MXPA01007251A - Quinoline derivatives and quinazoline derivatives - Google Patents

Abstract

Compounds having an antitumor activity and causing no morphological change in cells. Compounds of general formula (I), pharmaceutically acceptable salts of them and solvates thereof, and medicinal compositions containing the same. In formula (1), X and Z represent each CH or N;R1-3 represent each H, optionally substituted alkoxy, etc.;R4 represents H;R5-8 represent each H, halogeno, alkyl, alkoxy, alkylthio, nitro or amino, provided that all of R5-8 do not represent H simultaneously;R9 and R10 represent each H, alkyl or alkylcarbonyl;and R11 represents alkyl, alkenyl, alkynyl or aralkyl.

Description

QUINQLINE DERIVATIVES AND QUINAZOLINE DERIVATIVES BACKGROUND OF THE INVENTION FIELD OF THE INVENTION The present invention relates to quinoline derivatives and quinazoline derivatives having antitumor activity.

More particularly, the present invention relates to quinoline derivatives and quinazoline derivatives which are useful for the treatment of diseases such as, for example, tumors, diabetic retinopathy, chronic rheumatism, psoriasis, atherosclerosis, and Kaposi's sarcoma. BACKGROUND OF THE ART WO 97/17329 discloses quinoline derivatives and quinazoline derivatives having an antitumor activity. WO 97/17329, however, does not disclose the effects of these quinoline derivatives and quinazoline derivatives on cytomorphosis or the compounds according to the present invention. SUMMARY OF THE INVENTION The present inventors have found that a group of quinoline derivatives and quinazoline derivatives has an antitumor activity and, at the same time, has no significant effect on cytomorphosis. The activity of increasing the size of the cells can be considered as an induction activity of tissue disorders. An object of the present invention is to offer compounds that have antitumor activity and, at the same time, do not have a significant effect on cytomorphosis. In accordance with the present invention, there is provided a compound represented by the formula (I) or a pharmaceutically acceptable salt or solvate thereof: wherein X and Z represent, each, CH or N; R1, R2, and R3, which may be the same or different, represent a hydrogen atom, C? _6 alkyl, C? _6 alkoxy, C2_6 alkenyl, C2_6 alkynyl, nitro, or amino, said C? _6 alkyl? , C2-6 alkenyl C6-6 alkenyl and C2-e alkynyl are optionally substituted by a halogen atom; hydroxyl; C 4 -4 alkoxy; C 1 - alkoxycarbonyl; amino wherein one or two hydrogen atoms are optionally substituted by C ?_6 alkyl optionally substituted by hydroxyl or C? -4 alco alkoxy; group wherein R and R 3, which may be the same or different, represent a hydrogen atom or C 4 alkyl, said alkyl is optionally substituted by hydroxyl or C 1 alkoxy; or group R14- (S) -m- wherein R14 represents a saturated or unsaturated carbocyclic or heterocyclic group of three to seven members optionally substituted by C? -4 alkyl, and m is 0 or 1; R4 represents a hydrogen atom; R5, R6, R7 and R8, which may be the same or different, represent a hydrogen atom, a halogen atom, C? -4 alkyl / C ?4 alkoxy / C 1-4 alkylthio, nitro or amino, provided that R 5 , R6, R7 and R8 do not simultaneously represent a hydrogen atom; R9 and R10, which may be the same or different, represent a hydrogen atom, C? -6 alkyl or C? Alkylcarbonyl-the C? _6 alkyl or C? _ Alkylcarbonyl portion is optionally substituted by a halogen atom; C 4 -4 alkoxy, amino optionally substituted by C 1 - alkyl, optionally substituted by C 1 alkoxy; or a saturated or unsaturated carbocyclic or heterocyclic group of three to seven members; and R 11 represents C? -6 alkyl, C2-6 alkenyl or alkynyl C2-6 (said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted by a halogen atom or C6-6 alkoxy), or R 15- (CH2) n- wherein n is an integer from 0 to 4 and R 15 represents a saturated or unsaturated carbocyclic or heterocyclic group of three to seven members optionally substituted by a halogen atom, C? -6 alkyl, or Ci-e alkoxy and is optionally condensed with another carbocyclic ring or three to seven membered heterocyclic ring saturated or unsaturated to form a bicyclic ring. The compound according to the present invention is useful, for example for the treatment of tumor, diabetic retinopathy, chronic rheumatism, psoriasis, atherosclerosis, Kaposi's sarcoma and solid tumor. DETAILED DESCRIPTION OF THE INVENTION Compound As used hereinthe term "C ?_6 alkyl" and "C?-C6 alkoxy" as a group or part of a group mean respectively straight-chain or branched-chain alkyl and alkoxy having 1 to 6, preferably 1 to 4, atoms of carbon. As used herein, the term "C2_6 alkenyl" and "C2-6 alkynyl" as a group or part of a group mean respectively straight chain or branched alkenyl and alkynyl having from 2 to 6, preferably from 2 to 4. carbon atoms. Examples of C ?S alkyl include methyl, ethyl, n-propyl, isopropyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, and n-hexyl. Examples of C6-C6 alkoxy include methoxy, ethoxy, n-propoxy, i-prc-poxy, n-butoxy, i-butoxy, s-butoxy, and t-butoxy. Examples of C2 ~ 6 alkenyl include allyl, butenyl, pentenyl, and hexenyl. Examples of C2_ alkynyl include 2-propynyl, butynyl, pentynyl, and hexynyl. The term "halogen atom" means a fluorine, chlorine, bromine or iodine atom. The saturated or unsaturated three- or seven-membered carbocyclic or heterocyclic ring is preferably a saturated or unsaturated carbocyclic or heterocyclic ring of five to seven members, more preferably five or six members. Examples of three to seven saturated or unsaturated carbocyclic groups include phenyl, cycloheptyl, cyclohexyl, and cyclopentyl. The saturated or unsaturated three to seven membered heterocyclic ring contains at least one heteroatom selected from oxygen, nitrogen and sulfur atoms. The term "heteroatom" used herein refers to an oxygen, nitrogen or sulfur atom. Examples of three to seven saturated or unsaturated heterocyclic groups include pyridyl, piperidino, piperazino, morpholino, imidazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, pyrrolidinyl, and pyrazolyl. The saturated or unsaturated heterocyclic group which may be represented by R15 and R32 may be fused with another saturated or unsaturated heterocyclic ring to form a bicyclic ring. Such condensed cyclic groups include naphthyl, indanyl, quinolyl, and quinazolinyl. R1 preferably represents a hydrogen atom. R2 and R3, preferably represent C6-C6 alkoxy, optionally substituted. Alkyl C? -6, C? -6 alkoxy, C2_e alkenyl and C2-6 alkynyl, which may be represented by R1, R2, and R3, may be substituted by a group R14- (S) -m-. The carbocyclic or heterocyclic group, which may be represented by R 14, preferably represents a saturated or unsaturated carbocyclic or heterocyclic group of five or six members. The carbocyclic group more preferably represents phenyl. The heterocyclic group more preferably represents a saturated or unsaturated five-membered heterocyclic group containing one to four nitrogen atoms or a saturated or unsaturated six-membered heterocyclic group (preferably pyridyl) containing one or two heteroatoms selected from among atoms of nitrogen and oxygen. More specifically, the heteroatom constituting the six-membered heterocyclic group can be a nitrogen atom and an oxygen atom, or one or two nitrogen atoms. When m is 0 (zero), - (S) m- represents a link.

The substituted C6-6 alkoxy group, which may be represented by R1, R2, and R3, preferably represents a group R31- (CH2) -pO- wherein R31 represents a halogen atom, hydroxyl, C6 alkoxy, C 1 - alkoxycarbonyl, wherein one or two hydrogen atoms are optionally substituted by C 1 - alkyl optionally substituted by hydroxy or C 1 alkoxy - group R 12 R 13 N - C (= 0) - 0 - wherein R 12 and R 13 are conformity with that defined in formula (I); or group R14- (S) -m- wherein R14 may be in accordance with that defined in formula (I); P is an integer from 1 to 6, preferably from 1 to 4, with more preferably 1 or 2, particularly 1. A group of the preferred compounds represented by the formula (I) includes: Compounds wherein R 1 represents an atom of hydrogen and R.sup.2 and R.sup.3, represent C.sub.1-4 unsubstituted alkoxy, preferably methoxy; Compounds wherein R 1 represents a hydrogen atom and R 2 represents substituted C 4 -4 alkoxy, preferably a group R 31 - (CH 2) - p - O - and R 3 represents unsubstituted C 1 - 4 alkoxy, preferably methoxy; and Compounds wherein R 1 represents a hydrogen atom, R 2 represents C 1 -4 unsubstituted alkoxy, preferably methoxy, and R 3 represents substituted C 1 -4 alkoxy, preferably R31- (CH 2) -p-0- group.

Another group of preferred compounds represented by formula (I) includes: Compounds wherein at least one of R5, R6, R7 and R8 represents a halogen atom, preferably a chlorine atom or a fluorine atom; Compounds wherein at least one of R5, R6, R7 and R8 represents C? - alkyl; Compounds wherein two of R5, R6, R7 and R8 represent methyl and the other two represent a hydrogen atom; Compounds wherein at least one of R 5, R 6, R 7 and R 8 represents nitro, amino, C 1 - alkoxy, or C 1 -4 alkylthio; Compounds wherein R 5, R 7 and R 8 represent a hydrogen atom and R 6 represents a halogen atom, more preferably a chlorine atom or a fluorine atom; Compounds wherein R 5 and R 6 represent C 1 - alkyl, more preferably methyl, and R 7 and R 8 represent a hydrogen atom; Compounds wherein R 5 and R 8 represent a hydrogen atom and R 6 and R 7 represent C 1 -4 alkyl, more preferably methyl; and Compounds wherein R5, R7 and R8 represent a hydrogen atom and R6 represents a C ?4 alkyl, C? -4 alkoxy, C? _4 alkylthio, nitro or amino. In R9 and R10 the saturated or unsaturated three- or seven-membered carbocyclic or heterocyclic group as a substituent preferably represents a saturated or unsaturated five or six membered carbocyclic or heterocyclic group. R9 and R10 preferably represent a hydrogen atom, methyl, ethyl, propyl, methoxymethyl, formyl, acetyl, benzyl, or phenethyl. Another group of preferred compounds represented by formula (I) includes: Compounds wherein R 1, R 9 and R 10 represent a hydrogen atom; and Compounds wherein R 1 represents a hydrogen atom and either R 9 and R 10 or both represent a group other than a hydrogen atom. In the group R15- (CH2) n- which can be represented by R11, n is preferably an integer from 0 to 2, more preferably 0 or 1. Preferred examples of R15 include a saturated or six-membered carbocyclic group. unsaturated, optionally substituted, more preferably phenyl, and an optionally substituted saturated or unsaturated six-membered heterocyclic group, more preferably pyridyl. The heteroatom (s) constituting the six-membered heterocyclic group may (more) consist more specifically of a nitrogen atom or a nitrogen atom and a nitrogen atom. - oxygen . An additional group of preferred compounds represented by the formula (I) includes compounds wherein X represents N or CH or Z represents CH. An additional group of preferred compounds represented by the formula (I) includes compounds represented by the formula (Ia): wherein X represents CH or N; R21, and R22, which may be the same or different, represent Ci-e alkoxy, unsubstituted or a group R31- (CH2) -pO- wherein R31 represents a halogen atom, hydroxyl, C? -4 alkoxy, C? -4 alco alkoxycarbonyl, amino wherein one or two carbon atoms hydrogen are optionally substituted by C? _4 alkyl optionally substituted by hydroxyl or C? -4 alco alkoxy, group R12R13N ~C (= 0) -0- wherein R12 and R13, which may be the same or different, represent a hydrogen atom or C? -4 alkyl, said alkyl is optionally substituted by hydroxyl or C? -4 alkoxy; or group R1- (S) -m- wherein R14 represents a carbocyclic or heterocyclic group of three to seven saturated or unsaturated members optionally substituted by C? _4 alkyl, and m is 0 or 1; and P is an integer from 1 to 6; R23, R24, R25 and R26, which may be the same or different, represent a hydrogen atom, a halogen atom, C? -4 alquiloalkyl, C? -4 alcoalkoxy, C? -4 alqualkylthio, nitro or amino, provided that R23, R24, R25 and R26 do not simultaneously represent a hydrogen atom; R27 and R28, which may be the same or different, represent a hydrogen atom, C? -6 alkyl or C? -4 alkylcarbonyl, the alkyl portion of C? -6 alkyl or C1-4 alkylcarbonyl, is optionally substituted by a halogen atom; C 4 -4 alkoxy; amino optionally substituted by C 1-4 alkyl, optionally substituted by C 1-4 alkoxy; or a saturated or unsaturated carbocyclic or heterocyclic group of three to seven members; and R29 represents C6_6 alkyl, C2_6 alkenyl or C2_6 alkynyl / (said C1_6 alkyl, C2_6 alkenyl and C2_6 alkynyl are each, optionally substituted by a halogen atom or C1-4 alkoxy) , or R32- (CH2) q- where q is an integer from 0 to 4 and R32 represents a saturated or unsaturated six-membered carbocyclic or heterocyclic group optionally substituted by a halogen atom, C1-4alkyl, or alkoxy C4-4 and this is optionally condensed with another saturated or unsaturated five or six membered heterocyclic ring or carbocyclic ring to form a bicyclic ring. R 21 and R can represent unsubstituted C 1 -6 alkoxy, preferably methoxy. Any of R21 and R22 can represent unsubstituted C?-6 alkoxy, preferably methoxy and the other represents a group R31- (CH2) -p-0-. In the group R31- (CH2) -p-0-, P is preferably 1 to 4, more preferably 1 or 2, especially 1. A group of preferred compounds represented by the formula (la) include: wherein at least one of R23, R24, R25 and R26 represents a halogen atom, preferably a chlorine atom or a fluorine atom; Compounds wherein at least one of R23, R24, R25 and R26 represents C? _4 alkyl; Compounds wherein two of R23, R24, R25 and R26 represents methyl and the other two represent a hydrogen atom; Compounds wherein at least one of R 23, R 24, R 25 and R 26 represents nitro, amino, C 1 - alkoxy, or C 1 - alkylthio; Compounds wherein R23, R25 and R26 represent a hydrogen atom and R24 represents a halogen atom, more preferably a chlorine atom or a fluorine atom; Compounds wherein R 23 and R 24 represent C 1 - alkyl, more preferably methyl, and R 25 and R 25 represent a hydrogen atom; Compounds wherein R 23 and R 26 represent a hydrogen atom and R 24 and R 25 represent C 1-4 alkyl, more preferably methyl; and Compounds wherein R23, R25 and R26 represent a hydrogen atom and R24 represents a C4_4alkyl, C4_4alkylthioalkyl or nitro or amino. Another group of preferred compounds represented by formula (la) include compounds wherein R 27 and R 28 represent a hydrogen atom. Another group of preferred compounds represented by formula (la) include compounds wherein either R 27 and R 28 or both represent a group other than a hydrogen atom. In R32- (CH2) q- which may be represented by R29, q is preferably an integer from 0 to 2, more preferably 0 or 1. Preferred examples of R32 include optionally substituted phenyl and a six-membered heterocyclic group saturated or unsaturated optionally substituted, more preferably pyridyl. The heteroatom (s) constituting the six-membered heterocyclic group may (more) consist more specifically of a nitrogen atom or a nitrogen atom and an oxygen atom. The heterocyclic group or saturated or unsaturated six-membered carbocyclic group, which may be represented by R32 is preferably fused to another saturated or unsaturated six-membered heterocyclic ring or carbocyclic ring to form a bicyclic ring. An additional group of preferred compounds represented by the formula (la) include: compounds wherein X represents CH or N; R21 and R22 represent unsubstituted C alco -4 alkoxy; R23, R25, and R2e represent a hydrogen atom; R 24 represents a halogen atom, C? _4 alkyl / C? _4 alkoxy, or nitro; R27 and RB represent a hydrogen atom; and R 29 represents C? _6 alkyl, C2-6 alkenyl or alkynyl C2-6, (said C6-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted by a halogen atom or C-) alkoxy), or - (CH2) q-R32 wherein q is an integer from 0 to 1 and R32 represents phenyl, pyridyl, or naphthyl, said phenyl, pyridyl and naphthyl are optionally substituted by a halogen atom, alkyl C1-4 or alkoxy C? _4. compounds wherein X represents CH or N; R21 and R22 represent unsubstituted C?-4 alkoxy; R23, R25, and R26 represent a hydrogen atom; R 24 represents a halogen atom, C? -4 C alco -4 alkoxy alkyl or nitro; any between R27 and R28 or both represent a group other than a hydrogen atom; and R29 represents C6-6 alkyl, C2_6 alkenyl or C2-6 alkynyl > - (said C6_6 alkyl, C2_6 alkenyl and C2_6 alkynyl are each optionally substituted by a halogen atom or C4_4 alkoxy), or - (CH2) q_R32 where q is a integer of 0 or 1 and R32 represents phenyl, pyridyl, or naphthyl, said phenyl, pyridyl and naphthyl are optionally substituted by a halogen atom, C? -4 alkyl or C 1-4 alkoxy. compounds wherein X represents CH or N; R21 and R22 represent unsubstituted C alco -4 alkoxy; R, R, and R represent a hydrogen atom; R 24 represents a halogen atom, C? -4 alkyl, C? -4 alkoxy, or nitro; R27 represents a hydrogen atom; R28 represents a group other than a hydrogen atom; and R29 represents C6_6 alkenyl C2_6 alkenyl or C2_6 alkynyl, (said C6_6 alkyl, C2_6 alkenyl and C2_6 alkynyl are each, optionally substituted by a halogen atom or C1-4 alkoxy) , or else - (CH2) q-R32 where q is an integer of 0 or 1 and R32 represents phenyl, pyridyl, or naphthyl, said phenyl, pyridyl and naphthyl are optionally substituted by a halogen atom, alkyl C? -4 or C1-4 alkoxy. compounds wherein X represents CH or N; any of R21 and R22 represents unsubstituted C1-4 alkoxy and the other represents a group R31- (CH2) -p-O-, preferably R21 represents unsubstituted C1-4 alkoxy and R22 represents a group R31- (CH2) -p-0-; R23, R25, and R26 represent a hydrogen atom; R 24 represents a halogen atom, C? -4 alkyl, C? _4 alkoxy, or nitro; R27 and R28 represent a hydrogen atom; and R29 represents C1-6 alkyl, C2_6 alkenyl or C2_ alkynyl 6, (said C?-Β alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted by a halogen atom or C 1-4 alkoxy), or - (CH 2) q-R 32 wherein q is an integer of 0 or 1 and R32 represents phenyl, pyridyl, or naphthyl, said phenyl, pyridyl and naphthyl are optionally substituted by a halogen atom, alkyl C1-4 or C? -4 alkoxy. compounds wherein X represents CH or N; any of R21 and R22 represents unsubstituted C1-4 alkoxy and the other represents a group R31- (CH2) -p-0-, preferably R21 represents C?-unsubstituted alkoxy and R22 represents a group R31- (CH2) -p-0-; R23, R25, and R26 represent a hydrogen atom; R 24 represents a halogen atom, C? -4 alkyl, C 1-4 alkoxy, or nitro; any between R27 and R28 or both represent a group other than a hydrogen atom; and R29 represents C?-β alkyl, C 2-6 alkenyl or alkynyl C2-6, (said C6_6 alkyl, C2_6 alkenyl and C2_6 alkynyl are each optionally substituted by a halogen atom or C4_4 alkoxy), or - (CH2) q-R32 where q is an integer of 0 or 1 and R32 represents phenyl, pyridyl, or naphthyl, said phenyl, pyridyl and naphthyl are optionally substituted by a halogen atom, C 1-4 alkyl or C 1-4 alkoxy. compounds wherein X represents CH or N; any of R21 and R22 represents unsubstituted C1-4 alkoxy and the other represents a group R31- (CH2) -p-0-, preferably R21 represents unsubstituted C1-4 alkoxy and R22 represents a group R, R, and R > 26 represent a hydrogen atom; R '24 represents a halogen atom, C 1-4 alkyl, C 1-4 alkoxy, or nitro; R 127 represents a hydrogen atom; R) represents a group other than a hydrogen atom; Y R '29 represents C? _6 alkyl, C2-6 alkenyl or alkynyl C2-6, (said C6-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted by a halogen atom or C1-4 alkoxy), or - (CH2) q-R32 in where q is an integer of 0 or 1 and R32 represents phenyl, pyridyl, or naphthyl, said phenyl, pyridyl and naphthyl are optionally substituted by a halogen atom, C? -4 alkyl or C 1-4 alkoxy. compounds wherein X represents CH or N; any of R > 21 and R represents unsubstituted C1-4 alkoxy and the other represents a group R31- (CH2) -p-0-, preferably R21 represents unsubstituted C1-4 alkoxy and R22 represents a group R31- (CH2) -p-0-; R23 and R26 represent a hydrogen atom; R24 and R25 represent a halogen atom, C1-4 alkyl, alkoxy C1-4, or nitro; R27 and R28 represent a hydrogen atom; and R 29 represents C 1-6 alkyl, C 2-7 alkenyl or C 2-6 alkynyl / (said C 1-6 alkyl) C 2-6 alkenyl and C 2-6 alkynyl are each, optionally substituted by a halogen atom or C 1-4 alkoxy ), or else - (CH2) q-R32 where q is an integer of 0 or 1 and R32 represents phenyl, pyridyl, or naphthyl, said phenyl, pyridyl and naphthyl are optionally substituted by a halogen atom, alkyl C1-4 or alkoxy C? _. Examples of preferred compounds according to the present invention include compounds described in Examples 1 to 186. Other examples of preferred compounds according to the present invention include the following compounds: N-. { 2-Chloro-4- [(6,7-dimethyl-4-quinazolinyl) -oxy] -phenyl} -N'-isobutylurea; N- (4- { [7- (benzyloxy) -6-methoxy-4-quinazolinyl] -oxi.} -2-chlorophenyl) -N'-propylurea; N- (4- { [6- (benzyloxy) -7-methoxy-4-quinazolinyl] -oxi.} -2-chlorophenyl) -N'-propylurea; N- (2-chloro-4- { [7-methoxy-6- (3-morpholinopropoxy) -4-quinazolinyl] -oxi.}. Phenyl) -N'-propylurea; N- [2-chloro-4-. { [6-methoxy-7- [2- (lH-1-imidazolyl) -ethoxy] -4-quinazolinyl} -oxi) phenyl] -N'-ethylurea; N- [2-chloro-4- (. {6-methoxy-7- [2- (1 H-1,2,3-triazol-1-yl) ethoxy] -4-quinazolinyl.} Oxy) phenyl] -N'-ethylurea; N- [2-chloro-4- (. {6-methoxy-7- [3- (1H-1, 2, 3-triazol-1-yl) propoxy] -4-quinazolinyl}. Oxy) phenyl] -N'-ethylurea; N- [2-chloro-4- (. {6-methoxy-7- [2- (4-methyl-piperazino) ethoxy] -4-quinazolinyl}. Oxy) phenyl] -N'-ethylurea; N- [2-chloro-4-. { [6-methoxy-7- (2-morpholinoethoxy) -4-quinazolinyl] oxy} phenyl) -N'-ethylurea; N- (2-chloro-4- { [6-methoxy-7- (3-morpholinopropoxy) -4-quinazolinyl] oxy} phenyl) -N'-ethylurea; N- [2-chloro-4- (. {6-methoxy-7- [2- (dimethylamino) -ethoxy] -4-quinazolinyl}. Oxy) phenyl] -N'-ethylurea; N- [2-chloro-4- (. {6-methoxy-7- [2- (1H-1-imidazolyl) -ethoxy] -4-quinazolinyl}. Oxy) phenyl] -N'-propylurea; N- [2-chloro-4- (. {6-methoxy-7- [2- (1 H-1,2,3-triazol-1-yl) ethoxy] -4-quinazolinyl.} Oxy) phenyl] -N'-propylurea; N- [2-chloro-4- (. {6-methoxy-7- [3- (1 H-1,2,3-triazol-1-yl) propoxy] -4-quinazolinyl.} Oxy) phenyl] -N'-propylurea; N- [2-chloro-4-. { [6-methoxy-7- (3-morpholinopropoxy) -4-quinazolinyl] oxy} phenyl) -N'-propylurea; N- [2-chloro-4- (. {6-methoxy-7- [2- (dimethylamino) -ethoxy] -4-quinazolinyl}. Oxy) phenyl] -N'-propylurea; N- [2-chloro-4- (. {6-methoxy-7- [2- (lH-1-imidazolyl) -ethoxy] -4-quinazolinyl-oxy) -phenyl] -N '-butylurea; N- [2-Chloro-4- (. {6-methoxy-7- [2- (1 H-1,2,3-triazol-1-yl) -ethoxy] -4-quinazolinyl}. Oxy) phenyl ] -N'-propylurea; N- [2-chloro-4- (. {6-methoxy-7- [3- (1 H-1,2,3-triazol-1-yl) propoxy] -4-quinazolinyl.} Oxy) phenyl] -N'-butilurea; N- [2-chloro-4- (. {6-methoxy-7- [2- (4-methyl-piperazino) ethoxy] -4-quinazolinyl}. Oxy) phenyl] -N '-butylurea; N- [2-chloro-4-. { [6-methoxy-7- (2-morpholinoethoxy) -4-quinazolinyl] oxy} phenyl) -N'-butilurea; N- (2-chloro-4- { [6-methoxy-7- (3-morpholinopropoxy) -4-quinazolinyl] oxy} phenyl) -N '-butylurea; N- [2-chloro-4- (. {6-methoxy-7- [2- (dimethylamino) -ethoxy] -4-quinazolinyl} oxy) phenyl] -N '-butylurea; and N- [2-chloro-4- (. {6-methoxy-7- [2- (dimethylamino) -ethoxy] -4-quinazolinyl}. oxy) phenyl] -N'-propylurea. Examples of particularly preferred compounds according to the present invention include: (13) N-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] -phenyl} -N'-propylurea; (51) N- [2-chloro-4-. { [6-methoxy-7- (2-morpholino-ethoxy) -4-quinolyl] oxy} phenyl) -N '- (2,4-difluorophenyl) urea; (62) N-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) -oxi] phenyl} -NF-propylurea; (76) N-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) -oxi] phenyl} -N'-ethylurea; (117) N-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] phenyl} -N -methylurea; (119) N- (2-chloro-4- { [6-methoxy-7- (3-morpholino-propoxy) -4-quinazolinyl] -oxi.}. Phenyl) -N'-propylurea; (135) N- (2-chloro-4- { [6-met? Xi-7- (3-piperidino-propoxy) -4-quinazolinyl] -oxi.}. Phenyl) -N'-propylurea; (142) N- (2-Chloro-4. {[6-methoxy-7- (3-pyridyl-methoxy) -4-quinolyl] oxy} phenyl) -N'-propylurea; (143) N- (2-Chloro-4. {[6-methoxy-7- (4-pyridyl-methoxy) -4-quinolyl] oxy} phenyl) -N'-propylurea; (144) N- (2-chloro-4. {[6-methoxy-7- (2-morpholino-ethoxy) -4-quinolyl] oxy} phenyl) -N'-propylurea; (145) N- [2-Chloro-4-6-methoxy-7- [2- (1 H-1,2,3-triazol-1-yl) ethoxy] -4-quinolyl} oxy) phenyl] -N'-propylurea; (146) N- [2-chloro-4- (7- { [2- (lH-1-imidazolyl) -ethoxy] -6-methoxy-4-quinolyl} oxy) phenyl] -N '- propylurea; (148) N- [2-chloro-4- (6-methoxy-7-. {[2- (4-methyl-piperazino) ethoxy] -4-quinolyl} oxy) phenyl] -N'-propylurea; (149) N- (2-chloro-4-. {[7- (2-hydroxyethoxy) -6-methoxy-4-quinolii] oxy} phenyl) -N'-propylurea; (151) N- (2-chloro-4- { [6-methoxy-7- (3-morpholino-propoxy) -4-quinolyl] oxy} phenyl) -N'-propylurea; (152) N- [2-chloro-4- (6-methoxy-7- { [3- (4-ethyl-piperazino) propoxy] -4-quinolyl} oxy) phenyl] -N'-propylurea; (153) N- [2-chloro-4- (6-methoxy-7- { [3- (1 H-1,2,3-triazol-1-yl) propoxy] -4-quinolyl} oxy. ) phenyl] -N'-propylurea; (157) N-. { 2-Chloro-4- [(7- { 3- [(2-hydroxyethyl) - (methyl) amino] propoxy.} - 6-methoxy-4-quinolyl) oxy] phenyl} -N'-propylurea; (159) N-. { 2-Chloro-4- [(6-methoxy-7-. {[[5- (1 H-1,2,3-triazol-1-yl) pentyl] oxy] -4- quinolyl) oxy] phenyl} -N'-propylurea; (160) N- [2-chloro-4- (7- { [4- (lH-1-imidazolyl) -butoxy] -6-methoxy-4-quinolyl}. Oxy) phenyl] -N '- propylurea; (162) N- (2-chloro-4- { [6-methoxy-7- (2-morpholino-ethoxy) -4-quinazolinyl] oxy} phenyl) -N '- (2,4-difluoro) phenyl) urea; (163) N- (2-chloro-4- { [6-methoxy-7- (3-morpholino-propoxy) -4-quinazolinyl] oxy} phenyl) -N '- (2,4-difluoro) phenyl) urea; (164) N- [2-chloro-4- (6-methoxy-7-. {[3- (4-methyl-piperazino) propoxy] -4-quinazolinyl}. Oxy) phenyl] -N '- ( 2,4-difluorophenyl) urea; (165) N-. { 2-Chloro-4- [(7- { 3- [(2-hydroxyethyl) - (methyl) amino] propoxy.} - 6-methoxy-4-quinazolinyl) oxy] phenyl} -N'- (2,4-difluorophenyl) urea; (168) N- (2-chloro-4- { [6-methoxy-7- (3-morpholino-propoxy) -4-quinolyl] oxy} phenyl) -N '- (2,4-difluorophenyl) ) urea; (169) N- (2-Chloro-4. {[6-methoxy-7- (3-pyridyl-methoxy) -4-quinolyl] oxy} phenyl) -N '- (2,4-difluorophenyl) ) urea; (170) N- [2-chloro-4- (6-methoxy-7- { [2- (1 H-1,2,3-triazol-1-yl) ethoxy] -4-quinolyl.} Oxy ) phenyl] -N '- (2,4-difluorophenyl) urea; (184) N- (2-Chloro-4. {[6-methoxy-7- (3-piperidino-propoxy) -4-quinazolinyl] oxy} phenyl) -N '-methylurea; (185) N- (2-chloro-4- { [6-methoxy-7- (3-piperidino-propoxy) -4-quinazolinyl] oxy} phenyl) -N'-ethylurea; and (186) N- (2-chloro-4- { [6-methoxy-7- (4-pyridyl-methoxy) -4-quinolyl] oxy} phenyl) -N '- (2, 4- difluorophenyl) urea. Examples of more preferred compounds according to the present invention include the following compounds: (62) N-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) -oxy] phenyl} -NF-propylurea; (142) N- (2-Chloro-4. {[6-methoxy-7- (3-pyridyl-methoxy) -4-quinolyl] oxy} phenyl) -N'-propylurea; and (169) N- (2-chloro-4- { [6-methoxy-7- (3-pyridyl-methoxy) -4-quinolyl] oxy} phenyl) -N '- (2, -difluorophenyl) ) urea; The compounds according to the present invention can form pharmaceutically acceptable salts thereof. Preferred examples of such salts include: alkali metal salts or alkaline earth metal salts such as sodium salts, potassium salts or calcium salts; salts of hydrohalogenic acid such as hydrofluoride salts, hydrochloride salts, hydrobromide salts, or hydroiodide salts; salts of inorganic acids such as nitric acid salts, perchloric acid salts, sulfuric acid salts, or phosphoric acid salts; lower alkylsulfonic acid salts such as methanesulfonic acid salts, trifluoromethanesulfonic acid salts, or ethanesulfonic acid salts; salts of arylsulfonic acids such as benzenesulfonic acid salts or salts of p-toluenesulfonic acid; organic acid salts such as fumaric acid salts, succinic acid salts, citric acid salts, tartaric acid salts, oxalic acid salts, maleic acid salts, acetic acid salts, malic acid salts, lactic acid salts , or salts of ascorbic acid; and salts of amino acids such as for example glycine salts, phenylalanine salts, salts of glutamic acid, or salts of aspartic acid.

In addition, the compounds according to the present invention can form solvates (eg hydrates). Production of compounds The compounds according to the present invention can be produced, for example, in accordance with scheme 1 and according to scheme 2. Scheme 1 The initial compounds necessary for the synthesis of the compounds according to the present invention can be obtained commercially or alternatively can be produced according to a conventional process. For example, a 4-chloroquinoline derivative can be synthesized by a conventional process in accordance with that described in Org. Synth Col. Vol. 3, 272, 1955), Acta Chim. Hung., 112, 241 (1983) or in WO 98/4 ~ 373. A 4-chloroquinazoline derivative can be synthesized by conventional process according to those described in J. Am. Chem. Soc., 68, 1299 (1946) or J. Am. Che ::. Soc, 68, 1305 (1946). Alternatively, the 4-chloroqu.azoline derivative can be produced by a process comprising the steps of: (1) first reacting a benzoic ester with formamide to prepare a quinazolone derivative (see production example 34) and (2) heating then the derivative of 4-quir.azoione using toluene or sulfolane as a solvent in the presence of phosphorus oxychloride (see production example 35 and production example 36). The quinazclone derivative is generally synthesized in the presence of a benzoic ester, sodium methoxide, formamide, and a solvent such as DMF or methanol. In step (1), the reaction proceeds in a system where only the benzoic ester and formaldehyde are present. This is beneficial insofar as the synthesis can be carried out using a small number of initial compounds. The 4-quinazolone derivative is generally halogenated by heating the quinazolone derivative and phosphorus oxychloride. In this case, in many cases, due to the high reactivity of the quinazoloin derivative, the influence of the solvent has caused the quinazoline derivative to be returned to the initial compound and therefore it is impossible to complete the reaction. In step (2), the reaction is completed in the presence of toluene or sulfolane, and therefore this represents an advantage from the perspective of an increase in yield. Then, a 4-chloroquinoline derivative or a corresponding quinazoline derivative is allowed to act on nitrophenol in the presence of a suitable solvent or in the absence of a solvent to synthesize a 4- (nitrophenoxy) quinoline derivative or a corresponding quinazoline derivative which is then stirred in a suitable solvent, for example, N, N-dimethylformamide, in the presence of a catalyst, for example palladium-carbon hydroxide or palladium-carbon in a hydrogen atmosphere to provide a 4- (aminophenoxy) derivative quinoline or a corresponding quinazoline derivative. Alternatively, a corresponding 4-chloroquinoline derivative or a corresponding quinazoline derivative may be allowed to act on aminophenol in the presence of a base, eg, sodium hydride, to provide a 4- (aminophenoxy) quinoline derivative or a quinazoline derivative correspondent . Alternatively, the 4- (aminophenoxy) quinoline derivative or the corresponding quinazoline derivative can also be produced by dissolving aminophenol in the aqueous solution of sodium hydroxide and then subjecting the solution to a biphasic reaction with a solution of derivative of 4-chloroquinazoline or a corresponding quinazoline derivative in an organic solvent in the presence of a phase transfer catalyst or in the absence of a catalyst (see production example 37 and production example 38). In this reaction, for example, the remaining unreacted phenol and a decomposition product of 4-chloroquinazoline are left in an aqueous layer, while the target product is present in the organic layer. That is, the organic layer contains only the target product. Therefore, the subsequent treatment is simple what is convenient. In addition, the production of N-alkylaminophenoxy-quinazoline as a by-product can conveniently be suppressed. p or cp p M w |? C (D ro The 4- (aminophenoxy) quinoline derivative or corresponding quinazoline derivative obtained in this way can be reacted with an acid chloride or an acid anhydride in the presence of a base, followed by reduction, for example, with lithium aluminum hydride with the object of introducing a substituent in R9 (step 1A). Alternatively, derivative of 4- (aminophenoxy) quinoline or the corresponding quinazoline derivative can be reacted with an aldehyde or a ketone to produce an imine, followed by reduction, for example, with sodiumboroboro cyanohydride to introduce a substituent on R9 (step IB) ). The derivative with a substituent introduced in R9 is allowed to act on an isocyanate derivative (0 = C) N-R1: 1") by a conventional method (step 2), and a suitable alkylating agent is allowed ( R 10 Hal) acts in the presence of a base, for example sodium hydride (step 3) to produce the compound of the formula (I) Alternatively, R 9 and R 10 can also be introduced by allowing a suitable alkylating agent (R 9 Hal, R 10 Hal) acts on a urea derivative, wherein R 9 and / or R 10 represent a hydrogen atom, in the presence of a base, for example, sodium hydride (steps 5 and 7) The urea derivative, wherein R 9 and / or R10 represent a hydrogen atom, can be produced by allowing an isocyanate derivative to act on the 4- (aminophenoxy) quinoline derivative or the corresponding quinazoline derivative, produced in scheme 1, in accordance with a conventional method, or by adding a triphosgene to the der 4- (aminophenoxy) quinoline or the corresponding quinazoline derivative in the presence of a base, for example, triethylamine, and then reacting the mixture with a suitable alkylamine (R "NH2, R10RnNH) (steps 4 and 6). The derivative having a specific substituent at position 7 of the quinoline ring can be produced, for example, in accordance with scheme 3. Scheme 3 A suitable substituent (e.g., benzyl) may be allowed to act on a commercially available 4'-hydroxyacetophenone derivative to protect the hydroxyl group, followed by the action of a nitrating agent (e.g., nitric acid-acetic acid) to introduce a nitro group. The nitro group can then be reduced to an amino group which then reacts with a formic ester in the presence of a base to form a quinolone ring, followed by the action of a chlorinating agent, for example, phosphorus oxychloride, to produce a 4-chloroquinoline derivative.

The 4-chloroquinoline derivative thus obtained can be allowed to act on aminophenol and the presence of a base, for example sodium hydride, to produce a 4- (aminophenoxy) quinoline derivative. The urea portion can be synthesized by allowing an isocyanate derivative (0 = C = N-R29) to act on the derivative obtained in this manner in accordance with a conventional method, or by treating the derivative with triphosgene and then allowing an aromatic amine or alkylamine (R: 9NH2) acts on the treated derivative.

Then, the protecting group (PG) for the hydroxyl group at position 7 of the quinoline ring can be removed, followed by the action of an alkyl halide (R22 Hal wherein R22 'represents an alkyl portion when R22 represents alkoxy) in the presence of a base, or by the action of an alcohol derivative (R22 '? H) in accordance with a conventional method, for example, Mitsunobu reaction, to produce a compound, in accordance with the present invention, having a group alkoxy at position 7 of the quinoline ring. The alkyl halide employed in the substitution reaction may be commercially available or may be produced in accordance with a process described, for example in J. Am. Chem. Soc./ 1945, 67, 736. The alcohol derivative employed in the substitution reaction it may be commercially available or it may be produced in accordance with a described process, for example, in J. Antibiot. (1993), 46 (1), 177 and Ann. Pharm. Fr. 1977, 35, 503. The derivative having a specific substituent at the 6-position of the quinoline ring can be produced by employing a 3 '-hydroxyacetophenone derivative as the initial compound according to scheme 3. The derivative having a substituent specific at position 7 of the quinazoline ring can be produced in accordance with scheme 4 Scheme 4 Oxidation O Esterification " The 2-amino-benzoic ester derivative can be produced by esterification of a 2-nitro-benzoic acid derivative synthesized according to the method described, for example in J. Med. Chem. 1977, 20, 146, for example, with dimethylsulfuric acid in the presence of a base, for example, potassium carbonate and then reducing the nitro group, for example, with iron / acetic acid. Then, the compound thus obtained can be allowed to act in formamide in the presence of a base to form a 4-quinazolone ring, followed by the action of a chlorinating agent, for example, phosphorus oxychloride, to produce a derivative of 4-chloroquinazoline. The 4-chloroquinazoline derivative obtained in this way can be allowed to act on an aminophenol derivative in the presence of a base, for example, sodium hydride, to produce a 4- (aminophenoxy) quinazoline derivative. The urea portion can be synthesized by allowing an isocyanate derivative (0 = C = N-R29) to act on the derivative obtained in this manner according to a conventional method, or by treating the derivative with triphosgene and then allowing an aromatic amine or alkylamine (R29NH2) acts on the treated derivative. Then, the protecting group (PG) for the hydroxyl group in the 7-position of the quinazoline ring can be removed, followed by the action of an alkyl halide (R22? Wherein R22 'represents an alkyl portion when R22 represents alkoxy) in presence of a base, or else by the action of an alcohol derivative (R22 '? H) in accordance with a conventional method, for example, Mitsunobu reaction, to produce a compound according to the present invention, which has a group alkoxy in the 7-position of the quinazoline ring. The alkyl halide and the alcohol derivative employed in the substitution reaction may be commercially available or produced in accordance with a process described in the literature mentioned in the scheme description 3. The derivative having a specific substituent in the position 6 of the quinazoline ring can be produced by employing the 3-hydroxybenzaldehyde derivative as the initial compound according to scheme 4. USE OF COMPOSITE / PHARMACEUTICAL COMPOSITION The compounds according to the present invention have an inhibitory activity against tumor proliferation in vivo ( see Pharmacological Test Example 4). In addition, the compounds according to the present invention inhibit in vitro the activation of MAPK (mitogen-activated protein kinase) caused by the stimulation of vascular endothelial cells with VEGF (vascular endothelial growth factor) (see Examples 1 and 2 of Pharmacological Test ). By stimulating the vascular endothelial cells with VEGF, MAPK is activated through a signal transmission system downstream of the receptor, and therefore, an increase in phosphorylated MAPK is recognized (Abedi, H. and Zachary, I., J. Biol. Chem., 272, 15442-15451 (1997)). Activation of MAPK plays an important role in the growth of vascular endothelial cells in angiogenesis (Merenmies, J. et al., Cell Growth &Differ., 83-10 (1997); and Ferrara, N. and Davis-Smyth, T., Endocr. Rev., 18, 4-25 (1997)). Accordingly, the compounds according to the present invention have an activity of inhibiting angiogenesis. Angiogenesis in pathological sites is deeply involved mainly in diseases such as tumors, diabetic retinopathy, chronic rheumatism, psoriasis, atherosclerosis, and Kaposi's sarcoma, and metastases from solid tumors (Forman, J. Nature Med. 1: 27-31 ( nineteen ninety five); Bic nell, R., Harris, A. L. Curr. Opin. Oncol. 8: 60-65 (nineteen ninety six) ) . Accordingly, the compounds according to the present invention can be used in the treatment of diseases such as tumor, diabetic retinopathy, chronic rheumatism, psoriasis, atherosclerosis, and Kaposi's sarcoma, and metastasis of solid tumors. The compounds according to the present invention have no significant influence on cytomorphosis (see Pharmacological Test Example 3). Accordingly, the compounds according to the present invention can be administered to living bodies with excellent safety. In accordance with the present invention, there is provided a pharmaceutical composition comprising the compound according to the present invention. The pharmaceutical composition according to the present invention can be used in a treatment of diseases, such as tumor, diabetic retinopathy, chronic rheumatism, psoriasis, atherosclerosis, and Kaposi's sarcoma and solid tumor metastasis. Further, in accordance with the present invention, there is provided a method for the treatment of a selected disease within the group consisting of tumor, diabetic retinopathy, chronic rheumatism, psoriasis, atherosclerosis, and Kaposi's sarcoma, comprising the step of administering the compound according to the present invention, together with a pharmaceutically acceptable carrier to mammals. The compounds according to the present invention can be administered to humans or non-human animals orally or parenterally by routes of administration, for example, intravenous administration, intramuscular administration, subcutaneous administration, rectal administration, or percutaneous administration. Accordingly, the pharmaceutical composition comprising as active ingredient the compound according to the present invention is formulated into suitable dosage forms in accordance with the routes of administration. Specifically, oral preparations include tablets, capsules, powders, granules, and syrups, and parenteral preparations include injections, suppositories, tapes, and ointments. The various preparations can be prepared by conventional methods, for example, with commonly used components such as excipients, disintegrants, binders, lubricants, colorants and diluents. The excipients include, for example, lactose, glucose, corn starch, sorbitol, and crystalline cellulose. The disintegrants include, for example, starch, sodium alginate, gelatin powder, calcium carbonate, calcium citrate, and dextrin. Binders include, for example, dimethylcellulose, polyvinyl alcohol, polyvinyl ether, methylcellulose, ethylcellulose, gum arabic, gelatin, hydroxypropylcellulose, and polyvinyl pyrrolidone. Lubricants include, for example, talc, magnesium stearate, polyethylene glycol, and hydrogenated vegetable oils. In the preparation of injections, if necessary, for example, buffers, pH adjusters, stabilizers, tonicity agents, and preservatives can be added. The content of the compound according to the present invention in the pharmaceutical composition according to the present invention may vary according to the dosage form. In general, however, the content is from 0.5 to 50% by weight, preferably from 1 to 20% by weight, based on the entire composition. The dose may be appropriately determined taking into account, for example, the age, weight, sex, difference of diseases, and severity of patient condition, and the preparation may be administered, for example, in an amount of 0.1 to 100 mg / kg, preferably from 1 to 50 mg / kg. This dose is administered once a day or in divided doses several times a day. The compound according to the present invention can be administered in combination with another drug (s). In this case, the compound according to the present invention can be administered simultaneously with the administration of another drug (s) or sooner or later. For example, when the disease is a malignant tumor, the compound according to the present can be allowed to act on the target vascular endothelial cells to allow tumor regression., followed by the administration of a carcinostatic agent in order to effectively eliminate the tumor. The type, administration intervals and the like of the carcinostatic agent can be determined according to, for example, the type of cancer and the condition of the patients. This method of treatment is applicable to diseases other than the malignant tumor. Further, in accordance with the present invention, there is provided a method for inhibiting angiogenesis of target blood vessels, comprising the step of contacting the compound according to the present invention with vascular endothelial cells of target blood vessels. The target blood vessels include blood vessels involved in feeding the tissues that cause the diseases (eg, tumor tissues, tissues with retinopathy, or rheumatism tissues). The compound according to the present invention can come into contact with vascular endothelial cells, for example, by general administration (for example, intravenous administration or oral administration), local administration (for example, percutaneous administration or intra-articular administration), either pharmacological approach employing a vehicle (liposome, lipid microsphere, or form drug polymers). EXAMPLES The present invention will be described with reference to the following examples, even if it is not limited only to these examples. Production Example 1: 2-Chloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] aniline Sodium hydride (60% by weight, 0.72 g) was added to dimethyl sulfoxide (10 ml). The mixture was stirred at 50 ° C for 30 minutes and then cooled to room temperature. 4-Amino-3-chlorophenol hydrochloride (1.61 g) was added to the cooled mixture, and the mixture was stirred at room temperature for 10 minutes. Then, 4-chloro-6,7-dimethoxyquinoline (1.00 g) was added, and the mixture was stirred at a temperature of 100 ° C overnight. Water was added to the reaction solution, followed by extraction with chloroform. The chloroform layer was then washed with a saturated aqueous solution of sodium hydrogencarbonate and dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, and methanol was added to the residue. The precipitated crystal was collected by suction with filtration to provide 0.89 g (yield: 60%) of the title compound. ^ -H-NMR (CDC13, 400 Mhz): d 4.05 (s, 3H), 4.05 (s, 3H), 4.08 (s, 2H), 6.44 (d, J = 5.4 Hz, 1H), 6.85 (d, J = 8.5 Hz, 1H), 6.93 - 6.96 (m, 1H), 7.15 (d, J = 2.7 Hz, 1H), 7.41 (s, 1H), 7.54 (s, 1H), 8.48 (d, J = 5.1 Hz, 1H) Production example 2: 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2,3-dimethylaniline Sodium hydride (60% by weight, 0.72 g) was added to dimethyl sulfoxide ( 10 ml). The mixture was stirred at a temperature of 50 ° C for 30 minutes and then cooled to room temperature. 4-Amino-2,3-dimethylphenol hydrochloride (1.55 g) was added to the cooled mixture, and the mixture was stirred at room temperature for 10 minutes. Then 4-chloro-6,7-dimethoxyquinoline (1.00 g) was added, and the mixture was stirred at 100 ° C overnight. Water was added to the reaction solution, followed by extraction with chloroform. The chloroform layer was then washed with a saturated aqueous solution of sodium hydrogencarbonate and dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, and methanol was added to the residue. The precipitated crystal was collected by suction filtration to provide 0.94 g (yield: 65%) of the title compound. 1 H-NMR (CDC 13, 400 Mhz): 5 2.07 (s, 3 H), 2.15 (s, 3 H), 3.62 (s, 2H), 4.05 (s, 3H), 4.07 (s, 3H), 6.25 (d, J = 5.4 Hz, 1H), 6.64 (d, J = 8.5 Hz, 1H), 6.83 (d, J = 8.5 Hz, 1H), 7.42 (s, 1H), 7.64 (s, 1H), 8.42 (d, J = 5.4 Hz, 1H) Production example 3: 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2, 5- dimethylaniline Sodium hydride (60% by weight, 0.36 g) was added to dimethyl sulfoxide (10 ml), and the mixture was stirred at a temperature of 50 ° C for 30 minutes and then cooled to room temperature. 4-Amino-2,5-dimethylphenol (1.23 g) was added to the cooled mixture, and the mixture was stirred at room temperature for 10 minutes. Then 4-chloro-6,7-dimethoxy-quinoline (1.00 g) was added, and the mixture was stirred at a temperature of 100 ° C overnight. Water was added to the reaction solution, followed by extraction with chloroform. The chloroform layer was then washed with a saturated aqueous solution of sodium hydrogencarbonate and dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, and the residue was purified by chromatography on silica gel by development with chloroform / acetone (1/1) to provide the title compound. Production Example 4: 3,5-dichloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] aniline Sodium hydride (60% by weight, 0.36 g) was added to dimethyl sulfoxide (10 ml) , and the mixture was stirred at a temperature of 50 ° C for 30 minutes and then cooled to room temperature. 4-Amino-2,6-dichlorophenol (1.59 g) was added to the cooled mixture, and the mixture was stirred at room temperature for 10 minutes. Then 4-chloro-6,7-dimethoxy-quinoline (1.00 g) was added, and the mixture was stirred at a temperature of 100 ° C overnight. Water was added to the reaction solution, followed by extraction with chloroform. The chloroform layer was then washed with a saturated aqueous solution of sodium hydrogencarbonate and dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, and the residue was purified by chromatography on silica gel by development with chloroform / acetone (1/1) to provide 0.35 g (yield: 22%) of the title compound. 1H-NMR (CDC13, 400 Mhz): d 3.84 (s, 2H), 4.05 (s, 3H), 4.08 (s, 3H), 6.28 (d, J = 5.4 Hz, 1H), 6.74 (s, 2H) , 7.43 (s, 1H), 7.64 (s, 1H), 8.48 (d, J = 5.4 Hz, 1H) Production example 5: 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2- Nitroaniline Sodium hydride (60% by weight, 0.54 g) was added to dimethyl sulfoxide (15 ml), and the mixture was stirred at a temperature of 50 ° C for 30 minutes and then cooled to room temperature. 4-Amino-3-nitrophenol (2.07 g) was added to the cooled mixture, and the mixture was stirred at room temperature for 10 minutes. Then 4-chloro-6,7-dimethoxy-quinoline (1.50 g) was added, and the mixture was stirred at a temperature of 100 ° C for 4 hours. Water was added to the reaction solution, followed by extraction with chloroform. The chloroform layer was then washed with a saturated aqueous solution of sodium hydrogencarbonate and dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, and the residue was purified by chromatography on silica gel by development with chloroform / acetone (1/1) to provide 0.53 g (yield: 23%) of the title compound. Production Example 6: 1- [2-amino-4- (benzyloxy) -5-methoxyphenyl] -1-ethanone 1- (4-hydroxy-3-methoxyphenyl) -1-ethanone (20 g), carbonate of potassium (18.3 g), tetra-n-butylammonium iodide (4.45 g), and benzyl bromide (17.3 ml) in N, N-dimethylformamide (300 ml), and the reaction was allowed to proceed at a temperature of 100 ° C. C for 1 hour. The solvent was removed by distillation under reduced pressure, and water was added to the residue, followed by extraction with ethyl acetate. The ethyl acetate layer was dried over sodium sulfate. Then, the solvent was removed by distillation under reduced pressure. The residue and smoking nitric acid (12.47 ml) were dissolved in acetic acid (120 ml), and the reaction was allowed to proceed at room temperature for 2 hours. The reaction solution was neutralized at a temperature of 0 ° C through the addition of an aqueous solution of sodium hydroxide, followed by extraction with chloroform. The chloroform layer was then dried in sodium sulfate. Then, the solvent was removed by distillation under reduced pressure. The residue was dissolved in ethanol (1160 ml) and water (120 ml) with heating. Ammonium chloride (19.2 g) and zinc (101.7 g) were added. The mixture was heated under reflux for 3 hours. The reaction solution was filtered through Celite, followed by washing with chloroform / methanol (3/1). The solvent was removed by distillation under reduced pressure, and the residue was rendered alkaline with an aqueous solution of sodium hydroxide, and the alkaline solution was extracted with chloroform. The chloroform layer was dried in sodium sulfate. The solvent was removed by distillation under reduced pressure, and the residue was purified by silica gel chromatography by development with chloroform / ethyl acetate (10/1) to give 24.95 g (yield: 77%) of the title compound (3 Steps) . 1H-IÑt R (CDC13, 400 Mhz): d 2.51 (s, 3H), 3.84 (s, 3H), 5.14 (s, 2H), 6.12 (s, 2H), 7.15 - 7.62 (m, 7H) Example of Production 7: 7- (benzyloxy) -6-methoxy-1,4-dihydro-4-quinolinone 1- [2-amino-4- (benzyloxy) -5-methoxyphenyl] -1-ethanone (24.95 g) was dissolved in tetrahydrofuran (450 ml), and sodium methoxide (24.87 g) was added to the solution. The mixture was stirred at room temperature for 1 hour. Ethyl formate (37.07 ml) was then added, and the mixture was stirred at room temperature for 2 hours. Water (150 ml) was then added, and the mixture was stirred overnight. The reaction solution was adjusted to pH 4 by the addition of concentrated sulfuric acid at a temperature of 0 ° C. Water was added, and the mixture was extracted with chloroform.

