JPS62502685A - Phenylene derivative - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] name of invention Phenylene derivative Detailed description of the invention (Industrial application field) The present invention relates to pharmaceuticals, particularly SRS-A (S low reacting 5a Novel phenylene peptides useful as antagonists of anaphylaxis) This invention relates to ren derivatives and salts thereof.

(Means for solving problems) The compound of the present invention is a phenylene derivative represented by the following general formula (I).

(The symbols in the formula represent the following meanings.

A: Hydrogen atom, phenyl group or phenoxy group.

n: an integer from 3 to 1O.

R1: hydrogen atom or lower alkoxy group.

X double CHtCH2-, -CH=CH, -CH2YI (Y in the formula.

Knee 0-, -S- or HaNH-), Yt -CHt-1COYz- (Y in the formula z: NH, -CHx YI- or YrCHt-) or bar YtCO- The group shown.

Koxy group, carboxy group, cyano group, oxalamide group (-NHCOCOOH) , lower alkoxycarbonyl group, lower alkyl group, hydroxy lower alkyl group, Lower alkoxy lower alkyl group, carboxy lower alkyl group, lower alkoxy group Rubonyl lower alkyl group, carboxy lower alkylthio lower alkyl group, lower alkyl group, carboxy lower alkylthio lower alkyl group, Rukoxycarbonyl lower alkylthio lower alkyl group, halo lower alkyl group, Ruboxy lower alkoxy group, lower alkoxycarbonyl lower alkoxy group, lower Alkanoyl lower alkoxy group, lower alkoxycarbonyl lower alkoxyl Bonyl lower alkoxy group, lower alkanoyl group or Alkyl group, carboxy lower alkyl group, lower alkoxycarbonyl lower alkyl group lower alkanoyl group, carboxy lower alkanoyl group, lower alkoxy group Rubonyl lower alkanoyl group, substituted or unsubstituted phenyl lower alkoxycarbonyl group lower alkanoyl group.

Carbamoyl group, lower alkylene group or mono- or di-lower alkylaminocarbonyl group group).

R3: a hydrogen atom, a hydroxyl group, or a lower alkoxy group], X, and CH= CH-, -Y3-Y, - (Y in the formula: single bond, -0-.

-5- or -NH-; Y, + several carbon atoms which may be interrupted by a sulfur atom are 1 ~6 alkylene groups), D: carboxyl group, lower alkoxy group Rubonyl group or compound or pharmaceutically acceptable salt thereof.

Below are various definitions and preferred specific examples of the general formula (I) above or the general formulas described below. Explain in detail.

In this specification, the term "lower" refers to carbon atoms of several months to six carbon atoms, unless otherwise specified. means a straight or branched carbon chain.

Therefore, "lower alkyl groups j include methyl group, ethyl group, propyl group, iso Propyl group, butyl group, isobutyl group, 5ec-butyl group.

tert-butyl group, pentyl group, isopentyl group, hexyl group, isohexyl Examples include groups. Also, it is indicated by "lower alkoxy" and "lower alkoxy group". Examples of groups include methoxy group, ethoxy group, propoxy group, isopropoxy group, and butyl group. Toxy group, isobutoxy group, sec-butoxy group, tert-butoxy group , pentyloxy group, isopentyloxy group, hexyloxy group, isohexyl Examples include oxy group.

Y4 indicates "an alkali having 1 to 6 carbon atoms which may be interrupted by a sulfur atom" Examples of "kylene group" include methylene group, ethylene group, and alkylene group having 3 carbon atoms. to 6 specific examples are similarly listed, and any position of these alkylene groups A group in which the position is interrupted by one sulfur atom, specifically, a group having the formula -〇Hz-S　CHx　, -(CHt)2-S CH2, -(CHt):+-5-CHt, -(CHt )45-CH2, -(CH2)2 S (CHt)3, CHt-S (CHt )4-1CHtCH(CHs)CH2SCH-, and the like.

"A group represented by the formula -CHt-Y+- or -YICHt-" represented by X Specifically, it is a methyleneoxy group (-CHI-0-).

methylenethio group (-CH2-S-), methyleneimino group (CHt-NH-), xymethylene group (0-CHt), thiomethylene group (, -S -CH, -), A minomethylene group (NH-CHt) is mentioned.

In addition, as "a group represented by the formula -CoYt- or -Y-CO-" indicated by X, Specifically, carbonylimino group (-CONH-).

carbonylmethyleneoxy group (-COCHt-0-), carbonylmethylenethio group (-COCHt　S　), carbonylmethyleneimino group (-COCH2-NH -), iminocarbonyl group (-NHCO-), methyleneoxycarbonyl group (C Ht　OCo　), methylenethiocarbonyl group (-CH2-S-Co-), methyl Leniminocarbonyl group (-CH, NHCO-:' is oxymethylenecarbonyl group (-〇-CH!-Go-), thiomethylenecarbonyl group (-S CHt-CO -), iminomethylenecarbonyl group (-NHCH, -Co-).

Carbonyloxy group (-〇〇-0-), carbonylthio group (-C0-S-), Examples include oxycarbonyl group (-0-Co-) and thiocarbonyl group (-S-Co-). It will be done.

The "lower alkanoyl group" represented by Rt, R4 or R3 includes formyl group, Acetyl group, propionyl group, butyryl group, isobutyryl group, valeryl group, iso Valeryl group etc. are substituted phenyl lower alkoxycarbonyl lower alkanoyl group. ", for example, p-methoxybenzyloxycarbonylacetyl group, "lower Examples of the "alkoxy group" include methoxalyl group and ethoxalyl group.

Specifically, the group represented by the formula -Y3-Y-1 represented by x2 is methylene group (CHt), ethylene group (-CH-CHt), tetramethylene group (-( cHt), -), pentamethylene group (-(CHI)5-).

Methylenethiomethylene group (-〇H, -5-CH2-), oxymethylene group (-Q CH, -), oxyethylene group (OCH* CHt -), oxypropylene group (-0CH2CHt CHx-), oxypropylenethiomethylene group (- 〇　-CH2CHt　CHt　-S　CHx　-), thiomethylene group (-S- CH2-), thioethylene group (-S CH2CH2-), thiopropylene group (- S-CH, CH2Cl-1t-), thioethylenethiomethylene group (S CH2C H2S CHt-), iminomethylene group (-N HCHt-), iminoethylene N group (N HCHt CH2).

Iminoethylenethioethylene group (N HCHt CH2-S -CH2CH2) can be mentioned.

The compound of general formula (I) above has optical isomers and alkyl atoms based on the presence of an asymmetric carbon atom. Contains cis and trans stereoisomers based on the presence of nyl groups, etc. There is. The compounds of the present invention include separated isomers and mixtures thereof. Included.

Furthermore, some of the compounds of the present invention form salts. The present invention is based on the general formula ( It also includes salts of the compound of 1), and such salts include sodium , salts with inorganic bases such as potassium.

Ethylamine, propylamine, diethylamine, triethylamine 1 morphol N, piperidine, N-ethylpiperidine, jetanolamine, cyclohexyl Salts with organic bases such as amines, salts with basic amino acids such as lysine and ornithine, Examples include ammonium salts and salts with mineral acid salts such as hydrochloric acid, sulfuric acid, phosphoric acid, and hydrobromic acid. It will be done.

(Conventional technology) The object compound of the present invention has a strong antagonistic effect against 5RS-A.

allergic asthma and other atopic diseases in humans, or anaphila in animals. In oxyshock, various chemical messengers are released from the lungs and other tissues. , contract smooth muscles such as bronchial muscles and pulmonary blood vessels, and reduce the permeability of skin vessels. It is thought that this may cause damage to living organisms. As such chemical messengers Examples include histamine and 5RS-A. Histamine is guinea pig anaf Although it plays an important role in irractic shock, human allergic It is not a very important chemical mediator in asthma [E1ser, Phar macol, Ther, 17, 239-250 (19B2). on the other hand, 5RS-A is the most important chemical messenger in human allergic asthma. There is much evidence to suggest that [Brock-1ehurst, J., Phys. siol, 151, 416-435 (1960); Au5ten and O range, Am, Rev, Re5p.

Dis, 112, 423-436 (1975); Adams and allergy - The development of drugs to prevent or eliminate or alleviate the symptoms of sexual reactions is based on such chemistry. Aims to inhibit the production, release, or antagonize the effects of transmitters It was done as.

A drug that suppresses the release of histamine is disodium lactate (dis) cromoglycate) is well known and antagonizes histamine. Many antihistamines are commercially available.

On the other hand, 5R8-A shows that histamine is a fast-acting and short-lived chemical messenger. It was known as a slow-acting and long-lasting chemical mediator, but recently Samue Leukotriene C4,D, whose structure was determined by Lucin (Samaelsson), and E4. 5RS-A or leukotriene (L eukotriens) are polyunsaturated fatty acids (especially arachidonic acid). A metabolite of xygenase and a chemical mediator in the allergic reaction. In addition to the action of It has been revealed that it has effects such as reducing contraction force. Therefore, such 5 It is desired to develop drugs that suppress the production and release of RS-A or antagonize their effects. ing.

The present inventors have discovered that a drug or compound (I) that suppresses the production and release of 5R6-A It was discovered that it strongly antagonizes 5RS-A, and the present invention was completed.

