimethylamino-2-(2-methoxy-4 -methoxymethoxy-benzylfluorenyl) _methacrylate obtained in Example (104 d) The ester 10 g, 3,5-diethoxyaniline hydrochloride 7. 4 1 g and potassium carbonate 17 1 g were reacted according to the method of Example (1 1 e) to obtain the title compound as a white solid. 8. 9 7 g ° circle R (CDC13) (5ppm: 1. 43 (6H, t, J = 7. 3Hz), 3. 42 (3H, s), 3. 92 (3H, s), 4. 02-4. 07 (4H, m), 5. 14 (2H, s), 6. 51 (2H, d, J = 2. 2Hz), 6. 61 (1H, t, J = 2. 2Hz), 6. 67 (1H, d, J = 2. 2Hz), 7. 13 (1H, dd, 1 = 2. 2, 8. 8Hz), 8. 47 (1H, d, J = 8. 8Hz), 8. 49 (1H, s).  (136b) l- (3,5-diethoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid-358-200300349 Examples 1 3 6 a) 1-(3,5-diethoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid methyl ester 8. 97g and sodium hydroxide 4. 2 g, the reaction according to the method of Example (1 1 f), the title compound was obtained as a white solid 8. 6g. Draw R (CDC13) (5ppm: 1. 44 (6H, t, J = 7. 3Hz), 3. 44 (3H, s), 4.  02-4.  08 (4H, m), 5. 18 (2H, s), 6. 5K2H, d, 1 = 2. 2Hz), 6. 64 (1H, t, J = 2. 2Hz), 6. 81 (1H, d, J = 2. 2Hz), 7. 26 (1H, dd, J = 2. 2, 9. 5Hz), 8. 46 (1H, d, J = 8. 8Hz), 8. 74 (1H, s).  (136c) l- (3,5-diethoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N-(3-benzyloxybenzene ) -Amidinylamine 1- (3,5-diethoxyphenyl) 7-methoxymethoxy-4-oxo-1,4-dihydroquinoline obtained in Example (1 3 6 b)- 700 mg of 3-carboxylic acid and 0-isobutyl chloroformate. 24ml, triethylamine 0. 71 ml and 413 mg of 3-benzyloxyaniline were reacted according to the method of Example (54c) to obtain 994 mg of the title compound as a white solid. NMR (CDC13) δ ppm: 1. 44 (6H, t, J = 6. 6Hz), 3. 44 (3H, s), 4.  02-4.  07 (4H, m), 5. 10 (2H, s), 5. 17 (2H, s), 6. 53 (2H, d, J = 2. 2Hz), 6. 63 (1H, t, J = 2. 2Hz), 6. 73-6. 76 (lH, m), 6. 79 (1H, d, J = 2. 2Hz), 7. 20-7. 43 (8H, m), 7. 68 (1H, d, J = 2. 2Hz), 8. 50 (1H, d, 1 = 8. 8Hz), 8. 86 (1H, s).  (136d) l- (3,5-diethoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3-benzyloxybenzene Group) -N-acetamidinium 1- (3,5-diethoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-diamine obtained in Example (1 3 6 c) Hydroquinoline-3 -residue N- (3-benzyloxyphenyl) -amidamine 98091 ^, 55% sodium hydride 108mg and iodoethane 0. 52 ml was reacted in the same manner as in Example (54d) to obtain 910 mg of the title compound as a colorless foam. -359-200300349 NMR (CDC13) (5ppm: 1. 20 (3H, t, J = 7. 3Hz), 1. 39 (6H, t, J = 7. 3Hz), 3. 40 (3H, s), 3. 92-4. 00 (6H, m), 4. 94 (2H, s), 5. 10 (2H, s), 6. 3K2H, br), 6. 54-6. 57 (2H, m), 6. 77 (1H, d, 1 = 8.  1Hz), 6. 86 (1H, d, J = 8. 1Hz), 6. 92 (1H, s), 7. 02 (1H, d, J = 7. 3Hz), 7. 10-7. 20 (1H, m), 7.  28-7.  34 (5H, m), 7. 60 (1H, br), 8. 28 (1H, d, J = 8.  8Hz).  (136e) l- (3,5-diethoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3-benzyloxyphenyl) -N -Acetylamine 1- (3,5-diethoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3-carboxyl obtained in Example (136d) 870 mg of the acid N- (3-benzyloxyphenyl) -N-acetamide was reacted according to the method of Example (102d) to obtain 870 mg of the title compound as a white solid. NMR (CDCI3) (5ppm: 1. 29 (3H, t, J = 7. 3Hz), 1. 38 (6H, t, J-7. 3Hz), 3. 93-4. 02 (6H, m), 5. 06 (2H, s), 6. 10 (2H, d, J = 1. 5Hz), 6. 56 (1H, s), 6.  87-6. 93 (3H, m), 6. 99 (1H, dd, J = 2. 2, 8, 1Hz), 7.  18-7. 21 (1H, m), 7.  25-7.  38 (5H, m), 7. 45 (1H, s), 7. 76-7. 78 (1H, m), 8. 23 (1H, d, J = 9. 5Hz).  (1361?) 7- (7-bromoheptyloxy) -1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -residue N- (3 -Benoxyphenyl) -N-acetamidine 1- (3,5-diethoxyphenyl) -7-hydroxy-4-oxy-1,4-di Hydroquinoline-3 -carboxylic acid N- (3-benzyloxyphenyl) -N-acetamide 850 mg, 1,7-dibromoheptane. 79 ml and 427 mg of potassium carbonate were reacted and purified according to the method of Example (1 1 i) to obtain 650 mg of the title compound as a white solid. NMR.  (CDC13) δρρπι: 1. 20 (3H, t, J = 7. 3Hz), 1.  29-1. 47 (12H, m), 1. 68-1. 77 (2H, m), 1. 80-1. 88 (2H, m), 3. 39 (2H, t, J = 6. 6Hz), 3. 84 (2H, t, J-6. 6Hz), 3. 92-4. 00 C6H, m), 4. 94 (2H, s), 6. 25-6. 40 (3H, m), 6. 56 (1H, t,-360-200300349 J = 2. 2Hz), 6. 77 (1H, d, J = 8.  1Hz), 6.  85-6.  95 (3H, m), 7. 10-7.  20 (1H, m), 7. 29-7. 43 (5H, m), 7. 56 (1H, br), 8. 27 (1H, d, J = 8. 8Hz).  (136g) 7- (7-bromoheptyloxy) -1- (3,5 -monoethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N -ethyl- N- (3-hydroxyphenyl) -fluorenamine 7- (7-bromoheptyloxy) -1- (3,5-diethoxyphenyl) -4-oxy-1 obtained in Example (136f) To a solution of 400 mg of 4,4-dihydroquinoline-3-carboxylic acid N- (3-benzyloxyphenyl) -N-acetamide in 5 ml of ethanol and 10 ml of dichloromethane was added 100% 10% Pd-C. Stir under hydrogen at room temperature for 12 hours. The catalyst was filtered off, and the filtrate was evaporated under reduced pressure to remove the solvent. The residue was solidified with diisopropyl ether-diethyl ether and dried to obtain the title compound as a light brown solid 280 mg g.  (CDC13) (5ppm: 1. 18 (3H, t ,. J = 6. 6Hz), 1. 27-1. 47 (12H, m), 1. 68-1.88 (4Η, m), 3.39 (2Η, t, J = 6. 6Hz), 3. 82-4 · 04 (8H, m), 6. 25-6.40 (3Η, br), 6. 55-6.  65 (2H, br), 6. 73 (1H, d, J = 7. 3Hz), 6. 86 (1H, d, J-8. 1Hz), 7.  00-7.  07 (2H, m), 7. 66 (1H, br), 8. 11-8. 12 (1H, br).  (136h) bromide l- {7- [l- (3,5-diethoxyphenyl) -3- [N -ethyl-N- (3-hydroxyphenyl) -carbamoyl] -4 -Oxo-1,4 -dihydroquinoline-7 -yloxy] heptyl}-4 -acridyl-diazobicyclo [2. 2 · 2] Octane 7-(7 -bromoheptyloxy) -1-(3, 5 -diethoxyphenyl)-4 -oxo-1, 4- Dihydroquinoline-3 -carboxylic acid N -ethyl-N-(3-hydroxyphenyl) -amidamine 1 3 5 mg and 1,4-diazine-bicyclo [2,2 · 2] octane 4 6 mg, and reacted according to the method of Example (1 1 j) to obtain the title compound as a yellow powder 1 1 9 mg. NMR (DMS0-d6) δρρπι: 1. 07 (3H? T, J = 7. 3Hz), 1. 23-1.  35 (1 2H, m), 1. 58 ~ 1.  68 (4H, m), 3. 00 (6H, t, J-7. 3Hz), 3. 12-3. 16 (2H, in), 3. 21-3. 25 (6H, m), 3.  70-3.  75 (2H, m), 3.  86-3.  89 (2H, m), 4.  01-4.  07 (4H, m), 6. 30 (1H, s), 200300349 6. 35-6. 50 C2H, m), 6. 56 (1H, d, 1 = 7.  3Hz), 6.  64-6.  67 (3H, m), 6.  96-7.  03 (2H, m), 7. 83 (1H, br), 8. 02 (1H, d, 8. 8Hz).  Melting point ·· ~ 1 4 (TC Example 1 3 7 1- {7-Π- (3,5-diethoxyphenyl) -3- [N -ethyl-N- (3-hydroxyphenyl Carbamate] -4 -oxo-1,4-dihydroquinoline-7 -yloxy] heptylbu 1-methyl-piperidine (Exemplary compound number: 2-7 6 7) Examples ( 1 3 6 g) of the obtained 7-(7 -bromoheptyloxy) -1-(3,5-diethoxyphenyl) _4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- Ethyl-N- (3-hydroxyphenyl) -amidamine. 1 3 5 mg and dimepiperidine 0.1 2 m 1 ′ The reaction was carried out according to the method of Example (1 1 j) to obtain 103 mg of the title compound as a yellow powder 〇NMR ⑽S〇_d6) δρριη: 1.07 ( 3Η, t, J = 7. 3Hz), 1.27-1.34 (12Η, m), 46-1. 67 (6H, m), 1. 76 (4H, br), 2. 96 (3H, s), 3. 20-3. 40 (6H, m), 3. 73 (2H, q, J-7. 3Hz)? 3. 88 (2H, t, J = 5. 86Hz), 4.  02-4.  08 (4H, m), 6. 30 (1H, s), 6. 43 (2H, br), 6. 54 (1H, d, J = 7. 3Hz), 6.  61-6.  67 (3H, m), 6.  90-7. 00 (2H, m), 7. 83 (1H, br), 8. 03 (1H, d, J = 8. 8Hz).  Melting point: 1 2 3 ~ 1 2 5 ° C Example 1 3 8 (3,5-diethoxyphenyl) bromide 3- [N- (3-dimethylaminephenyl) _N-ethylamine Fluorenyl] -4 -oxo-I, 4 · dihydroΠquinolin-7-yloxy] heptyl}-4 -acyl-1 -azobicyclo [2 · 2 · 2] octane (exemplified compound numbers : 2-8 7 4) (138a) 7-benzyloxy-1- (3,5-diethoxyphenyl) -4-oxo-1,4-di- 362-200300349 hydroquinoline-3 -carboxyl Acid N- (3-dimethylaminephenyl) -amidamine The 7-benzyloxy-1- (3,5-diethoxyphenyl) -4-oxo-1 obtained in Example (44d). , 4-dihydroquinoline-3 -carboxylic acid 2. 0 g, isobutyl chloroformate 0. 64ml, triethylamine 3. 03ml and N, N-dimethyl-m-phenylenediamine dihydrochloride 1. 〇g, the reaction according to the method of Example (54c), the title compound was obtained as a white solid 2. 45g. NMR (CDC13) (5ppm: 1. 44 (6H, t, J = 6. 6Hz), 2. 98 (6H, s) ,.  3.  95-4.  06 (4H, m), 5. 03 (2H, s), 6. 45 (2H, d, J = 2. 2Hz), 6. 52 (1H, br), 6. 59 (1H, d, J = 2. 2Hz), 6. 63 (1H, t, J = 2. 2Hz), 7. 13-7. 16 (2H, m), 7. 21 (1H, t, J = 8. 1Hz), 7. 29-7. 38 (6H, m), 8. 47 (1H, d, J = 8. 8Hz), 8. 83 (1H, s).  (138b) 7-benzyloxy-1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N-(3-dimethylaminephenyl ) -N-Acetylamine 7-benzyloxy-1-(3,5-diethoxyphenyl) -4 -oxo-1,4-dihydroquinoline obtained in Example (1 3 8 a) -3 -carboxylic acid N-(3 -dimethylaminophenyl) -amidamine 1.  0 g, 5 5% sodium hydride 1 1 3 mg and iodoethane 0. 5 5 m 1, the reaction was carried out according to the method of Example (5 4 d) to obtain the colorless foam of the title compound 580 m g 〇 NMR (CDCI3) δ ppm: 1. 23 (3H ,.  t, J = 7. 3Hz), 1. 43 (6H, t, J = 7. 3Hz), 2. 83 (6H, s), 3. 92-3. 99 (6H, m), 4. 94 (2H, s), 6. 20 (2H, br), 6. 37 (1H, br), 6. 51-6.  60 (4H, m), 6. 95 (1H, d, J = 8. 8Hz), 7. 07 (1H, br), 7. 28-7.  36 (5H, m), 7. 44 (1H, br), 8. 20-8.  35 (1H, br).  (138c) l- (3,5-diethoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N-(3-dimethylaminephenyl)- N-acetamidine The 7-benzyloxy-1-(3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 obtained in Example (1 3 8 b) -Carboxylic acid N- (3-dimethylaminephenyl) -N--363-200300349 560 mg of acetamidine and 100 mg of 10% Pd-C, the reaction was carried out according to the method of Example (llh) to obtain the title compound as a white solid 4 4 2 mg. NMR (CDC13) δ ppm: 1. 21 (3H, t, J = 7. 3Hz), 1. 40 (6H, t, 1 = 7. 3Hz), 2. 78 (6H, br), 3.  85-4.  00 (6H, m), 6. 22 (2H, br), 6. 38 (1H, s), 6.  49-6.  63 (4H, in), 6. 9K1H, d; J = 8. 8Hz), 7. 05 (1H, br), 7. 44 (1H, br), 7. 97 (1H, d, J = 8. 8Hz).  (1380) 7- (7-bromoheptyloxy) -1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid Dimethylaminephenyl) -N-acetamidinium 1- (3,5-diethoxyphenyl) · 7-hydroxy-4 -oxy-1,4-diamine obtained in Example (1 3 8 c) Hydroquinoline-3 -carboxylic acid N- (3-dimethylaminephenyl) -N-acetamidamine 400mg, 1,7-dibromoheptane 0. 40 ml and 214 mg of potassium carbonate were reacted and purified according to the method of Example (1 1 i) to obtain 43.0 mg of the title compound as a colorless oil. NMR… (CDC13) (5ppm: 1. 24 (3H, t, J = 6. 6Hz), 1.  33-1. 47 (12H, m), 1. 67-1. 73 (2H, m), 1. 81-1. 88 (2H, m), 2. 84 (6H, br), 3. 39 (2H, t, J = 6. 6Hz), 3.  82-3.  85 (2H, m), 3.  93-4.  02 (6H, m), 6.  20-6.  35 (3H, m), 6.  50-6.  70 (4H, m), 6. 87 (1H, d, J = 8. 1Hz), 7. 08 (1H, br), 7. 45 (1H, br), 8. 27 (1H, br).  (1 3 8 e) bromide 1-{7-[1-(3,5-diethoxyphenyl) -3-[N-(3 -dimethylaminophenyl) -N -ethylaminomethylmethyl ] -4 -oxo-1,4-dihydroquinoline-7-yloxy] heptylbu 4 -acryl-buzozobicyclo [2 · 2 · 2] octane Example (1 3 8 d) The obtained 7- (7-bromoheptyloxy) -1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3-di 200 mg of methylamine phenyl) -N-acetamidine and 66 mg of 1,4-diazine-bicyclo [2 · 2 · 2] octane. The reaction was carried out according to the method of Example (1 1 j) to obtain the title. Compound as a white powder 209 mg. 200300349 Rei R.  ^ CDC13) δρριη: 1. 22 (3H, t, J = 6. 6Hz), 1. 33 (6H, br), 1. 42 (6H, t, J = 7. 3Hz), 1. 60-1. 85 (4H, m), 2. 83 (6H, s), 3. 27-3.  31 (6H, m), 3. 50-3.  55 (2H, m), 3.  68-3.  72 (6H, m), 3.  75-3.  81 (2H, m), 3.  85-3.  95 (2H, m), 4. 00 (4H, q, J = 7. 3Hz), 6. 22 (2H, br), 6. 32 (1H, br), 6.  50-6. 65 (4H, m), 6. 89 (1H, d, J-8. 1Hz), 7. 08 (1H, br), 7. 42 (1H, br), 8. 27 (1H, d, J-8. 8Hz).  Melting point: ~ 1 1 7 ° C Example 1 3 9 1- {7- [l- (3,5-diethoxyphenyl) -3- [N- (3-dimethylaminephenyl) bromide- N-ethylaminoformyl] -4 -oxo-1,4-diaminopyridinoline-7-yloxy] heptyl} _ i _ mepidol (Exemplary compound number: 2-7 5) Examples (1 3 8 d) 7-(7 -bromobutoxy) -1-(3,5-diethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3-dimethylaminephenyl) -N-acetamide 200mg and 1-methylpiperidine. 17ml, the reaction was carried out according to the method of Example (1 1 j), and the title compound was obtained as a pale yellow solid 206 m g 〇 RR (CDCl3) (5ppm: 1.23 (3Η, t, J = 6. 6Hz), 1.39 (6Η, br), 1.42 (6Η, t, J = 7. 3Hz), 1. 69 ~ 2. 00 (10H, m), 2. 84 (6H, s), 3. 3K3H, s), 3. 63-3. 75 (6H, m), 3.  80-3.  83 (2H, m), 3.  90-3.  95 (2H, m), 4.  00 (4H, q, J = 7. 3Hz), 6.  20-6.  40 (3H, m), 6. 50-6.  75 (4H, m), 6. 87 (1H, d, J = 8. 8Hz), 7. 09 (1H, br), 7. 46 (1H, br), 8. 24 (1H, d, J-8. 8Hz). .  Melting point: 1 2 0 ~ 1 2 3 ° C Example 1 4 0 Desertification {7- [3- [N- (3-Gasyl-5 -methoxybenzyl) -N-ethoxymethylenesulfonyl] -1- (3,5-diethoxyphenyl) -4-oxo-1, cardiodihydroquinoline-7-yloxy] heptylbuprofen (exemplified compound number: 2-8 7 6 )-365-200300349 (140a) l- (3,5-diethoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- ( 3-Cyano-5-methoxyphenyl) -fluorenamine 1- (3,5-diethoxyphenyl) -7-methoxymethoxy-4- obtained in Example (1 3 6 b) 431 mg of oxygen-1,4-dihydroquinoline-3-carboxylic acid, isobutyl chloroformate 0 · 1 5 m 1, triethylamine 0 · 4 4 m 1 and 3-amino-5 obtained in Reference Example 9 170 mg of -methoxy-benzonitrile was reacted according to the method of Example (54c) to obtain 397 mg of the title compound as a white solid. Bandit R (CDC13) δρρπι: 1. 44 (6H, t, J = 7. 3Hz), 3. 44 (3H, s), 3. 85 (3H, s), 4. 02-4. 08 (4H, m), 5. 17 (2H, s), 6. 53 (2H, d, J = 2. 2Hz), 6. 64 (1H, t, J = 2. 2Hz), 6. 79 (1H, d, J = 2. 2Hz), 6. 90 (1H, dd, J = 1. 5, 2. 9Hz), 7.  24 (1H, dd, J = 2. 2, 8.  8Hz), 7. 58 (1H, t, J = 2. 2Hz), 7. 78 (1H, s), 8. 48 (1H, d, J = 9. 5Hz), 8. 83 (1H, s).  (14013) 1- (3,5-diethoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3-cyano- 5-Methoxyphenyl) -N-acetamidine -Dihydroquinoline-3 -carboxylic acid N- (3-cyano-5-methoxyphenyl) -amidoamine 38〇1 ^, 55% sodium hydride 46〇1§ and iodoethane 0.1 221111, the reaction was carried out according to the method of Example (5 4 d), and 230 mg of the title compound was obtained as a pale yellow solid. Li R.  (CDC13) δρριη: 1. 20 (3H, t, J = 7. 3Hz), 1. 43 (6H, t, J = 7. 3Hz), 3. 4K3H, s), 3. 79 (3H, s), 3. 93 (2H, q, J-7. 3Hz), 4. 00-4. 06 (4H, m), 5.  11 (2H, s), 6. 43 (2H, d, J-2. 2Hz), 6. 59 (1H, t, J = 2. 2Hz), 6. 63 (1H, d, 1 = 2. 2Hz), 6. 95 (1H, s), 7. 04 (1H, dd, J = 2. 2, 8. 8Hz), 7. 08 (1H, s), 7. 19-7.  20 (1H, m), 7. 88 (1Η, s), 8. 20 (1H, d, J-8. 8Hz).  (14001- (3,5-diethoxyphenyl) -7-hydroxy-4-oxy1,4-dihydro-366-200300349 quinoline-3 -carboxylic acid N- (3-cyano- 5-methoxyphenyl) -N-acetamidine 1- (3,5-diethoxyphenyl) -7-methoxymethoxy-4-oxo obtained in Example (14 0b) 220 mg of 1,4-dihydroquinoline-3-carboxylic acid N- (3-cyano-5-methoxyphenyl) -N-acetamidamine was reacted according to the method of Example (102d), but The title compound was obtained as 199 mg of a pale yellow solid. NMR.  (CDC13) δρριη: 1.  29 (3H, t, J = 7. 3Hz), 1. 43 (6H, t, J = 7. 3Hz), 3. 88 (3H, s), 3. 98-4. 03 (6H, m), 6. 27 (2H, d, J = 1. 5Hz), 6. 57 (1H, s), 6. 6K1H, d, 1 = 2.  2Hz), 7. 07 (1H, s), 7. 14 (1H, s), 7.  46-7.  49 (1H, m), 7. 53 (1H, s), 7. 64 (1H, s), 8.  16 (1H, d, J = 8. 8Hz).  (140 (1) 7- (7-bromoheptyloxy) -1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinolin-3 3-Cyano-5-methoxyphenyl) -N-acetamidine The 1- (3,5-diethoxyphenyl) -7-hydroxy-4-oxo obtained in Example (14 ° c) 1,4-dihydroquinoline-3-carboxylic acid N- (3-cyano-5-methoxyphenyl ...)-N-acetamidamine 190mg, 1,7-dibromoheptane 0 18 ml and 100 mg of potassium carbonate were reacted and purified according to the method of Example (1 1 i) to obtain 90 mg of the title compound as a colorless foam. Rei R.  (CDCl3) 5ppm: 1.20 (3Η, t, J = 7. 3Hz), 1. 3 Bu 1. 48 (12H, Hi), 1. 69-1. 78 (2Η, m), 1. 81-1. 88 (2Η, m), 3. 40 (2Η, t, J = 7. 3Hz), 3. 78 (3H, s), 3. 86 (2¾ t, J = 6. 6Hz), 3. 92 (2H, q, J = 7. 3Hz), 4. 0H4. 06 (4H, m), 6. 40 (1H, d, J = 2. 2Hz >, 6. 43 (2H, d, J = 2. 2Hz), 6. 60 (1H, t, J = 2. 2Hz), 6. 90 (1H, dd, J = 2. 2, 8. 8Hz), 6. 95 (1H, s), 7. 09 (1H, s), 7. 18-7. 19 (1H, m), 7. 84 (1H, s), 8. 18 (1H, d, J = 8. 8Hz).  (140e) 1- {7- [3- [N- (3-cyano-5-methoxybenzyl) -N-ethylaminomethylmethyl] -1- (3,5-diethoxybenzene) Yl) -4-oxo-1,4-dihydro200300349 quinoline-7-yloxy] heptylb-methylpiperidine 7- (7-bromoheptyloxy) ) -1-(3,5-diethoxyphenyl) -4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3-cyano-5-methoxyphenyl)- N-acetamide 84 mg and 1-methylpiperidine 0. 07ml, the reaction was carried out according to the method of Example (1 1 j), and the title compound was obtained as a pale yellow solid 8 5 mg g 0 R (CDC13) δρριι: 1. 20 (3H, t, J = 7. 2Hz), 1. 42-1. 46 (12H, m), 1. 70-2.  00 (10H, m), 3. 30 (3H, br), 3. 68 (6H, br), 3. 79 (3H, s), 3.  86-3.  95 (4H, m), 4. 00-4. 10 (4H, m), 6. 40 (1H, s), 6. 43 (2H, s), 6. 60 (1H, s), 6. 90 (1H, d, J = 9. 0Hz), 6. 95 (1H, s), 7. 09 (1H, s), 7.  18 (1H, s), 7. 84 (1H, s), 8. 19 (1H, d, J = 7. 9Hz).  Melting point: 1 2 7 ~ 1 3 0 ° C Example 1 4 1 Bromide 1-{7 '[3-[N-(3, 5 -difluorophenyl) -N -ethylaminomethylmethyl] -1 -(3 -methoxy-5 -trifluorotolyl) -4 -oxo-1,4-dihydroquinoline-7 -yloxy] heptyl}-4 -acyl-1 -azobicyclo [2 . 2. 2] octane (exemplified compound number: 2-779) (141a) 7-benzyloxy-1- (3-methoxy-5-trifluorotolyl) -4-oxo-1, 4-dihydroquine Methyl phthaloline-3 -carboxylate The 2- (4-benzyloxy-2-methoxybenzyl) -3 -dimethylamino-acrylic acid methyl ester obtained in Example (44b) 1. Og, 3-methoxy-5-trifluorotoluidine 5 17 mg and potassium carbonate 7 4 8 mg were reacted according to the method of Example (1 1 e) to obtain 620 mg of the title compound as a white solid. NMR (CDC13) δρρπι: 3. 9Κ3Η, s), 3. 92 (3H, s), 5.  02 (2H, m), 6. 33 (1H, d, J = 2. 9Hz), 7. 07-7. 1K2H, m), 7. 25-7.  31 (3H, m), 7.  32-7.  36 (4H, m), 8. 42 (1H, s), 8. 46 (1H, d, J = 9. 5Hz).  -368-200300349 (Mlb) 7-benzyloxy-1- (3-methoxy-5-trifluorotolyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid (1 4 1 a) The obtained 7-benzyloxy-1- (3-methoxy-5-trifluorotolyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid methyl ester 600mg and 1 N-sodium hydroxide solution 1.  49 m 1 was reacted according to the method of Example (1 e) to obtain 524 mg of the title compound as a white solid. Draw r (DMS0-d6) δ ppm: 3. 90 (3H, s), 5. 14 (2H, m), 6. 46 (1H, d, J = 2. 2Hz), 7. 26-7. 34 (5H, m), 7. 38 (1H, dd, J = 2. 2, 8. 8Hz), 7. 59 (1H, s), 7. 6K1H, d, 1 = 2. 2Hz), 7. 70 (1H, s), 8. 35 (1H, d, 1 = 8. 8Hz), 8. 72 (1H, s).  (141c) 7-benzyloxy-1- (3-methoxy-5-trifluorotolyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5- Difluorophenyl) -amidine. The 7-benzyloxy-1-(3-methoxy-5 -trifluorotolyl) -4 -oxy-1,4-obtained in Example (1 4 1 b). Dihydro D quinoline-3-Junic acid 500mg, isobutyl chloroformate. 15ml, triethylamine 0. 3 ml and 206 mg of 3,5-difluoroaniline were reacted in the same manner as in Example (54c) to obtain 551 mg of the title compound as a white solid. Li R (CDC13) (5ppm: 3. 9Κ3Η, s), 5. 04 (2H, m), 6. 42 (1H, d, 1 = 2.  2Hz), 6. 51-6. 57 (1H, m), 7. 06 (1H, s), 7. 19 (1H, dd, J = 2. 2, 8. 8Hz), 7. 26-2.  28 (3H, m), 7. 31-7. 39 (6H, m), 8. 48 (1H, d, J = 9. 5Hz), 8. 74 (1H, s).  (141d) 7-benzyloxy-1- (3-methoxy-5-trifluorotolyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 5- Difluorophenyl) -N-acetamidamine, the 7-benzyloxy-1-(3-methoxy-5 -trifluorotolyl) -4 -oxo obtained in Example (1 4 1 c) 1,4-dihydroquinoline-3 -carboxylic acid N- (3, 5-difluorophenyl) -fluorenamine 500 mg, 55% sodium hydride 56 mg and iodoethane 0.27 m 1. The reaction was carried out according to the method of Example (54d), and the title compound, 200300349, was obtained as 401 mg as a pale yellow solid. Leg (CDC13) (5ppm: 1. 20 (3H, t, J = 7. 3Hz), 3. 89 (3H, s), 3.  91-3.  95 (2H, m), 4. 97 and 4. 99 (total 2H, each s), 6. 30 (1H? D, J-2. 2Hz), 6.  61-6. 67 (1H, m), 6. 83 (2H, dd, J = 2. 2, 8. 1Hz), 6.  98-7.  03 (2H, · m), 7. 18 (1H, s), 7. 25-7.  36 (6H, m), 7. 83 (1H, s), 8. 22 (1H, d, J = 9. 5Hz).  (141e) 7-hydroxy-1- (3-methoxy-5-trifluorotolyl) _4-oxo-l, 4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorobenzene -Acetylamine 7-benzyloxy-1-(3-methoxy-5 -trifluorotolyl) -4 -oxy-1,4 -dihydro obtained in Example (1 4 1 d) Quinoline-3 -carboxylic acid N- (3, 5-difluorophenyl) -N-acetamidamine 380 mg and 10% Pd-C80 mg were reacted according to the method of Example (llh) to obtain the title compound as a white 290m g NMR ^ (CDC13) δρριη: 1. 17 (3H, t, J = 6. 6Hz), 3.  86-3.  95 (5H, m), 6. 32 (1H, d, J = 2. 2Hz), 6. 62-6. 67 (lH, m), 6. 8K2H, d, J = 5. 9Hz), 6. 88-6. 91 (1H, m), 7.03 (1Η, s), 7.0 · (1Η, s), 7.28 (1Η, s), 7.76 (1Η, s), 7.98 (1Η, d , J = 8. 8Hz) · (141 f) 7- (7-bromoheptyloxy) -1- (3-methoxy-5-trifluorotolyl) -4 -oxo-1,4-dihydroquinoline-3- Carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 7-hydroxy-1-(3-methoxy-5 -trifluorotolyl group obtained in Example (1 4 1 e) ) 4-Oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 280mg, 1,7-dibromoheptane 0. 28 ml and potassium carbonate 149 mg were reacted and purified according to the method of Example (1 1 i) to obtain the title compound as a colorless foam 287 mg. Li R '(CDC13) δρρπι: 1.21 (3Η, t, J: 7. 3Hz), 1.29-1.47 (6Η, m), 1. 69-1. 76 (2H, m), 1. 81-1. 88 (2H, m), 3. 39 (2H, t? J-6. 6Hz), 3.  86 (2H, t, J = 6. 6Hz), 3. 90-4. 00 (5H, m), 6. 26 (1H, d, J-2. 2Hz), 6. 61-6. 67 (1H, m), 6. 84 (2H,-370-200300349 dd, J = 2. 2, 8. 1Hz), 6. 93 (1H, dd, J = 2.  2, 9. 5Hz), 7. 08 (1H, d, J = 2. 2Hz), 7. 2K1H, s), 7. 34 (1H, s), 7. 84 (1H, s), 8. 22 OH, d, J = 8. 8Hz).  (141g) bromide 1- {7- [3- [N- (3,5-mono-phenyl) -1 ^ -ethylaminomethylmethyl] -1- (3-methoxy-5-trifluoro Tolyl) -4 -oxo-1,4-dihydroquinolin-7 -yloxy] heptylbu 4 -acyl-;!-Azobicyclo [2 · 2 · 2] octane Example (1 4 1 f) 7-(7 -bromoheptyloxy) -1-(3-methoxy-5 -trifluorotolyl) -4 -oxo-1,4 -dihydro_line-3-end 136 mg of N- (3,5- —phenyl) -N-acetamidine and 1,4-diazine-bicyclo [2. 2. 2] Xin; I: finished 4 5 mg, the reaction was carried out according to the method of Example (1 1 j), and the title compound was obtained as a white powder 1251 mg NMR.  (CDC13) δρριη: 1. 20 (3H, t, J = 7. 3Hz), 1. 38 (6H, br), L71-1. 85 (4H, m), 3.  26-3.  30 (6H, m), 3.  52-3.  56 (2H, m), 3.  65-3.  69 (6H, m), 3.  84-3.  87 (2H, m), 3. 89-3. 93 (5H, m), 6. 26 (1H, d, 1 = 2. 2Hz), 6. 65 (1H, t,. J = 8. 8Hz), 6. 82-6. 84 (2H, m), 6. 93 (1H, dd, 1 = 2. 2, 8. 8Hz), 7. 00 (1H, s), 7. 18 (1H, s), 7. 33 (1H, s), 7.  78 (1H, s), 8. 20 (1H, d, J = 9. 5Hz).  Melting point: 1 3 0 to 1 3 3 ° C -(3-Methoxy-5-trifluorotolyl) -4 -oxo-1,4-dihydroquinoline-7-yloxy] heptyl}-1 _methylpiperazine (example compound number : 2-7 7 8) The 7-(7-bromoheptyloxy) -1-(3-methoxy-5-trifluorotolyl) -4 -oxo obtained in Example (1 4 1 f) 1,4-dihydroammonoquinoline-3 -unsaturated acid N- (3, 5-monofluorophenyl) -N-acetamidine 1 4 3 mg and 1-methylpiperidine 0.1 2 m 1, according to The reaction of Example (1 1 j) was carried out to obtain the title compound as a yellow solid, 150 mg 〇200300349 NMR.  (CDC13) (5ppm: 1. 20 (3H, t, J = 7. 3Hz), 1. 41 (6H, br), 1. 70-1.  91 (10H, m), 3. 32 (3H, s), 3. 62-3.  74 (6H, m), 3.  84-3.  87 (2H, m), 3.  90-3. 93 (5H, m), 6. 26 (1H? D, J = 2. 2Hz), 6.  62-6.  67 (1Ή, m), 6. 83 (2H? Dd, J = 2. 2, 8. 1Hz), 6. 93 (1H, dd, J = 2. 2, 8. 8Hz), 7. 08 (1H, s), 7. 20 (1H, s), 7. 34 (1H, s), 7. 82 (1H, s), 8. 2K1H, d, J = 9. 5Hz).

Melting point: 1 1 8 ~ 1 2 0 ° C Example 1 4 3 Bromide 1- {7- [3- [N- (3,5-difluorophenyl) -N_ethylaminomethylmethyl] -l -(3 -fluoro-4-methoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7 -yloxy] heptyl}-4 -acyl-1 -azobicyclo [2 · 2 2] Octane (Exemplified compound number: 2- 805) (143a) 7-benzyloxy-1- (3-fluoro-4-methoxyphenyl) -4-oxo-1,4-dihydroquinoline -3-Methyl carboxylate The 2- (4-benzyloxy-2-methoxybenzylfluorenyl) -3 -dimethylamino-acrylic acid methyl ester obtained in Example (44b) 1.0 g, 3-fluoro 382 mg of 4-methoxyaniline and 748 mg of potassium carbonate were reacted according to the method of Example (lie) to obtain 950 mg of the title compound as a white solid. NMR. (CDCI3) δ ppm: 3.9K3H, s), 4.02 (3H, s), 5.01 and 5. 02 (total 2H, each s), 6.37 (1H, d, J = 2.2Hz), 7. 06- 7.15 (4H, m), 7. 28-7. 30 (2H, m), 7.33-7.38 (3H, m), 8.43 (1H, s), 8.45 (1H, d, J = 8.8Hz). (143b ) 7-benzyloxy-1- (3-fluoro-4-methoxyphenyl) -4-oxo, 1,4-dihydroquinoline-3 -carboxylic acid. The compound obtained in Example (1 4 3 a) 7-benzyloxy-1-(3-fluoro · 4-methoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid methyl ester 9 2 0 mg and 1 N-hydroxide The sodium solution was 2.5 5 ml 1, and the reaction was carried out according to the method of Example (1e). The title compound was obtained as a yellow solid, 940 mg,-372-200300349. NMR, (DMS0-d6) δρρπ: 3.99 (3H, s), 5.14 (2H, s), 6.50 (1H, d, J = 2.2Hz), 7. 30-7. 38 (6H, m), 7. 40-7. 46 (2H, m), 7. 63-7. 66 (1H, m), 8.34 (1H, d, 1 = 8.8 Hz), 8.63 (1H, s). (143c) 7-benzyl Oxy-1- (3-fluoro-4_methoxyphenyl) _4_oxy-1,4_dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -fluorenamine will 500 mg of 7-benzyloxy-1-(3-fluoro-4 -methoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid obtained in Example (1 4 3 b), 0.17 ml of isobutyl chloroformate, 0.33 ml of triethylamine and 231 mg of 3,5-difluoroaniline were reacted according to the method of Example (5 4 c) to obtain the title compound as a yellow solid 5 17 mg ° NMR ( CDC13) (5ppm: 4.04 (3H, s), 5.04 (2H, m), 6.46 (1H, d, J = 2.2Hz), 6.51-6. 57 (1H, m), 7.10-7.19 (4H, m) , 7.28-7.40 (7H, m), 8.46 (1H, d, J = 9.5Hz), 8.74 (1H, s).… (143d) 7-benzyloxy-1- (3-fluoro-4-methoxy Phenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid. N- (3,5-difluorophenyl) -acetamidine 7 obtained in Example (1 4 3 c) -Benzyloxy-1-(3-fluoro-4 -methoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl)- Phenamine 50 11 ^, 55% sodium gaseous 6211 ^ and iodoethane 0.31111 were reacted according to the method of Example (5 4 d) to obtain the title compound as a colorless foam 4 1 2 mg 〇 leg (CD called δρριπ: 1 20 (3Η, t, J = 7.3Hz), 3.92 (2H, Q, J = 7.3Hz), 4.01 (3Η, s), 4.97 (2Η, s), 6.32 (1Η, d, > 2 · 2Ηζ), 6.60-6. 66 (1Η, m), 6.83 (2Η, dd, J-2.2, 8.1Hz), 6. 98-7. 14 (4H, m), 7.27-7. 37 ( 5H, m), 7.82 (1H, s), 8. 21 (1H, d, J-8.8Hz). 200300349 (143e) l- (3-fluoro-4 -methoxyphenyl) -7-hydroxy-4 -Oxygen-1,4 -dihydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl) -N -acetamidine The 7-benzyloxy-1- obtained in Example (143d) (3-Fluoro-4-methoxyphenyl) -4-oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 390 mg and 10% Pd-C80 mg was reacted according to the method of Example (11h) to obtain the title compound as a white solid 3 16 mg. Li R (CDC13) δρριη: 1.17 (3H, t, J = 6.6Hz), 3.88 (2H, q, J = 6.6Hz), 3.95 (3H, s), 6.34 (1H, d, J = 2.2Hz), 6.61-6.66 (1H, m), 6.8K2H, d, J = 5.9Hz), 6.87 (1H, d, 1 = 8.1Hz), 6.98-7.09 (3H, m), 7.76 (1H, s), 7.96 ( 1H, d, J = 8.8Hz). (143f) 7- (7-bromoheptyloxy) -1- (3-fluoro-4-methoxyphenyl) -4-oxo-1,4-dihydroquine N- (3,5-difluorophenyl) -acetamidinium carboxylic acid, 3- (4-fluoro-4 -methoxyphenyl) -7- Hydroxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 3 00 mg, 1,7-dibromoheptane 0.33 ml and 177 mg of potassium carbonate were reacted and purified according to the method of Example (1 1 i) to obtain 295 mg of the title compound as a colorless foam. Li R (CDC13) (5ppm: 1.20 (3H, t, J = 7.3Hz), 1. 30-1.48 (6H, m), 1.69-1.76 (2H, m), 1.81-1.88 (2H, m), 3.40 (2H, t, J = 6.6Hz), 3.86 (2H, t, J = 6.6Hz), 3.93 (2H, q, J = 7.3Hz), 4.0K3H, s)? 6.27 (1H, d, J-2.2 Hz), 6.60-6. 66 (1H, m), 6.83 (2H, dd, J = 2.2, 8.1Hz), 6.91 (1H, dd, J = 2.2, 8.8Hz), 7.09-7. 16 (3H, m), 7.83 (1H, s), 8.21 (1H, d, J = 8.8Hz). (143g) bromide {7- [3- [N- (3,5-difluorophenyl) -N- Ethylaminomethyl] -1- (3-fluoro-4 -methoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] heptylbu 4 Nitrobicyclo [2 · 2 · 2] octane The 7- (7-bromoheptyloxy) -1- (3-fluoro-4- 200300349 methoxyphenyl) -4 -oxo obtained in Example (143f) 147 mg of 1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine and 1,4-diazine-bicyclo [2 · 2 · 2] octane 52 mg. The reaction was carried out according to the method of Example (1 1 j) to obtain 152 mg of the title compound as a white solid. (CDC13) δρρπι: 1.20 (3H, t, J = 6.6Hz), 1.38 (6H, br), 1. 65-1. 85 (4H, m), 3.28 (6H, t, J = 7.3Hz), 3.51 -3.56 (2H, m), 3.66 (6H, t, J = 7.3Hz), 3.85 (2H, t, J = 6.6Hz), 3.9K2H, q, J = 6.6Hz), 4.0K3H, s), 6.26 (1H, d, J = 2.2Hz), 6.62-6.66 (lH, m), 6.83 (2H, dd, J = 2.2, 8.1Hz), 6.9K1H, dd, J = 2.2, 8.8Hz), 7.08-7.19 (3H, m), 7.77 (1H, s), 8.18 (1H, d, J = 9.5Hz). Melting point: ~ 1 4 0 ° C Example 1 4 4 Bromide 1- {7- [3- [N -(3,5-difluorophenyl) -N-ethylamine formamidine 1- (3-fluoro-4-methoxyphenyl) -4-oxo-1,4-dihydroquinolin-7-yl Oxy] heptylbupropane-methyl piperidine (exemplified compound number: 2-8 0 4) The 7- (7-bromoheptyloxy) -1- (3-fluoro- 4- Methoxyphenyl) -4 -oxy-1,4 -dihydro D quelin-3 -residual acid N- (3,5 -monogasyl) -N -acetamidine 1 4 1 mg and 1 -formamidine D was set to 0 · 1 3 m 1 and the reaction was carried out according to the method of Example (1 1 j) to obtain the title compound as a yellow powder 1 4 2 mg ο NMR. * (CDC13) δρριη: 1.20 (3H, t, J = 7.3Hz), 1.41 (6H, br), 1.70-1.95 (10H, m), 3.3K3H, s), 3.62-3.73 (6H5 m), 3.85 (2H, t, J = 5.9Hz), 3.9 2 (2H, q, J = 7.3Hz), 4.0K3H, s), 6.26 (1H, d, J = 2.2Hz), 6.61-6.66 (1H, m), 6.83 (2H, dd, J = 2.2, 8.1 Hz), 6.9K1H, dd, J = 2.2, 8.8Hz), 7.09-7.20 (3H, m), 7.8K1H, s), 8.20 (1H, d, J-8.8Hz).