The chloroform layer was dried in sodium sulfate. The solvent was removed by distillation under reduced pressure, and the residue was purified by chromatography on silica gel by growth with chloroform / methanol (10/1) to give 17.16 g (yield: 66%) of the title compound. 1 H-NMR (CDC 13, 400 Mhz): d 3.84 (s, 2 H), 5.19 (s, 3 H), 5.97 (d, J = 7.1 Hz, 1 H), 7.09 (s, 1 H), 7.28 - 7.51 (m, 6H), 7.78 (d, J = 7.3 Hz, 1H), 11.50 - 11.75 (br, 1H) Production example 8_ | 7- (benzyloxy) -4-chloro-6-methoxyquinoline Phosphorus oxychloride (14.19 ml) was added to 7- (benzyloxy) -6-methoxy-1,4-dihydro-4-quinolinone (17.16 g), and the mixture it was heated under reflux for 1 hour. The solvent was removed by distillation under reduced pressure. The residue was dissolved chloroform, and the solution was made alkaline through the addition of an aqueous solution of sodium hydroxide followed by extraction with chloroform. The chloroform layer was dried in sodium sulfate. The solvent was removed by distillation under reduced pressure, and the residue was purified by chromatography on silica gel by development with chloroform / acetone (10/1) to provide 3.82 g (yield: 21%) of the title compound. 1 H-NMR (CDCl 3, 400 Mhz): d 4.06 (s, 3 H), 5.32 (s, 2 H), 7.30 - 7.55 (m, 8 H), 8.56 (d, J = 4.9 Hz, 1 H) Production example 9: 4- . { [7- (benzyloxy) -6-methoxy-4-quinolyl] oxy} -2, 5-dimethylaniline Sodium hydride (60% by weight, 1.17 g) was added to dimethyl sulfoxide (25 ml), and the mixture was stirred at a temperature of 60 ° C for 30 minutes and then cooled to room temperature. ambient. Then 4-amino-2,5-dimethylphenol (4.00 g) was added and the mixture was stirred at room temperature for 10 minutes. Then 7- (benzyloxy) -4-chloro-6-methoxyquinoline (4.36 g) was added. The mixture was stirred for 22 hours before adding water to the reaction solution, followed by extraction with chloroform. The chloroform layer was then washed with a saturated aqueous solution of sodium hydrogencarbonate and dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, and methanol was added to the residue to prepare a suspension. The precipitated crystal was collected by suction filtration to provide 3.04 g (yield: 52%) of the title compound. ^? - MR (CDC13, 400 Mhz): d 2.05 (s, 3H), 2.16 (s, 3H), 3.58 (s, 2H), 4.06 (s, 3H), 5.32 (s, 2H), 6.28 (d, J = 5.1 Hz, 1H), 6.61 (s, 1H), 6.81 (s, 1H), 7.28 - 7.42 (m, 3H), 7.44 (s, 1H), 7.49 - 7.54 (m, 2H), 7.63 (s, 1H), 8.39 (d, J = 5.1 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 401 (M ++ l) Production example 10: N- (4- { [7- (benzyloxy) -6-methoxy- 4-quinolyl] oxy} -2,5-dimethylphenyl) -N '- (2,4-difluorophenyl) urea 4- was dissolved. { [7- (benzyloxy) -6-methoxy-4-quinolyl] oxy} -2,5-dimethylaniline (300 mg) in chloroform (5 ml). Then, 2,4-difluorophenyl isocyanate (200 μl) was added to the solution, and the mixture was stirred at a temperature of 70 ° C overnight. The reaction solution was purified by chromatography on silica gel developing with chloroform / acetone (75/25) to provide 3.68 g (yield: 88%) of the title compound. 1 H-NMR (CDC13, 400 Mhz): d 2.17 (s, 3 H), 2.26 (s, 3 H), 4.06 (s, 3 H), 5.33 (s, 2 H), 6.29 (d, J = 5.1 Hz, 1 H) , 6.42 (s, 1H), 6.76 - 6.93 (m, 3H), 6.70 (s, 3H), 7.30 - 7.54 (m, 7H), 7.60 (s, 1H), 8.04 - 8.12 (m, 1H), 8.44 (d, J = 5.4 Hz, 1H) Production example 11: N- (4- { [7- (benzyloxy) -6-methoxy-4-quinolyl] oxy} -2, 5-dimethylphenyl) - N '- (2-methoxyphenyl) urea 4- was dissolved. { [7- (benzyloxy) -6-methoxy-4-quinolyl] oxy} -2,5-dimethylaniline (300 mg) in chloroform (5 ml). Then 2-methoxyphenyl isocyanate (0.24 ml) was added to the solution, and the mixture was stirred at a temperature of 70 ° C overnight. The reaction solution was purified by silica gel chromatography by growth with chloroform / acetone (75/25) to provide 365 g (yield: 89%) of the title compound. 1 H-NMR (CDCl 3, 400 Mhz): d 2.17 (s, 3H), 2.28 (s, 3H), 3.83 5i (s, 3H), 4.07 (s, 3H), 5.33 (s, 2H), 6.26 (s, 3H), 6.29 (d, J = 5.4 Hz, 1H), 6.86 - 7.06 (m, 4H), 7.12 ( s, 1H), 7.30 - 7.41 (m, 3H), 7.46 (s, 1H), 7.50 - 7.56 (m, 3H), 7.61 (s, 1H), 8.11 - 8.16 (, 1H), 8.43 (d, J = 5.4 Hz, 1H) Production example 12: 4- [7- (benzyloxy) -6-methoxy-4-quinolyl] oxy} -2-chloroaniline Sodium hydride (60% by weight, 1.17 g) was added to dimethyl sulfoxide (3.6 ml), and the mixture was stirred at a temperature of 60 ° C for 30 minutes and then cooled to room temperature. Then 4-amino-3-chlorophenol hydrochloride (720 mg) was added there, and the mixture was stirred at room temperature for 10 minutes. 7- (Benzyloxy) -4-chloro-6-ethoxy-quinoline (600 mg) was added, and the mixture was stirred at a temperature of 105 ° C for 22 hours. Water was added to the reaction solution, followed by extraction with chloroform. The chloroform layer was then washed with a saturated aqueous solution of sodium hydrogencarbonate and dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, and methanol was added to the residue to prepare a suspension. The precipitated crystal was collected by suction filtration to provide 533 mg (yield: 66%) of the title compound. 1 H-NMR (CDC13, 400 Mhz): d 4.05 (s, 3 H), 4.08 (s, 2 H), 5.32 (s, 2 H), 6.42 (d, J = 5.1 Hz, 1 H), 6.84 (d, J = 8.5 Hz, 1H), 6.93 (dd, J = 2.4 Hz, 1H), 7.14 (d, J = 2.4 Hz, 1H), 7.29 -7.42 (m, 3H), 7.44 (s, 1H), 7.49 - 7.53 ( m, 2H), 7.55 (s, 1H), 8.45 (d, J = 5.3 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 497 (M ++ l) Production example 13: N- (4- { [7- (benzyloxy) -6-methoxy-4-quinolyl] oxy} -2-chlorophenyl) -N '- (2,4-difluorophenyl) urea 4- was dissolved. { [7- (benzyloxy) -6-methoxy-4-quinolyl] oxy} -2-clcroaniline (260 mg) in chloroform (10 ml). Then, 2,4-difluorophenyl isocyanate (198 mg) was added to the solution, and the mixture was stirred at room temperature for 2 hours. The reaction solution was purified by chromatography on silica gel by development with chloroform / acetone (10/1) to provide 337 mg (yield: 94%) of the title compound. 1 H-NMR (CDC13, 400 Mhz): d 4.04 (s, 3 H), 5.32 (s, 2 H), 6.49 (d, J = 5.1 Hz, 1 H), 6.86 - 6.96 (m, 3 H), 7.10 - 7.17 ( m, 2H), 7.22 - 7.28 (m, 1H), 7.28 - 7.41 (m, 3H), 7.45 - 7.53 (m, 4H), 7.96 - 8.04 (m, 1H), 8.27 (d, J = 9.0 Hz, 1H), 8.49 (d, J = 5.4 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 562, 564 (M ++ l) Production example 14: N-. { 2-Chloro-4- [7-hydroxy-6-methoxy-4-quinolyl] oxy] phenyl} -N '- (2,4-difluorophenyl) urea 4- was dissolved. { [7- (benzyloxy) -6-methoxy-4-quinolyl] oxy} -2-chlorophenyl) -N - (2,4-difluorophenyl) urea (215 mg) in dimethylformamide (11 ml). Palladium / carbon (215 mg) was added to the solution, and the mixture was stirred under an atmosphere of hydrogen at room temperature overnight. Thylum acetate (30 ml) was added to the reaction solution, and the mixture was then filtered through Celite. The solvent was removed by distillation under reduced pressure to provide 174 mg (yield: 96%) of the title compound. 1 H-NMR (DMSO-de, 400 Mhz): d 3.94 (s, 3 H), 6.47 (d, J = 5.1 Hz, 1 H), 7.01 - 7.11 (m, 1 H), 7.18 - 7.36 (m, 3 H), 7.44 -7.52 (m, 2H), 7.95 (s, 1H), 7.98 - 8.13 (, 1H), 8.23 (d, J = 9.5 Hz, 1H), 6.50 (d, J = 5.1 Hz, 1H), 8.81 ( s, 1H), 9.31 (s, 1H) Mass analysis, found (ESI-MS, m / z): 472 (M ++ l) Production example 15: 4-. { [7- (benzyloxy) -6-methoxy-4-quinolyl] oxy} -2,3-dimethylaniline Sodium hydride (60% by weight, 0.32 g) was added to dimethyl sulfoxide (6 ml), and the mixture was stirred at room temperature for 30 minutes. Then 4-amino-2,3-dimethylphenol (1.10 g) was added and the mixture was stirred at room temperature for 10 minutes. Then 7- (benzyloxy) -4-chloro-6-methoxyquinoline (1.20 g) was added, and the mixture was stirred at a temperature of 110 ° C for 6 hours. A saturated aqueous solution of sodium hydrogencarbonate was added followed by extraction with chloroform. The chloroform layer was dried in anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure and the residue was purified by chromatography on silica gel by development with chloroform / acetone (6/1) to provide 0.78 g (yield: 49%) of the title compound. 1 H-NMR (DMSO-de, 400 Mhz): d 1.87 (s, 3H), 1.96 (s, 3H), 3.97 (s, 3H), 4.78 (s, 2H), 5.23 (s, 2H), 6.12 (d, J = 5.3 Hz, 1H), 6.54 (d, J = 8.4 Hz, 1H), 6.69 (d, J = 8.4 Hz, 1H), 7.27 - 7.51 (m, 7H), 8.31 (d, J = 5.3 Hz, 1H) Production example 16: N- (4- { [7- (benzyloxy) -6-methoxy-4-quinolyl] oxy} -2, 3-dimethylphenyl) -N '- (2,4-difluoro-phenyl) urea It was dissolved 4-. { [7- (benzyloxy) -6-methoxy-4-quinolyl] oxy} -2,3-dimethylaniline (260 mg) in N, N-dimethylformamide (5 ml). Then, 2,4-difluorophenyl isocyanate (121 mg) was added to the solution, and the reaction was allowed to proceed at room temperature overnight. Methanol was added to the reaction solution, and the solvent was removed by distillation under reduced pressure. The residue was washed with ethanol and collected by filtration to provide 219 mg (yield: 61%) of the title compound. XH-NMR (DMSO-de, 400 Mhz): d 1.99 (s, 3H), 2.17 (s, 3H), 3.90 (s, 3H), 5.24 (s, 2H), 6.18 (d, J = 5.1 Hz, 1H), 6.95 - 6.98 (, 2H), 7.25 - 7.63 (m, 9H), 8.05 - 8.08 (, 1H), 8.34 - 8.36 (, 2H), 8.79 (s, 1H) Production example 17: 7- (benzyloxy) -4- ( 3-fluoro-4-nitrophenoxy) -6-methoxyquinoline 7- (benzyloxy) -4-chloro-6-methoxyquinoline (300 mg) and 3-fluoro-4-nitrophenol (785 mg) were dissolved in chlorobenzene (3 ml), and the solution was stirred at a temperature of 130 ° C for 5 hours. Chloroform and an aqueous solution of sodium hydroxide were added to the reaction solution, and the mixture was stirred for 1 hour. The reaction solution was extracted with chloroform, and the chloroform layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by thin layer chromatography on silica gel by development with hexane / ethyl acetate (1/1) to provide 197 mg (yield: 47%) of the title compound. -NMR (DMSO-de, 400 Mhz): d 3.83 (s, 3H), 5.25 (s, 2H), 6.91 (d, J = 5.1 Hz, 1H), 7.29 - 7.50 (m, 9H), 8.18 - 8.23 (, 1H), 8.56 (d, J = 5.1 Hz, 1H) Production example 18: 4- (4-amino-3-fluorophenoxy) -6-methoxy-7-quinolino1 7- (benzyloxy) -4- was dissolved (3-fluoro-4-nitrophenoxy) -6-methoxyquinoline (190 mg) in N, N-dimethylformamide (5 ml) and triethylamine (1 ml). Palladium hydroxide (40 mg) was added to the solution, and the mixture was stirred under a nitrogen atmosphere at room temperature overnight. The solvent was removed by distillation under reduced pressure. The residue was purified by thin layer chromatography on silica gel by growth with chloroform / methanol (20/1) to provide 75 mg (yield: 56%) of the title compound. 1 H-NMR (DMSO-de, 400 Mhz): d 3.87 (s, 3 H), 5.11 (s, 2 H), 6.29 (d, J = 5.1 Hz, 1 H), 6.77 - 6.80 (m, 2 H), 6.93 - 6.99 (m, 1H), 7.19 (s, 1H), 7.40 (s, 1H), 8.31 (d, J = 5.1 Hz, 1H), 10.03 (s, 1H) Production example 19: N- (2, 4 -difluorophenyl) -N '-. { 2-fluoro-4- [7-hydroxy-6-methoxy-4-quinolyl) oxy] phenyl} urea 4- (4-Amino-3-fluorophenoxy) -6-methoxy-7-quinolinol (70 mg) was dissolved in chloroform (1.5 ml) and N, -dimethylformamide (1 ml). Then, 2,4-difluorophenyl isocyanate (43 mg) was added to the solution, and the reaction was allowed to proceed at room temperature for 3 hours. Methanol was added to the reaction solution. The solvent was removed by distillation under reduced pressure. The residue was purified by thin layer chromatography on silica gel by chloroform / methanol (20/1) development to quantitatively give the title compound. XH-NMR (DMSO-de, 400 Mhz): d 3.94 (s, 3H), 6.47 (d, J = 5.1 Hz, 1H), 7.04 - 7.10 (m, 2H), 7.28 - 7.34 (m, 2H), 7.47 (s, 1H), 8.05 - 8.15 (m, 2H), 8.30 (s, 1H), 8.43 (d, J = 5.1 Hz, 1H), 8.97-9.03 (, 2H), 10.10 (s, 1H) Production example 20: 4-chloro-6-methoxy-7-quinolinol 7- (benzyloxy) -4-chloro-6-methoxyquinoline (100 mg), thioanisole (300 μl), and methanesulfonic acid (25 μl) in trifluoromethanesulfonic acid (1 ml). The solution was stirred at room temperature for 30 minutes. The solvent was removed by distillation under reduced pressure. The residue was rendered neutral by the addition of an aqueous solution of sodium hydroxide, and hexane was added to prepare a suspension. The crystal was collected by suction filtration in order to provide 53 mg (yield: 75%) of the title compound. 1 H-NMR (DMS0-d 6, 400 Mhz): d 3.98 (s, 3 H), 7.33 (s, 1 H), 7.36 (s, 1 H), 7.47 (d, J = 4.9 Hz, 1 H), 8.54 (d, J = 4.9 Hz, 1H), 10.37 (br, 1H) Production example 21: 4-chloro-6-methoxy-7- (2-methoxyethoxy) quinoline 4-chloro-6-methoxy-7-quinolinol (50 mg), potassium carbonate (40 mg), tetra-n-butylammonium iodide (9 mg), and 2-bromoethyl methyl ether (40 mg) in N, N-dimethylformamide (10 ml). The solution was stirred at a temperature of 70 ° C overnight. The solvent was removed by distillation under reduced pressure. A saturated aqueous solution of sodium hydrogencarbonate was added to the residue, followed by extraction with chloroform. The chloroform layer was dried in sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by development with hexane / acetone / dichloromethane (6/2/1) to provide 47 mg (yield: 74%) of the title compound. ^? - NMR (CDC13, 400 Mhz): d 3.49 (s, 3H), 3.88 - 3.90 (m, 2H), 4.04 (s, 3H), 4.32 - 4.35 (m, 2H), 7.35 (d, J = 4.9 Hz, 1H), 7.40 (s, 1H), 7.43 (s, 1H), 8.57 (d, J = 4.9 Hz, 1H) Production example 22: 2-chloro-4-. { [(6-methoxy-7- (2-methoxyethoxy) -4-quinolyl] oxy} aniline Sodium hydride (60% by weight, 153 mg) was added to dimethyl sulfoxide (2 ml)., The mixture was stirred at a temperature of 60 ° C for 30 minutes and then cooled to room temperature, 4-amino-3-chlorophenol hydrochloride (343 mg) was added, and the mixture was stirred at room temperature for 10 minutes. a solution of 4-chloro-6-methoxy-7- (2-methoxyethoxy) quinoline (254 mg) in dimethyl sulfoxide (2 ml) was added to the reaction solution, and the mixture was stirred at a temperature of 110 ° C. The water was added to the reaction solution, followed by extraction with chloroform.The chloroform layer was then washed with a saturated aqueous solution of sodium hydrogencarbonate and dried in anhydrous sodium sulfate.The solvent was removed by distillation under pressure The residue was purified by chromatography on silica gel by development with chloroform / acetone (7/1) to provide the title compound. 1 H-NMR (CDCl 3, 400 Mhz): d 3.49 (s, 3 H), 3.89 - 3.91 (m, 2 H), 4.02 (s, 3 H), 4.09 (s, 3 H), 4.33 - 4.35 (m, 2 H), 6.43 (d, J = 5.4 Hz, 1H), 6.85 (d, J = 8.5 Hz, 1H), 6.93-6.96 (m, 1H), 7.15 (d, J = 2.7 Hz, 1H), 7.41 (s, 1H) ), 7.52 (s, 1H), 8.47 (d, J = 5.1 Hz, 1H) Production example 23: 2-Chloro-4- [(6,7-dimethoxy-4-quinazoline) oxy] aniline. sodium (60% by weight, 5.80 mg) to dimethyl sulfoxide (40 ml). The mixture was stirred at a temperature of 60 ° C for 30 minutes and then cooled to room temperature. Then 4-amino-3-chlorophenol hydrochloride (13.05 g) was added. The mixture was stirred at room temperature for 10 minutes. Then a solution of 4-chloro-6,7-dimethoxyquinazoline (8.14 g), which is a chloroquinazoline derivative synthesized by a conventional method according to that described, for example, in J. Am. Chem. Soc., Was added. 68, 1229 (1946) or J. Am. Chem. Soc., 68, 1305 (1946). The mixture was stirred at a temperature of 110 ° C for 30 minutes. Water was added to the reaction solution, followed by extraction with chloroform. The chloroform layer was then washed with a saturated aqueous solution of sodium hydrogencarbonate and dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, and methanol was added to the residue to prepare a suspension. The precipitated crystal was collected by filtration with suction to provide 9.13 (yield: 76%) of the title compound. ^ • H-NMR (CDC13, 400 Mhz): d 4.05 - 4.08 (m, 8H), 6.85 (d, J = 8.5 Hz, 1H), 7.00 (dd, J = 2.7 Hz, 8.8 Hz, 1H), 7.21 (d, J = 2.7 Hz, 1H), 7.32 (s, 1H), 7.52 (s, 1H), 8.64 (s, 1H) Mass analysis, found (ESI-MS, m / z): 332 (M + + l) Production example 24: N-benzyl-N- (2,4-difluorophenyl) amine Magnesium sulfate (5.59 g) and a minor amount of acetic acid were added to a solution of 2,4-difluoroaniline (2.37 ml) and benzaldehyde (2.36 ml) in methanol (46 ml). The mixture was stirred at room temperature for 45 minutes.

Sodium borohydride (2.64 g) was added with ice cooling, and the mixture was stirred at room temperature for 1 hour. The solvent was removed by filtration under reduced pressure. Water and ethyl acetate were added to the residue. The mixture was stirred and filtered through Celite. The organic layer was extracted with ethyl acetate and dried over anhydrous sodium sulfate. The solvent was removed by filtration under reduced pressure. The residue was purified by chromatography on silica gel by development with hexane / acetone (30/1) to provide 3.04 mg (yield: 60%) of the title compound. ^ -NMR (CDCI3, 400 Mhz): d 4.34 (s, 2H), 6.56-6.82 (m, 3H), 7.25-7.38 (m, 5H) Production example 25: 4- (benzyloxy) -5-methoxy- Methyl 2-nitrobenzoate Methyl vanillate (50 g) commercially available and potassium carbonate (76 g) were dissolved in N, N-dimethylformamide (200 ml). Benzyl bromide (33 ml) was added dropwise to the solution over a period of 10 minutes. The mixture was stirred at room temperature overnight. Water (200 ml) was added, followed by extraction with ethyl acetate. Saturated brine was then added to the organic layer. And the mixture was extracted with ethyl acetate. Sodium sulfate was added to the organic layer to dry the organic layer. Then the organic layer was filtered, and the solvent was removed by distillation under reduced pressure. The residue was dried through a vacuum pump to provide 68 g of a white solid. Subsequently, 100 ml of acetic acid and 200 ml of nitric acid were added with ice cooling. The mixture was stirred for 8 hours and then water was added. The resulting solid was then collected by filtration, washed thoroughly with water and dried through a vacuum pump to provide 74 g (yield: 93%) of the title compound. 1H-NR (CDC13, 400 Mhz): d 3.90 (s, 3H), 3.98 (s, 3H), 5.21 (s, 2H), 7.08 (s, 1H), 7.31-7.45 (, 5H), 7.51 (s) , 1H) Example of production 26: 7- (benzyloxy) -6-methoxy-3,4-dihydro-4-quinazolinone Methyl 4- (benzyloxy) -5-methoxy-2-nitrobenzoate (15.0 g) was dissolved in acetic acid (200 ml) at room temperature. Iron (powder) (13.2 g) was then added to the solution. The temperature of the mixture was raised to 90 ° C, and the mixture was then stirred for one hour. The resulting gray solid was filtered through Celite, followed by washing with acetic acid. Concentrated hydrochloric acid was added to the mother liquor. The solvent was then removed by distillation under reduced pressure. This resulted in the precipitation of a solid. The solid was collected by filtration, washed with ethyl acetate and ether, and dried through a vacuum pump. Subsequently, chloroform and methanol were added to the solid to prepare a suspension, and a 10% aqueous solution of sodium hydroxide was added to dissolve the solid, followed by extraction with chloroform. After washing with water, the organic layer was dried in sodium sulfate. Then, the organic layer was filtered and the solvent was then removed by distillation under reduced pressure. The residue was dried through a vacuum pump to provide 9.5 g (yield: 70%) of a crude product of Methyl 2-amino-4- (benzyloxy) -5-methoxybenzoate. Methyl 2-amino-4- (benzyloxy) -5-methoxybenzoate was dissolved (650 mg) in N, N-dimethylformamide (15 ml) and methanol (3 ml). Formamide (0.46 ml) and sodium methoxide (373 mg) were added to the solution. The mixture was heated to a temperature of 100 ° C and was stirred overnight. The reaction solution was cooled to room temperature, and 10 ml of water was then added to the cooled reaction solution. The reaction solution was neutralized with an aqueous M-hydrochloric acid solution to precipitate a solid. The solid was collected by filtration, washed with water and ether, and then dried through a vacuum pump to provide 566 mg (yield: 87%) of the title compound. 1 H-NMR (DMSO-de, 400 Mhz): d 3.88 (s, 3H), 5.25 (s, 2H), 7.23 (s, 1H), 7.33-7.49 (m, 6H), 7.97 (s, 1H), 12.06 (br, 1H) Production Example 27: 7- (benzyloxy) -4-chloro-6-methoxyquinazoline Phosphorus oxychloride (515 ml) was added to 7- (benzyloxy) -6-methoxy-3,4-dihydro-4-quinazolinone (400 mg ) and diisopropylethylamine (0.3 ml), and the mixture was refluxed for 20 minutes. The reaction solution was cooled to room temperature. A 10% aqueous solution of sodium hydroxide was then added to the reaction solution, followed by extraction with chloroform. The organic layer was dried in sodium sulfate. The organic layer was filtered, and the solvent was then removed by distillation under reduced pressure. The residue was dried through a vacuum pump to provide 420 mg (yield: 99%) of the title compound. 1 H-NMR (CDCl 3, 400 Mhz): d 4.08 (s, 3 H), 5.34 (s, 2 H), 7.35 - 7.51 (m, 7 H), 8.86 (s, 1 H) Production example 28: 5- (benzyloxy) Methyl 4-methoxy-2-nitrobenzoate Methyl 3-hydroxy-4-methoxybenzoate (10 g) commercially available and potassium carbonate (23 g) were dissolved in N, N-dimethylformamide (50 ml). Benzyl bromide (6.5 ml) was added dropwise to the solution over a period of 10 minutes. The mixture was stirred at room temperature overnight. Water (200 ml) was added, followed by extraction with ethyl acetate. Saturated brine was then added to the organic layer, followed by extraction with ethyl acetate. Sodium sulfate was added to the organic layer to dry the organic layer. Then the organic layer was filtered, and the solvent was then removed by distillation under reduced pressure. The residue was dried through a vacuum pump to provide 8.4 g of a white solid. Subsequently, 7.0 g of the solid was added in a flask, and 100 ml of acetic acid and 200 ml of nitric acid were added with cooling with ice. The mixture was stirred for 8 hours, and then water was added. The resulting solid was then collected by filtration, washed thoroughly with water and dried through a vacuum pump to provide 7.9 g (yield: 96%) of the title compound. 1H-1'JMR (CDCl 3, 400 Mhz): d 3.89 (s, 3H), 3.96 (s, 3H), 5.21 (s, 2H), 7.15 (s, 1H), 7.34-7.45 (m, 6H) Example Production Line 29: 6- (Benzyloxy) -7-methoxy-3,4-dihydro-4-quinazolinone Methyl 5- (benzyloxy) -4-methoxy-2-nitrobenzoate (15.8 g) was dissolved in acetic acid (200 ml ) at room temperature. Iron (powder) (13.9 g) was then added to the solution. The temperature of the mixture was heated to 90 ° C, and was stirred for one hour. The resulting gray solid was filtered through Celite, followed by washing with acetic acid. Concentrated hydrochloric acid was added to the mother liquor, and the solvent was then removed by distillation under reduced pressure in order to precipitate a solid. The solid was collected by filtration, washed with ethyl acetate and ether, and dried through a vacuum pump. Subsequently, chloroform and methanol were added to the solid to prepare a suspension, and a 10% aqueous solution of sodium hydroxide was added to the suspension to dissolve the solid, followed by extraction with chloroform. The extract was washed with water, and the organic layer was dried in sodium sulfate. Then, the organic layer was filtered and the solvent was then removed by distillation under reduced pressure. The residue was dried through a vacuum pump to provide 10.4 g (yield: 73%) of a crude product of methyl 2-amino-5- (benzyloxy) -4-methoxybenzoate. Methyl 2-amino-5- (benzyloxy) -4-methoxybenzoate (5.0 g) was dissolved in N, N-dimethylformamide (150 ml) and methanol (30 ml). Formamide (3.5 ml) and sodium methoxide (2.8 g) were added to the solution. The mixture was heated to a temperature of 100 ° C and was then stirred overnight. The reaction solution was cooled to room temperature, and 10 ml of water was then added. The reaction solution was neutralized with an aqueous M-hydrochloric acid solution to precipitate a solid. The solid was collected by filtration, washed with water and ether, and then dried through a vacuum pump to provide 3.7 g (yield: 76%) of the title compound. 1 H-NMR (DMSO-de, 400 Mhz): d 3.92 (s, 3 H), 5.21 (s, 2 H), 7.16 (s, 1 H), 7.33 - 7.49 (m, 5 H), 7.55 (s, 1 H), 7.99 (s, 1H), 12.06 (br, 1H) Production example 30: 6- (benzyloxy) -4-chloro-7-methoxyquinazoline Phosphorus oxychloride (3.1 ml) was added to 6- (benzyloxy) -7-methoxy 3, 4-dihydro-4-quinazolinone (3.5 g) and diisopropylethylamine (11.5 ml). The mixture was refluxed for 20 minutes. The reaction solution was cooled to room temperature, and then a 10% aqueous solution of sodium hydroxide was added to the cooled reaction solution, followed by extraction with chloroform.

The organic layer was dried in sodium sulfate. The organic layer was filtered, and the solvent was then removed by distillation under reduced pressure. The residue was dried through a vacuum pump to provide 2.9 g (yield: 72%) of the title compound. ^ -H-NMR (CDC13, 400 Mhz): d 4.07 (s, 3H), 5.32 (s, 2H), 7.35 -7.53 (m, 7H), 8.86 (s, 1H) Production example 31: 4-. { [7- (benzyloxy) -6-methoxy-4-quinazolinyl] oxy} -2-chloroaniline 7- (benzyloxy) -4-chloro-6-methoxyquinazoline was dissolved (30.0 g) and tetrabutylammonium chloride (13.9 g) in acetone (400 ml), and the solution was stirred at room temperature.

A solution of 4-amino-3-chlorophenol hydrochloride (36.0 g) in a 20% aqueous solution of sodium hydroxide (64 ml) was added. The mixture was then heated under reflux for 3 hours. The reaction solution was cooled to room temperature, and chloroform and water were added to the cooled reaction solution followed by extraction with chloroform. The extract was washed with a saturated aqueous solution of sodium hydrogencarbonate and saturated brine and was then dried in anhydrous sodium sulfate. Then, the sodium sulfate was removed, and the solvent was then removed by distillation. The residue was washed with methanol, and the washed solid was subjected to evaporation to dryness in vacuo through a vacuum pump to provide 36.6 g (yield: 90%) of the title compound. 1 H-NMR (DMSO-de, 400 Mhz): d 3.96 (s, 3H), 5.34 (s, 2H), 6.86 (d, J = 8.8 Hz, 1H), 7.00 (dd, J = 2.7 Hz, 8.8 Hz , 1H), 7.22 (d, J = 2.7 Hz, 1H), 7.35-7.54 (m, 7H), 8.53 (s, 1H) Production example 32: N- (4- { [7- (benzyloxy) -6-methoxy-4-quinazolinyl] oxy.} -2-chlorophenyl) -N'-propylurea. 4- was dissolved. { [7- (benzyloxy) -6-methoxy-4-quinazolinyl] oxy} -2-chloroaniline (12.2 g) in anhydrous chloroform. Then triethylamine (8.4 ml) was added to the solution, and the mixture was stirred at room temperature. Separately, triphosgene (4.5 g) was dissolved in anhydrous chloroform (12 ml), and the solution was added dropwise to the mixed solution. The mixture was stirred at room temperature for 20 minutes, and n-propylamine (4.9 ml) was then added thereto, followed by stirring at room temperature for an additional 1 hour until a precipitate was obtained as a white solid. This solid was collected by filtration and then washed with chloroform to provide 9.4 g (yield: 63%) of the title compound. 1 H-NMR (DMSO-de, 400 Mhz): d 0.91 (t, J-7.3 Hz, 3 H), 1.44 -1.50 (, 2 H), 3.06 - 3.09 (m, 2 H), 3.98 (s, 3 H), 5.35 (s, 2H), 6.97 - 7.01 (, 1H), 7.23 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.37 - 7.57 (m, 9H), 8.20 (d, J = 9.3 Hz, 1H), 8.55 (s, 1H) Production example 33: N-. { 2-Chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl} -N'-propylurea N- (4- {[7- (benzyloxy) -6-methoxy-4-quinazolinyl] oxy} -2-chlorophenyl) -N'-propylurea (42.2 g) was dissolved in acid trifluoroacetic (200 ml). Methanesulfonic acid (11.1 ml) was then added to the solution, and the mixture was stirred at a temperature of 100 ° C for 4 hours. The reaction solution was cooled to room temperature, and trifluoroacetic acid was removed by distillation under reduced pressure. Chloroform and methanol were added to the mixture as a residue, followed by extraction with a 10% aqueous solution of sodium hydroxide, three times. The aqueous layer was neutralized with concentrated hydrochloric acid to precipitate a solid. The solid was washed with water, methanol, and ether in this order, and then vacuum dried through a vacuum pump to provide 20.7 g (yield: 60%) of the title compound. 1 H-NMR (DMSO-de, 400 Mhz): d 0.91 (t, J = 7.3 Hz, 3 H), 1.42 -1.49 (m, 2 H), 3.06 - 3.17 (m, 2 H), 3.84 (s, 3 H), 6.65 (s, 1H), 7.03 (m, 1H), 7.14 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.20 (s, 1H), 7.35 (d, J = 2.7 Hz, 1H), 8.05 ( s, 1H), 8.14 (dd, J = 2.7 Hz, 8.8 Hz, 1H), 8.19 (s, 1H) Production example 34: 6, 7-dimethoxy-4-quinazolone Formamide (150 ml) was added to methyl 2-amino-3,4-dimethoxybenzoate (20.0 g, 94.8 mmol). The mixture was heated to a temperature of 160 ° C for 8.5 hours. The reaction solution was cooled and then filtered. The collected precipitate was washed with water (100 ml x 2 times), and the washed precipitate was dried under vacuum to provide 17.85 g (yield: 91.5%) of the objective compound. 1 H-NMR (DMSO-de, 400 Mhz): d 4.01 (s, 3 H), 4.02 (s, 3 H), 7.14 (s, 1 H), 7.34 (s, 1 H), 7.61 (s, 1 H), 7.97 ( s, 1H) Production example 35: 4-chloro-6,7-dimethoxyquinazoline Sulfolane (250 ml) and phosphorus oxychloride (250 ml = 412.5 g, 2.69 mmol) were added to 6,7-dimethoxy-4-quinazolone ( 50.1 g, 0.24 mmol), and the mixture was stirred at a temperature of 120 ° C for one hour. The reaction mixture was cooled to room temperature, and the excess phosphorus oxychloride was then removed by distillation under reduced pressure. The residue was poured into ice water (1000 ml) and chloroform (1000 ml) was added. The aqueous layer was adjusted to pH 6.5 by the addition of a 20% sodium hydroxide solution, followed by separation of the organic layer from the aqueous layer. The separated organic layer was washed with water (1000 ml x 6 times), dried over sodium sulfate, and then concentrated under reduced pressure. Tetrahydrofuran (470 ml) was added to the residue, and the mixture was refluxed. The reaction solution was cooled to -5 C to -10 ° C and filtered and dried to provide 38.5 g (yield: 71.4%) of the target product. 1 H-NMR (DMSO-de, 400 Mhz): d 4.09 (s, 3 H), 4.09 (s, 3 H), 7.14 (s, 1 H), 7.34 (s, 1 H), 7.61 (s, 1 H), 7.97 ( s, 1H) Production Example 36: 4-chloro-6,7-dimethoxyquinazoline Toluene (100 ml) and phosphorus oxychloride (7.4 g), 48.6 mmol) were added to 6,7-dimethoxy-4-quinazolone (10.0 g) , 48.5 mmol), and the mixture was stirred at a temperature of 120 ° C for 6.5 hours. The reaction solution was cooled to room temperature, then filtered, washed with toluene (100 ml, 50 ml), and dried to provide 11.5 g (yield: 91%) of the objective product. Production Example 37: 4- (A '-amino-3'-chloro) -phenoxy-6,7-dimethoxyquinazoline Sodium hydroxide (8.5 g, 0.21 mmol) and water (90 mL) were added to 4-amino hydrochloride 3-chlorophenol (14.6 g, 81 mmol) and dissolved there. 4-Chloro-6,7-dimethoxyquinazoline (12 g, 53 mmol) and methyl ethyl ketone (225 ml) were added to the reaction, and the mixture was refluxed for 2 hours. The reaction solution was cooled to a temperature of about 50 ° C, and chloroform (500 ml) and water (500 ml) were then added to the cooled reaction solution. The mixture was stirred for 10 minutes, and the organic layer was then separated from the aqueous layer. Chloroform (250 ml) was added to the aqueous layer, and the mixture was stirred for 10 minutes, followed by layer separation. The organic layer was concentrated under reduced pressure. Methanol (50 ml) was added to the residue, and the mixture was stirred for 30 minutes. The reaction solution was then filtered and dried to provide 15.6 g (yield: 85%) of the objective product. aH-NMR (DMSO-de, 400 MHz): d 3.95 (s, 3H), 3.97 (s, 3H), 5.33 (s, 2H), 6.85 (d, J = 8.8 Hz, 1H), 6.98 (dd, J = 2.8 Hz, J = 8.8 Hz, 1H), 7.20 (d, J = 2.8 Hz, 1H), 7.36 (s, 1H), 7.51 (s, 1H), 8.53 (s, 1H) Production example 38: 4- (4'-amino-3'-chloro) -phenoxy-6,7-dimethoxyquinazoline A 20% aqueous solution of sodium hydroxide (3.5 ml) and water (2 ml) were added and dissolved in 4-hydrochloride. -amino-3-chlorophenol (1.3 g, 7.2 mmol). 4-Chloro-6,7-dimethoxyquinoline (0.8 g, 3.6 mmol), chloroform (6 ml), and tetrabutylammonium bromide (0.58 g, 1.8 mmol) were added to the solution and the mixture was refluxed for 2 hours. The reaction solution was cooled. Chloroform (10 ml) and water (10 ml) were then added to the cooled reaction solution, and the mixture was stirred for 10 minutes, followed by separation of the organic layer from the aqueous layer. Chloroform (10 ml) was added to the separated aqueous layer, and the mixture was stirred for 10 minutes, which was followed by layer separation. The organic layer was concentrated under reduced pressure. Methanol (2 ml) was added to the residue, and the mixture was stirred for 30 minutes. The reaction solution was then filtered and dried to provide 1.0 g (yield: 83%) of the target product. Example 1: N- (2,4-difluorobenzyl) -N '-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2-fluorophenyl} urea 4- [(6,7-Dimethoxy-4-quinolyl) -oxi] -2-fluoroaniline (100 mg) was dissolved in toluene (5.0 ml) and triethylamine (1.0 ml) with heating. A solution of triphosgene (103 mg) in dichloromethane (1.0 ml) was then added to the solution, and the mixture was heated under reflux for 3 minutes. Then, 2,4-difluorobenzylamine (54 mg) was added, and the mixture was heated under reflux for an additional 5 hours. A saturated aqueous solution of sodium hydrogencarbonate was then added to the reaction solution which was followed by extraction with chloroform. The chloroform layer was dried in anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by development with chloroform / acetone (2/1) to provide 123 mg (yield: 80%) of the title compound. XH-NMR (CDC13, 400 MHz): d 4.02 (s, 3H), 4.03 (s, 3H), 4.47 (d, J = 5.9 Hz, 2H), 5.78- 5.90 (m, 1H), 6.46 (d, J = 5.4 Hz, 1H), 6.74 - 6.99 (m, 4H), 7.03 - 7.14 (m, 1H), 7.35 - 7.44 (m, 2H), 7.50 (s, 1H), 8.16 (t, J = 9.0 Hz , 1H), 8.47 (d, J = 5.1 Hz, 1H) Mass analysis, found (FD-MS, m / z): 483 (M +) Example 2: N-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2-fluorophenyl} -N '- (2-fluoroethyl) urea 4- [(6,7-Dimethoxy-4-quinolyl) -oxy] -2-fluoroaniline (100 mg) was dissolved in toluene (10 ml) and triethylamine (0.5 ml) with heating. A solution of triphosgene (47 mg) in dichloromethane (1.0 ml) was then added to the solution, and the mixture was heated under reflux for 5 minutes. Then, 2-fluoroethylamine hydrochloride (42 mg) was added, and the mixture was heated under reflux for an additional 8 hours. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution, which was followed by extraction with ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / acetone (2/1) to provide 93 mg (yield: 72%) of the title compound. XH-NMR (DMSO-de, 400 MHz): d 3.40 ((m, 1H), 3.47 (m, 1H), 3.93 (s, 3H), 3.95 (s, 3H), 4.42 (t, J = 4.9 Hz , 1H), 4.54 (t, J = 4.9 Hz, 1H), 6.51 (d, J = 5.4 Hz, 1H), 6.88 (m, 1H), 7.05 (, 1H), 7.28 (dd, J = 2.7 Hz, J = 11.7 Hz, 1H), 7.40 (s, 1H), 7.49 (s, 1H), 8.21 (m, 1H), 8.47 (br, 1H), 8.48 (d, J = 5.4 Hz, 1H) Mass analysis , found (ESI-MS, m / z): 404 (M? l) Use 3 N- { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2-fluorophenyl}. N '- (2-pyridylmethyl) urea 4- [(6,7-Dimethoxy-4-quinolyl) -oxy] -2-f luoroaniline (100 mg) was dissolved in toluene (5 ml) and triethylamine (1 ml). A solution of triphosgene (104 mg) in dichloromethane was then added to the solution, and the mixture was refluxed for 5 minutes, then 2- (aminomethyl) pyridine (40 μl) was added, the mixture was heated under reflux for 2 hours A saturated aqueous solution of sodium hydrogencarbonate (1 ml) and chloroform (2 ml) was added to the reaction solution. It is supported on diatomaceous earth followed by extraction with chloroform. The solvent was removed by filtration under reduced pressure. The residue was purified by chromatography on silica gel by chloroform / methanol (8/1) development to provide 126 mg (yield: 88%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 4.07 (s, 3H), 4.09 (s, 3H), 4.61 (d, J = 5.4 Hz, 2H), 6.40-6.50 (br, 1H), 6.61 (d, J = 5.9 Hz, 1H), 6.92 - 7.01 (m, 2H), 7.21 - 7.25 (m, 1H), 7.36 (d, J = 7.8 Hz, 1H), 7.56 (s, 1H), 7.68 - 7.78 (m , 2H), 7.75 (s, 1H), 8.27 - 8.34 (m, 1H), 8.49 (d, J = 6.1 Hz, 1H), 8.55 (d, J = 4.1 Hz, 1H) Mass analysis, found (FD -MS, m / z): 448 (M +) Example 4: N-Allyl-N '-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2-fluorophenyl} -urea 4- [(6,7-Dimethoxy-4-quinolyl) -oxi] -2-fluoroaniline (100 mg) was dissolved in toluene (5 ml) and triethylamine (1 ml), and then a solution was added to the solution. Triphosgene solution (104 mg) in dichloromethane. The mixture was heated under reflux for 5 minutes. Then, allyla (22 mg) was added to the reaction solution, and the mixture was heated under reflux for an additional 4 hours. A saturated aqueous solution of sodium hydrogencarbonate (1 ml) and chloroform (2 ml) were then added to the reaction solution and the mixture was supported in diatomaceous earth, followed by extraction with chloroform. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / acetone (2/1) to provide 125 mg (yield: 98%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 3.91 - 3.96 (m, 2H), 4.06 (s, 3H), 4.09 (s, 3H), 5.14 - 5.20 (m, 1H), 5.26 - 5.33 (m, 1H ), 5.58 - 5.66 (br, 1H), 5.86 - 5.98 (m, 1H), 6.56 (d, J = 5.9 Hz, 1H), 6.88 - 7.01 (m, 2H), 7.23 (s, 1H), 7.55 ( s, 1H), 7.66 (s, 1H), 8.26 - 8.33 (m, 1H), 8.47 (d, J = 5.9 Hz, 1H) Mass analysis, found (FD-MS, m / z): 397 (M + Example 5 N-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2-fluorophenyl} -N'-propylurea 4- [(6,7-Dimethoxy-4-quinolyl) -oxi] -2-fluoroaniline was dissolved (100 mg) in toluene (10 ml) and triethylamine (2 ml), and a solution of triphosgene (104 mg) was then added to the solution. The mixture was heated under reflux for 5 minutes. Then, propylamine (29 mg) was added, and the mixture was heated under reflux for 40 minutes. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then dried in anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by thin layer chromatography on silica gel by development with chloroform / methanol (10/1) to provide 89 mg (yield: 71%) of the title compound. XH-NMR (CDC13, 400 MHz): 8 0.97 (t, J = 7.6 Hz, 3H), 1.55 - 1.64 (m, 2H), 3.24 - 3.29 (, 2H), 4.05 (s, 3H), 4.06 (s) , 3H), 5.11, 2H), 4.06 (s, 3H), 5.11 (t, J = 5.4 Hz, 1H), 6.51 (d, J = 5.4 Hz, 1H), 6.74 - 6.76 (m, 1H), 6.91 - 6.99 (m, 2H), 7.48 (s, 1H), 7.52 (s, 1H), 8.18 - 8.23 (m, 1H), 8.49 (d, J = 5.6 Hz, 1H) Mass analysis, found (FD- MS, m / z): 399 (M +) and 6 N-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2-fluorophenyl} -N '- (4-fluorobutyl) urea 4- [(6,7-Dimethoxy-4-quinolyl) -oxy] -2-fluoroaniline (100 mg) was dissolved in toluene (6 ml) and triethylamine (1.0 ml) with heating, and a solution of triphosgene (104 mg) in dichloromethane (1.0 ml) was then added to the solution. The mixture was heated under reflux for 5 minutes. Then, 4-fluorobutylane hydrochloride (55 mg) was added to the reaction solution, and the mixture was heated under water.