(Effect of the invention) As mentioned above, the compound (I) of the present invention strongly antagonizes 5RS-A. Various allergic diseases caused by A. (e.g. bronchial asthma, allergic rhinitis, Useful for prevention and treatment of ischemic heart disease, inflammation, etc. caused by hives diagnosis) and 5RS-A. It is.

In addition, the compounds of the present invention include those that have the same action as 5RS-A. Ru. Compounds with such 5RS-A agonist effects may cause intestinal paralysis after surgery. It is expected to be used for the treatment of leukotrienes, which are difficult to obtain stably in the past. Also as a reagent for use in research on alternative anti-5RS-A agents or 5RS-A antagonists. Useful.

Compound (I) of the present invention may be used as is or in a known pharmaceutically acceptable carrier. , excipients, etc. [e.g., tablets.

Capsules, powders, granules, gun powder, ointments, syrups, and injections.

It can be safely administered orally or parenterally as an inhaler or suppository.

The dosage varies depending on the subject, route of administration, symptoms, etc., but is usually the same as the daily dose for adults. 0.1 to 500 mg, preferably 1 to 200 mg, 2 to 3 times a day. Administer orally or parenterally in separate doses.

(Production method) The compound of the present invention can be produced, for example, by the method shown in the following reaction formula.

First manufacturing method or a reactive derivative thereof (Ia) Second manufacturing method or a reactive derivative thereof (!b) Third manufacturing method (■) (■) (Ie) Fourth manufacturing method (■) (■) (ld) Fifth manufacturing method (le) 6th manufacturing method (If) or its salt 7th manufacturing method (Xl[I) (Xff) (Ih) 8th manufacturing method (XV) 9th manufacturing method (X■) has the same meaning as , other symbols have the following meanings:

When M:Y is an oxygen atom or a sulfur atom, a hydrogen atom or an alkali metal source child, when Yl is an imino group, a hydrogen atom, Zl: halogen atom, or sulfonate residue, YS: methylene group, or methylene carbonyl group C-CH2CO-), Y,: methylene group, or carbonylmethylene Group (-coCH,-), Z,: halogen atom, R8: phenyl group or butyl group, R9-lower alkyl group, or lower alkoxyphenyl lower alkyl group, Y7: oxygen atom or sulfur atom, M2: hydrogen atom or alkali metal atom. ]In addition, the alkali metal represented by M, Mt Examples of atoms include sodium atoms, potassium atoms, etc., and the halogens represented by Zl and Z2. Examples of the ion atom include an iodine atom, a bromine atom, and a chlorine atom. Also sulfone Examples of residues include toluenesulfonic acid ester residue and benzenesulfonic acid ester residue. Residues and the like are preferably used.

First manufacturing method Among the compounds of the present invention, compounds (I) in which Xl is a carbonylimino group (-CONH-) a) is a substituted benzoic acid represented by the general formula (n) or a reactive derivative thereof and the general formula It is produced by reacting the amino compound represented by (III).

Reactive derivatives of compound (n) include acid chlorides, acid bromides, etc. Halide; acid azide: N-hydroxybenzotriazole and N-hydroxysulfate Active ester with cinimide; Symmetrical acid anhydride: Alkyl carbonic acid mixed acid anhydride, p - Mixed acid anhydride with toluenesulfonic acid; etc.

When reacting compound (n) with free carboxylic acid, dicyclohexylcarboxylic acid Diimide and 1. It is carried out in the presence of a condensing agent such as b-carbonyldiimidazole. is advantageous.

In the reaction, compound (II) or its reactive derivative and compound (1) are used in approximately equal moles. Alternatively, one may be used in excess and a finite solvent inert to the reaction, such as pyridine or tetra Trahydrofuran, dioxane, ether, benzene, toluene, xylene, methane Tylene chloride, dichloroethane, chloroform, dimethylformamide, acetic acid It is carried out in a solvent such as ethyl or acetonitrile.

Depending on the type of reactive derivative, triethylamine may be used during the reaction.

Pyridine, picoline, lutidine, N,N-dimethylaniline, potassium carbonate, water When it is advantageous to add a base such as sodium oxide to make the reaction proceed smoothly There is. Pyridine can also serve as a solvent.

The reaction temperature varies depending on the type of reactive derivative and is not particularly limited.

Second manufacturing method In the compound of the present invention, X is an iminocarbonyl group (NHCO-)T: a certain compound (I b) is a substituted aniline represented by the general formula (It/) and a compound represented by the general formula (V). It is produced by reacting with rubonic acid or its reactive derivative.

The reaction conditions are almost the same as in the first production method.

Third manufacturing method In the compound of the present invention, X is -Y, -CH! -i.e. -0-CHI-.

The compound group (Ic) which is S-CH2-, NHCHt- is represented by the general formula (VI) Substituted phenol or substituted phenyl mercaptan or its alkali metal as shown A genus substituted product or a substituted aniline and a halogen compound or a substituted aniline represented by the general formula (■) It can be produced by reacting with a sulfonate compound.

In the reaction, compound (■) and compound (~1) are mixed in 1 equimol or in excess of one of them. and dimethylformamide, dimethyl sulfoxide.

Methanol, ethanol, propatool, acetone, methyl ethyl ketone, tet Lahydrofuran, chloroform, dioxane, benzene, toluene, xylene, It is carried out in an organic solvent such as dichloromethane or dichloroethane.

The reaction is carried out in the presence of a base if necessary, and examples of such a base include potassium carbonate. um, triton B, potassium hydroxide, sodium hydride, sodium carbonate, piri gin, picoline, N,N-dimethylaniline, N-methylmorpholine, trimethy Preferred are amine, triethylamine, and the like.

The reaction temperature is not particularly limited, but is usually set at room temperature or under heating.

Fourth manufacturing method In the compound of the present invention, X is -CHtYl-, that is, -CH,O-.

The compound group (Id) which is -CH,S-, -CH,NH- is represented by the general formula (■). A halogen compound or sulfonate compound and a hydride represented by the general formula (■) Roxy or mercaptan compound or its alkali metal substituted product, or amine It can be produced by reacting with a compound.

The reaction conditions are almost the same as in the third production method.

Fifth manufacturing method Among the compounds of the present invention, the compound (Ie) in which X1 is a vinylene group (-CH=CH-) is , a substituted benzyl halide represented by general formula (X) and triphenyl (or triphenyl) Substituted benzyltriphenylphosphonium by avoiding reaction with (butyl)phosphine halides, then 1-butyllithium, alkali metal amides, alkaline Bases such as potash metal alkoxides, methylsulfinyl methylide, sodium salts, etc. to give a substituted benzyltriphenylphosphorane, which was isolated without isolation. It is produced by reacting with aldehydes represented by the general formula (■).

The first stage reaction can proceed without solvent, but usually benzene or toluene.

It is carried out in an organic solvent such as xylene. The reaction temperature is not particularly limited.

The latter reaction uses the organic solvent, tetrahydrofuran, and ether used in the earlier reaction. , dimethoxyethane, dimethyl sulfoxide, alcohol, etc. Ru. The reaction temperature is not particularly limited.

6th manufacturing method Among the compounds of the present invention, the compound (Ig) in which D is a carboxy group has the general formula (If) produced by removing the ester residue from the corresponding ester represented by be able to.

In this reaction, hydration is performed in the presence of a base such as sodium carbonate or sodium hydroxide. Conventional methods such as decomposition or treatment with acids such as trifluoroacetic acid or hydrochloric acid can be applied. Wear.

7th manufacturing method In the compound of the present invention, X is -YfuY4-, i.e. -○-Y4- or -5-Y, - Compound (Ih) is a hydroxy or metal compound represented by the general formula (XI[I) Lucapato, or an alkali metal substituted product thereof, and a substituted atom represented by general formula (XV) It can be produced by avoiding reaction with rukyl halide.

The reaction conditions and the like are almost the same as in the third and fourth production methods.

8th manufacturing method Compound (Ii), which is a monoyl group, is a nitrile compound represented by the general formula (XV). It can be synthesized by reacting sodium azide with ammonium chloride.

The reaction is carried out by heating in an organic solvent such as dimethylformamide or dimethyl sulfoxide. This is done by

9th manufacturing method The compound of the present invention is a hydroxy compound represented by the general formula (X■) or a metal-substituted compound thereof. By reacting the compound with a substituted alkyl halide represented by the general formula (X■), can be manufactured by The reaction conditions are almost the same as those in the third production method and the fourth production method.

In addition, when compound (I) has a vinylene group, palladium-charcoal can be prepared using a conventional method. By deprotecting a compound that is returned to an alkyl group using catalytic reduction with an element, etc. can get.

Furthermore, conversion between objects can be carried out by conventional methods.

By alkylation, acylation, etc. of a compound in which R3 is an amino group, The compound in which R7 is a halo lower alkyl group is the compound in which R1 is a hydroxy lower alkyl group. The compound in which R1 is a hydroxymethyl group is a compound in which R is a formyl group. R1 is a lower alkoxy-lower alkyl group by reduction of a compound in which R1 is a lower alkyl group. The compound is R.

lower alkoxylation of compounds in which is a halo-lower alkyl group, Rt is lower alkoxy A compound in which R is a carbonyl lower alkylthio lower alkyl group is a halo lower alkyl group. obtained by lower alkoxycarbonyl lower alkylthiolation of compounds that are kill groups. It will be done.