Melting point: 1 1 7 ~ 1 2 1 ° C 200300349 Example 1 4 5 Brominated l- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] _1_ (3-Methoxy-5-methoxycarbonylphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] heptylbuprofen (exemplified compound number: 2-7 8 0) (145a) 7-octyloxy-1- (3-second butoxycarbyl-5-methoxybenzyl) -4 -oxo-1, 4-dihydroquinoline-3 -carboxylic acid methyl ester As the ester, 5- (4-benzyloxy-2-methoxymethoxybenzyl) -3-dimethylamino-methyl acrylate obtained in Example (44b) was used. 5. 3 8 g, 3-obtained in Reference Example 8- 3.25 g of the third butoxycarbonyl-5-methoxyaniline and 4.02 g of potassium carbonate were reacted according to the method of Example (1 1 e) to obtain 5.40 g of the title compound as a white solid. NMR. (CDC13) 6ppm: 1.6K9H, s), 3.90 (3H, s), 3.92 (3H, s), 5.03 (2H, m), 6.36 (1H, d, J-2.2Hz), 7.03 (1H, t, J = 2.2Hz), 7.09 (1H, dd, J = 2.2, 8.8Hz), 7.28-7.36 (5H, m), 7.53 (1H, s), 7.74-7.75 (1H, m), 8.45 (1H , s), 8.48 (1H, d, J = 8.8 Hz). (145b) 7-benzyloxy-1- (3-tert-butoxycarbonyl-5-methoxyphenyl) -4-oxo-1 4, 4-dihydroquinoline-3 -carboxylic acid. The 7-benzyloxy-1-(3-tert-butoxycarbonyl_5-methoxyphenyl) -4-obtained in Example (1 4 5 a) Oxy-1,4-dihydroquinoline-3 -carboxylic acid methyl ester 5.40 g and 1 N -sodium hydroxide solution 1 1 m 1 'According to the method of Example (1 e), the title compound can be obtained. 2 · 0 4 § ° NMR,, (CDC13) δρριη: 1.62 (9H, s), 3. 91 (3H, s), 5.04 (2H, m), 6.48 (1H, d, J = 2.2Hz) , 7.00-7.01 (1H, m), 7.22 (1H, dd, J = 2.2, 8.8Hz), 7. 25-7. 29 (2H, m), 7.31-7.36 (3H, m), 7.52-7.53 ( 1H, m), 7.78 (1H, t, J = 1.5Hz), 8.47 (1H, d, J-9.5Hz), 8.68 (1H, s).-376-200300349 (145c) 7-benzyloxy-1 -(3-Third-butoxycarbonyl-5-methoxyphenyl) -4-oxo 1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -fluorene The 7-benzyloxy-1-(3-tert-butoxycarbonyl-5-methoxyphenyl) -4 -oxo-1,4-dihydroquinoline obtained in Example (1 4 5 b) was used as the amine. 2.0 g of 3-carboxylic acid, 0.58 ml of isobutyl chloroformate, 1.11 ml of triethylamine and 7 7 2 mg of 3,5-difluoroaniline were reacted according to the method of Example (5 4 c) to obtain the title. The compound was 2.29 g of a white solid. NMR. (CDC13) (5ppm: 1.62 (9H, s), 3.9K3H, s), 5.03 (2H, m), 6.46 (1H, d, J = 2.2Hz), 6.51-6.57 (1H, m), 7.03 (1H, t, J = 2.2Hz), 7.18 (1H, dd, J = 2.2, 8.8Hz), 7.26-7.41 (7H, m), 7.55 (1H, t, J = 1.5Hz), 7.77-7.78 ( 1H, m), 8.48 (1H, d, 1 = 8.8Hz), 8.76 (1H, s).

(145d) 7-benzyloxy-l- (3-t tert-butoxycarbonyl-5-methoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3 , 5-difluorophenyl) -N-acetamidinium 7-benzyloxy-1-(3-tert-butoxycarbonyl-5-methoxyphenyl) obtained in Example (1 4 5 c)- 4-oxyl, 4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -fluorenamine 2.27§, 55% sodium hydride 1701 ^ and iodoethane 1.171111, depending on The reaction of Example (54d) was carried out to obtain 1.80g of the title compound as a colorless foam. NMR (CDC13) δρριη: 1.20 (3H, t, J-7.3Hz), 1.6K9H, s), 3. 88-3. 95 (5H, m), 4.93 ~ 5.00 (2H, m), 6.32 (1H, d, J = 2.2Hz), 6.61-6.66 (1H, m), 6.84 (2H, dd, J = 2.2, 8.1Hz), 6.95 (1H, t, J = 2.2Hz), 7.00 (1H, dd, J = 2.2, 8.8Hz), 7. 25-7. 35 (5H, m), 7.48 (1H, d, J-1.5Hz), 7. 72-7. 73 (1H, m), 7.83 (1H, s ), 8.23 (1H, d, J = 8.8Hz). (145e) 7-benzyloxy-1- (3-carboxy-5-methoxyphenyl) -4-oxo-1,4-dihydroquinoline -3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine- 377-200300349 The 7-benzyloxy-1 obtained from Example (1 4 5 d)-(3 -1 Tert-Butoxycarbonyl-5-methoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidoamine 1.75 To a solution of 20 g of anhydrous dichloromethane was added 5 ml of trifluoroacetic acid. Stir at room temperature for 5 hours. The solvent and excess trifluoroacetic acid were distilled off. The residue was solidified with a small amount of dichloromethane and dissolved in diisopropyl ether. Filtration gave 1.51 g of the title compound as a white solid. NMR (DMS0-d6) (5ppm: 1.07 (3H, t, J = 7.3Hz), 3. 81-3. 88 (5H, m), 5.03 (2H, s), 6.33C1H, d, J = 2.2Hz ), 7. 02 ~ 7. 13 (4H, m), 7.25-7. 33 (6H, m), 7.46 (1H, s), 7.66 (1H, t, J = 1.5Hz), 8.00 (1H, d , J = 8.8Hz), 8.1K1H, s). (145f) 7-benzyl-1- (3-methoxy-5-methoxyphenyl) -4-oxy-1,4-dihydro Quinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 7-benzyloxy-1-(3-carboxy-5) obtained in Example (1 4 5 e) -Methoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine '50 Omg, potassium carbonate 236mg and 0.11 ml of iodoform is mixed with 5 ml of anhydrous N, N-dimethylformamide. Stir at room temperature for 2 hours. Dilute with ethyl acetate, rinse with dilute hydrochloric acid, water, saturated sodium bicarbonate water, and saturated brine in this order, dry over anhydrous magnesium sulfate, and concentrate the solvent under reduced pressure. The precipitated solid was dissolved in diisopropyl ether and filtered to obtain 495 mg of the title compound as a white solid. Li R (CDC13) δ ppm: 1.20 (3H, t, J = 7.3Hz), 3. 90-3.94 (5H, id), 3.96 (3H, s), 4.956 and 4.962 (total 2H, each s), 6.31 (1H, d, J = 2.2Hz), 6. 61-6.67 (1H, m), 6.84 (2H, dd, J-2.2, 8.1Hz), 6. 99-7. 02 (2H, m), 7.24 -7. 34 (5H, m), 7.56 (1H, d, J = 1.5Hz), 7.75-7.76 (lH, m), 7.84 (1H, s), 8.23 (1H, d, J = 8.8Hz). (145g) 7-Ethyl-1- (3-methoxy-5-methoxyphenyl) -4-oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5- Difluorophenyl) -N-acetamidamine-378-200300349 The 7-benzyloxy-1- (3-methoxy-5-methoxycarbonylphenyl) 4-oxy- 1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 480 mg and 10% Pd-C 100 mg were reacted according to the method of Example (llh) 3 5 6m g ο NMR (DMS0-d6) (5ppm: 1.07 (3H, t, J = 6.6Hz), 3.82 (2H, q, J = 6.6Hz), 3.90 (3H, s), 3.9K3H, s), 6.25 (1H, d, J = 2.2Hz), 6.80 (1H, dd, J = 2.2, 8.8Hz), 7.04-7.10 (3H, m), 7.43 (1H, s) , 7.5K1H, s), 7.66-7.67 (1H, m), 7.93 (1H, d, J = 8.8Hz), 8.06 (1H, s) ...

(145h) 7- (7-bromoheptyloxy) -1- (3-methoxy-5-methoxycarbonylphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N -(3, 5-difluorophenyl) -N-acetamidine The 7-hydroxy-1-(3-methoxy-5 -methoxycarbonylphenyl) obtained in Example (1 4 5 g)- 4-oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 340 mg, 1,7-dibromoheptane 0.34 ml and potassium carbonate 185 mg was reacted and purified according to the method of Example (1 1 i) to obtain 155 mg of the title compound as a colorless foam. Li R (CDC13) δρριη: 1.21 (3Η, t, J = 7.3Hz), · 1.3 · 1.41 (647, m), 1.68-1.75 (2H, m), 1.80-1.87 (2H, m), 3.39 (2H, t, .J = 6.6Hz), 3.85 (2H, t, J = 6.6Hz), 3.91-3.96 (8H, m), 6.27 (1H, d, J = 2.2Hz), 6.61 -6. 67 (1H, m), 6.84 (2H, dd, 1 = 2.2, 8.1Hz), 6.92 (1H, dd, J = 2.2, 8.8Hz), 7.08 (1H, t, J = 2.2Hz), 7. 61 (1H, d, J = 1.5Hz), 7.76 (1H, t, J = 1.5Hz), 7.85 (1H, s), 8.22 (1H, d, J = 8.8Hz). (145i) bromide l- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3-methoxy-5-methoxycarbonylphenyl) -4 -Oxy-1,4-dihydroquinoline-7-yloxy] heptylb-formamidine ingot-379-200300349 The 7-(7 -bromoheptyloxy) obtained in Example (1 4 5 h) ) -1-(3-methoxy-5 -methoxycarbonylphenyl) -4 -oxo-1,4-dihydroquinoline-carboxylic acid N- (3,5-difluorophenyl) -N- 145 mg of acetamidine and 0.13 ml of 1-methylpiperidine were reacted according to the method of Example (1 1 j) to obtain 159 mg of the title compound as a pale yellow solid. Wake R. (CDC13) δρριι: 1.20 (3H, t, J = 7.3 Hz), 1.40 (6H, br), 1.70-1.91 (10H, m), 3.32 (3H, s), 3. 62-3. 76 (6H, m), 3. 82-3. 86 (2H, m), 3. 90-3. 96 (8H, m), 6.27 (1H, d, J = 2.2Hz), 6. 62-6 . 67 (1H, m), 6.84 (2H, dd, J = 2.2, 8.1Hz), 6.92 (1H, dd, J = 2.2, 8.8Hz), 7.08 (1H, t, J = 2.2Hz), 7.60 ( 1H, d, J = 2.2Hz), 7.76 (1H, dd, J = 1.5, 2.9Hz), 7.83 (1H, s), 8.21 (1H, d, J = 8.8Hz). Melting point: 1 2 7 ~ 1 2 9 ° C Example 1 4 6 1-{7-[1- -N-ethylaminomethylmethyl] -4 -oxo-1,4-dihydroquinoline-7-yloxy] heptylb-methylpiperidine (exemplified compound number: 2-8 1 3) (146a ) 7-Benzyloxy-1- (3-aminomethylmethyl-5-methoxyphenyl) -4-oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-di Fluorophenyl) -N-acetamidine The 7-benzyloxy-1-(3-carboxy-5 -methoxyphenyl) -4 -oxy-1,4-obtained in Example (1 4 5 e) Dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 500 mg and triethylamine 0.24 ml anhydrous dichloromethane 5 m 1 solution was added dropwise to isobutyl chloroformate Esters 0. 1 2 m 1, stir at room temperature for 1 hour, add 28% ammonia aqueous solution in 3 hours, and add N, N -dimethylformamide 5 m 1 in 20 hours with stirring. Dilute with ethyl acetate, rinse with dilute hydrochloric acid, water, saturated sodium bicarbonate water, and saturated brine in this order. After drying over anhydrous magnesium sulfate, the solvent was concentrated. The residue was purified by silica gel column chromatography 200300349 (eluent ·· hexane / ethyl acetate 1/2 ~ o / l) to obtain 40 6 mg of the title compound as a colorless foam. NMR. (CDC13) δρριη: 1.17 (3H, t, J = 7.3 Hz), 3. 83-3. 93 (5Η, m), 4. 92 (2Η, s), 6.23 (1H, d, J = 2.2Hz), 6.57-6. 62 (1H, m), 6. 80-6. 82 (4H, m), 7. 23-7. 35 (5H, m), 7.45 (1H, s), 7.70 ( 1H, d, J = 1.5Hz), 7.79 (1H, s), 8.02 (1H, d, I = 8.8Hz). (146b) l- (3-aminomethylamido-5-methoxyphenyl)- 7-Hydroxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -acetamidine The 7-benzyloxy obtained in Example (146a) -1- (3-Aminomethylamido-5 -methoxybenzo.yl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl)- N-acetamide 320 mg and 10% Pd-C60 mg were reacted according to the method of Example (11 h) to obtain the title compound as a pale yellow solid, 2 4 3 mg NMR, (CDC13) δρρπι: 1.10-1. 25 (3Η, m), 3. 85-4.10 (5H, m), 5.90-8. 20 (1 OH, m). (146 (〇7- (7-Bromoheptyloxy) -1- (3- Carboxymethyl-5-methoxyphenyl) _4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine, to be implemented Example (1 4 6 b) 1- (3-Aminomethylamido-5-methoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorobenzene Group) -N-acetamidamine 230 mg, 1,7-dibromoheptane 0.24 ml and potassium carbonate 12 24 mg. The reaction was performed according to the method of Example (1 1 i) and purified to obtain the title compound as a colorless compound. Foam 204 mg. Bandit R (CDC13) (5ppm: 1.17 (3H, t, J-7.3Hz), 1. 31-1.48 (6H, m), 1.68-1.75 (2H, m), 1. 81- 1. 88 (2H, in), 3.40 (2H, t5 J = 6.6Hz), 3. 78-3. 91 (7H, m), 200300349 6.19 (1H, d, J = 2.2Hz), 6.57-6.63 ( 1H, m), 6.76-6. 83 (3H, m), 6.91 (1H, s), 7.49 (1H, s), 7.67 (1H, d, J = 1.5Hz), 7.8K1H, s), 8.06 ( 1H, d, J = 9.5Hz). (146d) bromide l- {7- [l- (3-aminomethylamino-5-methoxyphenyl) -3- [N- (3,5-di Fluorophenyl) -N-ethylaminomethylmethyl] -4-oxo-1,4-dihydroquinoline-7-yloxy] heptylb-methylpiperidine Example (1 4 6 c) The obtained 7- (7-bromoheptyloxy) -1- (3-aminomethylamidino-5-methoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-Difluorophenyl) -N-acetamidine 190 mg and 1-methylpiperidine 0.17 ml were reacted according to the method of Example (1 1 j) to obtain the title compound as a light yellow powder 1 8 8 mg. Surface R (CDCl3) (5ppni: 1.21 (3Η, t, J = 7.3Hz), 1.35 (6Η, br), 1.67-1. 88 (10H, m), 3.25 (3H, s), 3 61-3. 65 (6H, m), 3. 80-3. 93 (7H, m), 6.23 (1H, d, J = 2.2Hz), 6.60-6.64 (lH, m), 6.78-6.88 ( 4H, m), 7.66 (1H, s), 7.80 (1H, s), 7.84 (1H, s), 8.09 (1H, d, J = 9.5Hz). Melting point: 1 3 7 ~ 1 4 0 ° C Implementation Example 1 4 7 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine

] -l- (3-methoxy-5-nitrophenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] heptylbuprofen (Exemplified Compound Number: 2 -7 8 1) (147a) 7 -methoxymethoxyl 1- (3-methoxy-5-nitrophenyl) -4 -oxo-1, 4 -dihydroquinoline-3 -residue acid The ester was 1.6 4 g of methyl 3-dimethylamino-2- (2-methoxy-4-methoxymethoxybenzyl) acrylate obtained in Example (104d), and 3 of 3 obtained in Reference Example 7. -1.05 g of methoxy-5-nitroaniline hydrochloride and 2.81 g of potassium carbonate. The reaction was carried out according to the method of Example (1 1 e) to obtain 1.06 g of the title compound as an orange solid. -382-200300349 MR · (CDC13) (5ppm: 3.42 (3H, s), 3.92 (3H, s), 4.0K3H, s), 5.14 (2H, s), 6.540H, d, J = 2.2Hz), 7.150H, dd, J = 2.2, 8.8Hz), 7.36 (1H, t, J = 2.2Hz), 7. 92-7. 93 (1H, m), 7. 96 (1H, t, J = 2.2Hz ), 8. 45-8. 47 (2H, m). (147b) 7-methoxymethoxy-1- (3-methoxy-5-nitrophenyl) -4 -oxy-1,4- _Gasalin-3-Junic acid: 7-methoxymethoxy-1- (3-methoxy) obtained in Example (147a)

-5-nitrophenyl) 4-oxo-1,4-dihydroquinoline-3 -carboxylic acid methyl ester 1.04 g and sodium hydroxide 186 mg, according to Example (1e) The reaction was carried out by the method to obtain 950 mg of the title compound as a yellow solid. Bandit R. (CDC13) 0ppm: 3.44 (3H, s), 4.02 (3H, s), 5.18 (2H, s), 6.68 (1H, d, J = 2.2Hz), 7. 29-7.33 (2H, m ), 7.93 (1H, t, J = 2.2Hz), 8.00-8.01 (1H, m), 8.50 (1H, d, J = 8.8Hz), 8.7K1H, s). (147c) 7-methoxymethoxy -1- (3-methoxy-5-nitrophenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid

The 7-methoxymethoxy-1-(3-methoxy-5 -nitrophenyl) -4 -oxo-1,4-dihydroquinoline-3-obtained in Example (1 4 7 b) 920 mg of carboxylic acid, 0.30 ml of isobutyl chloroformate, 0.57 ml of triethylamine and 399 mg of 3,5-difluoroaniline were reacted according to the method of Example (5 4 c) to obtain the title compound as a yellow solid 1.07 g. Awake R (CDC13) δ ppm: 3. 44 (3H, s), 4.01 (3H, s), 5.17 (2H, s), 6.53-6.5δ (1Η, m), 6.65 (1H, d, 1 = 2.2Hz), 7.25-7.28 (1H, m), 7. 33-7. 41 (3H, in), 7.94-7.95 (lH, m), 7.99 (1H, t, J = 2.2Hz) , 8.5K1H, d, J = 8.8Hz), 8.78 (1H, s). (147d) 7-methoxymethoxy-1- (3-methoxy-5-nitrophenyl) -4 -oxy- 1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl) -N -acetamidin The 7 -methoxymethoxy group obtained in Example (1 4 7 c)- 1- (3 -methoxy- 383-200300349 -5 -nitrophenyl) -4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl)- Ammonium amine 1.05 g, 55% sodium hydride 134 mg and iodoethane 0.65 m 1 were reacted according to the method of Example (54 d) to obtain 790 mg of the title compound as a pale yellow solid. . NMR (CDC13) (5ppm: 1.2K3H, t, 1 = 7.3 Hz), 3.4K3H, s), 3. 90-4. 00 (5H, di), 5.1K2H, s), 6.5K1H, d, J = 2.2Hz), 6.63-6.68 (1H, m), 6.84 (2H, dd, J = 2.2, 8.1Hz), 7.08 (1H, dd, J = 2.2, 8.8Hz), 7.25 (1H, t, J = 2.2Hz), 7.86 (1H, s), 7.88 (1H, s), 7.93 (1H, t, J = 2.2Hz), 8.23 (1H, d, J = 8.8Hz). (147e) 7 -hydroxy-1 -(3-methoxy-5-nitrophenyl) -4_oxy-I, 4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine The 7-methoxymethoxy-1-(3-methoxy-5 -nitrophenyl) -4 -oxo-1,4-dihydroquinoline-3-obtained in Example (1 4 7 d) was used. The carboxylic acid N- (3, 5-difluorophenyl) -N-acetamidine 150 mg was reacted according to the method of Example (102 d) to obtain the title compound as a light yellow solid 1 3 5 mg. MR (CDCI3) (5ppm: 1.2K3H, t, J = 7.3Hz), 3. 80-4. 00 (5H, m), 6.53 (1H, s), 6.73-6.77 (1H, m), 6.88 (2H , br), 7.02 (1H, d, J = 8.1Hz), 7.26 (1H, br), 7.59 (1H, s), 7.76 (2H, br), 7.98 (1H, d, J = 8.8Hz). 147 f) 7- (7-Bromoheptyloxy) -1- (3-methoxy-5-nitrophenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- ( 3,5 -difluorophenyl) -N-acetamidine The 7-hydroxy-1-(3-methoxy-5 -nitrophenyl) -4 -oxo obtained in Example (1 4 7 e) 1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -1 ^ acetamido 13〇11 ^, 1,7-dibromoheptane 0.13 1111 and potassium carbonate 731 ^ The reaction was performed and purified according to the method of Example (1), and 130 mg of the title compound was obtained as a pale yellow foam. 200300349 LiR (CDC13) δρριη: 1.2K3Η, t, J = 7.3Hz), 1. 31-1.47 (6H, m), 1. 69-1. 76 (2H, m), 1. 80-1. 87 (2H, m), 3.39 (2H, t, J = 6.6Hz), 3. 86-3. 99 (7H, m), 6.25 (1H, d, J = 2.2 Hz), 6. 62-6. 68 (1H, m), 6.84 (2H, dd, J = 2.2, 8.1Hz), 6.95 (1H, dd, J = 2.2, 8.8Hz), 7.24-7. 26 (1H, m), 7. 84- 7. 86 (2H, m), 7.94 (1H, t, J = 2.2Hz), 8.22 (1H, d, 1 = 9.5Hz). (147g) bromide l- {7- [3- [N- ( 3,5-monophenyl) -N-ethylaminomethylmethyl] -1- (3-methoxy-5-nitrophenyl) -4-oxo-1,4-dihydroquinoline-7- Oxy] heptyl}-1-methylpiperidine (exemplified compound number)

The 7-(7-bromoheptyloxy) -1-(3-methoxy-5 -nitrophenyl) -4 -oxo-1,4-dihydroquinoline obtained in Example (1 4 7 f) -3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 120 mg and dimethoprim 0.1 μm 1 according to the method of Example (1 1 j) Reaction, 122 mg NMR (CDCI3) of the title compound as a yellow solid 6 ppm: 1.21 (3H, t, J = 7.3Hz), 1.40 (6H, br), 1.65-1.90 (10H, m), 3.3K3H, s), 3. 62-3. 71 (6H, m), 3. 85-3. 95 (4H, m), 4.00 (3H, s), 6.26 (1H, d, J = 1.5Hz), 6.63-6.68 (1H , m), 6.84 (2H, dd, J = 2.2, 8.1Hz), 6.93 (1H, dd, J = 2.2, 8.8Hz), 7. 26-7. 27 (1H, m), 7. 83 -7. 84 (2H, m), 7. 93-7. 94 (1H, m), 8.2K1H, d, J = 9.5Hz). Melting point: 1 2 0 ~ 1 2 5 ° C Example 1 4 8 1- {7- [1- (3-Ethamidinyl-5-methoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminomethylethenyl] 4-oxo-1,4-dihydroquinoline-7-yloxy] heptylb-methylpiperidine (exemplified compound number: 2-8 1 6) (148a) l- (3-amino group -5-methoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3-residue N- (3,5 -monophenyl) -N- Acetamide-385-200300 349 The 7-methoxymethoxy-1-(3-methoxy-5 -nitrophenyl) -4 -oxo-1, 4-dihydroquinoline-3 obtained in Example (1 4 7 d) -Carboxylic acid N-(3,5-difluorophenyl) -N -acetamide 640mg ethanol 5ml-dichloromethane 2ml mixed solution, 10% P d-C 1 50 mg was added under hydrogen, in Stir at room temperature for 2 hours. After the catalyst was filtered off, the solvent of the filtrate was distilled off under reduced pressure. The residue was solidified with ether. The solid was dissolved in diisopropyl ether. Filtration gave 564 mg of the title compound as a white solid. NMR; (CDC13) δ ppm: 1.20 (3Η, t, J = 7.3Hz), 3.41 (3H, s), 3.79 (3H, s), 3.92 (2H, q, 1 = 7.3Hz), 5.12 ( 2H, s), 6.27-6. 28 (2H, m), 6. 40-6. 42 (1H, m), 6.56-6.69 (2H, m), 6.84 (2H, dd, J = 2.2, 8.1Hz ), 7.03 (1H, dd, J = 2.2, 8.8Hz), 7.88 (1H, s), 8.2K1H, d, J = 8.8Hz). (148b) l- (3-acetamido-5 -formaldehyde (Oxyphenyl) -7-methoxymethoxy-4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine Example (1 4 8 a) of 1-(3-amino-5 -methoxyphenyl) -7 -methoxymethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 130 m and triethylamine 0.07 ml in a dichloromethane solution 2 m 1 were added dropwise with anhydrous acetic acid 0.0 3 m 1. Stir at room temperature for 20 hours. Dilute with ethyl acetate and rinse with dilute hydrochloric acid, water, saturated sodium bicarbonate water, and saturated brine in this order. After drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane / ethyl, ethyl acetate = 1/1 to 0/1) to obtain 101 mg of the title compound as a colorless foam. NMR (CDC13) (5ppm: 1.19C3H, t, J = 7.3Hz), 2.20 (3H, s), 3.40 (3H, s), 3.83 (3H, s), 3. 86-3. 95 (2H, m ), 5.10 and 5.11 (total 2H, each s), 6.53 (1H, s), 6.60-6.66 (2H, m), 6.83 (2H, dd, J = 2.2, 7.3Hz), 7.02 (1H, dd, J = 2.2, 8.8Hz), 7.12 (1H, s), 7.54 (1H, s), 7.89 (1H, s), 8.20 (1H, d, J = 8.8Hz). • 386-200300349 (148c) l- ( 3-Ethylamino-5 -methoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N -Acetylamine 1- (3-Acetylamino-5-methoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-di Hydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 95 mg. The reaction was carried out according to the method of Example (102d) to obtain the title compound as a pale yellow solid 8 8 mg . NMR, (CDCl3 + DMS0-d6) δρρπι: 1.2K3Η, t, J = 7.3Hz), 2.2K3H, s), 3. 80-4.00 (5H, m), 6.39 (1H, s), 6.60 (1H, s), 6.7K1H, t, J = 8.1 Hz), 6.87 (2H, br), 7.02 (1H, d, J = 8.1Hz), 7.23 (1H, br), 7.68 (1H, s), 7.86 ( 1H, s), 8.15 (1H, d, J = 8.8Hz). (148d) l- (3-acetamido-5-methoxyphenyl) -7- (7-bromoheptyloxy) -4 -Oxygen-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 1- (3- Acetylamino-5 -methoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 80 mg of amine, 0.08 ml of 1,7-dibromoheptanium, and 44 mg of potassium carbonate were reacted and purified according to the method of Example (1π) to obtain 70 mg of the title compound as a colorless foam. NMR (CDCl3 + DMS〇-d6) δ ppm: 1.18 (3H, t, 1-7.3Hz), 1. 30-1.48 (6H, m), 1.68-1.78 C2H, m), 1.81-1. 88 (2H , m), 2.29 (3H, s), 3.40 (2H, t, 1 = 6.6Hz), 3.76-4.00 (7H, m), 6.2K1H, d, J = 1.5Hz), 6.47 (1H, s), 6.57-6.64 (2H, m), 6.79-6.83 (3H, m), 7.72 (1H, s), 7.83 (1H, s), 8.12 (1H, d, J = 8.8Hz). (148e) Bromide 1 -{7- [1- (3 -Ethylamido-5-methoxyphenyl) -3- [N- (3,5-difluorophenyl) -1 ethylaminomethylamido] -4-oxo -1,4-dihydro-387-200300349 quinoline-7-yloxy] heptylb-methyl piperidine (exemplified compound number) 1- (3- Ethylamino-5 -methoxyphenyl) -7- (7-bromoheptyloxy) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluoro 65 mg of phenyl) -N-acetamidine and 0.06 ml of 1-methylpiperidine were reacted according to the method of Example (1 1 j) to obtain 21 mg of the title compound as a pale yellow foam. Surface R. (CDC13) δρριη: 1.19 (3H, t, J = 7.3Hz), 1.33 (6H, br), 1.62-1.86 (10H, m), 2.3K3H, s), 3.16 (3H, s), 3 47-3.65 (6H, m), 3. 83-3. 94 (7H, m), 6. 33-3. 36 (2H, m), 6. 63-6. 68 (1H? M), 6 83-6. 87 (3H, m), 7.44 (1H, br), 7.78 (1H, s), 7.85 (1H, s), 8.12 (1H, d, J = 8.8Hz). I b ^ vmax ( KBr) cm-l: 2940, 1614, 1459, 1 268, 1 253 · Example 1 4 9 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethyl bromide Aminemethyl] -l- (3-methoxy-5-methoxycarbonylaminophenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] heptyl-1-methyl Piperidine (Exemplary compound number: 2-8 7 7) (149a) 7-methoxymethoxy-1- (3-methoxy-5-methoxycarbonylaminophenyl) 4-oxy-1,4 -Dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 1- (3-amino-5 -formaldehyde) obtained in Example (14 8 a) (Oxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 130 mg and 0.07 ml of triethylamine in ice-free dichloromethane solution 2m], 0.024 ml of methyl chloroformate in 1 ml of anhydrous dichloromethane solution was added dropwise, and stirred at room temperature for 20 hours, and then Triethylamine 0.0 7 m 1 and methyl chloroformate in dry 0.0 2 4 m 1 m 1 1 of dichloromethane solution. Stir for another 24 hours. Dilute with ethyl acetate and rinse with dilute salt-388-200300349 acid, water, saturated sodium bicarbonate water, saturated brine, and dry over anhydrous magnesium sulfate, and then evaporate the solvent under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/2 to ethyl acetate / ethanol = 5/1) to obtain 491 mg of the title compound as a colorless oily substance. NMR.- (CDC13) δρριη: 1.20 (3H, t, J = 7.1Hz), 3.40 (3H, s), 3.80 (3H, s), 3.84 (3H, s), 3.85-3.97 (2H, m), 5.10 (2H, s), 6.56 (1H, t, J = 2.0Hz), 6. 60-6. 65 (2H, m), 6.84 (2H, dd, J = 2.2, 8.0Hz), 6. 98- 7. 03 (2H, m), 7.25 (1H, br), 7.88 (1H, s), 8.20 (1H, d, J = 9.0Hz). (149b) 7-Ethyl-1- (3--methoxy 5-Methoxyamine phenyl) -4oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine Example (149 a) The obtained 7-methoxymethoxy-1- (3-methoxy-5-methoxycarbonylaminophenyl) -4-oxo-1,4-dihydroquinoline 3-carboxylic acid 48 mg of N- (3,5-difluorophenyl) -N-acetamidamine was reacted according to the method of Example (102d) to obtain 3 2 mg of the title compound as a white solid. R 2 (CDC13) δρρπι: 1. 15-1. 30 (3H, m), 3.73 (3Η, s), 3.76 (3Η, s), 3. 85-4. 00 (2Η, m), 6.65 (1H, br), 6. 60-7 . 20 (6H, m), 7.43 (1H, s), 7. 71 (1H, br), 7.98 (1H, d, 1 = 7.3 Hz). Φ

(149c) 7- (7-moheptyloxy) -1- (3-methoxy-5-methoxymineamine radical) 4-oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 7-hydroxy-1- (3-methoxy-5-methoxycarbonylaminophenyl) -4 obtained in Example (149b) Oxy-I, 4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 30mg, 1,7-dibromoheptane 0.03ml and potassium carbonate 16 mg, which was reacted and purified according to the method of Example (1 1 i) to obtain 27 mg of the title compound as a colorless foam. -389-200300349 R. vCDC13) (5ppm: 1.20 (3H, t, J = 7.1Hz), 1. 34-1.48 (6H, m), 1.69-1.76 (2H, m), 1.81-1. 88 (2H , m), 3.39 (2H, t, J = 6.8Hz), 3. 81-3. 97 (10H, m), 6.37 (1H, d, J = 2.0Hz), 6.56 (1H, s), 6. 60-6. 65 (1H, m), 6.83-6. 96 (5H, m), 7.85 (1H, s), 8. 19 (1H, d, J = 8.8Hz). (149d) desertification l- {7- [3- [N- (3,5-monofluorophenyl) -N-ethylamine formamyl] -butanyl-methoxy- 5-.methoxycarbonylaminophenyl) -4 -oxo -1,4-dihydroquinoline-7-yloxy] heptyl} -1-methylpiperidine The 7- (7-bromoheptyloxy) -1- (obtained in Example (1 4 9 c)) 3 -methoxy-5-methoxycarbonylaminophenyl) -4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 5-difluorophenyl) -N-acetamidine 25 mg of amine and 0.02 ml of piperidine were reacted according to the method of Example (11j) to obtain 17 mg of the title compound as a yellow foam. NMR (CDC13) δρριη: 1.20 (3H, t, J = 7.1 Hz), 1. 30-1. 50 (6H, m), 1.65-1. 95 (10H, m), 3.20 (3H, s), 3. 50-3. 70 (6H, m), 3.77 (3H, s), 3. 85-3. 95 (7H, m), 6.40 (1H, s), 6.48 (1H, s), 6.60-6 65 (1H, m), 6. 84-6. 88 (4H, m), 7.55 (1H, s), 7.84 (1H, s), 8.19 (1H, d, J = 9.2Hz). IR (KBr ) cm-1: 2940, 1730, 1615, 1458, 1262, 1228. Example 1 5 0 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylamine bromide Methylfluorenyl] -1- (3-ethoxy-5-isopropoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] heptylb-az-1 -Azobicyclo [2 · 2.2] octane (Exemplified compound number: 2-7 9 0) (150a) 7-benzyloxy-1- (3-ethoxy-5-isopropoxyphenyl) -4 -Methyloxy-1,4-dihydroquinoline-3 -carboxylate The 2- (4-benzyloxy-2 -methoxybenzylhydrazone 200300349) -3 -dimethylamine obtained in Example (44b) -Methyl acrylate 8. 2 2 g, 3 -ethoxy-5 -isopropoxyaniline 4, 2 g and 2.76 g of potassium carbonate obtained in Reference Example 2 according to the method of Example (1 1 e) Reaction was performed to obtain 8.1 g of the title compound as a white solid. Response R (DMS0-d6) δρριη: 1.26-1. 35 (9Η, m), 3.72 (3H, s), 3. 99-4. 09 (2H, m), 4.68 (1H, quint, J = 6.1Hz ), 5.08 (2H, s), 6.46 (1H, d, J = 2.3Hz), 6. 69 (1H, in), 6.72 (1H, m), 6.77 (1H, m), 7.17 (1H, dd, J = 8.9, 2.3Hz), 7.28-7.37 (5H, m), 8.18 (1H, d, J = 8.9Hz), 8.36 (1H, s). (150b) 7-benzyloxy-1- (3- Ethoxy_5_isopropoxyphenyl) -4 · -oxo-1,4-dihydroquinoline-3-carboxylic acid The 7-benzyloxy-1- (3) obtained in Example (150a) -Ethoxy-5-isopropoxyphenyl) -4 -oxy-1,4-dihydroquinoline-3-carboxylic acid methyl ester 8.1g and 10% sodium hydroxide solution 30 m 1, according to implementation The reaction of Example (1e) was carried out to obtain 7.6 g of the title compound as a white solid. Lai R. (DMS0-d6) (5ppm: 1.27-1. 36 (9H, m), 3. 98-4.11 (2H, m), 4.66 (1H, quint, J = 5.9Hz), 5.14 (2H, s ), 6.59 (1H, d, J = 2.2Hz) ,. 6.73 (1H, m), 6.79 (1H, m), .84 (1H, m), 7.28-7. 38 (6H, m), 8.33 (1H, d, J = 9.5Hz), 8. 60 (1H, s). # (150c) 7-benzyloxy-1- (3-ethoxy-5-isopropoxyphenyl) -4 -Oxygen-1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl) -amidamine The 7 -benzyloxy-1-obtained in Example (1 5 0 b) (3-Ethoxy-5-isopropyloxyphenyl) 4-oxo-1,4-dihydroquinoline-3-carboxylic acid 1.0 g. Isobutyl chloroformate 0.31 ml, triethylamine 0.1. 59 ml and 409 mg of 3,5-difluoroaniline were reacted according to the method of Example (5 4 c) to obtain 1.09 g of the title compound as a white solid. -391- 200300349 (CDCl3) (5 ppm: 1.38 (6Η, t, J = 5.9Hz), 1.44 (3Η, t, J = 7.3Hz), 3.95-4. 06 (2H, m), 4.50-4.59 (1H, m), 5. 00-5 .07 (2H, m), 6.43 (1H, t, J = 2.2Hz), 6.47 (1H, t, J = 2.2Hz), 6. 51-6. 56 (1H, m), 6. 61-6 65 (2H, m), 7.14-7.17 (1H, m), 7.29-7.41 (7H, m), 8.45 (1H, d, J = 8.8Hz), 8.78 (1H, s). (150d) 7- Benzyloxy-1- (3-ethoxy-5-isopropyl Oxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine obtained in Example (1 5 0 c) 7-benzyloxy-1-(3 -ethoxy-5 -isopropoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5 -di Fluorophenyl) -amidamine 690mg '77% 55% sodium hydride and 0.37ml of iodoethane. The reaction was carried out according to the method of Example (54d) to obtain 639mg of the title compound as a white solid. NMR (CDC13) (5ppm: 1.20 (3H, t, J = 7.3Hz), 1.36 (6H, t, J = 5.1Hz), 1.44 (3H, t, J-6.6Hz), 3. 89-4. 02 (4H, m), 4.47 -4. 56 (1H, m), 4. 94-5. 00 (2H, m), 6. 34-6. 35 (1H, m), 6. 38 ~ 6. 39 (1H, m), 6.48 (1H, d, J = 2.2Hz), 6. 57-6.65 (2H, in), 6.83 (2H, dd, J = 2.2, 8.1Hz), 6. 96-6. 99 (1H, m), 7 26-7. 36 (5H, m), 7.84 (1H, s), 8.2K1H, d, J = 8.8Hz). (150e) Bu (3-ethoxy-5-isopropoxyphenyl)- 7-Hydroxy-4-oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The obtained product from Example (1 50 0 d) 7-benzyloxy-1-(3 -ethoxy-5 -isopropoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluoro Phenyl) -N-acetamide 610mg and 10% Pd-C150mg 'were reacted according to the method of Example (11 h) to obtain the title compound as a white solid 5 2 0 mg oli R (CDC13) (5ppm: 1.18 (3H, t, J = 7.3 Hz), 1.34 (6H? D, J = 4.4Hz), 1.4K3H, t, J = 6.6Hz), 3.90 (2H, q, J = 7.3Hz), 3.98 (2H, q, J = 6.6Hz), 4.45-4.54 (1H, m), 6, 38-6.39 (2H, m), 6.49 (1H, d, J = 2.2Hz), 6.54 (1H, t, 200300349 J = 2.2Hz), 6. 60-6.64 (1H, m), 6. 80-6. 83 (2H, m), 6.90 (1H, dd, J = 2.2, 9.5Hz), 7.8K1H, s), 8.03 (1H, d, J = 8.8Hz) (150f) 7- (7-bromoheptyloxy) -1- (3-ethoxy-5-isopropoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidinium 1- (3-ethoxy-5-isopropyloxyphenyl) -7-hydroxyl obtained in Example (150 0e) -4 -Oxygen-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamide 510mg, 1,7-dibromoheptane 0.50ml and carbonic acid Potassium 270 mg was reacted and purified according to the method of Example (1 1 i) to obtain the title compound as a colorless foam of 60 mg. NMR (CDC13) δρρπι: 1.20 (3H, t, J = 7.3Hz), 1.29-1.48 (15H, m), 1.69-1.76 (2H, .m), 1.81-1.88 (2H, m), 3.39 (2H, t, J = 6.6Hz), 3.86 (2H, t, 1 = 5.9Hz), 3.93 (2H, q, J = 6.6Hz), 4.02 (2H, q, J = 8.1Hz), 4.50-4.56 (1H, m), 6.41-6.43 (3H, m), 6.57-6. 65 (2H, m), 6.83 (2H, dd, J = 2.2, 8.1Hz), 6.90 (1H, dd, J = 2.2, 8.8Hz) , 7.84 (1H, s), 8.20 (1H, d, J = 8.8Hz). (150g) bromide l- {7- [3- [N- (3,5-difluorophenyl) -N-ethyl Carboxymethyl] -1- (3-ethoxy-5-isopropoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] heptylb 4-az- Pyrazinebicyclo [2 · 2 · 2] octane will be 7- (7-bromoheptyloxy) -1- (3-ethoxy-5 -isopropyloxyphenyl)- 200 mg of 4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine and 1,4-diazine-bicyclo [2 · 2 · 2] 67 mg of octane, and reacted according to the method of Example (1 1 j) to obtain 207 mg of the title compound as a white solid. 200300349 R (CDC13) δρρπι: 1.20 (3Η, t, J = 7.3Hz), 1. 34-1.45 (15Η, m), 1.65-1.80 (4H, in), 3.24 (6H, t, J-7.3Hz), 3. 52-3. 56 (2H, m), 3. 63-3 .67 (6H, m) , 3. 83-3. 86 (2H, m), 3.9K2H, q, J = 6.6Hz), 4. 03 (2H, q, J = 8.1 Hz), 4. 49-4.58 (1H, m) , 6.40-6.41 (3H, m), 6,58 (1H, t, J = 2.2Hz), 6. 60-6. 66 (1H, m), 6.82 (2H, dd,