Reflux for 2 additional hours. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution, followed by extraction with chloroform. The chloroform layer was dried in anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by development with chloroform / acetone (2/1) to provide 80 mg (yield: 55%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 1.66-1.87 (m, 4H), 3.33-3.40 (m, 2H), 4.04 (s, 3H), 4.05 (s, 3H), 4.44 (t, J = 5.6 Hz, 1H), 4.56 (t, J = 5.7 Hz, 1H), 4.90 (t, J = 5.7 Hz, 1H), 6.48 - 6.52 (m, 2H), 6.93 - 7.02 (m, 2H), 7.42 (s, 1H), 7.51 (s, 1H), 8.15 (t, J = 8.9 Hz, 1H), 8.50 (d, J = 5.1 Hz, 1H) Mass analysis, found (FD-MS, m / z): 431 (M +) Example! _: N-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2-fluorophenyl} -N '- (2-propynyl) urea 4- [(6,7-Dimethoxy-4-quinolyl) -oxy] -2-fluoroaniline (150 mg) was dissolved in chloroform (10 ml) and triethylamine (2 ml) and a solution of triphosgene (156 mg) in dichloromethane was added to the solution. The mixture was heated under reflux for 10 minutes. Then, propargylamine (53 mg) was added and the mixture was heated under reflux for an additional 30 minutes. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was dried in anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by silica gel chromatography by development with chloroform / acetone (2/1) to provide 164 mg (yield: 87%) of the title compound. ^ • H-NMR (DMSO-de, 400 MHz): d 2.49 - 2.51 (m, 1H), 3.90 - 3.95 (m, 8H), 6.52 (d, J = 5.1 Hz, 1H), 6.89 - 6.92 (m , 1H), 7.04 -7.06 (m, 1H), 7.26 - 7.29 (m, 1H), 7.39 (s, 1H), 7.49 (s, 1H), 8.16 - 8.20 (m, 1H), 8.46 - 8.49 (m , 2H) Example 8_: N-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2-fluorophenyl} -N, -ethylurea 4 - [(6,7-Dimethoxy-4-quinolyl) -oxy] -2-fluoroaniline (100 mg) was dissolved in toluene (8 ml) and triethylamine (1.0 ml) with heating, and added then a triphosgene solution (47 mg) in toluene (1.0 ml) to the solution. The mixture was heated under reflux for 5 minutes. After, ethylamine hydrochloride (60 mg) was added to the reaction solution, and the mixture was heated under reflux for an additional 5 hours. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / acetone (2/1) to provide 70 mg (yield: 53%) of the title compound. ^ - MR (CDC13, 400 MHz): d 1.21 (t, J = 7.3 Hz, 3H), 3.34 (, 2H), 4.06 (s, 3H), 4.08 (s, 3H), 5.64 (br, 1H), 6.55 (d, J = 5.6 Hz, 1H), 6.89 (dd, J = 2.7 Hz, J = 11.2 Hz, 1H), 6.97 (m, 1H), 7.26 (br, 1H), 7.54 (s, 1H), 7.62 (s, 1H), 8.28 (t, J = 9.0 Hz, 1H), 8.47 (d, J = 5.6 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 386 (M ++ l) Example 9: N-butyl-N '-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2-fluorophenyl} urea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2-fluoroaniline was dissolved (100 mg) in toluene (8 ml) and triethylamine (1.0 ml) with heating, and then a solution of triphosgene (47 mg) in toluene (1.0 ml) was added to the solution. The mixture was heated under reflux for 5 minutes. Then, butylamine (80 mg) was added to the reaction solution, and the mixture was heated under reflux for an additional 5 hours. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by development with chloroform / acetone (2/1) to provide 117 mg (yield: 81%) of the title compound. 1H-NR (CDCl 3, 400 MHz): d 0.94 (t, J = 7.3 Hz, 3H), 1.40 (m, 2H), 1.55 (m, 2H), 3.29 (dd, J = 7.1 Hz, J = 12.9 Hz , 2H), 4.06 (s, 3H), 4.09 (s, 3H), 5.72 (br, 1H), 6.56 (d, J = 5.9 Hz, 1H), 6.88 (dd, J = 2.7 Hz, J = 11.2 Hz , 1H), 6.97 (d, J = 9.0 Hz, 1H), 7.33 (s, 1H), 7.55 (s, 1H), 7.65 (s, 1H), 8.30 (t, J = 9.0 Hz, 1H), 8.46 (d, J = 5.9 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 414 (M "? l) Example 10 N- (sec-butyl) -N '-. [(6,7-dimethoxy-4-quinolyl) oxy] -2-fluorophenyl] urea 4 - [(6,7-dimethoxy-4-quinolyl) -oxy] -2-fluoroaniline was dissolved (100 mg) in chloroform (5 ml) and triethylamine (1 ml) and a solution of triphosgene (104 mg) in dichloromethane was then added to the solution. The mixture was heated under reflux for 5 minutes. Then, sec-butylamine (48 μl) was added to the reaction solution. The mixture was heated under reflux for 10 minutes. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / acetone (8/2) to provide 117 mg (yield: 89%) of the title compound. 1 H-NMR (CDCl 3, 400 MHz): d 0.95 (t, J = 7.6 Hz, 3 H), 1.18 (d, J = 6.6 Hz, 3 H), 1.47 - 1.55 (m, 2 H), 3.79 - 3.89 (m, 1H), 4.04 (s, 6H), 5.28 (d, J = 8.1 Hz, 1H), 6.48 (d, J = 5.4 Hz, 1H), 6.89-6.98 (m, 2H), 7.08 (d, J = 2.7 Hz, 1H), 7.42 (s, 1H), 7.51 (s, 1H), 8.20 - 8.24 (m, J = 9.0 Hz, 1H), 8.48 (d, J = 5.4 Hz, 1H) Mass analysis, found ( ESI-MS, m / z): 414 (M? L) Example 11: N-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2-fluorophenyl} -N'-Isobutylurea 4- [(6,7-Dimethoxy-4-quinolyl) -oxy] -2-fluoroaniline (100 mg) was dissolved in chloroform (5 ml) and triethylamine (1 ml), and then a Triphosgene solution (104 mg) in dichloromethane to the solution. The mixture was heated under reflux for 5 minutes. Then, isobutylamine (50 μl) was added to the reaction solution, and the mixture was heated under reflux for 10 minutes. The reaction solution was purified by chromatography on silica gel by development with chloroform / acetone (4/1). Thus, the title compound was obtained quantitatively. ^ • H-NMR (CDC13, 400 MHz): d 0.94 (d, J = 6.6 Hz, 6H), 1.77 - 1.84 (m, 1H), 3.10 - 3.13 (m, 2H), 4.03 (s, 3H), 4.03 (s, 3H), 5.58 (t, J = 5.4 Hz, 1H), 6.47 (d, J = 5.4 Hz, H), 6.88 - 6.97 (, 2H), 7.18 (s, 1H), 7.41 (s, 1H), 7.50 (s, 1H), 8.18 -8.23 (m, 1H), 8.48 (d, J = 5.1 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 414 (M ++) l) E emplo 12j N-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2-fluorophenyl} -N '- (1,2-dimethylpropyl) urea 4- [(6,7-Dimethoxy-4-quinolyl) -oxy] -2-fluoroaniline (100 mg) was dissolved in chloroform (5 ml) and triethylamine (1 ml). ), and then a solution of triphosgene (47 mg) in dichloromethane was added to the solution. The mixture was stirred at room temperature for 30 minutes. Then, 1,2-dimethylpropylamine (55 μl) was added to the reaction solution, and the mixture was stirred at room temperature for 10 minutes. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / acetone (2/1) to provide 89 mg (yield: 65%) of the title compound. 1H-NMR (CDC13, 400 MHz): d 0.93 (d, J = 2.2 Hz, 3H), 0.95 (d, J = 2.4 Hz, 3H), 1.14 (d, J = 6.8 Hz, 3H), 1.72 - 1.80 (m, 1H) , 3.76 - 3.84 (m, 1H), 4.04 (s, 3H), 4.05 (s, 3H), 4.91 (d, J = 8.5 Hz, 1H), 6.48 (d, J = 5.4 Hz, 1H), 6.74 ( d, J = 2.9 Hz, 1H), 6.91 - 6.98 (m, 2H), 7.42 (s, 1H), 7.51 (s, 1H), 8.18 -8.23 (m, 1H), 8.49 (d, J = 5.4 Hz , 1H) Mass analysis, found (ESI-MS, m / z): 428 (M? L) Example 13j N-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] phenyl} -N'-propylurea 2-Chloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] aniline (100 mg) was dissolved in chloroform (7.5 ml) and triethylamine (1 ml), and then a Triphosgene solution (99 mg) in chloroform to the solution. The mixture was heated under reflux for 5 minutes. Then, n-propylamine (21 mg) was added to the reaction solution, and the mixture was heated under reflux for an additional 2 hours. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution and the mixture was supported in diatomaceous earth, followed by extraction with chloroform. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by -development with chloroform / methanol (8/1). Thus, the title compound was obtained quantitatively. XH-NMR (CDC13, 400 MHz): d 0.99 (t, J = 7.3 Hz, 3H), 1.58-1.65 (m, 2H), 3.24-3.31 (m, 2H), 4.04 (s, 3H), 4.05 ( s, 3H), 4.94 (t, J = 5.9 Hz, 1H), 6.48 (d, J = 5.1 Hz, 1H), 6.77 (s, 1H), 7.11 (dd, J = 2.7 Hz, 9.0 Hz, 1H) , 7.21 (d, J = 2.7 Hz, 1H), 7.43 (s, 1H), 7.52 (s, 1H), 8.27 (d, J = 9.0 Hz, 1H), 8.50 (d, J = 5.1 Hz, 1H) Mass analysis, found (FD-MS, m / z): 415, 417 (M +) Example 14: N-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] phenyl} -N '- (4-fluoro-2-methylphenyl) urea 2-Chloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] aniline (122 mg) was dissolved in chloroform (10 ml) and triethylamine ( 1 ml), and then a solution of triphosgene (110 mg) in dichloromethane was added to the solution. The mixture was stirred at room temperature for 30 minutes. Then, 4-fluoro-2-methylaniline (126 μl) was added to the reaction solution, and the mixture was stirred at room temperature for 2 hours. Methane was added to the reaction of the solution and the solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / acetone (2/1) to provide 142 mg (yield: 79%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 2.37 (s, 3 H), 4.04 (s, 3 H), 4.04 (s, 3 H), 6.31 (s, 1 H), 6.47 (d, J = 5.1 Hz, 1 H) , 6.97 - 7.06 (m, 3H), 7.11 - 7.14 (m, 1H), 7.19 (d, J = 2.7 Hz, 1H), 7.41 -7.44 (m, 2H), 7.50 (s, 1H), 8.35 (d , J = 9.0 Hz, 1H), 8.50 (d, J = 5.4 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 482, 484 (M? L) Example 15: N- (5 -bromo-6-methyl-2-pyridyl) -Nf-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] phenyl} -urea 2-Chloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] aniline (122 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml), and a solution was then added to the solution. Triphosgene solution (110 mg) in dichloromethane. The mixture was stirred at room temperature for 30 minutes. Then, 6-amino-3-bromo-2-methylpyridine (208 mg) was added to the reaction solution, and the mixture was stirred at room temperature for 2 hours. Methanol was added to the reaction solution, and the solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / acetone (2/1) to provide 155 mg (yield: 77%) of the title compound. XH-NMR (CDCl 3, 400 MHz): d 2.69 (s, 3 H), 4.06 (s, 6 H), 6.53 (d, J = 5.4 Hz, 1 H), 6.56 (d, J = 8.5 Hz, 1 H), 7.14 - 7.17 (m, 1H), 7.30 (d, J = 2.7 Hz, 1H), 7.44 (s, 1H), 7.53 (s, 1H), 7.75 (d, J = 8.5 Hz, 1H), 7.93 (s, 1H), 8.49 (d, J = 9.0 Hz, 1H), 8.52 (d, J = 5.4 Hz, 1H), 11.92 (s, 1H) Mass analysis, found (ESI-MS, m / z): 543, 545, 547 (M? L) E pg 16: N-. { 2-chloro-4- [(6, 7-dimethoxy-4-quinolyl) oxy] phenyl} -N '- (5-chloro-2-pyridyl) urea 2-chloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] aniline was dissolved (122 mg) in chloroform (10 ml) and triethylamine (1 ml), and then a solution of triphosgene (110 g) in dichloromethane was added to the solution. The mixture was stirred at room temperature for 30 minutes. Then, 2-amino-5-chloropyridine (143 mg) was added to the reaction solution, and the mixture was stirred at room temperature for 2 hours. Methanol was added to the reaction solution and the solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by development with chloroform / acetone (2/1) to provide 148 mg (yield: 82%) of the title compound. ^ -NMR (CDC13, 400 MHz): d 4.06 (s, 3H), 4.06 (s, 3H), 6.53 (d, J = 5.1 Hz, 1H), 6.95 (d, J = 8.8 Hz, 1H), 7.14 - 7.17 (m, 1H), 7.31 (d, J = 2.7 Hz, 1H), 7.44 (s, 1H), 7.53 (s, 1H), 7.64 - 7.67 (m, 1H), 8.28 (d, J = 2.7 Hz, 1H), 8.50 - 8.53 (m, 2H), 8.92 (s, 1H), 12.11 (brs, 1H) Mass analysis, found (ESI-MS, m / z): 485, 487, 489 (M? l) Example 17 N- (5-Bromo-2-pyridyl) -N '- [2-chloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] phenyl} urea 2-Chloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] aniline (122 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml), and then a solution was added to the solution of triphosgene (110 mg) in dichloromethane. The mixture was stirred at room temperature for 30 minutes. Then, 2-amino-5-bromopyridine (192 mg) was added to the reaction solution, and the mixture was stirred at room temperature for 2 hours. Methanol was added to the reaction solution and the solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / acetone (2/1) to provide 108 mg (yield: 55%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 4.06 (s, 3 H), 4.06 (s, 3 H), 6.53 (d, J = 5.1 Hz, 1H), 6.80 (d, J = 8.8 Hz, 1H), 7.14 - 7.18 (m, 1H), 7.30 (d, J = 2.7 Hz, 1H), 7.45 (s, 1H), 7.53 (s, 1H), 7.77 - 7.80 (m, 1H), 8.15 (s, 1H), 8.39 (d, J = 2.4 Hz, 1H), 8.50 (d, J = 9.0 Hz, 1H), 8.52 (d, J = 5.4 Hz, 1H) , 12.09 (brs, 1H) Mass analysis, found (ESI-MS, m / z): 529, 531, 533 (M l) Example 18 N-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] phenyl} -N '- (2-methoxyphenyl) urea 2-Chloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] aniline (100 mg) was dissolved in chloroform (10 ml) and isocyanate 2- was added. methoxyphenyl (54 mg) to the solution. The mixture was stirred at a temperature of 60 ° C overnight. Methanol was added to the reaction solution, and the solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / acetone (6/4) to provide 111 mg (yield: 77%) of the title compound. ^ • H-NMR (CDC13, 400 MHz): d 3.85 (s, 3H), 4.04 (s, 3H), 4.05 (s, 3H), 6.50 (d, J = 5.1 Hz, 1H), 6.89-6.93 ( m, 1H), 6.98 -7.03 (m, 1H), 7.05-7.10 (m, 1H), 7.14 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.23 (d, J = 2.7 Hz, 1H), 7.35 (s, 1H), 7.36 (s, 1H), 7.44 (s, 1H), 7.52 (s, 1H), 8.05 - 8.07 (m, 1H), 8.34 (d, J = 9.0 Hz, 1H), 8.52 (d, J = 5.4 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 480, 482 (M? l) Example 19 N-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] phenyl} -N '- (2-methylphenyl) urea 2-chloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] aniline was dissolved (122 mg) in chloroform (10 ml), and o-toluilyl isocyanate (59 mg) was added to the solution. The mixture was stirred at room temperature overnight. Methanol was added to the reaction solution, and the solvent was removed by distillation under reduced pressure. The residue was dissolved in a minor amount of chloroform, and a large amount of ether was added to the solution to precipitate a crystal. The crystal was collected by filtration to provide 59 mg (yield: 34%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 2.38 (s, 3 H), 4.04 (s, 3 H), 4.05 (s, 3H), 6.22 (s, 1H), 6.47 (d, J = 5.1 Hz, 1H), 7.01 (s, 1H), 7.11 - 7.14 (, 1H), 7.18 (d, J = 2.7 Hz, 1H) ), 7.25 - 7.35 (m, 3H), 7.42 (s, 1H), 7.46 (d, J = 6.8 Hz, 1H), 7.50 (s, 1H), 8.37 (d, J = 8.8 Hz, 1H), 8.50 (d, J = 5.1 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 464, 466 (M ++ l) Example 20 N- [2-chloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] phenyl} -N '- (5-methyl-2-pyridyl) urea 2-Chloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] aniline was dissolved (122 mg) in chloroform (10 ml) and triethylamine (1 ml), and then a solution of triphosgene (110 mg) in dichloromethane was added to the solution. The mixture was stirred at room temperature for 30 minutes. Then, 2-amino-5-picoline (120 mg) was added to the reaction solution, and the mixture was stirred at room temperature for 2 hours. Methanol was added to the reaction solution and the solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by development with chloroform / acetone (2/1) to provide 119 mg (yield: 69%) of the title compound. 1H-NR (CDCl3, 400 MHz): d 2.31 (s, 3H), 4.06 (s, 6H), 6.53 (d, J = 5.4 Hz, 1H), 6.76 (d, J = 8.3 Hz, 1H), 7.13 - 7.16 (m, 1H), 7.29 (d, J = 2.7 Hz, 1H), 7.43 (s, 1H) , 7.49 - 7.52 (m, 1H), 7.54 (s, 1H), 8.00 (s, 1H), 8.14 (s, 1H), 8.52 (d, J = 5.1 Hz, 1H), 8.55 (d, J = 9.0 Hz, 1H), 12.57 (brs, 1H) Mass analysis, found (ESI-MS, m / z): 465, 467 (M ++ l) Example 21j N-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] phenyl} -N '- (6-methyl-2-pyridyl) urea 2-Chloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] aniline was dissolved (122 mg) in chloroform (10 ml) and triethylamine (1 ml), and then a solution of triphosgene (110 mg) in dichloromethane was added to the solution. The mixture was stirred at room temperature for 30 minutes. Then, 6-amino-2-picoline (120 mg) was added to the reaction solution, and the mixture was stirred at room temperature for 2 hours. Methanol was added to the reaction solution and the solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / acetone (2/1) to provide 73 mg (yield: 42%) of the title compound. 1H-IÍMR (CDC13, 400 MHz): d 2.57 (s, 3H), 4.06 (s, 6H), 6.54 (d, J = 5.4 Hz, 1H), 6.66 (d, J = 8.1 Hz, 1H), 6.83 (d, J = 7.6 Hz, 1H), 7.15 - 7.18 (m, 1H), 7.30 (d, J = 2.7 Hz, 1H), 7.44 (s, 1H), 7.54 - 7.59 (, 2H), 8.36 (s) , 1H), 8.52 (d, J = 5.1 Hz, 1H), 8.57 (d, J = 9.0 Hz, 1H), 12.45 (s, 1H) Mass analysis, found (ESI-MS, m / z): 465 , 467 (M ++ l) Example 22: N- Hydrochloride. { 2-Chloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] phenyl} -N '- (4-methoxyphenyl) urea 2-Chloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] aniline (100 g) was dissolved in chloroform (4 ml) and 4-isocyanate was then added. -methoxyphenyl (60 μl) to the solution. A reaction was then allowed to proceed at room temperature overnight. The solvent was removed by distillation under reduced pressure. The residue was dissolved in a minor amount of chloroform, and a large amount of ether was added. The resulting precipitate was collected by suction filtration to provide 90 mg (yield: 67%) of N-2-chloro-4 [(6,7-dimethoxy-4-quinolyl) oxy] phenyl-N '- (4-methoxy) phenyl) urea. This product was suspended in 4 ml of methanol, and a solution of hydrochloric acid-methanol was added to the suspension. The mixture was stirred at room temperature for 4 hours, and the solvent was then removed by distillation to provide the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 3.73 (s, 3 H), 4.03 (s, 3 H), 4.05 (s, 3H), 6.90 (d, J = 9.3 Hz, 2H), 6.97 (d, J = 6.6 Hz, 1H), 7.37 - 7.41 (m, 3H), 7.62 (s, 1H), 7.67 (d, J = 2.7 Hz, 1H), 8.39 (d, J = 9.0 Hz, 1H), 8.49 (s, 1H), 8.82 (d, J = 6.6 Hz, 1H), 9.49 (s, 1H) Example 23 N-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] phenyl} -N '- (1-naphthyl) urea 2-Chloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] aniline was dissolved (122 mg) in chloroform (10 ml), and 1-naphthyl isocyanate (75 mg) was added to the solution. The mixture was stirred at room temperature overnight. Methanol was added to the reaction solution and the solvent was removed by distillation under reduced pressure. The residue was dissolved in a minor amount of chloroform and a large amount of ether was added to the solution to precipitate a crystal. The crystal was collected by filtration to provide 105 mg (yield: 57%) of the title compound. 1H-NMR (CDC13, 400 MHz): d 4.03 (s, 3H), 4.04 (s, 3H), 6.44 (d, J = 5.4 Hz, 1H), 6.72 (s, 1H), 7.10 - 7.13 (m, 3H), 7.41 ( s, 1 H), 7.48 (s, 1 H), 7.55 - 7.69 (m, 4 H), 7.88 - 7.96 (m, 2 H), 8.15 (d, J = 7.6 Hz, 1 H), 8.38 - 8.40 (m, 1 H) , 8.48 (d, J = 5.1 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 500, 502 (M? L) Example 24: N- (2,4-difluorophenyl) -N ' -. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2,3-dimethylphenyl} urea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] 2,3-dimethyl-aniline (710 mg) was dissolved in chloroform (7 ml), and then 2,4-difluorophenyl isocyanate solution was added to the solution (310 μl). The mixture was heated under reflux for 1 hour and a large amount of ether was added to the reaction solution. The resulting precipitate was collected by suction filtration to provide 735 mg (yield: 70%) of the title compound. XH-NMR (CDCl 3, 400 MHz): d 2.14 (s, 3 H), 2.27 (s, 3 H), 4.04 (s, 3 H), 4.06 (s, 3 H), 6.27 (d, J = 5.4 Hz, 1 H) , 6.78 - 6.89 (m, 2H), 6.95 (s, 1H), 7.03 (d, J = 8.5 Hz, 1H), 7.10 (s, 1H), 7.40 - 7.45 (, 2H), 7.61 (s, 1H) , 8.03-8.12 (m, 1H), 8.46 (d, J = 5.4 Hz, 1H) Mass analysis, found (FAB-MS, m / z): 480 (M ++ l) Example 25: N- [4 - [(6,7-dimethoxy-4-quinolyl) oxy] -2,3-dimethylphenyl} -N '- (4-fluoro-2-methylphenyl) urea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2,3-dimethyl-aniline (120 mg) was dissolved in chloroform (10 ml) , and triethylamine (1 ml), and then a solution of triphosgene (110 mg) in dichloromethane was added to the solution. The mixture was stirred at room temperature for 30 minutes. Then 4-fluoro-2-methylaniline (126 μl) was added to the reaction solution, and the mixture was stirred at room temperature for 2 hours. Methanol was added to the reaction solution and the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel chromatography by growth with chloroform / methanol (91/9) to provide 160 mg (yield: 91%) of the title compound. ^ -H-NMR (CDC13, 400 MHz): d 2.12 (s, 3H), 2.22 (s, 3H), 2.25 (s, 3H), 4.05 (s, 3H), 4.06 (s, 3H), 6.24 ( d, J = 5.1 Hz, 1H), 6.33 (s, 1H), 6.42 (s, 1H), 6.94 - 7.03 (m, 3H), 7.43 (s, 1H), 7.46 - 7.55 (m, 2H), 7.60 (s, 1H), 8.43 (d, J = 5.1 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 476 (M ++ l) Example 26: N-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2,3-dimethylphenyl} -N '- (3-fluoro-2-methoxyphenyl) urea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2, 3-dimethyl-aniline (120 mg) was dissolved in chloroform (10 ml) , and triethylamine (1 ml), and then a solution of triphosgene (110 mg) in dichloromethane was added to the solution. The mixture was stirred at room temperature for 30 minutes. Then, 3-fluoro-o-anisidine (132 μl) was added to the reaction solution, and the mixture was stirred at room temperature for 2 hours. Methanol was added to the reaction solution and the solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / methanol (91/9) to provide 23 mg (yield: 13%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 2.15 (s, 3 H), 2.32 (s, 3 H), 3.84 (d, J = 1.7 Hz, 3 H), 4.05 (s, 3 H), 4.08 (s, 3 H) , 6.28 (d, J = 5.4 Hz, 1H), 6.72 - 6.77 (, 1H), 6.96 - 7.09 (m, 3H), 7.43 (d, J = 8.5 Hz, 1H), 7.46 (s, 1H), 7.60 (s, 1H), 7.62 (s, 1H), 8.02 - 8.05 (m, 1H), 8.46 (d, J = 5.4 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 492 ( Ml) Example 27: N- (5-Bromo-6-methyl-2-pyridyl) -N '-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2,3-dimethylphenyl} urea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2, 3-dimethyl-aniline (120 mg) was dissolved in chloroform (10 ml), and triethylamine (1 ml), and then a Triphosgene solution (110 mg) in dichloromethane to the solution. The mixture was stirred at room temperature for 30 minutes. Then 6-amino-3-bromo-2-methylpyridine (208 mg) was added to the reaction solution, and the mixture was stirred at room temperature for 2 hours. Methanol was added to the reaction solution and the solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / methanol (91/9) to provide 103 mg (yield: 52%) of the title compound. 1H-N R (CDC13, 400 MHz): d 2.16 (s, 3H), 2.42 (s, 3H), 2.65 (s, 3H), 4.06 (s, 3H), 4.08 (s, 3H), 6.32 (d, J = 5.1 Hz, 1H), 6.64 (d, J = 8.8 Hz, 1H), 7.04 (d, J = 8.8 Hz, 1H), 7.44 (s, 1H), 7.64 (s, 1H), 7.74 (d, J = 8.8 Hz, 1H), 7.91 (d, J = 8.8 Hz, 1H), 8.29 (s, 1H), 8.45 (d, J = 5.4 Hz, 1H), 11.30 (brs, 1H) Mass analysis, found (ESI-MS, m / z): 537, 539 (M ++ 1) Example 28: N- (5-chloro-2-pyridyl) -N '-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2,3-dimethylphenyl} urea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2, 3-dimethyl-aniline (3.00 g) was dissolved in chloroform (150 ml), and triethylamine (6 ml), and then added to The solution is a triphosgene solution (2.74 g). The mixture was stirred at room temperature for 30 minutes. Then 2-amino-5-chloropyridine (2.38 g) was added to the reaction solution, and the mixture was then stirred at room temperature for an additional 2 hours. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was dried in anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, and the residue was purified by chromatography on silica gel by development with chloroform / methanol (20/1) to provide 3.4 g (yield: 77%) of the title compound. XH-NMR (CDC13, 400 MHz): d 2.16 (s, 3H), 2.38 (s, 3H), 4.06 (s, 3H), 4.08 (s, 3H), 6.31 (d, J = 5.4 Hz, 1H) , 6.89 (d, J = 8.8 Hz, 1H), 7.04 (d, J = 8.8 Hz, 1H), 7.44 (s, 1H), 7.62 - 7.68 (m, 2H), 7.90 (d, J = 8.8 Hz, 1H), 8.23 (d, J = 2.4 Hz, 1H), 8.45 (d, J = 5.4 Hz, 1H), 8.50 (s, 1H), 11.23 (brs, 1H) Mass analysis, found (ESI-MS, m / z): 479, 481 (M ++ 1) Example 29: N- (5-bromo-2-pyridyl) -N '-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2,3-dimethylphenyl} urea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2, 3-dimethyl-aniline (120 mg) was dissolved in chloroform (10 ml), and triethylamine (1 ml), and then a Triphosgene solution (110 mg) in dichloromethane to the solution. The mixture was stirred at room temperature for 30 minutes. Then 2-amino-5-bromopyridine (192 mg) was added to the reaction solution, and the mixture was stirred at room temperature for 2 hours. Methanol was added to the reaction solution, and the solvent was removed by distillation under reduced pressure.

The residue was purified by chromatography on silica gel by development with chloroform / methanol (91/9). The solvent was removed by distillation and a crystal precipitated from a minor amount of methanol and a large amount of ether. The crystal was collected by filtration to provide 80 mg (yield: 41%) of the title compound. ^ -H-NMR (CDC13, 400 MHz): d 2.16 (s, 3H), 2.38 (s, 3H), 4.06 (s, 3H), 4.08 (s, 3H), 6.31 (d, J = 5.1 Hz, 1H), 6.96 (d, J = 8.5 Hz, 1H), 7.03 (d, J = 8.8 Hz, 1H), 7.45 (s, 1H), 7.64 (s, 1H), 7.75 - 7.77 (m, 1H), 7.89 (d, J = 8.8 Hz, 1H ), 8.31 (d, J = 2.4 Hz, 1H), 8.45 (d, J = 5.4 Hz, 1H), 8.81 (s, 1H), 11.17 (brs, 1H) Mass analysis, found (ESI-MS, m / z): 523, 525 (M ++ l) Example 30 N-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2,3-dimethylphenyl} -N '- (2-methoxyphenyl) urea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2,3-dimethyl-aniline (120 mg) was dissolved in chloroform (10 ml), and added 2-methoxyphenyl isocyanate (60 μl) to the solution. The mixture was stirred at room temperature overnight. Methanol was added to the reaction solution, and the solvent was removed by distillation under reduced pressure. The residue was dissolved in a minor amount of chloroform and a large amount of ether was added to precipitate a crystal which was then collected by filtration to provide 131 mg (yield: 75%) of the title compound. 1 H-NMR (CDCl 3, 400 MHz): d 2.16 (s, 3 H), 2.32 (s, 3 H), 3.81 (s, 3 H), 4.06 (s, 3 H), 4.08 (s, 3 H), 6.25 (s, 1H), 6.26 (d, J = 5.4 Hz, 1H), 6.85-6.87 (m, 1H), 6.97-7.07 (m, 4H), 7.41 (d, J = 8.5 Hz, 1H), 7.44 (s, 1H) ), 7.62 (s, 1H), 8.15 - 8.17 (m, 1H), 8.45 (d, J = 5.4 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 474 (M ++ l Example 31: N-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2,3-dimethylphenyl} -N '- (2-methylphenyl) urea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2, 3-dimethyl-aniline (120 mg) was dissolved in chloroform (10 ml), and added to the isocyanate solution of o-toluyl (55 μl). The mixture was stirred at room temperature overnight. Methanol was added to the reaction solution, and the solvent was removed by distillation under reduced pressure. The residue was dissolved in a minor amount of chloroform, and a large amount of ether was added to the solution to precipitate a crystal which was then collected by filtration to provide 130 mg (yield: 70%) of the title compound. X H-NMR (CDCl 3, 400 MHz): d 2.12 (s, 3 H), 2.22 (s, 3 H), 2.26 (s, 3H), 4.05 (s, 3H), 4.07 (s, 3H), 6.23 - 6.28 (m, 3H), 7. 02 (d, J = 8.5 Hz, 1H), 7.14 - 7.17 (m, 1H), 7.24 - 7.29 (m, 2H), 7.43 (s, 1H), 7.49 (d, J = 8.5 Hz, 1H), 7.60 (s, 1H), 7.63 (d, J = 7.3 Hz, 1H), 8.43 (d, J = 5.4 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 458 (M? l) Example 32: N- (4 -chloro-2-methylphenyl) -N '-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2,3-dimethylphenyl} 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2,3-dimethyl-aniline (120 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml), and then a solution was added of triphosgene (110 mg) in dichloromethane to the solution. The mixture was stirred at room temperature for 30 minutes. Then 4-chloro-2-methylaniline (130 μl) was added to the reaction solution and the mixture was stirred at room temperature for 2 hours. Methanol was added to the reaction solution, and the solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / methanol (91/9) to provide 136 mg (yield: 75%) of the title compound. 1H-NR (CDC13, 400 MHz): d 2.14 (s, 3H), 2.18 (s, 3H), 2.27 (s, 3H), 4.05 (s, 3H), 4.07 (s, 3H), 6.24 (d, J = 5.4 Hz, 1H), 6.33 (s, 1H), 6.40 (s, 1H), 7.03 (d, J = 8.5 Hz, 1H), 7.19-7.21 (m, 2H), 7.42 - 7.44 (m, 2H) ), 7.60 (s, 1H), 7.65 (d, J = 9.0 Hz, 1H), 8.44 (d, J = 5.1 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 492, 494 (M ++ l) Example 33: N-. { 4- [(6, 7-dimethoxy-4-quinolyl) oxy] -2,3-dimethylphenyl} -N '- (2-pyridyl) urea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2,3-dimethyl-aniline (120 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml), and then a solution of triphosgene (110 mg) in dichloromethane was added to the solution. The mixture was stirred at room temperature for 30 minutes. Then 2-aminopyridine (104 mg) was added to the reaction solution and the mixture was heated under reflux overnight. Methanol was added to the reaction solution, and the solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / methanol (91/9) to provide 72 g (yield: 44%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 2.16 (s, 3 H), 2.41 (s, 3 H), 4.06 (s, 3 H), 4.08 (s, 3 H), 6.32 (d, J = 5.4 Hz, 1 H) , 6.92 - 6.98 (m, 2H), 7.04 (d, J = 8.8 Hz, 1H), 7.44 (s, 1H), 7.65 (s, 1H), 7.67 - 7.69 (m, 1H), 7.97 (d, J = 8.8 Hz, 1H), 8.25 - 8.27 (m, 1H), 8.45 (d, J = 5.1 Hz, 1H), 8.72 (s, 1H), 11.77 (br, 1H) Mass analysis, found (ESI-MS , m / z): 445 (M? l) Example 34: N-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2,3-dimethylphenyl} -N '- (5-methyl-2-pyridyl) urea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2,3-dimethyl-aniline (120 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml), and then a solution of triphosgene (110 mg) in dichloromethane was added to the solution. The mixture was stirred at room temperature for 30 minutes. Then, 2-amino-5-picoline (120 mg) was added to the reaction solution and the mixture was stirred at room temperature for 2 hours. Methanol was added to the reaction solution, and the solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / methanol (91/9) to provide 122 mg (yield: 72%) of the title compound. 1 H-NMR (CDC1, 400 MHz): d 2.15 (s, 3 H), 2.28 (s, 3 H), 2.39 (s, 3 H), 4.04 (s, 3 H), 4.07 (s, 3 H), 6.32 (d, J = 5.4 Hz, 1H), 6.90 (d, J = 8.3 Hz, 1H), 7.02 (d, J = 8.8 Hz, 1H), 7.43 (s, 1H), 7.45 - 7.48 (m, 1H), 7.64 ( s, 1H), 7.99 (d, J = 8.8 Hz, 1H), 8.06 (d, J = 1.5 Hz, 1H), 8.44 (d, J = 5.4 Hz, 1H), 9.23 (s, 1H), 11.77 ( br, 1H) Mass analysis, found (FD-MS, m / z): 458 (M +) Example 35: N-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2,3-dimethylphenyl} -N '- (6-methy1-2-pyridyl) urea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2,3-dimethyl-aniline (120 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml), and then a solution of triphosgene (110 mg) in dichloromethane was added to the solution. The mixture was stirred at room temperature for 30 minutes. Then 6-amino-2-picoline (120 mg) was added to the reaction solution and the mixture was heated under reflux overnight. Methanol was added to the reaction solution, and the solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by development with chloroform / acetone (40/60) to provide 64 mg (yield: 38%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 2.16 (s, 3 H), 2.44 (s, 3 H), 2.54 (s, 3 H), 4.06 (s, 3 H), 4.08 (s, 3 H), 6.32 (d, J = 5.4 Hz, 1H), 6.61 (d, J = 8.3 Hz, 1H), 6.82 (d, J = 7.6 Hz, 1H), 7.04 (d, J = 8.8 Hz, 1H), 7.44 (s, 1H) , 7.53 - 7.57 (m, 1H), 7.65 (s, 1H), 7.79 (s, 1H), 7.99 (d, J = 8.8 Hz, 1H), 8.44 (d, J = 5.1 Hz, 1H), 11.76 ( br, 1H), 7 Mass analysis, found (FD-MS, m / z): 458 (M +) Example 36: N-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2,3-dimethylphenyl} -N '- (4-methoxyphenyl) urea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2,3-dimethyl-aniline (100 mg) was dissolved in chloroform (4 ml) and then added to the isocyanate solution of 4-methoxyphenyl (60 μl). The mixture was allowed to react at room temperature overnight and the solvent was removed by distillation under reduced pressure. The residue was dissolved in a minor amount of chloroform and a large amount of ether was added to the solution. The resulting precipitate was then collected by suction filtration to provide 115 mg (yield: 78%) of the title compound. 1 H-NMR (CDCl 3, 400 MHz): d 2.02 (s, 3H), 2.30 (s, 3H), 3.76 (s, 3H), 4.06 (s, 3H), 4.12 (s, 3H), 6.46 (d, J = 6.3 Hz, 1H), 6.78 (d, J = 9.0 Hz, 1H), 6.91 (d, J = 8.8 Hz, 1H), 7.39 (d, J = 9.0 Hz, 2H), 7.67 (s, 1H), 7.69 (d, J = 8.8 Hz, 1H), 7.92 (s, 1H), 8.20-8.23 (m, 1H) Mass analysis, found (ESI-MS, m / z): 474 (M? L) Example 37: N- ( 2,4-difluorophenyl) -N '-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2,5-dimethylphenyl} urea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2,5-dimethyl-aniline (200 mg) was dissolved in chloroform (15 ml) and then added to the isocyanate solution of 2-4. difluorophenyl (88 μl). The mixture was heated under reflux for 1 hour. The reaction solution was purified by chromatography on silica gel by growth with chloroform / acetone (4/1) to provide 287 mg (yield: 97%) of the title compound. 1 H-NMR (CDC13, 400 MHz): 5 2.17 (s, 3 H), 2.26 (s, 3 H), 4.05 (s, 3 H), 4.06 (s, 3 H), 6.31 (d, J = 5.4 Hz, 1 H) , 6.57 (s, 1H), 6.81 - 6.95 (, 3H), 7.00 (s, 1H), 7.43 (s, 1H), 7.55 (s, 1H), 7.59 (s, 1H), 8.05 - 8.13 (m, 1H), 8.47 (d, J = 5.4 Hz, 1H) Mass analysis, found (FD-MS, m / z): 479 (M +) Example 38: N-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2,5-dimethylphenyl} -N'-propylurea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2,5-dimethyl-aniline (150 mg) was dissolved in chloroform (13 ml) and triethylamine (1.5 ml), and Then, a solution of triphosgene (151 mg) in chloroform was added to the solution. The mixture was heated under reflux for 5 minutes. Then n-propylamine (33 mg) was added to the reaction solution, and the mixture was heated under reflux for an additional 2 hours. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution, and the mixture was supported on diatomaceous earth, followed by extraction with chloroform. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / acetone (4/1) to provide 178 mg (yield: 95%) of the title compound. ^ -H-NMR (CDC13, 400 MHz): d 0.94 (t, J = 7.3 Hz, 3H), 1.51-1.65 (m, 2H), 2.15 (s, 3H), 2.26 (s, 3H), 3.21- 3.28 (m, 2H), 4.05 (s, 3H), 4.06 (s, 3H), 4.63 - 4.69 (m, 1H), 5.97 (s, 1H), 6.31 (d, J = 5.1 Hz, 1H), 6.98 (s, 1H), 7.43 (s, 2H), 7.58 (s, 1H), 8.46 (d, J = 5.4 Hz, 1H) Mass analysis, found (FD-MS, m / z): 409 (M +) Example 39: N- (4-chloro-3-methylphenyl) -N '- [4- [(6,7-dimethoxy-4-quinolyl) oxy] -2,5-dimethylphenyl} urea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2,5-dimethyl-aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml), and then a solution was added of triphosgene (92 mg) in dichloromethane to the solution. The mixture was stirred at room temperature for 30 minutes. Then 4-chloro-2-methylaniline (44 μl) was added to the reaction solution and the mixture was stirred at room temperature overnight. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution, followed by extraction with chloroform. The chloroform layer was dried in sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was dissolved in a minor amount of chloroform and a large amount of ether was added to the solution to precipitate a crystal which was then collected by filtration to provide 118 mg (yield: 78%) of the title compound. XH-NMR (CDC13, 400 MHz): d 2.16 (s, 3H), 2.21 (s, 3H), 2.23 (s, 3H), 4.05 (s, 3H), 4.06 (s, 3H), 6.28 (d, J = 5.4 Hz, 1H), 6.30 (s, 1H), 6.32 (s, 1H), 6.98 (s, 1H), 7.22 - 7.23 (m, 2H), 7.43 (s, 1H), 7.58 (s, 1H) ), 7.59-7.63 (m, 2H), 8.45 (d, J = 5.1 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 492, 494 (M? L) Example AO. N-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2,5-dimethylphenyl} -N '- (4-fluoro-2-methylphenyl) urea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2,5-dimethyl-aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml), and a solution of triphosgene (92 mg) in dichloromethane was then added to the solution. The mixture was stirred at room temperature for 30 minutes. Then 4-fluoro-2-methylaniline (42 μl) was added to the reaction solution and the mixture was stirred overnight at room temperature. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was dried in sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was dissolved in a minor amount of chloroform, and a large amount of ether was added to the solution to precipitate a crystal which was then collected by filtration to provide 108 mg (yield: 74%) of the title compound. ^? - NMR (CDC13, 400 MHz): d 2.15 (s, 6H), 2.30 (s, 3H), 4.05 (s, 3H), 4.05 (s, 3H), 4.06 (s, 3H), 6.24 (s) , 2H), 6.28 (d, J = 5.1 Hz, 1H), 6.94 (s, 1H), 6.96 - 7.00 (m, 2H), 7.42 (s, 1H), 7.49 - 7.52 (m, 1H), 7.58 ( s, 1H), 7.64 (s, 1H), 8.44 (d, J = 5.1 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 476 (M ++ l) Example 41: N- . { 4- [(6,7-dimethoxy-quinolyl) oxy] -2,5-dimethylphenyl} -N '- (3-fluoro-2-methoxyphenyl) urea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2,5-dimethyl-aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml), and a solution of triphosgene (92 mg) in dichloromethane was added to the solution. The mixture was stirred at room temperature for 30 minutes. Then 3-fluoro-o-anisidine (44 μl) was added to the reaction solution and the mixture was stirred at room temperature overnight. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution and the mixture was extracted with chloroform. The chloroform layer was dried in sodium sulfate. The residue was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by development with chloroform / acetc-na (2/1) to provide 126 mg (yield: 83%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 2.16 (s, 3 H), 2.27 (s, 3 H), 3.83 (d, J = 1.7 Hz, 3H), 4.04 (s, 3H), 4.07 (s, 3H), 6.31 (d, J = 5.1 Hz, 1H), 6.74 - 6.79 (, 1H), 6.97 - 7.03 (m, 3H), 7.44 (s, 1H), 7.57 (s, 1H), 7.60 (s, 1H), 7.66 (s, 1H), 8.02 - 8.04 (m, 1H), 8.48 (d, J = 5.1 Hz, 1H) Mass analysis, found ( ESI-MS, m / z): 492 (M? L) Example 42: N-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2,5-dimethylphenyl} -N '- (2-methylphenyl) urea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2,5-dimethyl-aniline (100 mg) was dissolved in chloroform (10 ml) and isocyanate was added of o-toluyl (46 μl) to the solution. The mixture was stirred at room temperature overnight. Methanol was added to the reaction solution and the solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by development with chloroform / acetone (2/1) to provide 111 mg (yield: 79%) of the title compound. 1 H-NMR (CDCl 3, 400 MHz): d 2.12 (s, 6 H), 2.26 (s, 3 H), 4.03 (s, 3 H), 4.05 (s, 3 H), 6.27 (d, J = 5.1 Hz, 1 H) , 6.77 (s, 1H), 6.81 (s, 1H), 6.91 (s, 1H), 7.11 - 7.15 (m, 1H), 7.22 (s, 1H), 7.24 (s, 1H), 7.42 (s, 1H) ), 7.59 (s, 1H), 7.63 (d, J = 7.8 Hz, 1H), 7.68 (s, 1H), 8.43 (d, J = 5.4 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 458 (M ++ l) Example 43: N-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2,5-dimethylphenyl} -N '- (2-methoxyphenyl) urea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2,5-dimethyl-aniline (100 mg) was dissolved in chloroform (10 ml), isocyanate was added of 2-methoxyphenyl (49 μl) to the solution. The mixture was heated under reflux overnight. Methanol was added to the reaction solution. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by development with chloroform / acetone (2/1) to quantitatively give the title compound. 1 H-NMR (CDC13, 400 MHz): d 2.14 (s, 3 H), 2.24 (s, 3 H), 3.75 (s, 3 H), 4.03 (s, 3 H), 4.07 (s, 3 H), 6.31 (d, J = 5.1 Hz, 1H), 6.84-6.87 (m, 1H), 6.95-7.03 (m, 3H), 7.06 (s, 1H), 7.44 (s, 1H), 7.56 (s, 1H), 7.61 (s) , 1H), 7.63 (s, 1H), 8.17-8.20 (m, 1H), 8.46 (d, J = 5.1 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 474 (M + + l) Example 4_4 N- (5-bromo-6-methyl-2-pyridyl) -N '-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2,5-dimethylphenyl} urea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2,5-dimethyl-aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml), and then added to the solution a solution of triphosgene (92 mg) in dichloromethane. The mixture was stirred at room temperature for 30 minutes. Then, 6-amino-3-bromo-2-methylpyridine (69 mg) was added to the reaction solution, and the mixture was stirred at room temperature overnight. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was dried in sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was dissolved in a minor amount of chloroform and a larger amount of ether was added to the solution to precipitate a crystal which was then collected by filtration to provide 80 mg (yield: 48%) of the title compound. 1H-MR (CDC13, 400 MHz): d 2.18 (s, 3H), 2.42 (s, 3H), 2.65 (s, 3H), 4.06 (s, 3H), 4.08 (s, 3H), 6.34 (d, J = 5.4 Hz, 1H), 6.57 (d, J = 8.5 Hz, 1H), 6.98 (s, 1H), 7.43 (s, 1H), 7.62 (s, 1H), 7.70 (s, 1H), 7.74 ( d, J = 8.5 Hz, 1H), 8.05 (s, 1H), 8.46 (d, J = 5.4 Hz, 1H), 11.17 (br, 1H) Mass analysis, found (ESI-MS, m / z): 537, 539 (M? L) Example 45: N- (2,6-dimethoxy-3-pyridyl) -N '- (4- [(6,7-dimethoxy-4-quinolyl) oxy] -2,5- dimethylphenyl. urea 4 - [(6,7-Dimethoxy-4-quinolyl) oxy] -2,5-dimethyl-aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml), and Then, a solution of triphosgene (92 mg) in dichloromethane was added to the solution, the mixture was stirred at room temperature for 30 minutes, then 3-amino-2 was added., 6-dimethoxypyridine (70 mg) was added to the reaction solution, and the mixture was stirred at room temperature overnight. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was dried in sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was dissolved in a minor amount of chloroform and a large amount of ether was added to the solution to precipitate a crystal which was then collected by filtration to provide 124 mg (yield: 79%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 2.17 (s, 3 H), 2.27 (s, 3 H), 3.89 (s, 3 H), 3.95 (s, 3 H), 4.06 (s, 3 H), 4.07 (s, 3H), 6.31 (d, J = 5.1 Hz, 1H), 6.34 (d, J = 8.5 Hz, 1H), 6.36 (s, 1H), 6.74 (s, 1H), 6.99 (s, 1H), 7.44 ( s, 1H), 7.57 (s, 1H), 7.60 (s, 1H), 8.20 (d, J = 8.3 Hz, 1H), 8.46 (d, J = 5.1 Hz, 1H) Mass analysis, found (ESI- MS, m / z): 505 (M? L) Example 46: N-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2,5-dimethylphenyl} -N '- (4-methoxyphenyl) urea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2,5-dimethyl-aniline (100 mg) was dissolved in chloroform (4 ml) and then added to the isocyanate solution of -methoxyphenyl (60 μl) 4-methoxyphenyl isocyanate (60 μl) to the solution. The mixture was allowed to react at room temperature overnight.