Specific details are described in Examples.

The compounds of the present invention produced by these various methods include extraction.

Chemical operations commonly used in this field, such as recrystallization and column chromatography It is isolated and purified by applying

(1) Inhibition of guinea pig ileum and tracheal constriction by SRS-A and LTD system Method 2: A male Hartley guinea pig weighing 500-700g is given a head contusion. I killed more. The ileum was prepared using the method of Con5tantine (1965). The piece of trachea was placed in Tyrode solution (matrix) at 37°C with 95% 0□ + 5% CO1 aerated. It was suspended with a tension of 1 g in a Gnus tank with a volume of 10 m. Tissue was stabilized for 60 minutes During this time, the Tyrode solution was changed every 15 minutes and the tension was adjusted to Ig.

The generated tissue tension is measured isometrically using a strain gauge transducer. , recorded on the recticcorder. Submaximal concentration of 5RS-A in the ileum The response to 10-" MLTD of the trachea was measured. After this, the contractile effect of each agonist was measured again by adding various concentrations of the test compound. Established. The incubation time of the compound was 20 minutes. Results: Compound of the present invention For example, the compounds of Examples 23, 10.1B, 42°40.41 and 39 are It showed a strong anti-5RS-A effect in the guinea pig ileum (Table 1). Further implementation Example 23 Compounds 40 and 39 were tested by LTD in isolated guinea pig trachea. The contraction was suppressed (Table 1).

Table 1. Representative IClC50 of the present invention in isolated guinea pig ileum and trachea ( Compound Ileum Trachea //10 1.8XlO-'- 〃〃　18　3.3X10'-'- "42 8.1XlO-"- 40 3.6xlO-” 5.7xlO-” // 41 7.4XIO-’ − //39 7.3xlO-” 2.5xlO-’ (2) L in guinea pigs Method for suppressing advanced vascular permeability due to TD: Weight 270-30 after fasting for 16 hours Add 1% Evans Blae solution to 5 g of Hart Ley male guinea pigs. m/administered intravenously.

After 2 minutes, apply 5 nH2O, 1m//5i of LTD to the two shaved dorsal areas. te was administered. In addition, in order to examine non-specific stimulatory effects on animals, LTD, of solvent was administered at 0.1 m/m/intramembrane. exposed to the site where LTD4 and vehicle were administered. The pigment was extracted using the method of Harada et al. (1971), and Colorimetric determination was carried out. Vascular hyperpermeability caused by LTD4 is caused by LTD4 and solvent. It was expressed as the difference in the amount of dye exposed. Test compounds were administered at LTD, 30 minutes before administration. Orally administered.

Results; Compounds of Examples 23.39 and 40 showed no effect on LTD in guinea pigs. Increased vascular permeability was suppressed in a dose-dependent manner, with an ED50 value of 22.8. , 36.1 and 5, 5 mg/kgp, o. These results are Example 23. Compounds of 39 and 40 exhibit strong anti-leukotriene effects upon oral administration. This indicates that the

(3) Acute toxicity in rats Seven-week-old male F1scher 344 rats were used. Examples 39 and 4 Compound 0 was administered to rats at 1000 mg/kg p,o during a 7-day observation period. showed no toxic effects on

References Con5tantine, J, W, J, pharm, Pharmac ol,, ■, 384 Harada, M, et a, e,, J, Phar m, Pharmacol, 23, 218 Examples are listed below, and the present invention Detailed explanation.

In addition, a manufacturing example of the raw material compound is shown in Reference Example.

Reference example 1 3.9 g of 2-amino-5-mercapto-1,3,4-thiadiazole, potassium carbonate Ethyl bromoacetate 5 was added to a mixture of 4.2 g of aluminum and 50 mN of ethanol under ice cooling. After gradually adding g, the mixture was stirred at room temperature for 3 hours. Add 200ml of water to the reaction solution and add vinegar. Extracted with ethyl acid. The extract was washed with water, dried over anhydrous magnesium sulfate, and the solvent was distilled off. The resulting solid was washed with toluene and dried to give ethyl (5-amino-1,3, 2.7 g of 4-thiadiazol-2-ylthio)acetate were obtained. nuclear magnetic resonance Spectrum (CD (, j3. TMS, ppm) 1.25 (3H, t, -CHa ), 3.90 (2H,s, CHs-), 4.19 Reference Example 2 37.2 g of 2.5-dimercapto-1,3,4-thiadiazole was taken as Ethyl 3-[(5-merca) was washed with ethanol-water (roll) and dried under reduced pressure. 41.5 g of pt-1,3,4-thiadiazol-2-yl)thio]butyrate Obtained. Melting point 107-108℃ Reference example 3 A solution of 2.2 g of ethyl 0-nitrosinnamate dissolved in 30 m, e of ethanol. Add 2.2 g of reduced iron and a mixture of 0.5 m of concentrated hydrochloric acid and 2.5 m of water to the solution and leave for 1 hour. After heating under reflux, insoluble materials were separated from f, and liquid f was concentrated under reduced pressure. Sodium bicarbonate in the residue An aqueous solution was added, extracted with toluene, the extract was washed with water, and after drying, the solvent was distilled off and ethyl -1.6 g of yellow crystals of aminocinnamate were obtained.

Nuclear magnetic resonance spectrum (CD C1s, TMS, ppm) 1.30 (3 H, t+-CH3), 4.23 (2H, q, -o CHa), 6.30 (L H, d).

6.50-7.50 (4H, II+), 7.80 (IH, d) Reference example 4 4.7 g p-peptyloxybenzoic acid, 1-hydroxybenztriazole (H OBT) 2.7 g, tetrahydrofuran 50 m / dicyclohexy under water cooling. After adding 4.2 g of carbodiimide (DCC) and stirring at room temperature for 1 hour, Add 9 g of minophenol and stir overnight at room temperature. The resulting dicyclohexyl urea ? Concentrate the filtrate. The residue was dissolved in 500+n/ethyl acetate and diluted hydrochloric acid.

Fire washed with purified sodium hydrogen oxide solution and water, dried with anhydrous magnesium sulfate, and reduced. Concentrate under pressure. The residue was subjected to silica gel column chromatography. 500me) Elute with a mixture of toluene-ethyl acetate (1:l) and further evaporate with ethyl acetate. Recrystallized from p-hebutyloxy-N-(o-hydroxyphenyl) 5.6 g of benzamide was obtained.

Melting point 131-133℃ Reference examples 5 to 7 The following compound was obtained in the same manner as in Reference Example 4.

Reference example 5 m-hebutyloxy-N- Reference example 6 p-hebutyloxy-N- Reference example 7 m-hebutyloxy-N- Reference example 8 m-hebutyloxy-N-(0-hydroxyphenyl)benza obtained in Reference Example 5 Mido 1.6g, chloroacetonitrile 0.5g, anhydrous potassium carbonate 0.8g, iodine Potassium uride 0, 1 g, tetra-n-butylammonium bromide 0, A mixture of 1 g and 20 m of methyl ethyl ketone was vigorously stirred at 70 to 80°C for 1 hour. do. After cooling, add 100ml of ethyl acetate to the reaction solution, wash with water, and add anhydrous magnesium sulfate. The residue was recrystallized from ethanol to give m-hebutyloxy-N. 1.4 g of -(0-cyanomethoxyphenyl)benzamide was obtained.

Melting point 105-106°C Reference examples 9 to 11 The following compound was obtained in the same manner as in Reference Example 8.

Reference example i.

p-hebutyloxy-N- Reference example ll m-hebutyloxy-N- Example 1 Ethyl (5-amino-1,3,4-thiadiazol-2-y) obtained in Reference Example 1 0.5 g of m-hebutyloxybenzene, 0.7 g of dicycloacetate, Add 0.7 g of hexylcarbodiimide and 2 to 3 mg of p-toluenesulfonic acid to pyridine. The mixture was stirred at room temperature for 2 hours. After the reaction, insoluble matter is separated in a furnace and the f liquid is concentrated under reduced pressure. do. The residue was extracted with ethyl acetate, the extract was washed with water, dried, and the solvent was distilled off to solidify. Get a shape. The solid was washed with a mixture of toluene and n-hexane (2:1) and then dried. ethyl[[5-(m-hebutyloxybenzamide)-1,3,4-thiadiazine] 1.0 g of zol-2-yl]thiocoacetate was obtained. Melting point 114-116℃ Elemental analysis value (as CtoHttNsO, Sl) 0% H% 8% Theoretical value 54.90 6.22 9.60 Experimental value 55.20 6.29 9. 77 Compounds of Examples 7 and 10 described later were obtained in the same manner as in Example 1.