J = 2. 2, 8. 1Hz), 6. 9K1H, dd, J = 2. 2, 9. 5Hz), 7. 79 (1H, s), 8. 19 (1H, d, J = 8. 8Hz).  Melting point: 1 3 8 ~ 1 4 1 ° C Example 1 5 1 • Brominated 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl-ethyl Oxy-5-isopropoxyphenyl) 4-oxy-1,4-dihydroquinoline-7-yloxy] heptyl}-1-methylpiperidine (exemplified compound number · 2-7 8 9 ) The 7- (7-bromoheptyloxy) -1-(3-ethoxy-5-isopropoxyphenyl) -4-oxy-1,4-diamine obtained in Example (1 50 f) Hydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) acetamide 200 mg and dimepiridine 0. 18 ml. The reaction was carried out according to the method of Example (1 1 j) to obtain 186 mg of the title compound as a yellow solid. NMR7 ~ 々hJl / (CDCl3) 5ppm: 1.20 (3Η, t, J = 7 3Hz), 1.34-1 · 45 (15Η, m), 1. 67-1.  91 (10H, m), 3. 32 (3H.  s), 3.  63-3.  77 (6H, m), 3.  84-3.  87 (2H, m), 3. 92 (2H, q, J = 7. 3Hz), 4. 03 (2H, q, J = 6. 6Hz), 4. 49-4. 58 (1H, m), 6.  40-6.  41 (3H, m), 6. 58 (1H, t, 1 = 2. 2Hz), 6. 60-6.  . 65 (1H, m), 6. 83 (2H, dd, J = 2. 2, 8. 1Hz), 6. 89 (1H, dd, J = 2. 2, 8. 8Hz), 7. 83 (1H, s), 8. 20 (1H, d, J = 8. 8Hz).  Melting point: 1 4 5 ~ 1 4 7 t: Example 1 5 2 Bromide 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylamidino-dimethyl] Amine-5-methoxyphenyl) -4-oxo-I, 4-dihydroquinoline-7-yloxy] heptylbuprofen (exemplified compound number: 2-8 1 7)-394- 200300349 (152a) 7- (7-bromoheptyloxy) -1- (3-dimethylamino-5-methoxyphenyl) -4-oxo-1, 4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidinium 1- (3-amino-5-methoxyphenyl) -7-methoxymethoxy obtained in Example (148a) -4 -oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 160mg, iodoformin O. 1 ml of anhydrous N, N-dimethylformamide 4ml solution of potassium carbonate and 86 mg of potassium carbonate were stirred at room temperature for 24 hours. Dilute with ethyl acetate, rinse with citric acid aqueous solution, water, saturated sodium bicarbonate water, sodium thiosulfate aqueous solution, and saturated brine in that order, dry over anhydrous magnesium sulfate, and concentrate the solvent under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/2 to 1/3) to obtain 28 mg of a yellow oil. The obtained oily substance was reacted according to the method of Example (102d) to obtain 1- (3- ^ methylamino-5 -methoxyphenyl) -7-quinyl-4-oxo-1,4-di Hydroquinoline-3 -carboxylic acid N-(3, 5 -difluorophenyl) -N -acetamidine 20 mg as a pale yellow foam. The resulting foam was treated with 1,7-dibromoheptane 0.1. 0 2 m 1 and 10 mg of potassium carbonate were reacted and purified according to the method of Example (1 1 i) to obtain 14 mg of the title compound as a colorless foam. Li R (CDC1S) 5ppm: 1. 2K3H, t, J = 7. 1Hz), 1. 33-1. 48 (6H, m), 1. 70-1.  74 (2H, m), 1.  81-1. 88 (2H, m), 3. 00 (6H, s), 3.  39 (2H, t, J = 6. 8Hz), 3. 82-3. 94 (7H, m), 6.  24-6. 27 (2H, m), 6.  42-6.  44 (2H, m), 6. 55-6.  65 (1H, m), 6. 84-7. 00 (3H, m), 7. 85 (1H, s), 8. 21 (1H, d, J = 9. 0Hz).  (1 5 2 b) Bromide 1-丨 7-[3-[N-(3, 5 -difluorophenyl) -N -ethylaminomethylmethyl] -1- (3-dimethylamino-5 -Methoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] heptyl} -1-methyl-piperidine The 7- (7- Bromoheptyloxy) -1- (3-dimethylamine 200300349yl-5-methoxyphenyl) 4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 5-di Fluorophenyl) -acetamide 13mg and 1-methylpiperidine 0. 012 ml was reacted according to the method of Example (1 lj) to obtain 9 mg of the title compound as a pale yellow foam. Circle R.  .  (CDC13) 5ppm: 1. 2K3H, t, J = 7. 3Hz), 1. 42 (6H, br), 1.  72-1.  95 (10H, m), 2. 99 (6H, s), 3. 3K3H, s), 3.  63-3.  77 (6H, m), 3.  80-3.  87 (5H, m), 3.  90-3. 95 (2H, m), 6. 18-6.  20 (2H, m), 6. 33 (1H, t, 1 = 2. 2Hz), 6. 45 (1H, d, J = 2. 2Hz), 6. 60-6. 64 (lH, m), 6. 83-6. 90 (3H, m), 7. 84 (1H, s), 8. 20 (1H, d, J = 8. 8Hz).  I R (KBr) cm-l: 3418, 2938, 2862, 1615, 1458, 1272, 1241.  Example 1 5 3 1- {7- [1- (3,5-diethoxyphenyl) -3- | ^-(3,5-difluorophenyl) -N-isopropylaminemethane ] -4 -oxy-1,4-dihydroquinoline-7-yloxy] heptyl} -1-methyl-piperidine (Exemplary compound number: 2-7 5 9) (153a) 7-benzyloxy -1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -1 isopropylhydrazone The 7-benzyloxy-1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3 , 5-difluorophenyl) -ammonium amine 50 001 ^, 55% sodium hydride 5711 ^ and 2-iodopropane 0. 351111, the reaction was carried out according to the method of Example (5 4 d), and the white solid of the title compound was obtained as 1.06 m g ° R (CDCl3) (5ppm: 1.20 (6Η, d, J = 6. 6Hz), 1. 43 (6H, t, J = 7. 3Hz), 3.  94-4.  02 (4H, m), 4.  90-5.  05 (3H, m), 6. 3K2H, s), 6. 40 (1H, d, J = 1. 5Hz), 6. 58 (1H, t, J = 2. 2Hz), 6. 69 (1H, t, J = 8. 8Hz), 6. 80-6. 83 (2H, m), 6. 97 (1H, dd, J = 2. 2, 9. 5Hz), 7. 26 ~ 7. 36 (5H, m), 7. 59 (1H, s), 8. 24 (1H, d, J-8. 8Hz).  (153b) 1- (3,5-diethoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquine 200 300 349 Porphyrin-3-carboxylic acid N- (3,5-difluorophenyl ) -N-isopropylamidine The 7-benzyloxy-1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 obtained in Example (153a) -Carboxylic acid N- (3,5-difluorophenyl) -N-isopropylamidine 100 mg and 10% Pd-C 20 mg, the reaction was carried out according to the method of Example (llh), and the title compound was obtained in white color. 7 5 mg of solid.臓 (CDCl3-DMS0-d6) (5ppm: 1. 20 (6H, d, J = 6. 6Hz), 1. 42 (6H, t, J = 7. 3Hz), 4. 0K4H, q, J = 7. 3Hz), 4. 95 (1H, br), 6. 37 (2H, s), 6. 41 (1H, d, J = 1. 5Hz), 6. 55 (1H, t, J = 2. 2Hz), 6. 70 (1H, t, J = 8. 8Hz), 6. 82 (2H, dd, J = 2. 2, 8. 1Hz), 6.  86-6.  88 (1H, m), 7. 57 (1H, s), 8. 14 (1H, d, J = 9. 5Hz).  (153〇) 7- (7-bromoheptyloxy) -1- (3,5-diethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- ( 3,5-difluorophenyl) -N-isopropylamidine 1- (3,5-diethoxyphenyl) -7-hydroxy-4-oxy-1 obtained in Example (1 5 3 b) , 4-Dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -isopropylamidine 70mg, 1,7-dibromoheptene 0. 068 ml and 37 mg of potassium carbonate were reacted and purified according to the method of Example (1 1 i) to obtain 75 mg of the title compound as a colorless foam. Lu Bandit R (CDC13) (5ppm: 1. 20 (6H, d, J = 7. 3Hz), 1.  31-1. 48 (12H, m), 1. 68-1. 75 (2H.  m), 1. 81-1. 88 (2H, m), 3. 39 (2H, t, J = 6. 6Hz), 3. 85 (2H, t, J = 5. 9Hz), 4. 02 (4H, q, J = 8. 1Hz), 4.  90-5.  05 (1H, br), 6.  35-6.  37 (3Hy m), 6. 58 (1H, t5 J = 2. 2Hz), 6. 69 (1H, t, 1-8.  8Hz), 6. 82 (2H, dd, J = 2.  2, 8. 1Hz), 6.  88-6.  91 (1H, m), 7. 6K1H, s), 8. 24 (1H, d, J = 8. 8Hz).  , (153d) bromide l- {7- [l- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-isopropylaminemethane] -4 -oxo-1,4-dihydroquinoline-7-yloxy] heptylbuprofenide-397-200300349 The 7-(7 -bromoheptyloxy) obtained in Example (1 5 3 c) ) -1-(3,5-diethoxyphenyl) -4 -oxo-I, 4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-iso Promethazine 75mg and 1-Mepidolidine 0.1. 06 ml, the reaction was carried out according to the method of Example (1 1 j), and the title compound was obtained as a pale yellow solid, 71 mg oli R.  (DMS0-d6) δ ppm: 1. 11 (6H, d, J = 6. 6Hz), 1.  27-1.  37 (12H, m), 1. 46-1.  59 (2H, m), 1.  61-1.  67 (4H, m), 1. 76 (4H, br), 2. 96 (3H, s), 3.  24-3.  29 (6H, m), 3. 88 (2H, t, J = 5. 9Hz), 4. 06 (4H, q, 1 = 6. 6Hz), 4. 79 (1H, br), 6. 30 (1H, d, 1 = 2. 2Hz), 6. 48C2H, br), 6. 69 (1H, t, J = 2. 2Hz), 6. 98 (1H, dd, J = 2. 2, 9. 5Hz), 7. 03 (2H, d, J = 6. 6Hz), 7. 15-7.  20 (1H, m), 8.  00-8.  03 (2H, m).  Melting point: 1 3 1 ~ 1 3 4 ° C Example 1 5 4 Brominated l- {7- [l- (3-cyano-5-methoxyphenyl) -3- [N- (3,5- Difluorophenyl) -N-ethylaminomethylmethyl] -4 -oxyl, 4-dihydroquinoline-7-yloxy] heptyl}-1 -Milestone table (Example compound number: 2- 8 1 8) (154a) l- (3-cyano-5-methoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid methyl ester 89 mg of 3-dimethylamino-2- (2-methoxy-4-methoxymethoxybenzyl) -methyl acrylate obtained in Example (104d), -34 mg of cyano-5-methoxyaniline and 95 mg of potassium carbonate were reacted according to the method of Example (1 1 e) to obtain 60 mg of the title compound as a yellow solid. NMR (CDC13) (5 ppm: 3. 43 (3H, s), 3. 929 (3H, s), 3. 933 (3H, s), 5. 15 (2H, s), 6. 50 (1H, d, J = 2. 2Hz), 7. 15-7. 38 (4H, m), 8. 42 (1H, t, J-2. 2Hz), 8. 48 (1H, d, J-9. 0Hz).  -398-200300349 (154b) l- (3-cyano-5-methoxyphenyl) -7-methoxymethoxy-1-4-oxy-1,4-dihydroquinoline-3 -carboxylic acid The 1- (3-cyano-5-methoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3- obtained in Example (1 5 4a) 57 mg of methyl carboxylate and 1N of 1N-sodium hydroxide solution were reacted according to the method of Example (1e) to obtain 37 mg of the title compound as a yellow solid. Bandit R (CDC13) (5ppm: 3. 45 (3H, s), 3. 95 (3H, s), 5. 184 and 5. 187 (total 2H, eachs), 6. 63 (1H, d, J = 2. 2Hz), 7. 11-7.  34 (3H, m), 7.  41-7.  43 (1H, m), 8.  50 (1H, d, J = 9. 0Hz), 8. 68 (1H, s).  (154c) l- (3-cyano-5methoxyphenyl) -7-methoxymethoxy-4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N-(3,5- Difluorophenyl) -fluorenamine will be the 1- (3-cyano-5-methoxyphenyl) -7-methoxymethoxy_bu 4_oxy-1 obtained in Example (1 5 4 b), 4-Dihydroquinoline-3-carboxylic acid 35mg, isobutyl chloroformate 0. 015ml, triethylamine 0. 026 ml and 18 mg of 3,5-difluoroaniline were reacted according to the method of Example (5 4 c) to obtain 39 mg of the title compound as a pale yellow solid. surface.  (CDCI ^ ppib: 3. 45 (3H, s), 3. 95 (3H, s), 5. 18 (2H, s), 6. 53-6. 59 (1H, m), 6. 6K1H, d, J-2. 2Hz), 7. 22-7. 41 (6H, m), 8. 50 (1 ^ d, J-8. 8Hz), 8. 75 (1H, s).  (154d) 1- (3-cyano-5-methoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N-(3, 5-difluorobenzene Group) -N-acetamidinium 1- (3-cyano-5-methoxyphenyl) -7-methoxymethoxy-4-oxo-1,4 obtained in Example (1 5 4 c) -Dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -amidamine 36 mg, 55% sodium hydride 5 mg and iodoethane 0 · 0 2 3 m 1, according to implementation The reaction of Example (5 4 d) can be carried out to obtain a pale yellow solid. The obtained solid was dissolved in 4 N -H C 1 / ethyl acetate solution 2 m 1 and stirred at room temperature for 1 hour. The reaction was diluted with ether and the solids were collected by filtration. 18 mg of the title compound was obtained as a brown solid. Circle R (CDC13) (5 ppm: 1. 26 (3H, t, J = 7.  3Hz), 3.  80-4.  00 (5H, m), 6. 3K1H, s), 6. 67-7. 18 (7H, m), 7. 73 (1H, s), 8. 0K1H, d, J = 6. 0Hz).  (154e) 7- (7-Bromoheptyloxy) -1- (3-cyano-5-methoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- ( 3,5-difluorophenyl) -N-acetamidinium 1- (3-cyano-5-methoxyphenyl) -7-hydroxy-4-oxo obtained in Example (1 54 d) 1,4-dihydroquinol-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 17mg, 1,7-dibromoheptane 0. 018 ml and 10 mg of potassium carbonate were reacted and purified according to the method of Example (1 1 i) to obtain the title compound as a pale yellow oil 9. 4 m g. NMR (CDC13) (5ppm: 1.21 (3Η, t, J = 7. 2Hz), 1.35- 1.48 (6Η, m), 1. 71-1.  76 (2Η, m), 1.  81-1.  88 (2H, m), 3. 40 (2H, t, J = 6. 8Hz), 3.  87-3.  94 (7H, id), 6. 22 (1H, d, J = 2. 2Hz), 6.  62-6. 66 (1H, m), 6. 83 (2H, dd, J = 2. 4, 8. 1Hz), 6. 93 (1H, dd, J = 2. 0, 9. 0Hz), 7. 13-7. 36 (3H, m), 7. 80 (1H, s), 8. 2K1H, d, J = 9. 2Hz).  (154f) L- {7- [l- (3-cyano-5-methoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine [] Yl] -4 -oxyl, 4-dihydroquinoline-7 -yloxy] heptylbuproxil tablets 7-(7 -bromoheptyloxy) obtained in Example (1 5 4 e)- 1-(3-cyano-5 -methoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 5-difluorophenyl) -N-acetamidine Amine 8.9 mg and 1-methylpiperidine D. 0. 02ml. The reaction was carried out according to the method of Example (1 1 j). The brown powder of the title compound was obtained. 5 · 5 mg 〇 -400- 200300349 NMR (CDC1S) δρρπι: 1. 20 (3H, t, J = 7.  1Hz), 1. 42 (6H, br), 1.  73-1.  89 (10H, m), 3. 27 (3H, s), 3.  63-3.  71 (6H, m), 3.  87-3.  96 (7H, m), 6. 22 (1H, d, J = 2. 0Hz), 6.  62-6.  67 (1H, m), 6. 83 (2H, dd, J = 2. 2, 8. 1Hz), 6.  91 ~ 6.  94 (1H, m), 7.  14-7. 38 (3H, in), 7. . 80 (1H, s), 8. 20 (1H, d, 1 = 8. 8Hz).  Melting point: ~ 8 0 ° C Example 1 5 5 Desertification of l- (2- {4- [3- [N- (3,5-mono > chlorophenyl) -N-ethylenol) -1- (3, 5 -dimethoxyphenyl) -4 -oxo-1,4 -dihydroquinoline-7 -yloxymethyl] -phenylbuethyl) -4-acyl_buzozo [ 2. 2. 2] Octane (Exemplified compound number: 2-8 6 1) (155a) l- (3,5-dimethoxyphenyl) -7- [4- (2-transethyl) -fluorenyl]- 4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 1- (3, obtained from Example (1 1 h) 5-Dimethoxyphenyl) -7-hydroxy-4-oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 150mg, 81 mg of 2- (4-bromomethyl-benzyl) -ethanol, 86 mg of potassium carbonate, and 10 ml of N, N-dimethylformamide were obtained in Reference Example 16. The reaction was carried out according to the method of Example (1 Π). 1. The title compound was obtained as 174 mg of white foamy substance. (CDCl3) 5ppm: 1. 20 (3H, t, J = 7.  1Hz), 2. 87 (2H, t, J = 6. 5Hz), 3. 82 (6H, s), 3. 85 (2H, t, J = 6. 6Hz), 3. 92 (2H, q, J = 7. 0Hz), 4. 94 (2H, s), 6. 42 (2H, d, J-2. 3Hz), 6. 45 (1H, d, J-2. 3Hz), 6. 59-6. 66 (2H, m), 6. 83 (2H, dd, 1 = 2. 2, 8. 1Hz), 6. 98 (1H, dd, J = 2. 3, 9. 0Hz), 7. 19-7. 27 (4H, in), 7. 84 (1H, s), 8. 2K1H, d, J = 9. 5Hz).  (155b) 7- [4- (2-Bromoethyl) -benzyloxy] -1- (3,5-dimethoxybenzene 200 300 349) 4-oxy-1,4-dihydroquinoline-3 -Carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 1- (3,5-dimethoxyphenyl) -7- [4- ( 2-hydroxyethyl) -benzyloxyb 4-oxo-1,4-dihydroquinoline · 3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 170 mg of dichloro 20 ml of a methane solution was added dropwise at 90 ° C to a solution of 90 mg of phosphorus tribromide in dichloromethane 3 ml 1, stirred at the same temperature for 10 minutes, and then stirred at room temperature for 1 hour. After the reaction solution was cooled at -20 ° C, water was added dropwise to dilute it. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and then the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 1: 3) to obtain 34 mg of the title compound as a white solid. Li R (CDC13) δρριη: 1. 20 (3H, t, J = 7. 3Hz), 3. 16 (2H, t, J = 7. 3Hz), 3. 55 (2H, t, J = 7. 3Hz), 3. 82 (6H, s), 3. 92 (2H, q, J = 7. 3Hz), 4. 95 (2H, s), 6. 42 (2H, d, J = 2. 2Hz), 6,45 (1H, d, J = 2. 2Hz), 6. 60-6.  66 (2H, m), 6.  84 (2H, dd, 1 = 2. 2, 8. 1Hz), 6. 98 (1H, dd, J = 2.  2, 8. 8Hz), 7. 19 (2H, d, J = 8. 1Hz), 7. 25 (2H, d, J-8. 8Hz), 7. 84 (1H, s), 8. 2K1H, d, J = 9. 5Hz).  (155c) 1- (2- {4- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl 1.1- (3,5-dimethoxybenzene) bromide Yl) -4 -oxo-1,4 -dihydroquinoline-7 -yloxymethyl] -phenylbutyl) -4 -acryl-1-azobicyclo [2. 2. 2] Octane 7- [4-(2 -bromoethyl) -benzyloxy]-1- (3,5-dimethoxyphenyl) -4 -oxo obtained in Example (1 5 5 b) -1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 16. 5mg, 1,4-diazine-bicyclo [2 · 2. 2] Octane 8. 2 mg and acetonitrile 3 m 1 were reacted according to the method of Example (1 1 j) to obtain the title compound as a white solid 8. 5 mg. -402- 200300349 NMR (CDC13) (5ppm: 1. 19 (3H, t, J = 7. 3Hz), 3.  09-3. 14 (2H, m), 3. 12 (6H, t, J = 7. 3Hz), 3. 69 (6H, t, J = 7.  3Hz), 3.  78-3.  85 (8H, m), 3. 90 (2H, q J = 7. 3Hz), 4. 9K2H, s), 6.  38 (2H, d, J = 2. 2Hz), 6,45 (1H, d, J = 2. 2Hz), 6. 61-6. 67 (2H, m), 6. 82 (2H, dd, J = 2. 2, 7. 3Hz), 6. 91 (1H, dd, J = 2. 2, 8. 8Hz), 7.  22 (2H, d, J = 8.  1Hz), 7. 33 (2H, d, J = 8. 1Hz), 7. 76 (1H, s), 8. 13 (1H, d, J = 8. 8Hz).  Melting point: 1 7 2-1 7 6 ° C Example 1 5 6 3- {3- [3-[^ [-(3,5-difluorophenyl) 1-ethylaminomethylmethyl] -1- ( 3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] -propylaminemethylamidino}-1-methylpyridine mesylate (example compound number: 2-8 5 8) (156a) l- (3,5-dimethoxyphenyl) -7- [3- (1,3-dioxo-1,3-dihydroisoindole-2 -yl) -Propoxy] -4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine obtained in Example (1 1 h) 1- (3,5-dimethoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3-residue N- (3,5-difluorophenyl) -N -450 mg of acetamidine, 300 mg of N- (3-bromopropyl) phthalimide, 259 mg of potassium carbonate, and 10 m 1 of N, N-dimethylformamide, according to the method of Example (1 1 i) The reaction was performed to obtain 615 mg of a white foamy substance of the title compound. NMR '(CDCI3) δρριη: 1. 20 (3H, t, J = 7. 3Hz), 2. 13 (2H, it, J = 5. 9, 6.  6Hz), 3. 78-3.  87 (8H, m), 3.  89-3.  95 (4H, m), 6. 35 (1H, d, J = 2. 9Hz), 6,46 (2H, d, J-2. 2Hz), 6. 60-6. 67 (2H, m), 6. 74 (1H, dd, J = 2. 2, 8. 8Hz), 6. 84 (2H, dd, J = 2. 2, 8. 1Hz), 7. 70-7. 74 (2H, m), 7. 78-7. 83 (2H, m), 7. 84 (1H, s), 8. 15 (1H, d, J = 8. 8Hz).  7- (3-Aminopropoxy) -1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3 , 5 -difluorophenyl) · N-acetamidamine-403-200300349 The 1-(3,5-dimethoxyphenyl) -7-[3-(1 , 3-dioxo-1,3-dihydroisoindole-2 -yl) -propoxy] -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5- Difluorophenyl) -N-acetamidine 6 1 5 mg in ethanol solution 30 m Bu added hydrazine 1 hydrate 0. 5 m 1, heated to reflux for 1 hour. After cooling, the insoluble matter was filtered off, and the filtrate was diluted with ethyl acetate. The organic layer was washed with a 1 M sodium hydroxide solution and a saturated saline solution, dried over anhydrous magnesium sulfate, and then the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / ethanol = 10/1) to obtain 360 mg of the title compound as a colorless oily substance. Rei R-(CDC13) δρρπι: 1. 2Κ3Η, t, J = 7. 1Hz), 2.  01-2. 13 (2H, m), 3. 76-3. 87 (8H, m), 3. 88HL13 (4H, ffl), 6. 35 (lH, d, J = 2. 0Hz), 6,46 (2H, bs), 6. 60-6. 67 (2H, in), 6. 83 (2H, dd, J = 2. 1, 8. 0Hz), 6. 9K1H, dd, J = 2. 3, 9. 0Hz), 7. 84 (1H, s), 8. 20 (1H, d, J = 8. 8Hz).  (156c) l- (3,5-dimethoxyphenyl) -4 -oxo-7- {3-[(pyridine-3 · mineral) -amino] • propoxyl-1,4- ^ Gas -3 -residual acid N- (3,5-monofluorophenyl) -N-acetamidine Nicotinic acid 76 mg in dichloromethane solution 5 ml 1, add 3 at 0 ° C Ethylamine 0 · 17 m 1 and isobutyl chloroformate were stirred at the same temperature for 15 minutes. This solution was added dropwise to the 7- (3-aminopropoxy) -1-(3,5-dimethoxyphenyl) -4-oxy-1,4-dihydro obtained in Example (1 5 6 b). A solution of quinoline-3-carboxylic acid N- (3,5-difluorophenyl) -1 acetamide 221011 in methylene chloride 51111 was stirred at room temperature for 1 hour. It was diluted with dichloromethane, washed with a 1M sodium hydroxide solution and saturated saline, dried over anhydrous magnesium sulfate, and then the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / ethanol = 5/1) to obtain the title compound as a white foamy substance 96 mg -404- 200300349 NMR (CDC13) (5 ppm: 1. 2K3H, t, J = 7. 3Hz), 2.  05-2. 15 (2H, m), 3. 64 (2H, q, J = 6. 6Hz), 3. 83C6H, s), 3. 93 (2H? Q, J = 7. 3Hz), 4. 00 (2H, t, J = 5. 9Hz), 6. 40 (1H, d, J = 2. 2Hz), 6,47 (2H, d, J = 2. 2Hz), 6. 58 ~ 6. 64 (2H, m), 6. 84 (2H, dd, J = 2. 2, 8. 1Hz), 6. 89 (1H, dd, J = 2. 2, 8. 8Hz) f 7. 38 (1H, dd, J = 5. 1, 8. 1Hz), 7. 84 (1H, s), 8. 04-8. 09 (lH, m), 8. 2K1H, d, 1 = 9 5Hz), 8. 70-8. 75 (1H, m), 8. 94 (1H, s).  (156d) 3- {3- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3,5-dimethoxyphenyl) -4- 1- (3,5-dimethoxybenzene) obtained in Example (156c) ) -4-oxo-7-{3-[(pyridine-3 -carbonyl) -aminopropylpropoxyb 1,4-dihydroteroline-3-carboxylic acid N- (3,5-difluoro 41 mg of phenyl) -N-acetamidamine, 28 mg of methyl methanesulfonate and 5 ml of acetonitrile were reacted according to the method of Example (3b) to obtain the title compound as a white foamy substance 2 9 mg ° NMR (CDCI3) (5ppm: 1. 20 (3H, t, J = 7. 3Hz), 2. 13 (2H, t, J = 5. 9Hz), 2. 67 (3H, s), 3. 6K2H, t, J = 5. 9Hz), 3. 84 (6H, s), 3. 92 (2H, q, J = 7.  3Hz), 4. 04 (2H, t, J = 5. 9Hz), 4. 64 (3H, s), 6. 42 (1H, d, J = 2. 2Hz), 6,46 (2H, d, J = 2. 2Hz), 6. 60-6. 68 (2H, m), 6. 83 (2H, dd, J = 2. 2, 8. 1Hz), 6. 95 (1H, dd, J = 2. 2, 8. 8Hz), 7. 80 (1H, s), 8. 0K1H, dd, 1 = 1. 5, 6. 6Hz), 8. 17 (1H, d, J = 8. 8Hz), 8. 71 (1H, d, J = 5. 9Hz), 8. 95 (1H, d, J = 8. 1Hz), 9. 77 (1H, s).  Melting point: Π.  9 ° C Example 1 5 7 4- {3- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylamidino] -1 · (3, 5-dimethoxybenzene Radical) -4 -oxo-1,4-dihydroquinoline-7 -yloxybupramide formamidine and albippyridine mesylate (exemplified compound number: 2-8 5 7) -405-200300349 (157a) l- (3,5-dimethoxyphenyl) -4-oxo-7- {3-[(pyridine-4-carbonyl) -aminol · propoxy) -1,4-dihydro Quinoline-3 -carboxylic acid N- (3,5--* chlorophenyl) -N-acetic acid amine 7- (3-aminopropoxy) -1-( 144 mg of 3,5-dimethoxyphenyl) -4-oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine and triethyl Amine 0. 1 ml of a dichloromethane solution 10 ml 1 was added with isonicotinic acid chloride hydrochloride 7 2 m, and stirred at room temperature for 2 hours. It was diluted with dichloromethane, washed with a 1M sodium hydroxide solution and saturated saline, dried over anhydrous magnesium sulfate, and then the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / ethanol = 5/1) to obtain the title compound as a white foamy substance (131 mg). _ (CDC13) δρριη: 1. 2Κ3Η, t, J = 7. 3Hz), 2. 10 (2H, t, J = 5. 9Hz), 3. 68 (2H, q, J = 6. 6Hz), 3. 83 (6H, s), 3. 93 (2H, q, J = 7. 3Hz), 4.  01 (2H, t, J = 5.  9Hz), 6. 40 (1H, d, J = 2. 2Hz), 6,46 (2H, d, J = 2. 2Hz), 6. 58-6. 67 (2H, m), 6. 84 (2H; dd, J = 2. 2, 8. 1Hz), 6. 89 (1H, dd, J = 2.  2, 8. 8Hz), 7. 55 (2H, dd, J = 1. 5, 4. 4Hz), 7. 85 (1H, s), 8. 23 (1H, d, J = 8. 8Hz), 8. 72 (2H, dd, J = 1. 5, 4. 4Hz).  (157b) 4- {3- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3,5-dimethoxyphenyl) -4_ Oxy-1,4-dihydroquinoline-7-yloxy] -propylaminemethylamidinyl}-1 -methylpyridine mesylate sulfonylamine 1-(3,5 -Dimethoxyphenyl) -4 -oxo-7-{3-[(pyridine-4 -carbonyl) -aminopropylpropoxy}-1,4-dihydroquinoline-3 -carboxylic acid N- ( 90 mg of 3,5-difluorophenyl) -N-acetamidamine, 62 mg of methyl methanesulfonate and 8 ml of acetonitrile were reacted according to the method of Example (3b) to obtain the title compound as a white foam Substance 5 2 mg. -406- 200300349 NMR (CDC13) (5ppm: 1. 20 (3H, t, J = 7. 3Hz), 2.  05-2.  15 (2H, in), 2. 63 (3H, s), 3. 56 (2H, t, J = 5. 9Hz), 3. 83 (6H, s), 3. 9K2H, q, J = 7. 3Hz), 4. 02 (2H, t, J = 5. 9Hz), 4. 50 (3H, s), 6. 38 (1H, d, J = 1. 5Hz), 6,45 (2H, d, J = 2. 2Hz), 6. 58-6. 68 (2H, m), 6. 82 (2H, dd, J = 2. 2, 8. 1Hz), 6. 94 (1H, dd, J = 2. 2, 8. 8Hz), 7. 74 (1H, s), 8. 06 (1H, d, J = 8. 8Hz), 8. 5K2H, d5 J = 6. 6Hz), 8. 92 (2H, d, J = 6. 6Hz).  Melting point: 1 0 9 ° C Example 1 5 8 l- [2- (4- {2- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethyl]] -(3, 5 -dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7 -yloxybethylphenylphenyl) -ethyl] -4 -acyl-1 -azobicyclo [2. 2. 2] Octane bromide (example compound number 2-8 6 4) (158a) 7- {2- [4- (2-bromoethyl) -phenylbutethoxy}-1- (3, 5-Dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine Example (1 1 h) the resulting 1 · (3,5-dimethoxyphenyl) -7-hydroxy-4-oxy-1,4-dihydroquinoline-3-carboxylic acid N (3,5-difluorophenyl) 400 mg of N-acetamidine, 486 mg of 1,4-bis- (2-bromoethyl) -benzene obtained in Reference Example 17, 51 mg of sodium hydride and 8 ml of N, N-dimethylformamide, according to the example ( 1 h), the title compound and 1- (3,5-dimethoxyphenyl) -4-oxo-7 · [2- (4-ethoxyphenyl) ethoxy] '- 1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine, a white foamy substance of about 3: 1 mixture, 106 mg. Surface R (CDC13) δρριικ 1.20 (3Η, t, J: 7. 3Hz), 3.01 (2H, t, J = 7.3 Hz), 3. ^ 14 (2H, t, J = 7.  3Hz), 3. 55 (2H, t, J = 7. 3Hz), 3. 83 (6H, s), 3. 93 (2H, q, J = 7.  3Hz), -407-200300349 4. 07 (2H, t, J = 7. 3Hz), 6. 40 (1H, d, J = 1. 5Hz), 6,47 (2H, d, J = 2. 2Hz), 6. 59-6. 66 (2H, in), 6. 84 (2H, dd, J-2. 2, 8. 1Hz), 6. 9K1H, dd, J = 2. 2, 8. 8Hz), 7. 12-7. 18C3H, m), 7. 34 (1H, d, J = 8. 8Hz), 7. 84 (1H, s), 8. 20 (1H, d, J = 8. 8Hz).  (158b) bromide 1- [2- (4- {2- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3, 5 -di Methoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7 -yloxy] -ethyl} -phenyl) -ethyl] _4_ 卩 丫 -1- 偶 气 双 ί 哀2 · 2 · 2] octane 7-{2-[4-(2 -bromoethyl) -phenylbethoxyb 1-(3, 5 -di Methoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine and 1- (3,5-di Methoxyphenyl) -4 -oxo-7- [2_ (4-Ethylphenyl) ethoxy] -I, 4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluorobenzene Group) -N-acetamidine about 3: 1 mixture 97mg, 1,4-diazine-bicyclo [2 · 2 · 2] octane 49mg and acetonitrile 5ml, the reaction was carried out according to the method of Example (1i), 7 4 mg of the title compound was obtained as a white solid. NMR (CDC13) δρρι: 1. 20 (3Η, t, J-7. 3Hz), 2. 97 (2Η, t, J = 6. 6Hz), 3.  04-3. 10 (2H, m), 3. 22 (6H, t, J = 7. 3Hz), 3.  71 (6H, t, J = 7. 3Hz), 3.  78 > 3.  83 (2H, m), 3. 84 (6H, s), 3. 9K2H, q, J = 7. 3Hz), 4. 06 (2H, d, J = 2. 2Hz), 6. 38 (1H, d, J = 2. 2Hz), 6. 44 (2H, d, J = 2. 2Hz), 6.  59-6. 60 (2H, m), 6.  80-6.  83 (3H, m), 7. 14 (2H, d, 1 = 8.  1Hz), 7. 23 (2H, d, J = 8.  1Hz), 7. 79 (1H, s), 8.  12 (1H, d, J = 9. 5Hz).  Melting point: 1 5 3 ° C Example 1 5 9 1- (4- {2- [3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine 1- ( 3,5 -dimethoxyphenyl) -4 -oxo-1,4 -dihydroquinoline-7 -yloxy] ethyl} benzyl) -4 -azine-pyrazobicyclo [2. 2 · 2] Octane (Exemplified Compound-408-200300349 Number: 2-8 6 3) (159a) Acetic acid 4- {2- [3- [N- (3,5-difluorophenyl) -N-ethyl Aminemethyl] -1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] ethyl} benzyl ester · Example (1 1 h) 1- (3,5-dimethoxyphenyl) -7-hydroxy-4-oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorobenzene ) -N-acetamidamine 300 mg, 4- (2-bromoethyl) -benzyl acetate 24 1 mg obtained in Reference Example 18 ^ potassium carbonate 173 mg and Ν, Ν-dimethylformamide 10 ml was reacted according to the method of Example (1 1 i) to obtain 134 mg of the title compound as a white foamy substance. Li R (CDC13) δρρπι: 1. 20 (3H, t, J = 7. 3Hz), 2. 09 (3H, s), 3. 03 (2H, t, J = 6. 6Hz), 3. 83 (6H, s), 3. 92. (2H, q, J = 7. 3Hz), 4. 07 (2H, t, J = 6. 6Hz), 5. 07 (2H, s), 6. 39 (1H, d, J = 2. 2Hz), 6. 46 (2H, d, J = 2. 2Hz), 6. 58 ~ 6. 64 (2H, m), 6. 83 (2H, dd, 1 = 2. 2, 8. 1Hz), 6. 90 (1H, dd, J = 2. 2, 8. 8Hz), 7. 20 (2H, d, J = 8. 1Hz), 7. 29 (2H, d, J = 8. 1Hz), 7. 84 (1H, s), 8. 20 (1H, d, J = 8. 8Hz).  (15913) 1- (3,5-dimethoxyphenyl) -7- [2- (4-hydroxymethyl-phenyl) -ethoxy] -4-oxo-1,4-dihydroquinoline -3-Carboxylic acid N- (3,5-difluorophenyl) -N-acetamide -Difluorophenyl) -N-ethylaminomethylmethyl] -1- (3, 5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinolin-7-yloxy] ethyl 1} mg of benzyl ester in methanol solution, 6 mg of sodium methoxide was added, and stirred at room temperature for 4 hours. The reaction solution solvent was distilled off under reduced pressure, and ethyl acetate was added to dilute. The ethyl acetate layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 136 mg of the title compound as a colorless oily substance. -409-200300349 NMR.  (CDC13) (5ppm: 1. 20 (3H, t, J = 7.  3Hz), 3.  02 (2H, t, J = 6. 6Hz), 3. 82 (6H, s), 3. 92 (2H, q, J = 7. 3Hz), 4. 07 (2H, t, J = 6. 6Hz), 4. 66. (2H, s), 6. 40 (1H, d, J = 2. 2Hz), 6. 47 (2H, d, J = 2. 2Hz), 6. 57-6. 66 (2H, m), 6. 84 (2H, dd, J = 2. 2, 8. 1Hz), 6. 90 (1H, dd, J = 2. 2, 8. 8Hz), 7. 17 (2H, d, J = 7. 3Hz), 7. 29 (2H, d, J = 7. 3Hz), 7. 84 (1H, s), 8. 19 (1H, d, J = 9. 5Hz).  (159c) 7- [2- (4-Bromotolyl) -ethoxy] -1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3- Carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 1- (3,5-dimethoxyphenyl) -7- [2- (4- Hydroxymethyl-phenyl) -ethoxy] -4-oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 134mg, 47 mg of N-bromosuccinimide, 70 mg of triphenylphosphine and 10 ml of dichloromethane were reacted according to the method of Reference Example (17b) to obtain the title compound as a pale peach oily substance 7 7 mg. R ( CDC13) δρρπι: 1. 20 (3H, t, J = 7. 3Hz), 3. 02 (2H, t, J = 6. 6Hz), 3. 83 (6H, s), 3. 93 (2H, q, J = 7. 3Hz), 4. 07 (2H, t, J = 6. 6Hz), 4. 47 (2H, s), 6. 39 (1H, d, J = 2. 2Hz), 6. 47 (2H5 d, J = 2. 2Hz), 6. 58-6. 60 (2H, m), 6. 84 (2H, dd, J = 2. 2, 8. 1Hz), 6. 90 (1H, dd, J = 2. 2, 8. 8Hz), 7. 17 (2H, d, J = 8. 1Hz), 7. 32 (2H, d, J = 8. 1Hz), 7. 84 (1H, s), 8. 2K1H, d, J = 8. 8Hz).  (159d) Bromination: l- (4- {2- [3- [N- (3,5-difluorophenyl) -N · ethylaminomethylmethyl] -1- (3,5-dimethoxy Phenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] -ethylbenzyl) -4_acrid-1-azobicyclo [2 · 2 · 2] (159c) The obtained 7- [2- (4-bromotolyl) -ethoxy] -1-(3, 5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline- 3-carboxylic acid-410- 200300349 N- (3,5-difluorophenyl) -N-acetamidine 74mg, 1,4-diazine-bicyclo [2. 2. 2] Octane 25 mg and acetonitrile 4 ml 1, the reaction was carried out according to the method of Example (1i), and the title compound was obtained as a white foamy solid 6 2 mg g.  (CDC13) δρριη: 1. 20 (3H, t, J = 7. 3Hz), 2. 97 (2H, t, J = 6. 0Hz), 3. 16 (6H, t, J = 7. 4Hz), 3. 7K6H, t, J = 7. 4Hz), 3. 84 (6H, s), 3. 92 (2H, q, J = 7. 1Hz), 4. 08 (2H, t, J = 6. 0Hz), 5. 0K2H, s), 6. 40 (1H, d, J = 2. 2Hz), 6. 45 (2H, d, J = 2. 2Hz), 6.  58-6.  66 (2H, m), 6.  80-6.  90 (3H, m), 7. 29 (2H, d, 1 = 8. 0Hz), 7. 55 (2H, d, J = 8. 1Hz), 7. 82C1H, s), 8. 18 (1H, d, J = 9. 0Hz).  Melting point: 1 6 8-1 6 9 ° C · Example 16 0 Br (3- {4- [3- [N- (3,5-difluorophenyl) -N-ethylamine methylamidino) ] -1-(3, 5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7 -yloxymethyl] -phenylbupropyl) -4 -acyl-1 -azo Bicyclic [2 · 2 · 2] octane (Exemplified compound number: 2-8 6 2) (160 &) 7- [4- (3-bromopropyl) -benzyloxy] -1- (3,5- Dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine_ Examples (1 1 h ) The obtained 1-(3,5-dimethoxyphenyl) -7 -hydroxy-4 -oxo-1,4-diaminopyridin-3 -unsaturated acid N- (3,5-monofluorophenyl) 400 mg of N-acetamidine, 340 mg of 1-bromomethyl-4- (3-bromopropyl) -benzene obtained in Reference Example 19, 51 mg of sodium hydride and 8 ml of N, N-dimethylformamide The reaction of Example (1 h) was carried out to obtain the title compound as a white foamy substance 5 5 1 mg. Response R (CDCl3) 5ppm: 1. 20 (3H, t, J = 7. 3Hz), 2.  09-2. 11 (2H, m), 2. 77 (2H, t, J = 7. 3Hz), 3. 38 (2H, t, J-6. 6Hz), 3. 82 (6H, s), 3. 92 (2H, q, J = 7. 3Hz), 4. 93 (2H, s), 6. 42 (2H, d, J-2. 2Hz), 6. 45 (1H, d, J = 2. 2Hz), 6. 59-6. 66 (2H, in), 6. 84 (2H, -411- 200300349 dd, J = 2. 2, 8. 1Hz), 6. 98 (1H, dd, J = 2.  2, 8. 8Hz), 7. 17 (2H, d, J = 8.  1Hz), 7. 22 (2H, d, J = 8. 1Hz), 7. 84 (1H, s), 8. 21 (1H, d, J = 8. 8Hz).  (160b) 1- (3- {4- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -l- (3,5-dimethoxybenzene) Yl) -4 -oxo-1,4-dihydroquinoline-7-yloxymethyl] -phenylbupropyl) -4 -acyl-1-azobicyclo [2. 2. 2] Octane 7-[4-(3-bromopropyl) -benzyloxy] -1- (3,5-dimethoxyphenyl) -4 -oxo obtained in Example (1 6 0 a) -1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 164mg, 1,4-diazinebicycle_ [2. 2. 2] 55 mg of octane and 8 ml of acetonitrile were reacted according to the method of Example (li) to obtain 150 mg of the title compound as a white solid. Awake R (CDC13) δρρπι: 1. 19 (3H, t, J = 7. 3Hz), 2.  06-2. 18 (2H, m), 2. 7K2H, t, J = 7. 3Hz), 3. 22 (6H, t, J = 7. 3Hz), 3. 52-3. 69 (8H, m), 3. 82 (6H, s), 3. 90 (2H, q, J-7. 3Hz), 4. 93 (2H, s), 6. 38 (2H, d, J = 2. 2Hz), 6. 45 (1H, d, J = 2. 2Hz), 6. 60-6. 68 (2H, m), 6. 82 (2H, dd, J-2. 2, 8. 1Hz), 6. 94 (1H, dd, 1 = 2. 2, 8. 8Hz), 7. 16-7.  22 (4H, m), 7. 76 (1H, s), 8. 17 (1H, d, J = 9. 5Hz).  Melting point: 1 50-1 5 5 ° C φ Example 1 6 1 Br (4- {3- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl) BU1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] -propylbenzyl) -4 · 2 · 2] octane (Exemplified compound number: 2-8 6 5) (161a) acetic acid 4- {3- [3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine Yl] -1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-fluorenyloxy] -propyl 丨 -benzyl ester-412- 200300349 will be implemented Example (11 h) 1- (3,5-dimethoxyphenyl) -7-hydroxy-4-oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5- 500 mg of difluorophenyl) -N-acetamidamine, 395 mg of 4- (3-bromopropyl) -benzyl acetate obtained in Reference Example 20, 64 mg of sodium hydride, and N, N-dimethylformamidine 6 ml of amine was reacted according to the method of Example (1 h) to obtain the title compound as a white foamy substance, 67 mg. NMR (CDC13) δρριη: 1. 2Κ3Η, t, J = 6. 6Hz), 1.  97-2.  08 (2H, m), 2. 09 (3H, s), 2. 75 (2H, t, J = 7. 3Hz), 3. 82 (6H, s), 3. 87 (2H, t, J = 6. 6Hz), 3. 93 (2H, q, J = 7. 3Hz), 5. 06 (2H, s), 6. 40 (1H, d, J = 2. 2Hz), 6,47 (2H, d, J = 2. 2Hz), 6. 59-6. 67 (2H, m), 6. 84 (2H, dd, J = 2. 2, 8. 1Hz), 6. 90 (1H, dd, J = 2. 2, 8. 8Hz), 7. 15 (2H, d, I = 8. 1Hz), 7. 27 (2H, d, J = 8. 1Hz), 7. 85 (1H, s), 8. 21 (1H, d, J = 8.  8Hz).  (161b) l- (3,5-dimethoxyphenyl) -7- [3- (4-hydroxytolyl) -propoxy] oxy-I, 4-dihydroquinoline-3-carboxylic acid N · (3,5_difluorophenyl) -N-acetamidamine 'The acetic acid obtained in Example (1 6 1 a) was 4-{3-[3-[Ν-(3,5-difluorophenyl ) -N-Ethylaminomethyl] -1- (3,5-dimethoxyphenyl) -4-oxo-1,4-dihydro Uquindolin-7-yloxypropyl}} 460 mg, 19 mg of sodium methoxide and 40 ml of methanol were reacted in the same manner as in Example (15 9 b) to obtain 506 mg of the title compound as a colorless oil. Draw R.  (CDC13) (5ppm: 1. 2K3H, t, J = 6. 6Hz), 1.  98-2.  11 (2H, m), 2. 75 (2H, t, J = 7. 3Hz), 3. 82 (6H, s), 3. 86 (2H, t, J = 5. 9Hz), 3. 93 (2H, q, 1 = 7.  3Hz), 4. 66 (2H, s), 6. 39 (1H, d, J = 2. 2Hz), 6. 47 (2H, d, J = 2. 2Hz), 6. 59-6. 66 (2H, m), 6. 84 (2H, dd, 1 = 2. 2, 8. 1Hz), 6. 90 (1H, dd, J = 2. 2, 8. 8Hz), 7. 15 (2H, d, J = 8. 1Hz), 7. 27 (2H, d, J = 8. 1Hz), 7. 85 (1H, s), 8. 21 (1H, d, J-8. 8Hz).  (161〇7- [3- (4-bromomethyl-phenyl) -propoxy] -1- (3,5-di 200 300 349 methoxyphenyl) 4-oxo-1,4-dihydroquine N- (3,5-difluorophenyl) -N-acetamidinium carboxylic acid-3-carboxylic acid 1- (3,5-dimethoxyphenyl) -7 obtained in Example (1 6 1 b) -[3-(4-hydroxytolyl) -propoxy] -4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -1 ^- Acetamide 2521 ^, 1 ^ -bromobutanediimide 86mg, triphenylphosphine 126mg, and 15ml of dichloromethane were reacted according to the method of Reference Example (17b) to obtain the title compound as a colorless oil 3 3 9 mg ο NMR.  .  (CDC13) (5ppm: 1. 2K3H, t, 1 = 6.  6Hz), 1.  97-2.  10 (2H, m), 2. 74 (2H, t, J = 6. 6Hz), 3. 83 (6H, s), 3. 87 (2H, t, J = 6. 6Hz), 3. 93 (2H, q, J = 6. 6Hz), 4. 48 (2H, s), 6. 39 (1H, d, J = 2. 2Hz), 6. 47 (2H, d, J = 2. 2Hz), 6. 58-6. 68 (2H, m), 6. 85 (2H, dd, J = 2. 2, 8. 1Hz), 6. 90 (1H, dd, J = 2.  2, 8. 8Hz), 7. 13 (2H, d, J = 8.  1Hz), 7. 30 (2H, d, J = 8.  1Hz), 7. 86 (1H, s), 8. 2K1H, d, J = 8. 8Hz).  (16 1 (1) bromide 1- (4- {3, [3- [1 (3,5-difluorophenyl) -1 ethylaminomethylmethyl] -1- (3, 5-dimethoxy Phenyl) -4 -oxo-1,4-dihydroquinoline-7-yloxypropylbenzyl) -4 -acyl-; 1-azobicyclo [2 · 2. 2] Octane 7-[3-(4-bromomethyl-phenyl) -propoxy] -1- (3, 5 -dimethoxyphenyl) obtained in Example (1 6 1 c)- 165 mg of 4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine, 1,4-diazine bicyclo [2. 2 · 2] octane 54 mg and acetonitrile 8 ml 1 were reacted according to the method of Example (1 i) to obtain the title compound as a white foamy solid 13 2 mg. NMR (CDCI3) δ ppm: 1. 2K3H, t, J = 7. 3Hz), 2. 00-2. 09 (2H, m), 2. 73-2. 82 (2H, m), 3. 18 (6H, t, J = 7. 3Hz), 3. 71 (6H, t, J = 7. 3Hz), 3. 84 (6H, s), 3. 86-3. 96 (4H, m), 4. 98 (2H, s), 6. 41 (1H, d, J = 2. 2Hz), 6. 46 (2H, d, J = 2. 2Hz), 6. 59-6. 67 (2H, m), 6. 84 (2H, dd, 1 = 2. 2, 8. 1Hz), 6. 89 (1H, dd, J = 2. 2, 8. 8Hz), 7. 24 (2H, d, J = 8.  1Hz), 7. 52 (2H, d, J = 8. 1Hz), 7. 83 (1H, s), 8. 2K1H, d, J = 8.  8Hz).  200300349 Melting point: 1 5 4 ° c Example 1 6 2 1- (4- {3- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethyl)]-1 -(3,5 -dimethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7 -yloxy] -propylbenzyl) -4 -acyl-1 -azobicyclo [2 · 2 · 2] octane (exemplified compound number: 2-6 7 2) (162 &) 7- [3- (4-chlorotolyl) -propoxy] -1- (3,5-dimethoxybenzene ) -4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine _ obtained from Example (1 6 1 b) 1-(3,5-dimethoxyphenyl) -7-[3-(4-hydroxytolyl) -propoxy] -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N -(3,5-difluorophenyl) -1 ^ acetamidine 22611 ^, 1 ^ -chlorobutanedimine imine 58mg, triphenylphosphine 113mg and dichloromethane 20ml, according to the method of reference example (17b) The reaction gave the title compound as a colorless oil 1 4 8 mg ο R (CDC13) δρριη: 1. 2Κ3Η, t, 1 = 6.  6Hz), 1.  98-2. 10 (2Η, m), 2. 75 (2Η, t, J = 8.  1Hz), 3. 82 (6H, s), 3. 86 (2H, t, J = 5. 9Hz), 3. 93 (2H, q, J = 7. 3Hz), 4. 56 (2H, φ s), 6. 40 (1H, d, J = 2. 2Hz), 6. 48 (2H, d, J = 2. 2Hz), 6. 59-6. 67 (2H, m), 6. 85 (2H, dd, J = 2. 2, 8. 8Hz), 6. 9K1H, dd, J = 2. 2, 8. 8Hz), 7. 15 (2H, d, J = 8. 1Hz), 7. 29 (2H, d, J = 8. 1Hz), 7. 84C1H, s), 8. 22 (1H, d, J = 8. 8Hz).  (162b) 11- (4- {3- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethyl)]-1- (3,5-dimethoxybenzene ) -4 -oxo-1,4-dihydroquinoline-7-yloxy] -propyl-benzyl) -4 -acryl- azobicyclo [2 · 2 · 2] 6 2 a) 7-[3-(4-chlorotolyl) -propoxy