The solvent was removed by distillation under reduced pressure. The residue was dissolved in a minor amount of chloroform, and a large amount of ether was added to the solution. The resulting precipitate was then collected by suction filtration to provide 110 mg (yield: 74%) of the title compound. 1H-NMR (CDC13, 400 MHz): d 2.07 (s, 3H), 2.26 (s, 3H), 3.76 (s, 3H), 4.03 (s, 3H), 4.08 (s, 3H), 6.39 (d, J = 6.1 Hz, 1H), 6.80 (d, J = 9.0 Hz, 1H), 6.87 (s, 1H), 7.36 (d, J = 9.0 Hz, 2H), 7.55 (br, 1H), 7.62 (s, 1H), 7.67 (s, 1H), 7.80 (s, 1H), 8.19 (br, 1H), 8.27 (d, J = 6.1 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 474 (M ++ 1) Example 47: N-4- [(6,7-dimethoxy-4-quinolyl) oxy] -2-nitrophenyl} -N'-propylurea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2-nitroaniline was dissolved (150 mg) in chloroform (10 ml) and tritylamine (1.5 ml), and then a solution of triphosgene (144 mg) in chloroform was added to the solution. The mixture was heated under reflux for 5 minutes. Then n-propylamine (31 mg) was added. The mixture was heated under reflux for an additional 2 hours. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution, and the mixture was supported in diatomaceous earth, separated by extraction with chloroform. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / acetone (4/1) to give 160 mg (yield: 86%) of the title compound. 1H-NR (CDC13, 400 MHz): d 1.01 (t, J = 7.5 Hz, 3H), 1.59 - 1.69 (m, 2H), 3.27 - 3.34 (m, 2H), 4.05 (s, 3H), 4.06 ( s, 3H), 4.95 - 5.01 (br, 1H), 6.47 (d, J = 5.4 Hz, 1H), 7.43 - 7.51 (m, 3H), 8.04 (d, J = 2.7 Hz, 1H), 8.53 (d , J = 5.4 Hz, 1H), 8.81 (d, J = 9.3 Hz, 1H), 9.74 - 9.79 (br, 1H) Mass analysis, found (FD-MS, m / z): 426 (M +) Example 48 : N- (2,4-difluorophenyl) -N '-. { 4- [(6,7-dimethoxy-4-quinolyl) oxy] -2-nitrophenyl} urea 4- [(6,7-Dimethoxy-4-quinolyl) oxy] -2-nitroaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml), and a triphosgene solution (96 mg) was added. ) then to the solution. The mixture was heated under reflux for 5 minutes. Then, 2,4-difluoroaniline (45 mg) was added to the reaction solution, and the mixture was further heated under reflux overnight. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution and the mixture was supported in diatomaceous earth, followed by extraction with chloroform. The solvent was removed by distillation under reduced pressure. The residue was purified by thin layer chromatography on silica gel by development with chloroform / acetone (3/1) to provide 81 mg (yield: 56%) of the title compound. 1 H-NMR (CDCl 3, 400 Mhz): d 4.05 (s, 3 H), 4.06 (s, 3 H), 6.50 (d, J = 5.1 Hz, 1 H), 6.91 - 6.98 (m, 3 H), 7.45 (s, 1H), 7.49 (s, 1H), 7.50-7.54 (m, 1H), 7.88-7.97 (s, 1H), 8.05 (d, J = 2.9 Hz, 1H), 8.54 (d, J = 5.1 Hz, 1H ), 8.77 (d, J - 9.3 Hz, 1H), 9.98 (s, 1H) Mass analysis, found (FD-MS, m / z): 496 (M +) Example 49j N-. { 3, 5-dichloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] phenyl} -Nf- (2,4-difluorophenyl) urea 3,5-Dichloro-4- [(6,7-dimethoxy-4-quinolyl) oxy] -2-aniline (53 mg) was dissolved in chloroform (5 ml), and 2,4-difluorophenyl isocyanate (34 μl) was added to the solution. The mixture was heated under reflux overnight. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / acetone (2/1) to provide 56 mg (yield: 74%) of the title compound. ^ - MR (CDCI3, 400 Mhz): d 4.05 (s, 3H), 4.09 (s, 3H), 6.26 (d, J = 5.4 Hz, 1H), 6.86 - 6.93 (m, 2H), 7.05 (s, 1H), 7.44 (s, 1H), 7.46 (s, 1H), 7.60 (s, 2H), 7.64 (s, 2H), 8.01 -8.05 (m, 1H), 8.48 (d, J = 5.4 Hz, 1H) ) Mass analysis, found (FAB-MS, m / z): 520, 522, 524 (M? L) Example 50: N- (2,4-difluorophenyl) -N '- (2-fluoro-4- { [6-methoxy-7- (2-morpholinethoxy) -4- quinolyl] oxy} phenyl) -urea N- (2,4-difluorophenyl) -N '- (2-fluoro-4- [(7-hydroxy-6-methoxy-4-quinolyl) oxy] phenyljurea ( 20 mg), potassium carbonate (7 mg), tetra-n-butylammonium iodide (2 mg), and N- (2-chloroethyl) morpholine hydrochloride (10 mg) in N, N-dimethylformamide (1 ml), and the solution was stirred at a temperature of 70 ° C overnight A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution and the mixture was extracted with chloroform.The chloroform layer was dried in magnesium sulfate The solvent was removed by distillation under reduced pressure.The residue was purified by thin layer chromatography on silica gel developing with chloroform / methanol (30/1) to provide 14 mg (yield: 57%) of the title compound. ^ -H-NMR (CDC13, 400 Mhz): d 2.57 (t, J = 4.4 Hz, 4H), 2.88 (m, 2H), 3.69 (t, J = 4.4 Hz, 4H), 3.94 (s, 3H), 4.26 (t, J = 5.9 Hz, 2H), 6.43 (d, J = 5.1 Hz, 1H), 6.77 - 6.95 (m, 4H), 7.35 (s, 1H), 7.43 (s, 1H), 7.96 - 8.02 (m, 1H), 8.13 - 8.17 (m, 1H), 8.44 (d, J = 5.1 Hz, 1H) Example 51: N- (2-chloro-4- { [6-methoxy-7- (2-morpholinoethoxy) -4-uinolyl] oxy}. phenyl) -N '- (2,4-difluorophenyl) urea N- (2-chloro-4- [(7-hydroxy-6-methoxy-4-quinolyl) oxy] phenyl] - N' - ( 2,4-difluorophenyl) urea (174 mg) in N, N-dimethylformamide (9 ml), and potassium carbonate (64 mg), tetra-n-butylammonium iodide (14 mg), and N- (2-hydrochloride) -chloroethyl) morpholine (86 mg) were then added to the solution, the mixture was stirred at a temperature of 70 ° C for 17 hours, and a saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution, followed by The chloroform layer was dried over anhydrous sodium sulfate, the solvent was removed by distillation under reduced pressure, the residue was purified by chromatography on silica gel by chloroform / methanol (20/1) development to provide 75 mg (yield: 35%) of the title compound. H-NMR (CDC13, 400 Mhz): d 2.60 - 2.67 (m, 4H), 2.95 (t, J = 6.0 Hz, 2H), 3.71 - 3.79 (m, 4H), 4.01 (s, 3H), 4.33 ( t, J = 6.0 Hz, 2H), 6.50 (d, J = 5.1 Hz, 1H), 6.85 - 6.97 (m, 2H), 7.09 - 7.17 (m, 2H), 7.22 - 7.27 (m, 2H), 7.42 (s, 1H), 7.50 (s, 1H), 7.97 - 8.01 (m, 1H), 8.28 (d, J = 9.0 Hz, 1H), 8.51 (d, J = 5.1 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 585, 587 (M ++ 1) Example 52: N- (2,4-difluorophenyl) -N '- (4-. { [6-methoxy-7- (2-morpholinoethoxy) -4-quinolyl) oxy} -2,5-dimethyl-phenyl) urea N- (4- {[7- (benzyloxy) -6-methoxy-4-quinolyl] oxy} -2,5-dimethylphenyl) -N '- was dissolved (2,4-difluorophenyl) urea (366 mg) in N, N-dimethylformamide (6 ml), and palladium hydroxide (366 mg) was added to the solution. The mixture was stirred under an atmosphere of hydrogen at room temperature overnight. The solvent was removed by distillation under reduced pressure. The residue was dissolved in chloroform and methanol. The reaction solution was filtered through Celite. Then, the solvent was removed by distillation under reduced pressure. The residue (213 mg), potassium carbonate (109 mg), tetra-n-butylammonium iodide (12 mg), and N- (2-chloroethyl) morpholine hydrochloride (74 mg) were dissolved in N, N-dimethylformamide (5 ml), and the solution was stirred at a temperature of 70 ° C overnight. The solvent was removed by distillation under reduced pressure. Water was added to the residue, and the mixture was extracted with chloroform. The chloroform layer was dried in sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by thin layer chromatography on silica gel by growth with chloroform / methanol (10/1) to provide 106 mg (yield: 55%) of the title compound. 1 H-NMR (CDC13, 400 Mhz): d 2.17 (s, 3 H), 2.27 (s, 3 H), 2.64 (t, J = 4.6 Hz, 4 H), 2.96 (t, J = 6.0 Hz, 2 H), 3.76 (t, J = 4.6 Hz, 4H), 4.03 (s, 3H), 4.34 (t, J = 6.0 Hz, 2H), 6.31 (d, J = 5.4 Hz, 1H), 6.47 (s, 1H), 6.81 - 6.92 (m, 3H), 7.00 (s, 1H), 7.43 (s, 1H), 7.54 (s, 1H), 7.58 (s, 1H), 8.05 - 8.12 (, 1H), 8.47 (d, J = 5.4 Hz, 1H) Example 53: N- (4- { [6-methoxy-7- (2-morpholinoethoxy) -4-quinolyl] oxy} -2,5-dimethylphenyl) -N '- (2 -methoxyphenyl) -urea N- (4- {[7- (benzyloxy) -6-methoxy-4-quinolyl] oxy} -2,5-dimethylphenyl) -N '- (2, -difluorophenyl) was dissolved ) urea (363 mg) in N, N-di-ethylformamide (6 ml), and palladium hydroxide (363 mg) was added to the solution. The mixture was stirred under an atmosphere of hydrogen at room temperature overnight. The solvent was removed by distillation under reduced pressure. The residue was dissolved in chloroform and methanol and the reaction solution was filtered through Celite. Then, the solvent was removed by distillation under reduced pressure. The residue (191 mg), potassium carbonate (219 mg), tetra-n-butylammonium iodide (12 mg), and N- (2-chloroethyl) morpholine hydrochloride (148 mg) were dissolved in N, N-dimethylformamide (5 ml). The solution was stirred at a temperature of 70 ° C overnight. The solvent was removed by distillation under reduced pressure. Water was added to the residue, and the mixture was extracted with chloroform. The chloroform layer was dried in sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by thin layer chromatography on silica gel by growth with chloroform / methanol (10/1) to give 101 mg (yield: 55%) of the title compound. 1H-NMR (CDC13, 400 Mhz): d 2.17 (s, 3H), 2.28 (s, 3H), 2.64 (t, J = 4.5 Hz, 4H), 2.96 (t, J = 5.9 Hz, 2H), 3.76 (t, J = 4.6 Hz, 4H), 3.83 (s, 3H), 4.04 (s, 3H), 4.34 (t, J = 6.0 Hz, 2H), 6.30 (d, J = 5.4 Hz, 2H), 6.86 - 6.90 (m, 1H), 6.96 - 7.06 (m, 3H), 7.16 (s, 1H), 7.43 (s, 1H), 7.57 (s, 1H), 7.59 (s, 1H), 8.11 - 8.16 (m , 1H), 8.46 (d, J = 5.4 Hz, 1H) Example 54: N- (2-chloro-4- { [6-methoxy-7- (2-methoxyethoxy) -4-quinolyl] oxy} phenyl) -N '- (2,4-difluorophenyl) urea Sodium hydride (60% by weight, 153 mg) was added to dimethyl sulfoxide (2 ml), and the mixture was stirred at a temperature of 60 ° C. for 30 minutes and then cooled to room temperature. 4-Amino-3-chlorophenol hydrochloride (343 mg) was added to the reaction solution, and the mixture was stirred at room temperature for 10 minutes. Then, 4-chloro-6-methoxy-7- (2-methoxyethoxy) -quinoline (254 mg) in dimethyl sulfoxide (2 ml) was added to the reaction solution. The mixture was stirred at a temperature of 110 ° C overnight. Water was added to the reaction solution, followed by extraction with chloroform. The chloroform layer was then washed with a saturated aqueous solution of sodium hydrogencarbonate and dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by development with chloroform / acetone (7/3) to provide 332 mg of a mixture containing 2-chloro-4-. { [6-methoxy-7- (2-methoxyethoxy) -4-quinolyl] oxy} aniline as the main product. A portion of 83 mg of the mixture was dissolved in chloroform (5 ml), and 2, -difluorophenyl isocyanate (32 μl) was added to the 115 solution. The mixture was heated under reflux overnight. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel developing with chloroform / acetone (2/1) to give 50 mg of the title compound. ^ -H-NMR (DMSO-de, 400 Mhz): d 3.75 - 3.77 (m, 2H), 3.94 (s, 3H), 4.27 - 4.29 (m, 2H), 6.55 (d, J = 5.1 Hz, 1H ), 7.04 -7.09 (m, 1H), 7.25 - 7.36 (m, 2H), 7.42 (s, 1H), 7.50 (s, 1H), 7.51 (s, 1H), 8.09 - 8.15 (m, 1H), 8.24 (d, J = 9.0 Hz, 1H), 8.49 (d, J = 5.4 Hz, 1H), 8.82 (s, 1H), 9.31 (s, 1H) Example 55: N- (2-chloro-4- { [6-Methoxy-7- (2-methoxyethoxy) -4-quinolyl] oxy} phenyl) -N '- (2,4-methoxyphenyl) urea Sodium hydride (60% by weight, 153 mg ) to dimethyl sulfoxide (2 ml), and the mixture was stirred at a temperature of 60 ° C for 30 minutes and then cooled to room temperature. 4-Amino-3-chlorophenol hydrochloride (343 mg) was added to the reaction solution, and the mixture was stirred at room temperature for 10 minutes. Then, 4-chloro-6-methoxy-7- (2-methoxyethoxy) -quinoline (254 mg) in dimethyl sulfoxide (2 ml) was added to the reaction solution and the mixture was stirred at a temperature of 110. ° C during the night. Water was added to the reaction solution, followed by extraction with chloroform. The chloroform layer was then washed with a saturated aqueous solution of sodium hydrogencarbonate and then dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by development with chloroform / acetone (7/3) to provide 332 mg of a mixture containing 2-chloro-4-. { [6-methoxy-7- (2-methoxyethoxy) -4-quinolyl] oxy} aniline as the main product. An 83 mg portion of the mixture was dissolved in chloroform (5 ml), and 2-methoxyphenyl isocyanate (35 μl) was added to the solution. The mixture was heated under reflux overnight. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by development with chloroform / acetone (2/1) to provide 31 mg of the title compound. 1 H-NMR (DMSO-de, 400 Mhz): d 3.75 - 3.77 (m, 2H), 3.90 (s, 3H), 3.94 (s, 3H), 4.27 - 4.29 (m, 2H), 6.55 (d, J = 5.1 Hz, 1H), 6.89 - 7.05 (m, 3H), 7.24 - 7.27 (m, 1H), 7.42 (s, 1H), 7.48 (d, J = 2.7 Hz, 1H), 7.50 (s, 1H) , 8.08 - 8.11 (m, 1H), 8.18 - 8.22 (, 1H), 8.49 (d, J = 5.4 Hz, 1H), 8.99 - 9.03 (, 2H) Example 56: N- (2, 4-difluorophenyl) - N '- (4- { [6-methoxy-7- (2-methoxyethoxy) -4-quinolyl] oxy} -2, 3-dimethylphenyl) -urea N- (4- { [ 7- (benzyloxy) -6-methoxy-4-quinolyl] oxy} -2, 3-dimethylphenyl) -N'- (2,4-difluorophenyl) urea (213 mg) in N, N-dimethylformamide (5 ml) ), and triethylamine (1 ml), and palladium hydroxide (40 mg) was added to the solution. The mixture was stirred under an atmosphere of hydrogen at room temperature overnight. The reaction solution was filtered through Celite and then washed with chloroform / methanol. The solvent was removed by distillation under reduced pressure. A 90 mg portion of the residue (184 mg) was dissolved in N, N-dimethyl formamide (1.5 ml), and potassium carbonate (32 mg), tetra-n-butylammonium iodide (7 mg) were added, as well as 2-bromomethyl methyl ether (32 mg) to the solution. The mixture was stirred at a temperature of 70 ° C overnight. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was dried in anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by thin layer chromatography on silica gel by development with chloroform / methanol (2/1) to provide 110 mg of the title compound. 1 H-NMR (DMSO-de, 400 Mhz): d 1.97 (s, 3 H), 2.17 (s, 3 H), 3.31 (s, 3 H), 3.70 (t, J = 4.4 Hz, 2H), 3.90 (s, 3H), 4.21 (t, J = 4.4 Hz, 2H), 6.18 (d, J = 5.1 Hz, 1H), 6.95 - 6.98 (m, 2H), 7.22 - 7.31 (m, 2H), 7.34 (s, 1H), 7.51 (s, 1H), 7.62 (d, J = 8.8 Hz, 1H), 8.03 - 8.10 (m, 1H), 8.36 (d, J = 5.1 Hz, 1H), 8.38 (s, 1H), 8.79 (s, 1H) Example 57: N- (4- { [6-methoxy-7- (2- (methoxyethoxy) -4-quinolyl] oxy} -2-3 -dimethylphenyl) -N '- (2-methoxyphenyl) -urea N- (4- {[7- (benzyloxy) -6-methoxy-4-quinolyl] oxy} -2-, 3-dimethylphenyl) was dissolved -N '- (2-methoxyphenyl) urea (161 mg) in N, N-dimethylformamide (4 ml), and triethylamine (1 ml), and palladium hydroxide (32 mg) was added to the solution. The reaction solution was filtered through Celite and then washed with chloroform / methanol, the solvent was removed by distillation under reduced pressure, a portion of 110 mg was dissolved in a hydrogen atmosphere at room temperature overnight. residue (223 mg) in N, N-dimethylformamide (1.5 ml), and added n Potassium carbonate (23 mg), tetra-n-butylammonium iodide (5 mg), as well as 2-bromomethyl methyl ether (32 mg) to the solution.

The mixture was stirred at a temperature of 70 ° C overnight. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was dried in anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by thin layer chromatography on silica gel by development with chloroform / acetone (2/1) to provide 89 mg of the title compound. 1 H-NMR (DMSO-de, 400 Mhz): d 2.00 (s, 3H), 2.17 (s, 3H), 3.70 (t, J = 4.2 Hz, 2H), 3.83 (s, 3H), 3.90 (s, 3H), 4.22 (t, J = 4.2 Hz, 2H), 6.19 (d, J = 5.1 Hz, 1H), 6.81-6.88 (m, 2H), 6.94-6.97 (m, 2H), 7.34 (s, 1H) ), 7.51 (s, 1H), 7.58 (d, J = 8.8 Hz, 1H), 8.07 (d, J = 8.8 Hz, 1H), 8.36 (d, J = 5.1 Hz, 1H), 8.48 (s, 1H) ), 8.58 (s, 1H) Example 58: N- (2,4-difluorophenyl) -N '- (4. {- [6-methoxy-7- (2-methoxyethoxy-4-quinolyl] oxy}. -2,5-dimethylphenyl) urea N- (4- {[7- (benzyloxy) -6-methoxy-4-quinolyl] oxy} -2,5-dimethylphenyl) -N '- (2) was dissolved. , 4-difluorophenyl) urea (366 mg) in N, N-dimethylformamide (6 ml), and palladium hydroxide (366 mg) was added to the solution.The mixture was stirred under a hydrogen atmosphere at room temperature overnight The solvent was removed by distillation under reduced pressure, the residue was dissolved in chloroform and methanol and the solution was filtered through Celite, the solvent was removed by distillation. under reduced pressure. The residue (213 mg), potassium carbonate (109 mg), tetra-n-butylammonium iodide (12 mg), and 2-bromomethyl methyl ether (40 μl) were dissolved in N, N-dimethylformamide (5 ml), and the solution was stirred at a temperature of 70 ° C overnight. The solvent was removed by distillation under reduced pressure. Water was added to the residue and the mixture was extracted with chloroform. The chloroform layer was dried in sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by thin layer chromatography on silica gel by growth with chloroform / methanol (10/1) to provide 124 mg (yield: 73%) of the title compound. 1 H-NR (CDCl 3, 400 Mhz): d 2.17 (s, 3H), 2.26 (s, 3H), 3.49 (s, 3H), 3.90 (t, J = 4.8 Hz, 2H), 4.03 (s, 3H) , 4.34 (t, J = 4.8 Hz, 2H), 6.30 (d, J = 5.1 Hz, 1H), 6.57 (s, 1H), 6.81 -6.95 (m, 3H), 7.00 (s, 1H), 7.43 ( s, 1H), 7.55 (s, 1H), 7.57 (s, 1H), 8.05 - 8.14 (m, 1H), 8.46 (d, J = 5.4 Hz, 1H) Mass analysis, found (ESI-EM, m / z): 524 (M ++ 1) Example 59: N- (4- { [6-methoxy-7- (2- (methoxyethoxy) -4-quinolyl] oxy} -2,5-dimethylphenyl ) -N '- (2-methoxyphenyl) -urea N- (4- {[7- (benzyloxy) -6-methoxy-4-quinolyl] oxy} -2,5-dimethylphenyl) -N was dissolved '- (2-methoxyphenyl) urea (363 mg) in N, N-di-ethylformamide (6 ml), and palladium hydroxide was added (363 mg) to the solution. The mixture was stirred under an atmosphere of hydrogen at room temperature overnight. The solvent was removed by distillation under reduced pressure and the residue was dissolved in chloroform and methanol. The solution was filtered through Celite. Then, the solvent was removed by distillation under reduced pressure. The residue (191 mg), potassium carbonate (110 mg), tetra-n-butylammonium iodide (12 mg), and 2-bromomethyl methyl ether (80 mg) were dissolved in N, N-dimethylformamide (5 ml), and the solution was stirred at a temperature of 70 ° C overnight. The solvent was removed by distillation under reduced pressure. Water was added to the residue and the mixture was extracted with chloroform. The chloroform layer was dried in sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by thin layer chromatography on silica gel by growth with chloroform / methanol (10/1) to provide 128 mg (yield: 76%) of the title compound. ^? - NMR (CDC13, 400 Mhz): d 2.17 (s), 3H), 2.28 (s, 3H), 3.49 (s, 3H), 3.83 (s, 3H), 3.90 (t, J = 4.8 Hz, 2H), 4.04 (s, 3H), 4.35 (t, J = 4.9 Hz, 2H), 6.30 (d, J - 5.4 Hz, 1H), 6.33 (s, 1H), 6.86 - 6.90 (m, 1H), 6.96 - 7.06 (m, 3H), 7.17 (s, 1H), 7.43 (s, 1H), 7.56 (s, 1H), 7.58 (s, 1H), 8.12 -8.17 (m, 1H), 8.45 (d, J = 5.1 Hz, 1H) Mass analysis, found (ESI-EM , m / z): 518 (M ++ 1) Example 60: "N- (4- { [7- (benzyloxy) -6-methoxy-4-quinolyl] oxy} -2, 3-dimethylphenyl ) -N '- (2-methoxyphenyl) -urea 4- { [7- (Benzyloxy) -6-methoxy-4-quinolyl] oxy} -2, 3-dimethylaniline (260 mg) was dissolved in N , N-dimethylformamide (5 ml), and then 2-methoxyphenyl isocyanate (116 mg) was added to the solution.The mixture was allowed to react at room temperature overnight A saturated aqueous solution of sodium hydrogencarbonate was added to the solution. the reaction solution, and the mixture was extracted with chloroform.The chloroform layer was dried in anhydrous magnesium sulfate. It was removed by distillation under reduced pressure. The residue was purified by thin layer chromatography on silica gel by development with chloroform / acetone (2/1) to provide 169 mg (yield: 47%) of the title compound. XH-NMR (DMSO-d6, 400 Mhz): d 1.99 (s, 3H), 2.02 (s, 3H), 3.83 (s, 3H), 3.90 (s, 3H), 5.25 (s, 2H), 6.18 ( d, J = 5.3 Hz, 1H), 6.81-6.87 (m, 2H), 6.95 (d, J = 6.1 Hz, 1H); 7.29 -7.59 (m, 7H), 8.07 (d, J = 6.1 Hz, 1H), 8.35 (d, J = 5.3 Hz, 1H), 8.48 (s, 1H), 8.58 (s, 1H) Example 6_1_: N -. { 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] phenyl} -N '- (2,4-difluorophenyl) urea 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -aniline (214 mg) was dissolved in chloroform (5 ml), and then added 2,4-difluorophenyl isocyanate (180 μl) to the solution. The mixture was allowed to react at a temperature of 70 ° C for 4 hours, and an amount of ether was added to the reaction solution. The resulting precipitate was collected by suction filtration to provide 146 mg (yield: 46%) of the title compound. 1 H-NMR (DMSO-de, 400 Mhz): d 3.98 (s, 3 H), 3.99 (s, 3 H), 7.03 - 7.10 (m, 1 H), 7.28 - 7.37 (m, 2 H), 7.40 (s, 1 H) ), 7.56 (s, 2H), 8.08 - 8.21 (m, 2H), 8.57 (s, 1H) 8.80 (s, 1H), 9.30 (s, 1H) Mass analysis, found (ESI-MS, m / z ): 487, 489 (M ++ l) Example 62 N-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] phenyl} -N'-propylurea 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -aniline (5.13 g) was dissolved in chloroform (100 ml) and triethylamine (50 ml), and then added to the solution a solution of triphosgene (4.59 g) in chloroform (3 ml). The mixture was stirred for 30 minutes. Then, n-propylamine (2.74 g) was added to the reaction solution and the mixture was stirred for an additional 2 hours. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution and the mixture was extracted with chloroform. The chloroform layer was dried in anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / methanol (50/1) to provide 4.14 g (yield: 64%) of the title compound. 1 H-NMR (DMSO-de, 400 Mhz): d 0.91 (t, J = 7.3 Hz, 3 H), 1.41 -1.53 (m, 2 H), 3.05 - 3.12 (m, 2 H), 3.97 (s, 3 H), 3.99 (s, 3H), 6.99 (t, J = 5.4 Hz, 1H), 7.22 (dd, J = 2.7 Hz, 1H), 7.38 (s, 1H), 7.46 (d, J = 2.9 Hz, 1H), 7.54 (s, 1H), 8.04 (s, 1H), 8.20 (d, J = 9.3 Hz, 1H), 8.55 (s, 1H) Mass analysis, found (ESI-MS, m / z): 417 (M ?) Example 63: N- [4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl} -N'-ethylurea 4 - [(6,7-Dimethoxy-4-quinazolinyl) oxy] -aniline (50 mg) was dissolved in chloroform (3 ml) and triethylamine (0.2 ml), and then a solution was added to the solution. Triphosgene solution (50 mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then ethylamine hydrochloride (69 mg) was added to the reaction solution and the mixture was further stirred at room temperature overnight. Methanol was added to the reaction solution and the solution was purified by HPLC by growth with chloroform / methanol to provide 10 mg (yield: 16%) of the title compound. 1H-NR (DMSO-de, 400 Mhz): 6 1.07 (t, J = 7.3 Hz, 3H), 3.11 -3.14 (m, 2H), 3.97 (s, 3H), 3.99 (s, 3H), 6.10 ( t, J = 5.4 Hz, 1H), 7.14 (d, J = 9.0 Hz, 2H), 7.37 (s, 1H), 7.46 (d, J = 9.0Hz, 2H), 7.55 (s, 1H), 8.49 (br, 1H), 8.53 (s, 1H) Mass analysis, found (ESI-MS, m / z): 369 (M? L) Example 64: N-. { 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl} -N'-propylurea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] -aniline (50 g) was dissolved in chloroform (3 ml) and triethylamine (0.2 ml), and a solution was then added to the solution. Triphosgene solution (50 mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then propylamine (21 μl) was added to the reaction solution and the mixture was further stirred at room temperature overnight. Methanol was added to the reaction solution and the solution was purified by HPLC by growth with chloroform / methanol to provide 30 mg (yield: 47%) of the title compound.

XH-NMR (DMSO-de, 400 Mhz): d 0.89 (t, J = 7.6 Hz, 3H), 1.41 -1.50 (m, 2H), 3.04 - 3.08 (m, 2H), 3.97 (s, 3H), 3.99 (s, 3H), 6.15 (t, J = 5.9 Hz, 1H), 7.15 (d, J = 8.8 Hz, 2H), 7.37 (s, 1H), 7.46 (d, J = 9.0 Hz, 2H), 7.55 (s, 1H), 8.48 (br, 1H), 8.53 (s, 1H) Mass analysis, found (ESI-MS, m / z): 383 (M ++ 1) Example 65 N-butyl-N ' -. { 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] phenyl} urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] -aniline (50 mg) was dissolved in chloroform (3 ml) and triethylamine (0.2 ml), and then a solution of triphosgene was added to the solution ( 50 mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then butylamine (22 μl) was added to the reaction solution and the mixture was further stirred at room temperature overnight. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol to provide 29 mg (yield: 43%) of the title compound. ^ -NMR (DMSO-de, 400 Mhz): d 0.91 (t, J = 7.3 Hz, 3H), 1.28 -1.47 (m, 4H), 3.07 - 3.12 (m, 2H), 3.97 (s, 3H), 3.99 (s, 3H), 6.12 (t, J = 5.6 Hz, 1H), 7.15 (d, J = 8.8 Hz, 2H), 7.37 (s, 1H), 7.46 (d, J = 9.0 Hz, 2H), 7.55 (s, 1H), 8.47 (br, 1H), 8.53 ( s, 1H) Mass analysis, found (ESI-MS, m / z): 397 (M? l) Example 66: N- [4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] phenyl} -N'-pentyurea 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] aniline (50 mg) was dissolved in chloroform (3 ml) and triethylamine (0.2 ml), and then a solution was added to the solution of triphosgene (50 mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then amylamine (26 μl) was added to the reaction solution and the mixture was stirred at room temperature overnight. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol to provide 21 mg (yield: 30%) of the title compound. 1 H-NMR (DMSO-de, 400 Mhz): d 0.89 (t, J = 7.1 Hz, 3 H), 1.27 -1.47 (m, 4 H), 1.41 - 1.48 (m, 2 H), 3.06 - 3.11 (m, 2 H) ), 3.97 (s, 3H), 3.99 (s, 3H), 6.13 (t, J = 5.6 Hz, 1H), 7.15 (d, J = 9.0 Hz, 2H), 7.37 (s, 1H), 7.46 (d) , J = 8.8 Hz, 2H), 7.55 (s, 1H), 8.47 (br, 1H), 8.53 (s, 1H) Mass analysis, found (ESI-MS, m / z): 411 (M? L) Example 67 N- (sec-butyl) -N '-. { 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] phenyl} urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] aniline (50 mg) was dissolved in chloroform (3 ml) and triethylamine (0.2 ml), and then a solution of triphosgene (50 mg) was added to the solution. mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then sec-butylamine (23 μl) was added to the reaction solution and the mixture was stirred at room temperature overnight. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol to provide 33 mg (yield: 49%) of the title compound. XH-NMR (DMSO-de, 400 Mhz): d 0.88 (t, J = 7.3 Hz, 3H), 1.08 (d, J = 6.6 Hz, 3H), 1.40 - 1.47 (m, 2H), 3.58 - 3.64 ( m, 1H), 3.97 (s, 3H), 3.99 (s, 3H), 5.98 (t, J = 8.1 Hz, 1H), 7.15 (d, J = 9.0 Hz, 2H), 7.37 (s, 1H), 7.46 (d, J = 9.0 Hz, 2H), 7.55 (s, 1H), 8.38 (s, 1H), 8.53 (s, 1H) Mass analysis, found (ESI-MS, m / z): 397 (M ?) Example 68 N-allyl-N '-. { 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] phenyl} urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] aniline (50 mg) was dissolved in chloroform (3 ml) and triethylamine (0.2 ml), and then a solution of triphosgene (50 mg) was added to the solution. mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then, allylamine hydrochloride (31 mg) was added to the reaction solution and the mixture was stirred at room temperature overnight. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol to provide 21 mg (yield: 33%) of the title compound. 1 H-NMR (DMSO-de, 400 Mhz): d 3.73 - 3.76 (m, 2H), 3.97 (s, 3H), 3.99 (s, 3H), 5.07 - 5.21 (m, 2H), 5.84 - 5.92 (, 1H), 6.28 (t, J = 5.6 Hz, 1H), 7.16 (d, J = 9.0 Hz, 2H), 7.38 (s, 1H), 7.47 (d, J = 9.0 Hz, 2H), 7.55 (s, 1H), 8.53 (s, 1H), 8.59 (s, 1H) Mass analysis, found (ESI-MS, m / z): 381 (M? L) Example 69: N-. { 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] phenyl} -N '- (2-propynyl) urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] aniline (50 mg) was dissolved in chloroform (3 ml) and triethylamine (0.2 ml), and then added to the solution a solution of triphosgene (50 mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then propargylamine hydrochloride (31 mg) was added to the reaction solution and the mixture was stirred at room temperature overnight. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol to provide 26 mg (yield: 41%) of the title compound. 1 H-NMR (DMSO-d6, 400 Mhz): d 3.11 - 3.12 (m, 1H), 3.89 - 3.90 (m, 2H), 3.97 (s, 3H), 3.99 (s, 3H), 6.49 (t, J = 5.9 Hz, 1H), 7.17 (d, J = 9.0 Hz, 2H), 7.38 (s, 1H), 7.48 (d, J = 8.8 Hz, 2H), 7.55 (s, 1H), 8.53 (s, 1H), 8.68 (s, 1H) ) Mass analysis, found (ESI-MS, m / z): 379 (M? L) Example 70: N- (2,4-difluorobenzyl) -N '-. { 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] phenyl} urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] aniline (50 mg) was dissolved in chloroform (3 ml) and triethylamine (0.2 ml), and then a solution of triphosgene (50 mg) was added to the solution. mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then 2,4-difluorobenzylamine (22 μl) was added to the reaction solution and the mixture was stirred at room temperature overnight. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol to provide 32 mg (yield: 41%) of the title compound. 1 H-NMR (DMSO-de, 400 Mhz): d 3.97 (s, 3 H), 3.98 (s, 3 H), 4.32 - 4.33 (m, 2 H), 6.66 (t, J = 5.9 Hz, 1 H), 7.06 - 7.10 (m, 1H), 7.16 (d, J = 8.8 Hz, 2H), 7.19 - 7.24 (m, 1H), 7.37 (s, 1H), 7.40 - 7.44 (m, 1H), 7.48 (d, J = 9.0 Hz, 2H), 7.55 (s, 1H), 8.52 (s, 1H), 8.69 (s, 1H) Mass analysis, found (ESI-MS, m / z): 467 (M ++ l) Example 71 : N- { 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] phenyl} -N '- (2-pyridylmethyl) urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] aniline (50 mg) was dissolved in chloroform (3 ml) and triethylamine (0.2 ml), and then added to the solution a solution of triphosgene (50 mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then 2,4-difluorobenzylamine (31 μl) was added to the reaction solution and the mixture was stirred at room temperature overnight. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol to provide 31 mg (yield: 43%) of the title compound. 1 H-NMR (DMSO-de, 400 Mhz): d 3.42 (s, 2H), 3.98 (s, 3H), 3.99 (s, 3H), 7.16 - 7.19 (m, 2H), 7.22 - 7.27 (m, 3H ), 7.38 (s, 1H), 7.57 (s, 1H), 7.67 (d, J = 8.8 Hz, 2H), 7.88 - 7.92 (m, 1H), 8.46 - 8.48 (, 1H), 8.54 (s, 1H) ), 8.87 (s, 1H), 12.19 (s, 1H) Mass analysis, found (ESI-MS, m / z): 431 (M ++ 1) Example 72: N- (2,4-difluorophenyl) - N '- [4- [(6,7-dimethoxy-4-quinazolinyl) oxy] phenyl} urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] aniline (50 mg) was dissolved in chloroform (3 ml) and then 2,4-difluorophenyl isocyanate (24 μl) was added to the solution. The mixture was heated under reflux overnight. The precipitated crystal was collected by filtration and washed to provide 55 mg (yield: 72%) of the title compound. ^? - NMR (DMSO-de, 400 Mhz): d 3.98 (s, 3H), 3.99 (s, 3H), 7.04 - 7.08 (m, 2H), 7.24 (d, J = 8.8 Hz, 2H), 7.29 - 7.35 (m, 1H), 7.38 (s, 1H), 7.54 (d, J = 9.0 Hz, 2H), 7.56 (s, 1H), 8.06 - 8.14 (m, 1H), 8.51 - 8.54 (m, 1H) ), 8.54 (s, 1H), 9.11 - 9.12 (, 1H) Mass analysis, found (ESI-MS, m / z): 453 (M ++ l) Example 73: N-. { 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] phenyl} -N '- (4-fluorophenyl) urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] aniline (50 mg) was dissolved in chloroform (3 ml) and then p-fluorophenyl isocyanate (23 mg) was added. μl) to the solution. The mixture was heated under reflux overnight. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol to provide 26 mg (yield: 36%) of the title compound. 1 H-NMR (DMSO-de, 400 Mhz): d 3.98 (s, 3 H), 3.99 (s, 3 H), 7.11 - 7.15 (m, 2H), 7.22 (d, J = 8.8 Hz, 2H), 7.38 (s, 1H), 7.46 - 7.50 (m, 2H), 7.54 (d, J = 9.0 Hz, 2H), 7.56 (s, 1H), 8.54 (s, 1H), 8.72 (s, 1H), 8.75 (s, 1H) Mass analysis , found (ESI-MS, m / z): 435 (M ++ 1) Example 74: N-. { 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] phenyl} -N '- (2-methylphenyl) urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] aniline (50 mg) was dissolved in chloroform (3 ml) and then o-toluyl isocyanate (25 ml) was added. μl) to the solution. The mixture was heated under reflux overnight. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol to provide 30 mg (yield: 41%) of the title compound. X H-NMR (DMSO-d 6, 400 Mhz): d 2.26 (s, 3 H), 3.98 (s, 3 H), 3.99 (s, 3 H), 6.93 - 6.98 (m, 1 H), 7.13 - 7.19 (m, 2 H) ), 7.22 (d, J = 8.8 Hz, 1H), 7.38 (s, 1H), 7.54 - 7.56 (m, 3H), 7.83 - 7.86 (m, 1H), 7.93 (s, 1H), 8.54 (s, 1H), 9.10-9.11 (m, 1H) Mass analysis, found (ESI-MS, m / z): 431 (M ++ 1) Example 75: N-. { 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl} -N '- (2-methoxyphenyl) urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] aniline (50 mg) was dissolved in chloroform (3 ml) and then 2-methoxyphenyl isocyanate (27 mg) was added. μl) to the solution. The mixture was heated under reflux overnight. Methanol was added to the reaction solution, and the mixture was purified by HPLC by growth with chloroform / methanol to provide 34 mg (yield: 45%) of the title compound. X H-NMR (DMSO-de, 400 MHz): d 3.89 (s, 3 H), 3.98 (s, 3 H), 3.99 (s, 3 H), 6.89 - 7.05 (m, 3 H), 7.22 (d, J = 8.8 Hz, 2H), 7.38 (s, 1H), 7.54 (d, J = 8.8 Hz, 2H), 7.56 (s, 1H), 8.13 - 8.15 (m, 1H), 8.23 - 8.24 (m, 1H), 8.54 (s, 1H), 9.40-9.41 (m, 1H) Mass analysis, found (ESI-MS, m / z): 447 (M ++ 1) Example 76: N-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl} -N'-ethylurea 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] aniline (200 mg) was dissolved in chloroform (5 ml) and triethylamine (1 ml), and then added to The solution contains a solution of triphosgene (179 mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then ethylamine hydrochloride (246 mg) was added to the reaction solution and the mixture was stirred at room temperature overnight. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution and the mixture was extracted with chloroform. The chloroform layer was dried in anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by HPLC by growth with chloroform / methanol to provide 159 mg (yield: 65%) of the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 1.08 (t, J = 7.1 Hz, 3H), 3.11 -3.16 (m, 2H), 3.97 (s, 3H), 3.99 (s, 3H), 6.96 ( t, J = 5.6 Hz, 1H), 7.23 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.39 (s, 1H), 7.47 (d, J = 2.7 Hz, 1H), 7.55 (s, 1H) , 8.02 (s, 1H), 8.20 (d, J = 9.3 Hz, 1H), 8.56 (s, 1H) Mass analysis, found (ESI-MS, m / z): 403 (M ++ l) Example 77_ | N-butyl-N '-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl} urea 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] aniline (50 mg) was dissolved in chloroform (5 ml) and triethylamine (1 ml), and then a solution was added to the solution of triphosgene (45 mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then, butylamine (22 μl) was added to the reaction solution and the mixture was stirred at room temperature for an additional 30 minutes. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution and the mixture was extracted with chloroform. The chloroform layer was dried in anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by HPLC by growth with chloroform / methanol to provide 30 mg (yield: 46%) of the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 0.91 (t, J = 7.3 Hz, 3H), 1.31 -1.46 (m, 4H), 3.09 - 3.14 (m, 2H), 3.97 (s, 3H), 3.99 (s, 3H), 6.96 (t, J = 5.6 Hz, 1H), 7.23 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.39 (s, 1H), 7.47 (d, J = 2.7 Hz, 1H), 7.55 (s, 1H), 8.03 (s, 1H), 8.20 (d, J = 9.0 Hz, 1H), 8.56 (s, 1H) Mass analysis, found (ESI-MS, m / z): 431 (M? L) Example 78: N- [2-chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl} -N'-pentyurea 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] aniline (50 mg) was dissolved in chloroform (5 ml) and triethylamine (1 ml), and then added to The solution contains a solution of triphosgene (45 mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then, amylamine (26 μl) was added to the reaction solution, and the mixture was stirred at room temperature for an additional 30 minutes. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution and the mixture was extracted with chloroform. The chloroform layer was dried in anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by HPLC by growth with chloroform / methanol to provide 33 mg (yield: 49%) of the title compound. 1 H-NR (DMSO-de, 400 MHz): d 0.90 (t, J = 7.1 Hz, 3 H), 1.24 -1.34 (m, 4 H), 1.43 - 1.48 (m, 2 H), 3.08 - 3.14 (m, 2 H) ), 3.97 (s, 3H), 3.99 (s, 3H), 6.97 (t, J = 5.1 Hz, 1H), 7.23 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.39 (s, 1H), 7.47 (d, J = 2.8 Hz, 1H), 7.55 (s, 1H), 8.03 (s, 1H), 8.20 (d, J = 9.0 Hz, 1H), 8.56 (s, 1H) Mass analysis, found ( ESI-MS, m / z): 445 (M? L) Example 79: N- (sec-Butyl) -N '-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] phenyl} urea 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] aniline (50 mg) was dissolved in chloroform (5 ml) and triethylamine (1 ml), and then a solution was added to the solution of triphosgene (45 mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then sec-butylamine (23 μl) was added to the reaction solution, and the mixture was stirred at room temperature for an additional 30 minutes. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was dried in anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by HPLC by growth with chloroform / methanol to provide 34 mg (yield: 52%) of the title compound. XH-NMR (DMSO-de, 400 MHz): d 0.89 (t, J = 7.6 Hz, 3H), 1.09 (d, J = 6.6 Hz, 3H), 1.43-1.46 (m, 2H), 3.58-3.66 ( m, 1H), 3.97 (s, 3H), 3.99 (s, 3H), 6.88 (d, J = 7.6 Hz, 1H), 7.22 (dd, J = 2.4 Hz, 9.3 Hz, 1H), 7.39 (s, 1H), 7.47 (d, J = 2.7 Hz, 1H), 7.55 (s, 1H), 7.98 (s, 1H), 8.23 (d, J = 9.0 Hz, 1H), 8.55 -8.56 (m, 1H) Analysis mass, found (ESI-MS, m / z): 431 (M? l) Example 80 N-Allyl-N '-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl} urea 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] aniline (50 mg) was dissolved in chloroform (5 ml) and triethylamine (1 ml), and then a solution was added to the solution. solution of triphosgene (45 mg) in chloroform The mixture was stirred at room temperature for 30 minutes, then allylamine hydrochloride (21 mg) was added to the reaction solution, and the mixture was stirred at room temperature for an additional 30 minutes. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution, and the mixture was extracted with chloroform.The chloroform layer was dried over anhydrous sodium sulfate.The solvent was removed by distillation under reduced pressure.