Example 2 0.4 g of ethyl 0-aminocinnamate obtained in Reference Example 3 was added to 4 m/p of pyridine. The dissolved solution was cooled to below -20°C, and p-(4-phenylbutoxy)benzoic acid was obtained by thionyl chlorination in benzene with dimethylformamide as a catalyst. After adding 0.7 g of (4-phenylbutoxy)benzoyl chloride, it was kept at room temperature for 30 minutes. I stirred it up for a while. Add 30ml of water to the reaction solution and extract with ethyl acetate. Extract with water After washing with 5% hydrochloric acid and water sequentially, drying with anhydrous magnesium sulfate, the solvent was distilled off. A solid was obtained. After heating and dissolving the solid in 10 m/toluene, add 2 m/n-hexane. The crystals precipitated by cold leaching were dried, and ethyl o-[p-(4-phenylbutylene) was added. 0.8 g of benzamitococinnamate was obtained. Melting point 129-131'c Elemental analysis value (CI8HtsN O-bound) 0% H% N% Theoretical value 75.82 6.59 3.16 Experimental value 75.83 6.53 3. 14 In the same manner as in Example 2, compounds of Examples 5.6 and 8 below were obtained.

Example 3 p-hebutyloxy-2-bromoacetophenone 0.6 g, ethyl (5-merca Butyrate 0.6g, carbonic acid 0.4 g of potassium was heated under reflux with 20 me of acetone for 30 minutes. cold soaked, insoluble Separate the materials in a furnace, concentrate the liquid under reduced pressure, wash the resulting solids with ethanol, dry them, and evaporate them. Chil-4-[[5-[(p-hebutyloxyphenacyl)thio]-1,3,4-thi 1.0 g of adiazol-2-ylcothio]butyrate was obtained. Melting point 72-73℃ Elemental analysis value (as CtyH32N 204S3) 0% Hz 8% Theoretical value 55.62 6.49 5.64 Experimental value 55.54 6.52 5. 52 In the same manner as in Example 3, the compound of Example 9 described later was obtained.

Example 4 190 mg of ethyl 5-hydroxy-1-methoxyindan-2-acetate and p -220 mg of hebutyloxybenzyl chloride in 2 ml of dimethylformamide 180 mg of potassium carbonate was added thereto, and the mixture was stirred at 60°C overnight. After cooling, water Add ethyl acetate and shake well, and separate the organic layer. Wash the organic layer with water, dry it, The residue obtained by concentration was subjected to flash chromatography (eluent: toluene/acetic acid). Purification with ethyl (25/1) yields 220 mg of ethyl 5-(p-hebutyl). xybenzyloxy)-1-methoxy-2-indane acetate as a colorless oil. n0 nuclear magnetic resonance spectrum (CDCl2.TMs, pI) m): 1 , 89 (3H.

br), 1.23 (3H, t, J = 7 Hz), 1.2 to 1.9 (10H ), 2.3-3.4 (5H), 3.41 (3H, s), 3.96 (2H, t, J =7Hz).

4.17 (2H, q, J = 7Hz), 4.48 (IH, d, J = 3.5Hz) .

4.96 (2H, s), 6.8-7.4 (7H) obtained by Examples 5-10 The compounds and their physical properties are shown below.

Example 5 Ethyl [[5-(p-hebutyloxybenzamide)-1,3,4-thiadiazole R-2-ylcothiocoacetate i) Melting point 159-160°C ii) Elemental analysis value (Ct. H*7N304S2) 0% Hz 8% Theoretical value, ) 4.90 6.22 9.60 Experimental value 55.18 G, 39 9 ．． 63 raw material compounds Example 6 Ethyl [[5-(p-(4-phenylbutoxy)benzamide]-1゜3.4- Thiadiazol-2-yl]thio]acetate i) Melting point 147-148°C ii) Elemental analysis value (as C**HtsN 304S 2) 0% Hz N% Theory @ 58.58 5.34 8', 91 Experimental value 58.37 5.23 8 ．． 89 raw material compounds Example 7 Ethyl [[5-(m-(4-phenylbutoxy)benzamide]-1゜3.4- Thiadiazol-2-yl]thiocoacetate i) Melting point 124-126°C ii) Elemental analysis value (as CtsHtsNaO4St) 0% Hz 8% Theoretical value 5B, 58 5.34 8.91 Experimental value 58.80 5.36 8. 83 raw material compounds Example 8 Ethyl o-[p-(4-phenylbutoxy)benzamide]cinnamate i) Melting point: 129-131'C 11) Elemental analysis value (C, aHzaN as O4) 0% Hz N% Theoretical value 75.82 6.59 3.16 Experimental value 75.83 6.53 3. 14 raw material compounds Example 9 Ethyl 4-[[5-(p-hebutyloxybenzyl)thio-1,3,4-thiazidi Azol-2-yl]thiocobutyrate i) Melting point 56-57°C ii) Elemental analysis value (as CstHstNtOsSs), 0% 8% 8% Theoretical value 56.38 6.88 5.98 Experimental value 56.32 7.0B, 5.87 Raw material compounds Example 10 Ethyl 3-[o-(p-(4-phenylbutoxy)benzamide]phene Propionate i) Oily substance ii) Nuclear magnetic resonance spectrum (CD Cl s, TM S, ppm) 1.10 (3H, t), 1.5 ~2.0 (4H), 2.4~3.0 (6H), 3.8~4.3 (4) (), 6. 8-8.2 (13H) raw material compound Example 11 Ethyl o-[p-(4-phenylbutoxy)benzamide] obtained in Example 2 Add 0.5 g of cinnamate to 2 ml of 50% potassium hydroxide and 20 a+ methanol. The mixture was heated under reflux for 10 minutes. After adding 20ml of water to the reaction solution, 10% hydrochloric acid Add acid to remove precipitated crystals, wash with water and ethanol sequentially, and dry. 0.15 g of o-(p-(4-phenylbutoxy)benzamido]cinnamic acid was obtained. .

i) Melting point: 129-131'C (recrystallized from ethanol) ii) Elemental analysis value ( C*aHt*N　O, as) 0% 8% 8% Theoretical value 75.82 6.59 3.16 Experimental value 75.83 6.53 3. 14 In the same manner as in Example 11, compounds of Examples 12 to 18 described later were obtained.

Example 12 [[5-(p-Hebutyloxybenzamide)-1,3,4-thiadiazole- 2-ylcothiocoacetic acid i) Melting point 246-248°C 11) Elemental content 'tR@ (as Cls Ht 3 Ns O4S t) 0% 8% 8% Theoretical value 52.79 5.66 10.26 Experimental value 52.93 5,75 1 0.19 raw material compound Compound of Example 5 Example 13 [[5-[1)-(4-phenylbutoxy)benzamide]-1,3,4-thia Diazol-2-ylcothiocoacetic acid i) Melting point 244-245°C ii,) Elemental analysis value (as C31H□Ns O4S t) 0% 8% 8 % 8% Theoretical value 56.87 4.77 9.47 14.46 Experimental value 56,68 4 ．． 57 9.43 14.31 Raw material compound Compound of Example 6 Example 14 [C5(m(47E:luptoxy)benzamide it,a,4-thiadiazole) Melting point: 182-183°C 11) Elemental analysis value (as Ct + H21Ns O4S 2) 0% H% 8 % 8% Theoretical value 56.87 4.77 9.47 14.46 Experimental value 56.93 4 ．． 62 9.37 14.30 Raw material compound Compound of Example 7 Example 15 [[5-(m-heptyloxybenzamide)-1,3,4-thiadiazole- 2-ylcothio]acetic acid i) Melting point: 196-198°C 11) Elemental analysis value (as C + e Hz 3 N s O4S t) 0% H %　N% Theoretical value 52.79 5.66 10.26 Experimental value 52.78, ), 58 10-. 14 raw material compounds Compound of Example 1 Example 16 4-[[5-(p-hebutyloxyphenacyl)thio]-1,3,4-thiadias Sol-2-yl]thio]butyric acid i) Melting point 116-117°C ii) Elemental analysis value (as C21HtsN 204Ss) 0% H%N % Theoretical value 53.82 6.02 5.9B Experimental value 53.60 6.05 5. 87 raw material compounds Compound of Example 3 Example 17 4-[[:5-[(p-hebutyloxybenzyl)thio]-1,3.4-thi Asiazol-2-ylcothiocobutyric acid i) Melting point: 106-107℃ ii) Elemental analysis value (as C2oH2sNtOsS3) 0% H% N% Theoretical value 54.51 6.40 6.36 Experimental value 54.49 6.54 6. 36 raw material compounds Compound of Example 9 Example 18 3-[o-[p-(4-phenylbutoxy)benzamido]phenylcobrobio acid i) Melting point: 154-1569C ii) Elemental analysis value (as C!IIH*tN O4) 0% H% N% Theoretical value 74.80 6.52 3.35 Experimental value 74.48 6.87 3. 63 raw material compounds Compound of Example IO Example 19 Ethyl 5-[p-hebutyloxybenzyloxy)-1-methane obtained in Example 4 220 mg of toxy-2-indan acetate was added to 1 m of tetrahydrofuran, meta Dissolve in 8me of alcohol, add 1ml of 5% aqueous sodium hydroxide solution and stir at room temperature for 8 hours. Stirred. It was diluted with water, acidified with hydrochloric acid, and extracted with ethyl acetate. Ethyl acetate layer Wash with water.