BU 1- (3, 5-dimethoxyphenyl) -4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N-415- 200300349-(3,5-difluorophenyl) -N -135 mg of acetamidine, 47 mg of 1,4-diazinebicyclo [2.2.2] octane and 12 ml of acetonitrile. The reaction was carried out according to the method of Example (li) to obtain 98 mg of the title compound as a white foamy solid. Li R (CDC13) δρριη: 1.2Κ3Η, t, J = 7.3Hz), 2. 00-2. 09 (2H, m), 2.78 (2H, t, 1-7.3Hz), 3.18 (6H, t, J -7.3Hz), 3.71 (6H, t, J = 7.3Hz), 3.84 (6H, s), 3.88 (2H, t, J = 6.6Hz), 3.93 (2H, q, J = 7.3Hz), 4.98 ( 2H, s), 6.4K1H, d, J = 2.2Hz), 6.46 (2H, d, J = 2.2Hz), 6.59-6.67 (2H, m), 6.84 (2H, dd, J = 2.2, 8.1Hz) , 6.89 (1H, dd, J = 2.2, 9.5Hz), 7.24 (2H, d, J = 8.1Hz), 7.52 (2H, d, J = 8.1Hz), 7.83 (1H, s), 8.2K1H, d , J = 8.8Hz). Example 1 6 3 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3- Methoxy-5-propoxy-phenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] heptylb 4-az-1-azobicyclo [2 · 2.2] Octane (Exemplified compound number: 2-7 7 2) (163a) 7-methoxymethoxy-1- (3-methoxy-5-propoxyphenyl) -4-oxo-1,4-di Hydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 1-(3-hydroxy-5 -methoxyphenyl) obtained in Example (1 8 5 e) ) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 2.15 g, n-propyl 0.57 ml of bromine, 1.164 g of potassium carbonate and 20 ml of N, N-dimethylformamide According to the method of Example (1 85f) of the line into the reaction, the title compound as a colorless oil of 2 · 0 8 g. NMR (CDC13) δρρπι: 1.06 (3H, t, J = 7.3Hz), 1.22 (3H? T, J = 7.3Hz), 1.77-1.90 (2H, m), 3.44 (3H, s), 3.83 (3H, s), 3.88-3.98 (4H, m), 5.12 (2H, s), 6. 44-6. 48 (2H, m), 6. 58-6. 67 (3H, m), 6.85 (2H, dd , J = 2.2, 8.8Hz), 7.05 (1H, dd, J = 2.2, 8.8Hz), 7.89C1H, s), 8.23 (1H, d, J = 8.8Hz). -416- 200300349 (163b) 7- Hydroxy-1- (3-methoxy-5-propoxy-phenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 7-methoxymethoxy-1- (3-methoxy-5-propoxyphenyl) -4-oxo-1,4-dihydroquine obtained in Example (163a) 2.06 g of N- (3,5-difluorophenyl) -N-acetamidoline-3-carboxylic acid and 60 ml of 4N HC1-ethyl acetate solution were reacted according to the method of Example (5 4 e). This gave 1.761 g of the title compound as a white solid. Bandit (CDC13) δρριη: 1.05 (3H, t, J = 7.3Hz), 1.29 (3H, t, J = 7.3Hz), 1.76-1.87 (2H, m), 3.81 (3H, s), 3.85-3.89 (2H, m), 4.00 (2H, q ·, J = 7.3Hz), 6.25 (1H, s), 6.3K1H, s), 6. 60 (1H, s), 6.75-6. 84 ( 2H, in), 7.0K2H, dd, J = 1.5, 6.6Hz), 7.6K1H, dd, J = 1.5, 8.8Hz), 7.7K1H, s), 8.2K1H, d, J = 9.5Hz). (163c ) 7- (7-Bromoheptyloxy) -1- (3-methoxy-5-propoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3 , 5-difluorophenyl) -N-acetamidamine 'The 7-hydroxy-1-(3-methoxy-5 -propoxy-benzyl) -4 obtained in Example (1 6 3 b) -4 -Oxygen-1,4-monoanhydroquinine-3-residue N- (3,5-__ ^ benzyl) -N-acetamidine 761mg, 1,7-dibromoheptane 1.02ml, sodium hydride 92 mg and 20 ml of N, N-dimethylformamide were reacted according to the method of Example (lh) to obtain 672 mg of the title compound as a white foamy substance. Face R (CDC13) δρρπκ 1.05 (3Η, t, J = 7.3Hz), 1.21 (3H, t, J = 7.3Hz), 1.30-1.49 (6H, m), 1.68-1.89 (6H, m), 3.40 (2H, t, J = 6.6Hz), 3.83 (3H, s), 3.87 (2H, t, J = 6.6Hz), 3.89-3.97 (4H, m), 6.40 (1H, d, J = 2.2Hz ), 6.46 (2H, d, J-2.2Hz), 6.59-6.67 (2H, m), 6.84 (2H, dd, J = 2.2, 8.1Hz), 6.90 (1H, dd, J = 2.2, 8.8Hz) , 7.85 (1H, s), 8.21 (1H, d, J-8.8Hz). (163d) bromide l- {7- [3- [N- (3,5-difluorophenyl) -N-ethyl Amine methyl-417- 200300349 fluorenyl] -1- (3-methoxy-5-propoxy-phenyl) -4-oxo-1,4-dihydroquinolin-7-yloxy] heptyl Bu 4 -Acryl-1 -azobicyclo [2 · 2.2] octane The 7-(7 -bromoheptyloxy) -1-(3 -methoxy-5- Propoxyphenylbenzene 4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 234mg, 1,4-diazine bicyclic [ 2 · 2 · 2] 7 mg of octane and 10 ml of acetonitrile were reacted according to the method of Example (1 1 j) to obtain 242 mg of the title compound as a white solid. R * (CDC13) 5ppm: 1.05 ( 3H, t, J = 7.3Hz), 1.20 (3H, t, J = 7.2Hz), 1.30-1.47 (6H, m), 1. 65-1.89 (6H, m), 3.24 (6H, t, 1 = 7. 4Hz), 3. 53-3. 60 (2H, m), 3.65 (6H, t, J = 7.4Hz), 3.81-3.88 (5H, m), 3.89-3.96 (4H, m), 6.50 (1H, d, J = 2.2Hz), 6.43 (2H, d, J = 2.2Hz), 6. 59-6. 67 (2H, m), 6.83 (2H, dd, J = 2.2, 7.9Hz),. > 6.9K1H, dd, J = 2.2, 9.2Hz), 7.79 (1H, s), 8.20 (1H, d, J = 9.0Hz). Melting point: 1 2 4 ° C Example 1 6 4 Bromide 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl} 1- (3-methoxy-5-propoxybenzyl) -4-oxo-1 ， 4-oxoquinolin-7-yloxy] heptyl] -pyrazinebicyclo [2 · 2 · 2] octane (exemplified compound number: 2- 771) Example (1 6 3 c) The obtained 7- (7-bromoheptyloxy) -1- (3-methoxy-5-propoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- ( 3,5-difluorophenyl) -N-acetamidamine 230 mg, panquinidine 75 mg and acetonitrile 10 m 1 were reacted according to the method of Example (1 1 j) to obtain the title compound 237mg of white solid. NMR (CDC13) όρριι: 1.05 (3Η, t, J = 7.4Hz), 1.20 (3H, t, J = 7.1Hz), 1.32-1.47 (6H, m), 1.65-1. 92 (6H, m), 2. 02-2.12 (6H, m), 2. 21-2.28 (1H, m), -418- 200300349

3.46-3 · 52 (2H, m), 3.70 (6H, t, J = 7.9Hz), 3.81-3 · 86 (5H, m), 3.89-3. 97 (4H, m), 6.40 (1H, d, J = 2.1Hz), 6.45 (2H, d, J = 2.2Hz), 6.58-6.67 (2H, m), 6.84 (2H, dd, J = 2.1, 7.9Hz), 6.90 (1H, dd, J = 2.2, 9.0Hz), 7.82 (1H, s), 8.20 (1H, d, J = 9.0Hz). Melting point · 1 2 3 ° C Example 1 6 5 Bromide 1- {7- [ 3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3-methoxy-5-propoxyphenyl) -4 -oxy-1,4- Dihydroquinoline-7-yloxy] heptylpyridine (exemplified compound number: 2-7 6 9) 7-(7 -bromoheptyloxy) -1 obtained in Example (1 6 3 c) -(3-methoxy-5 -propoxyphenyl) -4.oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N -acetamidine 178 mg of amine, 2 ml of pyridine and 4 m 1 of N, N-dimethylformamide were reacted according to the method of Example (1 1 j) to obtain 183 mg of the title compound as a white solid. Li R (CDC13) δρριη: 1.04 (3H, t, J = 7.3Hz), 1.20 (3H, t, J = 7.3Hz), 1.32-1.44 (6H, m), 1. 77-1. 88 (2H, m), 1. 99-2.19 (2H, m), 3. 81-3. 88 (5H, m), 3. 88-3. 98 (4H, m), 5.03 (2H, t, J = 7.3Hz ), 6. 36-6. 47 (3H, m), 6. 59-6. 66 (2H, m), 6.83 (2H, dd, J = 2.2, 8.1Hz), 6.89 (1H, dd, J = 2.2, 8.8Hz), 7.80 (1H, s), 8.09 (2H, t, 1 = 7.3 Hz), 8.18 (1H, d, J-8, 8Hz), 8.47 (1H, d, J = 7.3Hz), 9.52 (2H, d, J = 5.9Hz). Melting point: 9 8-9 9 ° C Example 1 6 6 Bromide 1- {8- [3- [N- (3,5 -2 Fluorophenyl) -N-ethylaminomethylmethyl] -1- (3-methoxy-5-propoxyphenyl) -4-oxy-1,4-dihydroquinoline-7-yloxy] Octylb 4 -acyl-1 -azobicyclo [2 · 2.2] octane (Exemplified compound number: 2-8 3 1) (166a) 7- (8-bromooctyloxy) -1- (3-form Oxy-5-propoxyphenyl) -4- 200300349 Oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine Example (1 6 3 b) 7-Hydroxy-1-(3-methoxy-5 -propoxy-phenyl) 4-oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3, 5-difluorophenyl) -N-acetamidine 8 700 mg, 1,8-dibromooctane 1. 2 6 m 1 105mg sodium hydride and Ν, Ν - dimethylformamide 25ml, reaction was carried out according to Example (LH) of the method, the title compound of white solid 6 9 0mg. NMR .. (CDC13) δρριη: 1.05 (3H, t, J = 7.3Hz), 1.2K3H, t, J-7.3Hz), 1.39-1.48 C8H, m), 1. 60-1. 76 (2H, m ), 1. 78-1. 89 (4H, m), 3.40 (2H, t, J = 6.6Hz), 3.83 (3H, s), 3.86 (2H, t, J = 6.6Hz), 3.89-3.97 ( 4H, m), 6.40 (1H, d, J = 2.2Hz), 6.46 (2H, d, J = 2.2Hz), 6.58-6.66 (2H, m), 6.84 (2H, dd, J = 2.2, 8.1Hz ), 6.90 (1H, dd, J = 2.2, 8.8Hz), 7.84 (1H, s), 8.21 (1H, d? 1 = 8.8Hz). (166b) bromide l- {8- [3- (N -(3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3-methoxy-5-propoxyphenylbenzene 4-oxy-1,4-dihydroquinoline- 7-yloxy] octylb- 4-az-1-azobicyclo [2.2.2] octane The 7-(8-bromooctyloxy) -1-( 3 -methoxy-5 -propoxyphenyl) -4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -1 ^ -acetamidine 24〇11 ^, 1,4-diazine-bicyclo [2.2.2] octane 77 mg and acetonitrile 25 m 1 were reacted according to the method of Example (1 1 j) to obtain the title compound as a white solid. 237mg. Li R (CDC13) (5ppm: 1.06 (3H, t5 J = 7.3Hz), 1.2K3H, t, J = 7.2Hz), 1.28-1.44 (8H, m), 1.66-1.78 (4H, m), 1.79-1. 89. (2H, m), 3.26 (6H, t, J = 7.3Hz), 3.51-3.58 (2H, m), 3.65 (6H, t, J = 7.3Hz), 3.84 (3H, s), 3.87 (2H, t, J = 6.6Hz ), 3.90-3.96 (4H, m), 6.40-6.46 (3H, m), 6. 60-6.68 (2H, in), 6.84 (2H, dd, J = 2.2, 5.9Hz), 6.92 (1H, dd , J = 2.2, 8.8Hz), 7.82 (1H, s), 8.2K1H, d, J = 8.8Hz). 200300349 Melting point: 1 2 0 ° C Example 1 6 7 Bromide 1- {8- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethoxy-5 -propoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7 -yloxy [Alkyl] octyl 1-azobicyclo [2.2 · 2] · octane (exemplified compound number ·· 2-8 3 0) 7-(8 -bromooctyloxy) obtained in Example (1 6 6 a) ) -1-(3-methoxy-5-propoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N -240 mg of acetamidine, 76 mg of panaxidine and 10 ml of acetonitrile, and reacted according to the method of Example (1 1 j) to obtain 250 mg of the title compound as a white solid. NMR (CDC13) δρρπι: 1.05 (3Η, ί, J = 7.3Hz), 1.20 (3Η, t, J = 7.3Hz), 1. 27-1.43 (8Η, m), 1. 65-1. 88 (6Η , m), 2. 02-2.12 (6H, m), 2. 20-2. 25 (1H, m), 3.44-3.51 (2H, m), 3.70 (6H, t, J = 7.3Hz), 3 81-3. 88 (5H, m), 3. 89-3. 96 (4H, m), 6.40 (1H, d, 1 = 2.2Hz), 6.44 (2H, d, J = 1.5Hz), 6.59 -6.67 (2H, m), 6.81-6.84 (2H, m), 6.90 (1H, dd, J = 1.5, 8.8Hz), 7.83 (1H, s), 8.20 (1H, d, J = 9.5Hz). Melting point: 1 17 ° C Example 1 6 8 1- [8- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethyl]]-1- (3- Methoxy-5 -propoxyphenyl) -4 -oxy-I, 4-dihydroquinoline-7-yloxy] octyl] -pyridine (exemplified compound number: 2-8 2 8) will be implemented Example 7- (8-Bromooctyloxy) -1- (3-methoxy-5_propoxyphenyl) -4-oxy-1,4-dihydroquinoline-3-carboxyl obtained from Example (166a) The acid N- (3,5-difluorophenyl) -N-acetamidine 219 mg, pyridine D 2 ml and acetonitrile 4 ml were reacted according to the method of Example (1 1 j) to obtain the title compound as a white solid 200300349 210mg ° NMR. (CDC13) δρρη: 1.04 (3H, t, J = 7.3Hz), 1.20 (3H, t ,, J = 7.3Hz), 1.25-1.43 (8H, m), 1. 77-1. 88 (2H, m), 1. 98-2. 08 (2H, m), 3.83 (3H, s), 3.84 (2H, t, J = 6.6Hz), 3.89-3.96 (4H, m), 5.02 (2H , t, J = 7.3Hz), 6.39 (1H, d, J = 2.2Hz), 6.43 (2H, d, J = 2.2Hz), 6.60-6. 66 (2H, m), 6.84 (2H, dd, J = 2.2, 8.1Hz), 6.89 (1H, dd, J = 2.2, 8.8Hz), 7.80 (1H, s), 8.10 (2H, t, J = 7.3Hz), 8.18 (1H, d, J = 8.8 Hz), 8.47 (1H, d, 1 = 7.3Hz), 9.50 (2H, d, 1 = 5.9Hz).

Melting point: 94- 9 6 ° C Example 1 6 9 · 1- (7- {l- (3-butoxyphenyl) -3- [N- (3,5-difluorophenyl) -N -Ethylaminomethyl] -4 -oxo-1,4-dihydroquinoline-7 -yloxy 丨 heptyl) -4-acyl-1 -azobicyclo [2,2 · 2] octane ( Exemplified compound number: 2-8 1 2) (169a) 7-benzyloxy-1- (3-methoxymethoxyphenyl) -4-oxo-I, 4 · dihydroquinoline-3 -carboxylic acid methyl ester The ester was 3-methoxymethoxyaniline obtained in Reference Example 11 and 2- (4-benzyloxy-2-methoxymethoxybenzyl) -3-dimethylamino-methyl acrylate obtained in Example (44b). 18.47 g, potassium carbonate 13.82 g, and Ν, Ν-dimethylformamide 100 m were reacted according to the method of Example (44c) to obtain 18.20 g of the title compound as a white solid. Wake R (CDC13) (5ppm: 3.5K3H, s), 3.92 (3H, s), 5.00 (2H, s), 5.16-5.26 (2H, m), 6.46 (1H) d, 1 = 2.2Hz), 6.99 (1H, dd, J = 2.2, 8.8Hz), 7.04-7.10 (2H, m), 7.23-7.37 (6H, m), 7.49 (1H, t, J = 8.1Hz), 8.46 (1H, d, J -8.8Hz), 8.47 (1H, s). (169b) 7-benzyloxy-1- (3-methoxymethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxyl Acid-422-200300349 The 7-benzyloxy-1- (3-methoxymethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid obtained in Example (169a) The ester 18.1 g, 20 g sodium hydroxide, 200 ml methanol and 200 ml water were reacted according to the method of Example (le) to obtain 16.49 g of the title compound as a white solid. Rei R (DMS0-d6) (5ppm: 3.42 (3H, s), 5.11 (2H, s), 5. 23-5. 35 (2H, in), 6.52C1H, d, J = 2.2Hz), 7.22 ( 1H, d, J = 8.1Hz), 7.27-7.38 (8H, m), 7.60 (1H, t, J = 8.8Hz), 8.32 (1H, d, J = 8.8Hz), 8.55 (1H, s). (169c) 7-benzyloxy-1- (3-methoxymethoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N-(3, 5-difluorophenyl ) -N-Acetylamine The 7-benzyloxy-1- (3-methoxymethoxyphenyl) -4-oxo-1,4-dihydroquinoline obtained in Example (16 9b)- 16.24 g of 3-carboxylic acid, 13.12 ml of triethylamine, 5.83 ml of isobutyl chloroformate, 13.60 g of N-ethyl-3.5-difluoroaniline obtained in Reference Example 2 and 200 ml of dichloromethane, according to Example (If) The reaction was carried out by the method to obtain the title compound as a white solid 1 0.90 g NMR (CDCI3) δρριη: 1.20 (3H, t, J = 7.3Hz), 3.5K3H, s), 3.-92 (2H, q, J-7.3Hz), 4.95 (2H, s), 6.42 (1H, d, J = 2.2Hz), 6.59-6.66 (1H, m), 6.83 (2H, d, J = 6.6Hz), 6.92 ( 1H, d, J-6.6Hz), 6.99 (2H, dd, J = 2.2, 8.8Hz), 7. 21-7. 36 (6H, m), 7.46 (1H, t, J = 8.1Hz) , 7.85 (1H, s), 8.22 (1H, d, J = 8.8Hz). (169d) 7-benzyloxy-1- (3-hydroxyphenyl) -4-oxo-1,4-dihydroquine -3 -carboxylic acid N-(3,5-difluorophenyl) -N -acetamidine The 7 -benzyloxy-1-(3-methoxymethoxybenzene) obtained in Example (1 6 9 c) N- (3,5-difluorophenyl) -N-acetamidine 5.90 g and 4 NHCI -ethyl acetate solution 6 0 m 1, the reaction was carried out according to the method of Example (5 4 e), and the title compound was obtained as a white solid 200 300 349 4.9 4 g 0 R, (CDC13) δ ppm: 1.20 (3H, t, J = 7.3Hz), 3. 87-3. 97 (2H, m), 4.96-5. 16 (2H, m), 6.30 (1H, d, J = 8.1Hz), 6.69 (1H, d, J = 2.2Hz), 6.72- 6.80 (1H, m), 6.93 (2H, dd, J = 2.2, 7.3Hz), 7.16-7.38 (9H, m), 8.03 (1H, s), 8.38 (1H, d, J = 9.5Hz). ( 169e) 7-Benzyloxy-1- (3-butoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N -Acetylamine 7-benzyloxy-1- (3-hydroxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3 obtained in Example (16 9d) , 5-difluorophenyl) -N-acetamidine 3.11 g, n-butyl bromide 1.27 m sodium hydride 361 mg, and N, N-dimethylformamide 3 0 m 1, according to the example (1 8 5 f) The reaction was carried out to obtain the title compound as a white solid 2.14 gBandit R (CDC13) δρρπι: 1.00 (3Η, t, J = 7.3Hz), 1.20 (3H, t, J = 7.3Hz), 1.45-1. 57 (2H, in), 1. 75-1. 85 (2H, m), 3. 88-4. 00 (4H, m), 4.95 (2H, s), 6.40 (1H, d, J = 2.2Hz), 6. 58-6. 66 (1H, m ), 6. 76-6. 87 (4H, m), 6.98 (1H, dd, J = 2.2, 8. 8Hz), 7.08 (1H, t, J-8.8Hz), 7.23-7.36 (5H, m) , 7.44 (1H; s), 7.85 (1H, s), 8.22 (1H, d, J = 8. 0Hz). (169f) l- (3-butoxyphenyl) -7-hydroxy-4-oxo- 1,4-Dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N acetamidine The 7-benzyloxy-1-( 3-butoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -acetamidine 2.2 7 g and 10% P d -C 400 mg, the reaction was carried out according to the method of Example (1 g) to obtain the title compound as a white solid, 1.87 g. NMR (CDCI3) δρριη: 〇.98 (3H, t, J = 7.3Hz), 1.17 (3H, t, J = 7..3Hz), 1.42-1. 55 (2H, m), 1.72-1.82 (2H , m), 3.89 (2H, q, J = 7.3Hz), 3.94 (2H, q, 200300349 J = 7.1Hz), 6.39C1H, bs), 6.58-6 · 65 (1Η, m), 6.74-6 · 89 (5Η, m), 7.02 (1H, dd, J = 2.2, 8.8Hz), 7.37 (1H, t, J = 8. 1Hz), 7.79 (1H, s), 8.00 (1H, d, I = 8.00 Hz). (169g) 7- (7-bromoheptyloxy) -1- (3-butoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3, 5-Difluorophenyl) -N-acetamidine The 1- (3-butoxyphenyl) -7-hydroxy_4_oxy-1,4-dihydroquinoline-3- obtained in Example (169f) Carboxylic acid N- (3,5-difluorophenyl) -N acetamide 922 mg, 1,7-dibromoheptanium 1.45 g, sodium hydride 163 mg and N, N-dimethylformamide 2 0 m 1 8 8 g。 According to the method of Example (1 h), the reaction was carried out to obtain the title compound as a white foamy substance 0.88 g. NMR (CDC13) (5ppm: 0.99 (3H, t, J = 7.4Hz), 1.2K3H, t, J = 7.2Hz), 1.26-1.57 (8H, m), 1.65-1.90 (6H, m), 3.39 (2H, t, J = 6.7Hz), 3.84 (2H, t, J = 6.3Hz), 3.93 (2H, q, J = 7.1 Hz), 3.98-4.05 (2H, m), 6.34 (1H, d , J = 2.3Hz), 6.58-6. 67 (1H, m), 6. 80-6. 86 (3H, m), 6. 88-6. 94 (2H, m), 7.08 (1H, dd, J = 2.3, 8.5Hz), 7.47 (1H, t, J = 8.2Hz), 7.86 (1H, s), 8.22 (1H, d, J = 9.0Hz). (169h) bromide 1- (7- ( l- (3-butoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -4 -oxo-1,4-dihydroquinoline-7 -Yloxy} heptyl) -4 -azol-1-azobicyclo [2,2.2] octane calls for the 7- (7-bromoheptyloxy) -1- obtained in Example (169g) (3-Butoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 226mg, 1,4-- Diazine bicyclic [2 · 2 · 2] octane 76 mg and acetonitrile 10 ml were reacted according to the method of Example (1 1 j) to obtain 233 mg of the title compound as a white solid. NMR (CDC13) δρριη: 0.99 (3H, t, J = 7.3Hz), 1.20 (3H, t, J = 7.2Hz), 1.34-1.42 (6H, m), 1.45-1.56 (2H, m), 1.64- 1. 84 (6H, m), 3.24 (6H, t, J = 7.3Hz), -425-200300349 3.51-3.57 (2H, m), 3.65 (6H, t, J = 6.6Hz), 3.83 (2H, t, J = 6.6Hz), 3.92 (2H, q, J-7.3Hz), 4.00 (2H, t, J = 6.6Hz), 6.34 (1H, d, J = 2.2Hz), 6.60-6.68 (1H, m), 6. 80-6. 85 (3H, m), 6. 88-6. 93 (2H, m), 7.09 (1H, dd, J = 2.2, 8.8Hz), 7.48 (1H, t, J = 8.1 Hz), 7.80 (1H, s), 8.20 (1H, d, J = 8.8Hz).

Melting point: 1 1 4 ° C Example 1 7 0 1- (8- {l- (3-butoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethyl bromide Carboxamidine] -4-oxo-l, 4-dihydroquinolin-7-yloxy} octyl) -4-azol-l-azobicyclo [2.2.2] octane (Exemplary compound number: 2-853) (17 (^) 7- (8-bromooctyloxy) -1- (3-butoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3, 5-difluorophenyl) -N-acetamidine The 1- (3-butoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquine obtained in Example (169f) N- (3,5-difluorophenyl) -N acetamide, 917 mg, 1.52 g of 1,8-dibromooctane, 163 mg of sodium hydride, and N, N-dimethylformamide 2 0 m 1, the reaction was carried out according to the method of Example (1 h), and the white foamy substance of the title compound was obtained. 0.88 g. R R (CDC13) δρρπι: 0 · 99 (3Η, t, J = 7.4 Hz), 1.21 (3Η, t, 1 = 7.2Ηζ), 1.22-1.45 (8H, m), 1.46-1. 57 (2H, m), 1. 65-1. 90 (6H, in) , 3.40 (2H, t, J = 6.9Hz), 3.84 (2H, t, J-6: 4Hz), 3.93 (2H, q, J = 7.2Hz), 3.96-4.04 (2H, m), 6.34 (1H , d, 1 = 2.2 Hz), 6. 60-6. 68 (1H, m), 6. 82-6. 87 (3H, m), 6. 88-6. 95 (2H, m), 7.08 (1H, dd, J-2.4, 8.3Hz), 7.46 (1H, t, 1 = 8.1Hz), 7.86 (1H, s), 8.22 (1H, d, J = 8.9Hz). (17〇b) bromide 1- (8- {l- (3-butoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -4-oxy-1,4-dihydro Quinoline-7-yloxy} octyl) -4-acyl-1-azobicyclo [2.2.2] octane The 7- (8-bromooctyloxy) obtained in Example (1 7 0 a) 157 mg of -1-(3 -butoxybenzene 200 300 349) -4 -oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3, 5 -difluorophenyl) -N-acetamidamine, 52 mg of 1,4-diazabicyclo [2 · 2 · 2] octane and 10 ml of acetonitrile were reacted according to the method of Example (1 1 j) to obtain 163 mg of the title compound as a white solid. Li R. (CDC13) όρριη: 0 · 99 (3Η, t, J = 7.3Hz), 1.20 (3H, t, J = 7.3Hz), 1.25-1.42 (8H, m), 1.45 ~ 1.58 (2H, m ), 1. 64-1. 84 (6H, m), 3.25 (6H, t, J = 7.3Hz), 3.49-3.55 (2H, m), 3.64 (6H, t, J = 7.3Hz), 3.84 ( 2H, t, J = 6.6Hz), 3.92 (2H, q, J = 7.3Hz), 4.00 (2H, t, J = 6.6Hz), 6. 34 (1H, d, J = 2.2Hz), 6.60- 6.67 (1H, m), 6. 80-6. 86 (3H, m), 6. 88-6. 93 (2H, m), 7.08 (1H, dd, J = 2.2, 8.1Hz), 7.47 (1H, d, J = 8.8Hz), 7.80C1H, s), 8.20 (1H, d, J-8.8Hz). Melting point: 1 1 5 ° C Example 1 7 1 Bromide l- (8- {l -(3-butoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -4 -oxo-1,4-dihydroquinoline-7- Alkoxy} octyl) -1-azobicyclo [2 · 2 · 2] octane (exemplified compound number: 2-8 5 2) 7-(8 -bromo) obtained in Example (1 7 0 a) Octyloxy) -1-(3 -butoxyphenyl) -4 -oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The amine 1 8 mg, panquinidine 5 2 mg and acetonitrile 10 m 1 were reacted according to the method of Example (1 1 j) to obtain the title compound as a white solid 1 3 8 mg NMR (CDC13) δ ppm : 0.99 (3 H, t, J = 7.3Hz), 1.20 (3H, t, J = 7.3Hz), 1.26-1.42 (8H, m), 1.46-1.56 (2H, m), 1. 64-1. 73 (4H, id), 1.76-1. 84 (2H, m), 2. 01-2. 09 (6H, m)? 2. 21-2. 25 (1H, m), 3. 45-3. 51 (2H, m), 3.69 (6H, t, J = 8.1 Hz), 3.83 (2H, t, J = 5.9Hz), 3.92 (2H, q? J = 7.3Hz), 4.00 (2.H, t, J = 6.6Hz), 6.34 (1H, d, J-2.2Hz), 6. 60-6. 67 (1H, m), 6. 81-6. 87 (3H, m), 6. 88 ~ 6. 93 ( 2H, m), 7.08 (1H, dd, J = 2.2, 8.8Hz), 7.47 (1H, d, J = 8.8Hz), 7.83 (1H, s), 8.04 (1H, d, J-8.8Hz). 200300349 Melting point: 10 2 ° C Example 1 7 2 1- (7- {1- (3-butoxyphenyl) -3- [N- (3,5-difluorophenyl) -N- Ethylaminomethyl] -4-oxo-1,4-dihydroquinoline-7-yloxy} heptyl) -pyridine (exemplified compound number: 2-8 0 9) Example (1 6 9 g) The obtained 7- (7-bromoheptyloxy) -1- (3-butoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5- 241 mg of difluorophenyl) -N-acetamidamine, 2 ml of pyridine and 3 ml of N, N-dimethylformamide, were reacted according to the method of Example (1 1 j) to obtain the title compound as a white solid 1 2 8 mg. NMR. (CDC13) δρρπι: 0.99 (3H, t, J-7.3Hz), 1.20 (3H, t, J = 7.3Hz), 1.33-1.45 (6H, m), 1.47-1.57 (2H, m), 1.63 -1. 73 (2H, m), 1. 75-1. 85 (2H, m), 1.99-2.09. (2H, m), 3.82 (2H, t, J = 6.6Hz), 3.92 (2H, q , J = 7.3Hz), 3.96-4.04 (2H, m), 5.03 (2H, t, J = 7.3Hz), 6.32 (1H, d, J = 2.2Hz), 6.59-6.66 (1H, m), 6.90 -6.93 (5H, m), 7.09 (1H, dd, J = 2.9, 8.1Hz), 7.48 (1H, t, J = 8.1Hz), 7.82 (1H, s), 8.08 (2H, t, J = 7.3 Hz), 8.19 (1H, d, J = 9.5Hz), 8.46 (1H, t, J-7.3Hz), 9.5K2H, d, 1 = 5.9 Hz). Melting point · 8 2-8 5 ° C Implementation Example 1 7 3 (3-Butoxyphenyl) bromide 3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl ^ 4-oxo-1,4-dihydroquine Phenolin-7-yloxy} heptyl) -dimethapine (exemplified compound number: 2-810) The 7- (7-bromoheptyloxy) -1-( 3-butoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 240 mg, 1-methylpiperidine 0.20 ml and N, N-dimethylformamide-428-200300349 3 m 1 were reacted according to the method of Example (1 1 j) to obtain 20 8 mg of the title compound as a white solid. NMR (CDC13) (5ppm: 0.99 (3H, t, J = 7.3Hz), 1.20 (3H, t, J = 7.3Hz), 1.35-1.46 (6H, m), 1.47-1. 57 (2H, m) , 1. 66-1. 97 (12H, m), 3.32 (3H, m), 3.62-3. 77 (6H, m), 3.83 (2H, t, J = 6.6Hz), 3.93 (2H, q, J = 7. 3Hz), 3. 97-4.04 (2H, in), 6.34 (1H, d, J = 2.2Hz), 6. 60-6. 67 (1H, m), 6. 81-6. 86 (3H, m), 6. 88-6. 93 (2H, m), 7.09 (1H, dd, J = 2.2, 8.1Hz), 7.48 (1H, t, J = 8.1 Hz), 7.84 (1H, s), 8.11 (1H, d, J = 9.5Hz).