The residue was purified by HPLC by growth with chloroform / methanol to give 45 mg (yield: 72%) of the title compound. 1 H-NMR (DMSO-d 6, 400 MHz): d 3.76-3.79 (, 2 H), 3.97 (s, 3 H), 3.99 (s, 3 H), 5.10 - 5.24 (m, 2 H), 5.85 - 5.94 (m, 1H), 7.11 (t, J = 5.4 Hz, 1H), 7.24 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.39 (s, 1H), 7.49 (d, J = 2.7 Hz, 1H), 7.55 (s, 1H), 8.14 (s, 1H), 8.19 (d, J = 9.0 Hz, 1H), 8.56 (s, 1H) Mass analysis, found (ESI-MS, m / z): 415 (M? l) Example 81: N-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl} -N '- (2-propynyl) urea 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] aniline (50 mg) was dissolved in chloroform (5 ml) and triethylamine (1 ml), and a solution of triphosgene (45 mg) in chloroform was then added to the solution. The mixture was stirred at room temperature for 30 minutes. Then propargylamine hydrochloride (21 mg) was added to the reaction solution and the mixture was stirred at room temperature for an additional 30 minutes. The precipitated crystal was collected by filtration and washed to provide 38 mg (yield: 61%) of the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 3.16 - 3.17 (m, 1H), 3.93 - 3.95 (m, 2H), 3.97 (s, 3H), 3.99 (s, 3H), 7.25 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.30 (t, J = 5.6 Hz, 1H), 7.39 (s, 1H), 7.50 (d, J = 2.7 Hz, 1H), 7.55 (s, 1H), 8.16 (d, J = 9.3 Hz, 1H), 8.18 (s, 1H), 8.56 (s, 1H) Mass analysis, found (ESI-MS, m / z): 413 (M ++ l) Example 82: N- [2-chloro- 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl} -N '- (2, -difluorobenzyl) urea 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] aniline (50 mg) was dissolved in chloroform (5 ml) and triethylamine (1 ml) , and a solution of triphosgene (45 mg) in chloroform was then added to the solution. The mixture was stirred at room temperature for 30 minutes. Then 2,4-difluorobenzylamine (22 μl) was added to the reaction solution, and the mixture was stirred at room temperature for an additional 30 minutes. The precipitated crystal was collected by filtration and washed to provide 48 mg (yield: 64%) of the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 3.97 (s, 3 H), 3.99 (s, 3 H), 4.33 - 4.36 (m, 2 H), 7.08 - 7.12 (m, 1 H), 7.22 - 7.28 (m , 2H), 7.39 (s, 1H), 7.42 - 7.46 (m, 1H), 7.49 (d, J = 2.7 Hz, 1H), 7.54 (s, 1H), 8.18 - 8.20 (m, 2H), 8.56 ( s, 1H) Mass analysis, found (ESI-MS, m / z): 501 (M ++ l) Example 83: N-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl} -N '- (2-pyridylmethyl) urea 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] aniline (50 mg) was dissolved in chloroform (5 ml) and triethylamine (1 ml), and a solution of triphosgene (45 mg) in chloroform was then added to the solution. The mixture was stirred at room temperature for 30 minutes. Then 2- (methylamino) pyridine (19 μl) was added to the reaction solution and the mixture was stirred at a temperature of 60 ° C for an additional hour. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution and the mixture was extracted with chloroform. The chloroform layer was dried in anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by HPLC by growth with chloroform / methanol to provide 26 mg (yield: 37%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 3.51 (s, 2H), 4.07 (s, 3H), 7.03 -7.10 (m, 2H), 7.19 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.35 (s, 1H), 7.36 (d, J = 2.7 Hz, 1H), 7.54 (s, 1H), 7.76 - 7.81 (, 1H), 8.38 - 8.43 (, 1H), 8.56 (d, J = 9.0 Hz, 1H), 8.64 (s, 1H), 13.53 (s, 1H), Mass analysis, found (ESI-MS, m / z): 466 (M ++ 1) Example 85: N- [2-chloro-4 - [(6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl} -N '- (4-fluorophenyl) urea 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] aniline (50 mg) was dissolved in chloroform (5 ml) and then added to the solution p-fluorophenyl isocyanate (21 μl). The mixture was stirred at a temperature of 60 ° C for one hour. The precipitated crystal was collected by filtration and washed to provide 57 mg (yield: 81%) of the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 3.98 (s, 3H), 3.99 (s, 3H), 7.13 - 7.17 (m, 2H), 7.30 (dd, J = 2.4 Hz, 8.8 Hz, 1H), 7.40 (s, 1H) , 7.48 - 7.51 (m, 2H), 7.55 - 7.56 (, 2H), 8.21 (d, J = 9.0 Hz, 1H), 8.31 (s, 1H), 8.57 (s, 1H) Mass analysis, found (ESI) -MS, m / z): 469 (M? L) Example 86: N- [2-chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl} -N '- (2-methoxyphenyl) urea 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] aniline (50 mg) was dissolved in chloroform (5 ml) and then isocyanate 2 was added. -methoxyphenyl (24 μl) to the solution. The mixture was stirred at a temperature of 60 ° C for one hour. Methanol was added to the reaction solution, and the mixture was purified by HPLC by growth with chloroform / methanol to provide 39 mg (yield: 54%) of the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 3.90 (s, 3 H), 3.98 (s, 3 H), 3.99 (s, 3 H), 6.89 - 7.05 (m, 3 H), 7.29 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.40 (s, 1H), 7.54 (d, J = 2.7 Hz, 1H), 7.56 (s, 1H), 8.09 - 8.16 (m, 2H), 8.58 (s, 1H), 8.96 - 9.02 (m, 2H) Mass analysis, found (ESI-MS, m / z): 418 (M ++ 1) Example 87: N- [2-chloro-4- [(6,7-dimethoxy- 4-quinazolinyl) oxy] -phenyl} -N '- (5-chloro-2-pyridyl) urea 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] aniline (50 mg) was dissolved in chloroform (5 ml) and triethylamine ( 1 ml), and a solution of triphosgene (45 mg) in chloroform was then added to the solution. The mixture was stirred at room temperature for 30 minutes. Then, 2-amino-5-chloropyridine (23 mg) was added to the reaction solution and the mixture was stirred at a temperature of 60 ° C for an additional hour. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution and the mixture was extracted with chloroform. The chloroform layer was dried in anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by HPLC by growth with chloroform / methanol to provide 39 mg (yield: 53%) of the title compound. 1 H-NMR (DMSO-dβ, 400 MHz): d 3.98 (s, 3 H), 4.00 (s, 3 H), 7.33 (d, J = 2.7 Hz, 9.3 Hz, 1 H), 7.40 (s, 1 H), 7.43. - 7.48 (m, 1H), 7.56 (s, 1H), 7.60 (d, J = 2.7 Hz, 1H), 7.91 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 8.35 (d, J = 8.8 Hz , 1H), 8.40 (d, J = 2.4 Hz, 1H), 8.58 (s, 1H), 10.17 (s, 1H) Mass analysis, found (ESI-MS, m / z): 486 (M ++ l Example 88: N-. { 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -2-fluorophenyl} -N'-propylurea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] -2-fluoroaniline (50 mg) was dissolved in chloroform (3 ml) and triethylamine (0.3 ml), and then added to the solution a solution of triphosgene (47 mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then propylamine (20 μl) was added to the reaction solution and the mixture was further stirred at room temperature overnight. Methanol was added to the reaction solution, and the mixture was puirified by HPLC by growth with chloroform / methanol to provide 9 mg (yield: 14%) of the title compound. 1 H-NR (DMSO-de, 400 MHz): d 0.90 (t, J = 7.6 Hz, 3 H), 1.43 -1.49 (m, 2 H), 3.05 - 3.10 (m, 2 H), 3.97 (s, 3 H), 3.99 (s, 3H), 6.61 (t, J = 5.6 Hz, 1H), 7.05 - 7.07 (m, 1H), 7.27 - 7.31 (m, 1H), 7.38 (s, 1H), 7.54 (s, 1H) , 8.14 - 8.19 (m, 1H), 8.28 - 8.29 (m, 1H), 8.55 (s, 1H) Mass analysis, found (ESI-MS, m / z): 401 (M? -1) Example 89: N-Butyl-N '-. { 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -2-fluorophenyl} urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] -2-fluoroaniline (50 mg) was dissolved in chloroform (3 ml) and triethylamine (0.3 ml), and a solution of triphosgene (47 mg) was then added. mg) in chloroform to the solution. The mixture was stirred at room temperature for 30 minutes. Then butylamine (24 μl) was added and the mixture was further stirred at room temperature overnight. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol to provide 25 mg (yield: 38%) of the title compound.

^? - NMR (DMSO-de, 400 MHz): d 0.91 (t, J = 7.3 Hz, 3H), 1.30 -1.47 (, 4H), 3.09 - 3.13 (m, 2H), 3.97 (s, 3H), 3.99 (s, 3H), 6.58 (t, J = 5.6 Hz, 1H), 7.04 - 7.07 (m, 1H), 7.28 - 7.31 (, 1H), 7.38 (s, 1H), 7.54 (s, 1H), 8.14 - 8.19 (m, 1H), 8.26 - 8.28 (m, 1H), 8.55 (s, 1H) Mass analysis, found (ESI-MS, m / z): 415 (M ++ l) Example 90 N- (sec-Butyl) -N'-. { 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -2-fluorophenyl} urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] -2-fluoroaniline (50 g) was dissolved in chloroform (3 ml) and triethylamine (0.3 ml), and then a solution was added to the solution. triphosgene solution (47 mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then, sec-butylamine (25 μl) was added to the reaction solution and the mixture was stirred overnight at room temperature. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol to provide 12 mg (yield: 18%) of the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 0.89 (t, J = 7.6 Hz, 3H), 1.08 (d, J = 6.6 Hz, 3H), 1.39-1.48 (m, 2H), 3.58-3.64 ( m, 1H), 3.97 (s, 3H), 3.99 (s, 3H), 6.51 (d, J = 7.6 Hz, 1H), 7.04 - 7.08 (m, 1H), 7.30 (dd, J = 2.4 Hz, 11.7 Hz, 1H), 7.39 (s, 1H), 7.54 (s, 1H), 8.16 - 8.22 (m, 2H), 8.56 (s, 1H) Mass analysis, found (ESI-MS, m / z): 415 (M? L) Example 91: N-Allyl-N '-. { 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -2-fluorophenyl} urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] -2-fluoroaniline (50 mg) was dissolved in chloroform (3 ml) and triethylamine (0.3 ml), and then a solution of triphosgene (47 mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then, allylamine hydrochloride (30 mg) was added to the reaction solution and the mixture was further stirred at room temperature overnight. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol to provide 18 mg (yield: 28%) of the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 3.75-3.79 (m, 2 H), 3.97 (s, 3 H), 3.99 (s, 3 H), 5.08 - 5.22 (m, 2 H), 5.84 - 5.94 (m , 1H), 6.72 (t, J = 5.9 Hz, 1H), 7.06 - 7.08 (m, 1H), 7.30 - 7.33 (m, 1H), 7.39 (s, 1H), 7.54 (s, 1H), 8.13 - 8.18 (m, 1H), 8.40 (s, 1H), 8.56 (s, 1H) Mass analysis, found (ESI-MS, m / z): 399 (M? L) Example 92: N-. { 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -2-fluorophenyl} -N '- (2-propynyl) urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] -2-fluoroaniline (50 mg) was dissolved in chloroform (3 ml) and triethylamine (0.3 ml) , and a solution of triphosgene (47 mg) in chloroform was then added to the solution. The mixture was stirred at room temperature for 30 minutes. Then propargylamine hydrochloride (29 mg) was added to the reaction solution, and the mixture was further stirred at room temperature overnight. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution and the mixture was extracted with chloroform. The chloroform layer was dried in anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was washed with chloroform to provide 21 mg (yield: 33%) of the title compound. XH-NMR (DMSO-de, 400 MHz): d 3.15 (t, J = 2.4 Hz, 3H), 3.91 -3.94 (m, 2H), 3.97 (s, 3H), 3.99 (s, 3H), 7.07 - 7.11 (m, 1H), 7.33 (dd, J = 2.4 Hz, 11.7 Hz, 1H), 7.39 (s, 1H), 7.54 (s, 1H), 8.09 - 8.15 (m, 1H), 8.47 - 8.48 (m , 1H), 8.56 (s, 1H) Mass analysis, found (ESI-MS, m / z): 397 (M ++ 1) Example 93: N- (2,4-difluorobenzyl) -N '-. { 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -2-fluorophenyl} urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] -2-fluoroaniline (50 mg) was dissolved in chloroform (3 ml) and triethylamine (0.3 ml), and then a solution of triphosgene (47 mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. After, 2,4-difluorobenzylamine (28 μl) was added to the reaction solution and the mixture was further stirred at room temperature overnight. The precipitated crystal was collected by filtration and washed to provide 20 mg (yield: 26%) of the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 3.97 (s, 3 H), 3.99 (s, 3 H), 4.34 (d, J = 5.8 Hz, 2 H), 7.07 - 7.11 (m, 3 H), 7.21 - 7.27 (m, 1H), 7.30 - 7.33 (m, 1H), 7.39 (s, 1H), 7.41 - 7.47 (m, 1H), 7.54 (s, 1H), 8.12 - 8.16 (m, 1H), 8.46 - 8.47 (m, 1H), 8.55 (s, 1H) Mass analysis, found (FD-MS, m / z): 484 (M +) Example 94: N- (2,4-difluorophenyl) -N '- [4 - [(6,7-dimethoxy-4-quinazolinyl) oxy] -2-fluorophenyl} urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] -2-fluoroaniline (50 mg) was dissolved in chloroform (3 ml), and then 2,4-difluorophenyl isocyanate (29 μl) was added to the solution. The mixture was stirred at a temperature of 60 ° C overnight. The precipitated crystal was collected by filtration and washed to provide 50 mg (yield: 67%) of the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 3.98 (s, 3 H), 3.99 (s, 3 H), 7.04 - 7.08 (m, 1 H), 7.13 - 7.15 (m, 1 H), 7.29 - 7.40 (m , 3H), 7.55 (s, 1H), 8.10 - 8.23 (m, 2H), 8.57 (s, 1H), 8.97 - 9.04 (m, 2H) Mass analysis, found (ESI-MS, m / z): 471 (M ++ l) Example 95: N-. { 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -2-fluorophenyl} -N '- (2-methylphenyl) urea 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -2-fluoroaniline (50 mg) was dissolved in chloroform (3 ml) and then isocyanate was added. o-toluyl (30 μl) to the solution. The mixture was stirred at a temperature of 60 ° C overnight. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol to provide 17 mg (yield: 24%) of the title compound. (DMSO-de, 400 MHz): d 2.27 (s, 3H), 3.98 (s, 3H), 3.99 (s, 3H), 6.95-6.98 (m, 1H), 7.12-7.20 (m, 3H), 7.36 -7.39 (m, 2H), 7.55 (s, 1H), 7.86 (d, J = 7.8 Hz, 1H), 8.21 -8.26 (m, 1H), 8.35 (s, 1H), 8.57 (s, 1H), 9.00 - 9.02 (m, 1H), Mass analysis, found (ESI-MS, m / z): 449 (M ++ 1) Example 96: N-. { 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -2-fluorophenyl} -N '- (2-methoxyphenyl) urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] -2-fluoroaniline (50 mg) was dissolved in chloroform (3 ml) and then added to the 2-methoxyphenyl isocyanate solution (32 μl). The mixture was stirred at a temperature of 60 ° C overnight. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol to provide 22 mg (yield: 30%) of the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 3.89 (s, 3 H), 3.98 (s, 3 H), 3.99 (s, 3 H), 6.88 - 7.04 (m, 3 H), 7.11 - 7.14 (m, 1 H) ), 7.35 -7.39 (m, 1H), 7.40 (s, 1H), 7.56 (s, 1H), 8.12 - 8.15 (m, 1H), 8.19 - 8.25 (m, 1H), 8.57 (s, 1H), 8.75 - 8.78 (m, 1H), 9. 26-29.9 (m, 1H) Mass analysis, found (ESI-MS, m / z): 465 (M ++ 1) Example 97: N-. { 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -3-methylphenyl} -N'-propylurea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] -3-methyl-aniline (50 mg) was dissolved in chloroform (3 ml) and triethylamine (0.2 ml), and then added to the solution a solution of triphosgene (48 mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then, propylamine was added (20 μl) to the reaction solution, and the mixture was further stirred at room temperature overnight. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol to provide 30 mg (yield: 47%) of the title compound. 1 H-NR (DMSO-de, 400 MHz): d 0.89 (t, J = 7.5 Hz, 3 H), 1.41 -1.50 (m, 2 H), 2.03 (s, 3 H), 3.03 - 3.08 (m, 2 H), 3.98 (s, 3H), 3.99 (s, 3H), 6.13 (t, J = 5.4 Hz, 1H), 7.04 (d, J = 8.5 Hz, 1H), 7.28 (dd, J = 2.4 Hz, 8.5 Hz, 1H), 7.36 (d, J = 2.4 Hz, 1H), 7.38 (s, 1H), 7.58 (s, 1H), 8.39 (s, 1H), 8.50 (s, 1H) Mass analysis, found (ESI- MS, m / z): 397 (M ++ 1) Example 98: N-Butyl-N '- [4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -3-methylphenyl} urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] -3-methyl-aniline (50 mg) was dissolved in chloroform (3 ml) and triethylamine (0.2 ml), and then a solution was added to the solution. Triphosgene solution (48 mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then, butylamine (24 μl) was added to the reaction solution, and the mixture was further stirred at room temperature overnight. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol to provide 31 mg (yield: 47%) of the title compound. 1H-lvIMR (DMSO-de, 400 MHz): d 0.91 (t, J = 7.3 Hz, 3H), 1.29 -1.46 (m, 4H), 2.03 (s, 3H), 3.07 - 3.12 (m, 2H), 3.98 (s, 3H), 3.99 (s, 3H), 6.11 (t, J = 5.6 Hz, 1H), 7.05 (d, J = 8.8 Hz, 1H), 7.27 (dd, J = 2.3 Hz, 8.5 Hz, 1H), 7.36 (d, J = 2 Hz, 1H), 7.38 (s, 1H), 7.58 (s, 1H), 8.39 (s, 1H), 8.51 (s, 1H) Mass analysis, found (ESI) -MS, m / z): 411 (M ++ 1) Example 99: N- (2, 4-Difluorophenyl) -N '- [4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -3 -methylphenyl} urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] -3-methyl-aniline (50 mg) was dissolved in chloroform (3 ml), and then 2,4-difluorophenyl isocyanate was added to the solution (23 μl). The mixture was heated under reflux overnight. The precipitated crystal was collected by filtration and washed to provide 59 mg (yield: 79%) of the title compound.

XH-NMR (DMSO-de, 400 MHz): d 2.07 (s, 3H), 3.99 (s, 3H), 3.99 (s, 3H), 7.03- 7.08 (m, 1H), 7.14 (d, J = 8.5 Hz, 1H), 7.29 -7.37 (m, 2H), 7.39 (s, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.60 (s, 1H), 8.07 - 8.14 (m, 1H), 8.52 (s, 1H), 9.03 - 9.05 (m, 1H) Mass analysis, found (ESI-MS, m / z): 467 (M ++ 1) Example 100: N-. { 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -3-methylphenyl} -N '- (4-fluorophenyl) urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] -3-methyl-aniline (50 mg) was dissolved in chloroform (3 ml) and then isocyanate was added. p-fluorophenyl (22 μl) to the solution. The mixture was heated overnight under reflux. The precipitated crystal was collected by filtration and washed to provide 42 mg (yield: 58%) of the title compound. TEI-NMR (DMSO-dβ, 400 MHz): d 2.07 (s, 3H), 3.98 (s, 3H), 3.99 (s, 3H), 7.10 - 7.14 (m, 3H), 7.35 (dd, J = 8.5 Hz, 2.4 Hz, 1H), 7.39 (s, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.46 - 7.49 (, 2H), 7.59 (s, 1H), 8.51 (s, 1H), 8.66 (s, 1H), 8.70 (s, 1H) Mass analysis, found (ESI-MS, m / z): 449 (M? l) Example 101: N- [4- [(6,7-dimethoxy-4 -quinazolinyl) oxy] -3-methylphenyl} -N '- (2-methoxyphenyl) urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] -3-methyl-aniline (50 mg) was dissolved in chloroform (3 ml) and then added to the 2-methoxyphenyl isocyanate solution (26 μl). The mixture was heated under reflux overnight. Methanol was added to the reaction solution, and the mixture was purified by HPLC by growth with chloroform / methanol to provide 41 mg (yield: 55%) of the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 2.07 (s, 3H), 3.89 (s, 3H), 3.99 (s, 3H), 3.99 (s, 3H), 6.88-6.97 (m, 2H), 7.01 - 7.03 (m, 1H), 7.12 (d, J = 8.5 Hz, 1H), 7.35 (dd, J = 2.4 Hz, 8.5 Hz, 1H), 7.39 (s, 1H), 7.44 (d, J = 2 Hz, 1H), 7.60 (s, 1H), 8.13 -8.15 (m, 1H), 8.23 (s, 1H), 8.52 (s, 1H), 9.33 (s, 1H) Mass analysis, found (ESI- MS, m / z): 461 (M? L) Example 102: N- (4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -2-methylphenyl.} - N'-propylurea was dissolved. - [(6,7-dimethoxy-4-quinazolinyl) oxy] -2-methyl-aniline (50 mg) in chloroform (3 ml) and triethylamine (0.2 ml), and a triphosgene solution was added to the solution ( 48 mg) in chloroform The mixture was stirred at room temperature for 30 minutes, then propylamine (20 μl) was added to the reaction solution, and the mixture was further stirred at room temperature overnight. The solution of the reaction and the mixture was purified by HPLC by de of chloroform / methanol to give 30 mg (yield: 47%) of the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 0.90 (t, J = 7.3 Hz, 3H), 1.42-1.51 (m, 2H), 2.21 (s, 3H), 3.04-3.09 (m, 2H), 3.97 (s, 3H), 3.99 (s, 3H), 6.53 (t, J = 5.6 Hz, 1H), 7.02 (d, J = 2.7 Hz, 8.8 Hz, 1H), 7.08 (d, J = 2.7 Hz, 1H), 7.37 (s, 1H), 7.54 (s, 1H), 7.65 (s, 1H), 7.85 (d, J = 8.8 Hz, 1H), 8.53 (s, 1H) Mass analysis, found (ESI- MS, m / z): 397 (M? L) Example 103: N-Butyl-N '-. { 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -3-methylphenyl} urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] -2-methyl-aniline (50 mg) was dissolved in chloroform (3 ml) and triethylamine (0.2 ml), and then a solution was added to the solution. Triphosgene solution (48 mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then, butylamine (24 μl) was added to the reaction solution, and the mixture was further stirred at room temperature overnight. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol to provide 37 mg (yield: 56%) of the title compound. 1 H-MR (DMSO-de, 400 MHz): d 0.92 (t, J = 7.1 Hz, 3 H), 1.31 -1.48 (m, 4 H), 2.21 (s, 3 H), 3.08 - 3.13 (m, 2 H), 3.97 (s, 3H), 3.99 (s, 3H), 6.50 (t, J = 5.4 Hz, 1H), 7.02 (dd, J = 2.7 Hz, 8.8 Hz, 1H), 7.08 (d, J = 2.7 Hz, 1H), 7.37 (s, 1H), 7.54 (s, 1H), 7.64 (s, 1H), 7.86 (d, J = 8.8 Hz, 1H), 8.53 (s, 1H) Mass analysis, found (ESI- MS, m / z): 411 (M ++ 1) Example 104: N- (2, 4-Difluorophenyl) -N '- [4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -2- methylphenyl} urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] -2-methyl-aniline (50 mg) was dissolved in chloroform (3 ml), and then 2,4-difluorophenyl isocyanate solution was added to the solution (23 μl). The mixture was heated under reflux overnight. The precipitated crystal was collected by filtration and washed to provide quantitatively the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 2.29 (s, 3 H), 3.98 (s, 3 H), 3.99 (s, 3 H), 7.03 - 7.11 (m, 2 H), 7.16 (d, J = 2.7 Hz, 1H), 7.29 -7.35 (, 1H), 7.38 (s, 1H), 7.55 (s, 1H), 7.87 - 7.90 (m, 1H), 8.13 - 8.19 (m, 1H), 8.36 - 8.39 (m , 1H), 8.55 (s, 1H), 8.92 - 8.95 (, 1H) Mass analysis, found (ESI-MS, m / z): 467 (M ++ l) Example 105: N- (4- [( 6,7-dimethoxy-4-quinazolinyl) oxy] -2-methylphenyl.} - N '- (4-fluorophenyl) urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] was dissolved. methyl aniline (50 mg) in chloroform (3 ml), and p-fluorophenyl isocyanate (22 μl) was then added to the solution.The mixture was heated under reflux overnight.The precipitated crystal was collected by filtration and was washed to provide quantitatively the title compound.1H-1'MR (DMSO-de, 400 MHz): d 2.28 (s, 3H), 3.98 (s, 3H), 3.99 (s, 3H), 7.08 - 7.15 (m, 4H), 7.38 (s, 1H), 7.47-7.50 (m, 2H), 7.55 (s, 1H), 7.84-7.88 (m, 1H), 7.98 (s, 1H), 8.55 (s, 1H), 9.03 - 9.05 (m, 1H) Mass analysis, found (ESI-MS, m / z): 449 (M? L) Example 106: N-. { 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -2-methylphenyl} -N '- (2-methoxyphenyl) urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] -2-methyl-aniline (50 mg) was dissolved in chloroform (3 ml) and then added to the 2-methoxyphenyl isocyanate solution (26 μl). The heated mixture was collected by filtration and washed to provide 70 mg (yield: 95%) of the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 2.29 (s, 3 H), 3.90 (s, 3 H), 3.98 (s, 3 H), 3.99 (s, 3 H), 6.87 - 6.97 (m, 2 H), 7.02 - 7.04 (m, 1H), 7.08 (dd, J = 2.9 Hz, 8.8 Hz, 1H), 7.14 (d, J = 2.7 Hz, 1H), 7.38 (s, 1H), 7.55 (s, 1H), 7.84 (d, J = 8.8 Hz, 1H), 8.13 -8.15 (m, 1H), 8.55 (s, 1H), 8.58 (s, 1H), 8.61 - 8.62 (m, 1H) Mass analysis, found (ESI) -MS, m / z): 461 (M ++ 1) Example 107: N- [4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -2-nitrophenyl} -N'-propylurea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] -2-nitroaniline (50 mg) was dissolved in chloroform (10 ml) and triethylamine (0.2 ml), and then added to the solution a solution of triphosgene (43 mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then, propylamine (18 μl) was added to the reaction solution, and the mixture was further stirred at room temperature overnight. Methanol was added to the reaction solution, and the mixture was purified by HPLC by growth with chloroform / methanol to provide 24 mg (yield: 38%) of the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 0.91 (t, J = 7.6 Hz, 3H), 1.45-1.51 (m, 2H), 3.06-3.09 (m, 2H), 3.98 (s, 3H), 4.00 (s, 3H), 4.70 (s, 1H), 7.52 (br, 1H), 7.58 (s, 1H), 7.67 - 7.70 (m, 1H), 8.04 - 8.06 (m, 1H), 8.38 - 8.41 ( m, 1H), 8.57 (s, 1H), 9.35 (s, 1H) Mass analysis, found (ESI-MS, m / z): 428 (M ++ 1) Example 108: N-Butyl-N '- . { 4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -2-nitrophenyl} urea 4- [(6,7-Dimethoxy-4-quinazolinyl) oxy] -2-nitroaniline (50 mg) was dissolved in chloroform (10 ml) and triethylamine (0.2 ml), and then a solution was added to the solution. Triphosgene solution (43 mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then, butylamine (22 μl) was added to the reaction solution, and the mixture was further stirred at room temperature overnight. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol to provide 15 mg (yield: 23%) of the title compound. ^ -NMR (DMSO-de, 400 MHz): d 0.91 (t, J = 7.3 Hz, 3H), 1.30 -1.49 (m, 4H), 3.10 - 3.15 (m, 2H), 3.98 (s, 3H), 4.00 (s, 3H), 7.40 (s, 1H), 7.51 (br, 1H), 7.57 (s, 1H), 7.68 (dd, J = 2.9 Hz, 9.3 Hz, 1H), 8.05 (d, J = 2.9 Hz, 1H), 8.40 (d, J = 9.2 Hz, 1H), 8.57 (s, 1H), 9.35 (s, 1H) Mass analysis, found (ESI-MS, m / z): 442 (M? L) Example 109: N-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl} -N-methoxymethyl-N'-propylurea N- [2-chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl was dissolved} -N'-propylurea (100 mg) in anhydrous tetrahydrofuran (30 ml) and sodium hydride (60% by weight, 88 mg) was added to the solution. The mixture was stirred at room temperature for 15 minutes. Then, chloromethyl methyl ether (67 μl) was added to the reaction solution, and the mixture was stirred at room temperature for an additional 30 minutes. The solvent was removed by distillation under reduced pressure, and water was added to the residue. The mixture was extracted with chloroform. The chloroform layer was dried in anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by HPLC by growth with chloroform / methanol to provide 18 mg (yield: 18%) of the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 0.89 (t, J = 7.6 Hz, 3H), 1.46 -1.55 (m, 2H), 3.20 (br, 2H), 3.48 (s, 3H), 4.07 (s, 3H), 4.08 (s, 3H), 4.54 (br, 2H), 7.29 (dd, J = 2.7 Hz, 8.5 Hz, 1H), 7.37 (s, 1H), 7.47 (d, J = 8.8 Hz, 1H), 7.50 (s, 1H), 7.50 (d, J = 2.7 Hz, 1H), 8.66 (s, 1H) Mass analysis, found (ESI-MS, m / z): 461 (M ++ 1) Example 110: N-Acetyl-N-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl} -N'-propylurea N- [2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl was dissolved} -N'-propylurea (100 mg) in anhydrous tetrahydrofuran (30 ml), and sodium hydride (60% by weight, 88 mg) was added to the solution. The mixture was stirred at room temperature for 15 minutes. Then, acetyl chloride (63 μl) was added and the mixture was stirred at room temperature for an additional 2 hours. The solvent was removed by distillation under reduced pressure, and water was added to the residue. The mixture was extracted with chloroform. The chloroform layer was dried in anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by HPLC by growth with chloroform / acetone to provide 27 mg (yield: 26%) of the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 0.98 (t, J = 7.3 Hz, 3 H), 1.59 -1.68 (m, 2 H), 2.04 (s, 3 H), 3.27 - 3.36 (, 2 H), 4.07 (s, 3H), 4.08 (s, 3H), 7.31 - 7.33 (, 1H), 7.35 (s, 1H), 7.41 (d, J = 9.0 Hz, 1H), 7.50 - 7.51 (m, 2H), 8.63 (s, 1H), 9.08 (br, 1H) Mass analysis, found (ESI-MS, m / z): 459 (M? l) Example 111: N '-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl} -N-methyl-propylurea 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] aniline (56 mg) was dissolved in chloroform (4 ml) and triethylamine (0.3 ml), and then added to the solution a solution of triphosgene (50 mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then, N-methyl-propylamine (26 μl) was added to the reaction solution and the mixture was stirred at room temperature for an additional hour. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol. The solvent was removed by distillation, and the resulting crystal was washed with hexane to provide 42 mg (yield: 58%) of the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 0.99 (t, J = 7.3 Hz, 3 H), 1.64 -1.74 (m, 2 H), 3.08 (s, 3 H), 3.34 (t, J = 7.6 Hz, 2H), 4.07 (s, 3H), 4.08 (s, 3H), 7.00 (s, 1H), 7.17 (dd, J = 2.7 Hz, 9.3 Hz, 1H), 7.31 (d, J = 2.7 Hz, 1H) , 7.38 (s, 1H), 7.53 (s, 1H), 8.41 (d, J = 9.0 Hz, 1H), 8.64 (s, 1H) Mass analysis, found (ESI-MS, m / z): 431 ( M ++ l) Example 112: N '-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl} -N-ethyl-N-propylurea 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] aniline (80 mg) was dissolved in chloroform (3 ml) and triethylamine (0.3 ml), and Then, a solution of triphosgene (72 mg) in chloroform was added to the solution. The mixture was stirred at room temperature for 15 minutes. Then, N-ethylpropylamine (44 μl) was added to the reaction solution, and the mixture was stirred at room temperature for an additional 30 minutes. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol. The solvent was removed by distillation, and the resulting crystal was washed with hexane to provide 40 mg (yield: 37%) of the title compound. 1 H-NMR (DMSO-d 6, 400 MHz): d 1.00 (t, J = 7.3 Hz, 3H), 1.28 (t, J = 7.1 Hz, 3H), 1.69-1.74 (m, 2H), 3.32 (t, J = 7.6 Hz, 2H), 3.43 (q, J = 7.1 Hz, 2H), 4.07 (s, 3H), 7.02 (s, 1H), 7.17 (dd, J = 2.9 Hz, 9.2 Hz, 1H), 7.31 (d, J = 2.7 Hz, 1H), 7.36 (s, 1H), 7.53 (s, 1H), 8.42 (d, J = 9.0 Hz, 1H), 8.63 (s, 1H) Mass analysis, found (ESI) -MS, m / z): 445 (M? L) Example 113: N '-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl} -N, N-dipropylurea. 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] aniline (100 mg) was dissolved in chloroform (3 ml) and triethylamine (0.3 ml)., and a solution of triphosgene (90 mg) in chloroform was then added to the solution. The mixture was stirred at room temperature for 15 minutes. Then, dipropylamine (62 μl) was added to the reaction solution, and the mixture was stirred at room temperature for an additional 30 minutes. Methanol was added to the reaction solution, and the mixture was purified by HPLC by growth with chloroform / methanol. The solvent was removed by distillation, and the resulting crystal was washed with hexane to provide 48 mg (yield: 35%) of the title compound. 1 H-NR (DMSO-de, 400 MHz): d 0.99 (t, J = 7.3 Hz, 6H), 1.66 -1.76 (m, 4H), 3.32 (t, J = 7.8 Hz, 4H), 4.07 (s, 3H), 7.03 (s, 1H), 7.16 (dd, J = 2.7 Hz, 9.3 Hz, 1H), 7.31 (d, J = 2.7 Hz, 1H), 7.34 (s, 1H), 7.52 (s, 1H) , 8.43 (d, J = 9.0 Hz, 1H), 8.63 (s, 1H) Mass analysis, found (ESI-MS, m / z): 459 (M ++ 1) Example 114: N-Butyl-N ' - [2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl} -N-methylurea 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] aniline (80 mg) was dissolved in chloroform (3 ml) and triethylamine (0.3 ml), and then added to the solution a solution of triphosgene (72 mg) in chloroform. The mixture was stirred at room temperature for 15 minutes. Then, N-methylbutylamine (43 μl) was added to the reaction solution, and the mixture was stirred at room temperature for an additional 30 minutes. Methanol was added to the reaction solution, and the mixture was purified by HPLC by growth with chloroform / methanol. The solvent was removed by distillation and the resulting crystal was washed with hexane to provide 26 mg (yield: 24%) of the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 0.99 (t, J = 7.3 Hz, 3H), 1.38-1.43 (m, 2H), 1.62-1.66 (m, 2H), 3.07 (s, 3H), 3.40 (t, J = 7.3 Hz, 2H), 4.07 (s, 3H), 4.07 (s, 3H), 7.00 (s, 1H), 7.17 (dd, J = 2.7 Hz, 9.3 Hz, 1H), 7.31 ( d, J = 2.7 Hz, 1H), 7.36 (s, 1H), 7.53 (s, 1H), 8.41 (d, J = 9.3 Hz, 1H), 8.63 (s, 1H) Mass analysis, found (ESI- MS, m / z): 445 (M ++ 1) Example 115: N '-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl} -N- (4-chlorophenyl) -N-methylurea. 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] aniline (80 mg) was dissolved in chloroform (3 ml) and triethylamine (0.3 ml. ), and a solution of triphosgene (72 mg) in chloroform was then added to the solution. The mixture was stirred at room temperature for 15 minutes. Then, 4-chloro-N-methylaniline (35 μl) was added to the reaction solution, and the mixture was heated under reflux for an additional 30 minutes. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol, and the solvent was removed by distillation. The resulting crystal was washed with ether to provide 83 mg (yield: 69%) of the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 3.36 (s, 3 H), 4.06 (s, 3 H), 4.07 (s, 3 H), 6.89 (s, 1 H), 7.17 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.23 (d, J = 2.7 Hz, 1H), 7.33-7.35 (m, 3H), 7.48-7.50 (m, 3H), 8.41 (d, J = 9.0 Hz, 1H), 8.61 ( s, 1H) Mass analysis, found (ESI-MS, m / z): 499 (M ++ l) Example 116; N'-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl} -N, N-diethylurea 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] aniline (50 mg) was dissolved in chloroform (2 ml) and triethylamine (0.5 ml), and then added to the solution a solution of triphosgene (48 mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then, diethylamine (0.5 ml) was added to the reaction solution, and the mixture was further stirred at room temperature overnight. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol to provide 37 mg (yield: 93%) of the title compound. XH-NMR (CDC13, 400 MHz): d 1.30 (t, J = 7.1 Hz, 6H), 3.44 (q, J = 7.1 Hz, 4H), 4.12 (s, 3H), 4.20 (s, 3H), 7.16 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.27 (s, 1H), 7.31 (d, J = 2.7 Hz, 1H), 7.59 (s, 1H), 8.15 (s, 1H), 8.48 (d , J = 9.0 Hz, 1H), 8.81 (s, 1H) Mass analysis, found (ESI-MS, m / z): 431 (M ++ 1) Example 117: N- [2-chloro-4- [ (6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl} -N'-methylurea 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] aniline (50 mg) was dissolved in chloroform (2 ml) and triethylamine (0.5 ml), and added to the solution a solution of triphosgene (48 mg) in chloroform. The mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was cooled to -78 ° C and methylamine hydrochloride (130 mg) was added to the cooled reaction solution. The temperature of the mixture was raised spontaneously and the mixture was further stirred at room temperature overnight. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol to provide 41 mg (yield: 70%) of the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 2.68 (d, J = 4.4 Hz, 3 H), 3.97 (s, 3 H), 3.99 (s, 3 H), 6.86 - 6.88 (m, 1 H), 7.21 ( dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.37 (s, 1H), 7.43 (d, J = 2.7 Hz, 1H), 7.53 (s, 1H), 8.07 (s, 1H), 8.17 (d, J = 9.0 Hz, 1H), 8.54 (s, 1H) Mass analysis, found (ESI-MS, m / z): 389 (M ++ 1) Example 118: N '-. { 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] -phenyl} -N, N'-dimethylurea 2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] aniline (50 mg) was dissolved in chloroform (2 ml) and triethylamine (0.5 ml), and then A solution of triphosgene (48 mg) in chloroform was added to the solution. The mixture was stirred at room temperature for 30 minutes. Then, the reaction solution was cooled to a temperature of -78 ° C, and dimethylamine hydrochloride (250 mg) was added to the solution of the cooled reaction. The temperature of the mixture was raised spontaneously, and the mixture was further stirred at room temperature overnight. Methanol was added to the reaction solution and the mixture was purified by HPLC by growth with chloroform / methanol to provide 33 mg (yield: 53%) of the title compound. ^ -H-NMR (CDC13, 400 MHz): d 3.11 (s, 6H), 4.12 (s, 3H), 4.20 (s, 3H), 7.05 (s, 1H), 7.17 (dd, J = 2.4 Hz, 9.3 Hz, 1H), 7.31 (d, J = 2.4 Hz, 1H), 7.59 (s, 1H), 8.15 (s, 1H), 8.46 (d, J = 9.3 Hz, 1H), 8.82 (s, 1H) Mass analysis, found (ESI-MS, m / z): 403 (M? L) Example 119: N- (2-chloro-4- [[6-methoxy-7- (3-morpholinopropoxy) -4-quinazolinyl ] oxy] phenyl) -N'-propyl-urea N- [2-chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl was dissolved} -N'-propylurea (75 mg), potassium carbonate (51 mg), and 1,3-dibromopropane (76 μl) in N, N-dimethylformamide (4 ml) and the solution was stirred at room temperature for 3 hours. The solvent was removed by distillation under reduced pressure. Water was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure.

The residue was washed with ether to provide 74 mg (yield: 78%) of N-. { [7- (3-bromopropoxy) -6-methoxy-4-quinazolinyl] -oxi} -2-chlorophenyl) -N'-propylurea as an intermediate product. The intermediate product (74 mg), potassium carbonate (51 mg), and morpholine (130 μl) were dissolved in N, N-dimethylformamide (4 ml), and the solution was stirred at room temperature overnight. The solvent was removed by distillation under reduced pressure. A saturated aqueous solution of sodium hydrogencarbonate was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / methanol to provide 49 mg (yield: 63%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 0.89 (t, J = 7.44 Hz, 3 H), 1.41 -1.50 (, 2 H), 1.97 (t, J = 6.83 Hz, 1 H), 2.33-2.49 (m, 4 H) ), 3.04 - 3.09 (m, 2H), 3.32 - 3.38 (, 4H), 3.52 - 3.68 (m, 3H), 4.03 (s, 3H), 4.23 - 4.29 (m, 1H), 4.32 (t, J = 5.89 Hz, 1H), 6.98 (t, J = 5.49 Hz, 1H), 7.21 (dd, J = 2.68, 9.3 Hz, 1H), 7.36 (s, 1H), 7.46 (d, J = 2.68 Hz, 1H) , 7.53 (d, J = 7.81 Hz, 1H), 8.03 (s, 1H), 8.18 (d, J = 9.27 Hz, 1H), 8.54 (d, J = 4.39 Hz, 1H) Mass analysis, found (ESI) -MS, m / z): 529 (M ++ 1) Example 120: N- (2-chloro-4- { [6-methoxy-7- (2-morpholinoethoxy) -4-quinazolinyl] oxy} phenyl) -N'-propyl-urea N- [2-chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl was dissolved} -N'-propylurea (72 mg), potassium carbonate (30 mg), and 1,2-dibromoethane (62 μl) in N, N-dimethylformamide (4 ml) and the solution was stirred at room temperature for 3 hours. The solvent was removed by distillation under reduced pressure. Water was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 40 mg (yield: 45%) of N- (4- { [7- (3-bromoethoxy) -6-methoxy-4-quinazolinyl] -oxi.} -2- chlorophenyl) -N'-propylurea as an intermediate product. The intermediate product (45 mg), potassium carbonate (30 mg), and morpholine (80 μl) were dissolved in N, N-dimethylformamide (2 ml), and the solution was stirred at room temperature overnight. The solvent was removed by distillation under reduced pressure. A saturated aqueous solution of sodium hydrogencarbonate was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / methanol to provide 42 mg (yield: 56%) of the title compound. XH-1MR (CDC13, 400 MHz): d 0.89 (t, J = 7.32 Hz, 3H), 1.43 -1.49 (m, 2H), 2.32-2.38 (m, 2H), 2.66 (bs, 1H), 2.79 ( t, J = 5.86 Hz, 1H), 3.04 - 3.09 (m, 2H), 3.29 - 3.36 (m, 4H), 3.53 (m, 1H), 3.57 - 3.59 (m, 2H), 3.96 (s, 3H) , 4.31 (t, J = 5.85 Hz, 1H), 6.98 (, 1H), 7.21 - 7.23 (m, 1H), 7.41 (s, 1H), 7.46 - 7.47 (m, 1H), 7.55 (d, J = 12.69 Hz, 1H), 8.03 (s, 1H), 8.19 (d, J = 9.27 Hz, 1H), 8.55 (d, J = 5.37 Hz, 1H) Mass analysis, found (ESI-MS, m / z) : 517 (M? L) Example 121: N- (2-chloro-4- { [7- (3-hydroxypropoxy) -6-methoxy-4-quinazolinyl] oxy} phenyl) -N'-propylurea N- was dissolved. { 2-Chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl} -N'-propylurea (55 mg), potassium carbonate (20 mg), and 3-bromo-l-propanol (62 μl) in N, N-dimethylformamide (4 ml) and the solution was stirred at room temperature for 3 hours. hours. The solvent was removed by distillation under reduced pressure. Water was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / methanol to provide 25 mg (yield: 40%) of the title compound. ^? - MR (CDC13, 400 MHz): d 0.91 (t, J = 7.44 Hz, 3H), 1.24 (bs, 1H), 1.43 - 1.52 (m, 2H), 1.97 (t, J = 6.22 Hz, 2H), 3.06 -3.11 ( m, 2H), 3.56 - 3.71 (m, 2H), 3.97 (s, 3H), 4.27 (m, 2H), 6.99 (t, J = 5.62 Hz, 1H), 7.23 (dd, J = 2.68, 9.03 Hz , 1H), 7.38 (d, J = 9.03 Hz, 1H), 7.47 (d, J = 2.68 Hz, 1H), 7.54 (s, 1H), 8.05 (s, 1H), 8.20 (d, J = 9.03 Hz , 1H), 8.55 (s, 1H) Mass analysis, found (ESI-MS, m / z): 461 (M? L) Example 122: N- (2-chloro-4- { [7- ( 2-hydroxyethoxy) -6-methoxy-4-quinazolinyl] oxy} phenyl) -N'-propylurea N- was dissolved. { 2-Chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl} -N-propylurea (50 mg), potassium carbonate (30 mg), and ethylene bromide (44 μl) in N, N-dimethylformamide (4 ml), and the solution was stirred at room temperature for 3 hours. The solvent was removed by distillation under reduced pressure. Water was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / methanol to provide 12 mg (yield: 22%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 0.91 (t, J = 7.44 Hz, 3 H), 1.42 -1.49 (m, 2 H), 3.06 - 3.11 (m, 2 H), 3.80 - 3.83 (m, 2 H), 3.98 (s, 3H), 4.22 (t, J = 4.64 Hz, 2H), 4.98 (t, J = 5.37 Hz, 1H), 6.99 (t, J = 5.37 Hz, 1H), 7.33 (dd, J = 2.69 Hz, 9.03 Hz, 1H), 7.39 (s, 1H), 7.48 (d, J = 2.68 Hz, 1H), 7.55 (s, 1H), 8.05 (s, 1H), 8.19 (d, J = 9.27 Hz, 1H), 8.55 (s, 1H) Mass analysis, found (ESI-MS, m / z): 447 (M ++ l) Example 123: N- (2-chloro-4- { [6-methoxy -7- (4-pyridylmethoxy) -4-quinazolinyl] oxy} phenyl) -N'-propylurea An initial compound N- [2-chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl} -N'-propylurea (80 mg), potassium carbonate (138 mg), and 4-chloromethylpyridine hydrochloride (41 mg) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at a temperature of 80 ° C for 3 hours. Water was added to the reaction mixture, followed by extraction with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by HPLC to give 65 mg (yield: 66%) of the title compound. ^ -NMR (CDC13, 400 MHz): d 0.96 (t, J = 7.6 Hz, 3H), 1.53-1.64 (m, 2H), 3.25 (dd, J = 7.3 Hz, 12.9 Hz, 2H), 4.07 (s) , 3H), 5.32 (s, 2H), 6.66 (s, 1H), 7.14 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.27 (s, 1H), 7.29 (d, J = 2.7 Hz, 1H), 7.41 (d, J = 5.9 Hz, 2H), 7.54 (s, 1H), 8.24 (d, J = 9.0 Hz, 1H), 8.59 (s, 1H), 8.63 (d, J = 6.1 Hz, 2H) Mass analysis, found (ESI-MS, m / z): 494 (M? L) Example 124: N- [2-chloro-4- ((6-methoxy-7- [(5-morpholinopentyl ) oxy] -4-quinazolinyl.} oxy) phenyl] -N'-propylurea N-. {2-Chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl was dissolved} - N'-propylurea (70 mg), potassium carbonate (30 mg), and pentamethylene bromide (80 μl) in N, N-dimethylformamide (5 ml) and the solution was stirred at room temperature for 3 hours. The solvent was removed by distillation under reduced pressure, water was added to the residue, and the mixture was extracted with chloroform.The organic layer was dried in anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. with ether to give 43 mg (yield: 46%) of N- [4- (. {7- (5-bromopentyl) oxy] -6-methoxy-4-quinazolinyl) -oxy] -2-chlorophenyl] -N'-propylurea as intermediate: the intermediate product (43 mg), potassium carbonate (30 mg), and morpholine (70 μl) were dissolved in N, N-dimethylformamide (4 ml), and the solution was stirred at room temperature overnight. The solvent was removed by distillation under reduced pressure. A saturated aqueous solution of sodium hydrogencarbonate was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by development with chloroform / methanol to provide 30 mg (yield: 68%) of the title compound. XH-NMR (CDC13, 400 MHz): d 1.71 (t, J = 7.32 Hz, 3H), 2.28 (t, J = 7.20 Hz, 2H), 2.63 (, 2H), 3.08 - 3.14 (m, 5H), 3.29 -3.30 (m, 5H), 3.47 (bs, 1H), 3.73 (m, 1H), 3.86 - 3.90 (m, 2H), 4.36 (t, J = 4.65 Hz, 3H), 4.46 (t, J = 4.76 Hz, 1H), 4.77 (s, 1H), 4.99 (t, J = 6.34 Hz, 2H), 7.80 (m, 1H), 8.02 (dd, J = 2.68 Hz, 9.27 Hz, 1H), 8.18 (s) , 1H), 8.27 (d, J = 2.68 Hz, 1H), 8.34 (s, 1H), 8.85 (s, 1H), 9.00 (d, J = 9.03 Hz, 1H), 9.35 (s, 1H) Analysis of mass, found (ESI-MS, m / z): 559 (M ++ 1) Example 125: N- (2-chloro-4- [(6-methoxy-7 ~. [5- (1H-1) , 2, 3-triazol-1-yl) pentyl] oxy.} -4-quinazolinyl) oxy] phenyl.} - N '-propylurea Triazole (0.41 ml), l-bromo-5-chloropentane (1.0 ml), tetrabutylammonium iodide (10 mg), and a 3 M aqueous solution of sodium hydroxide (1 ml) in acetone (10 ml), and the solution was stirred at a temperature of 50 ° C for 18 hours. water to the reaction mixture, and the mixture was extracted with chloroform. nica was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by flash chromatography with chloroform to give an intermediate product (390 mg). An initial compound (N- [2-chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl} -. N'-propylurea (80 mg), potassium carbonate (138 mg) , and the previous intermediate (52 mg) were dissolved in N, N-dimethylformamide (1 ml) and the solution was stirred at a temperature of 120 ° C for 5 hours.Water was added to the reaction mixture, and the The mixture was extracted with chloroform-propanol (3/1), the organic layer was dried over anhydrous sodium sulfate, the solvent was removed by distillation under reduced pressure, the residue was purified by HPLC to give 41 mg (yield: 38%). of the title compound? t-NMR (CDCls, 400 MHz): d 0.96 (t, J = 7.6 Hz, 3H), 1.50 - 1.65 (m, 4H), 1.90 - 2.08 (m, 4H), 3.24 (dd) , J = 7.1 Hz, 12.8 Hz, 2H), 4.01 (s, 3H), 4.17 (t, J = 6.6 Hz, 2H), 4.44 (t, J = 7.3 Hz, 2H), 4.88 - 4.94 (, 1H), 6.32 (s, 1H), 7.14 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.25 (s, 1H), 7.29 (d, J = 2.7 Hz, 1H), 7.48 (s, 1H), 7.55 (s, 1H), 7.70 (s, 1H), 8.23 (d, J = 9.0 Hz, 1H), 8.58 (s, 1H) Mass analysis, found (ESI-MS, m / z): 540 (M? L) Example 126: N '- (2-chloro-4- { [6-methoxy-7- (4-pyridylmethoxy) -4-quinazolinyl] oxy} phenyl) -N, N-diethylurea A starting compound (N '-. {2-chloro-4- [(7 -hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl.} - N, N, -diethylurea, (83 mg), potassium carbonate (138 mg), and 4-chloromethylpyridine hydrochloride (49 mg) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours.Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic was dried over anhydrous sodium sulfate, the solvent was removed by distillation under reduced pressure, the residue was purified by HPLC to give 57 mg (yield: 56%) of the title compound.1H-NMR (CDC13, 400 MHz): d 1.26 (t, J = 7.3 Hz, 6H), 3.41 (q, J = 7. 1 Hz, 4H), 4.08 (s, 3H), 5.32 (s, 2H), 6.98 (s, 1H), 7.14 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.27 (s, 1H), 7.29 (d, J = 2.7 Hz, 1H), 7.41 (d, J = 5.9 Hz, 2H), 7.55 (s, 1H), 8.37 (d, J = 9.0 Hz, 1H), 8.58 (s, 1H), 8.63 (d, J = 5.9 Hz, 2H) Mass analysis, found (ESI-MS, m / z): 508 (M ++ l) Example 127: N- (2-Chloro-4 { [6-methoxy-7- (4-morpholinobutoxy) -4-quinazolinyl] oxy} phenyl) -N'-propylurea N- was dissolved. { 2-Chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl} -N'-propylurea (70 mg), potassium carbonate (30 mg), and pentamethylene bromide (80 μl) in N, N-dimethylformamide (5 ml) and the solution was stirred at room temperature for 3 hours. The solvent was removed by distillation under reduced pressure. Water was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure.