Dry and concentrate. The obtained crystalline residue is recrystallized from ether-pentane. and 5-(p-hebutyloxybenzyloxy)-1-methoxy-2-yne 150 mg of danacetic acid was obtained.

i) Melting point 80-82°C 11) Elemental analysis value (as CzeH:++Os) 0% H% Theoretical value 73.21 8.03 Experimental value 73.20 8.26 Example 20 p-hebutyloxy-N-(o-cyanomethoxyphenyl) obtained in Reference Example 10 ) Benzamide 500mg, sodium azide 116mg, ammonium chloride 9 Stir a mixture of 5 mg and dimethylformamide at 140-150°C overnight. Ru. Cool immersion, add 50 mN of water to the reaction solution, and wash with ethyl acetate. Acidify the aqueous layer with dilute hydrochloric acid and extracted with ethyl acetate. Wash the extract with water and dry with anhydrous magnesium sulfate. The residue was recrystallized from ethanol to give 4-hebutyloxy-2'- 300 mg of (5-tetrazolylmethoxy)benzanilide was obtained.

i) Melting point: 148-150℃ ii) Elemental analysis value (as C*tHttNsOs) 0% H% N% Theoretical value 64.53 6.65 17.10 Experimental value 64.65 6.70 1 7.13 In the same manner as in Example 20, the following compounds of Examples 21 to 23 were obtained.

Example 21 4-Hebutyloxy-3'-(5-tetrazolylmethoxy)benzanilide i) Melting point: 187-190℃ ii) Elemental analysis value (as C*zHtyNsOs) 0% H% Calculated value 64.53 6.65 Actual value 64.64 6;81 raw material compound Compound of Reference Example 9 Example 22 3-Hebutyloxy-3'-(5-tetrazolylmethoxy)benzanilide i) Melting point: 149-150℃ ii) Elemental analysis value (CttH!?N as 503) 0% H% N% Calculated value 64.53 6.65 17.10 Actual value 64.55 6.77 1 7.02 Raw material compounds Compound of Reference Example 11 Example 23 3-hebutyloxy-2'-(5-tetrazolylmethoxy)benzanilide i) Melting point: 108-110℃ ii) Elemental analysis value (as C*tHztNsOs) 0% H% N% Calculated value 64.53 6.65 17.10 Actual value 64.59 6.77 1 7.13 Raw material compounds Compound of Reference Example 8 Reference example 12 Add 1 drop of N,N-dimethylformamide to 5 ml of solution and oxidize at below -30°C. Add 2 ml of zaryl chloride and stir at room temperature for 3 hours. Concentrate the reaction solution under reduced pressure. , to obtain crude p-(4-phenylbutoxy)benzoyl chloride. this thing was dissolved in 5 m/m of methylene chloride, and 1 g of 2-amino-4-methylphenol was added. , added to a solution of 5 m/pyridine under water cooling, and left at room temperature for 3 hours. Add concentrated salt to the reaction solution. Pour into acid-ice and extract with ethyl acetate. Wash the extract with water and dilute with sodium bicarbonate water. After washing with a solution, further washing with water, drying with anhydrous magnesium sulfate, and concentrating under reduced pressure, '-Hydroxy-5'-methyl-4-(4-phenylbutoxy)benzanilide 1.4g was obtained.

Melting point: 138-140°C.

Reference example 13 Treated in the same manner as in Reference Example 12 using 2-amino-4-chlorophenol Ig as the starting material. 5'-chloro-2'-hydroxy-4-(4-phenylbutoxy)ben 1.4.2 g of Zuanilide was obtained.

Melting point: 137-139°C.

Reference example 14 Same as Reference Example 12 using 400 mg of 2-amino-4-nitrophenol as the starting material. 2'-hydroxy-5'-di)rho-4-(4-phenylbutoxy) c) 450 mg of benzanilide was obtained.

Melting point: 174-176°C.

Reference example 15 Using 400 mg of 2-aminophenol as the starting material, it was treated in the same manner as in Reference Example 12. , 2'-hydroxy-4-(4-phenylbutoxy)benzanilide 630 mg I got it. Melting point 116-117°C.

Reference example 16 Ethyl 3-(3-amino-4-hydroxyphenyl)propionate hydrochloride 1g was treated as the starting material in the same manner as in Reference Example 12 to obtain ethyl 3-[4-hydroxy- 3-[p-(4-phenylbutoxy)benzoyl]amidophenyl]propione 1.6 g of salt was obtained.

Melting point 94-96℃ Reference example 17 1.6 g sodium hydride (60%, oily), 60 m dimethyl sulfoxide / was stirred at 55 to 606C for 1 hour. After returning to room temperature, (4-carbo xybutyl) triphenylphosphonium bromide 9g, dimethyl sulfoxy After adding 20 mf' of O-nitrobenzalde solution and incubating at room temperature for 30 minutes, Add a solution of 3 g of hydrogen and 10 me of dimethyl sulfoxide, and stir at room temperature for 2 hours. do. Pour the reaction solution into cold dilute hydrochloric acid and extract with Ni-chill. After washing the extract with water, anhydrous Dry over magnesium sulfate and reduce in vacuo to give an oily 6-(0-nitrophenyl)- 5-hexenoic acid was obtained. Dissolve this in 20ml of ethanol, ff, and 4ml of concentrated hydrochloric acid. Add to the liquid, heat under reflux for 3 hours, wash with water, wash with purified sodium hydrogen oxide water, and wash with water. After drying over anhydrous magnesium sulfate, concentrate under reduced pressure. Transfer the residue to a silica gel column Chromatography and elution with toluene yielded ethyl 6-(0-nitrophe). 0.73 g of Nyl)-5-hexenate was obtained.

Dissolve this in 10me of ethanol and add 0.1g of 10% palladium-carbon. Then, catalytic reduction is carried out until hydrogen absorption stops. The catalyst was filtered off, concentrated under reduced pressure, and ethyl 6 0.6 g of -(o-aminophenyl)hexenate was obtained.

Nuclear magnetic resonance spectrum (CD C1, medium, TMS internal standard, ppm) 124 ( t, 3H), '1.0-2.0 (m, 6H), 2.30 (t, 2H).

2.49 (t, 2H), 2.8-3.8 (2H), 4.10 (q, 2H).

6.5-7.2 (m, 4H) Reference example 18 2 g of 0-ethoxycarbonylmethoxybenzoic acid and tg of p-aminophenol. As a raw material, ethyl 0-[(p-hydroxyphenyl ) 1.5 g of carbamoyl coquinoxy acetate was obtained. Melting point 208-210℃ .

Reference example 19 CI(CH2)3sCHtCOOC2I(sethyl mercaptoacetate 2. 0g, 1-bromo-3-chloropropane 3.13g, anhydrous potassium carbonate 2.29 A mixture of g and N, N-dimethylformamide 10m// was heated at room temperature for 3 hours. Mix it up.

The reaction solution is diluted with toluene and insoluble matter is filtered. Add the filtrate to aqueous sodium hydroxide solution , washed successively with water, dried over anhydrous magnesium sulfate, and vacuumed. residue Subjected to silica gel column chromatography, hexane-ethyl acetate (15:1) ), and the oily ethyl [(3-chloropropyl)thio]acetate 2 ．． 65g was obtained.

Nuclear magnetic resonance spectrum (in CDCIs, TMS internal standard, ppm) 1.28 ( t, 3H), 1.9-2.2 (2H), 2.7-2.9 (2H).

3.20 (s, 3H), 3.64 (t, 2H), 4.19 (q, 2H) mass spec m/z: 196 (M+) Reference example 20 Vanillin 860mg, 4-bromobutylbenzene 1. OOg, potassium carbonate 1. A mixture of oog and 2-butanone 8+nf was heated to reflux for 3 hours. reaction mixture Poured into water and extracted the product with ether. Wash the ether layer with water, dry it, and concentrate it. The residue obtained was subjected to silica gel column chromatography and eluted with toluene. 500mg of 4-(4-phenylbutoxy)-3-methoxybenzaldehyde I got it.

Nuclear magnetic resonance spectrum (in CDC13, TMS internal standard, ppm) 1.8 ~2.0 (4H), 2.71 (t, 2H, J=7Hz), 3.89 (s.

3H), 4.08 (t, 2H, J = 7Hz), 6.92 (d, IH, J = 9.5 Hz), 7.15 to 7.50 (7H), 9.85 (s, IH) Reference Example 21 4-(4-phenylbutoxy)-3-methoxybenzaldehy obtained in Reference Example 20 Dissolve 660 mg of sodium borohydride in 5 m of methanol and add 2 ml of sodium borohydride at 0°C. 00 mg was added gradually. After stirring for 1 hour, add water and ethyl acetate and mix vigorously. I stirred it up. The ethyl acetate layer obtained by separating the layers was washed successively with water and 9 brine, and concentrated. did. The residue was subjected to silica gel column chromatography using toluene:ethyl acetate. Elute with 4-(4-phenylbutoxy)-3-methoxybendi 430 mg of alcohol was obtained.

Nuclear magnetic resonance spectrum (in CDC13, TMS internal standard, ppm) 1. 7-1.9 (4H), 2.68 (t, 2H, J=7H2), 3.87C5°3H ), 4.00 (t, 2H, J = 7Hz), 4.60 (d, IH, J = 5.5 Reference Example 22 4-(4-phenylbutoxy)-3-methoxybenzyl alcohol obtained in Reference Example 21 Add nitrogen chloride to a solution of 410 mg of alcohol, 0.5 m of toluene, and 2 m of benzene at 0°C. Onyl 0.5[+1/] was added. After stirring for 20 minutes, saturated sodium bicarbonate solution was added. Separate the liquid Then, the organic layer was washed with water and brine and concentrated. Chromatograph the residue on a silica gel column. Raffy and eluted with toluene:hexane:ethyl acetate (20:15:1) , 4-chloromethyl-2-methoxy-1-(4-phenylbutoxy)benzene 3 00 mg was obtained.