Melting point: 9 4 ° C Example 1 7 4 · 1- (8- {Br (3-butoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylamine bromide Formamyl] -4-oxo-1,4-dihydroquinoline-7-yloxy} octyl) -1-methylpiperidine (exemplified compound number: 2-8 5 1) Example (1 7 0 a) of the obtained 7-(8 -bromooctyloxy) -1-(3 -butoxyphenyl) -4 -oxo-1,4-dihydroquinolinoline-3-carboxylic acid N- (3, 158 mg of 5-monofluorophenyl) -N-acetic acid, 0.20 ml of 1-methylpiperidine and 3 m 1 of N, N-dimethylformamide. The reaction was carried out according to the method of Example (1 lj). 129 mg of the title compound was obtained as a white solid. Call circle R (CDC13) δρριη: 0.99 (3H, t, J = 7.3Hz), 1.20 (3H, t, J = 7.3Hz), 1.28-1.43 (8H, in), 1.45-1.57 (2H, m)? L 68-1.98 (12H, m), 3.32 (3H, m), 3.61-3.69 (4H, m), 3.70-3.78 (2H, m), 3.83 (2H, t, J-6.6Hz), 3.92 (2H , q, J-7.3Hz), 3.99 (2H, t? J = 6.6Hz), 6.34 (1H, d, J-2.2Hz), 6.59-6.66 (1H, m), 6. 80-6. 87 ( 3H, m), 6. 88-6. 93 (2H, m), 7.08 (1H, dd, 1 = 2.2, 8.8Hz), 7.47 (1H, t, J = 8.1Hz), 7.83 (1H, s) , 8.20 (1H, d, J = 8.8Hz). Melting point: 8 9 ° C Example 1 7 5 -429-200300349 Brominated 1- (7- {l- (3-butoxyphenyl) -3- [ N- (3,5-difluorophenyl) -N-ethylamine formamidine 4-oxo-1,4-dihydroquinoline-7-yloxy 丨 heptyl) -1-azobicyclo [ 2.2 · 2] octane (exemplified compound number: 2-8 1 1) 7-(7 -bromoheptyloxy) -1-(3 -butoxyphenyl)- 4-O-l, 4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 193 mg, D-quinidine 6.4 mg, and acetonitrile 1 0 m 1, the reaction was carried out according to the method of Example (1 1 j) to obtain the title compound as a white solid 150 m g ο R R (CDCl3) (5ppm: 0 · 99 (3Η, t J = 7.3Hz), 1.21 (3Η, t, J = 7.3Hz), 1. 34-1.43 (6H, m), 1.46-1. 53 (2H, m), 1.65-1. 75 (4H, m), 1. 76-1. 85 (2H, m), 2.01-2.09 (6H, m), 2. 21-2.27 (1H, m), 3. 47-3. 53 (2H, m), 3.70 (6H, t, J-7.3Hz), 3.83 (2H, t, J = 6.4Hz), 3.93 (2H, q, J = 7.3Hz), 3.97-4.03 (2H, m), 6.34 (1H, d, J = 2.2Hz), 6. 60-6. 67 (1H, m), 6. 81-6. 87 (3H, m), 6. 88-6. 93 (2H, m), 7.09 (1H, dd , J = 2.2, 8.1Hz), 7.48 (1H, t, J = 8.1Hz), 7.84 (1H, s), 8.11 (1H, d, J = 9.5Hz). Melting point: 1 0 2 ° C Example 1 7 6 · 1- (8- {l- (3-butoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine 4-oxo- 1,4-dihydroquinoline-7-yloxy} octyl) -pyridine (exemplified compound number: 2-8 5 〇) 7-(8 -bromooctyl) obtained in Example (1 7 0 a) (Oxy) -1-(3 -butoxyphenyl) -4 -oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 158 mg, 2 m 1 of pyridine and 3 m 1 of N, N-dimethylformamide were reacted according to the method of Example (1 1 j) to obtain 142 mg of the title compound as a white solid. -430- 200300349 NMR (CDC13) δρριιι: 0.98 (3H, t, J = 7.3Hz), 1.20 (3H, t, J = 7.3Hz), 1.23-1.58 (8H, m), 1. 61-1. 74 (2H, m), 1. 75-1. 85 (2H, m), 1. 91-2.10 (4H, m), 3.78-3.85 (2H, m), 3.92 (2H, q, J = 7.3Hz) , 3.95-4.05 (2H, m), 4.96 (2H, t, J = 7.3Hz), 6.34 (1H, bs), 6.60-6.68 (1H, m), 6.77-6.96 (5H, in), 7.08 (1H , d, J = 7.3Hz), 7.47 (1H, t, J = 8.1Hz), 7.79 (1H, s), 8.1K2H, t, J = 7.3Hz), 8.18 (1H, d, 1 = 9.5Hz) , 8.49 (1H, t, J = 7.3Hz), 9.50 (2H, d, J = 5.9Hz). Melting point: 1 8 2 ° C Example 1 7 7 Bromide 1- {6- [3- [Ν- (3,5 · difluorophenyl) -N-ethylaminomethyl]-(3-methoxy-5-propoxyphenyl) -4 -oxo 1,4-dihydro Dquinoline-7 -Alkyloxy] -hexylb 4 -Acryl-1 -azobicyclo [2 · 2 · 2] octane (Exemplified compound number: 2-7 3 5) (177a) 7- (6-bromohexyloxy) -1- (3-methoxy-5-propoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N- Acetylamine was used to obtain the 7-transyl-1- (3-methoxy-5-propane and phenyl) _4-oxo-1,4-dihydro Dquinoline-3 obtained in Example (163b). Acid N- (3,5-difluorophenyl) -N-acetamidamine 0.74g, 1,6- Bromine hexane 1.12m 402mg potassium carbonate and N, N-dimethylformamide 2 5m 1 were reacted according to the method of Example (1 1 i) to obtain the title compound as a white foamy substance 0 · 7 8 § ° (CDCl3) 6ppm: 1.05 (3H, t, J = 7.3Hz), 1.21 (3H, t, J = 7.3Hz), 1.40-1. 52 (4H, m), 1. 70-1. 78 (2H, m), 1. 79-1. 90 (4H, m), 3.40 (2H, t, J = 6.6Hz), 3.83 (3H, s), 3.87 (2H, t, J = 6.6Hz), 3.89-3.97 (4H, m), 6.40 (1H, d, J = 2.2Hz), 6.46 (2H, d, J = 2.2Hz), 6. 6C-6. 66 (2H, m), 6.84 (2H, dd, J = 2.2, 8.1Hz), 6.90 (1H, dd, 1 = 2.2, 8.8Hz), 7.85 (1H, s), 8.2K1H, d, J-8.8Hz). 200300349 (177b) bromide 1- {6- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3-methoxy-5-propoxyphenyl) -4-oxy-1 , 4-dihydroquinoline-7-yloxy] -hexylbu 4 -acyl-1 -azobicyclo [2.2.2] octane The 7- (6-bromo) obtained in Example (1 7 7 a) Hexyloxy) -1-(3-methoxy-5 -propoxyphenyl) -4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 5-difluorophenyl ) -1 Ethylamine 24311 ^, 1,4-diazine bicyclic [2.2.2] octane 80 mg and acetonitrile 20 ml, the reaction was performed according to the method of Example (llj), and the standard was obtained The compound as a white solid 244 mg. NMR. (CDC13) δρρπι: 1.05 (3H, t, J = 7.3Hz), 1.20 (3H, t, 1 = 7.3Hz), 1.36-1. 54 (4H, m), 1. 67-1. 89 ( 6H, m), 3.24 (6H, t, J = 7.3Hz), 3. 52-3. 59 (2H, m), 3.64 (6H, t, 1 = 7.3Hz), 3.83 (3H, s), 3.85 (2H; t, J = 6.6Hz), 3.87-3.96 (4H, m), 6.39 (1H, d, 1 = 2.2Hz), 6.43 (2H, d, J = 2.2Hz), 6.60-6.66 (2H, m >, 6.83 (2H, dd, J = 2.2, 8.1Hz), 6.90 (1H, dd, J = 2.2, 9.5Hz), 7.79 (1H, s), 8.19 (1H, d, J = 8.8Hz ). Melting point: 1 3 1 ° C · Example 1 7 8 Bromide 1- {6-[3-[N-(3, 5 -difluorophenyl) -N -ethylaminomethylmethyl] -1- (3-Methoxy-5-propoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] -hexylb-methylpiperidine (Exemplified compound numbers: 2-7 3 4) The 7-(6-bromohexyloxy) -1-(3-methoxy-5 -propoxyphenyl) -4 -oxo-1,4-obtained in Example (1 7 7a) Dihydroquinoline-3 -carboxylic acid N- (3, 5-difluorophenyl) 1-acetamidine 28001, 1-methylpiperidine 49511 ^, and acetonitrile 201111, according to Example (1 1 j) method. The reaction was carried out to obtain 200 mg of the title compound as a white solid. NMR (⑶Cl3) όρριι: 1.05 (3Η, t, J = 7.3Hz), 1.2 0 (3H, t, J = 7.3Hz), 1.41-1.56 (4H, m), 1. 67-1. 98 (12H, m), 3.32 (3H, s), 3. 61-3. 75 (6H , m), 3.84 (3H, 200300349 s), 3.86 (2H, t, J = 5.9Hz), 3.88-3.97 (4H, m), 6.39 (1H, d, 1 = 2.2Hz), 6.45 (2H, d , J = 2.2Hz), 6.59-6. 66 (2H, m), 6.83 (2H, dd, J = 2.2, 8.1Hz), 6.89 (1H, dd, 1 = 2.2, 9.5Hz), 7.83 (1H, s), 8.20 (1H, d, J = 8.8Hz). Melting point: 1 1 3 ° C Example 1 7 9 Brominated l- {8- {3- {3- [N- (3,5-difluoro Phenyl) -N-ethylaminomethylmethyl] -7-methoxy-4-oxo-4H-quinolin-1-ylb 5-methoxy-phenoxy} octyl}-4 -acyl- Azobicyclo [2 · 2 · 2] octane (Exemplified compound number: 1 -4 5 0) # (179a) l- [3- (8-bromooctyloxy) -5-methoxyphenyl] -7 -Methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 1 obtained in Example (1 g) -(3-hydroxy-5 -methoxyphenyl) -7 -methoxy-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl)- N-acetamidine 135 mg, 55% sodium hydride 25. 2 mg and 1, 8-dibromooctane 612 mg. The reaction was carried out according to the method of Example (1 h) and purified. White bubble of title compound Like substance 1 4 7 mg. _ NMR (CDC13) δ ppm: 1.2K3H, t, J = 7.1Hz), 1.37-1.59 (8H, m), 1.78-1.88 (4H, m), 3.41 (2H, t, J = 6.8Hz), 3.73 (3H, s), 3.83 (3H, s), 3. 90-3. 97 (4H, m), 6.42 (1H, d, J = 2.3Hz), 6.46 (2H, d, 1 = 2.2Hz), 6.59-6. 65 (2H, m), 6.84 (2H, dd, J = 2.3, 8.1Hz), 6.92 (1H, dd, J = 2.3, 9.0Hz), 7.86 (1H, s), 8.22 (1H, d, J = 9.0Hz). (179b) Brominated 1- {8- {3- {3- [N- (3,5-difluorophenyl) -N-ethylaminemethylmethyl] -7-formyl Oxy-4-oxo- 4H -quinolin-1-ylbu 5 -methoxy-phenoxy} yangtyl} -4_ ί 气 气 双 丨 丨 [2 · 2 · 2] 半 院 -433 -200300349 The 1- [3-(8-bromooctyloxy) -5 -methoxyphenyl] methoxy-4-oxo-I, 4-dihydroquinoline obtained in Example (1 7 9 a) 144-carboxylic acid N- (3,5-diphenylphenyl) -N-acetamidamine 144mg and 1,4-diazinebicyclo [2.2.2] Xinyuan 2 5.2 mg, according to Example (1 i) The reaction was carried out in this manner to obtain 130 mg of a white foamy substance of the title compound. Wake-up R (DMS0-d6) δ ppm: 1.08 (3H, t, J = 7.1Hz), 1. 23-1.42 (8H, m), 1.60-1.78 (4H, m), 3.0K6H, t, J = 7.1 Hz), 3. 16 (2H, t, J = 8.6Hz), 3.25 (6H, t, J = 7.8Hz), 3.69 (3H, s), 3.8K3H, s), 3.81-3.85 (2H, m) , 4.02 (2H, t, J = 6.0Hz), 6.39 (1H, d, J = 2.2Hz), 6.63 (1H, d, J = 2.2Hz), 6. 65 (1H, s), 6.71 (1H, t, J = 2.0Hz), 7.0K1H, dd, J = 2.2, 8.9Hz), 7.04-7. 12 (3H, m), 8.01 (1H, d, J = 8.9Hz), 8.07 (1H, s) Example 1 8 0 3- {3- {3- {3- [N- (3,5-difluorophenyl) -N-ethylaminemethylmethyl] -7-methoxy-4-oxy- 4H-quinolin-1-yl}-5-methoxy-phenoxypropylpropyl}-1-methylpyridine mesylate (exemplified compound number: 1-2 7) (180a) l- [3 -formyl Oxy-5- (3- (pyridin-3-yl) -propoxy) phenyl] -7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- ( 3,5-Difluorophenyl) -acetamidinium 1- (3-hydroxy-5-methoxyphenyl) -7-methoxy-4-oxo-1,4-obtained in Example (lg) Dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 109 mg of N, N-dimethylformamide 20ml solution was added to the solution obtained in Reference Example 13 3-(3-bromopropyl) pyridine 1 hydrobromide 1 9 1 mg and potassium carbonate 159 mg, stirred at 70 ° C for 3 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The combined ethyl acetate layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol = 1 0/1) to obtain the title compound as a white foamy substance (128 mg). Bandit R (CDC13) (5ppm: 1.2K3H, t, J = 7.1Hz), 2. 09-2.17 (2H, m), 2.85 (2H, t, J = 7.9Hz), 3.73 (3H, s), 3.83 (3H, s), 3. 90-3. 99 (4H, m), 6.41 (1H, d, J-2.3Hz), 6.47 (2H, dt, J = 1.8, 9.0Hz), 6.58-6.65 ( 2H, m), 6.84 (2H, dd, J = 2.2, 8.1Hz), 6.92 (1H, dd, J = 2.3, 9.0Hz), 7.22-7.28 (1H, m), 7.54 (1H, dd, J = 1.7, 6.1Hz), 7.86 (1H, s), 8.22 (1H, d, J = 9.0Hz), 8.46-8.49 (2H, m). (180b) 3- {3- {3- {3- (N -(3,5-difluorophenyl) -N-ethylaminomethyl] -7-methoxy-4-oxo-4H-quinolin-1-ylb 5-methoxy-phenoxy} -Propyl}-1 -methylpyridine mesylate The 1-[3 -methoxy-5-(3-(pyridine-3 -yl) • propoxy obtained in Example (1 8 0 a) ) Phenyl] -7-methoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -1 ^ -acetamido 12511 ^ and 46.3 mg of methyl methanesulfonate was reacted in the same manner as in Example (3b) to obtain 92.0 mg of the title compound as a white foamy substance. Li R (DMSO-d6) δ ppm: 1.08 (3H, t, J = 7.1Hz), 2. 11-2. 15 (2H, m), 2.29 (3H, s), 2.96 (2H, t, 1 = 7.8Hz), 3.69 (3H, s), 3.8K3H, s), 3.83-3.86 (2H, m), 4.08 (2H, t, 1 = 6.3Hz), 4.3K3H, s), 6.39 (1H, d, J = 2.2Hz), 6.67 (2H, d, J = 7.7Hz), 6.72 (1H, t, J = 2.0Hz), 7.00 ~ 7.12 (4H, m), 8.0K1H, d, J = 8.9Hz), 8.03-8.07 (1H, m), 8.08 (1H, s), 8. 50 (1H, d, J = 8.0Hz), 8.84 (1H, d, J = 6.0Hz), 8.97 (1H, s). Implementation Example 1 8 1 4- {3- {3- {3- [N- (3,5-difluorophenyl) -1 ethylaminomethylmethyl] -7-methoxy-4 -oxy-4 H- Quinoline-1 -ylbu 5 -methoxy-phenoxybupropyl}-1 -methylpyridine mesylate (exemplified compound number: 1-2 6) 200300349 (181a) l- [3 -methoxy -5- (3- (pyridin-4-yl) -propoxy) phenyl] -7-methoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 5-Difluorophenyl) -N-acetamidine The 1- (3-hydroxy-5-methoxyphenyl) -7-methoxy-4-oxy-1,4 obtained in Example (1 g) -Dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 1 2 8 mg, 4-(3-bromopropyl) -pyridine obtained in Reference Example 12 1 228mg hydrobromide and 221mg potassium carbonate The reaction of the method of Example (180a), the white foamy substance of the title compound was obtained 148 mg (CDC13) δρριι: 1.2K3Η, t, 1 = 7.1Hz), 2.11-2.18 (2H, m), 2.83 (2H, t, J = 7.9Hz), 3.73 (3H, s), 3.83 (3H, s), 3. 91-3. 99 (4H, m), 6.42 (1H, d, J = 2.3Hz), 6.46 (1H, t, J = 2.0Hz), 6.48 (1H, t, J = 2.0Hz), 6.57-6.65 (2H, m), 6.84 (2H, dd, J = 2.2, 8.0Hz), 6.92 (lH , 'dd, J = 2.4, 9.0Hz), 7.16 (2H, d, 1 = 5.9Hz), 7.86 (1H, s), 8.22 (1H, d, J = 9.0Hz), 8.52 (2H, d, J = 5.8Hz). (181b) 4- {3- {3- {3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine 7-methoxy-4-oxy -4H-quinoline-l-yl} -5 -methoxy-phenoxy} -propyl}-1-methylpyridine mesylate φ 1- [obtained in Example (1 8 1 a)] 3 -methoxy-5-(3-(pyridine-4-yl) -propoxy) phenyl] -7 -methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 141 mg of N- (3,5-difluorophenyl) -acetamidine and 77.6 mg of mesylate were reacted according to the method of Example (3b) to obtain the title compound as a white foamy substance 9 2.0 mg. NMR (DMS0-d6) δ ppm: 1.08 (3H, t, J: 7.0 Hz), 2.12-2 · 19 (2H, m), 2.29 (3H, s), 3.05 (2H, t, J = 7.7Hz), 3.69 (3H, s), 3.81 (3H, s), 3.81-3.86 (2H, m) 5 4.07 (2H, t, J-6.2Hz), 4.27 (3H, s), 6.38 ( 1H, d, J = 2.2Hz), 6.65 (1H, s), -436-200300349 6.67 (1H, s), 6.7K1H, d, J = 2.0Hz), 7.01 (1H, dd, J = 2.2, 9.1 Hz), 7. 04-7. 12 (3H, in), 8.00-8.04 (lH, m), 8.03 (2H, d, J = 6.8Hz), 8.08 (1H, s), 8.86 (2H, d, J = 6.6Hz). Example 1 8 2 7 -methoxy- -methoxy- 5- (2- (1-oxopyrrolidin-1-ylmethyl) -benzyloxy) phenyl] -4 -Oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine (exemplified compound number: 1-9 3 6) (182a) 7- Methoxy-l- [3-methoxy- 5- (2- (pyrrolidin-1-ylmethyl) -benzyloxy) phenyl] -4 -oxo-1,4-dihydroquinoline- 3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 1- [3-(2-(bromomethyl) benzyloxy) -5 obtained in Example (1 h) -Methoxyphenylbenzene 7-methoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 497mg and pyrrole 107 mg of pyrimidine, according to the formula of Example (20a) The reaction was carried out to obtain a white foamy substance of the title compound (376 mg). … NMR (⑶Cl3) δ ppm: 1.20 (3H, t, J = 7.1Hz), 1.63-1.68 (4H, m), 2. 40_2. 45 (4H, m), 3.65 (2H, br), 3.68C3H, s), 3.82 (3H, s), 3.91 (2H, q, J-7.1Hz), 5.30 (2H, d, I = 4.4Hz), 6.38 (1H, d, J = 2.3Hz), 6.46 (1H, d, J = 1.9Hz), 6.59-6.64 (2H, m), 6.72 (1H, t, J = 2.1Hz), 6. 84 (2H, dd, J = 2.2, 8.0Hz), 6.9K1H, dd, J = 2.3, 9.0Hz), 7. 26-7. 33 (3H, m), 7. 42-7. 49 (1H, m), 7.86 (1H, s), 8.2K1H, d, J = 9.0Hz). (182b) 7-methoxy-l- [3-methoxy- 5- (2- (1-oxopyridin-1-ylmethyl) -benzyloxy) phenyl]- 4-O-l, 4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamido 7-methoxy obtained in Example (1 8 2 a) -1-[3 -methoxy-5- (2- (pyrrolidin-1-ylmethyl) -benzyloxy) phenyl] -4 -oxo-1,4-dihydro 200 300 349 quinoline-3 -Carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 123 mg and 67% m-chloroperbenzoic acid 5 4 2 mg, the reaction was carried out according to the method of Example (20 b), but 104 mg of the title compound was obtained as a white foamy substance. R (DMS0-d6) δ ppm: 1.08 (3H, t, J = 7.1 Hz), 1. 73-1. 79 (2H, m), 1.98-2.09 (2H, m), 2. 81-2 87 (1H, m), 2. 91-2. 96 (1H, m), 3. 42-3. 47 (2H, m), 3.63 (3H, s), 3.79 (3H, s), 3.80- 3.83 (2H, m), 4.52 (2H, d, J = 2.5Hz), 5.71-5.76 (1H, m), 5.88-5.93 (1H, m), 6.33 (1H, d, J = 2.2Hz), 6.59 (1H, s), 6.93 (2H, t, J = 2.2Hz), 6.97 (1H, dd, J = 2.2, 8.9Hz), 7.05-7.11 (3H, m), 7.32-7.41 (2H, m ), 7.48 (1H, dd, J = 0.8, 8.0Hz), 7.53 (1H, dd, J = 1.0, 7.3Hz), 7.99 (1H, d, J = 9.1Hz), 8.07 (lH, s). Implementation Example 1 8 3 4- [4- {3- {3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -7-methoxy-4-oxo-4H- Quinoline-l-yl} -5 -methoxy-phenoxybutylbutyl] -1 -methylpyridine mesylate (exemplified compound number: 1-3 2) (183a) 1- [3 -methoxy -5- (4- (pyridin-4-yl) -butoxy) -phenylbenzene 7-methoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 5-Difluorophenyl) -N-acetamidine The 1- [3-hydroxy-5-methoxyphenyl] -7-methoxy-4-oxy-1,4 obtained in Example (1 g) -Dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 1 6 2 mg, reference The 4- (4-bromobutyl) -pyridine 1 hydrobromide 3 300 mg and potassium carbonate 276 mg obtained in 14 were reacted according to the method of Example (18 0 a) to obtain the title compound. White foamy substance 180 mg NMR (CDC13) δ ppm: 1.2K3H, t, J-7.1Hz), 1.81-1.87 (4H, m), 2.68-2.72 (2H, m), 3.73 (3H, s), 3.82 (3H, s), 3.91-4.00 (4H, m), 6.41 (1H, d,-438-200300349 J = 2.4Hz), 6.45-6.48 (2H, m), 6.58-6.63 (2H, m), 6.83 (2H, dd, 1 = 2.2, 8.1Hz), 6.92 (1H, dd, J = 2.4, 9.0Hz), 7.14 (2H, dd, J = 1.4, 6.0Hz), 7.85 (1H, s ), 8.22 (1H, d, J = 9.1Hz), 8.50 (2H, dd, J = 1.5, 4.5Hz). (183b) 4- [4- {3- {3- [N- (3,5- Difluorophenyl) -N-ethylaminemethyl] -7-methoxy-4-oxo-4H-quinolin-1-ylb 5-methoxy-phenoxy} -butyl] -1 -Mepyridine mesylate The 1- [3-methoxy-5-(4- (pyridin-4-yl) -butoxy) -phenyl]-obtained in Example (1 8 3 a)- 7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 173mg and methyl methanesulfonate Book 1 0 3 mg, the reaction was carried out according to the method of Example (3 b), and the title compound was obtained in white color. Substance 1 5 0 m g. NMR (DMS0-d6) δ ppm: 1.08 (3H, t, J = 7.0Hz), 1.72-1.86 (4H, in), 2.29 (3H, s), 2.95 (2H, t, J = 7.0Hz), 3.69 (3H, s), 3.8K3H, s), 3.81-3.86 (2H, m), 4.06 (2H, t, J = 5.8Hz) ,: 4.27 (3H, s), 6.39 (1H, d, J = 2.2Hz), 6.65 (2H, s), 6.72 (1H, t, J = 2.0Hz), 7.01 (1H, dd, J = 2.4, 9.2Hz), 7.01-7.12 (1H, m), 7.11 (2H, dd, J = 1.8, 8.5Hz), 8.0K2H, d, J-6.0Hz), 8.01-8.04 (1H, m), 8.08 (1H, s), 8.85 (2H, d, J = 6.5Hz). Implementation Example 1 8 4 φ 3- {4- {3- {3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -7-methoxy-4-oxo-4H -Quinoline-1-ylbu 5 -methoxy-phenoxybubutylbu 1-methylpyridine mesylate (exemplified compound number: 1-3 3) (184a) l- [3-methoxy- 5- (4- (D than hydradin-3-yl) -butoxy) -benzyl] _7_methoxy-4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- ( 3,5-difluorophenyl) -N-acetic acid, 1- [3-hydroxy-5-methoxyphenyl] -7-methoxy-4-oxo-1 obtained in Example (1 g) 3,4-Dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N- -439-200300349 Acetamide 1 9 2 mg, 3-(4- Bromobutyl) -Ladine 1 Hydrobromide 550mg and 442 mg of potassium carbonate was reacted in accordance with the method of Example (180a) to obtain the title compound as a white foamy substance 197 mg ο NMR (CDC13) δρρπ: 1.2K3H, t, J = 7.1Hz), 1.80-1.88 ( 4H, m), 2.7K2H, t, J = 6.9Hz), 3.73 (3H, s), 3.82 (3H, s), 3. 90-4. 01 (4H, in), 6.4K1H, d, J = 2.0Hz), 6.45 (1H, t, J = 1.7Hz), 6.47 (1H, s), 6.58-6.65 (2H, m), 6.84 (2H, dd, J = 1.6, 7.8Hz), 6.92 (1H , dd, J = 2.0, 9.0Hz), 7. 22 (1H, dd, J = 4.8, 7.7Hz), 7.53 (1H, dd, J = 1.3, 7.9Hz), 7.85 (1H, s), 8.22 ( 1H, d, J = 8.9Hz), 8.45 (1H, d, J = 4.9Hz), 8.48 (1H, s). (184b) 3- {4- {3- {3- [N- (3,5 -Difluorophenyl) -N-ethylaminomethylmethyl] -7-methoxy-4-oxo-4H-quinolin-1-yl} -5 -methoxy-phenoxy} -butyl}- 1-methylpyridine mesylate The 1- [3 -methoxy-5-(4-(pyridine-3 -yl) -butoxy) -phenylbenzene 7 obtained in Example (1 84 a) 7 -Methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 194 mg and methyl methanesulfonate 1 2 5 mg, and reacted according to the method of Example (3b) to obtain 199 mg of the title compound as a white foamy substance. NMR (DMS0-d6) (5 ppm: 1.08 (3H, t, J = 7.0Hz), 1.77 ~ 1. 85 (4H, m), 2.29 (3H, s), 2.87 (2H, t, J = 7. 1Hz), 3.69 (3H, s), 3.8K3H, s), 3.81 ~ 3.86 (2H, m), 4.06-4.09 (2H, m), 4.3K3H, s), 6.38 (1H, d, J = 2.2Hz ), 6.65 (1H, s), 6.66 (1H, s), 6.72 (1H, t, J = 2.0Hz), 7.0K1H, dd, J = 2.2, 9.0Hz), 7.02-7.10 (1H, m), 7.10 (2H, dd, J = 2.2, 9.0Hz), 8.0K1H, d, J = 9.0Hz), 8. 01-8.06 (1H, m), 8.08 (1H, s), 8.47 (1H, d, J = 8.0Hz), 8.84 (1H, d, J = 6.0Hz), 8.95 (1H, s). Example 1 8 5 -440- 200300349 1- {7- {3- [Ν- (3,5- 二Fluorophenyl) -N-ethylaminomethylmethyl] -1- (3-ethoxy-5 -methoxyphenyl) -4 -oxo 1,4-dihydroquinoline-7 -yloxy 丨 heptyl } • 4 -Acryl-1 -azobicyclo- [2.2.2] -octane bromide (exemplified compound number: 2-7 8 4) (185a) l- (3 -benzyl-5-methoxy Phenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid methyl ester The 3-dimethylamino-2 obtained in Example (104 d) -(2 -methoxy-4 -methoxymethoxybenzyl) -methyl acrylate 6.46 g of N, N -dimethylformamide solution 1 2 0 m 1, potassium carbonate 5.29 and reference From Example 1 3 - benzyloxy-5 - methoxy aniline 4 · 6 8 g, was stirred at 9 0 ° C 1 hour and then stirred at 1 4 0 ° C 1 hour. The reaction solution was added with dilute hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was combined, washed with water and saturated brine, and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The solid was collected by filtration, washed with diisopropyl ether, and dried to obtain the title compound as a white solid 8.35 g. R. (CDCl3) 6 ppm: 3.43 (3H, s), 3.83 (3H, s), 3.92 (3H, s), 5.08 (2H, s), 5.14 (2H, s), 6.44 (1H, d, J = 2.3Hz), 6.56 (1H, t, J = 2.0Hz), 6.63 (1H, t, ❿ J = 2.0Hz), 6.67 (1H, d, J = 2.2Hz), 7.13 (1H, dd, J = 2.3, 9.0Hz), 7. 34-7.45 (5H, m), 8.47 (1H, d, J = 8.9Hz), 8.50 (1H, s). (185b) l- (3-benzyloxy-5-methoxyphenyl) -7-methoxymethoxy-- 4 -oxy-1,4- Dihydroquinoline-3 -carboxylic acid The 1- (3-benzyloxy-5-methoxyphenyl) obtained in Example (185a) _7_methoxymethoxy-4 -oxy-1,4-dihydro 8.35 g of methyl quinoline-3-carboxylic acid and 2.81 g of sodium hydroxide were reacted according to the method of Example (1e) to obtain 7.85 g of the title compound as a white solid. -441-200300349

Ml, (CDC13) δρριη: 3.44 (3H, s), 3.84 (3H, s), 5.09 (2H, s), 5.17 (2H, s), 6.55 (1H, d, J = 2.2Hz), 6.63 (1H t, J = 1.5Hz), 6.74 (1H, s), 6.80 (1H, t, J = 1.0Hz), 7.28-7.43 (6H, m), 8.48 (1H, d, J = 9.1Hz), 8.75 (1H, s). (185c) l- (3-benzyloxy-5-methoxyphenyl) -7-methoxymethoxy- 4-oxo-1,4-dihydroquinoline-3-carboxyl The acid N- (3,5-difluorophenyl) fluorenamine will be the 1- (3-benzyloxy-5 -methoxyphenyl) -7-methoxymethoxy obtained in Example (185b) ... 4- 7.85 g of oxygen-1,4-dihydroquinoline-3-carboxylic acid and 7. 1 m of N, N-dimethylformamide solution of 1.2 m 1 were added under ice cooling with isochlorochloroformate Butyl ester 2.5 ml 1, stirred for 10 minutes, then added 3,5-difluoroaniline 9.28 g, and stirred at 70 ° C for 1.5 hours. The reaction solution was added with dilute hydrochloric acid, extracted with ethyl acetate, and the ethyl acetate layer was combined, followed by washing with water, a saturated aqueous sodium hydrogen carbonate solution and a saturated saline solution, and drying over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: dichloromethane / ethyl acetate = 2/1) to obtain 8.02 g of the title compound as a white solid. NMR. (CDCI3) (5ppm: 3.44 (3H, s), 3.84 (3H, s), 5.09 (2H, s), 5.17 (2H, s), 6.57 (1H, t, J = 2.0Hz), 6.65 ( 1H, t, J-2.1Hz), 6.73 (1H, t, J = 2.2Hz), 6.78 (1H, d, J-2.2Hz), 7.23 (1H, dd, J = 2.2, 9.0Hz), 7.36- 7.45 (8H, m), 8.48 (1H, d, 1 = 9.0Hz), 8.83 (1H, s). (185d) l- (3-benzyloxy-5-methoxyphenyl) -7-methoxy Methoxy_4_oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 1 obtained from Example (1 8 5 c) -(3-benzyloxy-5 -methoxyphenyl) -7 -methoxymethoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 5 -difluoro 8.02 g of phenyl) fluorenamine in 120 ml of Ν, Ν-dimethylformamide solution, and under ice cooling, 1.25% of 55% sodium hydride was added. After stirring for 10 minutes, iodoethyl 200300349 was added. 50 g, stirred for 1.5 hours at 60 ° C. The reaction solution was added with dilute hydrochloric acid, extracted with ethyl acetate, combined with the ethyl acetate layer, washed sequentially with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (eluent ·· dichloromethane / ethyl acetate = 1/2) to obtain the title compound as a pale yellow foam. Quality 7. 30 g ° · R. (CDC13) (5ppm: 1.2K3H, t, J = 7.2Hz), 3.4K3H, s), 3.82 (3H, s), 3.93 (2H, q, J = 7.1 Hz), 5.07 (2H, s), 5.1K2H, s), 6.49 (1H, t, J = 2.0Hz), 6.57 (1H, t, J = 2.1Hz), 6.62 (2H, d, J = 2.1Hz ), 6.69 (1H, t, J = 2.2Hz), 6.84 (2H, dd, J = 2.3, 8.2Hz), 7.04 (1H, dd, J = 2.2, 9.0Hz), 7.33-7.45 (5H, m) , 7.88 (1H, s), 8.22 (1H, d, J = 9.0Hz). (185e) l- (3-hydroxy-5-methoxyphenyl) -7-methoxymethoxy-4-oxy- 1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 1- (3-benzyloxy) obtained in Example (18 5 d) -5 -methoxymethoxy) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3, 5-difluorophenyl) -N-ethyl 7.30 g of amidine and 10% of Pd-C2.0 g were reacted according to the method of Example (lg) to obtain 5.7 1 g of the title compound as a white solid. NMR (CDC13) (5ppm: 1.16 (3H, t, J = 7.2Hz), 3.39 (3H, s), 3.8K3H, s), 3.82-3.91 (2H, m), 5.08 (2H, s), 6.18 ( 1H, t, J = 1.9Hz), 6.38 (1H, t, J = 2.0Hz), 6.60 (2H, d, J-2.2Hz), 6.6K1H, t, J = 2.2Hz), 6.8K2H, dd, J = 1.8, 7.4Hz), 6.99 (1H, dd, J = 2.1, 9.1Hz), 8.13 (1H, s), 8.13-8.16 (1H, m). (185f) l- (3-ethoxy- 5-methoxyphenyl) -7-methoxymethoxy- 4-oxo-1,4-dihydroquinoline · 3-carboxylic acid N- (3,5-difluorophenyl) -N -acetamidine The 1- (3-hydroxy-5-methoxyphenyl) -7-200300349 obtained from Example (1 8 5e) was used as the amine. The methoxymethoxy-4-oxy-1,4-dihydroquinoline-3 -Carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 2.02g of Ν, Ν-dimethylformamide solution 40ml, and 55% sodium hydride 3 4 6 mg was added under ice cooling After stirring for 10 minutes, 2.47 g of iodoethyl was added, and the mixture was stirred at 60 ° C for 1 hour. The reaction solution was added to dilute hydrochloric acid, extracted with ethyl acetate, and the ethyl acetate layer was combined, washed with water and saturated brine in this order, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: dichloromethane / ethyl acetate = 1/2) to obtain the title compound as a white foamy substance (2.1 g). Li R (CDC13) δρρπι: 1.2K3Η, t, J = 7.1Hz), 1.44 (3H, t, J = 7.0Hz), 3.4K3H, s), 3.82 (3H, s), 3.93 (2H, q, J = 7.2Hz), 4.03 (2H, q, J = 7.3Hz), 5.07 (2H, s), 6.46 (2H, d, J = 2.2Hz), 6.60 (1H, t, J = 2.1Hz), 6.63 ( 2H, d, J = 2.0Hz), 6.84 (2H, dd, J = 2.2, 8.1Hz), 7.04 (1H, dd, J = 2.2, 9.0Hz), 7.88 (1H, s), 8.22 (1H, d , 8.9Hz). (185§) 1- (3-ethoxy-5-methoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- ( 3, 5-difluorophenyl) -N-acetamidine 1- (3-ethoxy-5-methoxyphenyl) -7-methoxymethoxy-4-obtained in Example (185f) Oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 2. 0 1 g of ethyl acetate solution 8 ml 1 and 4 NHC added 1-ethyl acetate solution 20 m 1, and stirred at room temperature for 2 hours. The solid was collected by filtration, washed with ether, and dried to obtain 1.72 g of the title compound as a white solid. NMR (CDC13) δ ppm: 1.29 (3H, t, J = 7.2Hz), 1.42 (3H, t, J = 6.8Hz ), 3.81 (3H, s), 3.96-4 · 07 (4Η, m), 6.26-6 · 37 (2Η, m), 6.60 (1Η, d, J = 1.0Hz), 6.80 -6.86 (2H, m), 6.97-7.07 (2H, m), 7.58 (1H, d, J = 8.3Hz), 7.71 (1H, d, J = 1.3Hz), 8.20 (1H, d, 1 = 1.6 Hz). -444- 200300349 (185h) 7- (7-bromoheptyloxy) -1- (3-ethoxy-5-methoxyphenyl) -4-oxo-1,4-dihydroquinoline -3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 1- (3-ethoxy-5-methoxymethoxy) obtained in Example (1 8 5 g) -7-Hydroxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 5 1 0 mg, 1, 7-di Bromine heptane 1.81 g and 55% sodium hydride 90 mg were reacted according to the method of Example (1 h) to obtain the title compound as a white foamy substance 5 48 mg. Rei R (CDC13) δρριη: 1.2Κ3Η, t, J = 7.1Hz), 1. 32-1.48 (6H, m), 1.44 (3H, t, J = 7.2Hz), 1. 69-1.76 (2H, m ), 1.81-1.88 (2H, m), 3.40 (2H, t, J = 6.7Hz), 3.83 (3H, s) 5 3.86 (2H, t, J = 6.4Hz), 3.93 (2H, q, J = 7.2Hz), 4.04 (2H, q, J = 6.7 Hz), 6.40 (1H, d, J = 2.2Hz), 6.46 (2H, d, J = 2.1Hz), 6.60-6.63 (2H, m), 6.84 (2H, dd, J = 2.1, 8.0Hz), 6.9K1H, dd, J = 2.2, 9.2Hz), 7.85 (1H, s), 8.22 (1H, d, J = 9.0Hz). 185i) 1- {7- {3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3-ethoxy-5-methoxyphenyl ) -4 -oxo 1,4-dihydroquinoline-7-yloxy} heptylbu 4 -acyl-1 -azobicyclo- [2.2.2] -octane Example (1 8 5 h) The obtained 7- (7-bromoheptyloxy) -1- (3-ethoxy-5-methoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- ( 125 mg of 3,5-difluorophenyl) -N-acetamidine and 1,4-diazinebicyclo [2.2.2] octane 2 1.0 mg. The reaction was carried out according to the method of Example (1 i). 1 3 2 mg of the title compound was obtained as a white solid. Li R (DMS0-d6) δ ppm: 1.08 (3H, t, J = 7.1Hz), 1. 26-1. 36 (6H, m), 1.34 (3H, t, J-7.1Hz), 1.61-1.69 (4H, m), 3.0K6H, t, J = 7.2Hz), 3.15 (2H, dd, J-8. 6, 11.0Hz), 3.24 (6H, t, J = 7.9Hz), 3.8K3H, s) , 3. 81-3. 85 (2H, m), 3.89 (2H, 200300349 t, 1 = 6.2Hz), 4.08 (2H, q, J = 7.0Hz), 6.36 (1H, d, J = 2.1Hz) , 6.62 (2H, d, 1 = 1.5Hz), 6.73 (1H, t, J = 2.2Hz), 6.99 (1H, dd, J = 2.3, 9.1Hz), 7. 04-7.10 (1H, m), 7.11 (2H, dd, J = 2.0, 8.6Hz), 8.00 (1H, d, J = 8.9Hz), 8.08 (1H, s).