The residue was washed with ether to provide 43 mg (yield: 46%) of N- (4- { [7- (4-bromobutoxy) -6-methoxy-4-quinazolinyl] -oxi.} -2-chlorophenyl) -N'-propylurea in the form of intermediate product. The intermediate product (43 mg), potassium carbonate (30 mg), and morpholine (40 μl) were dissolved in N, N-dimethylformamide (4 ml), and the solution was stirred at room temperature overnight. The solvent was removed by distillation under reduced pressure. A saturated aqueous solution of sodium hydrogencarbonate was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / methanol to provide 23 mg (yield: 53%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 0.99 (t, J = 7.32 Hz, 3H), 1.56-1.62 (, 13H), 2.00-2.08 (m, 2H), 3.26-3.28 (m, 2H), 4.04 (s, 1H), 4.24 (m, 2H), 4.72 - 4.77 (m, 1H), 6.65 (s, 1H), 6.99 (s, 1H), 7.19 - 7.26 (m, 1H), 7.30 (s, 1H) ), 7.32 - 7.34 (m, 1H), 7.51 (s, 1H), 8.25 (d, J = 9.03 Hz, 1H), 8.61 (s, 1H) Mass analysis, found (ESI-MS, m / z) : 545 (M ++ l) Example 128: N- [2-chloro-4- (. {6-methoxy-7- [2- (4-methylpiperazino) ethoxy] -4-quinazolinyl}. Oxy) phenyl ] -N'-propylurea N- [2-Chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl was dissolved} -N'-propylurea (60 mg), potassium carbonate (30 mg), and 1,2-dibromoethane (70 μl) in N, N-di-ethylformamide (4 ml), and the solution was stirred at room temperature for 3 hours. hours. The solvent was removed by distillation under reduced pressure. Water was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 46 mg (yield: 62%) of N- (4- { [7- (2-bromoethoxy) -6-methoxy-4-quinazolinyl] -oxi.} -2-chlorophenyl) -N'-propylurea in the form of an intermediate product The intermediate product (46 mg), potassium carbonate (20 mg), and N-methylpiperazine (50 μl) were dissolved in N, N-dimethylformamide (3 ml), and the solution was stirred at room temperature overnight. The solvent was removed by distillation under reduced pressure. A saturated aqueous solution of sodium hydrogencarbonate was added to the residue and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / methanol to provide 24 mg (yield: 50%) of the title compound. XH-NMR (CDC13, 400 MHz): d 0.99 (t, J = 7.32 Hz, 3H), 1.61 -1.64 (m, 2H), 2.75 (m, 2H), 3.00-3.36 (m, 4H), 3.25- 3.16 (m, 4H), 3.25 - 3.29 (m, 2H), 4.02 (s, 3H), 4.27 - 7.35 (m, 2H), 4.78 - 4.83 (m, 2H), 5.33 (s, 3H), 6.69 ( s, 1H), 7.17 (dd, J = 2.68 Hz, 9.03 Hz, 1H), 7.31 (s, 1H), 7.49 (s, 1H), 8.26 (d, J = 9.27 Hz, 1H), 8.59 (s, 1H) Mass analysis, found (ESI-MS, m / z) : 530 (M? L) Example 129: N- [2-chloro-4- [(7- { 2- [(2-hydroxyethyl) - (methyl) amino] ethoxy.} - 6-methoxy-4 -quinazolinyl) oxy] -phenyl} -N'-propylurea N- was dissolved. { 2-Chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl} -N'-propylurea (65 mg), potassium carbonate (30 mg), and 1,2-dibromoethane (30 μl) in N, N-dimethylformamide (4 ml), and the solution was stirred at room temperature for 3 hours . The solvent was removed by distillation under reduced pressure. Water was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 36 mg (yield: 45%) of N- (4- { [7- (2-bromoethoxy) -6-methoxy-4-quinazolinyl] -oxi.} -2- chlorophenyl) -N'-propylurea in the form of an intermediate product. The intermediate product (36 mg), potassium carbonate (30 mg), and N-methylethanolamine (30 μl) were dissolved in N, N-dimethylformamide (3 ml), and the solution was stirred at room temperature overnight. The solvent was removed by distillation under reduced pressure. A saturated aqueous solution of sodium hydrogencarbonate was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / methanol to provide 21 mg (yield: 55%) of the title compound. 1 H-NMR (CDC1, 400 MHz): d 0.98 (t, J = 7.32 Hz, 3 H), 1.59 (m, 2 H) 1.94 (bs, 1 H), 3.23 (m, 2 H), 4.03 (s, 3 H), 4.04 - 4.15 (m, 4H), 4.76 (m, 4H), 5.35 (s, 3H), 7.10 - 7.17 (m, 1H), 7.28 (s, 3H), 7.40 (s, 1H), 7.54 (s, 1H), 8.37 (d, J = 9.03 Hz, 1H), 8.64 (s, 1H) Mass analysis, found (ESI-MS, m / z): 504 (M ++ 1) Example 130: N- [2 -chloro-4- ([6-methoxy-7- [3- (4-methylpiperazino) propoxy] -4-quinazolinyl}. oxy) phenyl] -N'-propylurea N- was dissolved. { 2-Chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl} -NF-propylurea (75 g), potassium carbonate (30 mg), and 1,3-dibromopropane (75 μl) in N, N-dimethylformamide (4 ml) and the solution was stirred at room temperature for 3 hours. The solvent was removed by distillation under reduced pressure. Water was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 50 mg (yield: 52%) of N- (4- { [7- (3-bromopropoxy) -6-methoxy-4-quinazolinyl] -oxi.} -2- chlorophenyl) -N'-propylurea in the form of an intermediate product. The intermediate product (30 mg), potassium carbonate (20 mg), and N-methylpiperazine (40 μl) were dissolved in N, N-dimethylformamide (3 ml), and the solution was stirred at room temperature overnight. The solvent was removed by distillation under reduced pressure. A saturated aqueous solution of sodium hydrogencarbonate was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / methanol to give 20 mg (yield: 63%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 0.99 (t, J = 7.32 Hz, 3H), 1.58 -1.62 (m, 2H), 2.25-2.50 (m, 3H), 2.70-2.85 (m, 3H), 2.92 - 2.98 (m, 3H), 3.25 (m, 2H), 4.04 (s, 3H), 4.25 (m, 2H), 4.83 (m, 3H), 5.34 (s, 3H), 6.70 (s, 1H) , 7.21 (dd, J = 2.68 Hz, 9.03 Hz, 1H), 7.26 (s, 2H), 7.31 (s, 1H), 7.49 (s, 1H), 8.18 (d, J = 9.27 Hz, 1H), 8.59 (s, 1H) Mass analysis, found (ESI-MS, m / z): 544 (M ++ l) Example 131: N '- [2-chloro-4- (. {6-methoxy-7- [2- (1H-1, 2, 3-triazol-1-yl) ethoxy] -4-quinazolinyl} oxy) phenyl] -N, N-diethylurea An initial compound (N '- [2-chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl} - N, N-diethylurea (83 mg), potassium carbonate (138 mg), and 2- (lH-1, 2,3-triazol-1-yl) ethyl 4-methyl-1-benzenesulfonate (59 mg) were dissolved in N, N -dimethylformamide (1 ml), and the solution was stirred at a temperature of 80 ° C for 18 hours.Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic was dried in anhydrous sodium sulfate, the solvent was removed by distillation under reduced pressure, the residue was washed with ether to provide an intermediate product, triphosgene (90 mg) was added to a solution of the intermediate product and triethylamine (0.027 ml). ) in chloroform (1 ml) at a temperature of 0 ° C, and the mixture was stirred for 30 minutes.The reaction mixture was cooled to 0 ° C, and then diethylamine (0.044 ml) was added dropwise to the mixture of the reaction e The temperature of the mixture was raised to room temperature over a period of 2 hours. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction mixture, followed by extraction with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by HPLC to give 30 mg (yield: 29%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 1.26 (t, J = 7.1 Hz, 6H), 3.41 (q, J = 7.1 Hz, 4H), 4.03 (s, 3H), 4.53 (t, J = 4.9 Hz , 2H), 4.94 (t, J = 5.1 Hz, 2H), 6.98 (s, 1H), 7.13 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.26 (s, 1H), 7.73 (s, 1H) ), 7.94 (s, 1H), 8.38 (d, J = 9.0 Hz, 1H), 8.60 (s, 1H) Example 132: 3-. { [4- (3-chloro-4-. {[[(Diethylamino) -carbonyl] amino] phenoxy) -6-methoxy-7-quinazolinyl] oxy} -propyl-N, -diethylcarbamate An initial compound (N '- {2-chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl.} - N, N-diethylurea ( 83 mg), potassium carbonate (138 mg), and 3-bromo-l-propanol (0.027 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at a temperature of 80 ° C for 18 hours Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1) The organic layer was dried over anhydrous sodium sulfate The solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide an intermediate product, Triphosgene (90 mg) was added to a solution of the intermediate product and triethylamine (0.027 ml) in chloroform (1 ml) at a temperature of 0 ° C, and the mixture was stirred for 30 minutes The reaction mixture was cooled to a temperature of 0 ° C, and diethylamine (0.044 ml) was then added dropwise to the cooled reaction mixture. The mixture was elevated at room temperature for a period of 2 hours. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction mixture and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by HPLC to provide 19 mg (yield: 17%) of the title compound.XH-NMR (CDC13, 400 MHz): d 1.04 (t, J = 7.1 Hz, 6H), 1.22 (t, J = 7.3 Hz, 6H), 3.09 (q, J = 7.1 Hz, 4H), 3.36 (q, J = 7.1 Hz, 4H), 3.75 (t, J = 6.3 Hz, 2H), 3.97 (s, 3H), 4.29 (t, J = 6.1 Hz, 2H), 6.93 (s, 1H), 7.10 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.24 (d, J = 2.7 Hz, 1H), 7.27 (s, 1H), 7.45 (s, 1H), 8.33 (d, J = 9.3 Hz, 1H), 8.55 (S, 1H) Example 133: N- [2-chloro-4- (. {6-methoxy-7- [3- (4-pyridylthio) propoxy] -4-quinazolinyl}. Oxy) phenyl] -N'-propylurea An initial compound (N- (4- { [7- (3-bromopropoxy) -6-methoxy -4-quinazolinyl] oxy} -2-chlorophenyl) -N'-propylurea (80 mg), potassium carbonate (138 mg), and 4-mercaptopyridine (22 mg) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 3 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 60 mg (yield: 72%) of the title compound. ^ -H-NMR (CDC13, 400 MHz): d 0.91 (t, J = 7.6 Hz, 3H), 1.50 - 1.60 (m, 2H), 2.24 - 2.32 (m, 2H), 3.11 - 3.24 (m, 4H ), 3.99 (s, 3H), 4.25 (t, J = 5.9 Hz, 2H), 4.70 - 4.80 (m, 1H), 6.62 (s, 1H), 7.11 (dd, J = 2.7 Hz, 9.0 Hz, 1H) ), 7.11 - 7.16 (, 2H), 7.23 (s, 1H), 7.25 (d, J = 2.7 Hz, 1H), 7.45 (s, 1H), 8.19 (d, J = 9.0 Hz, 1H), 8.30 - 8.34 (m, 2H), 8.55 (s, 1H) Mass analysis, found (ESI-MS, m / z): 554 (M ++ 1) Example 134: N- [2-chloro-4- [(6 -methoxy-7- {3- [(1-methyl-lH-1, 2, 3, 4-tetrazol-5-yl) thio] propoxy.} -4-quinazolinyl) oxy] phenyl} -N'-propylurea An initial compound (N- (4 { [7- (3-bromopropoxy) -6-methoxy-4-quinazolinyl] oxy} -2-chlorophenyl) -N'-propylurea (80 mg), potassium carbonate (138 mg), and 5-mercapto-l-tetrazole (23 mg) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 3 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1), the organic layer was dried over anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure. to give 71 mg (yield: 85%) of the title compound. ^ -H-NMR (CDC13, 400 MHz): d 0.91 (t, J = 7.3 Hz, 3H), 1.51-1.56 (, 2H), 2.39- 2.48 (m, 2H), 3.17 - 3.23 (m, 2H), 3.56 (t, J = 7.1 Hz, 2H), 3.86 (s, 3H), 3.97 (s, 3H), 4.27 (t, J = 5.9 Hz , 2H), 4.75 - 4.82 (m, 1H), 6.63 (s, 1H), 7.10 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.24 (d, J = 3.7 Hz, 1H), 7.44 (s) , 1H), 8.19 (d, J = 9.0 Hz, 1H), 8.55 (s, 1H) Mass analysis, found (ESI-MS, m / z): 559 (M ++ l) Example 135: N- (2-chloro-4-. { [6-methoxy-7- (3-piperidino-propoxy) -4-quinazolinyl] oxy} phenyl) -N-propylurea N-. { 2-Chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl} -N'-propylurea (500 mg), potassium carbonate (857 mg), and 1,3-dibromopropane (0.5 ml) were dissolved in N, N-dimethylformamide (5 ml), and the solution was stirred at room temperature for 3 hours. The solvent was removed by distillation under reduced pressure. Water was added to the residue, and the mixture was extracted with chloroform / 2-propanol (4/1). The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 451 mg (yield: 71%) of N- (4- {[7- (3-bromopropoxy) -6-methoxy-4-quinazolinyl] oxy} -2-chlorophenyl ) -N'-propylurea. N- (4- { [7- (3-bromopropoxy) -6-methoxy-4-quinazolinyl] oxy} -2-chlorophenyl) -N'-propylurea (70 mg), potassium carbonate (54 mg) ), and piperidine (39 μl) were dissolved in N, N-dimethylformamide (2 ml), and the solution was stirred at room temperature overnight. The solvent was removed by distillation under reduced pressure. A saturated aqueous solution of sodium hydrogencarbonate was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / methanol (20/1) to provide 35 mg (yield: 50%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 0.98 (t, J = 7.6 Hz, 3 H), 1.46 (br, 2 H), 1.54 - 1.66 (, 8 H), 2.15 (br, 2 H), 2.44 (br, 2 H) ), 2.55 (br, 2H), 3.20 - 3.30 (m, 2H), 4.04 (s, 3H), 4.27 (t, J = 6.6 Hz, 2H), 4.77 (t, J = 5.9 Hz, 1H), 6.65 (s, 1H), 7.17 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.32 (d, J = 2.7 Hz, 1H), 7.33 (s, 1H), 7.49 (s, 1H), 8.24 (d) , J = 9.0 Hz, 1H), 8.61 (s, 1H) Example 136: N- [2-chloro-4- (. {7-methoxy-6- [2- (4-methylpiperazino) ethoxy] -4- quinazolinyl.} oxy) phenyl] -N'-propylurea N-. { 2-Chloro-4- [(6-hydroxy-7-methoxy-4-quinazolinyl) oxy] phenyl} -N'-propylurea (500 mg), potassium carbonate (857 mg), and 1,3-dibromopropane (0.5 ml) were dissolved in N, N-dimethylformamide (5 ml), and the solution was stirred at room temperature for 3 hours. The solvent was removed by distillation under reduced pressure. Water was added to the residue, and the mixture was extracted with chloroform / 2-propanol (4/1). The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 451 mg (yield: 71%) of N- (4- {[6- (2-bromoethoxy) -7-methoxy-4-quinazolinyl] oxy} -2-chlorophenyl ) -N'-propylurea. N- (4- { [6- (2-bromoethoxy) -7-methoxy-4-quinazolinyl] oxy} -2-chlorophenyl) -N'-propylurea (50 mg), potassium carbonate (40 mg) ), and N-methylpiperazine (50 μl) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature overnight. The solvent was removed by distillation under reduced pressure. A saturated aqueous solution of sodium hydrogencarbonate was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / methanol to give 20 mg (yield: 44%) of the title compound. 1H-NMR (CDC13, 400 MHz): d 0.98 (t, J = 7.3 Hz, 3H), 1.56-1.65 (m, 2H), 1.77 (br, 4H), 2.31 (s, 3H), 2.53 (br, 2H), 2.71 (br, 2H), 2.97 (t, J = 6.1 Hz, 3H), 3.24 - 3.29 (, 2H), 4.04 (s, 3H), 4.32 (t, J = 6.1 Hz, 2H), 4.83 (br, 1H), 6.69 (s, 1H), 7.16 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.30 (s 1H), 7.31 (s, 1H), 7.55 (s, 1H), 8.25 ( d, J = 9.0 Hz, 1H), 8.62 (s, 1H) Mass analysis, found (ESI-MS, m / z): 529 (M ++ 1) Example 137: N- [2-chloro-4- ([7-methoxy-6- [3- (4-methyl-piperazino) propoxy] -4-quinazolinyl}. Oxy) phenyl] -N'-propylurea N- [2-Chloro-4- [(6-hydroxy-7-methoxy-4-quinazolinyl) oxy] phenyl was dissolved} -N'-propylurea (500 mg), potassium carbonate (857 mg), and 1,3-dibromopropane (0.5 ml) in N, N-dimethylformamide (5 ml), and the solution was stirred at room temperature for 3 hours . The solvent was removed by distillation under reduced pressure. Water was added to the residue, and the mixture was extracted with chloroform / 2-propanol (4/1). The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 451 mg (yield: 71%) of N- (4- {[6- (3-bromopropoxy) -7-methoxy-4-quinazolinyl] oxy} -2-chlorophenyl ) -N'-propylurea. N- (4- { [6- (3-bromopropoxy) -7-methoxy-4-quinazolinyl] oxy} -2-chlorophenyl) -N'-propylurea (50 mg), potassium carbonate (40 mg) ), and N-methylpiperazine (50 μl) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature overnight. The solvent was removed by distillation under reduced pressure. A saturated aqueous solution of sodium hydrogencarbonate was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / methanol to give 20 mg (yield: 44%) of the title compound. ^ - MR (CDC13, 400 MHz): d 0.98 (t, J = 7.6 Hz, 3H), 1.58 - 1.64 (m, 2H), 1.71 (br, 4H), 2.31 (s, 3H), 2.53 (br, 2H), 2.71 (br, 2H), 2.11 - 2.17 (m, 2H), 2.30 (s, 3H), 2.59 - 2.62 (, 2H), 3.24 - 3.29 (m, 2H), 4.04 (s, 3H), 4.26 (t, J = 6.6 Hz, 2H), 4.80 (br, 1H), 6.67 (s, 1H), 7.17 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.31 (s 1H), 7.31 (s) , 1H), 7.52 (s, 1H), 8.25 (d, J = 9.0 Hz, 1H), 8.61 (s, 1H) Mass analysis, found (ESI-MS, m / z): 543 (M? L) Example 138: N- (2-chloro-4- [[7-methoxy-6- (2-pyridyl-methoxy) -4-quinazolinyl] oxy} phenyl) -N'-propylurea An initial compound (N-. {2-Chloro-4- [(6-hydroxy-7-methoxy-4-quinazolinyl) oxy] phenyl} -N'-propylurea (80 mg), potassium carbonate (138 mg), and 2-hydrochloride. - (chloromethyl) pyridine (41 mg) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at a temperature of 120 ° C for 3 hours.Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1 The organic layer was dried in anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was washed with ethyl acetate to provide 54 mg (yield: 55%) of the title compound. ^ -H-NMR (CDC13, 400 MHz): d 0.91 (t, J = 7.6 Hz, 3H), 1.51 - 1.58 (m, 2H), 3.17 - 3.22 (, 2H), 4.02 (s, 3H), 4.69 (br, 1H), 5.36 (s, 2H), 6.57 (s, 1H), 7.08 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.21 - 7.29 (m, 2H), 7.53 - 7.55 (m, 2H), 7.66-7.71 (m, 1H), 8.15 (d, J = 9.0 Hz, 1H), 8.55 - 8.57 (m, 2H) Mass analysis, found (ESI-MS, m / z): 494 (M ~~ l) Example 139: N- (2-chloro-4- { [7-methoxy-6- (3-morpholino-propoxy) -4-quinazolinyl] oxy} phenyl) ~ N '-propylurea A starting compound (N- (4- { [6- (3-propoxy) -7-methoxy-4-quinazolinyl] oxy} -2-chlorophenyl) -N'-propylurea (54 mg), potassium carbonate (138 mg), and morpholine (0.017 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at a temperature of 120 ° C for 3 hours.Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1) .The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under pressure. n reduced. The residue was washed with ethyl acetate to provide 42 mg (yield: 77%) of the title compound. 1H-NMR (CDC13, 400 MHz): d 0.91 (t, J = 7.6 Hz, 3H), 1.47-1.59 (m, 4H), 1.88-2.00 (m, 2H), 2.35-2.48 (m, 4H), 3.20 (dd, J = J, 3 Hz, 12.9 Hz, 2H), 3.62 - 3.74 (m, 4H), 3.97 (s, 3H), 4.15 (t, J = 6.3 Hz, 2H), 4.74 - 4.80 (m, 1H), 6.63 (s, 1H), 7.09 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.24 (d, J = 2.7 Hz, 1H), 7.42 (s, 1H), 8.18 (d, J = 9.0 Hz, 1H), 8.54 (s, 1H) Mass analysis, found (ESI-MS, m / z): 530 (M? L) Example 140: N- [2-chloro-4- [(6- (3- (2-hydroxyethyl) - (methyl) amino] propoxy.} - 7-methoxy-4-quinazolinyl) oxy] phenyl} -N'-propylurea An initial compound (N- (4 { [6- (3-bromopropoxy) -7-methoxy-4-quinazolinyl] oxy} -2-chlorophenyl) -N'-propylurea (51 mg), potassium carbonate (68 mg), and 2- (methylamino) ethanol (15 mg) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at a temperature of 80 ° C for 3 hours Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1), the organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. was purified by HPLC by growth with chloroform / methanol to provide 25 mg (yield: 48%) of the title compound.1H-NMR (CDC13, 400 MHz): d 0.95 (t, J = 7.6 Hz, 3H), 1.53 - 1.62 (m, 2H), 2.08 - 2.15 (m, 2H), 2.30 (s, 3H), 2.58 (t, J = 5.4 Hz, 2H), 2.68 (t, J = 7.1 Hz, 2H), 3.21 - 3.26 (m, 2H), 3.60 (t, J = 5.4 Hz, 2H), 4.02 (s, 3H), 4.23 (t, J = 6.3 Hz, 2H), 5.06 (t, J = 5.6 Hz, 1H), 6.79 (s, 1H), 7.13 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.27 - 7.28 (m, 2H), 7.48 (s, 1H), 8.21 (d, J = 9.0 Hz, 1H), 8.58 (s, 1H) Example 141: N- (2-chloro-4- { [6-methoxy-7- (2-pyridyl-methoxy) -4-quinolyl] oxy} phenyl) -N'-propylurea An initial compound (N-. {2-chloro-4- [(7 -hydroxy-6-methoxy-4-quinolyl) oxy] phenyl.} - N'-propylurea (80 mg), potassium carbonate (138 mg), and 2-chloromethylpyridine hydrochloride (41 mg) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at a temperature of 80 ° C for 3 hours.Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, the solvent was removed by distillation under reduced pressure, the residue was purified by HPLC to give 81 mg (yield: 82%) of the title compound.1H-NR (CDCl3, 400 MHz) : d 0.97 (t, J = 7.6 Hz, 3H), 1.54 - 1.65 (m, 2H), 3.25 (dd, J = 7.1 Hz, 12.9 Hz, 2H), 4.05 (s, 3H), 4.75 - 4.82 (m , 1H), 5.42 (s, 2 H), 6.46 (d, J = 5.4 Hz, 1H), 6.67 (s, 1H), 7.08 (dd, J = 2.9 Hz, 9.0 Hz, 1H), 7.19 (d, J = 2.7 Hz, 1H), 7.44 (s, 1H), 7.53 (s, 1H), 7.56 (d, J = 7.8 Hz, 1H), 7.69 (dt, J = 2.0 Hz, 7.8 Hz, 1H), 8.25 (d, J = 9.0 Hz, 1H), 8.46 (d, J = 5.1 Hz, 1H), 8.61 (d, J = 4.6 Hz, 1H), Mass analysis, found (ESI-MS, m / z): 493 (M ++ l) Example 142: N- (2-chloro-4- { [6-methoxy-7- (3-pyridyl-methoxy) -4-quinolyl] oxy} phenyl) -N'-propylurea A starting compound (N- [2-Chloro-4- [(7-hydroxy-6-methoxy-4-quinolyl) oxy] phenyl] -. N'-propylurea (80 mg), potassium carbonate (138 mg), and hydrochloride of 3-chloromethylpyridine (41 mg) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at a temperature of 80 ° C for 3 hours.Water was added to the reaction mixture, and the mixture it was extracted with chloroform-propanol (3/1), the organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure, the residue was purified by HPLC to give 70 mg (yield: 71%). of the title compound.XH-NMR (CDC1 3, 400 MHz): d 0.97 (t, J = 7.3 Hz, 3H), 1.54 - 1.65 (, 2H), 3.25 (dd, J = 7.3 Hz, 12.9 Hz, 2H), 4.02 (s, 3H), 4.82 - 4.90 (m, 1H), 5.30 (s, 2H), 6.47 (d, J = 5.4 Hz, 1H), 6.72 (s, 1H), 7.09 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.19 (d, J = 2.7 Hz, 1H), 7.32 (dd, J = 4.9 Hz, 7.8 Hz, 1H), 7.47 (s, 1H), 7.52 (s, 1H), 7.84 (d, J = 7.8 Hz, 1H ), 8.26 (d, J = 9.3 Hz, 1H), 8.47 (d, J = 5.4 Hz, 1H), 8.48 (d, J = 3.2 Hz, 1H), 8.75 (s, 1H) Mass analysis, found ( ESI-MS, m / z): 493 (M ++ 1) Example 143: N- (2-chloro-4- { [6-methoxy-7- (4-pyridyl-methoxy) -4-quinolyl] oxy} phenyl) -N-p-propylurea An initial compound (N-. {2-chloro-4- [(7-hydroxy-6-methoxy-4-quinolyl) oxy] phenyl}. (80 mg), potassium carbonate (138 mg), and 4-chloromethylpyridine hydrochloride (41 mg) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at a temperature of 80 ° C for 3 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1), the organic layer was dried in anhydrous sodium sulfate and the solvent was removed by distillation. reduced pressure garlic. The residue was purified by HPLC to provide 71 mg (yield: 71%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 0.97 (t, J = 7.6 Hz, 3H), 1.54 - 1.65 (, 2H), 3.25 (dd, J = 7.1 Hz, 12.9 Hz, 2H), 4.05 (s, 3H), 4.86 - 4.92 (m, 1H), 5.32 (s, 2H), 6.48 (d, J = 4.7 Hz, 1H), 6.73 (s, 1H), 7.08 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.19 (d, J = 2.9 Hz, 1H), 7.38 (s, 1H), 7.41 (d, J = 6.1 Hz, 2H ), 7.54 (s, 1H), 8.26 (d, J = 9.0 Hz, 1H), 8.46 (d, J = 5.4 Hz, 1H), 8.61 (d, J = 6.1 Hz, 2H), Mass analysis, found (ESI-MS, m / z): 493 (M ++ 1) Example 144: N- (2-chloro-4- ([6-methoxy-7- (2-morpholinoethoxy) -4-quinolyl] oxy} phenyl) -N'-propylurea An initial compound (N-. {2-chloro-4- [(7-hydroxy-6-methoxy-4-quinolyl) oxy] phenyl}. N -propylurea (100 mg), potassium carbonate (172 mg), and 1,2-dibromoethane (0.086 mg) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 3 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide an intermediate product (N- (4 { [7- (2-bromoethoxy) -6-methoxy-4-quinolyl] oxy} -2-chlorophenyl) -N '- propylurea). The intermediate product, potassium carbonate (138 mg), and morpholine (0.17 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at a temperature of 80 ° C for 2 hours. Water was added to the reaction mixture and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / methanol to provide 70 mg (yield: 54%) of the title compound. ^? - MR (CDC13, 400 MHz): d 0.91 (t, J = 7.6 Hz, 3H), 1.50 - 1.59 (m, 2H), 2.57 (t, J = 4.6 Hz, 4H), 2.88 (t, J) = 5.9 Hz, 2H), 3.18 - 3.23 (m, 2H), 3.68 (t, J = 4.6 Hz, 4H), 3.94 (s, 3H), 4.26 (t, J = 5.9 Hz, 2H), 4.98 (t , J = 5.3 Hz, 2H), 6.41 (d, J = 5.3 Hz, 1H), 6.74 (br, 1H), 7.03 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.14 (d, J = 2.7 Hz, 1H), 7.34 (s, 1H), 7.43 (s, 1H), 8.42 (d, J = 5.1 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 515 (M ++ l) Example 145: N- [2-chloro-4- (. {6-methoxy-7- [2- (1 H-1,2,3-triazol-1-yl) ethoxy] -4-quinolyl} oxi) phenyl] -N'-propylurea An initial compound (N- {2-chloro-4- [(7-hydroxy-6-methoxy-4-quinolyl) oxy] phenyl}. (80 mg), potassium carbonate (138 mg), and 2- (lH-1, 2,3-triazol-1-yl) ethyl 4-methyl-1-benzenesulfonate (59 mg) were dissolved in N, N -dimethylformamide (1 ml), and the solution was stirred at a temperature of 120 ° C for 5 hours.Water was added to the reaction mixture, and the mixture was extracted with chlorofo rmo-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure. The residue was purified by HPLC by growth with chloroform-methanol to provide 92 mg (yield: 92%) of the title compound. 1H-NMR (CDC13, 400 MHz): 8 0.97 (t, J = 7.6 Hz, 3H), 1.57 - 1.63 (m, 2H), 3.23 - 3.28 (m, 2H), 4.01 (s, 3H), 4.52 (t, J = 5.1 Hz, 2H), 4.81 (br, 1H), 4.93 (t, J = 5.1 Hz, 2H), 6.47 (d, J = 5.4 Hz, 1H), 6.69 (s, 1H), 7.08 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.18 (d, J = 2.7 Hz, 1H), 7.37 (s, 1H), 7.51 (s, 1H), 7.72 (d, J = 1.0 Hz, 1H), 7.97 (d, J = 1. O Hz, 1H), 8.26 (d, J = 9.0 Hz, 1H), 8.48 (d, J = 5.4 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 497 (M ++ 1) Example 146: N- [2-chloro-4- ([7- [2- (lH-1 -imidazolyl) ethoxy] -6-methoxy-4-quinolyl.} oxy) phenyl] -N'-propylurea An initial compound (N-. {2-chloro-4- [(7-hydroxy-β-methoxy) 4-quinolyl) oxy] phenyl.} - N'-propylurea (80 mg), potassium carbonate (138 mg), and 2- (lH-1-imidazolyl) ethyl 4-methyl-1-benzenesulfonate (59 mg were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at a temperature of 120 ° C for 5 hours.Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol ( 3/1) .The organic layer was dried over anhydrous sodium sulfate.The solvent was removed by distillation under reduced pressure, and the residue was purified by HPLC by Development with chloroform / methanol to provide 81 mg (yield: 82%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 0.96 (t, J = 7.6 Hz, 3H), 1.50 - 1.65 (m, 2H), 1.90 - 2.08 (m, 2H), 3.24 (dd, J = 7.1 Hz, 12.9 Hz, 2H), 4.01 (s, 3H), 4.17 (t, J = 6.6 Hz, 2H), 4.44 (t, J = 7.3 Hz, 2H), 4.88 - 4.94 (m, 1H), 6.32 (s, 1H), 7.14 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.25 (s, 1H), 7.29 (d, J = 2.7 Hz, 1H), 7.48 (s, 1H), 7.55 (s, 1H), 7.70 (s, 1H), 8.23 (d, J = 9.0 Hz, 1H), 8.58 (s, 1H) Mass analysis, found (ESI-MS, m / z): 496 (M ++ 1) Example 147: N- (2-chloro-4- { [7- (3-hydroxypropoxy) -6-methoxy-4-quinolyl] oxy} phenyl) -N '-propylurea An initial compound (N- {2-chloro-4- [(7-hydroxy-6-methoxy-4-quinolyl) oxy] phenyl.}. -N'-propylurea (80 mg), carbonate of potassium (138 mg), and 3-bromo-l-propanol (0.027 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours. The reaction was then extracted with chloroform-propanol (3/1), the organic layer was dried over anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure, the residue was purified by HPLC by chloroform development. methanol to provide 94 mg (yield: 100%) of the title compound.1H-1MMR (CDC13, 400 MHz): d 0.92 (t, J = 7.6 Hz, 3H), 1.45 - 1.62 (m, 2H), 2.09 - 2.18 (m, 2H), 3.21 (dd, J = 7.1 Hz, 12.9 Hz, 2H), 3.87 (t, J = 5.6 Hz, 2H), 3.94 (s, 3H), 4.31 (t, J = 6.1 Hz, 2H), 4.81 - 4.87 (m, 1H), 6.42 (d, J = 5.1 Hz, 1H), 6.69 (s, 1H), 7.03 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.14 ( d, J = 2.7 Hz, 1H), 7.36 (s, 1H), 7.43 (s, 1H), 8.20 (d, J = 9.0 Hz, 1H), 8.42 (d, J = 5.4 Hz, 1H) Example 148: N- [2-chloro-4- (. {6-methoxy-7- [2- (4-methyl-piperazino) ethoxy] -4-quinolyl}. Oxy) phenyl] -N'-propylurea One starting compound (N- (4- { [7- (2-bromoethoxy) -6-methoxy-4-quinolyl] oxy} -2-chlorophenyl) -N'-propylurea (50 mg), potassium carbonate (138) mg), and 1-methylpiperazine (0.55 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours.Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1) The organic layer was dried over anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure The residue was washed with ether to provide 54 mg (yield: 100%) of the compound of the title 1H-NMR (CDC13, 400 MHz): d 0.92 (t, J = 7.3 Hz, 3H), 1.49 - 1.62 (m, 2H), 2.24 (s, 3H), 2.35 - 2.70 (m, 2H), 2.90 (t, J = 4.6 Hz, 2H), 3.21 (dd, J = 7.3 Hz, 12.9 Hz, 2H), 3.94 (s, 3H), 4.26 (t, J = 6.1 Hz, 2H), 4.75 - 4.85 (m, 1H), 6.41 (d, J = 5.1 Hz, 1H), 6.67 (s, 1H), 7.04 (dd, J = 2.7 Hz, 9.0 Hz , 1H), 7.14 (d, J = 2.7 Hz, 1H), 7.34 (s, 1H), 7.42 (s, 1H), 8.19 (d, J = 9.0 Hz, 1H), 8.42 (d, J = 5.1 Hz , 1H) Mass analysis, found (ESI-MS, m / z): 528 (M ++ l) Example 149: N- (2-chloro-4- { [7- (2-hydroxyethoxy) -6 -methoxy-4-quinolyl] oxy} phenyl) -N'-propylurea An initial compound (N- [2-chloro-4- [(7-hydroxy-6-methoxy-4-quinolyl) oxy] phenyl} .-N'-propylurea (80 mg), potassium carbonate (138 mg), and 2-bromoethanol (0.021 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1), the organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. residue was purified by HPLC by growth with chloroform / methanol to provide 80 mg (yield: 90%) of the title compound. 1H-NR (CDC13, 400 MHz): d 0.96 (t, J = 7.6 Hz, 3H), 1.54 - 1.65 (m, 2H), 3.25 (dd, J = 7.1 Hz, 12.9 Hz, 2H), 3.99 (s) , 3H), 4.07 (t, J = 4.4 Hz, 2H), 4.28 (t, J = 4.6 Hz, 2H), 6.46 (d, J = 5.4 Hz, 1H), 6.77 (d, J = 8.3 Hz, 1H ), 7.08 (s, 1H), 7.08 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.42 (s, 1H), 7.49 (s, 1H), 8.25 (d, J = 9.0 Hz, 1H), 8.48 (d, J = 2.9 Hz, 1H) Example 150: N-. { 2-Chloro-4- [(7- { 2- [(2-hydroxyethyl) - (methyl) amino] ethoxy.} - 6-methoxy-4-quinolyl) oxy] phenyl} -N'-propylurea An initial compound (N- (4 { [7- (2-bromoethoxy) -6-methoxy-4-quinolyl] oxy} -2-chlorophenyl) -N'-propylurea (50 mg), potassium carbonate (138 mg), and 2- (methylamino) ethanol (0.040 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours. The mixture was extracted with chloroform-propanol (3/1), the organic layer was dried over anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure. provide 53 mg (yield: 106%) of the title compound.XH-NMR (CDC13, 400 MHz): d 0.97 (t, J = 7.6 Hz, 3H), 1.54 - 1.65 (m, 2H), 2.42 (s, 3H), 2.69 (t, J = 5.1 Hz, 2H), 3.00 (t, J = 5.6 Hz, 2H), 3.26 (dd, J = 7.1 Hz, 12.7 Hz, 2H ), 3.64 (t, J = 5.1 Hz, 2H), 3.99 (s, 3H), 4.26 (t, J = 5.6 Hz, 2H), 4.66 - 4.69 (, 1H), 6.46 (d, J = 5.1 Hz, 1H), 6.70 (s, 1H), 7.09 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.19 (d, J = 2.7 Hz, 1H), 7.39 (s, 1H), 7.47 (s, 1H), 8.24 (d, J = 9.0 Hz, 1H), 8.47 (d, J = 5.1 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 503 (M? l) Example 151: N- (2-chloro-4- { [6-methoxy-7- (3-morpholinopropoxy) -4-quinolyl] oxy} phenyl) -N'-propylurea An initial compound (N- ( 4- { [7- (3-bromopropoxy) -6-methoxy-4-quinolyl] oxy} -2-chlorophenyl) -N'-propylurea (52 mg), potassium carbonate (138 mg), and morpholino (0.044 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 23 mg (yield: 44%) of the title compound. ^ • H-NMR (CDCl 3, 400 MHz): d 0.92 (t, J = 7.6 Hz, 3H), 1.49-1.60 (m, 2H), 2.02-2.11 (m, 2H), 2.40-2.47 (m, 4H) ), 2.52 (t, J = 7.1 Hz, 2H), 3.21 (dd, J = 7.1 Hz, 12.9 Hz, 2H), 3.62 - 3.69 (m, 4H), 3.95 (s, 3H), 4.20 (t, J) = 6.6 Hz, 2H), 4.70 - 4.78 (m, 1H), 6.41 (d, J = 5.1 Hz, 1H), 6.64 (s, 1H), 7.04 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.15 (d, J = 2.7 Hz, 1H), 7.37 (s, 1H), 7.43 (s, 1H), 8.20 (d, J = 9.0 Hz, 1H), 8.42 (d, J = 5.4 Hz, 1H) Example 152: N- [2-chloro-4- (6-methoxy-7-. {[3- (4-methyl-piperazino) propoxy] -4-quinolyl} oxy) phenyl] -N'-propylurea An initial compound (N- (4- { [7- (3-bromopropoxy) -6-methoxy-4-quinolyl] oxy} -2-cyclophenyl) -N'-propylurea (52 mg), carbonate of potassium (138 mg), and 1-methylpiperazine (0.055 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours.Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1), the organic layer was dried over anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure, the residue was washed with ether to give 41 mg (yield: 76%). ) of the title compound.1H-NMR (CDC13, 400 MHz): d 0.92 (t, J = 7.6 Hz, 3H), 1.49-1.64 (m, 2H), 2.02-2.10 (m, 2H), 2.23 (s) , 3H), 2.30 - 2.56 (m, 8H), 2.52 (t, J = 7.3 Hz, 2H), 3.20 (dd, J = 7.1 Hz, 12.9 Hz, 2H), 3.94 (s, 3H), 4.19 (t , J = 6.8 Hz, 2H) , 4.83 - 4.92 (m, 1H), 6.40 (d, J = 5.1 Hz, 1H), 6.69 (s, 1H), 7.03 (dd, J = 2.9 Hz, 9.3 Hz, 1H), 7.14 (d, J = 2.7 Hz, 1H), 7.35 (s, 1H), 7.42 (s, 1H), 8.19 (d, J = 9.0 Hz, 1H), 8.42 (d, J = 5.4 Hz, 1H) Mass analysis, found (ESI) -MS, m / z): 542 (M ++ 1) Example 153: N- [2-chloro-4- (6-methoxy-7-. { [3- (1H-1, 2, 3-triazol-1-yl) propoxy] -4-quinolyl} oxy) phenyl] -N'-propylurea Triazole (0.41 ml), l-bromo-3-chloropropane (0.79 ml), tetrabutylammonium iodide (10 mg), and a 3 M aqueous solution of sodium hydroxide (1 ml) were dissolved in acetone (10 ml), and the solution was stirred at a temperature of 50 ° C for 18 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by flash chromatography with chloroform to provide an intermediate product (327 mg). An initial compound (N- [2-chloro-4- [(7-hydroxy-6-methoxy-4-quinolyl) oxy] phenyl} -. N'-propylurea (80 mg), potassium carbonate (138 mg) , and the intermediate product (43 mg) were dissolved in N, N-dimethylformamide (1 ml) and the solution was stirred at a temperature of 80 ° C for 3 hours.Water was added to the reaction mixture, and the mixture It was extracted with chloroform-propanol (3/1), the organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure.The residue was purified by HPLC by development with chloroform / methanol to provide 54 mg. (yield: 52%) of the title compound. 1H-R (CDCl3, 400 MHz): d 0.97 (t, J = 7.6 Hz, 3H), 1.54 - 1.65 (m, 2H), 2.49 - 2.58 (m, 2H), 3.26 (dd, J = 7.1 Hz, 13.2 Hz, 2H), 4.01 (s, 3H), 4.15 (t, J = 5.9 Hz, 2H), 4.69 (t, J = 6.6 Hz, 2H), 4.90 - 5.00 (m, 1H), 6.46 (d, J = 5.1 Hz, 1H), 6.77 (s, 1H), 7.08 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.19 (d, J = 2.7 Hz, 1H), 7. 36 (s, 1H), 7.51 (s, 1H), 7.61 (s, 1H), 7.67 (s, 1H), 8.26 (d, J = 9.0 Hz, 1H), 8.47 (d, J = 5.4 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 511 (M ++ l) Example 154: N- [ 2-Chloro-4- ((7- [3- (lH-1-imidazolyl) -propoxy] -6-methoxy-4-quinolyl}. Oxy) phenyl] -N'-propylurea Imidazole (680 mg), l -bromo-3-chloropropane (0.79 ml), tetrabutylammonium iodide (10 mg), and a 3 M aqueous solution of sodium hydroxide (1 ml) were dissolved in acetone (10 ml), and the solution was stirred at a temperature 50 ° C for 18 hours Water was added to the reaction mixture, and the mixture was extracted with chloroform.The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. it was purified by chloroform development chromatography to give an intermediate (l- (3-chloropropyl) -lH-imidazole, 525 mg) An initial compound (N- [2-chloro-4- [(7-hydroxy-6) -methoxy-4-quinolyl) oxy] phenyl.} - N'-propylurea (80 mg), potassium carbonate (138 mg), and the intermediate product (42 mg) were dissolved in N, N-dimethylformamide (1 ml) and the solution was stirred at a temperature of 80 ° C for 3 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by HPLC by growth with chloroform / methanol to provide 23 mg (yield: 23%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 0.91 (t, J = 7.3 Hz, 3 H), 1.48 - 1.60 (m, 2 H), 2.27 - 2.36 (m, 2 H), 3.20 (dd, J = 6.8 Hz, 12.9 Hz, 2H), 3.97 (s, 3H), 4.06 (t, J = 5.9 Hz, 2H), 4.21 (t, J = 6.8 Hz, 2H), 6.39 (d, J = 5.4 Hz, 1H), 6.90 (s, 1H), 6.98 - 7.04 (m, 2H), 7.12 (d, J = 2.7 Hz, 1H), 7.30 (s, 1H), 7.44 - 7.48 (m, 2H), 8.22 (d, J = 9.0 Hz, 1H), 8.41 (d, J = 5.4 Hz, 1H) Example 155: N-. { 2-Chloro-4- [(7-. {2- [di (2-hydroxyethyl) -amino] ethoxy} - 6-methoxy-4-quinolyl) oxy] phenyl} -N'-propylurea An initial compound (N- (4 { [7- (2-bromoethoxy) -6-methoxy-4-quinolyl] oxy} -2-chlorophenyl) -N'-propylurea (50 mg), potassium carbonate (138 mg), and 1-methylpiperazine (0.055 ml) were dissolved in N, N-dimethylformamide (1 ml), and the mixture was stirred at room temperature for 18 hours. of the reaction, and the mixture was extracted with chloroform-propanol (3/1) .The organic layer was dried over anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure.The residue was washed with ether to provide 46 mg (yield: 92%) of the title compound.1H-NR (CDC13, 400 MHz): d 0.92 (t, J = 7.3 Hz, 3H), 1.50-1.60 (m, 2H), 2.74 (t, J = 4.9 Hz, 4H), 3.04 (t, J = 4.9 Hz, 2H), 3.15 - 3.24 (m, 2H), 3.60 (t, J = 5.1 Hz, 4H), 3.94 (s, 3H), 4.17 (t, J = 5.0 Hz, 2H), 6.41 (d, J = 5.4 Hz, 1H), 6.75 (s, 1H), 7.04 (dd, J = 2.4 Hz, 8.8 Hz, 1H), 7.14 (d, J = 2.7 Hz, 1H), 7.38 (s, 1H), 7.43 (s, 1H), 8.19 (d, J = 9.0 Hz, 1H), 8.42 (d, J = 5.4 Hz, 1H) Example 156: N- [2-chloro-4- [(7-. { 3- [di (2-hydroxyethyl) -amino] propoxy} -6-methoxy-4-quinolyl) oxy] phenyl} -N'-propylurea An initial compound (N- (4- { [7- (2-bromoethoxy) -6-methoxy-4-quinolyl] oxy} -2-chlorophenyl) -N'-propylurea (52 mg), potassium carbonate (138 mg), and diethanolamine (53 mg) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours. The reaction was then extracted with chloroform-propanol (3/1), the organic layer was dried over anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure, the residue was washed with ether to give 41 mg (yield 82%) of the title compound.1H-NMR (CDCl3, 400 MHz): d 0.89 (t, J = 7.3 Hz, 3H), 1.46-1.56 (m, 2H), 1.97-2.05 (m, 2H), 2.63 (t, J = 5.1 Hz, 4H), 2.69 (t, J = 6.1 Hz, 2H), 3.19 (dd, J = 7.1 Hz, 13.2 Hz, 2H), 3.60 (t, J = 4.9 Hz, 4H) , 3.94 (s, 3H), 4.32 (t, J = 5.9 Hz, 2H), 5.27 -5.35 (m, 1H), 6.37 (s, J = 5.4 Hz, 1H), 6.94 (s, 1H), 7.01 ( dd, J = 2.9 Hz, 9.0 Hz, 1H), 7.10 (d, J = 2 .7 Hz, 1H), 7.42 (s, 1H), 7.53 (s, 1H), 8.19 (d, J = 9.0 Hz, 1H), 8.35 (d, J = 5.4 Hz, 1H) Mass analysis, found ( ESI-MS, m / z): 547 (M ++ 1) Example 157: N-. { 2-Chloro-4- [(7- { 3- [(2-hydroxy-ethyl) (methyl) amino] propoxy.} - 6-methoxy-4-quinolyl) oxy] phenyl} -N'-propylurea An initial compound (N- (4- { [7- (2-bromopropoxy) -6-methoxy-4-quinolyl] oxy} -2-chlorophenyl) -N'-propylurea (52 mg), potassium carbonate (138 mg), and 2- (methylamino) ethanol (0.040 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours. The mixture was extracted with chloroform-propanol (3/1), the organic layer was dried over anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure. yield 51 mg (yield: 98%) of the title compound. -NMR (CDC13, 400 MHz): d 0.91 (t, J = 7.6 Hz, 3H)1.45 - 1.59 (m, 2H), 2.05 (t, J = 6.8 Hz, 2H), 2.24 (s, 3H), 2.51 (t, J = 5.1 Hz, 1H), 2.59 (t, J = 7.1 Hz, 2H), 3.20 (dd, J = 6.8 Hz, 12.9 Hz, 2H), 3.57 (t, J = 5.4 Hz, 2H), 3.95 (s, 3H), 4.22 (t, J = 6.3 Hz, 2H), 5.00 - 5.08 (m, 1H), 6.40 (d, J = 5.1 Hz, 1H), 6.79 (s, 1H), 7.03 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.13 (d, J = 2.7 Hz, 1H), 7.426 (s, 1H), 7.433 (s, 1H), 8.19 (d, J = 9.0 Hz, 1H), 8.40 (d, J = 5.4 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 517 (M ++ 1) Exe 158: N- [2-chloro-4- (. {6-methoxy-7- [4- (1H-1, 2, 3 -triazol-1-yl) butoxy] -4-quinolyl.} oxy) phenyl] -N'-propylurea Triazole (0.41 ml), l-bromo-4-chlorobutane (0.93 ml), tetrabutylammonium iodide (10 mg) , and a 3 M aqueous solution of sodium hydroxide (1 ml) were dissolved in acetone (10 ml), and the solution was stirred at a temperature of 50 ° C for 18 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by flash chromatography with chloroform to provide an intermediate product (1- (4-chlorobutyl) -1H-1,2,3-triazole, 314 mg). An initial compound (N- {2-chloro-4- [(7-hydroxy-6-methoxy-4-quinolyl) oxy] phenyl.} - N'-propylurea, 80 mg), potassium carbonate (138) mg), and the intermediate product (48 mg) were dissolved in N, N-dimethylformamide (1 ml) and the solution was stirred at a temperature of 80 ° C for 3 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by HPLC by growth with chloroform / methanol to provide 42 mg (yield: 40%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 0.96 (t, J = 7.3 Hz, 3 H), 1.54 - 1.65 (m, 2 H), 1.88 - 1.98 (m, 2 H), 2.14 - 2.24 (, 2 H), 3.26 (dd, J = 6.6 Hz, 13.2 Hz, 2H), 3.99 (s, 3H), 4.20 (t, J = 5.9 Hz, 2H), 4.55 (t, J = 7.1 Hz, 2H), 5.00 - 5.06 (m , 1H), 6.46 (d, J = 5.4 Hz, 1H), 6. "80 (s, 1H), 7.08 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.19 (d, J = 2.7 Hz, 1H), 7.37 (s, 1H), 7.49 (s, 1H), 7.68-7.72 (m, 2H), 8.26 (d, J = 9.0 Hz, 1H), 8.47 (d, J = 5.1 Hz, 1H) Analysis mass, found (ESI-MS, m / z): 525 (M ++ 1) Exe 159: N-. {2-chloro-4- [(6-methoxy-7- { [5- ( 1H-1, 2, 3-triazol-1-yl) pentyl] oxy.} -4-quinolyl) oxy] phenyl.} - N'-propylurea Triazole (0.41 ml), l-bromo-5-chloropentane ( 1.0 ml), tetrabutylammonium iodide (10 mg), and a 3 M aqueous solution of sodium hydroxide (1 ml) were dissolved in acetone (10 ml), and the solution was stirred at a temperature of 50 ° C for 18 hours Water was added to the reaction mixture, and the mixture was extracted with chloroform. ica was dried in anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by chloroform development chromatography to provide an intermediate (l- (5-chloropentyl H-1,2,3-triazole, 390 mg) An initial compound (N-. {2-chloro-4-) [(7-hydroxy-6-methoxy-4-quinolyl) oxy] phenyl] -N'-propylurea, 80 mg), potassium carbonate (138 mg), and the intermediate product (51 mg) were dissolved in N , N-dimethylformamide (1 ml) and the solution was stirred at a temperature of 80 ° C for 3 hours.Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure.The residue was purified by HPLC by growth with chloroform / methanol to provide 33 mg (yield: 31%) of the title compound. MR (CDC13, 400 MHz): d 0.92 (t, J = 7.6 Hz, 3H), 1.47 - 1.59 (, 2H), 1.85 - 2.03 (m, 4H), 3.21 (dd, J = 6.6 Hz, 13.2 Hz, 2H), 3.94 (s, 3H), 4.11 (t, J = 6.3 Hz, 2H), 4.38 (t, J = 7.1 Hz, 2H), 4.86 - 4.94 (m, 1H), 6.41 (d, J = 5.4 Hz, 1H), 6.71 (s, 1H), 7.03 (dd, J = 2.4 Hz, 9.0 Hz, 1H), 7.14 (d, J = 2.7 Hz, 1H), 7.31 (s, 1H), 7.43 (s, 1H), 7.51 (s, 1H), 7.64 (s, 1H), 8.20 (d, J = 9.0 Hz, 1H), 8.41 (d, J = 5.4 Hz, 1H) Mass analysis, found ( ESI-MS, m / z): 539 (M? L) Example 160: N- [2-chloro-4- (. {7- [4- (lH-1-imidazolyl) -butoxy] -6-methoxy -4-quinolyl.}. Oxy) phenyl] -N'-propylurea imidazole (680 mg), l-bromo-4-chlorobutane (0.93 ml), tetrabutylammonium iodide (10 mg), and a 3 M aqueous solution of hydroxide of sodium (1 ml) were dissolved in acetone (10 ml), and the solution was stirred at a temperature of 50 ° C for 18 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by flash chromatography with chloroform to provide an intermediate product (1- (4-chlorobutyl) -1H-imidazole, 756 mg). An initial compound (N- [2-chloro-4- [(7-hydroxy-6-methoxy-4-quinolyl) oxy] phenyl] -N'-propylurea, 80 mg), potassium carbonate (138 mg) , and the intermediate product (48 mg) were dissolved in N, N-dimethylformamide (1 ml) and the solution was stirred at a temperature of 80 ° C for 3 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by HPLC by growth with chloroform / methanol to provide 29 mg (yield: 28%) of the title compound. XH-NMR (CDC13, 400 MHz): d 0.96 (t, J = 7.3 Hz, 3H), 1.54 - 1.65 (m, 2H), 1.83 - 1.95 (, 2H), 1.98 - 2.08 (m, 2H), 3.25 (dd, J = 6.8 Hz, 12.7 Hz, 2H), 4.00 (s, 3H), 4.10 (t, J = 7.1 Hz, 2H), 4. 20 (t, J = 6 Hz, 2H), 5.08 - 5.16 (m, 1H), 6.46 (d, J = 5.1 Hz, 1H), 6.83 (s, 1H), 6.97 (s, 1H), 7.06 (s, 1H), 7.08 (dd, J = 2.9 Hz, 9.3 Hz, 1H), 7.18 (d, J = 2.7 Hz, 1H), 7.37 (s, 1H), 7.49 (s, 1H), 7.58 (s, 1H), 8.26 (d, J = 9.0 Hz, 1H), 8.46 (d, J = 5.4 Hz, 1H) Example 161: N- (2-Chloro-4. {[6-methoxy-7- (4-pyridyl-methoxy) -4-quinazolinyl] oxy} phenyl) -N '- (2,4-difluoro-phenyl) urea An initial compound (N '- {2-Chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl.} - N' - (2,4-difluoro-phenyl) urea, 80 mg) potassium carbonate (138 mg), and 4-chloromethylpyridine hydrochloride (41 mg) were dissolved in N, N-dimethylformamide (1 ml) and the solution was stirred at room temperature for 18 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 50 mg (yield: 52%) of the title compound. 1 H-NR (CDC13, 400 MHz): d 4.03 (s, 3 H), 5.46 (s, 2 H), 7.03 -7.11 (m, 1 H), 7.28 - 7.38 (m, 1 H), 7.47 (s, 1 H), 7.50 (d, J = 5.9 Hz, 2H), 7.56 (d, J = 2.7 Hz, 1H), 7.61 (s, 1H), 7.95 (s, 1H), 8.09 - 8.18 (, 1H), 8.19 (d, J = 9.0 Hz, 1H), 8.57 (s, 1H), 8.63 (d, J = 5.9 Hz, 2H), 8.81 (s, 1H), 9.30 (s, 1H) Example 162: N- (2-chloro- 4- { [6-methoxy-7- (2-morpholino-ethoxy) -4-quinazolinyl] oxy} phenyl) -N '- (2,4-difluoro-phenyl) -urea An initial compound (N '- {2-Chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl} -. N' - (2,4-difluoro-phenyl) urea, 100 mg), Potassium carbonate (857 mg), and 1,2-dibromoethane (0.085 ml) were dissolved in N, N-dimethylformamide (1 ml) and the solution was stirred at room temperature for 18 hours. Water was added to the reaction mixture and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide an intermediate product (N- (4 { [7- (2-bromoethoxy) -6-methoxy-4-quinazolinyl] oxy} -2-chlorophenyl) -N '- (2,4-difluorophenyl) urea). The intermediate product, potassium carbonate (138 mg), and morpholine (0.05 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by HPLC by growth with chloroform / methanol to provide 57 mg (yield: 46%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 2.54-2.63 (m, 4H), 2.85-2.94 (, 2H), 3.66-3.73 (m, 4H), 3.97 (s, 3H), 4.25-4.32 (, 2H) ), 6.77 - 6.88 (m, 2H), 7.09 (s, 1H), 7.14 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.257 (s, 1H), 7.264 (s, 1H), 7.44 (s) , 1H), 7.90 - 7.99 (m, 1H), 8.22 (d, J = 9.0 Hz, 1H), 8.56 (s, 1H) Mass analysis, found (ESI-MS, m / z): 586 (M + + l) Example 163: N- (2-chloro-4- { [6-methoxy-7- (3-morpholino-propoxy) -4-quinazolinyl] oxy} phenyl) -N '- (2, 4-difluoro-phenyl) -urea An initial compound (N- (4 { [7- (3-bromopropoxy) -6-methoxy-4-quinazolinyl] oxy} -2-chlorophenyl) -N '- (2,4-difluorophenyl) urea, 59 mg), potassium carbonate (857 mg), and morpholine (0.043 ml) were dissolved in N, N-dimethylformamide (1 ml) and the solution was stirred at room temperature for 18 hours . Water was added to the reaction mixture and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 53 mg (yield: 89%) of the title compound. 1H-NMR (CDC13, 400 MHz): d 2.06 - 2.16 (m, 2H), 2.43 - 2.57 (m, 4H), 2.56 (t, J = 6.8 Hz, 2H), 3.68 - 3.75 (m, 4H), 4.03 (s, 3H ), 4.27 (t, J = 6.6 Hz, 2H), 6.79 - 6.91 (m, 2H), 7.14 (s, 1H), 7.19 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.28 (s, 1H) ), 7.29 (d, J = 9.0 Hz, 1H), 7.33 (s, 1H), 7.49 (s, 1H), 8.26 (d, J = 9.0 Hz ", 1H), 8.61 (s, 1H) Mass analysis , found (ESI-MS, m / z): 600 (M? l) Example 164: N- [2-chloro-4- (. {6-methoxy-7- [3- (4-methyl-piperazino) propoxy] -4-quinazolinyl.}. oxy) phenyl] -N '- (2,4-difluoro-phenyl) -urea An initial compound (N- (4- { [7- (3-bromopropoxy) -6) -methoxy-4-quinazolinyl] oxy} -2-chlorophenyl) -N '- (2,4-difluorophenyl) urea, 59 mg), potassium carbonate (138 mg), 1-methylpiperazine (0.055 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours.Water was added to the reaction mixture and the mixture was extracted with chloroform-propanol (3/1). it was dried in sulphate of anhydrous sodium, and the solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 58 mg (yield: 95%) of the title compound. ^ - MR (CDC13, 400 MHz): d 2.01 - 2.12 (m, 2H), 2.23 - 2.80 (s, 3H), 2.51 (t, J = 7.1 Hz, 2H), 3.97 (s, 3H), 4.20 ( t, J = 7.2 Hz, 2H), 6.73 - 6.87 (m, 2H), 7.13 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.24 (d, J = 2.7 Hz, 1H), 7.27 (s, 1H), 7.30 (s, 1H), 7.44 (s, 1H), 7.91 - 8.00 (, 2H), 8.21 (d, J = 9.0 Hz, 1H), 8.56 (s, 1H) Example 165: N- [2 -chloro-4- [(7- { 3- [(2-hydroxyethyl) - (methyl) amino] propoxy.} - 6-methoxy-4-quinazolinyl) oxy] phenyl} -N '- (2,4-difluorophenyl) -urea An initial compound (N- (4 { [7- (3-bromopropoxy) -6-methoxy-4-quinazolinyl] oxy} -2-chlorophenyl ) -N '- (2,4-difluorophenyl) urea, 59 mg), potassium carbonate (138 mg), and 2- (methylamino) ethanol (0.040 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours. Water was added to the reaction mixture and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 58 mg (yield: 100%) of the title compound. ^? - NMR (CDC13, 400 MHz): d 2.06 - 2.16 (m, 2H), 2.30 (s, 3H), 2.57 (t, J = 5.1 Hz, 2H), 2.65 (t, J = 6.8 Hz, 1H ), 3.63 (t, J = 5.4 Hz, 2H), 4.02 (s, 3H), 4.28 (t, J = 6.1 Hz, 2H), 6.79 -6.91 (m, 2H), 7.18 (dd, J = 2.7 Hz) , 9.0 Hz, 1H), 7.28 (d, J = 2.7 Hz, 1H), 7.37 (s, 1H), 7.48 (s, 1H), 7.96 - 8.06 (m, 2H), 8.26 (d, J = 9.0 Hz , 1H), 8.59 (s, 1H) Mass analysis, found (ESI-MS, m / z): 588 (M ++ 1) Example 166: N- [2-chloro-4- (. {6- methoxy-7- [2- (4-methyl-piperazino) ethoxy] -4-quinolyl.} oxy) phenyl] -N '- (2,4-difluorophenyl) -urea An initial compound (N- (4- { [7- (2-bromoethoxy) -6-methoxy-4-quinolyl] oxy} -2-chlorophenyl) -N '- (2,4-difluorophenyl) urea, 50 mg), potassium carbonate (138 mg), and 1-methylpiperazine (0.055 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours. Water was added to the reaction mixture and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 48 mg (yield: 93%) of the title compound. 1 H-NMR (CDCl 3, 400 MHz): d 2.31 (s, 3 H), 2.40 - 2.75 (, 8 H), 2.95 (t, J = 6.1 Hz, 2 H), 3.99 (s, 3 H), 4.31 (t, J = 5.9 Hz, 2H), 6.48 (d, J = 5.1 Hz, 1H), 6.85 - 6.96 (m, 3H), 7.12 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.15 (s, 1H), 7.22 (d, J = 2.7 Hz, 1H), 7.40 (s, 1H), 7.47 (s, 1H), 7.94 - 8.03 (m, 1H), 8.25 (d, J = 9.0 Hz, 1H), 8.49 (d , J = 5.1 Hz, 1H) Example 167: N-. { 2-Chloro-4- [(7- { 2- [(2-hydroxyethyl) - (methyl) amino] ethoxy.} - 6-methoxy-4-quinolyl) oxy] phenyl} -N '- (2,4-difluorophenyl) urea An initial compound (N- (4 { [7- (3-bromoethoxy) -6-methoxy-4-quinolyl] oxy} -2-chlorophenyl) -N '- (2,4-difluorophenyl) urea, 50 mg), potassium carbonate (138 mg), 2- (methylamino) ethanol (0.040 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours. Water was added to the reaction mixture and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 48 mg (yield: 97%) of the title compound. 1 H-NMR (CDCl 3, 400 MHz): d 2.44 (s, 3 H), 2.71 (t, J = 4.9 Hz, 2 H), 3.02 (t, J = 5.6 Hz, 4 H), 3.66 (t, J = 5.1 Hz , 2H), 3.97 (s, 3H), 4.27 (t, J = 5.6 Hz, 2H), 6.46 (d, J = 5.4 Hz, 1H), 6.80 -6.93 (m, 2H), 7.11 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.19 (d, J = 2.7 Hz, 1H), 7.45 (s, 1H), 7.96 - 8.04 (m, 1H), 8.25 (d, J = 9.0 Hz, 1H), 8.48 (d, J = 5.1 Hz, 1H) Example 168: N- (2-chloro-4- { [6-methoxy-7- [3-morpholino-propoxy) -4-quinolyl) oxy} phenyl) -N '- (2,4-difluorophenyl) -urea An initial compound (N- (4 { [7- (3-bromopropoxy) -6-methoxy-4-quinolyl] oxy} -2 -chlorophenyl) -N '- (2,4-difluorophenyl) urea, 50 mg), potassium carbonate (138 mg), and morpholine (0.044 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours. Water was added to the reaction mixture and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 32 mg (yield: 64%) of the title compound. ^ • H-NMR (CDC13, 400 MHz): d 2.06 - 2.16 (m, 2H), 2.43 - 2.51 (m, 4H), 2.56 (t, J = 7.3 Hz, 2H), 3.68 - 3.74 (m, 4H ), 4.00 (s, 3H), 4.25 (t, J = 6.6 Hz, 2H), 6.47 (d, J = 5.1 Hz, 1H), 6.84 - 6.93 (, 2H), 7.06 (s, 1H), 7.12 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.22 (d, J = 2.9 Hz, 1H), 7.42 (s, 1H), 7.47 ( s, 1H), 7.95 - 8.04 (m, 1H), 8.25 (d, J = 9.0 Hz, 1H), 8.48 (d, J = 5.4 Hz, 1H) Example 169: N- (2-chloro-4- { [6-methoxy -7- (3-pyridyl-methoxy) -4-quinolyl] oxy} phenyl) -N '- (2,4-difluorophenyl) -urea N- was dissolved. { 2-Chloro- (4- [(7-hydroxy-6-methoxy-4-quinolyl) oxy] phenyl} - N '- (2,4-difluorophenyl) urea (55 mg), potassium carbonate (31 mg ), and 3-picolyl chloride hydrochloride (22 mg) in N, N-dimethylformamide (1 ml), and the solution was stirred at 80 ° C for 1 hour.The solvent was removed by distillation under reduced pressure. A saturated aqueous solution of sodium hydrogencarbonate was added to the residue, and the mixture was extracted with chloroform.The chloroform layer was dried over anhydrous sodium sulfate.The solvent was removed by distillation under reduced pressure. yield 30 mg (yield: 48%) of the title compound.1H-NMR (CDC13, 400 MHz): d 4.03 (s, 3H), 5.31 (s, 2H), 6.49 (d, J = 5.4 Hz, 1H) , 6.77 - 6.88 (m, 2H), 7.10 - 7.16 (m, 2H), 7.31 - 7.35 (m, 1H), 7.48 (s, 1H), 7.54 (s, 1H), 7.86 (d, J = 7.8 Hz, 1H), 7.96 ( s, 1H), 8.03 - 8.10 (m, 1H), 8.32 (d, J = 9.0 Hz, 1H), 8.42 (s, 1H), 8.49 (d, J = 5.4 Hz, 1H), 8.59 (d, J = 3.9 Hz, 1H), 8.77 (s, 1H) Example 170: N- [2-chloro-4- (. {6-methoxy-7- [2- (1H-1, 2, 3-triazole-1 -yl) ethoxy] -4-quinolyl.} oxy) phenyl] -N '- (2,4-difluorophenyl) urea N- was dissolved. { 2-Chloro-4- [(7-hydroxy-6-methoxy-4-quinolyl) oxy] phenyl} -N '- (2,4-difluorophenyl) urea (55 mg), potassium carbonate (31 mg), and 4-methyl-1-benzenesulfonate of 2- (lH-1, 2,3-triazol-1-yl) ethyl) (36 mg) in N, N-dimethylformamide (1 ml), and the solution was stirred at a temperature for one hour. The solvent was removed by distillation under reduced pressure. A saturated aqueous solution of sodium hydrogencarbonate was added to the residue, and the mixture was extracted with chloroform. The chloroform layer was dried in anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 46 mg (yield: 72%) of the title compound. XH-NMR (CDC13, 400 MHz): d 4.02 (s, 3H), 4.53 (d, J = 4.9 Hz, 2H), 4.95 (d, J = 5.1 Hz, 2H), 6.47 (d, J = 5.1 Hz , 1H), 6.83 - 6.92 (m, 2H), 7.11 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.16 (d, J = 2.7 Hz, 1H), 7.39 (s, 1H), 7.52 (s, 1H), 7.58 (s, 1H), 7.70 (s, 1H), 7.76 (s, 1H), 8.00 (s, 1H), 8.01 - 8.07 (m, 1H), 8.29 (d, J = 9.0 Hz, 1H), 8.49 (d, J = 5.4 Hz, 1H) Example 171: N- (2-methoxy-4- { [6-methoxy-7- (3-morpholino-propoxy ) -4-quinazolinyl] oxy} phenyl) -N'-propylurea N-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] -2-methoxyphenyl} -N'-propylurea (100 mg), potassium carbonate (138 mg), and 1,3-dibromopropane (56 mg) were dissolved in N, N-dimethylformamide (5 ml) and the solution was stirred at room temperature for 3 hours. hours. The solvent was removed by distillation under reduced pressure. Water was added to the residue, and the mixture was extracted with chloroform / 2-propanol (4/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 53 mg (yield: 41%) of N- (4- [7- (3-bromopropoxy) -6-methoxy-4-quinazolinyl] oxy-2-methoxy-phenyl} - N'-propylurea N- (4- {[6- (3-bromopropoxy) -7-methoxy-4-quinazolinyl] oxy} -2-chlorophenyl} - N'-propylurea (50%) was dissolved. mg), potassium carbonate (60 mg), and N-methylpiperazine (100 μl) in N, N-dimethylformamide (2 ml), and the solution was stirred at room temperature for 16 hours.The solvent was removed by distillation under pressure A saturated aqueous solution of sodium hydrogencarbonate was added to the residue, and the mixture was extracted with chloroform.The organic layer was dried over anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure.The residue was purified by chromatography silica gel by development with chloroform / methanol to provide 22 mg (yield: 42%) of the title compound.1H-NMR (CDC13, 400 MHz): d 0.97 (t, J = 7.6 Hz, 3H), 1.56 - 1.60 (m, 2H), 2.14 (br, 2H), 2.50 (br, 4H), 2.58 (br, 2H), 3.23 -3.26 (m, 2H), 3.74 (br, 4H), 3.87 (s, 3H), 4.04 (s, 3H), 4.27-4.31 (m, 2H), 4.62-4.64 (m, 1H), 6.65 (s, 1H), 6.79-6.85 (m, 2H), 7.33 (s, 1H) , 7.53 (s, 1H), 8.10 (d, J = 8.5 Hz, 1H), 8.62 (s, 1H) Mass analysis, found (ESI-MS, m / z): 526 (M ++ l) Example 172 : N- (2, 4-Difluorophenyl) -N '- (2-methoxy-4-. { [6-methoxy-7- (3-morpholinopropoxy) -4-quinazolinyl] oxy} phenyl) urea N- (2,4-Difluorophenyl) -N '-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] -2-methoxyphenylurea (375 mg), potassium carbonate (442) was dissolved mg), and 1,3-dibromopropane (242 mg) in N, N-dimethylformamide (5 ml), and the solution was stirred at room temperature for 3 hours. The solvent was removed by distillation under reduced pressure. Water was added to the residue, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 210 mg (yield: 45%) of N- [4- [7- (3-bromopropoxy) -6-methoxy-4-quinazolinyl] oxy-2-methoxyphenyl} -N '- (2,4-difluoro-phenyl) urea. N- (4- {[6- (3-bromopropoxy) -7-methoxy-4-quinazolinyl] oxy} -2-chlorophenyl} -. N'-propylurea (130 mg), triethylamine ( 0.5 ml), and morpholine (0.5 ml) in N, N-dimethylformamide (4 ml), and the solution was stirred at room temperature for 18 hours.The solvent was removed by distillation under reduced pressure.A saturated aqueous hydrogencarbonate solution of Sodium was added to the residue, and the mixture was extracted with chloroform.The organic layer was dried in anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure.The residue was purified by chromatography on silica gel by development with chloroform methanol to provide 81 mg (yield: 62%) of the title compound. 1H-3SIMR (CDCl 3, 400 MHz): d 1.97 - 2.00 (m, 2H), 2.39 (br, 4H), 2.49 - 2.51 (m, 2H), 3.58 - 3.60 (m, 4H), 3.88 (s, 3H ), 3.98 (s, 3H), 4.25 (t, J = 6.3 Hz, 2H), 4.27 - 4.31 (m, 2H), 4.62 -4.64 (m, 1H), 6.84 (dd, J = 2.7 Hz, 8.8 Hz , 1H), 7.03 - 7.07 (m, 2H), 7.28 - 7.34 (m, 1H), 7.38 (s, 1H), 7.55 (s, 1H), 8.11 - 8717 (m, 2H), 8.55 (s, 1H), 8.74 (s, 1H), 9.18 (s) , 1H) Mass analysis, found (ESI-MS, m / z): 596 (M ++ 1) Example 173: N- (2-Methoxy-4- { [6-methoxy-7- (3- morpholino-propoxy) -4-quinolyl] oxy} phenyl) -N'-propylurea An initial compound (N-. {4 - [(7-hydroxy-6-methoxy-4-quinolyl) oxy] -2- methoxyphenyl.}. -N'-propylurea, 80 mg), potassium carbonate (138 mg), and 1,3-dibromopropane (0.10 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide an intermediate product. The intermediate product, potassium carbonate (138 mg), and morpholine (0.040 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by growth with chloroform / methanol to provide 74 mg (yield: 71%) of the title compound. 1H-HMR (CDC13, 400 MHz): d 0.95 (t, J = 7.6 Hz, 3H), 1.52 - 1.69 (m, 2H), 2.06 - 2.15 (m, 2H), 2.43 - 2.49 (m, 4H), 2.55 (t, J = 7.3 Hz, 2H), 3.23 (dd, J = 6.1 Hz, 12.9 Hz, 2H), 3.67 - 3.72 (m, 4H), 3.81 (s, 3H), 4.00 (s, 3H), 4.24 (t, J = 6.8 Hz, 2H), 6. 44 (d, J = 5.1 Hz, 1H), 6.68 (d, J = 2.4 Hz, 1H), 6.76 (dd, J = 2.4 Hz, 8.8 Hz, 1H), 7.40 (s, 1H), 7.53 (s, 1H), 8.12 (d, J = 8.8 Hz, 1H), 8.44 (d, J = 5.1 Hz, 1H) Example 174: N- (2-methoxy-4- { [6-methoxy-7- (4-pyridylmethoxy) -4-quinolyl ] oxy] phenyl) -N'-propylurea An initial compound (N-4- [(7-hydroxy-6-methoxy-4-quinolyl) oxy] -2-methoxyphenyl} - N'-propylurea, 80 mg), potassium carbonate (138 mg), and 4-chloromethylpyridine hydrochloride (48 mg) were dissolved in N, N-dimethylformamide (1 ml) and the solution was stirred at room temperature for 18 hours.

Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by HPLC by growth with chloroform / methanol to provide 65 mg (yield: 67%) of the title compound.

^ - MR (CDCI3, 400 MHz): d 0.95 (t, J = 7.3 Hz, 3H), 1.56 - 1.69 (, 2H), 3.24 (dd, J = 7.3 Hz, 12.9 Hz, 2H), 3.82 (s, 3H), 4.06 (s, 3H), 4.63 - 4.69 (, 1H), 5.32 (s, 2H), 6.46 (d, J = 5.4 Hz, 1H), 6.68 (d, J = 2.7 Hz, 1H), 6.77 (dd, J = 2.4 Hz, 8.5 Hz, 1H), 7.37 (s, 1H), 7.42 (d, J = 6.1 Hz, 2H), 7.59 (s, 1H), 8.14 (d, J = 8.5 Hz, 1H ), 8.43 (d, J = 5.4 Hz, 1H), 8.61 (d, J = 6.1 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 526 (M ++ l) Example 175: N-Ethyl-N '- (4- { [6-methoxy-7- (2-morpholino-ethoxy) -4-quinolyl] oxy} -2,5-dimethylphenyl) -urea An initial compound (N -ethyl-N '- { 4- [(7-hydroxy-6-methoxy-4-quinolyl) oxy] -2,5-dimethylphenyl} urea, 76 mg), potassium carbonate (138 mg), and 1,2-dibromoethane (0.085 ml) were dissolved in N, N-dimethylformamide (1 ml) and the solution was stirred at room temperature for 18 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was washed with ether to give an intermediate product (N- (4- {[7- (2-bromoethoxy) -6-methoxy-4-quinolyl] oxy} -2,5-dimethylphenyl) -N '-ethylurea). The intermediate product, potassium carbonate (138 mg), and morpholine (0.044 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by HPLC by growth with chloroform / methanol to provide 72 mg (yield: 73%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 1.10 (t, J = 7.3 Hz, 3H), 2.07 (s, 3H), 2.16 (s, 3H), 2.53-2.59 (m, 4H), 2.88 (t, J = 5.9 Hz, 2H), 3.20 - 3.30 (m, 2H), 3.66 - 3.71 (m, 4H), 3.96 (s, 3H), 4.26 (t, J = 5.9 Hz, 2H), 4.73 - 4.82 (m , 1H), 6.16 (s, 1H), 6.23 (d, J = 5.4 Hz, 1H), 6.88 (s, 1H), 7.35 (s, 1H), 7.40 (s, 1H), 7.50 (s, 1H) , 8.38 (d, J = 5.1 Hz, 1H) Example 176: N- [4- (. {6-methoxy-7- [3- (4-methylpiperazino) -propoxy] -2,5-dimethylphenyl] -N '-propylurea A "starting compound (N- {4- [(7-hydroxy-6-methoxy-4-quinolyl) oxy] -2,5-dimethylphenyl} - N'-propylurea, 80 mg), Potassium carbonate (138 mg), and 1,3-dibromopropane (0.10 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours. The reaction was then extracted with chloroform-propanol (3/1), the organic layer was dried in anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide an intermediate product (N- (4-. { [7- (3-Bromopropoxy) -6-methoxy-4-quinolyl] oxy} -2,5-dimethylphenyl) -N'-propylurea). The intermediate product, potassium carbonate (138 mg), and 1-methylpiperazine (0.055 ml) were dissolved in N, N-dimethylformamide (1 ml), and the mixture was stirred at room temperature for 18 hours. Water was added to the reaction mixture and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 33 mg (yield: 31%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 0.91 (t, J = 7.6 Hz, 3H), 1.50 - 1.58 (m, 2H), 2.07 - 2.20 (m, 2H), 2.12 (s, 3H), 2.23 ( s, 3H), 2.28 (s, 3H), 2.33 - 2.70 (m, 10H), 3.21 (dd, J = 7.3 Hz, 13.4 Hz, 2H), 4.00 (s, 3H), 4.24 (t, J = 6.6 Hz, 2H), 4.64 - 4.76 (m, 1H), 5.95 - 6.05 (m, 1H), 6.27 (d, J = 5.1 Hz, 1H), 6.95 (s 1H), 7.39 - 7.43 (m, 2H), 7.54 (s, 1H), 8.42 (d, J = 5.1 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 536 (M? L) Example 177: N- (2,4-Difluorophenyl) ) -N '- [4- ( {6-methoxy-7- [2- (1H-1, 2, 3-triazol-1-yl) ethoxy] -4-quinolyl.} Oxy] -2, 5-dimethylphenyl] urea An initial compound N- (2,4-Difluorophenyl) -N '-. { 4- [(7-Hydroxy-6-methoxy-4-quinolyl) oxy] -2,5-dimethylphenyl} urea, 93 mg), potassium carbonate (138 mg), and 2- (1 H-1,2,3-triazol-1-yl) ethyl 4-methyl-1-benzenesulfonate (52 mg) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at a temperature of 80 ° C for 5 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by HPLC by growth with chloroform / methanol to provide 33 mg (yield: 30%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 2.10 (s, 3 H), 2.19 (s, 3 H), 4.01 (s, 3 H), 4.51 (t, J = 4.9 Hz, 2 H), 4.93 (t, J = 5.4 Hz, 2H), 4.94 (s, 1H), 6.28 (d, J = 5.1 Hz, 1H), 6.75-6.88 (m, 2H), 6.90 (s, 1H), 7.36 (s, 1H), 7.58 ( s, 1H), 7.60 (s, 1H), 7.73 (s, 1H), 7.99 (s, 1H), 8.08 (dd, J = 9.3 Hz, 15.1 Hz, 1H), 8.41 (d, J = 5.1 Hz, 1H) Example 178: N '- (2-chloro-4- { [6-methoxy-7- (2-morpholino-ethoxy) -4-quinazolinyl] oxy} phenyl) -N, -dimethylurea A compound Initial (N '- [2-chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl] -. N, -dimethylurea, 80 mg), potassium carbonate (138 mg), and 1,2-dibromoethane (0.085 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide an intermediate product * "(N '- (4 { [7- (2-bromoethoxy) -6-methoxy-4-quinazolinyl] oxy} -2-chlorophenyl) - N, N-dimethylurea) The intermediate product, potassium carbonate (138 mg), and morpholine (0.043 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1), the organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. purified by HPLC by growth with chloroform / methanol to provide 72 mg (yield: 72%) of the title compound.1H-NR (CDC13, 400 MHz): d 2.58-2.66 (m, 4H), 2.90-2.98 (m, 2H), 3.08 (s, 6H), 3.70-3.79 (m, 4H), 4.02 (s, 3H), 4. 29 - 4.37 (m, 2H), 6.97 (s, 1H), 7.15 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.24 - 7.26 (m, 1H), 7.29 (s, 1H), 7.49 (s, 1H), 8.36 (d, J = 9.3 Hz, 1H), 8.60 (s, 1H) Mass analysis, found (ESI-MS, m / z): 502 (M? l) Example 179: N '- (2-chloro-4- { [6-methoxy-7- (4-morpholino-butoxy) -4- quinazolinyl] oxy} phenyl) -N, N-dimethylurea A starting compound (N '-. {2-chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl}. -N, N-dimethylurea, 80 mg), potassium carbonate (138 mg), and 1,4-dibromobutane (0.12 ml) were dissolved in N, -dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was washed with ether to give an intermediate product (N '- (4- {[7- (4-bro-obutoxy) -6-methoxy-4-quinazolinyl] oxy} -2-chlorophenyl) -N , N-dimethylurea). The intermediate product, potassium carbonate (138 mg), and morpholine (0.043 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by HPLC by growth with chloroform / methanol to provide 47 mg (yield: 44%) of the title compound. 1H-NR (CDC13, 400 MHz): d 1.67-1.77 (m, 2H), 1.93-2.03 (m, 2H), 2.39-2.50 (m, 4H), 3.67 (s, 6H), 3.64 - 3.75 (m , 4H), 4.02 (s, 3H), 4.21 (t, J = 6.6 Hz, 2H), 6.97 (s, 1H), 7.16 (dd, J = 2.7 Hz, 9.3 Hz, 1H), 7.26 (s, 1H) ), 7.28 (s, 1H), 7.29 (d, J = 2.7 Hz, 1H), 7.48 (s, 1H), 8.36 (d, J = 9.3 Hz, 1H), 8.59 (S, 1H) Example 180: N '- (2-chloro-4- { [6-methoxy-7- (4-pyridyl-methoxy) -4-quinazolinyl] oxy} phenyl) -N, N-dimethylurea A starting compound (N' - {.2-Chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl} - N, N-dimethylurea, 50 mg), potassium carbonate (138 mg), and hydrochloride of 4-chloromethylpyridine (49 mg) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by HPLC by growth with chloroform / methanol to provide 37 mg (yield: 60%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 3.07 (s, 6H), 4.07 (s, 3H), 5.32 (s, 2H), 6.97 (s, 1H), 7.15 (dd, J = 2.7 Hz, 9.0 Hz , 1H), 7.26 (s, 1H), 7.29 (d, J = 2.7 Hz, 1H), 7.41 (d, J = 6.1 Hz, 1H), 7.55 (s, 1H), 8.37 (d, J = 9.0 Hz , 1H), 8.58 (s, 1H), 8.63 (d, J = 6.1 Hz, 1H) Mass analysis, found (ESI-MS, m / z): 480 (M ++ 1) Example 181: 2-. { [4- (3-chloro-4- [[(dimethylamino) carbonyl] amino] phenoxy) -6-methoxy-7-quinazolinyl] oxy} methyl acetate An initial compound (N '- [2-chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl.} - N, N-dimethylurea, 50 mg), carbonate potassium (138 mg), and bromoethyl acetate (49 mg) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by HPLC by growth with chloroform / methanol to provide 37 mg (yield: 60%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 3.07 (s, 6H), 3.82 (s, 3H), 4.06 (s, 3H), 4.87 (s, 2H), 6.97 (s, 1H), 7.14 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.18 (s, 1H), 7.29 (d, J = 2.7 Hz, 1H), 7.54 (s, 1H), _8.36 (d, J = 9.0 Hz, 1H), 8.60 (s, 1H) Example 182: N '- [2-chloro-4- (. {6-methoxy-7- [3- (4-methylpiperazino) propoxy] -4-quinazolinyl}. Oxy) phenyl] -N, N- dimethylurea An initial compound (N '- {2-chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl.} - N, N-dimethylurea, 400 mg), carbonate potassium (966 mg), and 1,3-dibromopropane (0.51 ml) were dissolved in N, N-dimethylformamide (5 ml), and the solution was stirred at room temperature for 18 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 398 mg (yield: 78%) of an intermediate product (N '- (4 { [7- (3-bromopropoxy) -6-methoxy-4-quinazolinyl] oxy} -2-chlorophenyl) -N, N-dimethylurea). The intermediate product (51 mg), potassium carbonate (138 mg), and 1-methylpiperazine (0.055 ml) were dissolved in N, N-dimethylformamide (1 ml), and the solution was stirred at room temperature for 18 hours. Water was added to the reaction mixture and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 46 mg (yield: 85%) of the title compound. ^ -NMR (CDC13, 400 MHz): d 2.06 - 2.16 (m, 2H), 2.29 (s, 3H), 2.30 - 2.60 (m, 10H), 3.07 (s, 6H), 4.02 (s, 3H), 4.25 (t, J = 6.8 Hz, 2H), 6.96 (s, 1H), 7.15 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.29 (d, J = 2.7 Hz, 1H), 7.30 (s 1H) ), 7.48 (s, 1H), 8.36 (d, J = 9.0 Hz, 1H), 8.59 (s, 1H) Mass analysis, found (ESI-MS, m / z): 529 (M ++ l) Example 183: N '- [2-chloro-4- [(7- { 3- [(2-hydroxyethyl) - (methyl) amino] propoxy.} - 6-methoxy-4-quinazolinyl.] Oxy] -phenyl] -N, N-dimethylurea A starting compound (N '- [2-chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl] -N, N-dimethylurea , 400 mg), potassium carbonate (966 mg), and 1,3-dibromopropane (0.51 ml) were dissolved in N, N-dimethylformamide (5 ml), and the mixture was stirred at room temperature for 18 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1), the organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation. under reduced pressure. The residue was washed with ether to provide 398 mg (yield: 78%) of an intermediate product (N '- (4 { [7- (3-bromopropoxy) -6-methoxy-4-quinazolinyl] oxy} -2-chlorophenyl) -N, N-dimethylurea). The intermediate product (51 mg), potassium carbonate (138 mg), and 2- (methylamino) ethanol (0.040 ml) were dissolved in N, N-dimethylformamide (1 ml). The solution was stirred at room temperature for 18 hours. Water was added to the reaction mixture and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 49 mg (yield: 97%) of the title compound. 1 H-NMR (CDC13, 400 MHz): d 2.01 - 2.11 (m, 2H), 2.25 (s, 3H), 2.52 (t, J = 5.1 Hz, 2H), 2.61 (t, J = 7.1 Hz, 2H) , 3.03 (s, 6H), 3.57 (t, J = 5.1 Hz, 2H), 3.98 (s, 3H), 4.23 (t, J = 6.6 Hz, 2H), 6.92 (s, 1H), 7.10 (dd, J = 2.7 Hz, 9.3 Hz, 1H), 7.24 (d, J = 2.7 Hz, 1H), 7.31 (s 1H), 7.44 (s, 1H), 8.31 (d, J = 9.0 Hz, 1H), 8. 54 (s, 1H) Mass analysis, found (ESI-MS, m / z): 504 (M ++ 1) Example 184: N- (2-chloro-4- { [6-methoxy-7- (3-piperidino-propoxy) -4-quinazolinyl] oxy} phenyl) -N'-methylurea N- was dissolved. { 2-Chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl} -N'-methylurea (2.0 g) in N, N-dimethylformamide (50 ml), and triphenylphosphine (2.8 g), piperidinopropanol (0.9 g), and diethyl azodicarboxylate (1.9 g) were added to the solution. The mixture was stirred at room temperature for 2 hours. Triphenylphosphine (2.8 g), piperidinopropanol (0.6 g), and diethyl azodicarboxylate (1.9 g) were then added again to the reaction solution, followed by stirring at room temperature for an additional 10 hours. The solvent was removed by distillation under reduced pressure. The residue was purified by chromatography on silica gel by development with chloroform / methanol (20/1) to provide 650 mg (yield: 25%) of the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 1.37-1.43 (m, 2H), 1.43-1.53 (, 4H), 1.96-2.00 (m, 2H), 2.29-2.50 (m, 6H), 2.68 ( d, J = 4.6 Hz, 3H), 3.97 (s, 3H), 4.23 (t, J = 6.3 Hz, 2H), 6.82 -6.85 (m, 1H), 7.23 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.38 (s, 1H), 7.47 (d, J = 2.7 Hz, 1H), 7.54 (s 1H), 8.07 (s, 1H), 8.17 (d, J = 9.0 Hz, 1H), 8.55 (s) , 1H) Mass analysis, found (ESI-MS, m / z): 500 (M ++ l) Example 185: N- (2-chloro-4- { [6-methoxy-7- (3- piperidino-propoxy) -4-quinazolinyl] oxy} phenyl) -N'-ethylurea N- [2-chloro-4- [(7-hydroxy-6-methoxy-4-quinazolinyl) oxy] phenyl was dissolved} -N'-ethylurea (2.7 g) in N, N-dimethylformamide (30 ml), and triphenylphosphine (3.6 g), piperidinopropanol (1.2 g), and diethyl azodicarboxylate (2.4 g) were added to the solution. The mixture was stirred at room temperature for 2 hours. The triphenylphosphine reaction (3.6 g), piperidinopropanol (0.8 g), and diethyl azodicarboxylate were then added again to the reaction solution. (1.9 g) the mixture was stirred at room temperature during additional hours. The solvent was removed by distillation under reduced pressure and the residue was purified by chromatography on silica gel by growth with chloroform / methanol (20/1) to provide 1.5 g (yield: 42%) of the title compound. XH-NMR (DMSO-de, 400 MHz): d 1.08 (t, J = 7.0 Hz, 3H), 1.38 -1.41 (m, 2H), 1.47-1.53 (m, 4H), 1.95-2.00 (m, 2H) ), 2.31 - 2.46 (m, 6H), 3.10 - 3.17 (m, 2H), 3.97 (s, 3H), 4.23 (t, J = 6.3 Hz, 2H), 6.96 (t, J = 5.6 Hz, 1H) , 7.23 (dd, J = 2.7 Hz, 9.0 Hz, 1H), 7.37 (s, 1H), 7.47 (d, J = 2.7 Hz, 1H), 7.54 (s 1H), 8.02 (s, 1H), 8.19 ( d, J = 9.3 Hz, 1H), 8.55 (s, 1H) Mass analysis, found (ESI-MS, m / z): 514 (M? l) Example 186: N- (2-chloro-4- { [6-methoxy-7- (4-pyridyl-methoxy) -4-quinolyl] oxy} phenyl) -N- (2,4-difluorophenyl) -urea N- [2-chloro-4-] was dissolved [(7-hydroxy-6-methoxy-4-quinolyl) oxy] phenyl} -N '- (2,4-difluorophenyl) urea (55 mg), potassium carbonate (62 mg), and 4- (chloromethyl) pyridine hydrochloride (22 mg) in N, N-dimethylformamide (1 ml), and the solution was stirred at a temperature of 80 ° C for 1 hour. The solvent was removed by distillation under reduced pressure. A saturated aqueous sodium hydrogencarbonate solution was added to the residue and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was washed with ether to provide 35 mg (yield: 55%) of the title compound. 1 H-NMR (DMSO-de, 400 MHz): d 3.98 (s, 3 H), 5.41 (s, 2 H), 6.56. (d, J = 5.1 Hz, 1H), 7.04-7.10 (m, 1H), 7.25-7.37 (m, 2H), 7. 47 (s, 1H), 7.49 - 7.52 (m, 4H), 7.55 (s, 1H), 8.08 - 8.15 (m, 1H), 8.24 (d, J = 9.0 Hz, 1H), 8.49 (d, J = 5.4 Hz, 1H), 8.60 - 8.63 (m, 1H), 8.81 - 8.83 (m, 1H), 9.30 - 9.31 (m, 1H) Mass analysis, found (ESI-MS, m / z): 563 (M ++ l) The structures of The compounds described in the examples are the following.