Nuclear magnetic resonance spectrum (CD in CI!, TMS internal standard, ppm) 1.75 ~1.95 (4H), 2.68 (t, 2H, J=7Hz), 3.87 (s, 3H ), 4.01 (d, 2H, J=7Hz), 4.52 (s, 2H), 6.80-6 ．． 90 (3H), 7.15-7.25 (5H) The above product was dissolved in xylene 2me. The mixture was dissolved and treated with 304 mg of triphenylphosphine at reflux temperature for 1.5 hours. cold The precipitated colorless crystals were collected by suction and dried under reduced pressure to give l:4-(4-phenylene). (rubutoxy)-2-methoxypenzylcotriphenylphosphonium chloride 260 mg was obtained. Melting point 119-128°C.

Mass spectrum m/z: 531 (M”-CI) Reference example 23 By the same operation as in Reference Examples 10 to 22, o- (4-phenylbutoxy)benzyltriphenylphosphonium chloride was obtained . Melting point 214-216°C.

Reference example 24 390mg of 4-chloromethyl-1-(4-phenylbutoxy)benzene and cateco 180 mg of potassium carbonate and 270 mg of potassium carbonate were mixed with 1. The mixture was stirred overnight at room temperature in a 5 m/m medium. Disperse the reaction mixture in water and ethyl acetate and separate the liquids. did. The ethyl acetate layer was sequentially washed with Izumi 9 brine, dried, and concentrated. the residue obtained was subjected to silica gel column chromatography, eluted with toluene, arp- 240 mg of (4-phenylbutoxy)benzyloxy]phenol was obtained. nuclear magnetism Gas resonance spectrum (CD CI, medium, TMS internal standard, ppm) 1.7-2.0 (4H), 2.5-2.8 (2H), 3. B~4.1 (2H).

4.95 (s, 2H), 5.63 (disappeared with s, IH, DzO), 6.5-7.5 Reference example 25 -(4-phenylbutyloxy)benzylcothiocoaniline was obtained.

Nuclear magnetic resonance spectrum (in CDCh, TMS internal standard, pp[11) 1.7~ 1.9 (4H), 2.6-2.8 (2H), 3.85 (s, 2H).

368-4.0 (2H), 4.2 (broad, 2H, disappeared with DtO).

6.5-7.3 (13H) -0.64g, anhydrous potassium carbonate 0.48g, 2-butanone 20ml. catalyst of tetra n-butylammonium bromide was heated under reflux for 3 hours. . Add toluene LGO ml to the reaction solution and wash sequentially with dilute sodium hydroxide solution and water. , dried over anhydrous magnesium sulfate, compressed under reduced pressure, and recrystallized from isopropyl alcohol. and ethyl 4-methyl-2(p-(4-phenylbutoxy)benzamide rough 1.5 g of enoxy acetate was obtained.

physical and chemical properties 1) Melting point: 79-80℃ 2) Elemental analysis values (as CzgH5+NO5) C (%) H (%) N (%) Theoretical value 72.86 6.77 3.03 Experimental value 72.80 6.63 2. Compounds of Examples 25 to 32 were obtained in the same manner as in Example 24.

Example 25 Ethyl 4-chloro-2-1: p-(4-phenylbutoxy)benzamide rough enoxy acetate physical and chemical properties l) Melting point: 81-84℃ 2) Elemental analysis value (C2?H28CIN Os;!-Site) C (%) H (% ) N (%) CI (%) Theoretical value 67.28 5°86 2.91 7.36 Actual Experimental value 67.33 5.87 2.82 7.31 Raw material compound: Reference example 13 Compound+BrCHZCOOCtHs Example 26 Ethyl 4-nitro 2-(p-(4-phenylbutoxy)benzamide lafe) Noxyacetate physical and chemical properties 1) Melting point: 113℃ 2) Elemental analysis value (C2?H2as tO7) N (%) Theoretical value 5.09 Experimental value 5.39 Raw material compound: Compound of Reference Example 14: B r CH2COOCz Hs ethyl o-(p-(4-phenylbutoxy)benzamide dolphenoxy acetate physical and chemical properties I) Oily substance 2) Elemental analysis value (as CttH2sN Os) C (%) H (%) N ( %) Theoretical value 72.46 6.53 3.13 Experimental value 72.22 6.53 3. 05 raw material compound: Compound of Reference Example 15 + BrCH, C00C, H3 Example 28 Ethyl 3-[4-ethoxycarbomethoxy-3-(p-(4-phenylbutoxy) C) Physical and chemical properties of benzamide phenyl propionate 1) Melting point: 61-62℃ 2) Elemental analysis values (as C32H37N Ot) C (%) H (%) N ( %) Theoretical value 70.18 6,81 2.56 Experimental value 7Q, 13 6.73 2. 47 Raw material compound: Compound of Reference Example 16 + B r CHt COOCt I (5 Example 29 Ethyl ((3-(4-chloro-2-(p-(4-phenylbutoxy)benza Midophenoxypropylthioacetate physical and chemical properties l) Melting point: 70-73°C 2) Element content Fi-f direct (C3oH34N, 05S as C1) N (%) Theoretical value 2.52 Experimental value 2.71 Raw material compound: Compound of Reference Example 13 Compound of Reference Example 19 Ethyl o-(N-(p -(4-phenylbutoxy)phenyl]carbamoyl]phenoxyacetate physical and chemical properties 1) Melting point: 86-88℃ 2) Elemental analysis values (as CttHtsNOs) C (%) H (%) N (% ) Theoretical value 72.46 6.53 3.13 Experimental value? 2.54 6.62 3. IQ raw material compound: Compound of Reference Example 18+Br(CH,). Ph ethyl o-(p -(4-phenylbutoxy)benzyloxyfuphenoxy acetate physical and chemical properties l) Oily substance 2) Nuclear magnetic resonance spectrum (CD in CI3, TMS internal standard, ppm ) 1.24 (t, 3H), L, S ~ 1.8 (4H), 2.5 ~ 2.7 (2H) , 3.8-4.0 (611), 4.16 (Q, 211), 4.61 (s, 2H) , 5.02 (s, 211), 6.7-7.3 (1311) Raw material compound: Reference example 2 Compound 4÷BrCHtCOOC2Hiethyl N-(o-((p-(4- phenylbutoxy)benzyl]thio]phenyl]glycine physical and chemical properties l) Oily substance 2) Nuclear magnetic resonance spectrum (CDC1, medium, TMS internal standard, ppm) 1.2 8 (t, 3H), 1.7-1.9 (4H), 2.6-2.8 (21 (), 3.8 ~4.0 (61), 4. z7 (q, 2) 1), 5.84 (11 (), 6.6-7 ．． 3 (13H) raw material compound: Compound B r CH * G 00 of Reference Example 25 Ct H5p-(phenylbutoxy)benzoic acid 1g and oxalyl chloride 2m Methylene of p-(4-phenylbutoxy)benzoyl chloride prepared from The chloride solution was added to the ethyl 6-(〇-aminophenyl) obtained in Reference Example 17. Add to a solution of 0.6 g of xanate and 10 ml of pyridine at -30°C or below. at room temperature Stir overnight and compress under reduced pressure. Add toluene to the residue, wash with dilute hydrochloric acid, and then with water. , dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain oily ethyl 6-(o-( p-(4-phenylbutoxy)benzamide]phenyl]hexanate 1.0g I got it.

physical and chemical properties 1) Oily substance 2) Nuclear magnetic resonance spectrum (CD C’rs, TMS internal standard, ppm) 1 ．． 20(t, 3H), 1.0-2.0(::m, l0H), 2.28( t, 2H), 2.4-2.8 (m, 4tl), 4. O2(t , 21), 4.08 (q, 2H), 8.8-8.2 (m, 13) 1) 3) Mass Spectrum m/z: 487 (M”) Prepared from Lml of 3-phere (oxypropoxy)benzoyl chloride and ethyl O-aminocinname) G. 0.52 g of p-(3-phenoxypropoxy)benzado]cinnamate was obtained. Ta.

physical and chemical properties l) Melting point: 155-157℃ 2) Elemental analysis values (as CztHttNOs) C (%) H (%) N (% ) Theoretical value 72.79 B, 11 3.14 Experimental value 72.69 6.10 3. 15 Ethyl o-(p-(3-phenoxypropoxy) obtained in Example 34) Benzamide] Cinname) 2 + Omg, methanol 10ml, ethyl acetate 20 Add 10% palladium-carbon to ml of solution and perform catalytic reduction until hydrogen absorption stops. Ru. The catalyst was filtered off, concentrated under reduced pressure, and the residue was recrystallized from isopropyl alcohol. and ethyl 3-Co-(p-(3-phenoxypropoxy)benzamide) 200 mg of phenyl]propionate was obtained.

physical and chemical properties 1) Melting point: 89-90℃ 2) Elemental analysis value (as C2tHtsN Os) C (%) H (%) N ( %) Theoretical value 72.4B 6.53 3.13 Experimental value 72.27 6.54 3. 12toxybenzyl]-triphenylphosphonium chloride 260mg Trahydrofuran2. 1.42 M n-butyllithium at 0°C in suspension in 5 mL 0.36 ml of a hum/hexane solution was added dropwise. After flying for 10 minutes, a dark red solution appears. became. Using a syringe, add this solution to ethyl 0-formylphenoxy acetate. 114 mg was added dropwise to a solution of 1 ml of tetrahydrofuran at O''C. After stirring, saturated ammonium chloride water was added. The product was extracted with ether.