Melting point: ~ 1 3 4 ° C Example 1 8 6 1- {7- {3- [N- (3,5-difluorophenyl) -N-ethylaminemethylmethyl] -1- (3 -Ethoxy-5-methoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7-yloxy} heptyl} -pyridine (exemplified compound number: 2-7 8 2) will 7-(7 -bromoheptyloxy) -1-(3-ethoxy-5-methoxyphenyl) -4 -oxo-1,4-dihydroquinoline obtained in Example (1 8 5 h) -3 -Carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 139 mg and pyridine D 32.7 mg, the reaction was carried out according to the method of Example (1 i) to obtain the title compound as a white solid 103 mg mgR (DMS0-d6) δ ppm: 1.08 (3H, t, 1 = 7.0Hz), 1.27-L36 (6H, m), 1.33 (3H, t, J = 7.0Hz), 1.60- 1.66 (2H, m), 1.86-1.93 (2H, m), 3.80 (3H, s), 3.81-3.86 (2H, m), 3.88 (2H, t, J = 6.2Hz), 4.07 (2H, q, J = 7.0Hz), 4.58 (2H, t, J = 7.3Hz), 6.34 (1H, d, 1 = 2.1Hz), 6.62 (2H, s), 6.72 (1H, t, 1 = 2.1 Hz), 6.98 (1H, dd, J = 2.2, 8.9Hz), 7.05-7. 10 (1H, m), 7.10 (2H, dd, J = 2.0, 8.6Hz), 8.00 (1H, d, J = 8.9Hz) , 8.07 (1H, s)? 8.16 (2H, t, J = 7.5Hz), 8.60 (1H, t, J = 7.9Hz), 9.08 (2H, d, 1 = 5.6Hz). Melting point: ~ 1 0 6 ° C Example 1 8 7卜 {7- {3- [N- (3,5-difluorophenyl) -1 ethylaminomethyl] -l- (3-ethoxy-5-methoxyphenyl) -4 -oxo -1,4-dihydroquinoline-7-yloxy} heptyl 丨 -pazobicyclo [2 · 2.2] octane (Exemplified compound number: 2-7 8 3) -446- 200300349 Examples ( 1 8 5 h) of 7-(7 -bromoheptyloxy) -1-(3-ethoxy-5-methoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3- 132 mg of carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine and 24.0 mg of eyeidine were reacted according to the method of Example (1 i) to obtain the title compound as a white solid 1 3 8 mg . Wake-up R (DMS0-d6) δ ppm: 1.08 (3H, t, J = 7.1Hz), 1. 22-1. 36 (6H, m), 1.34 (3H, t, 1 = 7.1Hz), 1. 58 -1. 69 (4H, m), 1. 80-1. 86 (6H, m), 2. 04-2. 07 (1H, m), 3. 03-3. 07 (2H, m), 3 30-3. 36 (6H, m), 3. 81 (3H, s), 3. 81-3. 85 (2H, m), 3.89 (2H, .t, J = 6.3Hz), 4.08 (2H , q, J = 7.0Hz), 6.35 (1H, d, J = 2.1Hz), 6.62 (2H, s), 6.73 (1H, Φ t, J = 2.1Hz), 6.99 (1H, dd, 1 = 2.2 , 9.2Hz), 7,05-7.10 (1H, m), 7.1K2H, dd, J = 2.1, 8.6Hz), 8.00 (1H, d, J = 9.0Hz), 8.08 (1H, s). '' Melting point : ~ 1 3 2 ° C Example 1 8 8 Bromide 1- {8- {3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine 1- (3-ethyl Oxy-5-methoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy} octylb 4-az-1-azobicyclo [2.2.2] octane ( Exemplified compound number: 2-8 3 8) · (188a) 7- (8-bromooctyloxy) -1- (3-ethoxy-5-methoxyphenyl) -4 -oxy-1,4- Dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N · acetamidine The 1- (3 -ethoxy-5 -formaldehyde) obtained in Example (1 8 5 g) (Oxyphenyl) -7-hydroxy-4 -oxy-1,4-dihydroquinoline-3 -carboxylic acid N-(3,5-difluorophenyl) -N -acetamidamine 4 5 2 mg, 1, 8-dibromooctane 1.99 g, and 55% sodium hydride 119 mg were reacted according to the method of Example (1 h) to obtain the title compound as a white foamy substance. 5 0 5 mg. -447-200300349 area R (CDC13) δρριη: 1.21 (3H, t, J = 7.0Hz), 1.30-1 · 46 (8Η, m), 1.44 (3Η, t, J = 7.1Hz), 1.68-1.75 (2H, m), 1.81-1.88 (2H, m), 3.40 (2H, t, J = 7.0Hz), 3.83 (3H? S), 3.86 (2H, t, J = 6.5Hz), 3.93 (2H, q, J = 7.2Hz), 4.04 (2H, q, 1 = 6.4 Hz), 6.40 (1H, d, J = 2.2Hz), 6.46 (2H, d, J = 2.0Hz), 6.60- 6.66 (2H, m), 6.84 (2H, dd, J = 2.1, 8.0Hz), 6.9K1H, dd, J = 2.2, 8.9Hz), 7.85 (1H, s), 8.22 (1H, d, J = 9.0 Hz). (188b) bromide l- {8- {3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -l- (3-ethoxy-5- Methoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy} octylbu 4-azine-1-azobicyclo [2.2.2] octane Example (1 8 8 a) 7- (8-Bromooctyloxy) -1-(3-ethylφoxy-5-methoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxyl Acid N- (3,5-difluorophenyl) -N-acetamidine 120 mg and 1,4-diazinebicyclo [2.2.2] octane 2 1.6 mg, according to the method of Example (1 i) The reaction was performed to obtain 3 mg of the title compound as a white solid. Bandit R (DMS0-d6) δ ppm: 1.08 (3H, t, J = 7.1Hz), 1. 25-1. 38 (8H, m), 1.34 (3H, t, J = 7.0Hz), 1. 63 -1.67 (4H, m), 3.0K6H, t, J = 7.1Hz), 3.12-3.16 (2H, m), 3.24 (6H, t, J = 7.8Hz), 3.80 (3H, s), 3. 80 -3. 85 (2H, m), 3.89 (2H, t, J = 6.4Hz), 4.08 (2H, q, J = 7.0Hz), 6.35 (1H, d, J = 2.2Hz), 6.62 (2H, d, J ^ l.OHz), 6.72 (1H, φ t, J-2.1Hz), 6.98 (1H3 dd, J-2.1, 8.9Hz), 7. 04-7. 10 (1H, m), 7. 11 (2H, dd, J = 2.0, 8.7Hz), 8.00 (1H, d, J = 9.0Hz), 8.08 (1H, s). Melting point: ~ 1 2 8 ° C Example 1 8 9 Bromination 1- {8- {3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine 1- (3-ethoxy-5-methoxybenzyl) -4-oxy -1,4 -monoaminopyridine-7-yloxy} octylbu 1-azobicyclo [2 · 2.2] octane (exemplified compound number: 2-8 3 7) Example (1 8 8 a) The obtained 7- (8-bromooctyloxy) -1- (3-ethyl-448-200300349oxy-5-methoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -Carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 126 mg, 13 quindine 22.9 mg, the reaction was carried out according to the method of Example (1 i), and the title compound was obtained as a white solid 130 mg ° circle R (DM S0-d6) δ ppm: 1.08 (3H, t, J = 7.1Hz), 1. 21-1. 36 (8H, m), 1.34 (3H, t, J = 7.1Hz), 1. 57-1. 66 (4H, m), 1. 81-1.86 (6H, m), 2. 04-2. 07 (1H, m), 3. 03-3. 07 (2H, m), 3.3〇-3.38 (6H , m), 3.80 (3H? s), 3. 80-3. 85 (2H, m), 3.89 (2H, t, J = 6.3Hz), 4. 08 (2H, q, J = 7.0Hz), 6.35 (1H, d, J = 2.2Hz), 6.62 (2H, s), 6.72 (1H, t, J = 2.1Hz), 6.99 (1H, dd, J = 2.2, 8. 9Hz >, 7. 04-7.10 (1H, m), 7.1K2H, dd, J = 2.0, 8.6Hz), 8.00 (1H, d, J = 8.9Hz), 8.08 (1H, s). Melting point: ~ 1 2 5 ° C Implementation Example 1 9 0 1- {8- {3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3-ethoxy-5-methoxy Phenyl) -4_oxy-I, 4-dihydroquinoline-7-ylbusinyl} -pyridine (exemplified compound number: 2-8 3 6) 7 obtained from Example (1 8 8 a) -(8 -bromooctyloxy) -1-(3-ethoxy-5 -methoxyphenyl) -4 -oxo-I, 4-dihydroquinoline-3 -carboxylic acid N- (3,5 -Difluorophenyl) -N-acetamidine 120 mg and pyridine 27.3 mg 'were reacted according to the method of Example (Π) to obtain 97.0 mg of the title compound as a white foamy substance. Circle R (DMS0-d6) δ ppm: 1.08 (3H, t, J = 7.0Hz), 1. 27-1. 34 (8H, m), 1.33 (3H, t, J = 7.0Hz), 1.60-1.66 (2H, m), 1.88-1.93 (2H, m), 3.80 (3H, s), 3.80-3.85 (2H, m), 3.88 (2H, t, J = 6.4Hz), 4.07 (2H, q, J = 7.0Hz), 4.58 (2H, t, J-7.4Hz), 6.35 (1H, d, J = 2.2Hz), 6.62 (2H, s), 6.72 (1H, t, J = 2.0Hz), 6.98 ( 1H, dd, J-2.1, 8.9Hz), 7. 04-7. 10 (1H, m), 7. 10 (2H, dd, J-1.6, 8.3Hz), 8.00 (1H, d, 200300349 J = 9.0Hz), 8.07 (1H, s), 8.16 (2H, t, J = 7.0Hz), 8.60 (1H, t, J = 7.0Hz), 9.08 (2H, d, J = 5.9Hz). Example 1 9 1 l- {7- {3- [N- (3,5-difluorophenyl) -1 ^ -ethylaminomethylmethyl] -l- (3-ethoxy-5-propoxybenzene ) -4_oxo-l, 4-dihydroquinolin-7-yloxy} heptylbu 4 -acyl-1 -azobicyclo [2 · 2 · 2] octane (Exemplified compound number: 2- 7 8 8) (191a) l- (3-benzyloxy-5-propoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid methyl ester The ester was 5.72 g of 3-dimethylamino-2-(2-methoxy-4 -methoxymethoxy-benzyl) -methyl acrylate and 4.97 potassium carbonate obtained in Example (104 d). g. 3-Benzyloxy-5 -propoxybenzene obtained in Reference Example 10 5.01g 'by of Example (1 8 5 a) of the method of reaction, to give the title compound as a white solid of 7.73g. NMR, (CDC13) δρριη: 1.04 (3H, t, J = 7.5Ez), 1. 78-1.87 (2H, m), 3. 43 (3H „s), 3.91-3.95 (2H, m), 3.93 (3H, s), 5.07 (2H, s), 5.14 (2H, s), 6.56 (1H, t, J = 1.9Hz), 6.62 (1H, t, J = 1.7Hz), 6. 66-6. 71 (2H, m), 7.13 (1H, dd, J = 2.2, 8.8Hz), 7.34-7.43 (5H, in), 8.47 (1H, d, J = 8.9Hz), 8.5K1H, s). (191b ) l- (3-benzyloxy-5-propoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid Example (1 9 1 a) 7.73 g of methyl 1- (3-benzyloxy-5-propoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid obtained And sodium hydroxide 1.84 g, and reacted according to the method of Example (1 e) to obtain the title compound as a white solid 7.18 g -450- 200300349 (R) (CDC13) δρρίϋ: ι.〇4 (3Η, t , J = 7.4Hz), 1. 78-1. 87 (2Η, m), 3.44 (3Η, s), 3. 89-3. 97 (2Η, m), 5.08 (2H, s), 5.17 (2H , s), 6.55 (1H, t, J = 2.0Hz), 6.61 (1H, t, J = 2.0Hz), 6.74 (1H, t, J = 2.2Hz), 6.81 (1H, d, J = 2.2Hz ), 7.25-7.28 (1H, m), 7.34-7.44 (5H, m), 8.47 (1H, d, J = 9.2Hz), 8.75 (1H, s). (191c) l- (3-benzyloxy -5_propoxyphenyl) -7-methoxymethoxy-4 Oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) fluorenamine The i_ (3-benzyloxy-5) obtained in Example (1 9 1 b) -Propoxyphenyl) -7-methoxymethoxy-4 -oxo, hydrazone, 4-dihydroquinoxaline · 3-18 residual acid 7.18 g, triethylamine 4.45 g, isobutyl chloroformate 2.21 g and 7.58 g of 3,5-difluoroaniline was reacted according to the method of Example (1 8 5 c) to obtain 7.43 g of the title compound as a white solid. NMR (CDC13) δ ppm: 1.04 (3H, t, J = 7.4 Hz), 1.78-1. 87 (2H, m), 3.45 (3H, s), 3.91-3.95 (2H, m), 5.08 (2H, s), 5.17 (2H, s), 6.52-6.57 (2H, m), 6.73 (1H, t, J = 2.1Hz), 6.79C1H, d, 1 = 2.2Hz), 7.23 (1H, dd, J = 2.2, 9.2Hz), 7.34-7.45 (8H, m), 8.48 C1H, d, J = 8.9Hz), 8.83 (1H, s). (191d) l- (3-benzyloxy-5-propoxyphenyl) -7-methoxymethoxy-4-4-oxo-1 1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 1- (3-benzyloxy- 5-propoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline 3-carboxylic acid N- (3,5-difluorophenyl) amidine 7.43 g, 1.05g of 55% sodium hydride and 7.49g of iodoethyl, according to the method of Example (1 8 5 d) By reaction, 7.62 g of the title compound was obtained as a pale yellow foamy substance. ^ NMR (CDC13) δρριη: 1.04 (3H, t, J = 7.4Hz), 1.2K3H, t, J = 7.〇Hz), 1.78-1.87 (2H, m), 3.4K3H, s), 3.90-3.96 (4H, m), 5.06 (2H, s), 5.11 (2H s) -451- 200300349 6.48 (1H, d, J = 2.0Hz), 6.55 (1H, t, J = 2.0Hz), 6.57-6.69 ( 1H, m), 6.64 (1H, d, J = 2.2Hz), 6.68 (1H, d, J = 2.1Hz), 6.84 (2H, dd, J-2.1, 8.0Hz), 7.05 (1H, dd, J = 2.1, 8.9Hz), 7.33-7.45 (5H, m), 7.89 (1H, s), 8.23 (1H, d, 1 = 8.9Hz). (191e) l- (3-hydroxy-5-propoxybenzene Group) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N · (3,5-difluorophenyl) -N-acetamidine 191d) 1- (3-benzyloxy-5-propoxyphenyl) -7-methoxymethoxy-4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3 , 5-difluorophenyl) -N-acetamidamine 7.62g and 10% Pd-C2.0g, the reaction was carried out according to the method of Example (lg), to obtain 6.25g of the title compound as a white solid. NMR (CDC13) δρριη: 1.03 (3H, t, J = 7.5Hz), 1.16 (3H, t, J = 7.1Hz), 1.76-1.84 (2H, m), 3.39 (3H, s), 3.85-3.92 ( 4H, m), 5.08 (2H, d, J = 4.8Hz), 6.2K1H, s), 6.33 (1H, d, J = 1.9Hz), 6.53-6.65 (3H, m), 6.82 (2H, dd, J = 2.0, 7.9Hz), 7.00 (1H, dd, J = 2.1, 8.9Hz), 8.13 (1H, s), 8.14 (1H, d, J = 9.0Hz). (191f) l- (3 -B Oxy-5-propoxyphenyl) -7-methoxymethoxy-4 -oxy-1,4 · dihydroquinoline-3 -carboxylic acid N- (3, 5-difluorophenyl) -N -Acetylamine 1- (3-hydroxy-5-propoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3 obtained in Example (191e)- Carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 2.18 g, 55% sodium hydride 353 mg, and iodoethyl 2.56 g. OO 1 g of the title compound was obtained as a foamy substance. NMR (CDCl3) 5ppm: 1.05 (3H, t, J = 7.5Hz), 1.2K3H, t, J = 7.2Hz), 1.43C3H, t, J = 7.1Hz), L 78-1.87 (2H, m), 3.4K3H, s), 3.90-3.96 (4H, m), 4.03 (2H, q, J = 6.8Hz), 5.11 (2H, s), 6.44 (2H, d, J = l. 4Hz), 6. 59 (1H, t, J = 2.2Hz), 6.59-6.68 (lH, m), 6.64 (1H, d, J = 2.2Hz), 6.84 (2H, dd, 1 = 2.2, 8.0Hz), 7.04 (1H, dd, J = 2.2, 8.9Hz), 7.89 (1H, s), 8.23 (1H, d, 9.1Hz). -452- 200300349 (191g) l- (3-ethoxy-5-propoxyphenyl) -7-Hydroxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 1- obtained in Example (191f) (3-ethoxy-5-propoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorobenzene 2.01 g of N-acetamidine and 10 ml of 4NHC1-ethyl acetate solution, and the reaction was carried out according to the method of Example (185 g) to obtain 1.84 g of the title compound as a white solid. NMR.. (CDC1S) δρριι: 1.04 (3H, t, J = 7.4Hz), 1.29 (3H, t, J = 7.1Hz), 1.42C3H, t, J = 6.7Hz), 1.76-1.85 (2H, m ), 3.89 (2H, t, J = 6.3Hz), 4.0K4H, q, J = 7.2Hz), 6.26C1H, s), 6.30 (1H, s), 6.59 (1H, s), 6.76-6.81 (2H , m), 7.03 (2H, s), 7.59-7.64 (1H, m), 7.74 (1H, s), 8.20 (1H, dd, J = 3.5, 8.9Hz). (191h) 7- (7-Br Heptyloxy) -1- (3-ethoxy-5-propoxyphenyl) -oxy-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl)- N-acetamidine The 1- (3-ethoxy-5-propoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid obtained in Example (191g) N- (3,5-difluorophenyl) -N-acetamidine 691 mg, 55% sodium hydride 183 mg, and 1,7-dibromoheptane 1.8 1 g were carried out according to the method of Example (1 h) By reaction, 720 mg of the title compound was obtained as a white foamy substance. NMR (CDC13) (5ppm: 1.05 (3H, t, J = 7.4Hz), 1.2K3H, t, J = 7.1Hz), 1.32-1. 50 (6H, m), 1.44 (3H, t, J = 7.0 Hz), 1. 72-1. 78 (2H, m), 1. 80-1. 90 (4H, m), 3.39 (2H, t, 1 = 6.7Hz), 3.86 (2H, t, J = 6.5 Hz), 3.93 (4H, q, J = 7.2Hz), 4.03 (2H, q, J = 7.4Hz), 6.4K1H, d, J = 2.4Hz), 6.44 (2H, t, J = 1.9Hz), 6. 59-6.65 (2H, m), 6.84 (2H, dd, J = 2.3, 8.9Hz), 6.90 (1H, dd, J = 2.3, 9.0Hz), 7.84 (1H, s), 8.20 ( 1H, d, J = 8.8Hz). (191i) bromide l- {7- {3- [N- (3,5-difluorophenyl) -1 ethylamine-453-200300349 methylfluorenyl] -1 -(3 -ethoxy-5-propoxyphenyl) -4 -oxo-1,4 -dihydroquinoline · 7 -yloxy} heptylbu 4 -acyl-1 -azobicyclo [2.2 · 2] Octane uses the 7- (7-bromoheptyloxy) -1-(3-ethoxy-5 -propoxyphenyl) -oxy-1,4 -di obtained in Example (19.1 h) Hydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N acetamidine 181mg and 1,4-diazinebicyclo [2 · 2 · 2] octane 3 1.9 mg, according to The reaction of Example (1i) was carried out to obtain 187 mg of the title compound as a white solid. NMR. (DMS0-d6) δρριη: 0.98 (3H, t, J = 7.4Hz), 1.08 (3H, t, J = 6.9Hz), 1.26-1.36 (6H, m), 1.33 (3H, t, J = 7.0Hz), 1.61-1.76 (6H, m), 3.0K6H, t, J = 7.2Hz), 3.12-3.16 (2H, m), 3.23 (6H, t, J = 7.9Hz), 3.82 (2H, q , J = 6.9Hz), 3.89 (2H, t, J = 6.2Hz), 3.97 (2H, t, J = 6.1Hz), 4.07 (2H, q, J = 7.0Hz), 6.36 (1H, d, J = 2.2Hz), 6.60 (2H, s), 6.7K1H, t, J = 2.0Hz), 6. * 98 (1H, dd, J = 2.2, 9.1Hz), 7.03-7.09 (1H, m), 7.10 (2H, dd, J = 2.2, 8.7Hz), 8.00 (1H, d, J = 8.9Hz), 8.07 (1H, s). Melting point: ~ 1 2 7 ° C Example 1 9 2 Bromide 1- { 7- {3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3-ethoxy-5-propoxyphenyl) -4 -oxy-1 , 4-dihydroquinoline-7-yloxy} heptyl}-1-azobicyclo [2 · 2 · 2] octane (Exemplified compound number: 2-7 8 7) Examples (1 9 1 h) The obtained 7- (7-bromoheptyloxy) -1- (3-ethoxy-5-propoxyphenyl) -oxy-1,4-dihydroquinoline-3-carboxylic acid N- ( 230 mg of 3,5-difluorophenyl) -N acetamidine and 40.2 mg of quinidine were reacted according to the method of Example (li) to obtain the title compound as a white solid 2 3 1 mg -454- 200300349 NMR (D MS0-d6) δρριη: 0.98 (3H, t, J = 7.3Hz), 1.08 (3H, t, J = 6.9Hz), 1.23-1.36 (6H, m), 1.33 (3H, t, J = 7.1Hz) , 1.58-1.76 (6H, m), 1.82-1.86 (6H, m), 2.03-2. 07 (1H, m), 3. 03-3. 07 (2H, m), 3. 29-3. 33 (6H, m), 3.82 (2H, q, J = 7.1Hz), 3.89 (2H, t, J = 6.3Hz), 3.97 (2H, t, J = 6.3Hz)? 4.07 (2H, q, J = 6.9Hz), 6.36 (1H, d, J = 2.1Hz), 6.60 (2H, d, J = l.lHz), 6.71 (1H, t, J = 2.1Hz), 6.98 (1H, dd, J = 2.2 , 9.2Hz), 7.03-7.07 (1H, m), 7.10 (2H, dd, J = 2.2, 8.4Hz), 8.00 (1H, d, J = 9.1 1Hz), 8.〇7 (lH, s) Melting point ·· ~ 1 2 9 ° C Example 1 9 3 Bromide 1- {7- {3- [N- (3,5-difluorophenyl) 4-ethylaminomethylmethyl] -1- ( 3-ethoxy-5-propoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7-yloxy} heptylbupyridine (exemplified compound number: 2-7 8 5) will 7-(7 -bromoheptyloxy) -1-(3-ethoxy-5 -propoxyphenyl) -oxy-1,4-dihydroquinoline-3 obtained in Example (19.1 h) -Carboxylic acid N- (3,5-difluorophenyl) -N acetamide 299 mg and pyridine 270 mg. The reaction was carried out according to the method of Example (1 i) to obtain the title compound as a white solid. 3 1 7 mg. NMR (DMS0-d6) δρριη: 0.97 (3H, t, J = 7.4Hz), 1.09 (3H, t, J = 6.8Hz), 1.25-1.35 (6H, m), 1.33 (3H, t, J = 7.1 Hz), 1. 60-1. 65 (2H, m), 1. 68-1.77 (2H, m), 1.86-1.93 (2H, m), 3.82 (2H, q, J = 7.1Hz), 3.88 ( 2H, t, J = 6.4Hz), 3.97 (2H, t, J = 6.4Hz), 4.07 (2H, q, J = 7.1Hz), 4.58 (2H, t, J = 7.4Hz), 6.35 (1H, d, J = 2.1Hz), 6.60 (2H, s), 6.70 (1H, t, J = 2.0Hz), 6.97 (1H, dd, J = 2.2, 8.9Hz), 7.03-7. 08 (1H, m ), 7.10 (2H, dd, J = 2.2, 8.7Hz), 8.00 (1H, d, J = 8.9Hz), 8.07 (1H, s), 8. 15 (2H, t, J = 6.9Hz), 8.60 (1H, t, J = 8.0Hz), 9.08 (2H, d, J = 5.6Hz). Melting point: ~ 1 1 2 ° C Example 1 9 4 200300349 Bromide 1- {7- {3- [N- (3,5-difluorophenyl) -ethylaminomethyl]-1- (3-ethoxy-5 -propoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7- Oxy} heptyl}-1 -methylpyridine (exemplified compound number: 2-7 8 6) 7-(7 -bromoheptyloxy) -1-(3 -Ethoxy-5-propoxyphenyl) -oxy-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N acetamidine 182 mg and N-formyl 206 mg of piperidine was reacted according to the method of Example (1 i) to obtain the title. The compound was a pale yellow solid 191 mg. NMR. (DMS0-d6) δρριι: 0.98 (3H, t, J = 7.4Hz), 1.08 (3H, t, J = 6.4Hz), 1.27-1.35 (6H, in ), 1.33 (3H, t, J = 6.9Hz), 1.46-1.76 (12H, m), 2.96 (3H, s), 3.24-3.36 (6H, m), 3.82 (2H, q, J = 7.1Hz) , 3.90 (2H, t, J = 6.2Hz), 3.98 (2H, t, J = 6.2Hz), 4.08 (2H, q, J = 7.0Hz), 6.36 (1H, d, J = 2.1Hz), 6.6 K2H, s), 6.71 (1H, t, J = 2.1Hz), 6.99 (1H, dd, J = 2.2, 8. 9Hz), 7. 04-7. 07 (1H, m), 7.10 (2H , dd, J = 2.1, 8.6Hz), 8.00 (1H, d, J = 9.0Hz), 8.07 (1H, s). Melting point: ~ 1 2 9 ° C Example 1 9 5 Bromide 1- {8- {3-[? ^-(3,5-difluorophenyl) -1 ethylaminomethylmethyl] -1- (3-ethoxy-5 -propoxyphenyl) -4 -oxy-1,4 -Dihydroquinoline-7-yloxy} octyl}-4 -acyl-1 -azobicyclo [2.2 · 2] octane (Exemplified compound number: 2-8 4 1) (195a) 7- (8 -Bromooctyloxy) -1- (3-ethoxy-5-propoxyphenyl) -4-oxo-1,4-dihydroquinoline-3 -unsaturated acid N- (3,5-difluoro Phenyl) -N-acetamidinium 1- (3-ethoxy-5-propoxybenzyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline obtained in Example (191g) -3-carboxylic acid N- (3,5-difluorophenyl) -456- 2003003 49-N-acetamidine 60711 ^, 55% sodium hydride 1601 ^, and 1,8-dibromoxin 1.36 g, the reaction was carried out according to the method of Example (1 h) to obtain the title compound. White foamy substance 626mg. NMR * (CDC13) δρρπι: 1.06 (3H, t, J = 7.4Hz), 1.22 (3H, t, J = 7.1Hz), 1.32-1.46 (6H, m), 1.45 (3H, t, J = 6.9Hz), 1.70-1.88 (6H, m), 3.41 (2H, t, J = 6.9Hz), 3.86-3.97 (6H, m), 4.05 (2H, q, J = 6.9Hz), 6.42 (1H , d, J = 2.2Hz), 6.45 (2H, s), 6. 60-6. 66 (2H, m), 6.85 (2H, dd, J = 2.0, 7.9Hz), 6.9K1H, dd, J = 2.2, 9.1Hz), 7.85 (1H, s), 8.22 (1H, d, J = 9.0Hz). (1951)) bromide 1- {8- {3- [1 (3,5-difluorophenyl) )-: ^-Ethylaminomethylmethyl] -1- (3-ethoxy-5-propoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy} octyl Bu 4 -Acryl-1-azobicyclo [2 · 2 · 2] octane The 7- (8-bromoepoxy) -1- (3-ethoxy-5-propion) obtained in Example (195a) Oxyphenyl) -4 -oxo-I, 4-dihydroquinoline-3 · carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 156mg and 1,4-diazine bicyclic ring [ 2 · 2 · 2] octane 2 7.0 mg, the reaction was carried out according to the method of Example (1 i), and 143 mg of the title compound was obtained as a white solid. NMR (DMS0-d6) 0ppm: 0.98C3H, t, J = 7.4Hz), 1.08 (3H, t, J = 7.1Hz), 1.25-1.35 (8H, m), 1.33 (3H, t, J = 7.0Hz ), 1. 62-1.78 (6H, m), 3.01 (6H, t, J = 7.5Hz), 3.12-3.16 (2H, m), 3.24 (6H, t, J = 7.9Hz), 3.82 (2H, q, J = 7.1Hz), 3.89 (2H, q, J = 6.2Hz), 3.97 (2H, t, J = 6.1Hz), 4.07 (2H, q, J = 6.9Hz), 6.36 (1H, d, J = 2.2Hz), 6.60 (2H, d, J = l.lHz), 6.70 (1H, t, J = 2.1Hz), 6.98 (1H, dd, J = 2.3, 9.1Hz), 7.03-7.09 (lH , in), 7.10 (2H, dd, J = 2.1, 8.5Hz), 8.00 (1H, d, J = 8.9Hz), 8.07 (1H, s) ... Melting point: ~ 1 2 5 ° C Example 1 9 6 -457-200300349 1- {8- {3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl]-1- (3-ethoxy-5 -propane Oxyphenyl) -4 -oxo-1,4-dihydroquinoline-7-yloxy} octyl}-1-azobicyclo [2 · 2.2] octane (Exemplified compound number: 2- 840) will 7-(8 -bromooctyloxy) -1-(3-ethoxy-5-propoxyphenyl) -4 -oxo-1,4-dihydroquinoline obtained in Example (1 9 5 a) -3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 248 mg and panquinidine 42.5 mg. The reaction was carried out according to the method of Example (1 i) to obtain the title compound as a white solid. 2 3 8 mg 〇NMR (DMS0-d6) όρριη: 0.98 (3H, t, J = 7.5Hz), 1.08C3H, t, J = 6.5Hz), 1.22-1.34 (8H, in), 1.33 (3H, t, J = 7.1Hz), 1. 60-1.78 (6H, m), 1.81-1. 86 (6H, m), 2. 04-2. 07 (1H, m), 3. 03-3. 07 (2H, in ), 3. 29 ~ 3. 35 (6H, m), 3.82 (2H, q, J = 7.1 Hz), 3.89 (2H, t, J = 6.2Hz), 3. 97 (2H, t, J = 6.8Hz), 4.07 (2H, q, J = 7.0Hz), 6.36 (1H, d, J = 2.1Hz), 6.60 (2H, d, J = l.lHz), 6.70 (1H, t, J = 2.1 Hz), 6.98 (1H, dd, J = 2.2, 9.0Hz), 7.03-7.08 (1H, m), 7.10 (2H, dd, J = 2, 2, 8. 6Hz), 8.00 (1H, d , J = 9.0Hz), 8.07 (1H, s). Melting point: ~ 1 2 3 ° C Example 1 9 7 Brominated l- {8- {3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -l- (3-ethoxy-5-propoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy} octyl Mepidol (Exemplary compound number: 2-8 3 9) The 7-(8-bromooctyloxy) -1-(3 -ethoxy-5 -propoxybenzene) obtained in Example (1 9 5 a) N- (3,5-difluorophenyl) -N-acetamidamine 2 3 0 mg and N-methylpiperidine 2 5 5 mg, reacted according to the method of Example (li) to obtain the title compound as white Solid 200 300 349 2 5 2 mg NMR (DMS0-d6) δρριη: 0.98 (3H, t, J = 7.4Hz), 1.09 (3H, t, J = 6.2Hz), 1.26-1.36 (8H, m), 1.33 ( 3H, t, J = 7.1Hz), 1. 52-1. 69 (6H, in), 1. 72-1.76 (6H, m), 2.96 (3H, s), 3. 24-3.36 (6H, m ), 3.82 (2H, q, J = 7.1Hz), 3.89 (2H, t, J = 6.2Hz), 3.97 (2H, t, J = 6.3Hz), 4.08 (2H, q, J = 7.0Hz), 6.36 (1H, d, J = 2.1Hz), 6.60 (2H, d, J = 2.1Hz), 6.70 (1H, t, J = 2.1Hz), 6.98 (1H, dd, J = 2.2, 8.9Hz), 7.03-7.08 (1H, m), 7.10 (2H, dd, J = 2.2, 8.4Hz), 8.90, (1H, d, J = 8.9Hz), 8.07 (1H, s). Melting point: ~ 1 2 2 ° C Example 1 9 8 Bromide 1- {7- {3- [N- (3,5-difluorophenyl) -1 ^ -ethylaminomethylmethyl] -1- (3,5-dipropoxyl Phenyl) -4 -oxo-1,4 · dihydroquinolin-7 -yloxy} heptylbu 4 -acyl-1 -azobicyclo [2 · 2 · 2] octane (Exemplified compound number ·· 2-7 9 3) (198 &) 1- (3,5-dipropoxyphenyl) -7-methoxymethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N -(3,5-difluorophenyl) -N-acetamidine The 1- (3-trisyl-5-propoxybenzyl) -7-methoxymethoxy-4 obtained in Example (191e) -Oxy-1,4-dihydroquinoline-3 -carboxylic acid> 1- (3,5-difluoro Group) -N-acetamidamine 2. 0 2 g, 5 5% sodium hydride 3 2 8 mg and iodopropane 2. 5 8 g. The reaction was carried out according to the method of Example (1 8 5 f) to obtain the title compound. White foamy substance 1.85 g NMR. (CDC13) (5ppm: 1.05 (6H, t, J = 7.3Hz), 1.2K3H, t, J = 7.2Hz), 1.76-1.87 (4H, m), 3.4K3H, s), 3.90-3.96 (6H, m), 5.12 (2H, s), 6.45 (2H, d, J = 2.1Hz), 6.60 (1H, t, J = 2.0Hz), 6.61-6.65 ( 1H, m), 6.65 (1H, d, J = 2.2Hz), 6.84 (2H, dd, J = 2.1, 8.0Hz), 7.05 (1H, dd, J = 2.2, 9.0Hz), 7.90 (1H, s ), 8.24 (1H, d, J = 8.9Hz). -459-200300349 (198b) l- (3,5 · dipropoxyphenyl) -7 · hydroxy · 4 · oxy-1,4-dihydroquine Porphyrin-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 1- (3,5-dipropoxyphenyl) -7-methoxymethyl obtained in Example (198a) Oxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N · (3,5-difluorophenyl) -N-acetamidine 1.85g and 4N HC1-ethyl acetate solution 10ml, The reaction was carried out according to the method of Example (185 g) to obtain the title compound as a white solid 1.59 g ° NMR, (CDC13) δρριι: 1.04 (6H, t, J = 7.4Hz), 1.30 (3H, t, J = 7.2Hz), 1.76-1.85 (4H, m), 3.88 (4H, t, J = 6.5Hz), 4.02 (2H, q, J = 7.1Hz), 6.27 (2H, s), 6.60 (1H, s), 6.70 (1H, s), 6.79 (1H, t, J = 8.4Hz), 7.05 (2H, d, J = 5.1Hz), 7.66 (1H, d, J = 9.2Hz), 7.76 (1H, s), 8.23 (1H, d, 1 = 9.2Hz). (198〇07- ( 7-bromoheptyloxy) -1- (3,5-dipropoxyphenyl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl ) -N-acetamidine The 1- (3,5-dipropoxyphenyl) -7-hydroxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid obtained in Example (198b) 574111 N- (3,5-difluorophenyl) -N-acetamidamine, 157111 55% sodium hydride and 1.55 1,7-dibromoheptane were reacted according to the method of Example (1 h) 430 mg of white foamy substance of the title compound can be obtained. NMR (CDC13) δρριη: 1.05 (6H, t, J = 7.3Hz), 1.20 (3H, t, J = 7.1Hz), 1.28-1.53 (8H, m), 1.44 (3H, t, J = 7.0Hz) , 1.69-1.92 (6H, m), 3.39 (2H, t, J = 6.8Hz), 3. 86-3. 96 (8H, m), 6.4K1H, d, J = 2.2Hz), 6.44 (2H, s), 6. 60-6. 66 (2H, m), 6.83 (2H, d, J = 9.7Hz), 6.89 (1H, dd, J = 2.1, 9.8Hz), 7.84 (1H, s), 8.20 (1H, d, J = 8.9Hz). (198d) Brominated 1. {7- {3- [N- (3,5-difluorophenyl) -N-ethylaminemethyl}]-1- ( 3, 5-dipropoxyphenyl) _ 4-oxo-1,4-dihydroquinoline-7- 200300349 alkoxy} heptylbu 4 -az-1-azobicyclo [2 · 2 · 2] The 7- (7-bromoheptyloxy) -1- (3,5-dipropoxyphenyl) -4-oxo-1,4-dihydroquinoline obtained in Example (19 8 c) was obtained by octane -3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 149mg and 1,4-diazinebicyclo [2 · 2 · 2] octane 2 5 · 7 mg, according to the examples (1i) The reaction was carried out to obtain 140 mg of the title compound as a white solid. NMR (DMS0-d6) δρρπι: 0.98 (6H, t, J = 7.3Hz), 1.08 (3H, t, J = 7.1Hz), 1.25-1.39 (6H, m), 1.60-1. 78 (8H, m ), 3.0K6H, t, J = 7.2Hz), 3.12-3.16 (2H, m), 3.23 (6H, t, J = 7.9Hz), 3.82 (2H, q, J = 7.2Hz), 3.89 (2H, t, J = 6.2Hz), 3.98 (4H, t, J = 6.2Hz), 6.36 (1H, d, J = 2.2Hz), 6.60 (2H, d, J = l.lHz), 6.7K1H, t, J = 2.1Hz), 6.98 (1H, dd, J = 2.2, 8.9Hz), 7.03-7.08 (1H, m), 7.10 (2H, dd, J = 2.2, 8.6Hz), -8.00 (1H, d, J = 8.9Hz), 8.07 (1H, s). Melting point: ~ 1 1 8 ° C Example 1 9 9 Brominated l- {7- {3- [N- (3,5-difluorophenyl)- 1 ethylaminomethyl] -l- (3,5-dipropoxyphenyl) -4 -oxo-1,4-dihydroquinoline-7 -yloxy} heptyl}-1 -azobicyclo [2 · 2 · 2] Octane (Exemplified compound number: 2-792) The 7-(7-bromoheptyloxy) -1-(3,5-dipropoxy) obtained in Example (1 9 8 c) Phenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidamine 1 2 8 mg and panquinidine 2 1 · 9 mg was reacted according to the method of Example (1i) to obtain 126 mg of the title compound as a white solid. NMR. (DMS0-d6) δ ppm: 0.98 (6H, t, J = 7.3Hz), 1.08 (3H, t, J = 7.2Hz), 1.23-1. 34 (6H, m), 1. 58-1 78 (8H, m), 1. 83-1. 86 (6H, m), 2. 03-2. 09 (1H, m), 3. 03-3. 08 (2H, m), 3. 29 -3. 37 (6H, m), 3.82 (2H, q, 1 = 7.2 Hz), 3.89 (2H, t, 200300349 J = 6.2Hz), 3.98 (4H, t, J = 6.3Hz), 6.36 ( 1H, d, 1 = 2.1Hz), 6.6K2H, s), 6.7K1H, t, J = 2.0Hz), 6.98 (1H, dd, J = 2.1, 8.9Hz), 7. 03-7. 08 (1H , i), 7.10 (2H, dd, J = 2.0, 8.5Hz), 8.00 (1H, d, J = 9. 0Hz), 8.07 (1H, s).