X Z R 'R ¿RJ R' 1 CH CH H CH 3 CH 3 O H 3 CH CH H CH 3 O CH 3 O H 4 CH CH H CH3O CH3O H CH CH H CH 3 O CH 3 O H 7 CH CH H CH 3 O CH 3 O H 8 CH CH H CH3O CH3O H 9 CH CH H CH3O CH3O H CH CH H CH3O CH3O H 11 CH CH H CH3O CH3O H 12 CH CH H CH3O CH3O H 13 CH CH H CH3O CH3O H 14 CH CS H CH30 CH3O H CH CH H CH3O CH3O H 16 CH CH H CH3O CH3O H 17 CH CH H CH3O CH3O H 18 CH CH H CH3O CH3O H 19 CH CH H CH3O CH3O H CH CH H CH3O CH3O H 21 CH CH H CH3O CH3O H 22 CH CH H CH3O CH3O H 23 CH CH H CH3O CH3O H 24 CH CH H CH 3 O CH 3 O H 25 CH CH H CH 30 CH 3 O H 2 6 CH CH H CH3O CH3O H 27 CH CH H CH3O CH3O H 28 CH CH H CH3O CH3O H 29 CH CH H CH3O CH3O H CH CH H CH3O CH3O H 31 CH CH H CH3O CH3O H 32 CH CH H CH3O CH3O H 33 CH CH H CH3O CH3O H 34 CH CH H CH3O CH3O H CH CH H CH3O CH3O H 36 CH CH H CH 3 O CH 3 O H 38 CH CH H CH 3 O CH 3 O H 39 CH CH H CH3O CH3O H 4 0 CH CH H CH3O CH3O H 41 CH CH H CH3O CH3O H 42 CH CH H CH3O CH3O H 43 CH CH H CH3O CH3O H 44 CH CH H CH3O CH3O H 45 CH CH H CH3O CH3O H 4 6 CH CH H CH3O CH3O H 47 CH CH H CH3O CH3O H 48 CH CH H CH3O CH3O H 49 CH CH H CH3O CH3O H 50 CH CH H CH30 H 54 CH CH H CH3O CH30 (CH2) 20 H 55 CH CH H CH3O CH30 (CH2) 20 H 56 CH CH H CH3O CH30 (CH2) 20 H 57 CH CH H CH3O CH30 (CH2) 20 H 58 CH CH H CH3O CH30 (CH2) 20 H 59 CH CH H CH3O CH30 (CH2) 20 H 60 CH CH H CH3O C? 0 'H 62 N CH H CH3O CH3O H 63 N CH H CH3O CH3O H 64 N CH H CH3O CH3O H 65 N CH H CH3O CH3O H 66 N CH H CH3O CH3O H 67 N CH H CH3O CH3O H 68 N CH H CH3O CH3O H 69 N CH H CH30 CH3O H 70 N CH H CH3O CH3O H 71 N CH H CH3O CH3O H 72 N CH H CH3O CH3O H 73 N CH H CH3O CH3O H 74 N CH H CH3O CH3O H 75 N CH H CH3O CH3O H 7 6 N CH H CH3O CH3O H 77 N CH H CH3O CH3O H 78 N CH H CH3O CH3O H 79 N CH H CH3O CH3O H 80 N CH H CH3O CH3O H 81 N CH H CH3O CH3O H 82 N CH H CH3O CH3O H 83 N CH H CH3O CH3O H 84 N CH H CH3O CH3O H 85 N CH H CH3O CH3O H 86 N CH H CH3O CH3O H 87 N CH H CH3O CH3O H 88 N CH H CH3O CH3O H 89 N CH H CH3O CH3O H 90 N CH H CH3O CH3O H 91 N CH H CH3O CH3O H 92 N CH H CH3O CH3O H 93 N CH H CH 3 O CH 3 O H 94 N CH H CH 30 CH 3 O H 95 N CH H CH3O CH3O H 96 N CH H CH3O CH3O H 97 N CH H CH3O CH3O H 98 N CH H CH3O CH3O H 99 N CH - H CH3O CH3O H 100 N CH H CH3O CH3O H 101 N CH H CH3O CH3O H 102 N CH H CH 3 O CH 3 O H 104 N CH H CH 3 O CH 3 O H 105 N CH H CH3O CH3O H 106 N CH H CH 3 O CH 3 O H 108 N CH H CH 3 O CH 3 O H 109 N CH H CH3O CH3O H 110 N CH H CH3O CH3O H 111 N CH H CH3O CH3O H 112 N CH H CH 3 O CH 3 O H 114 N CH H CH 3 O CH 3 O H 115 N CH H CH3O CH3O H 116 N CH H CH3O CH3O H 117 N CH H CH3O CH3O H 118 N CH H CH 3 O CH 3 O H 119 N CH H CH 30 O N v O H 121 N CH H CH30 H H0 / ^ 0 / 122 N CH H CH3O HO ?? H 124 N CH H CH3O cf? /? / H 125 N CH H CH 3 O "H O '126 N CH H CH 3 O H / \ O 128 N CH H CH3O H 131 N CH H CH 3 O H N-N 134 N CH H CH 3 O H "o 139 N CH H ° _N ^^ - 0- CH3O H O U N -U N // ° x x 144 CH CH H CH30 H 145 CH CH H CH30 H N- HO ^^^ O '147 CH CH H CH3O H 151 CH CH H CH3O H or ^^ o ' 154 CH CH H CH3O O "H HO ^ 155 CH CH H CH3O HO "H CH CH H CH3O H 164 N CH H CH3O -fTY H N CH H CH 3 O H 171 N CH H CH 3 O CT ?? H 172 CH CH H CH30 cT A? H O. 175 CH CH H CH3O OR H 176 CH CH H CH3O H 177 CH CH H CH3O r V U. ° "\ H 178 N CH H CH3O O N ^ O H 180 N CH H CH3O t? C H 181 N CH H CH3O H? ° - 182 N CH H CH3O - H 183 N CH H CH3O H [Continuation of the table) R ° Rc R7 Ry R5 R 10 Rx " H H H H H 4 H F H H H H 5 H F H H H H 6 H F H H H H 7 H F H H H H H H H H H H H H H H 10 H H H H H 13 H Cl H H H H H Cl H H H H CH 3 21 H Cl H H H H N. H3 27 CH3 CH3 H H H H ^ CH3 Br N. 28 CH3 CH3 H H H H Cl XH3 O 30 CH3 CH3 H H H H 34 CH3 CH3 H H H H CH3 N CH3 CH3 CH3 H H H H 36 CH3 CH3 H H H H or CH3 38 H CH3 CH3 H H H N ^ CH3 44 H CH3 CH3 H H H Br 47 H N02 H H H H 62 H Cl H H H H 63 H H H H H H? / 64 H H H H H H? /? 65 H H H H H H 66 H H H H H H 68 H H H H H H? / \ 69 H H H H H H 76 H Cl H H H U U 77 H Cl H H H H 78 H Cl H H H H V 80 H Cl H H H H VS 81 H Cl H H H H / 82 H Cl H H H H 8 H H H H H? H H H H? /? / 91 H H H H H 92 H H H H H 97 CH, H H H H H? /? 98 CH3 H H H H H H CH3 H H H? /? 103 H CH3 H H H H ? /? 107 H N02 H H H H 108 H N02 H H H H / V 109 H Cl H H CH 2 OCH 3 H? /? ? /? 110 H Cl H H CH 3 C (= 0) - H 111 H Cl H H H CH5 \ / \ 113 H Cl H H H CH3 (CH2; v \ 114 H Cl H H H CH3 116 H Cl H H H CH3CH2? / 117 H Cl H H H H CH3 118 H Cl H H H CH3 CH, 119 H Cl H H H H /? / 120 H Cl H H H H v 121 H Cl H H H /? / 122 H Cl H H H H? / 123 H Cl H H H H /? / 124 H Cl H H H H? / 125 H Cl H H H H T 126 H Cl H H H CH 3 CH 2 127 H Cl H H H 128 H Cl H H H H 129 H Cl H H H H 130 H Cl H H H 131 H Cl H H CH 3 CH 2 132 H Cl H H CH 3 CH 2 133 H Cl H H H H 134 H Cl H H H H 135 H Cl H H H H 136 H Cl H H H H 137 H Cl H H H H 138 H Cl H H H H 139 H Cl H H H H 140 H Cl H H H H 141 H Cl H H H H 142 H Cl H H H H 143 H Cl H H H H 144 H Cl H H H H 145 H Cl H H H H 146 H Cl H H H H 147 H Cl H H H H 148 H Cl H H H H 149 H Cl H H H H 150 H Cl H H H H 151 H Cl H H H H 152 H Cl H H H H 153 H Cl H H H H 154 H Cl H H H H 155 H Cl H H H H 156 H Cl H H H H 157 H Cl H H H H 158 H Cl H H H H 159 H Cl H H H H 160 H Cl H H H H 171 H CH 30 H H H H 173 H CH3O H H H H 174 H CH3O H H H H 175 H CH 3 CH 3 H H H 176 H CH 3 CH 3 H H H 178 H Cl H H H CH3 CH, 179 H Cl H H H CH3 CH3 180 H Cl H H H CH3 CH3 181 H Cl H H H CH3 CH3 182 H Cl H H H CH 3 CH, 183 H Cl H H H CH 3 CH 3 184 H Cl H H H H CH, 185 H Cl H H H H 186 H Cl H H H H Pharmacological Test Example 1: Measurement of inhibition activity against MAPK activation in vascular endothelial cells induced by VEGF stimulation. Human funicular venous vascular endothelial cells (purchased in Chronetics) were cultured in an EGM-2 medium (purchased from Chronetics). in an incubator containing 5% carbon dioxide to a confluence of 50 to 70%, and the culture was inoculated into wells, which contained the same medium, in a 96-well flat-bottomed plate in an amount of 1.5 x 105 per well. After cultivation at a temperature of 37 ° C overnight, the medium was replaced with an EBM-2 medium containing 0.5% fetal calf serum (purchased from Chronetics), followed by culture for 24 hours. A solution of the dimethyl sulfoxide test compound was added to each well and the culture was continued at a temperature of 37 ° C for an additional 1 hour. A human recombinant vascular endothelial growth factor (hereinafter abbreviated as "VEGF") was added at a final concentration of 50 ng / ml and stimulation of the cells was performed at a temperature of 37 ° C for 8 minutes. The medium was removed, the cells were washed with phosphate-buffered saline (pH 7.4), and then 10 μl of a solubilization buffer (Tris buffered saline (pH 7.4) containing 1% Triton X100, was added. 2 mM sodium orthovanedrylate, and 1 mM disodium ethylenediamine tetraacetate). The mixture was stirred at a temperature of 4 ° C for 1 hour to solubilize the cells. An equal amount of saline buffered with Tris containing 1% sodium luaryl sulfate was added and mixed with the solution. This solution (2 μl) was adsorbed on an OVDF filter by spot blots, and this filter was subjected to immunoblotting with MAPK antibody phosphorylated with anti-tyrosine (purchased from Daiichi Pure Chemicals). The level of phosphorylated MAPK was determined quantitatively in a densitometer, and the percentage of phosphorylated MAPK in the presence of the test compound was determined by considering the level of phosphorylated MAPK with the addition of VEGF in the absence of the test compound as 100% and the level of phosphorylated MAPK. Phosphorylated MAPK in the absence of the test compound and VEGF as 0%. The concentration of test compound (IC50) needed to inhibit 50% of MAPK activation was calculated based on the percentage of phosphorylated MAPK. The results are presented in Table 1. Table 1 Compound IC50 (nM) 1 1.8 4 2.1 5 2.9 7 5.2 11.0 5.1 10 7.8 11 15.0 13 2.2 14 0.7 16 2.9 17 11.0 18 0.6 19 0.6 20 8.5 21 3.4 22 0.4 23 5.4 24 0.6 25 3.9 26 5.3 28 4.0 29 4.4 30 1.7 31 2.5 32 7.3 33 3.5 34 4.2 35 3.7 36 3.3 37 2.3 40 12.0 41 4.9 42 5.9 43 3.8 45 2.0 46 4.3 47 4.0 48 0.5 49 4.3 50 0.5 52 4.4 53 5.9 54 0.5 55 2.8 56 5.1 57 6.5 58 5.1 59 5.8 62 16.0 63 70.0 64 42.0 65 36.0 66 21.0 67 345. Q 68 45.0 69 67.0 70 6.8 71 750.0 72 3.9 73 < 2 74 6.0 75 1.2 76 8.0 77 71.0 78 4.1 79 30.0 80 13.0 82 3.8 83 > 1000 85 0.7 86 0.6 87 58.0 89 45.0 90 42.0 92 46.0 93 14.0 94 1.8 95 2.7 96 < 1 97 518.0 98 450.0 99 100 5.2 102 150.0 103 53.0 104 5.3 105 2.3 106 < 1 107 10.2 Example of Pharmacological Test 2: Measurement of inhibition activity against KDR phosphorylation by ELISA NIH 3T3 cells (Sawano A et al., Cell Growth &Differentation, 7 213-221 (1996), "Flt-1 but no KDR / Flk-1 tyrosine kinase is a receptor for placental growth factor, related to vascular endothelial growth factor ") prepared by transfection of human KDR were cultured in a DMEM medium containing 10% fetal calf serum (purchased from GIBCO BRL) in a 5% carbon dioxide incubator until a confluence of 50 to 70% is obtained. Harvested cells were inoculated into wells, which contained the same medium, in a 96 well plate of plaque bottom of a collagen type coating in an amount of 1.5 x 10 4 per well, followed by culture at a temperature of 37 ° C during the night. The medium was replaced by a DMEM medium containing 0.1% fetal calf serum. A solution of the test compound in dimethyl sulfoxide was added to each well, and the culture was continued at a temperature of 37 ° C for an additional 1 hour. A human recombinant vascular endothelial growth factor (hereinafter abbreviated as "VEGF") was added at a final concentration of 100 ng / ml and the stimulation of the cells was carried out at a temperature of 37 ° C for 2 minutes. . The medium was removed, the cells were washed with phosphate-buffered saline (pH 7.4), and then 50 μl of a solubilization buffer (20 mM HEPES (pH 7.4), 150 mM NaCl, 0.2% Triton was added. X100, 10% glycerol, 5 mM sodium orthovanedrylate, 5 mM disodium ethylenediamine tetraacetate, and 2 mM Na4P2 7 7). The mixture was stirred at a temperature of 4 ° C for 2 hours to prepare a cell extract. Separately, a phosphate-buffered saline solution (50 μl, pH 7.4) containing 5 μm / ml anti-phospho-tyrosine antibody (PY20, purchased from Transduction Laboratories) was added to a microplate for ELISA (Maxisorpo, purchased from NUNC) , followed by rest at a temperature of 4 ° C during the night to form a solid phase in the wells. After washing the plate, 300 μl of a blocking solution was added, followed by standing at room temperature for 2 hours to effect blockage. After washing, the entire amount of the cell extract was transferred to the wells, and the plate was allowed to stand at a temperature of 4 ° C overnight. After washing, an anti-KDR antibody (purchased from Santa Cruz) was allowed to react at room temperature for 1 hour, and, after washing, an anti-rabbit Ig antibody labeled with peroxidase (purchased from Amersham) was allowed to react at room temperature for 1 hour. After washing, a chromophoric substrate for peroxidase (purchased from Sumitomo Bakelite Co., Ltd) was added to initiate a reaction. After an appropriate level of color development, a reaction termination solution was added to stop the reaction, and the absorbance at 450 nm was measured with a microplate reader. The phosphorylation activity of KDR for each well was determined considering that the absorbance with the addition of VEGF and without addition of the drug was 100% phosphorylation activity of KDR and the absorbance without the drug and VEGF was 0% phosphorylation activity of KDR. The concentration of the test compound was varied at several levels, the inhibition (percentage) of phosphorylation of KDR was determined for each case, and the concentration of the test compound needed to inhibit 50% of the phosphorylation of KDR (IC50) was calculated. • The results are summarized in Table 2. Table 2 Compound IC50 (nM) 62 11.0 63 150.0 64 150.0 65 27.0 66 15.0 67 63.0 68 24.0 69 64.0 70 32.0 71 350.0 72 3.5 73 1.0 74 11.0 75 1.4 76 3.5 77 6.0 78 3.4 79 18.0 80 2.7 81 4.1 82 8.4 83 840.0 85 0.5 86 1.5 87 110.0 61.0 89 24.0 90 57.0 92 63.0 93 37.0 94 2.3 95 3.8 96 0.4 97 490.0 98 330.0 99 25.0 100 13.0 101 3.0 102 105.0 103 78.0 104 3.9 105 2.0 106 1.5 107 11.0 108 5.0 110 > 1000 111 > 1000 112 > 1000 113 > 1000 114 > 1000 115 > 1000 116 > 1000 117 24.0 118 > 1000 119 3.6 120 3.9 121 12.5 122 5.8 123 8.9 124 1.9 125 2.6 126 > 1000 127 1.1 131 > 1000 132 > 1000 133 8.3 134 5.0 135 1.0 136 160.0 137 24.0 138 40.0 139 15.0 140 36.0 141 14.0 142 2.6 143 3.5 144 1.6 145 0.8 146 1.0 147 1.0 148 15.0 149 1.6 150 1.8 151 0.5 152 0.8 153 1.5 154 1.5 155 2.1 156 0.8 157 0.4 158 1.6 159 1.9 160 0.9 161 3.9 162 1.0 163 1.4 164 0.9 165 0.6 166 2.2 167 2.1 168 4.0 169 3.7 170 1.1 175 4.7 176 3.7 177 2.3 178 > 1000 179 > 1000 '180 > 1000 181 > 1000 182 > 1000 183 > 1000 184 0.2 185 0.5 186 6.3 Example of Pharmacological Test 3: Cariomorphosis Testing A375 (2 x 104) human melanoma cells (obtained from the Japanese Foundation for Cancer Research) were inoculated onto a platinum culture (manufactured by Falcon) and were cultured at a temperature of 37 ° C. After a period of 5 hours from the start of the culture, the test compound was added to 10 μM, and 1 μM and the culture continued for 48 hours. additional hours After fixation of the cells, 50 μg / ml of a solution of propidium iodide containing ribonuclease (200 μg / ml) was added to stain the nuclei. The stained nuclei were observed through a fluorescent microscope to analyze the nuclei to determine the abnormality of the karyomorphosis. The change of karyomorphosis to test compound was evaluated as (2+) when the change of karyomorphosis of the cells was performed at 1 μM; it was evaluated as (+) when the change of karyomorphosis of the cells was made at 10 μM; and was evaluated as (-) when the change of cell cariomorphosis was not effected at 10 μM. The results are summarized in Table 3. Table 3 Compound No. Change in terms of morphosis 13 14 15 16 17 18 20 21 22 24 25 26 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 52 53 55 58 59 60 61 62 Example of Pharmacological Test 4: Antitumor effect on human glioma cells (GL07) Human glioma cells GL07 (obtained from Central Laboratories for Experimental Animáis) were transplanted in nude mice. When the tumor volume reached approximately 100 mm3, the mice were pooled. In this case, the grouping was carried out in such a way that each group consisted of four mice and the average tumor volume was equal between the groups. The test compound was administered oxal or intraperitoneally at a dose of 20 mg / kg to the test groups every day once a day for 9 days, while the medium was administered to the control group in the same manner as in the groups test. The rate of inhibition of tumor growth (TGIR) was calculated as follows: The tumor growth inhibition rate (TGIR) = (1 - Tx / Cx) x 100 where Cx represents the volume of the tumor on day x for the control group when the volume of the tumor on the day of the start of administration was considered 1; and Tx represents the tumor volume for the groups that received the test compound. The rate of inhibition of tumor growth for representative examples of a group of compounds according to the present invention appears in Table 4. Table 4 (Part 1) Example No. Site of TGIR,% Administration 4 Oral 61 5 Oral 59 9 9 Intraperitoneal 59 13 Intraperitoneal 52 14 Intraperitoneal 81 16 Intraperitoneal 77 17 Intraperitoneal 85 18 Oral 57 24 Oral 63 25 Intraperitoneal 68 28 Intraperitoneal 84 29 Oral 64 3 377 Intraperitoneal 70 48 Intraperitoneal 90 50 Oral 59 51 Oral 65 54 Oral 59 62 Oral 78 64 Oral 37 66 Oral 26 102 Oral 24 103 Oral 23 104 Oral 22 105 Oral 20 107 Oral 49 109 Oral 71 110 Oral 26 111 Oral 78 112 Oral 81 113 Oral 61 114 Oral 60 115 Oral 74 116 Oral 83 119 Oral 40 120 Oral 30 121 Oral 22 122 Oral 21 123 oral 31 124 oral 27 125 oral 30 147 oral 34 148 oral 54 149 oral 47 150 oral 22 151 oral 44 152 oral 44 153 oral 53 154 _ oral 34 155 oral 29 156 oral 24 157 oral 44 158 oral 39 159 oral 40 160 Oral 43 161 Oral 39 162 Oral 40 163 Oral 52 164 Oral 55 165 Oral 44 166 Oral 27 TGIR,% = Tumor growth inhibition rate (%) Table 4 (Part 2) Example No. TGIR site,% Administration 67 Oral 30 68 Oral 57 69 Oral 26 71 Oral 67 73 Oral 34 74 Oral 28 77 Oral 26 78 Oral 21 79 Oral 28 80 Oral 52 82 Oral 27 83 Oral 31 85 Oral 26 89 Oral 40 93 Oral 29 94 Oral 29 97 Oral 48 98 Oral 38 99 Oral 33 100 Oral 36 101 Oral 44 126 Oral 52 127 Oral 25 128 Oral 21 129 Oral 25 130 Oral 32 131 Oral 31 132 Oral 24 133 Oral 20 134 Oral 29 135 Oral 62 136 Oral 23 137 Oral 20 138 Oral 21 139 Oral 27 140 Oral 21 141 Oral 28 142 Oral 48 143 Oral 53 144 Oral 56 145 Oral 57 146 Oral 48 167 Oral 28 168 Oral 42 169 Oral 55 170 Oral 64 171 Oral 13 172 Oral 42 173 oral 21 174 oral 19 175 oral 17 176 oral 22 177 oral 35 178 oral 28 179 oral 33 180 oral 45 181 oral 21 182 oral 31 183 oral 22 184 oral 48 185 oral 59 186 oral 47 TGIR,% = Rate of inhibition of tumor growth (%

Claims (52)

1. CLAIMS 1. A compound represented by the formula (I) or a pharmaceutically acceptable salt or solvate thereof: wherein X and Z represent, each, CH or N; R1, R2, and R3, which may be the same or different, represent a hydrogen atom, C? -6 alkyl, C? _6 alkoxy, C2_6 alkenyl, C2_4 alkynyl, nitro, or amino, said C? Alkyl? -6, C6-6 alkoxy, C2-6 alkenyl, and C2-β alkynyl are optionally substituted by a halogen atom; hydroxyl; C 4 -4 alkoxy; C 4 -4 alkoxycarbonyl; amino wherein one or two hydrogen atoms are optionally substituted by C? _6 alkyl optionally substituted by hydroxyl or C? _4 alkoxy; group R1R13N-C (= 0) -0- wherein R12 and R13, which may be the same or different, represent a hydrogen atom or C? -4 alkyl, said alkyl is optionally substituted by hydroxyl or C? _4 alkoxy; or group R1- (S) -m- wherein R14 represents a saturated or unsaturated carbocyclic or heterocyclic group of three to seven members optionally substituted by C? - alkyl, and m is 0 or 1; R4 represents a hydrogen atom; R5, R6, R7 and R8, which may be the same or different, represent a hydrogen atom, a halogen atom, C? -4 alquiloalkyl, C? -4 alcoalkoxy, C? -4 alqualkylthio, nitro or amino, provided that R5, Rd, R7 and R8 do not simultaneously represent a hydrogen atom; R9 and R10, which may be the same or different, represent a hydrogen atom, C? -6 alkyl or C? - alkylcarbonyl, the alkyl C? _6 alkyl or C? -4 alkylcarbonyl portion, is optionally substituted by an atom halogen; C 4 -4 alkoxy, amino optionally substituted by C 4 -4 alkyl, optionally substituted by C 1-4 alkoxy; or a saturated or unsaturated carbocyclic or heterocyclic group of three to seven members; and R11 represents C6-6alkyl, C2-ealkenyl or C2-βalkynyl, (said C1-6alkyl, alkenyl Ce and C2-alkynyl are each, optionally substituted by a halogen atom or C-alkoxy? _6), or else R15- (CH2) n- wherein n is an integer from 0 to 4 and R15 represents a saturated or unsaturated carbocyclic or heterocyclic group of three to seven members optionally substituted by a halogen atom, Ci- β, or Ci-β alkoxy and is optionally fused with another carbocyclic ring or three to seven membered heterocyclic ring, saturated or unsaturated, to form a bicyclic ring.
2. 2. The compound according to claim 1, wherein R1, R9 and R10 represent a hydrogen atom.
3. 3. The compound according to claim 1, wherein R1 represents a hydrogen atom and one or both R9 and R10 represent a group other than a hydrogen atom.
4. 4. The compound according to claim 1, wherein X represents N or CH and Z represents CH.
5. 5. A compound represented by the formula (Ia) or a pharmaceutically acceptable salt or solvate thereof: wherein X represents CH or N; R21, and R22, which may be the same or different, represent C?-6, unsubstituted alkoxy or a group R31- (CH2) -pO- wherein R31 represents a halogen, hydroxyl, C? _4 alkoxy, alkoxycarbonyl C atom? - amino, wherein one or two hydrogen atoms are optionally substituted by C? alkyl - optionally substituted by hydroxyl or C? -4 alkoxy, group R12R13N-C (= 0) -0- wherein R12 and R13, which may be equal or different, represent a hydrogen atom or C alquilo _ alkyl, said alkyl is optionally substituted by hydroxyl or C? _ alkoxy; or group R14- (S) -m- wherein R14 represents a saturated or unsaturated carbocyclic or heterocyclic group of three to seven members optionally substituted by C? -4 alkyl, and m is 0 or 1; and P is an integer from 1 to 6; R23, R24, R25 and R26, which may be the same or different, represent a hydrogen atom, a halogen atom, C? - alkyl, C? -4 alkoxy, C? -4 alkylthio, nitro or amino, provided that R23, R24, R25 and R26 do not simultaneously represent a hydrogen atom; R27 and R28, which may be the same or different, represent a hydrogen atom, C? -S alkyl or C? - alkylcarbonyl, the C? -6 alkyl or C? _4 alkylcarbonyl portion is optionally substituted by a carbon atom. halogen; C 4 -4 alkoxy; amino optionally substituted by C? -4 alquiloalkyl, optionally substituted by C alco - alkoxy; or a saturated or unsaturated carbocyclic or heterocyclic group of three to seven members; and R29 represents Ci-e alkyl, C2-6 alkenyl or C2-e alkynyl, (said Ci-e alkyl, C2-6 alkenyl and C2_6 alkynyl are each, optionally substituted by a halogen atom or C1-6 alkoxy) 4), or R32- (CH2) q- where q is an integer from 0 to 4 and R32 represents a saturated or unsaturated six-membered carbocyclic or heterocyclic group optionally substituted by a halogen atom, C1-4alkyl, or C 1 alkoxy and is optionally fused to another saturated or unsaturated five or six membered heterocyclic ring or carbocyclic ring to form a bicyclic ring.
6. 6. The compound according to claim 5, wherein R21 and R22 represent unsubstituted C1-4 alkoxy.
7. The compound according to claim 5, wherein any of R21 and R22 represents unsubstituted C?-4 alkoxy and the other represents a group R31- (CH2) -p-O-.
8. The compound according to claim 5, wherein at least one of R23, R24, R25 and R26 represents a halogen atom.
9. 9. The compound according to claim 5, wherein at least one of R23, R24, R25 and R2d represents a chlorine atom or a fluorine atom.
10. The compound according to claim 5, wherein at least one of R23, R24, R25 and R26 represents C? -? 11 alkyl.
11. The compound according to claim 5, wherein two of R23, R24, R25 and R26 represent methyl and the other two represent a hydrogen atom.
12. The compound according to claim 5, wherein at least one of R23, R24, R25 and R26 represents nitro, amino, C4-4alkoxy, or C4-4alkylthio.
13. The compound according to claim 5, wherein R23, R25, and R26 represent a hydrogen atom and R24 represents a halogen atom, C? -4 alkyl / C? -4 alkoxy, nitro, or amino.
14. The compound according to claim 5, wherein both R27 and R28 represent a hydrogen atom.
15. 15. The compound according to claim 5, wherein either or both R27 and R28 represent a group other than a hydrogen atom.
16. 16. The compound according to claim 5, wherein X represents CH or N; R21 and R22 represent unsubstituted C alco -4 alkoxy; R23, R25, and R26 represent a hydrogen atom; R 24 represents a halogen atom, C 1-4 alkyl, C 1-4 alkoxy, or nitro; R27 and R28 represent a hydrogen atom; and R 29 represents C? -6 alkyl, C2-6 alkenyl or alkynyl C2-e, (said C6-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted by a halogen atom or C4-4 alkoxy), or - (CH2) q-R32 wherein q is an integer from 0 to 1 and R32 represents phenyl, pyridyl, or naphthyl, said phenyl, pyridyl and naphthyl are optionally substituted by a halogen atom, C? -4 alquiloalkyl or C? _ alcoalkoxy.
17. 17. The compound according to claim 5, wherein X represents CH or N; R21 and R22 represent unsubstituted C alco -4 alkoxy; R23, R25, and R26 represent a hydrogen atom; R 24 represents a halogen atom, C? -4 alkyl, C 1-4 alkoxy, or nitro; either R27 and R28 or both represent a group other than a hydrogen atom; and R29 represents C6-6 alkyl, C2_s alkenyl or C2-β alkynyl, (said Ci-e alkyl, C2-alkenyl and C2_6 alkynyl are each, optionally substituted by a halogen atom or C1-4 alkoxy) , or else - (CH2) q-R32 where q is an integer of 0 or 1 and R32 represents phenyl, pyridyl, or naphthyl, said phenyl, pyridyl and naphthyl are optionally substituted by a halogen atom, C1- alkyl 4 or C? -4 alkoxy.
18. 18. The compound according to claim 5, wherein X represents CH or N; R21 and R22 represent C4-4 unsubstituted alkoxy; R23, R25, and R26 represent a hydrogen atom; R 24 represents a halogen atom, C 4 -C 4 alkoxy C 4 -4 alkyl or nitro; R27 represents a hydrogen atom; R28 represents a group other than a hydrogen atom; and R29 represents C6_6 alkyl, C2_e alkenyl or alkynyl C2-6, (said C6_6 alkyl, C2_6 alkenyl and C2_6 alkynyl are each optionally substituted by a halogen atom or C4_4 alkoxy), or - (CH2) q-R32 where q is a integer of 0 or 1 and R32 represents phenyl, pyridyl, or naphthyl, said phenyl, pyridyl and naphthyl are optionally substituted by a halogen atom, alkyl C? -4 or C1-4 alkoxy.
19. 19. The compound according to claim 5, wherein X represents CH or N; any of R21 and R22 represents unsubstituted C4-4 alkoxy and the other represents a group R31- (CH2) -p-O-; R23, R25, and R26 represent a hydrogen atom; R 24 represents a halogen atom, C? _4 alkyl, C? _ Alkoxy, or nitro; R and R > 28 represent a hydrogen atom; and R 29 represents C? -6 alkyl, C2-6 alkenyl or alkynyl C2-6, (said C6_6 alkyl, C2-6 alkenyl and C2_6 alkynyl are each optionally substituted by a halogen atom or C1-4 alkoxy), or - (CH2) q-R32 wherein is an integer of 0 or 1 and R32 represents phenyl, pyridyl, or naphthyl, said phenyl, pyridyl and naphthyl are optionally substituted by a halogen atom, C 1-4 alkyl or C 1-4 alkoxy.
20. 20. The compound according to claim 19, wherein R21 represents C? -4 unsubstituted alkoxy and R22 represents a group R31- (CH2) -p-O-.
21. 21. The compound according to claim 19 or according to claim 20, wherein R31 represents hydroxyl, amino wherein one or two hydrogen atoms are optionally substituted by C1-4 alkyl optionally substituted by hydroxyl or group R14- (S) -m- wherein R 14 represents a saturated or unsaturated 5-membered heterocyclic group containing from 1 to 4 nitrogen atoms and optionally substituted by C 1 alkyl, or a saturated or unsaturated six-membered heterocyclic group containing one or two heteroatoms selected from nitrogen atom and oxygen atom and optionally substituted by C 1 -4 alkyl, and m is 0 (zero); and p is an integer from 1 to 4.
22. 22. The compound according to any of claims 19 to 21, wherein p is 1.
23. 23. The compound according to any of claims 19 to 21, wherein R31 represents group R14- (S) -m- wherein R14 represents an unsaturated six-membered heterocyclic group containing one or two nitrogen atoms and optionally substituted by C alquilo alkyl; and m is 0 (zero); 24. The compound according to any of claims 19 to 21, wherein R31 represents group R14- (S) -m- wherein R14 represents an unsaturated six-membered heterocyclic group containing one or two nitrogen atoms and optionally substituted for alkyl C? _4 and m is 0 (zero); and p is 1. 25. The compound according to any of claims 23 or 24, wherein R14 represents optionally substituted pyridyl. 26. The compound according to claim 5, wherein X represents CH or N; any of R21 and R22 represents unsubstituted C1-C4 alkoxy and the other represents a group R31- (CH2) -p-0-; R23, R25, and R26 represent a hydrogen atom; R 24 represents a halogen atom, C 1 -4 alkyl, C 1-4 alkoxy, or nitro; either R27 and R28 or both represent a group other than a hydrogen atom; and R '29 represents C? _e alkyl, C2_6 alkenyl or alkynyl C2-e, (said C6_6 alkyl, C2_6 alkenyl and C2_6 alkynyl are each optionally substituted by a halogen atom or C4_4 alkoxy), or - (CH2) q-R32 wherein is an integer of 0 or 1 and R32 represents phenyl, pyridyl, or naphthyl, said phenyl, pyridyl and naphthyl are optionally substituted by a halogen atom, C? -4 alkyl or C? -4 alkoxy. 27. The compound according to claim 26, wherein R21 represents unsubstituted C? _4 alkoxy and R22 represents a group R31- (CH2) -p-O-. The compound according to claim 26 or according to claim 27, wherein R31 represents hydroxyl, amino wherein one or two hydrogen atoms are optionally substituted by C? -4 alkyl optionally substituted by hydroxyl or group R14 - (S) -m- wherein R 14 represents a saturated or unsaturated 5-membered heterocyclic group containing from 1 to 4 nitrogen atoms and optionally substituted by C? -4 alquiloalkyl or a saturated or unsaturated six-membered heterocyclic group containing one or two heteroatoms selected from nitrogen atom and oxygen atom and optionally substituted by C? -4 alkyl, and m is 0 (zero); and p is an integer from 1 to 4. 29. The compound according to any of claims 26 to 28, wherein p is 1. 30. The compound according to any of claims 26 to 28, wherein R31 represents group R14- (S) -m- wherein R14 represents an unsaturated six-membered heterocyclic group containing one or two nitrogen atoms and optionally substituted by C? -4 alkyl and m is 0 (zero); The compound according to any of claims 26 to 28, wherein R31 represents group R14- (S) -m- wherein R14 represents an unsaturated six-membered heterocyclic group containing one or two nitrogen atoms and optionally substituted for alkyl C? - ym is 0 (zero); and p is 1. 32. The compound according to claim 30 or according to claim 31, wherein R14 represents optionally substituted pyridyl. 33. The compound according to claim 5, wherein X represents CH or N; any of R21 and R22 represents C4-4 unsubstituted alkoxy and the other represents a group R31- (CH2) -p-O-; R23, R25, and R26 represent a hydrogen atom; R 24 represents a halogen atom, C 1 -4 alkyl, C 4 4 alkoxy, or nitro; R27 represents a hydrogen atom; R28 represents a group other than a hydrogen atom; and R29 represents Ci-e alkyl, C2-β alkenyl or C2_e alkynyl, (said C6_6 alkyl, C2_6 alkenyl and C2_6 alkynyl are each optionally substituted by a halogen atom or C4_4 alkoxy), or - (CH2) q-R32 where q is an integer of 0 or 1 and R32 represents phenyl, pyridyl, or naphthyl, said phenyl, pyridyl and naphthyl are optionally substituted by a halogen atom, C? alkyl? 4 or C? -4 alkoxy. 34. The compound according to claim 33, wherein R21 represents unsubstituted C4-4 alkoxy and R22 represents a group R31- (CH2) -p-0-. 35. The compound according to claim 33 or according to claim 34, wherein R31 represents hydroxyl, amino wherein one or two hydrogen atoms are optionally substituted by C? _4 alkyl optionally substituted by hydroxyl or group R1 - (S) -m- wherein R 14 represents a saturated or unsaturated 5-membered heterocyclic group containing from 1 to 4 nitrogen atoms and optionally substituted by C? -4 alkyl, or a saturated or unsaturated six-membered heterocyclic group containing one or two heteroatoms selected from nitrogen atom and oxygen atom and optionally substituted by C? ~ 4 alkyl, and m is 0 (zero); and p is an integer from 1 to 4. 36. The compound according to any of claims 33 to 35, wherein p is 1. 37. The compound according to any of claims 33 to 35, wherein R31 represents group R14- (S) -m- wherein R14 represents an unsaturated six-membered heterocyclic group containing one or two nitrogen atoms and optionally substituted by C? _4 alkyl and m is 0 (zero); 38. The compound according to any of claims 33 to 35, wherein R31 represents group R14- (S) -m- wherein R14 represents an unsaturated six-membered heterocyclic group containing one or two nitrogen atoms and optionally substituted for alkyl C? _4 and m is 0 (zero); and p is 1. 39. The compound according to claim 37 or according to claim 38, wherein R14 represents optionally substituted pyridyl. 40. The compound according to claim 5, wherein X represents CH or N; any of R21 and R22 represents unsubstituted C4-4 alkoxy and the other represents a group R, 31- (CH2) -p-O-; R23 and R26 represent a hydrogen atom; R 24 and R 25 represent a halogen atom, C 1 4 alkyl, C 4 alkoxy, or nitro; R27 and R28 represent a hydrogen atom; R29 represents C6_6alkyl, C2_6alkenyl or C2_6alkynyl, (said C1_6alkyl, C2_6alkenyl and C2_6alkynyl are each optionally substituted by a halogen atom or C _ alkoxy), or - (CH2) q-R32 where q is an integer of 0 or 1 and R32 represents phenyl, pyridyl, or naphthyl, said phenyl, pyridyl and naphthyl are optionally substituted by a halogen atom, C? alkyl? 4 or C 4 -4 alkoxy • 41. The compound according to claim 40, wherein R 21 represents unsubstituted C 4 -4 alkoxy and R 22 represents a group R 31- (CH 2) - pO-. 42. The compound according to claim 40 or according to claim 41, wherein R31 represents hydroxyl, amino wherein one or two hydrogen atoms are optionally substituted by C1-alkyl optionally substituted by hydroxyl or group R14- ( S) -m- wherein R 14 represents a saturated or unsaturated 5-membered heterocyclic group containing from 1 to 4 nitrogen atoms and optionally substituted by C 1-4 alkyl, or a saturated or unsaturated six-membered heterocyclic group containing one or two heteroatoms selected from nitrogen atom and oxygen atom and optionally substituted by alkyl CL_4, and m is 0 (zero); and p is an integer from 1 to 4. 43. The compound according to any of claims 40 to 42, wherein p is 1. 44. The compound according to any of claims 40 to 42, wherein R31 represents group R14- (S) -m- wherein R14 represents an unsaturated six-membered heterocyclic group containing one or two nitrogen atoms and optionally substituted by C? -4 alkyl and m is 0 (zero); 45. The compound according to any of claims 40 to 42, wherein R31 represents group R14- (S) -m- wherein R14 represents an unsaturated six-membered heterocyclic group containing one or two nitrogen atoms and optionally substituted for alkyl C? -4 and m is 0 (zero); and p is 1. 46. The compound according to claim 44 or according to claim 45, wherein R14 represents optionally substituted pyridyl. 47. The compound according to claim 1, which is a compound selected from the group consisting of the following compounds, or a pharmaceutically acceptable salt or solvate thereof: (13) N- [2-chloro-4- [ (6,7-dimethoxy-4-quinolyl) oxy] -phenyl} -N'-propylurea; (51) N- [2-chloro-4-. { [6-methoxy-7- (2-morpholino-ethoxy) -4-quinolyl] oxy} phenyl) -N '- (2,4-difluorophenyl) urea; (62) N- [2-chloro-4- [(6,7-dimethoxy-4-quinazolinyl) -oxy] phenyl} -N'-propylurea; (76) N- [2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) -oxy] phenyl} -N'-ethylurea; (117) N- [2-Chloro-4- [(6,7-dimethoxy-4-quinazolinyl) oxy] phenyl} -N'-methylurea; (119) N- (2-chloro-4- { [6-methoxy-7- (3-morpholino-propoxy) -4-quinazolinyl] -oxi.} Phenyl) -N'-propylurea; (135) N- (2-chloro-4- { [6-methoxy-7- (3-piperidino-propoxy) -4-quinazolinyl] -oxi.}. Phenyl) -N'-propylurea; (142) N- (2-Chloro-4. {[6-methoxy-7- (3-pyridyl-methoxy) -4-quinolyl] oxy} phenyl) -N'-propylurea; (143) N- (2-Chloro-4. {[6-methoxy-7- (4-pyridyl-methoxy) -4-quinolyl] oxy} phenyl) -N'-propylurea; (144) N- (2-chloro-4. {[6-methoxy-7- (2-morpholino-ethoxy) -4-quinolyl] oxy} phenyl) -N'-propylurea; (145) N- [2-Chloro-4-6-methoxy-7- [2- (1 H-1,2,3-triazol-1-yl) ethoxy] -4-quinolyl} oxy) phenyl] -N'-propylurea; (146) N- [2-chloro-4- (7- { [2- (lH-1-imidazolyl) -ethoxy] -6-methoxy-4-quinolyl.] Oxy) phenyl] -N '- propylurea; (148) N- [2-chloro-4- (6-methoxy-7-. {[2- (4-methyl-piperazino) ethoxy] -4-quinolyl} oxy) phenyl] -N'-propylurea; (149) N- (2-chloro-4-. {[7- (2-hydroxyethoxy) -6-methoxy-4-quinolyl] oxy} phenyl) -N'-propylurea; (151) N- (2-chloro-4- { [6-methoxy-7- (3-morpholino-propoxy) -4-quinolyl] oxy} phenyl) -N-propylurea; (152) N- [2-chloro-4- (6-methoxy-7- { [3- (4-ethyl-piperazino) ropoxy] -4-quinolyl} oxy) phenyl] -N'-propylurea; (153) N- [2-chloro-4- (6-methoxy-7- { [3- (1 H-1,2,3-triazol-1-yl) propoxy] -4-quinolyl} oxy. ) phenyl] -N'-propylurea; (157) N-. { 2-Chloro-4- [(7- { 3- [(2-hydroxyethyl) - (methyl) amino] propoxy.} - 6-methoxy-4-quinolyl) oxy] phenyl} -NF-propylurea; (159) N-. { 2-Chloro-4- [(6-methoxy-7-. {[[5- (1 H-1,2,3-triazol-1-yl) pentyl] oxy] -4- quinolyl) oxy] phenyl} -N'-propylurea; (160) N- [2-chloro-4- (7- { [4- (IH-1-imidazolyl) -butoxy] -6-methoxy-4-quinolyl.} Oxy) phenyl] -N '- propylurea; (162) N- (2-chloro-4- { [6-methoxy-7- (2-morpholino-ethoxy) -4-quinazolinyl] oxy} phenyl) -N '- (2,4-difluoro) phenyl) urea; (163) N- (2-chloro-4- { [6-methoxy-7- (3-morpholino-propoxy) -4-quinazolinyl] oxy} phenyl) -N '- (2,4-difluoro) phenyl) urea; (164) N- [2-chloro-4- (6-methoxy-7-. {[3- (4-methyl-piperazino) propoxy] -4-quinazolinyl}. Oxy) phenyl] -N '- ( 2,4-difluorophenyl) urea; (165) N- [2-chloro-4- [(7- { 3- [(2-hydroxyethyl) - (methyl) amino] propoxy] .6-methoxy-4-quinazolinyl) oxy] phenyl} -N '- (2,4-difluorophenyl) urea; (168) N- (2-chloro-4- { [6-methoxy-7- (3-morpholino-propoxy) -4-quinolyl-oxy} phenyl) -N '- (2,4-difluorophenyl) urea; (169) N- (2-Chloro-4. {[6-methoxy-7- (3-pyridyl-methoxy) -4-quinolyl] oxy} phenyl) -N '- (2,4-difluorophenyl) ) urea; (170) N- [2-chloro-4- (6-methoxy-7- { [2- (1 H-1,2,3-triazol-1-yl) ethoxy] -4-quinolyl.} Oxy ) phenyl] -N '- (2,4-difluorophenyl) urea; (184) N- (2-Chloro-4. {[6-methoxy-7- (3-piperidino-propoxy) -4-quinazolinyl] oxy} phenyl) -N '-methylurea; (185) N- (2-chloro-4- { [6-methoxy-7- (3-piperidino-propoxy) -4-quinazolinyl] oxy} phenyl) -N'-ethylurea; and (186) N- (2-chloro-4- { [6-methoxy-7- (4-pyridyl-methoxy) -4-quinolyl] oxy} phenyl) -N '- (2, 4- difluorophenyl) urea. 48. A pharmaceutical composition comprising as active ingredient the compound according to any of claims 1 to 47 or a pharmaceutically acceptable salt or solvate thereof. 49. The pharmaceutical composition according to claim 48, for use in the treatment of a selected disease within the group consisting of tumor, diabetic retinopathy, chronic rheumatism, psoriasis, atherosclerosis, and Kaposi's sarcoma. 50. The use of the compound according to any one of claims 1 to 47 or a pharmaceutically acceptable salt or solvate thereof for the production of a therapeutic agent for use in the treatment of a selected disease within the group consisting of tumor, Diabetic retinopathy, chronic rheumatism, psoriasis, atherosclerosis, and Kaposi's sarcoma. 51. A method for the treatment of a selected disease within the group consisting of tumor, diabetic retinopathy, chronic rheumatism, psoriasis, atherosclerosis, and Kaposi's sarcoma, comprising the step of administering an effective amount of the compound in accordance with any of claims 1 to 47 or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier, to mammals. 52. A method for inhibiting angiogenesis of target blood vessels, comprising the step of contacting the compound according to any one of claims 1 to 47 or a pharmaceutically acceptable salt or solvate thereof with vascular endothelial cells of the blood vessels. objectives.