The ether layer was washed with water and brine, dried and concentrated, and the crude product was analyzed by preparative TLC. When separated (developing solution, hexane; methylene chloride: acetone = 8:2 + 1), 17 0 mg ethyl o-[3-methoxy, 4-(4-phenylbutoxy)styryl ] Phenoxy acetate was obtained.

physical and chemical properties 1) Nuclear magnetic resonance spectrum (CDC1j, TMS internal standard, ppm ) 1.27, 1.29 (respectively t1 total 3H, J = 7.2Hz), 1.7 5-1.9 (4H), 2.6-2.75 (2H), 3.52 (s), 3H ), 3.95-4.40 (4H), 4.61.4.66 (S.

Combined with 2) 1), 6.6-7.6 (14H) phenylphosphonium chloride A suspension of 230 mg of L4Mn-butylene in 2 ml of tetrahydrofuran was added at 0°C. A lithium/hexane solution was added dropwise. After flying for 20 minutes, this deep red solution was Ethyl 0-formylphenoxyacetate) 100mg tetrahydrofuran 1 ml solution at 0°C. After flying for 50 minutes, saturated ammonium chloride Add an aqueous solution of aluminum and extract the product with ethyl acetate. Add the ethyl acetate layer to water (twice) , Washed successively with saturated brine, dried, and concentrated under reduced pressure. 380 mg of the obtained residue Purified by silica gel preparative thin layer chromatography, ethyl o-(o-(4-ph) phenylbutoxy)styryl]phenoxyacetate-1-180mg as a colorless curved product I got two.

physical and chemical properties ■) Oily substance 2) Nuclear magnetic resonance spectrum (CD C13, TMS internal standard, ppm ) 1.2-1.4 (3) 1), 1.7-1, 9 (41(), 2, 6- 2.8 (2) 1), 3.9-4.4 (4H), 4.61 and 4.63 (respectively S9 total 2H), 6. tl+-7,7(15H) Ethiobtained in Example 26 4-nitro-2-(p-(4-phenylbutoxy)benzamide)phenoki Cyacetate 2.81g and ethanol-tetrahydrofuran (1:l) 50 Add 0.5 g of 10% palladium-carbon to ml of the mixed solution, and absorb hydrogen at room temperature and normal pressure. Catalytic reduction is carried out until the yield stops. The catalyst was removed by filtration, the filtrate was condensed under reduced pressure, and the obtained F-2 crystals were obtained. Wash with isopropyl alcohol and add ethyl 4-amino-2-(p-(4-ph). 1.72 g of nylbutoxybenzamide]phenoxyacetate was obtained.

physical and chemical properties ■) Melting point: 88-90°C 2) Nuclear magnetic resonance spectrum (CD in CI3, TMS internal standard, ppm) , 26(t, 3[), 1.5~2.0(m), 4t(), 2.4~ 2.8(m, 2t(), 3.8-4.2(m, 2)1j, 4.

22 (Q, 2H), 4.60 (s, 2H), 6.0-7.0 (m, 12H) actual rniethyl 4-methyl-2-(p-(4-phenylbutoxy) obtained in Example 24 ) Benzamide] 1.5 g of phenoxy acetate in 10% potassium hydroxide-90 % methanol solution and stirred at 50-60°C for 1 hour. saturated salt After adding LO ml of water, acidify with dilute hydrochloric acid and extract with ethyl acetate. Wash the extract with water , dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Residue from ethyl acetate It crystallized and gave 4-methyl-2-(p-(4-phenylbutoxy)benzamide)phene. 1.12 g of noxyacetic acid was obtained.

physical and chemical properties 1) Melting point: 122-123℃ 2) Elemental analysis value (as CtaH2?N Os) C (%) H (%) N ( %) Theoretical value 72.04 6.28 3.23 Experimental value? 1.79 6.23 3. Compounds of Examples 10 to 52 were obtained in the same manner as in Example 39.

4-chloro-2-(p-(4-phenylbutoxy)benzamide) phenoxy vinegar acid physical and chemical properties l) Melting point: 139-140℃ 2) Elemental analysis value (as czsHx4No5C1) C (%) H (%) N (%) Theoretical value 66.15 5゜33 3.09 Experimental value 66.01 5J4 3.1 6 Raw material compound; Compound of Example 25 4-nitro-2-(p-(4-phenylbutoxy)benzamide) phenoxy vinegar acid physical and chemical properties 1) Melting point: 168-170℃ 2) Elemental analysis values (as Ct, Ht, NtQ□) C (%) H (%) N ( %) Theoretical value 64.65° 5.21 6.03 Experimental value 64.47 5.29 5 ．． 89 Raw material compound: Compound of Example 26 acid physical and chemical properties l) Melting point: 135-137℃ 2) Elemental analysis value (as C*sH□No) C (%) H (%) N (%) Calculated value 71.5g 6.01 3,34 Actual value 71.54 5.98 3J 5 Raw material compound: Compound of Example 27 3-[4-carbomethoxy-3-(p-(4-phenylbutoxy)benzamide) [Phenyl]propionic acid physicochemical properties l) Melting point: 218-220℃ 2) Elemental analysis value (as C*aHtsN Ot) C (%) H (%) N ( %) Theoretical value 68.42 5.95 2.85 Experimental value 68.27 6.00 2, 9G raw material compound: Compound of Example 28 ((3-(4-chloro-2-(p-(4-phenylbutoxy)benzamide) Physical and chemical properties of phenoxy[propyl]thio]acetic acid l) Melting point: 94-96℃ 2) Elemental analysis value (as CzsHsoN OsS C1) C (%) H (%) N (%) Theoretical value 63.69 5.73 2.65 Experimental value 63.54 5.78 2. 56 Raw material compound: Compound of Example 29 o-(N-(p-(4-phenylbutoxy)phenyl]carbamoyl]pheno xyacetic acid physical and chemical properties Melting point: 150-152℃ 2) Elemental analysis value (as C!sHtsN Os) C (%) H (%) N ( %) Theoretical value 71.5g 6.01 3.34 Experimental value? 1.41 6, 12 3. 43 Raw material compound: Compound of Example 30 ]hexanoic acid physical and chemical properties l) Melting point: 125-127℃ 2) Elemental content’F value (as CtsHs+NO4) C (%) H (%) N (% ) Total W (i 75, 79 7, 24:a, O5 actual value 75.61 7.27 3.01 Raw material compound: Compound of Example 33 propionic acid physical and chemical properties Engineering) Melting point: 161-163°C 2) Elemental analysis values (as C□H*5NOs) C (%) H (%) N (%) Calculated value 71.58 6.01 3J4 Missing value 71.49 B, 05 3. SQ raw material compound: Compound of Example 35 4-amino-2-(p-(4-phenylbutoxy)benzamide) phenoxy vinegar acid physical and chemical properties l) Melting point: 178~tao℃ 2) Elemental analysis value (as C25H28N tos) N (%) Calculated value 6.45 Actual value 6.32 Raw material compound: Compound of Example 38 acetic acid physical and chemical properties 1) Oily substance 2) Elemental analysis value (as CzsHteOs) C (%) H (%) Theoretical value 73.78 6.45 Experimental value 73.65 6.47 Raw material compound: Compound of Example 31 nilcoglycine physical and chemical properties ■) Melting point: 135-137°C 2) Elemental analysis values (as CzsHt7NOsS) C (%) H (%) N ( %) S (%) Theoretical value 71.23 6.46 3.32 7.61 Experimental value 7 1. OL 6.43 3.32 7.7.3 Raw material compound: Compound of Example 32 (rubutoxy)styryl]phenoxyacetic acid was obtained. However, instead of recrystallization, silica Gel column chromatography (eluent = chloroform:methanol (12: 1)).

physical and chemical properties l) Oily substance 2) Nuclear magnetic resonance spectrum (CD in CIs, TMS internal standard, ppm) 1 , 7-1.9 (4H), 2.6-2.8 (2H), 3.63 (s, 3H) , 3. ．． 9-4.1. (2H), 4.60, 4.74 (each combined with S2) 2H), 5.35 (broad, disappears at lI20), 6.6-7.8 (14H) Physical and chemical properties of o-(o-(4-phenylbutoxy)styryl)phenoxyacetic acid 1) Oily substance 2) Nuclear magnetic resonance spectrum (CD C1, medium, TMS internal standard, ppm) 1 ．． 7-2.0 (4H), 2.6-2.8 (2H), 3.9-4.1 (2B), 4 ．． 54 and 4.69 (each S2 combined 2H), 6.1 (broad, Dt Disappeared with O), 6.6-7.7 (15H) Raw material compound: Compound of Example 37 Reference example 26 3.32 g of ethyl 3-hydroxy-4-nitrocinnamate was dissolved in 30 g of tetrahydrofuran. m1. Dissolve in 130ml of ethanol and add 100mg of 10% palladium-carbon. Then, stir under a normal pressure hydrogen atmosphere until hydrogen absorption stops.