Melting point: ~ 1 1 6 ° C Example 2 0 0 Bromide 1- {7- {3- [N- (3,5-difluorophenyl) -N-ethylaminemethylmethyl] -l- (3 , 5-dipropoxyphenyl) -4-oxo-1,4-dihydroquinolin-7_yl} -heptyloxy}-1-m piperidine (exemplified compound number: 2-7 9 1) will The 7-(7 -bromoheptyloxy) -1-(3,5-dipropoxybenzyl) -4 -oxy-1,4 -one ^ chlorine command -3 obtained in Example (1 9 8 c) -Junic acid N-(3,5-chlorobenzyl) -N-acetamide 171 mg and N-methylpiperidine 190 mg, the reaction was carried out according to the method of Example (li) to obtain the title compound as a white solid 148 mg 〇NMR (DMS0-d6) δρριι: 0.98 (6H, t, J = 7.4Hz), 1.08 (3H, t, J = 6.1Hz), 1.25-1.35 (6H, m), 1.49-1.78 (14H, m) , 2.96 (3H, s), 3. 23-3. 28 (6H, m), 3.82 (2H, q, J = 7.1Hz), 3.90 (2H, t, J = 6.2Hz), 3.98 (4H, t , J = 6.3Hz), 6.36 (1H, d, J = 2.2Hz), 6.60 (2H, d, J = 1.2Hz), 6.71 (1H, t, J = 2.1Hz), 6.99 (1H, dd, J = 2.2, 8.9Hz), 7. 03-7. 08 (1H, m), 7.10 (2H, dd, J = 2.1, 8.6Hz), 8.00 (1H, d, J = 9.1Hz), 8.07 (1H, s). Melting point: ~ 1 2 0 ° C Example 2 Ο 1 1- {8- {3- [N- (3,5-difluorophenyl) -N-ethylaminomethyl] -l bromide -(3,5 -Dipropoxyphenylbenzene 4-oxo-1,4-dihydroquinoline-7-yloxy} octyl}-4 -acyl-1 -azobicyclo [2 · 2 · 2] octane (exemplified Compound Number: 2- 842) -462-200300349 (201a) 7- (8-bromooctyloxy) -l- (3,5-dipropoxyphenyl) -4oxo-1,4-dihydroquinoline -3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 1- (3,5-dipropoxyphenyl) -7- obtained from Example (1 9 8 b) Hydroxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N- (3,5-difluorophenyl) -N-acetamido 68〇11 ^, 55% sodium hydride 17〇11 ^ And 1,8-dibromooctane 1.77§, the reaction was carried out according to the method of Example (1 h) to obtain 727 mg of the title compound as a white solid. NMR (CDC13) δρριη: 1.05 (6H, t, J = 7.4Hz), 1.20 (3H, t, J = 7.2Hz), 1.35-1.44 (8H, m), 1. 68-1.86 (8H, m), 3.39 (2H, t, J = 6.8Hz), 3. 85-3. 95 (8H, m), 6.4K1H, d, J = 2.1Hz), 6.44 (2H, d, J = 2.2Hz), 6.60- 6.65 (2H, m), 6.84 (2H, dd, J = 2.2, 7.9Hz), 6.90 (1H, dd, J = 2.2, 9.0Hz), 7.84 (1H, s), 8.20 (1H, d, J = 8.6Hz). (201b) 1- {8- {3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3,5-dipropoxylate) bromide Phenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy} octyl}-4 -acyl-1 -azobicyclo [2 · 2 · 2] octane Example (20 la) 7- (8-Bromooctyloxy) -1-(3,5-dipropoxyphenyl) -4oxo-1,4 · dihydroquinoline-3-carboxylic acid N- (3, 155 mg of 5-difluorophenyl) -N-acetamidamine and 26.3 mg of 1,4-diazinebicyclo [2.2.2] octane were reacted according to the method of Example (1 i) to obtain the title compound as a white color Garden body 149mg. NMR (DMS0-d6) (5ppm: 0,98 (6H, t, 1 = 7.4Hz), 1.08 (3H, t, J = 7.2Hz), 1.28-1.38 (8H, m), 1. 61-1. 78 (8H, m), 3.01 (6H, t, J = 7.2Hz), 3. 12-3.16 (2H, m), 3.24 (6H, t, J = 7.0Hz), 3.82 (2H, q, J = 7.1Hz), 3.89 (2H, t, J = 6.3Hz), 3.98 (4H, t, J = 6.4Hz), 6.36 (1H, d, J = 2.2Hz), 6.6K2H, s), 6.7K1H, t , J = 2.1Hz), 6.99 (1H, dd, J = 2.2, 8. 9Hz), 7. 03-7. 09 (1H, m), 7.10 (2H, dd, J = 2.2, 8. 6Hz), 8.00 (1H, d, J = 9.1Hz), 8.08 (1H, s). 200300349 Melting point: ~ 1 1 8 ° C Example 2 0 2 Chloride 1- {7- {1- (3,5 -diethyl Oxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminemethyl] -4 -oxo-1,4-dihydroquinoline-7-yloxypeptyl 1-Methylpiperidine (Exemplified compound number: 2-8 8 6) (202a) 1- (3,5-diethoxyphenyl) -7- (7- (piperidin-1-yl) -heptyloxy ) -4 -Oxygen-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine The 7- (7- Bromoheptyloxy) -1- (3,5-diethoxyphenyl) -4 -oxo-1,4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl)- 567 mg of N-acetamidine and 141 mg of piperidine were reacted according to the method of Example (20a) to obtain White foamy substance of the title compound 5 2 5 mg ο NMR (DMS0-d6) δ ppm: 1.20 (3H, t, J = 7.1Hz), 1. 20-1.78 (16H, in), 1.43 (6H, t, J = 7.0Hz), 2.21-2.42 (6H, m), 3.85 (2H, t, J = 6.7Hz), 3.93 (2H, q, J = 7.1Hz), 4.03 (4H, q, J = 7.0Hz) , 6.39 (1H, d, J = 2.3Hz), 6.43 (2H, d, J = 2 „2Hz), 6.58-6.65 (2H, m), 6.81-6.92 (3H, m), 7.84 (1H, s) , 8.00 (1H, d, J = 9.1Hz). (202b) 1- {7- {l- (3,5-diethoxyphenyl) -3- [N- (3, 5-difluoro) chloride Phenyl) -N-ethylaminomethylmethyl] -4-oxo-1,4-dihydroquinoline-7-yloxybuheptylbupipidol Tablets 1- (3 obtained in Example (202a) , 5-diethoxyphenyl) -7- (7- (piperidin-1-yl) -heptyloxy) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid N-(3 , 5-Difluorophenyl) -N-acetamidamine 104mg, acetonitrile 3.2ml and 0.8 1M chloroformin acetonitrile solution 1 · 8 m 1 in a pressure-resistant metal reaction container at 16 (TC Reaction for 6 hours. After the solvent of the reaction solution 200300349 was concentrated under reduced pressure, the residue was dissolved in a small amount of dichloromethane, and ether was added to solidify. The solid was collected by filtration, washed with ether, and dried to obtain 101 mg of the title compound as a pale yellow solid. NMR, (DMS0-d6) (5ppm: 1.08 (3H, t, J = 7.0Hz), 1. 25-1.41 (8H, m), 1.33 (6H, t, J = 7.0Hz), 1. 50-1 75 (8H, m), 2.96 (3H, s), 3. 23-3. 30 (6H, m), 3.82 (2H, q, J = 7.0Hz), 3.90 (2H, t, J = 7.2Hz ), 4.07 (4H, t, J = 7.0Hz), 6.36 (1H, d, J = 2.1Hz), 6.60 (2H, s), 6.70 (iH, t, J = 1.6Hz), 6.99 (1H, dd , J = 2.2, 9.0Hz), 7.02-7.08 (lH, m), 7.10 (2H, dd, J = 1.6, 8.3Hz), 8.00 (1H, d, J = 8: 9Hz), 8.07 (1H, s ). Melting point: ~ 1 3 6 ° C Example 2 0 3 Bromide 1- {7- {l- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorobenzene ) -N-ethylaminomethylmethyl] -4 -oxo-1,4-dihydroquinoline-7 · yloxy} • heptyl}-1-Epiperium (Exemplary Compound Number: 2-8 8 7) The 1- (3,5-diethoxyphenyl) -7- (7- (piperidin-1-yl) -heptyloxy) -4-oxo-1,4 obtained in Example (202a) -Dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 123 mg and bromoethane 60 mg. The reaction was carried out according to the method of Example (2 0 2 b). 8 3 · 2 mg NMR of the title compound was obtained. (DMS0-d6) δ ppm: 1.08 (3H, t, J = 7.0Hz), 1.15 (3H, t, J = 5.9Hz), 1.30-1.42 (8H , m), 1.33 (6H, t, J = 7.1Hz), 1. 52-1.80 (8H, m), 3.16-3. 21 (2H, m), 3.26-3.37 (6H, m), 3.82 (2H, q, J = 7.1Hz), 3.90 (2H, t, J = 6.2Hz), 4.07 (4H, t, J = 7.0Hz), 6.36 (1H, d, J = 2.2Hz), 6.60 (2H, d, J = l.lHz), 6.70 (1H, t, J = 1.8Hz), 6.99 (1H, dd, J = 2.1, 8.9Hz), 7. 04-7. 07 (1H, m), 7.1K2H, dd, J = 1.9, 8.3Hz), 8.00 (1H, d, 1 = 9.0Hz), 8.07 (1H, s). -465-200300349 Melting point: ~ 1 1 8 ° C Example 204 Bromination;! _ {7 · {1_ (3,5-diethoxyphenyl)- 3- [1 ^-(3,5-difluorophenyl) -N-ethylaminomethylmethyl] -4 -oxo-1,4-dihydroquinoline-7-yloxy} -heptyl}- 1-Prometam (Exemplified compound number: 2-8 8 8) The compound (3,5-monoethoxyphenyl) obtained in Example (202a) -7- (7- (piperidin-1-yl) -Heptyloxy) -4 -oxo-I, 4-dihydroquinoline-3 -carboxylic acid N- (3,5-difluorophenyl) -N-acetamidine 105 mg and bromopropane 150 mg, according to The reaction of Example (202b) was performed to obtain 107 mg of the title compound as a pale yellow solid. NMR (DMS0-d6) δ ppm: 0.90 (3H, t, J = 7.2 Hz), 1.08 (3H, t, J = 7.2Hz), 1.26- 1.34 (8H, in), 1.33 (6H, t, J = 7.0Hz), 1. 52-1.81 (10H, m), 3.16-3. 23 (2H, m), 3.26- 3.30 (6H, m), 3.82 (2H, q, J = 7.0Hz), 3.90 ( 2H, t, J = 6.3Hz), 4.07 (4H, t, J = 7.0Hz), 6.36 (1H, d, J = 2.2Hz), 6.60 (2H, s), 6.70 (1H, t, J = 2.1 Hz), 7.00 (1H, dd, J = 2.2, 9.0Hz), 7.04-7.07 (1H, m), 7.11 (2H, dd, J = 2.6, 8.2Hz), 8.00 (1H, d, J = 9.0Hz), 8.07 (1H, s). Melting point: ~ 1 1 2 ° c Example 2 0 5 Bromide 1- {7- {1- (3-butoxy-5-methoxyphenyl) -3 -[N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -4 -oxo-1,4-dihydroquinoline-7-yloxyphenyl} -1-piperidine (Exemplified compound number: 2- 8 89) The 7-(7-bromoheptyloxy) -1-(3 -butoxy-5-methoxyphenyl) obtained in Example (1 1 8 c) _4 · Oxy-1,4-dichlorohydrazine 11 Lin-3 -residual acid N- (3,5-difluorophenyl) -N-acetamidine 150 mg and dimethoprim 170 mg, according to Example (Π) The reaction was carried out in this way to obtain the title compound as a white 200,300,349 colored solid, 161 mg. NMR: (DMS0-d6) δ ppm: 0.94 (3H, t, .I-7.4Hz), 1.08 (3H, t, 1 = 6.9Hz), 1.25-1. 76 (20H, m), 2.96 (3H , s), 3.24-3. 31 (6H, m), 3.8K3H, s), 3. 81-3. 85 (2H, m), 3.90 (2H, t, J = 6.2Hz), 4.02 (2H, t, J = 6.4Hz), 6.36 (1H, d, J = 2.3Hz), 6.63 (2H, s), 6.73 (1H, t, J = 2.1Hz), 6.99 (1H, dd, J = 2.2, 8.9 Hz), 7.04-7.08 (1H, m), 7.10 (2H, dd, J = 2.0, 8.5Hz), 8.00 (1H, d, J = 9.0Hz), 8.08 (1H, s). Melting point: ~ 1 1 5 ° c Reference Example 1 3 -Benzyloxy-5-methoxyaniline Reference Example (1 a) 3-Benzyloxy-5 -hydroxybenzoic acid methyl ester will contain 25.6g of 3,5-dihydroxybenzoic acid methyl ester Of N, N-dimethylformamide solution: 100 ml, add 55% sodium hydride 7.3 1 g under ice cooling, stir for 10 minutes, then add benzyl bromide 2 8.2 g of N, N -30 ml of dimethylformamide solution, stirred at room temperature for 1 hour. The reaction solution was diluted with hydrochloric acid, and extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 3/2) to obtain 13.6 g of the title compound as a white solid. NMR (CDC13) δρρπι: 3.90 (3H, s), 5.08 (2H, s), 6.68 (1H, t; J = 1.6Hz), 7.12 (1H, s), 7. 29-7. 44 (6H, m ). Melting point: 8 9-9 1 ° C. Reference Example (1b) 3-benzyloxy-5-methoxybenzoic acid methyl ester will contain 3-benzyloxy-5 -hydroxybenzoic acid methyl ester obtained in Reference Example (1a) 200300349 1 3.5 g of N, N-dimethylformamide solution 80 m 1 was added with 55% sodium hydride 2.64 under ice cooling, and after stirring for 15 minutes, methyl iodide 14 · 3 g was added, followed by stirring at room temperature for 1 hour. The reaction solution was added with dilute hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent ·· hexane / ethyl acetate = 2/1) to obtain 1 3.9 g of the title compound as a colorless oily substance. _R_ (CDC13) (5ppm: 3.82 (3H, s), 3.9K3H, s), 5.08 (2H, s), 6.73 (1H, t, J = 2.3Hz), 7.20 (1H, dd, J = 1.3, 2.2 Hz), 7 · 28-7 · 45 (6Η, m). Reference Example (1c) 3-Benzyloxy-5-methoxybenzoic acid A solution of 3-benzyloxy-5 -methoxybenzoic acid methyl ester obtained in Reference Example (1b) 1 3.9 g of a methanol solution 1 6 Add 0. 12 g of sodium hydroxide and 40 m 1 of water, and heat to reflux for 1.5 hours. Dilute hydrochloric acid was added to the reaction solution, and methanol was distilled off under reduced pressure, followed by extraction with ethyl acetate. The ethyl acetate layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The solid was collected by filtration, washed with hexane, and the title compound was obtained as a white solid 1 2 · 6 g NMR (CDC13) δριη: 3.83 (3H, s), 5.10 (2H, s), 6.77 (1H, t, J = 2.3Hz), 7. 33-7. 48 (7H, m). Melting point: 1 3 1-1 3 3 ° C. Reference Example (1 d) (3-Benzyloxy-5-methoxyphenyl) -carboxylic acid third butyl ester will contain 3 · Benzyloxy-5 -methoxybenzoic acid 1 obtained in Reference Example (1 c) 300 ml of a toluene solution of 2 · 6 g and 10.1 ml of triethylamine, 16.2 g of diphenyl azide-468-200300349 phosphine were added, and after heating under reflux for 1.5 hours, 60 ml of third butanol was added, followed by heating under reflux for 4 hours. After the reaction solution was concentrated under reduced pressure, water was added thereto, followed by extraction with ethyl acetate. The ethyl acetate layer was washed successively with dilute hydrochloric acid, water and saturated brine, and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 3/1) to obtain 13.5 g of the title compound as a colorless oil. NMR. (CDC13) δρρπι: 1.52 (9H, s), 3.77 (3H, s), 5.03 (2H, s), 6.43 (1H, t, J = 1.4Hz), 6.60 (1H, s), 6.70 (1H , d, J = 1.2Hz), 7.30-7.44 (5Η, m). Reference Example (1e) 3-benzyloxy-5-methoxyaniline will contain 13.5g of (3-benzyloxy-5-methoxyphenyl) -carboxylic acid third butyl ester obtained in Reference Example (Id). 80 ml of ethyl acetate solution, 4NHC1 // ethyl acetate solution 80 m 1 was added, and stirred at 60 ° C for 1.5 hours. The reaction solution was added to a saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/1) to obtain the title compound as a colorless oily substance 7.43 g ° NMR (CDC13) δρρπι: 3.74 (3H, s), 5.00 (2H, s), 5.89 (1H, t, J = 2.0Hz), 5.95 (1H, t, J = 2.0Hz), 6.01 (1H, t, J = 2.2Hz), 7.30—7.43 (5H, m) . Reference Example 2 N-ethyl-3,5-difluoroaniline Reference Example (2a) N- (3,5-difluorophenyl) acetamidamine will contain 3,5-difluoroaniline 7 5.0 g of pyridine Add 200 ml of anhydrous 200 300 349 acetic acid to the solution 2 0 m 1 and stir for 30 minutes. The solvent was distilled off under reduced pressure, and the obtained solid was washed with diisopropyl ether and filtered to obtain the title compound as a white solid, 90.6 g. NMR. (CDC13) δρρη: 2.19 (3H, s), 6.55 (1H, tt, J = 2.2, 8.8Hz), 7.13 (2H, d, J = 6.6Hz). Reference Example (2b) N-ethyl-3,5-difluoroaniline A solution of 32.5 g of N- (3,5-difluorophenyl) acetamide obtained in Reference Example (2a) 3 3 0 m 1 Add 36 ml of borane-dimethylsulfide complex under ice cooling, stir for 10 minutes and heat to reflux for 2 hours. The reaction solution was stirred with methanol under ice-cooling, and then the solvent was distilled off under reduced pressure. Dilute hydrochloric acid was added to the residue, followed by washing with ethyl acetate. The aqueous layer was basified with a sodium hydroxide solution, extracted with ethyl acetate, and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: hexane / ethyl acetate = 1 0/1) to obtain the title compound as a colorless oily substance 20.0 g. (CDC13) dppm: L26 (3H, t, J = 7.3Hz), 3.09 (2H, q, J = 7.3Hz), 3.86 (1H, bs), 6.00-6 · 13 (3Η, m). Reference Example 3 N-methyl-3,5-difluoroaniline 3,5-difluoroaniline 50. Og triethyl orthoformate solution 193 m was added to trifluoroacetic acid 1 m 1 and heated under reflux for 2 hours. The solvent was distilled off under reduced pressure, 200 ml of ethanol was added to the residue, and 2.0 g of sodium borohydride was added under ice-cooling, followed by heating under reflux for 1 hour. The reaction solution was added with dilute hydrochloric acid and washed with ethyl acetate. The aqueous layer was basified with sodium hydroxide solution and extracted with ethyl acetate-470-200300349. After the ethyl acetate layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1 0/1) to obtain the title compound as a colorless oily substance 3 8 · 8 g NMR (CDC13) (5ppm: 2.82 ( 3H, d, J = 4.8Hz), 3.97 (1H, bs), 6. 05-6. 20 (3H, m). Reference Example 4 3 -methoxy-5-propoxyaniline 'Reference Example (4 a ) 3-Hydroxy-5-methoxybenzoic acid methyl ester 14.7 g of 3,5-dihydroxybenzoic acid methyl ester in 70 ml of N, N-dimethylformamide solution, and add potassium tert-butoxide under ice cooling 14.7 g, after stirring for 30 minutes, 150 ml of a solution of 6.5 ml of iodomethane in N, N-dimethylformamide was added dropwise, and stirred at 0 ° C for 3 hours. The reaction solution was added with dilute hydrochloric acid and extracted with ethyl acetate The ethyl acetate layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent ·· ethyl acetate / hexane = 1 / 3), 6.25g of the title compound was obtained as a white solid. NMR (CDC13) (5ppm: 3.82 (3H, s), 3.91 (3H, s), 6.63 (1H, t, J = 2.2Hz); 7.14-7.19 ( 2H, m). Reference Example (4b) 3-Hydroxy-5-methoxy obtained from Reference Example (4a) methyl 3-methoxy-5-propoxybenzate 6.25 g of methyl benzate, 7.11 g of potassium carbonate, and 6.23 ml of propyl bromide were reacted according to the method of Reference Example (lb) to obtain the title compound as a yellow oily substance, 7 · 5 9 g. NMR (CDC13) δ ppm: 1.03 (3H, t, J = 7.3Hz), 1.80 (2Η, sextet, M.3Ηζ), 3.82 (3Η, s), 3.90 (3Η, s); 3.93 (2Η, t, J = 7.3Hz) , 6.62-6.66 (1Η, m), 7.16-7.19 (2H, m). '-471- 200300349 Reference example (4c) 3-methoxy-5-propoxynanoic acid 3 of Reference Example (4b) -Methoxy-5-propoxybenzoic acid methyl ester 7.59g and sodium hydroxide 4.06g, and reacted according to the method of Reference Example (lc) to obtain the title compound as a white solid 6.99g. NMR. (CDC13) δ ppm : 1.05 (3H, t, J = 7.3Hz), 1.82 (2H, sextet, J = 7.3Hz), 3.84 (3H, s), 3.96 (2H, t, J = 7.3Hz), 6.70 (1H, t, J = 2.2Hz), 7.24-7. 27 (2H, m). Reference Example (4d) (3-methoxy-5-propoxyphenyl) -carboxylic acid third butyl ester 6.99g of 3-methoxy-5-propoxybenzyl acid and 6.95ml of triethylamine, 8.60ml of diphenylphosphine azide, and tertiary butanol can be reacted according to the method of Reference Example (1d) The title compound was 9.35 g as a white solid. NMR (CDC13) δρρπι: 1.0Κ3Η, t, J = 7.3Hz), 1.5K9H, s), 1.78 (2H, sextet, J = 7.3Hz), 3.76 (3H, s), 3.89 (2H, t, J = 7.3Hz), 6.16 (1H, t, J = 2.2Hz), 7.22-7. 29 (1H, m), 7. 36-7. 42 (1H, m). Reference example (4e) 3_methoxy -5-propoxyaniline: (35-methoxy-5-propoxyphenyl) -carboxylic acid tert-butyl ester obtained in Reference Example (4d) 9.35 g, 4N HCl / ethyl acetate 60 ml, according to the reference example (le ) Method to obtain the title compound as a yellow oily substance 5.30 g ° NMR (CDC13) δ ppm: 1.0K3H, t, J = 7.3Hz), 1.77 (2H, sextet, J = 7.3Hz), 3.64 ( 2H, br), 3.74 (3H, s), 3.85 (2H, t, J = 7.3Hz), 5. 84-5. 89 (2H, m), 5.92 (1H, t, J = 2.2Hz). Reference Example 5 3,5-Diethylaniline-472- 200300349 Reference Example (5a) N- (2,6-diethylphenyl) -4-toluenesulfonylamine 2,6-diethylaniline 7. 0 6 g A 20 m 1 solution of pyridine was added to 9.84 g of p-toluenesulfonic acid chloride, and the mixture was stirred at room temperature for 3 hours. The reaction solution was added with dilute hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The solidified residue was recrystallized from ethyl acetate to obtain 13.8 g of the title compound as a pale yellow solid. NMR (CDC13) δ ppm: 1.01-1.07 (6H, in), 2. 39-2. 48 (7H, m), 5. 91 (1H, s), 7. 05-7. 09 (2H, m) , 7.17-7. 26 (3H, m), 7. 56-7. 60 (2H, m). Reference example (5b) N- (2,6-diethyl-4-nitrophenyl) -4- Tosyl sulfonamide was added to N- (2,6-diethylphenyl) -4-tolusulfonamide 1 3.8 g of acetic acid 80 m 1 obtained in Reference Example (5a), and fuming nitric acid 15 m 1 was added. Stir at 60 t for 3 hours. The reaction solution was poured into ice water, and the solid was collected by filtration. The residue was purified by silica gel column chromatography (eluent: ethyl acetate / hexane = 1/8) to obtain 6.88 g of the title compound as a pale orange solid. NMR (CDC13) δρριη: 1.12 (6H, t, J = 7.3Hz), 4.28 (3H, s), 2.54 (4H, q, I = 7.3Hz), .6.1 (lH, t, J = 6.6Hz), 7.28 (2H, d, J = 8.8Hz), 7.59 (2H, d, J = 8.8Hz), 7.95 (2H, s). Reference example (5c) 2,6-diethyl-4-nitroaniline will 30 ml of sulfuric acid was added to 4.8 Og of N- (2,6-diethyl-4-nitrophenyl) -4-toluenesulfonamide obtained in Reference Example (5b), and the mixture was stirred at room temperature for 2 hours. The reaction solution was poured into ice water, ammonia water was added to alkalize, and the solid was collected by filtration. The solid was washed with water and dried to obtain 1.98 g of the title compound as a yellow solid. 〇-473-200300349 NMR. (CDC13) δρρη: 1.32 (6H, t, J = 7.3Hz), 2.55 (4H, q, J = 7.3 Hz), 4.35 (2H, s), 7.93 (2H, s). Reference example (5d) l, 3-diethyl-5-nitrobenzene will be obtained from reference example (5c) 2,6- To 6 ml of an aqueous solution of 1.98 g of diethyl-4-nitroaniline was added 6 ml of hydrochloric acid, and after stirring for several minutes, 2 ml of a saturated sodium nitrite aqueous solution was added under ice cooling, and the mixture was stirred for 1.5 hours. 50% hypophosphite 30 m 1 was added to the reaction solution, and the mixture was further stirred for 1 hour and at room temperature overnight. The reaction solution was extracted with ethyl acetate, and the ethyl acetate layer was combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate / hexane 1/10) to obtain 1.05 g of the title compound as a pale orange solid. NMR (CDC13) δρρη: 1.28 (6H, t, J = 7.3Hz ), 2.72 (4H, q, J = 7.3Hz), 7.35C1H, s), 7.88 (2H, s). Reference Example (5 e) 3,5-Diethylaniline will be obtained as 1 of Reference Example (5 d) To 30 ml of a 1.05 g ethanol solution of 3-diethyl-5-nitrobenzene was added 10% Pd-C, and the mixture was stirred at room temperature for 3 hours under hydrogen. The reaction solution was filtered, and the catalyst was washed with ethyl acetate. The filtrate was combined and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate / hexane = 1/10) to obtain the title compound as a yellow oily substance (36 mg). NMR. (CDC13) δ ppm: 1.20 (6H, t, J = 7.3Hz), 2.53 (4H, q, J = 7.3Hz), 6.36 (2H, s), 6.46 (1H, s). Reference Example 6 3 , 5-Diethoxyaniline hydrochloride -474-200300349 Reference Example (6 a) 3, 5-Diethoxybenzoic acid methyl ester 5.0 g of 3, 5-Dihydroxybenzyl methyl acid, potassium carbonate 1 5 · A mixture of 9 g of iodoethane 6.92 ml and 100 ml of N, N-dimethylformamide was stirred at room temperature for 30 hours. The reaction solution was diluted with water. Extract with ethyl acetate. The extract was sequentially washed with saturated saline, dilute hydrochloric acid, saturated saline, aqueous sodium thiosulfate, saturated sodium bicarbonate, and saturated saline. After drying over anhydrous magnesium sulfate, the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1 0/1) to obtain 6.32 g of the title compound as colorless crystals. _ NMR (CDC13) δρριη: 1.4Κ6Η, t, J = 7.0Hz), 3.90 (3H, s), 4.02 (4H, d, J = 7.0Hz), 6.63 (1H, s), 7. 16 (1H, s), 7. 17 (1H, s). Reference Example (6b) 3,5-Diethoxybenzoic acid 6.3 g of 3,5-diethoxybenzoic acid methyl ester obtained in Reference Example (6a) 1 5.6 g of sodium oxide was added to the mixed solution of 0 0 m 1 to 50 m 1 of water, and the mixture was stirred at room temperature for 1 hour. The methanol in the reaction solution was distilled off under reduced pressure, diluted with water, and the dichloromethane extract was discarded. The aqueous layer was adjusted to pH 1 with dilute hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was combined, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was concentrated under reduced pressure, and the precipitated solid was dissolved in hexane. Filtration gave 5.55 g of the title compound as colorless crystals. NMR (CDC13) (5ppm: 1.43 (6H, t, J = 7.0Hz), 4.07 (4H, d3 J = 7.0Hz), 6.69 (1H, s), 7.23 (1H, s), 7.24 (1H, s) Reference Example (6c) (3,5-Diethoxyphenyl) Carbamate Tert-Butyl The 3,5-Diethoxybenzoic Acid 5.0 3 g obtained in Reference Example (6 b), 5.0 ml of triethylamine And 100 ml of toluene solution of 6.17 ml of diphenylphosphine azide were heated under reflux for 1.5 hours. After cooling, the third butanol 20 m 1 was added, and then heated under reflux for 1-475-200300349 hours. The reaction solution was diluted with ethyl acetate, Rinse successively with an aqueous citric acid solution, saturated brine, saturated sodium bicarbonate water, saturated brine, and dry over anhydrous magnesium sulfate. The solvent was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane / acetic acid). Ethyl ester = 10/1), 5.81 g of the title compound was obtained as a white solid. NMR (CDC13) (5ppm: 1.38 (6H, t, J = 6.7Hz), 1.51 (9H, s), 3.99 (4H, d, J = 6.8Hz), 6.15 (1H, t, J = 2.1Hz), 6.55-6.57 (2H, m). Reference example (6d) 3, 5-diethoxyaniline hydrochloride Reference example (6c) (3,5 -diethoxyphenyl) carbamic acid tert-butyl ester 5.75 g of ethyl acetate 10 0 m 1 solution was added to 4 NHC 1 / ethyl acetate solution 2 5 ml 1, stirred at room temperature for 18 hours. Additional 4 NHC 1 / ethyl acetate solution 25 ml was added, and stirred for another 5 hours. The solid was collected by filtration and dried to give the title compound as colorless crystals 4.3 3 g. NMR (DMS0-d6) δ ppm: 1.3K6H, t, J = 6.9Hz), 4.00 (4H, d, J = 6.9Hz), 6.38 (3H, s). Reference Example 7 3 -methoxy -5-Nitaniline hydrochloride Reference Example (7a) 3-Methoxy-5-nitrobenzic acid methyl ester 3,5-Dinitrobenzic acid 25 g and sodium methoxide 13.4 g hexamethylphosphorus The osmium triamine 1 30 m 1 solution was stirred at 80 ° C for 5 hours. The reaction solution was poured into concentrated sulfuric acid 40 ml / ice water 200 ml and extracted with ether. The ether layer was washed with water and extracted with sodium hydroxide solution. The object was obtained. The sodium hydroxide solution was extracted with dichloromethane and discarded, and then adjusted to pH 1 with dilute hydrochloric acid, and extracted with ether. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was concentrated. A solid, a mixture of 3,2 g of potassium carbonate, 14.7 m 1 of methyl iodide, and Ν, Ν-bis-476- 200300349 methyl formamide 1 50 m 1 was stirred at room temperature for 20 hours. The reaction solution was diluted with water and extracted with ethyl acetate. The ethyl acetate layer was washed successively with dilute hydrochloric acid, water, saturated brine, saturated sodium bicarbonate water, aqueous sodium thiosulfate solution, and saturated brine. After drying over anhydrous magnesium sulfate, the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 8/1 to 5/1) to obtain the title compound as a yellow solid 8.6 1 g NMR (CDC13) δρριη: 3.95 (3H, s), 3.98 (3H, s), 7.88 (1H, dd, J = 1.4, 2.5Hz), 7.92 (1H, t, J = 2.4Hz), 8.46 (1H, t, J = 1.6Hz). Reference example (7 b) 3-methoxy-5-nitrobenzic acid 8.65 g of methyl 3-methoxy-5-nitrobenzate obtained in Reference Example (7a) was mixed with methanol m 1 -water 50 m 1 Then, 3.26 g of sodium hydroxide was added to the mixture, and the mixture was stirred at room temperature for 2 hours. The reaction solution was diluted with water. Extract with dichloromethane and discard. It was adjusted to pH 1.1 with dilute hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure. The precipitated solid was dissolved in hexane and collected by filtration to obtain 7.84 g of the title compound as a pale orange solid. NMR (CDC13) δρριη: 3.97 (3H, s), 7. 94-7. 95 (1H, m), 7. 97-7. 99 (1H, m), 8.53 (1H, d, I-1.9Hz) Reference Example (7 c) 3-methoxy-5 -nitroaniline hydrochloride The 3-methoxy-5 -nitrobenzic acid obtained in Reference Example (7 b) 3 · 0 g, triethylamine 3 · A solution of 2 m 1 of diphenylphosphine azide 3 · 7 m 1 and 5 m 1 of third butanol in anhydrous toluene 100 m 1 was heated under reflux for 3 hours. The reaction solution was washed successively with an aqueous citric acid solution, a saturated saline solution, a saturated sodium bicarbonate water solution, and a saturated saline solution, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure. 4N H C1 / -477-200300349 ethyl acetate solution 50 m 1 was added and stirred at room temperature for 1 hour. The reaction solution was diluted with ether, and the solid was collected by filtration and dried to obtain 2.82 g of the title compound as a yellow solid. N.MR/⑽S〇-d6) 5ppm: 3.77 (3Η, s), 6.59 (1Η, t,] = 2.2Ηζ), 6.92 (1Η, t, J = 2.2Hz), 7 10 (1H, t, J = 2.2Hz) Reference example 8 3 -Amino-5 -methoxy-benzoic acid tert-butyl ester Reference example (8 a) 3-methoxy-5-nitrobenzoic acid Tributyl ester To a solution of 3.0 g of 3-methoxy-5-nitrobenzic acid in 15 m of anhydrous dichloromethane obtained in Reference Example (7b), 2.61 ml of chloramphenicol and N, N-dimethylformamide were added. 2 drops, and stirred at room temperature for 1.5 hours. The solvent and excess grasshopper chlorine were distilled off under reduced pressure, and the residue was dissolved in anhydrous dichloromethane 3 m 1. Under ice cooling, a mixture of 4.34 ml of tertiary butanol and 3.0 6 ml of pyridine was added dropwise, and the mixture was stirred at room temperature for 18 hours. It was diluted with ethyl acetate, washed with water, dilute hydrochloric acid, saturated brine, saturated sodium bicarbonate water, saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/1) to obtain 3.7 g of the title compound as a yellow oily substance. NMR ^ (CDC13) δ ppm: 1.62 0H, s), 3.93 (3H, s), 7.83-7. 84 (1H, m), 7.88 (1H, t, J = 2.2Hz), 8.37 (1H, d, J-1.9Hz). Reference Example (8b) 3-Amino-5 -methoxy-benzoic acid tert-butyl ester The 3-methoxy-5 -nitrobenzyl acid obtained in Reference Example (8a) To a solution of 3.71 g of ethyl acetate in 50 ml of third butyl ester was added 10% P d-C 700 mg, and the mixture was stirred at room temperature for 30 minutes under hydrogen. The catalyst was filtered off, and the filtrate was distilled off under reduced pressure to obtain 3.25 g of the title compound as a colorless oil. -478-200300349 NMR (CDC13) 5ppm: 1.57 (9H, s), 3.80 (3H, s), 6.39 (1H, t, J = 2.2Hz), 6.92-6. 94 (2H, m). Reference Example 9 3-Amino-5 -methoxy-benzoic acid reference example (9a) 3-methoxy-5-nitrobenzylamine The 3-methoxy-5 -nitrobenzyl acid obtained in reference example (7b) A solution of 1.0 g and triethylamine 2.12 m 1 in anhydrous dichloromethane 20 m 1 was added dropwise under ice-cooling to isobutyl chloroformate 0.74 ml. Stir at room temperature for 30 minutes. Add 28% ammonia solution and stir for 30 minutes. Diluted with ethyl acetate, washed with dilute hydrochloric acid, saturated brine, saturated sodium bicarbonate water, and saturated brine in this order, dried over anhydrous magnesium sulfate, and concentrated the solvent under reduced pressure. The precipitated solid was dissolved in hexane and filtered to obtain the title compound as a pale yellow solid 7 90m g NMR (CDC13) (5ppm: 3.93 (3H, s), 7. 85-7. 88 (2H, m), 8 ~ 29-8. 30 (1H, m). Reference Example (9 b) 3-methoxy-5 -nitrobenzonitrile The 3-methoxy-5-nitrobenzylamine obtained in Reference Example (9a) 720 mg of a 20 m solution of anhydrous dichloromethane was added dropwise to 5 m 1 of anhydrous dichloromethane containing titanium tetrachloride 0.5 2 m 1 under ice cooling, and the mixture was stirred at room temperature for 1 hour. Saturated sodium bicarbonate water and Ethyl acetate was stirred for 15 minutes, and the insoluble matter was filtered off. The organic layer of the filtrate was sequentially washed with water, dilute hydrochloric acid, saturated saline, saturated sodium bicarbonate water, saturated saline, and dried over anhydrous magnesium sulfate. The solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain 560 mg of the title compound as a pale orange solid. -479-200300349 NMR (CDC13) δρριη: 3.96 (3H, s ), 7.47 (1H, dd, J = 1.5, 2.9Hz), 7.96 (1H, t, J = 2.2Hz), 8.10 (1H, d, J = 1.5Hz). Reference example (9 c) 3 -amino -5 -methoxy-benzonitrile The 3-methoxy obtained in Reference Example (9b) -5-Nitrobenzonitrile 550 mg and nickel chloride (II) 6 hydrate 1 · 4 7 g of methanol 20 m 1, and sodium borohydride 492 mg was added under stirring at room temperature. The reaction solution was acetic acid Ethyl acetate-saturated sodium bicarbonate diluted with water. The insoluble matter was filtered off. The organic layer of the filtrate was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent : Ethyl acetate) to obtain 178 mg of the title compound as a yellow solid. NMR (CDC13) δρριη: 3.78 (3H, s), 6.39 (1Η, s), 6.53 (1Η, s), 6.55 (1Η, s) ... Reference Example 10 3-Methoxy-5-propoxyl Female Reference Example of the Month (10a) 3-Octyloxy-5-propoxyacetic acid methyl vinegar 3-benzyloxy obtained from Reference Example (1a) 16-5 g of methyl-5 -hydroxybenzoic acid, 3 3.5 g of 55% sodium hydride and 15.7 g of bromopropyl, according to the method of Reference Example (1 b), the title can be obtained. Colorless oily substance of the compound 17 · 3 g, NMR (CDC13) δρριη: 1.04 (3H, t, J = 7.3Hz), 1. 78 ~ 1. 88 (2H, m), 3-9K3H, s), 3.94 (2H, t, J = 7.6Hz), 5.08 (2H, s), 6.72 (1H, s), 7.22 (lH, s), 7. 27-7. 48 (6H, m). Reference example (l 〇b) 3-benzyloxy-5-propoxybenzyl acid. 7.3 g of 3 benzyloxy-5-propoxybenzyl methyl ester obtained in Reference Example (10a) and 6.92 g of sodium hydroxide, according to reference. The reaction of Example (1c) was carried out to obtain 15 · 3 g of the title compound as a white solid. -480- 200300349 NM R. (CDC13) δρριη: 1.04 (3H, t, J = 7.3Hz), 1.78-1.85 (2H3 m), 3.96 (2H, t, J = 7.1Hz), 5.09 (2H, s) , 6.78 (1H, s), 7.26-7.51 (7H, m). Reference Example (10c) (3-Benzyloxy-5-propoxyphenyl) -Thirty-Butyl Carbamate Reference Example (1 〇b) The obtained 3-benzyloxy-5-propoxybenzic acid 15 · 3 g, triethylamine 11.0 ml, 17.5 g diphenylphosphine azide and 90 ml tertiary butanol, according to the reference example (1 d ) To carry out the reaction to obtain 17.2 g of the title compound as a yellow oily substance. NMR (CDC13) δ ppm: 1.05 (3H, t, J = 7.1Hz), 1.52 (9H, s), 1.78-1.88 (2H, m), 3.97 (2H, t, J- 6.9Hz), 5.03 (2H , s), 6.44 (1H, s), 6.60 (1H, s), 6.7K1H, s), 7. 28-7. 49 (5H, m). Reference example (10d) 3 -benzyloxy-5- Propoxyaniline was obtained from the reference example (10c) (3-benzyloxy-5-propoxyphenyl) -carbamic acid third butyl ester 1 7.2 g and 4 NHC 1 / ethyl acetate solution 70 m 1 The reaction was carried out according to the method of Reference Example (1e) to obtain 9.45 g of the title compound as a yellow oily substance. NMR (CDC13) (5ppm: 1.04 (3H, t, 1-7.1Hz), 1. 72-1. 89 (2H, m), 3.98 (2H, t, J = 7.0Hz), 5.01 (2H, s) , 5.89 (1H, t, J = 1.8Hz), 5.94 (1H, t, J ^ l.lHz), 6.0K1H, t, J = 1.9Hz), 7.28-7.49 (5H, m). Reference example n 3 -Methoxymethoxy-aniline reference example (1 1 a) 1-methoxymethoxy-3 -nitrobenzene 3-nitrophenol 2 4. 1 3 g of dichloromethane solution 2 0 0 m 1 in A small amount of 9.46 g of sodium hydride was added under ice-cooling, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was added under ice cooling, and chlorochloromethyl ether was added dropwise. After the dropwise addition was completed, the mixture was stirred at room temperature -481- 200300349 for 0.5 hours. The reaction solution was added to water, and the organic layer was separated, washed with saturated sodium bicarbonate water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 4: 1) to obtain the title compound as a yellow oil 3 1 · 17 g ° NMR (CDC13) ( 5ppm: 3.50 (3H, s), 5.25 (2H, s), 7.36 (1H, dd, J = 2.2, 7.3Hz), 7.44 (1H, t, J = 8. LHz \ 7. 86-7. 91 ( 2H, m). Reference Example (llb) 3-methoxymethoxy-aniline The 1-methoxymethoxy-3 -nitrobenzene 3 1 · 0 g of ethanol-di obtained from Reference Example (1 1 a) Chloromethane (1: 1) mixed solution of 200 m 1 was added with 10% P d-C 1 · 50 g, and stirred at room temperature for 2 hours under hydrogen. The reaction solution was filtered through celite to remove insoluble matter. The filtrate was concentrated under reduced pressure to obtain the title compound as a red oil 2 4.97 g. NMP (CDC13) (5ppm: 3.47 (3H, s), 5.14 (2H, s), 6.34 (1H, dd, J = 2.2, 6.6Hz)., 6.40 (1H, t, J = 2.2Hz), 6.44 (1H, dd, J = 2.2, 8.8Hz), 7.06 (1H, t, 1 = 8.1Hz). Reference example 1 2 4-(3 -bromopropyl) -pyridine 1 hydrobromide will be a solution of 3-(pyridin-4-yl) -propanol 1 0 · 0 g 4 8% hydrobromic acid-acetic acid 80 m 1, Stir at 14 ° C for 5 hours. The reaction solution was concentrated under reduced pressure, and the obtained solid was The ketone was recrystallized to obtain 1.0 g of the title compound as a white solid. NMR. (CDC13) δρρη: 2.21-2.37 (2Η, m), 3.02 (2H, t, J = 7.3Hz), 3.5K2H, t, 1 = 6.6Hz), 7.9K2H, d, J = 6.1Hz), 8.63 (2H, d, J = 6.0Hz). Reference example 1 2003200349 3-(3-bromopropyl) -pyridine 1 hydrobromide By reacting 5.0 g of 3- (pyridine-3-yl) -propanol and 40 ml of 48% hydrobromic acid-acetic acid according to the method of Reference Example 12, 6.18 g of the title compound was obtained as a white solid. NMR · (CDC13) δρριη: 2.26-2 · 33 (2Η, m), 3.11 (2Η, t, J = 7.4Hz), 3.46C2H, t, J = 6.1Hz), 7.96 (1H, dd , J = 5.8, 8.9Hz), 8.38 (1H, d, J = 7.0Hz), 8.8K1H, d, J = 5.5Hz), .8.88 (1H, s). Reference example 1 4 4-(4- Bromobutyl) -pyridine 1 hydrobromide

Reference example (1 4 a) 4-(pyridine-4 -yl) -but- 3 -ene-1 -ol

(3 -hydroxypropyl) triphenylphosphine bromide 16 · 4 g of 250 ml of tetrahydrofuran was added dropwise under nitrogen at -78 ° C to a 1.52N n-butyllithium / hexane solution 5 4 ml 1 and stirred for 30 minutes 4.20 g of a tetrahydrofuran solution of 4.2 8 g of pyridine-4 -aldehyde was added dropwise, warmed to room temperature and stirred for 2 hours. Hydrochloric acid was added to oxidize, and the reaction solution was extracted with ethyl acetate. It was basified with a sodium hydroxide solution, and the aqueous layer was extracted with ethyl acetate. The ethyl acetate layer was combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol = 1 0/1) to obtain 2.46 g of the title compound as a yellow oily substance. NMR (CDC13) δρριη: 2. 51- 2. 64 (2Η, m), 3.8K2H, t, J = 6.2Hz), 6.42-6.48 (2H, m), 7. 18-7. 23 (2H, m ), 8.51-8. 57 (2H, m). &Quot; Reference Example (1 4 b) 4-(pyridin-4-yl) -but-1- 1-ol. 4-(obtained from Reference Example (1 4 a)- Pyridine-4 -yl) -but-3 -en-1 -ol 2 · 4 6 g of a solution of methanol 3 0 m 1 was added with 260 mg of platinum oxide, and the mixture was stirred at 50 ° C for 5 hours under hydrogen. After the catalyst was filtered off, the filtrate was added with hydrochloric acid and the solvent was concentrated under reduced pressure. Sodium hydroxide solution was added for alkalization and extraction with ether. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure to obtain 1. 37 g of the title compound as a yellow oily substance. NMR (CDC13) δρρπι: 1.58-1. 79 (4Η, m), 2.65 (2H, t, J = 7.5Hz), 3.68 (2H, t, J = 6.3Hz), 7.12 (2H, d, J = 6.1 Hz), 8.49 (2H, d, J = 6.0Hz). Reference Example (1 4 c) 4-(4-bromobutyl) -pyridine 1 hydrobromide. 4 obtained from Reference Example (1 4 b) -(Pyridin-4-yl) -butanol 1. 37 g, 48% hydrobromic acid-acetic acid 10 m 1, and reacted according to the method of Reference Example 12 to obtain the title compound as a white solid 1.1 4 g. NMR (CDC13) δρριη: 1.78-2.06 (4Η, m), 2.86 (2H, t, J = 6.4Hz), 3.52 (2H, t, J = 6.3Hz), 7.88 (2H, d, J = 6.1Hz) , 8.65 (2H, d, J = 6.0Hz). Reference example 1 5 3- (4-Bromobutyl) -pyridine 1 hydrobromide Reference example (1 5 a) 4-(Pyridine-3 -yl)- Butan-3-en-1-ol will be (3-hydroxypropyl) triphenylphosphine bromide 16 · 5 g, 1. 5 9 N n-butyllithium / hexane solution 5 2 m 1, pyridine-3 -aldehyde 5 · 2 6 g, reacted according to the method of Reference Example (1 4 a) to obtain the title compound as a yellow oily substance 3.09 g ° NMR (CDC13) δρριη: 2.53 (2H, q, J = 6.8Hz), 3.49 (2H, br), \ 6. 23-6. 51 (2H, m), 7. 21-7. 24 (1H, m), 7. 63-7. 69 (1H, m), 8. 44- 8. 47 (1H, m), 8.58 (1H, d, J = 2.0Hz). Reference example (1 5 b) 4-(pyridine-3 -yl) -but-1- 1-ol will refer to reference example (1 5 a ) Of the obtained 4- (pyridin-3-yl) -but-3-3-en-1-ol 3.0 8 g, platinum oxide 250 mg, the reaction was carried out according to the method of Reference Example (1 4 b) to obtain the title compound Yellow oily substance 2.48 g. NM R (CDC13) (5ppm: 1.58-1. 78 (4H, m), 2.66 (2H, t, J = 7.7Hz), 3.68 (2H, t, J = 6.1Hz), 7.21 (1H, dd, J -5.0, 7.9Hz), 7.45-7.52 (1H, m), 8. 43-8. 46 (2H, m).-484- 200300349 Reference example (1 5 c) 3-(4-bromobutyl)- Pyridine 1 hydrobromide will be the 4-((tridyn-3-yl) -butanol) obtained in Reference Example (1 5 b) 2.48 g, 48% hydrobromic acid-acetic acid 20 m 1, according to the reference example The reaction was carried out by the method of (1 4 c) to obtain 3.55 g of a red foamy substance of the title compound. NMR. (CDC13) δρριι: 1.82-2.02 (4Η, in), 2.92 (2H, t, J = 6.4 Hz), 3.46 (2H, t, J = 6.0Hz), 7. 91-7. 94 (1H, m), 8. 31 (1H, d, J = 7.7Hz), 8. 64-8. 74 ( 2H, m). Reference Example 1 6 2 _ (4-Bromotolyl) -ethanol 4-Bromotolueneacetic acid 5. 0 1 g of a tetrahydrofuran solution 30 m 1 was added dropwise under ice cooling to 2.0M borane-di 24.1 ml of methyl ether in ether. Stir at room temperature for 0.5 hours, add 5 O ml of water, and extract with ethyl acetate. Wash the organic layer with saturated brine, dry over anhydrous magnesium sulfate, and concentrate. Reduce the solid. The residue was dissolved in n-hexane and filtered to obtain the title compound. Color solid 4.70g. NMR (CDC13) δρριι: 2.87 (2H, t, J = 6.6Hz), 3.86 (2H, t, J = 6.6Hz), 4.49 (2H, s), 7.2K2H, d, J = 8 1Hz), 7.35 (2H, d, J = 8. 1Hz). Reference example 1 7 1,4-bis- (2-bromoethyl) benzene Reference example (1 7 a) 2-[4-(2- Hydroxyethyl) -phenyl] -ethanol. A solution of 6.00 g of tetrahydrofuran (50 ml) in 1,4-phenylenediacetic acid was added dropwise under ice-cooling to a 2.0 M borane-dimethylsulfide ether solution. 6 m 1. After stirring at room temperature for 1 hour, 50 ml of water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and then concentrated-485-200300349. The residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 1: 2) to obtain 2.50 g of the title compound as a white solid. NMR (CDC13) 6ppm: 2.85 (4H, t, J = 6.6Hz), 3.86 (4H, t, J = 6.6Hz), 7.19 (4H, s). Reference example (17b) l, 4 -double- (2 -Bromoethyl) -benzene 40 ml of a dichloromethane solution of 2.58 g of 2- [4- (2-hydroxyethyl) -phenyl] -ethanol obtained in Reference Example (17a), and a small amount of N-bromobutane A mixture of 6.63 g of imine and 9.77 g of triphenylphosphine was stirred at room temperature for 5 minutes. Saturated sodium bicarbonate water 50 m 1 was added to the reaction solution, and the separated organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and then the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 4: 1) to obtain the title compound as a white solid 4.26 g NMR (CDC13) δρρπι: 3.15 (4H, t, J = 7.3Hz) , 3.56 (4H, t, J = 7.3Hz), 7.17 (4H, s). Reference Example 1 8 4-(2-bromoethyl) benzyl acetate Reference Example (1 8 a) 4-(2 -hydroxyacetic acid) Ethyl) benzyl ester Add 4.90 g of acetonitrile solution of 4. 0 g of 2- (4-bromomethyl-phenyl) -ethanol 90 g obtained in Reference Example 16 to 4.29 g of potassium acetate and 18-crown-6 5 7 6 mg, and heat Reflux for 20 minutes. The acetonitrile of the reaction solution was distilled off under reduced pressure, and the residue was dissolved in ethyl acetate. The ethyl acetate layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent ·· n-hexane / ethyl acetate = 1/1) to obtain 4.0 2 g of the title compound as a colorless oily substance. -486-200300349 NMR, (CDC13) δ ppm: 2.10 (3H, s), 2.88 (2H, t, J = 6.5Hz), 3.83-3.91 (2H, m), 5.08 (2H, s), 7.24 (2H , d, J = 8.1Hz), 7.32 (2H, d, J = 8.1Hz). Reference example (18b) 4- (2-bromoethyl) benzyl acetate The reference example (18a) obtained 4- (2-bromoethyl) acetate A solution of 2-hydroxyethyl) benzyl ester in dichloromethane of 150 m 1 was added at room temperature to a mixture of 4.4 1 g of N-bromosuccinimide and 6.50 g of triphenylphosphine and stirred at room temperature for 5 minutes. Saturated sodium bicarbonate water was added to the reaction solution, and the organic layer was separated. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 2/1) to obtain 4.30 g of the title compound as a colorless oily substance. NMR (CDC13) δ ppm: 2.10 (3H, s), 3.17 (2H, t, J = 7.3Hz), 3.57 (2H, t, J = 7.3Hz), 5.09 (2H, s), 7.22 (2H, d , J = 8. 1Hz), 7.32 (2H, d, J = 8.1Hz). Reference Example 1 9 1-Bromomethyl-4- (3-bromopropyl) -benzene Reference Example (1 9 a) 3- (4-hydroxytolyl) -propan-1-alcohol Lithium aluminum hydride 3.91 g of a tetrahydrofuran solution 100 m 1 was added dropwise under ice-cooling to a solution of 3- (p-carboxyphenyl) -propionic acid in tetrahydrofuran. 3 5 0ml. Stir under ice cooling for 15 minutes and heat to reflux for 4 hours. Water and sulfuric acid were added to the reaction solution under ice-cooling, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was concentrated under reduced pressure to obtain the title compound as a colorless oil (4.21 g ° NM R. (CDC13) δρριι: 1.83-1.94 (2H, m), 2.7K2H, t, J = 7.3Hz), 3.68 (2H, t, J-6.6Hz), 4.67 (2H, s), 7.20 (2H, d, J = 7.3Hz), 7.30 (2H, d, J = 8.1Hz). Reference example (19b) l- Bromomethyl 4- (3-bromopropyl) -benzene • 487-200300349 3.75 g of 3- (4-hydroxytolyl) -propan-1-ol obtained from Reference Example (19a), N-bromobutane 9.36 g of amidine imine and 14.20 g of triphenylphosphine were reacted according to the method of Reference Example (17 b) to obtain 4.4 4 g of the title compound as a colorless oil. NMR (CDC13) 5ppm: 2.16 (2H, tt, P = 6.6, 7.3Hz), 2.78 (2H, t, J = 7.3Hz), 3.39 (2H, t, J = 6.6Hz), 4.49 (2H, s) , 7.18 (2H, d, J = 8.1Hz), 7.33 (2H, d, J = 8.1Hz). Reference Example 2 0 Acetic acid 4-(3-bromopropyl) -benzyl ester will refer to Reference Example (1 9 b ) The obtained 1-bromomethyl-4-(3-bromopropyl) -benzene 3.73 g, potassium acetate 1.25 g and 18-crown-6 338 mg were reacted according to the method of Reference Example (18a) to obtain the title compound Colorless oil 2.72 g NMR (CDC13) (5ppm: 2.10 (3H, s), 2.16 (2H, tt, J = 6.6, 7.3Hz), 2.78 (2H, t, J = 7.3 Hz ), 3.39 (2H, t, J = 6.6Hz), 5.08 (2H, s), 7.20 (2H, d, J = 8.1 Hz), 7.29 (2H, d, J = 8.1 Hz). Reference example 2 1 3 -Isopropoxy ... 5-methoxyaniline Reference Example (2la) 3-Hydroxy-5-isopropoxy-benzoic acid methyl ester 3,5-Dihydroxybenzoic acid methyl ester 3 3 · 6 g Of N, N-dimethylformamide solution 3 0 0 m 1, add 55% sodium hydride 8.0 g under ice cooling and stir for 30 minutes, add 40 g of 2-iodopropane dropwise at room temperature Stir for 3 hours. Dilute hydrochloric acid was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated brine, and anhydrous sodium sulfate. After drying, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate / -488- 200300349 hexane = 1/3) to obtain 17.0 g of the title compound as a colorless oil. NMR. (CDC13) (5ppm: 1.33 (6H, d, 1 = 6. OHz), 3.90 (3H, s), 4. 57 (1H, septet, J-6.0Hz), 6.59 (1H, m), 7.10 (1H, m), 7.15 (1H, m). Reference Example (21b) 3-Isopropoxy-5-methoxybenzoic acid methyl ester 3-hydroxy-5-isopropyl obtained in Reference Example (2la) 8.3 g of methyl benzyl acid, 6.0 g of potassium carbonate and 9.O g of methyl iodide were reacted according to the method of Reference Example (lb) to obtain 8.4 g of the title compound as a yellow oily substance. NMR (CDC13) (5 ppm: 1.34 (6H, d, J = 6.0Hz), 3.82 (3H, s), 3.90 (3H, s), 4.59 (1H, septet, J = 6.0Hz), 6.63 (1H, m), 7.15-7.19 (2H , m). ⑩ Reference Example (21c) 3-isopropoxy-5-methoxybenzoic acid The 3-isopropoxy-5-methoxybenzoic acid methyl ester obtained in Reference Example (2 1 b) 8.4 g And 3.0 g of sodium hydroxide were reacted according to the method of Reference Example (1c) to obtain 7.6 g of the title compound as a white solid. NMR (CDC13) δρριη: 1.36 (6H, d, J = 6.0Hz), 3.84 (3H, s), 4.60 (1H, septet, J = 6.0Hz), 6.69 (1H, m), 7.21-7.26 (2H, m). Reference Example (21d) (3-isopropoxy-5-methoxyphenyl) -carboxylic acid tert-butyl ester_ 3 -isopropoxy-5-obtained from Reference Example (2 1 c) 7.6 g of methoxybenzyl acid and 3.7 g of triethylamine, 10.0 g of diphenylphosphine azide, and 10 ml of third butanol. The reaction was carried out according to the method of Reference Example (1 d) to obtain 5.5 g of the title compound as a white solid. . NMR (CDC13) δρριιι: 1.3Κ6Η, d, J = 6.0Hz), 1.5K9H, s), 3.77 (3H, s), 4.52 (1H, septet, J = 6.0Hz), 6.15 (1H, m), 6.40 (1H, br.s), 6. 54-6.58 (2H, m). Reference Example (21e) 3-isopropoxy-5-toluidine The (3-isopropoxy) obtained from Reference Example (21d) -5-methoxyphenyl) -residue-489-200300349 tert-butyl acid 5.5 g, 4 NHC 1 / ethyl acetate solution 30 m 1, the reaction can be carried out according to the method of reference example (1e), but 3.8 g of the title compound was obtained as a yellow oily substance. NMR (CDC13) (5ppm: 1.3K6H, d, J = 6.1Hz), 3.74 (3H, s), 4.47 (1H, septet, J = 6.1Hz), 5.85-5. 88 (2H, m), 5.92 ( 1H, m). Reference Example 2 2 3 -ethoxy-5-isopropoxyaniline Reference Example (22a) 3-ethoxy-5-isopropoxy-benzoic acid methyl ester Reference Example (2 la) 8.3 g of the obtained methyl 3-hydroxy-5-isopropoxybenzoate, 6.0 g of potassium carbonate and 10 g of iodoethane were reacted according to the method of Reference Example (lb) to obtain the title compound as a yellow oily substance 8.4 g. NMR (CDC13) δρρπι: 1.34 (6H, d, J = 6.0Hz), 1.4K3H, t, J = 7.2Hz), 3.89 (3H, s), 4.05 (2H, q, J-7.2Hz), 4.58 ( 1H, septet, 1 = 6.0Hz), 6.62 (1H, m), 7.14-7.17 (2H, m). Reference example (22b) 3-ethoxy-5-isopropoxy-benzoic acid 2 2 a) The obtained 8.4 g of methyl 3-ethoxy-5 -isopropoxybenzoate and 3.0 g of sodium hydroxide were reacted according to the method of Reference Example (1 c) to obtain the title compound as a white solid 8.0 g. NMR (CDC13) δρρπι: 1.35 (6H, d, J = 6.0Hz), 1.43 (3H, t, J = 7.2Hz), 4.06 (2H, q, J = 7.2Hz), 4.59 (1H, septet, J = 6.0Hz), 6.68 (1H, m), 7. 19 ~ 7. 24 (2H, m). Reference example (22c) (3-ethoxy-5-isopropoxyphenyl) -carboxylic acid tert-butyl The ester was 8. Og of 3-ethoxy-5-isopropoxybenzoic acid obtained in Reference Example (22b) and 3.7 g of triethylamine, 10.0 g of diphenylphosphine azide, and 10 ml of third butanol. -490- 200300349. The reaction was carried out according to the method of Reference Example (1d) to obtain 6.5 g of the title compound as a white solid. NMR (CDC13) δρριη: 1.3Κ6Η, d, J = 6.3Hz), 1.38 (3H, t, J = 7.0Hz), 1.5K9H, s), 3.99 (2H, q, J = 7.0Hz), 4.51 (1H , septet, J = 6.3Hz), 6.14 (1H, m), 6.38 (1H, br.s), 6.52-6.57 (2H, m). Reference example (22d) 3-ethoxy-5-isopropoxy -Aniline 6.5 g of (3-ethoxy-5-isopropoxyphenyl) -carboxylic acid third butyl ester obtained in Reference Example (22c), 40 ml of 4N HC1 / ethyl acetate solution, according to Reference Example (1 The method e) was carried out to obtain 4.2 g of the title compound as a yellow oily substance. NMR (CDC13) 6ppm: 1.3K6H, d, J = 6.0Hz), 1.37 (3H, .t, J = 7.0Hz), 3.96 (2H, q, J = 7.0 Hz), 4.46 (1H, septet, J = 6.0Hz), 5.85-5.88 (2H, m), 5.92 (1H, m). Test Example 1 Measurement of inhibitory activity of ileal cholic acid carrier using voles-hamster everted ileal rings In the example, the inhibitory activity of ileal cholic acid carrier was measured as [Pharm.Res. 12,693-699 (1995)] The methods described by Stewar et al. That is, the material of the ileal cholic acid carrier uses an inverted intestinal loop. 5-7 week-old Syrian male voles were extracted with diethyl ether moth, ileum and about 10 cm from the blind end, reversed, and cut into 5 in sequence from the blind end in ice cold Ringer's solution. Inverted bowel ring. In order to correct for the difference in the expression of bile acid carriers in the ileal region, the loops were appropriately selected from above and below the ileum. Within the 5 groups, 1 group is the -491-200300349 control group without specimens, and considering the specific inhalation of bile acid to the ring, a group is added with a 1000 times higher concentration of non-radioactive labeling taurocholic acid ( Background group). The remaining 3 groups were groups with various specimens. Each ring was oscillated in a 1 ml radioactive taurocholic acid solution at 37 ° C and 90 rpm while inhaling the radiotauric acid from the ileal cholic acid carrier in the ring for 5 minutes. The composition of the radioactive taurocholic acid solution contains 1.0 // Ci radioactive taurocholic acid, 0.037mm non-radioactive taurocholic acid (but the background group is 37mM), various specimens and forests at appropriate concentrations Grid slow balance liquid. After washing the ring with Ringer's buffer solution 3 times, measure the wet weight and inject it into the vial, add the tissue dissolving agent NCS -11 (manufactured by AM ERSHA M) 0.5 m 1. Place at 50 ° C-late to completely dissolve . 2.5 ml of liquid scintillation mixture was added, and radioactivity was measured with a liquid scintillation meter (trade name: LC-6500, HP). The activity of the ileal cholic acid carrier is obtained by correcting the radioactivity of the inhalation ring with wet weight and expressing it in pm / mg (radioactivity per mg). Inhibition rate of ileal cholic acid carrier activity at a concentration of the compound of the present invention at 30 // g / ml. The results are shown in Table 3.表 [Table 3] Ileum type cholic acid carrier activity Example compound number inhibition rate (%) Example 1 83.3 Example 4 8 3.1 Example 1 1 100 Example 1 6 8 8.2 Example 1 7 9 6.0- 492-200300349 Example 1 8 9 3.9 It can be seen that the compound of the present invention has excellent ileal cholic acid carrier inhibitory activity. Test Example 2 Measurement of ileal bile acid carrier inhibitory activity using voles-hamster everted ileal rings. The test of ileal bile acid carrier inhibitory activity in this test example is similar to [Pharm.Res .. 12,693-699 (1995)] The method implemented by Stewart et al. That is, the material of the ileal cholic acid carrier uses an inverted intestinal loop. From 5 to 7 weeks, Syrian male voles were evacuated with diethyl ether and ileum to remove about 10 cm from the blind end. After reversing, they were cut into 15 pieces from the blind end in the cold Ringer's buffer. Invert the bowel ring. In order to correct for the difference in the expression of bile acid carriers in the ileum, the loops were appropriately selected from the top and bottom of the ileum, three groups of 1 and a total of 5 groups. Within the 5 groups, 1 group was the control group without specimens, taking bile acid into the ring specific inhalation, and 1 group plus 1000 times high concentration non-radioactive labeling taurocholic acid group (background group). The remaining three groups were groups with various specimens. Each ring was oscillated in a radioactive taurocholic acid solution at 1 ° C at 37 ° C and 90 rpm, while radioactive taurocholic acid was inhaled in the ring by an ileal cholic acid carrier for 5 minutes. The composition of the radioactive taurocholic acid solution contains 1.0 μC i of radioactive taurocholic acid, 0.03 7 mM non-radioactive taurocholic acid (but the background group is 37 mM), various specimens at appropriate concentrations, and Ringer retardation Liquid. After washing the ring with Ringer's buffer solution 3 times, measure the wet weight, inject the vial, add tissue to dissolve NCS -11 (manufactured by A ERSHA) 0.5 m 1. Place at 50 ° C-late completely dissolved. Added-493-200300349 2.5 m 1 liquid scintillation mixture, and measured radioactivity with a liquid scintillometer (trade name: LC-6500, HP). The activity of the ileal cholic acid carrier is obtained by correcting the radioactivity of the inhalation ring with wet weight and expressing it in pm / mg (radioactivity per mg). Inhibition rate of ileal-type cholic acid carrier activity at a concentration of the compound of the present invention at 1 μg / ml. The results are shown in Table 4. [Table 4] Ileum type bile acid carrier activity Example compound number inhibition rate (%) Example 9 3 6 7 Example 9 5 7 6 Example 9 6 6 8 The above shows that the compound of the present invention has excellent ileal type bile Acid carrier inhibitory activity. Formulation Example 1 Lozenge Example of the compound of Example 95 10 mg of lactose 68.5 crystalline cellulose

Claims (1)

200300349 Scope of patent application 1. A compound of the following formula (I) or (II), its pharmacologically acceptable salt, its ester or other derivative of general formula (I) In the formula, R1 is aryl, or substituted with 1 to 3 groups selected from halogen, lower alkyl, halogen lower alkyl, hydroxyl, lower alkoxy, lower alkylthio, cyano, and diloweramino. Aryl, R2 is lower alkyl, lower alkenyl or lower alkynyl, R3 is a group of formula -ADE-Gn + (X_) n, [wherein A is an oxygen atom, a sulfur atom, and a formula containing -CH2O -Or formula-CH2S-, D is C! _! 2 alkylene, C 2 _ i 2 alkylene having oxygen or sulfur atom in the carbon chain, or C 2 _ having aromatic group in the carbon chain 2 alkylene, -495-200300349 E is a single bond, formula-NR8CO-group and formula-CONR8-group (in the above formula, R8 is hydrogen or low alkyl group), Gn + is (i) selected from substitution The lower alkyl group substituted with the group b and the same or different 3 substituted ammonium group of the lower alkyl group, (ii) the ammonium group in which the nitrogen atom on the ring is bound to E, and the lower substituted group selected from the substituent b Alkyl, and 1- to 3-substituents selected from substituents b, which may be fused with a benzene ring, 1-pyridinyl, 1-pyridinyl, or 1-pyridinyl, (iii) carbon on the secondary mesogenic ring The atom is bonded to E, and at least one nitrogen atom on the ring is substituted with a lower alkyl group or an oxy group to form an ammonium group. Pyridinyl, pyridyl, or pyrimidyl, which can be fused with a benzene ring, (iv) a nitrogen atom on the secondary mediate ring is combined with E, and the nitrogen atom is substituted with a lower alkyl group or an oxygen group to form an ammonium group, 1 -Piperidinyl, 1-piperidinyl, or 4-morpholinyl, (v) may have a lower alkyl substituted with a group selected from substituent b, and may have 1 substituted with a group selected from substituent b and oxy -(1 -Azobicyclo [2.2.2] octyl) yl or 1- (4 -az-1-azobicyclo [2.2.2] octyl) yl, (vi) the carbon atom on the secondary median ring is bound to E 1, at least one nitrogen atom on the ring is substituted with a lower alkyl group or an oxy group to form an (1-azobicyclo [2.2.2] octyl) group or (4-azol-1-azobicyclo [2 · 2 · 2] octyl) group, (vii) may have 1 to 3 substituted 1-tetrahydrothienyl groups or 1-tetrahydrothiopyranyl groups, and (viii) has a group selected from substituent b -Substituted lower alkyl and lower alkyl identical or different groups 2 substituted sulfonyl groups, 200300349 (ix) have the same or different groups selected from lower alkyl and lower alkyl substituted with substituent b 3 substituted phosphino, or nitrogen atom on (X) meso ring is bound to E, and the nitrogen atom is lower alkyl or oxygen 1-pyrrolidinyl group substituted with ammonium group, X_ is an anion, η is an integer of 1 or 2], R4, R6, and R7 are the same or different, each of which is a hydrogen or a substituent group R5 is optional A group derived from hydrogen or substituent b, ring Ar is an aryl group substituted with 1 to 3 groups selected from aryl or substituent b, and substituent a is halogen, low-density, low-density, low-density oxygen, and Low sulfur, the substituent b is a group of halogen, lower alkyl, cyano, nitro and formula -Ο R ', formula -〇CONR9R10, formula -NR9R10, formula -NR8COR9, formula -C02R9 and formula -CONR9R1q ( In the above formula, R8 is as defined above, and R9 and R1 are the same or different, and each is selected from hydrogen, lower alkyl, lower alkoxy, aryl, or substituents 1 to 3 (substituted aryl). 2. If the compound in the scope of patent application No. 1, its pharmacologically acceptable salt, its ester or other derivative, wherein R1 is aryl, or is selected from halogen, lower alkyl, halogen lower alkyl, hydroxyl, lower oxygen And 1 to 3 substituted aryl groups of low alkylthio, R 2 is low alkyl, low alkenyl or low alkynyl, R 3 is a group of formula-ADE-Gn + (X_) n, [wherein in the above formula, -497-200300349 A is an oxygen atom, a sulfur atom, a group of the formula -CH20-and a formula -CH2S- group, D is a C 2 alkylene group, a C 2-! 2 alkylene group containing an oxygen atom or a sulfur atom in the carbon chain Group, or C 2 _! 2 alkylene group containing aryl group in the carbon chain, E is a single bond or a group of the formula-NR8CO-(in the above formula, R 8 is hydrogen or a lower alkyl group), and Gn + is (i) A lower alkyl group substituted with a group selected from the substituent b and an ammonium group substituted with the same or different group 3 of the lower alkyl group, (ii) an ammonium group in which a nitrogen atom on the ring is bound to E, and further selected from a substituent b-substituted low alkyl, and 1-pyridyl, 1-pyridyl, or 1-pyridinyl, which may be substituted with a group 1 ~ 3 selected from substituent b, and may be fused with a benzene ring, ( iii) the carbon atom on the meso ring is bonded to E, and at least one nitrogen atom on the ring Pyridinyl, pyridyl, or pyrimidyl, which can be substituted with a lower alkyl group or an oxy group to form an ammonium group, and can be fused with a benzene ring. (Iv) The nitrogen atom on the intermediate ring is bonded to E, and the nitrogen atom is low. 1-piperidinyl, 1-piperidinyl, or 4-morpholinyl substituted with cinnyl or oxy to form an ammonium group, (v) may have a lower alkyl group or a substituent substituted with a group selected from the substituent b b and oxy-substituted 1- (1-azobicyclo [2.2.2] octyl) yl or 1- (4-acyl-1-azobicyclo [2.2.2] octyl) (Vi) the carbon atom on the meso ring is bonded to E, and at least one nitrogen atom on the ring is substituted with a lower alkyl group or an oxy group to form an ammonium group (1-azobicyclo [2.2.2] octyl) Or (4-acyl-1 -azobicyclo [2 · 2. 2] octyl),-498-200300349 (vii) may have 1 to 3 substituted 1-tetrahydrothienyl or hydroxy groups or Tetrahydrothiopyranyl, (viii) a lower alkyl substituted with a group selected from the substituent b and a sulfofluorenyl substituted with the same or different group of the lower alkyl group, or (i X) has a substituent selected from the group b-substituted low alkyl and low-alkyl same or different group 3 substituted phosphino, X- is anion , Η is an integer of 1 or 2], R4, R6 and R7 are the same or different groups, each of which is hydrogen or a substituent a, R5 is a group selected from hydrogen or a substituent b, and the ring Ar is selected from an aromatic group 1 to 3 substituted aryl groups of substituent or substituent b, substituent a is halogen, lower alkyl, hydroxyl, lower alkoxy, and lower alkylthio, and substituent b is halogen, lower alkyl, amino, Nitro and formula-OR9, formula-oconr9r1 (), formula-nr9r1 (), formula-nr8cor9, formula-co2r9 and formula-CONR9R1g (in the above formula, R8 is as defined above, R9 and R 1 ^ are the same or Different, each selected from the group consisting of hydrogen, lower alkyl, aryl, or 1 to 3 substituted aryl groups of substituent a). 3. If the compound or pharmacologically acceptable salt thereof according to item 1 or 2 of the patent application scope, it is the compound of formula (I) or its pharmacologically acceptable salt. 4. If the compound or pharmacologically acceptable salt thereof according to item 1 or 2 of the patent application scope, it is the compound of formula (II) or its pharmacologically acceptable salt. 5. The compound or any of its medicines-499-200300349, such as R1 is an aryl group, or R1 is selected from the group consisting of halogen, lower alkyl and lower alkoxy. ~ 3 radicals substituted aryl. 6. The compound or pharmacologically acceptable salt thereof according to any one of items 1 to 4 of the scope of patent application, wherein R1 is a phenyl group, or has a member selected from the group consisting of a fluorine atom, a chlorine atom, an alkyl group, and (^ _2 alkoxy group 1 ~ 3 groups substituted phenyl. 7. The compound or any of its pharmacologically acceptable salts according to any one of items 1 to 4 of the scope of patent application, wherein R1 is substituted with 1 ~ 3 groups selected from fluorine atom or chlorine atom 8. The compound or pharmacologically acceptable salt thereof according to any one of claims 1 to 4 in the scope of application for patent, wherein R1 is 3-fluorophenyl, 3,5-dichlorophenyl, 3,4-di Fluorophenyl or 3,5-difluorophenyl. 9. The compound or pharmacologically acceptable salt thereof according to any one of claims 1 to 4, in which R1 is 3,5-difluorophenyl. 1 0 A compound or a pharmacologically acceptable salt thereof according to any one of items 1 to 9 of the scope of patent application, wherein R 2 is a lower alkyl group, a C 2 _ 3 alkenyl group or a C 2 _ 3 alkynyl group. 1 1. The compound or the pharmacologically acceptable salt thereof according to any one of the items 1 to 9 in which R2 is a low alkyl group. 1 2. The compound or the pharmacologically acceptable salt thereof according to any one of the claims 1 to 9 -500- 200300349 R2 is C i _ 4 alkyl group. 1 3. As the compound or pharmacologically acceptable salt of any one of items 1 to 6 in the scope of patent application, wherein R 2 is Ci 2 alkyl group. 1 4. A compound or a pharmacologically acceptable salt thereof according to any one of the items 1 to 6 in which A is an oxygen atom or a sulfur atom. 1 5 · The compound or any of its pharmacologically acceptable items according to any of the claims 1 to 13 in the scope of the application for a patent A salt, where A is an oxygen atom. 16. The compound of any one of items 1 to 15 or a pharmacologically acceptable salt thereof, wherein D is C! _I 2 alkylene, or a carbon chain C 2 _ i 2 alkylene group containing an oxygen atom or a sulfur atom. 1 7. The compound or a pharmacologically acceptable salt thereof according to any one of claims 1 to 15 of the scope of application for a patent, wherein D is C4_1 () alkylene Or C2-6 oxo radical containing 1 to 2 oxygen atoms or sulfur atoms in the carbon chain. 1 8. The compound or a pharmacologically acceptable salt thereof according to any one of items 1 to 15 in the scope of patent application, wherein D is C 4 _ i 0 alkylene. 1 9. The compound or a pharmacologically acceptable salt thereof according to any one of items 1 to 15 of the scope of patent application, wherein D is Hexamethylene, heptamethylene or octamethylene. 2 0. The compound according to any one of items 1 to 15 of the scope of application for a patent or its -501- 200300349 pharmacologically acceptable salt, where D is a carbon bond C2-12 has a square base. 2 1 · As a compound or a pharmacologically acceptable salt of any one of the items 1 to 15 in the scope of patent application, where D is a C2-4 containing a square base in the carbon bond. Yuanji. 2 2. The compound or a pharmacologically acceptable salt thereof according to any one of claims 1 to 15 in the scope of application for a patent, wherein D is a C2_4 alkylene group containing a phenyl group in the carbon chain. 2 3. The compound or pharmacologically acceptable salt thereof according to any one of claims 1 to 22 in the scope of patent application, wherein E is a single bond. 24. The compound or a pharmacologically acceptable salt thereof according to any one of claims 1 to 23 in the scope of application for a patent, wherein Gn + is: (i) selected from the group consisting of a formula-OR9 group and a formula-NR9R1 () group with low substitution Alkyl and lower alkyl with the same or different 3 substituted ammonium groups, (ii) an ammonium group in which the nitrogen atom on the ring is bound to E, a lower alkyl substituted with a group selected from substituent b, and may have 1-pyridinyl, 1-pyridinyl, or 1-pyridinyl substituted with 1 to 3 substituents of the substituent b, which can be fused with a benzene ring, (iii) the carbon atom on the secondary mesogenic ring is bound to E, At least one nitrogen atom on the ring is substituted with a lower alkyl group or an oxy group to form an ammonium group, and a pyridinyl group, a pyridyl group, or a pyrimidyl group which can be fused with a benzene ring. (Iv) The nitrogen atom and E on the intermediate ring 1-piperidinyl, 1-piperidinyl, or 4-morpholinyl in which the nitrogen atom is substituted with a lower alkyl group or an oxy group to form an ammonium group, -502-200300349 (V) may have a substituent selected b-substituted lower alkyl, substituted b and oxy-substituted 1- (1-azobicyclo [2.2.2] octyl) yl or 1- (4-azol-1-azobicyclo [ 2 · 2 · 2] octyl) group, (vi) the carbon atom on the meso ring is bonded to E, and at least 1 on the ring A nitrogen atom is substituted with a lower alkyl group or an oxy group to form an (1-azobicyclo [2 · 2 · 2] octyl) group or an (4-az-1-azobicyclo [2.2.2] octyl group) ) Group, (vii) may have 1 to 3 substituted 1-tetrahydrothienyl groups having oxy or hydroxyl groups, and (viii) is selected from the group consisting of lower alkyl groups and lower alkyl groups containing formula-OR9 group and formula-NR9R1 () group Sulfofluorene group substituted with the same or different group of the same group or (ix) is selected from the same or different groups substituted with the same or different group containing the lower alkyl group of the formula-OR9 group and the formula-NR9R1 () group Phosphonium. 25. The compound or a pharmacologically acceptable salt thereof according to any one of claims 1 to 23 in the scope of patent application, wherein Gn + is: π (i) selected from the group consisting of hydroxy or di-lower alkylamine-substituted low alkyl and low 3 ammonium groups substituted with the same or different alkyl groups, (ii) ammonium groups in which the nitrogen atom on the ring is bound to E, lower alkyl groups substituted with a group selected from substituent b, and optionally selected from substituents The 1 to 3 substituents of b are substituted with 1-pyridinyl, 1-pyridinyl, or 1-pyridinyl, which can be fused with a benzene ring. (iii) A carbon atom on the meso ring is bonded to E, and at least one is on the ring. A nitrogen atom is substituted by a lower alkyl group or an oxy group to form an ammonium group, and can be fused with a benzene ring, such as pyridinium, pyridinium, or pyridinium. (Iv) The nitrogen atom on the secondary mediate ring is bound to E, and the nitrogen 1-piperidyl, 1-piperidinyl, or -503-200300349 4-morpholinyl in which an atom is substituted with a lower alkyl group or an oxy group, (v) may be substituted with a group selected from substituent b 1- (1-Azobicyclo [2.2.2] octyl) substituted with 1- (1-azobicyclo [2.2.2] octyl) or 1- (4 -az-1-azobicyclo [2 · 2 · 2 ] Octyl), (vi) the carbon atom on the meso ring is bonded to E and at least one nitrogen on the ring (1 -Azobicyclo [2.2.2] octyl) or (4 -Acryl-1-azobicyclo [2 · 2 · 2] octyl) is substituted by a lower alkyl group or oxy group to form an ammonium group. (Vii) 1-tetrahydrothienyl, (viii) selected from the group consisting of hydroxy or di-loweramino substituted lower alkyl and lower alkyl identical or different 2 substituted sulfonyl, or (i X ) Selected from the group consisting of hydroxy or di-loweralkylamino-substituted lower alkyl groups and the same or different 3 -substituted phosphino groups of lower alkyl groups. 2 6. The compound or a pharmacologically acceptable salt thereof according to any one of claims 1 to 23 in the scope of the patent application, wherein G η + is: (i) a tri-low alkylammonium group, (ii) a nitrogen atom on the ring and E-bound ammonium group, a lower alkyl group substituted with a group selected from substituent b, and a 1-pyridinyl group substituted with a group 1 to 3 selected from substituent b and fused with a benzene ring, 1 -Pyridyl or 1-pyridinyl, (iii) the carbon atom on the secondary median ring is combined with E, at least one nitrogen atom on the ring is replaced by a lower alkyl group or an oxy group to form an ammonium group, and can be fused with a benzene ring Pyridinyl, pyridinyl or pyrimidyl, (iv) a nitrogen atom on the secondary median ring is bound to E, and the nitrogen atom is substituted with a lower alkyl or oxy group to form an ammonium group. Piperazinyl or 4-morpholinyl, -504-200300349 (V) may have a 1- (1-azobicyclic ring substituted with a lower alkyl group substituted with a substituent b, a substituted b and an oxy group [2.2.2] octyl) group or 1- (4- -az-1-azobicyclo [2 · 2 · 2] octyl) group, (vi) the carbon atom on the meso ring is bonded to E, and at least 1 on the ring (1-Azobicyclo [2.2.2] octyl Group), or (4-acyl-1-azobicyclo [2 · 2 · 2] octyl) group, (ν i i i) dioxosulfonyl group, or (i X) tri-oligoalkylphosphonium group. 27. The compound or pharmacologically acceptable salt thereof according to any one of claims 1 to 23, wherein Gn + is: (ii) an ammonium group in which a nitrogen atom on the ring is bound to E, and is further selected from a substituent b-substituted low alkyl, and 1-pyridinyl, 1-pyridinyl, or 1-pyridinyl, which may be substituted with 1 to 3 substituents of the substituent b and may be fused with a benzene ring, ( iii) A pyridinyl, pyridyl or pyrimidyl group that is bonded to a carbon atom on the meso ring and E, at least one nitrogen atom on the ring is substituted with a lower alkyl group or an oxy group to form an ammonium group, and can be fused with a benzene ring , (I ν) The nitrogen atom on the secondary meso ring is combined with E, and the nitrogen atom is substituted with a lower alkyl group or an oxy group to form an ammonium group, a 1-piperidinyl group, a 1-piperidinyl group or a 4-morpholinyl group '( ν) may be selected from the group consisting of a lower alkyl group substituted with substituent b, a 1- (1-azobis (2.2.2) amyl) group substituted with a substituent b and an oxy group, or a 1- ( 4-acyl-1-azobicyclo [2 · 2 · 2] octyl) group, or (vi) the carbon atom on the secondary meso ring is bonded to E, and at least one nitrogen atom on the ring is substituted with a lower alkyl group or an oxy group, and Formation of (1-azobicyclo200300349 [2.2.2] octyl) or ammonium [2 · 2 · 2] octyl) group. 28. The compound or pharmacologically acceptable salt thereof according to any one of claims 1 to 23 in the scope of patent application, wherein Gn + is: (ii) a low-alkyl group selected from the group substituted with substituent b, and optionally A 1-pyridinyl group which is substituted by the groups 1 to 3 of the substituent b and can be fused with a benzene ring. (Iii) The carbon atom on the secondary meso ring is combined with E, and at least one nitrogen atom on the ring is lower alkyl or oxygen. (Iv) an ammonium group which can be fused with a benzene ring to form an ammonium group, (iv) a nitrogen atom on the ring is substituted with a lower alkyl group or an oxy group to form an ammonium 1-piperazinyl group, (v) may have Selected from the group consisting of a lower alkyl substituted with a substituent b, a 1- (buzobicyclo [2 · 2 · 2] octyl) group substituted with a substituent b and an oxy group or a 1- (4-acyl-1 -Azobicyclo [2.2.2] octyl), or (vi) the carbon atom on the secondary meso ring is combined with E, and at least one nitrogen atom on the ring is replaced by a lower alkyl group to form an (1-azobicyclo [2 · 2 · 2] octyl) group or (4-az-pyrazobicyclo [2.2.2] octyl) group. 29. The compound or pharmacologically acceptable salt thereof according to any one of claims 1 to 23 in the scope of application for a patent, wherein Gn + is: (ii) 1-pyridine which may be substituted with a group 1 to 3 selected from substituent b Pyridinyl (iii) the carbon atom on the secondary mediate ring is bonded to E, at least one nitrogen atom on the ring is substituted with a low alkyl group to form an ammonium pyridinium group, and (iv) the nitrogen atom on the ring is substituted with a low alkyl group to form ammonium 1-piperazinyl, or -506- 200300349 (V) may have a 1- (1-azobicyclo [2 · 2 · 2] octyl) group substituted with a group selected from substituent b and oxy group, or 1- (4 -Acryl-1-azobicyclo [2 · 2 · 2] halfyl) group ° 3 0. The compound or pharmacologically acceptable salt thereof according to any one of items 1 to 23 of the scope of patent application, wherein Gn + is: (ii) a 1-pyridinyl group which may be substituted with a low alkyl group, a formula-OR9 group and a formula -NR9R1C) group, or (v) may have a low alkyl group, a formula-OR9 group, and a formula -NR9R1 ( ) Group and oxy-substituted 1- (1-azobicyclo [2.2.2] octyl) group or 1- (4-az-1-azosinobicyclo [2.2.2] octyl) group. 31. A compound or a pharmacologically acceptable salt thereof according to any one of claims 1 to 23 in the scope of patent application, wherein Gn + is: (i) may have a low alkyl group, a hydroxyl group, a low alkoxy group, and a diloweramine 1-pyridinyl, or (v) may have a low radical, a radical, a lower radical, a lower radical and a 1- (1-azobicyclo [2.2. 2] octyl) or 1- (4-acyl-azobicyclo [2.2.2] octyl). · 32. A compound or a pharmacologically acceptable salt thereof according to any one of claims 1 to 23 in the scope of patent application, wherein G n + is: (i) 1-pyridinyl group which may be substituted by a hydroxyl group and a lower alkoxy group , Or (v) may have 1-(1-azobicyclo [2 · 2 · 2] octyl) or 1-(1-azobicyclo [2 · 2 · 2] octyl) substituted with lower alkyl, hydroxyl, lower alkoxy, diloweramino and oxy. (4-Acryl-azobicyclo [2 · 2 · 2] octyl) yl. 3 3. The compound or pharmacologically acceptable salt thereof according to any one of claims 1 to 23, wherein Gn + is:-507-200300349 1-pyridinyl, 1- (1-azobicyclo [2.2 .2] octyl) group and 1- (4-az-1--1-azobicyclo [2 · 2,2] octyl) group. 34. The compound or pharmacologically acceptable salt thereof according to any one of claims 1 to 23 in the scope of application for a patent, wherein Gn + is: (iv) a nitrogen atom on the ring is substituted with a low alkyl group to form an ammonium group. Well base. 35. The compound or pharmacologically acceptable salt thereof according to any one of claims 1 to 23 in the scope of patent application, wherein Gn + is: (ii) a formula -C02R9 group and a formula -CONR9R1 () group or an aryl group ♦ Replaced by 1-pyridinyl. 36. The compound according to any one of claims 1 to 23 or a pharmacologically acceptable salt thereof, wherein Gn + is (i) substituted with 1-pyridinyl group of aryl. 37. The compound according to any one of claims 1 to 36 or a pharmacologically acceptable salt thereof, wherein X_ is a halogen ion. 38. The compound of any one of claims 1 to 37 or a pharmacologically acceptable salt thereof, wherein R5 is hydrogen, a formula-OR9 group and a formula-NR9R1 () group. 39. The compound according to any one of claims 1 to 37 or a pharmacologically acceptable salt thereof, wherein R5 is a group of formula-OR9. 40. The compound or pharmacologically acceptable salt thereof according to any one of claims 1 to 37 in the scope of patent application, wherein R5 is a low-oxyl group. -508-200300349 4 1. The compound or pharmacologically acceptable salt thereof according to any one of claims 1 to 40 in the scope of patent application, wherein R4, R6 and R7 are the same or different, each is hydrogen, halogen, low alkyl Or low alkoxy. 4 2. A compound or a pharmacologically acceptable salt thereof according to any one of claims 1 to 40 in the scope of patent application, wherein R4, R6 and R7 are the same or different, and each is hydrogen, fluorine atom, chlorine atom, C i _ 2 alkyl or C i _ 2 alkoxy. 4 3. The compound or pharmacologically acceptable salt thereof according to any one of claims 1 to 40 in the scope of patent application, wherein R4, R6 and R7 are hydrogen. 4 4. The compound or pharmacologically acceptable salt thereof according to any one of claims 1 to 40 in the scope of patent application, wherein R4, R6 and R7 are methoxy groups. 4 5. The compound according to any one of claims 1 to 44 or a pharmacologically acceptable salt thereof, wherein ring Ar is an aryl group substituted with a group 1 to 3 selected from substituent b. 4 6. The compound or a pharmacologically acceptable salt thereof according to any one of claims 1 to 44 in the scope of the patent application, wherein the ring Ar is an aryl group substituted with a group 1 to 3 selected from the group of the formula-OR9 group and the formula-NR9R1 () group. . 47. The compound or a pharmacologically acceptable salt thereof according to any one of claims 1 to 4 in the scope of the patent application, wherein the ring Ar is an aryl group substituted with a group 1 to 3 of the formula -OR9. 48. The compound according to any one of claims 1 to 44 or its pharmacologically acceptable salt, wherein ring A is an aryl group substituted with 1 to 3 lower alkoxy groups. 49. The compound according to any one of claims 1 to 44 or a pharmacologically acceptable salt thereof, wherein ring A is 3-methoxyphenyl or 3,5-dimethoxyphenyl. 50. The compound or a pharmacologically acceptable salt thereof according to any one of claims 1 to 4 in the scope of the patent application, wherein ring A is 3,5-diethoxyphenyl or 3-ethoxy-5-propoxybenzene base 51. The compound or pharmacologically acceptable salt thereof according to any one of claims 1 to 50 in the scope of patent application, wherein η is an integer of 1. 5 2. The compound or pharmacologically acceptable salt thereof according to item 1 or 2 of the scope of patent application, which is 1- {2- {3- {3- [N- (3,5-difluorophenyl) -N -Ethylaminomethylmethyl] -7-methoxy-4-oxo-4H-quinoline-l-yl} -5 -methoxyphenoxymethyl} benzyl} P ratio ingots,. Chloride 1-{ 2- {3- {3- [N- (3,5-difluorophenyl) -ethylaminomethyl] -7-methoxy-4-oxo-4H-quinoline-l-yl} -5 -Methoxyphenoxymethyl} benzyl} azobicyclo [2.2 · 2] octane, 1- {2- {3- {3- [N- (3,5-difluorophenyl) -ethyl chloride Carbamoyl 7-methoxy-4-oxo-4,4-quinoline-1-yl bu 5-methoxyphenoxymethyl} benzyl bu 4-acyl-1 -azobicyclo [2.2.2] Octane, 1- {2- {3- {3- [N- (3,5-difluorophenyl) -ethylaminomethyl] -7-methoxy-4-oxo-4, -quinine Porphyrin-l-yl} -5 -methoxyphenoxymethyl} -510- 200300349 benzylbenzene 4 -acyl-1 -azobicyclo [2 · 2 · 2] octane, bromide 1- {7- [ 3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquine Phenolin-7-yloxy] heptyl, pyridinium, 1- {7- [3- [N- (3,5-difluorophenyl) -ethylaminomethylmethyl] -1- (3, 5-Dimethoxy Phenyl) -4 -oxo-1,4-dihydroquinolin-7-yloxy] heptylbu 1-azobicyclo [2 · 2 · 2] octane, 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3, 5-dimethoxyphenyl) -4-oxy -1,4 -dihydroquinoline-7-yloxy] heptylbu 1-azobicyclo [2 · 2 · 2] octane, 1- {7- [3- [Ν- (3, 5 -difluorophenyl) -ethylaminomethyl] -1- (3, 5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinolin-7-yloxy] heptyl Bu 4-Acridine-1-azobicyclo [2.2.2] octane, 1- {7- [3- [N- (3,5-difluorophenyl) -ethylaminomethyl] -1 -(3,5-monomethoxybenzyl) -4 -oxo-1,4-_ * aspirin-7 -yloxy] heptylub 4_az-1-azobicyclo [2.2.2] Octane, 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3,5 -monomethoxybenzyl) -4-oxy -1,4-monoquinone-7-ylsulfanyl] heptyl} pyridine, 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethyl bromide Carbamate 1- (3,5-dimethoxyphenyl) -4 -oxo-1,4-dihydroquinolin-7-ylsulfanyl] heptyl} -1_azobicyclo [2 · 2 · 2] octane and 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine 1- (3,5 -dimethyl) bromide (Oxyphenyl) -4-oxo-1,4-dihydroquinolin-7-ylsulfanyl] heptylb 4-azyl-1 -azobicyclo [2.2 · 2] octane. -511- 200300349 5 3. If the compound or the pharmacologically acceptable salt thereof in the scope of the application for patent 1 or 2 is brominated 1- (7- {1- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -4-oxo-1,4-dihydroquinolin-7-yloxy} heptyl) _4 · Acryl-1 -Azobicyclo [2.2.2] octane, 1- {7- [3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3 , 5-dimethoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy] heptyl} -1-carboxamidine, m 1- (8- {1- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -4-oxo-1,4-dihydroquinoline- 7-yloxy} octyl) -1-methylpiperidine, 1- (7- {1- (3,5-diethoxyphenyl) -3- [N- (3,5-difluoro Phenyl) -N-ethylaminomethylmethyl] -5 -methoxy-4-oxo-1,4-dihydroquinoline-7-'yloxy} heptyl) -1 -methylpiperidine, 1- (7- {1- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -5 -methyl Oxy-4-oxo-1,4-dihydroquinoline-7-yloxy} heptyl) -4 -acyl-1 -azobicyclo [2 · 2 · 2] octane, dibromide (8 -{1- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine 5-methoxy-4-oxo- 1,4-dihydroquinoline-7-yloxy} octyl) -4-acyl-1-azobicyclo [2.2.2] octane, bromide 1- (7- {1- (3,5 -Diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -4 -oxy-1,4-dihydroquinoline-7-yloxy Methyl} heptyl) -1-piperidine, and 1- {7- {3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -1- (3 -Ethoxy-5-propoxyphenyl) -4 -oxo-1,4-one-stop command-7-yl-512- 200300349 oxy} heptylbu 4 -az-1-azobicyclo [2 · 2 · 2] octane. 54. The compound or pharmacologically acceptable salt thereof according to item 1 or 2 of the scope of patent application, wherein 1- (7- {1- (3,5-diethoxyphenyl) -3- [N- (3 , 5 -difluorophenyl) ethylaminomethyl] -4-oxo-1,4-dihydroquinoline-7-yloxy} heptyl) -4-acid-1-azobicyclo [2 · 2 · 2] octane, 1- {7- [3- [N- (3,5-difluorophenyl) -ethylaminomethyl] -1- (3,5-dimethoxyphenyl) -4 -oxy-1 , 4-dihydroquinolin-7-yloxy] heptyl 丨 -1-methylpiperidine, 1- (8- {1- (3,5-diethoxyphenyl) -3- [N -(3,5 -difluorophenyl) -N-ethylamine formamidine 4-oxo-1,4-dihydroquinoline-7-yloxy} octyl) -1-methylpiperidine, chlorine 1- (7- {1- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -ethylaminomethylmethyl] -5 -methoxy- 4-oxo-1,4-dihydroquinoline-7-yloxy} heptyl) -1-methylpiperidine, 1- (7- {1- (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminomethylmethyl] -5 -methyl Oxy-4-oxo-1,4-dihydroquinoline-7 · yloxy} heptyl) -4 -acridyl-pyrazobicyclo [2.2.2] octane trichloride (3,5-diethoxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylaminemethylmethyl] -5-methoxy-4-oxo-1,4 -Dihydroquinoline- 7-yloxy 丨 octyl) -4 -azine-1-azobicyclo [2.2.2] octane, 1- (7- {1- (3,5 -diethyl chloride) Oxyphenyl) -3- [N- (3,5-difluorophenyl) -N-ethylamine formamidine 4-oxo-1,4-dihydroquinolin-7-yloxy} heptyl ) -1-methylpiperidine and 1- {7- {3- [N- (3,5-difluorophenyl) -ethylaminomethylmethyl-513- 200300349] -l- (3-ethyl Oxy-5-propoxyphenyl) -4-oxo-1,4-dihydroquinoline-7-yloxy 丨 heptylbu 4-azine-1-azobicyclo [2.2.2] octane. 55. A pharmaceutical composition containing the compound according to any one of claims 1 to 54 of the scope of patent application, a pharmacologically acceptable salt, an ester or other derivative thereof as an active ingredient. 56. The pharmaceutical composition according to item 55 of the patent application scope is used for preventing or treating hyperlipidemia. 57. The pharmaceutical composition according to item 55 of the scope of patent application, for preventing or treating arteriosclerosis. 58. The compound according to any one of claims 1 to 54 of the scope of application for a patent, its pharmacologically acceptable salt, its ester or other derivative is used to manufacture a pharmaceutical composition for preventing or treating hyperlipidemia. 59. The compound according to any one of claims 1 to 54 of the scope of application for a patent, its pharmacologically acceptable salt, its ester or other derivative thereof is used to manufacture a pharmaceutical composition for preventing or treating arteriosclerosis. -514-