The catalyst was taken out by suction, and the liquid was condensed under reduced pressure to obtain crude ethyl 4-amino-3-hydride. Roxybenzene propionate 3. Obtain lOg.

1) Oily substance 2) Nuclear magnetic resonance spectrum (in CD C13, TMS internal standard, ppm) 1. 22 (3H, t), 2.4-2.8 (28), 3.5-3.8 (2H), 4.　 to(211,4), 6.60(3H) p-(4-phenylbutoxy) rest number a 1.41. N,N-dimethylforma was added to a solution of 35 ml of methylene chloride. Add 1 drop of Mido, add 1.5 mt of oxalyl chloride under water cooling, and stir for 30 minutes. and stir for an additional hour at room temperature. The reaction solution was concentrated under reduced pressure to obtain the crude 1)-(4-phthalate). phenylbutoxy)benzoyl chloride is obtained. Add this to methylene chloride 15 0.93 g of ethyl 3-amino-4-hydroxybenzony) dissolved in Added to a solution of 8 ml of pyridine and 10 ml of methylene chloride under water cooling for 1.5 hours. Stir. The reaction mixture was poured into 10% hydrochloric acid at 0°C, and the product was extracted with ethyl acetate. do. The ethyl acetate layer was washed sequentially with saturated aqueous sodium bicarbonate solution, water, and saturated brine. The solution is dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained crystalline residue is Recrystallized from xane-ethyl acetate to yield 1.47 g of ethyl 3-hydroxy-4- (p-(4-phenylbutoxy)benzamide)benzoate is obtained.

■) Melting point: 156-158℃ 2) Elemental analysis values (as CzaHt7N Os) C (%) H (%) N ( %) Calculated value 72.04 6.28 3.24 Experimental value 71.97 6,26 3. Compounds of Reference Examples 28 to 36 were obtained in the same manner as below.

5'-Bromo-2'-hydroxy-4-(4-phenylbutoxy)benzanili de Melting point: 145-147℃ 2) Elemental analysis value (as C*3Hz2N O3Br) C (%) H (%) N (%) Br (%) Theoretical value 62,74 5.04 3.18 18.13 Experimental value 62.5? 5.01 3.05 18.21B r COC1 2”-hydroxy-4-(4-phenylbutoxy)-5°-phenylsulfonyl oxybenzanilide Melting point: 169-171℃ Elemental analysis value (as CzsH*, N0aS) C (%) H (%) N (%) S (%) theoretical value 67.29 5.26 2.71 6.205°-ethyl- 2°-Hydroxy-4-(4-phenylbutoxy)benzanilide Melting point: 122-124℃ Elemental analysis value (as CzsH!?N Ox) C (%) H (%) N (%) Theoretical value 77.09 6.99 3.60 Experimental value? ? , Go? , 14 3. 622°-hydroxy-4-(4-phenylbutoxy)-5°-propylbenz Anilide 1) Melting point: 125-128℃ 2) Elemental analysis value (as CtsHtsN Os) C (%) H (%) N ( %) Theoretical value 77.39 7.24 3.47 Experimental value? ? , 55 7.24 3. 44・5′-cyano-2′-hydroxy-4-(4-phenylbutoxy)ben Zuanilide l) Melting point: 133-154℃ 2) Elemental analysis value (as Cz4Ht2N tOs) C (%) H (%) N (%) Theoretical value ? 4.59 5.73 7.25 Experimental value 74.69 5.79 7. 21 Ethyl 4-hydroxy-3-(p-(4-phenylbutoxy)benzami [Do] Phenyl acetate l) Oily substance 2) Nuclear magnetic resonance spectrum (CD C13, TMS internal FFJ, ppm ) 1.23 (3H, t), 1.7-2.0 (4H), 2.6-2.8 (2H), 3.45 (2H, s), 3.9-4.2 (21i), 4.08 (2H, q), 6 ．． 8-8.2 (12H) CH:C00C:H+ COCl Ethyl 3-hydroxy-4-(p-(4-phenylbutoxy)benzamidera) benzoate 1) Melting point: 148-149°C 2) Elemental analysis fia (as C211827N Os) C (%) H (%) N (%) Theoretical value ? 2.04 6.28 3.23 Experimental value 71.81 6.31 3. 602゛-Hydroxy-5゜-isopropyl-4-(4-phenylbutoxy) base nzanilide l) Melting point: 105-107°C 2) Elemental division (as C28HteN O3) C (%) H (%) N (% ) Theoretical value 77.39 7.24 3.47 Experiment @ 77.47 7.23 34 5CH (CHlh COCl Ethyl 3-[3-hydroxy-4-(p-(4-phenylbutoxy)benza Mido]phenyl]propionate l) Melting point: 105-107°C 2) Elemental analysis values (as CtsHsrN Os) C (%) H (%) N ( %) Theoretical value 72.86 6.77 3.03 Experimental value 72,71 6,81 2. 91 Reference example 37 4-hydroxy-3-nitrobenzaldehyde 8 g, 1.3-7' lopandio 16 g, catalytic amount of pyridinium para-toluenesulfonic acid and 25 toluene 0 ml of the mixed liquid is subjected to azeotropic dehydration under heating and reflux. The reaction solution was cooled, washed with water, and anhydrous FM Dry with magnesium acid and concentrate under reduced pressure. The residue was extracted from toluene-〇-hexane. Recrystallize to give 4-(1,3-dioxan-2-yl)-2-nitrophenol9. 2g was obtained.

l) Melting point 70-71℃ Reference example 38 Reference example using 3 g of 4°-hydroxy-3′-nitroacetophenone as a starting material 4-(1-methyl-1,3-dioxan-2-yl)-2 -2.8 g of nitrophenol were obtained.

1) Melting point: 109-111℃ Reference example 39 4-(1,3-dioxan-2-yl)-2-nitropheno obtained in Reference Example 37 4 g of alcohol was dissolved in 50 ml of tetrahydrofuran, and 10% palladium-carbon was added. Catalytic reduction is carried out in the presence of 5 g at room temperature and normal pressure until hydrogen absorption stops. remove the catalyst, Add 5+nl of pyridine to the mother liquor and cool to below -20°C. Add p-( 1 prepared according to Reference Example 27 from 4.8 g of 4-phenylbutoxy)benzoic acid, Add p-(4-phenylbutoxy)benzoyl chloride. 2 hours at room temperature Stir, add 200 ml of ethyl acetate, dilute hydrochloric acid, water, and purified sodium/lium hydrogen oxide water. The solution was washed sequentially with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give 5°-( 1,3-dioxan-2-yl)-2°-hydroxy-(4-phenylbutoxy ) 7.5 g of benzanilide was obtained.

■) Melting point: 122-123℃ 2) Elemental analysis values (e *7HtsHOs) C (%) H (%) N ( %) Calculated value 72.46' 6.53 3.13 Experimental value? 2.50 6.60 3.06 Reference example 40 4-(l-methyl-1,3-dioxan-2-yl)-2- obtained in Reference Example 38 5°- Acetyl-2'-hydroxy-(4-phenylbutoxy)benzanilide 2.5 I got g.

l) Melting point: 134-135°C 2) Elemental analysis values (as CtsHtsH04) C (%) H (%) N (%) Calculated value ? 4.42 6.25 3.47 Experimental value 74.20 6.27 3. 43 Reference example 41 f25''(IJ-dioxan-2-yl)-2'-hydroxy obtained in Reference Example 39 -(4-phenylbutoxy)benzanilide 7.5g, ethyl bromoacetate 2.97 g of anhydrous potassium carbonate, 2.7 g of anhydrous potassium carbonate, and a catalytic amount of tetra-n-butylammonium Stir a mixture of nium bromide and 100ml of 2-butane at 60-65℃ for 6 hours. Ru. Add 300ml of toluene to the reaction solution, wash with dilute aqueous sodium hydroxide solution, and add water. Washed, dried over anhydrous magnesium sulfate, concentrated under reduced pressure to obtain ethyl 4-(1,3- dioxan-2-yl)-2-(p-(4-phenylbutoxy)benzamide] 8.69 g of phenoxy acetate was obtained.

1) Melting point 736C 2) Elemental analysis values (as Cs+HisNOy) C (%) H (%) N (% ) Calculated value 69.78 6.61 2.62 Experimental value 89.68 6.58 2. 49 Reference example 42 2'-hydroxy-4-(4-phenylbutoxy)-5°- obtained in Reference Example 29 Reference example 4 using 0.80 g of phenylsulfonyloxybenzanilide as a starting material Treat in the same manner as in 1 to obtain ethyl 2-(p-(4-phenylbutoxy)benzamide). 0.91 g of Dotsu 4-phenylsulfonyloxyphenoxy acetate was obtained.

C (%) H (%) N (%) S (%) Calculated value 85.66 5.51 2. 32 5.31 Experimental value 65.45 5.45 2.23 5.48 Reference example 43 Ethyl 4-hydroxyindan-1-one-2-acetate 2.27g and p- 2.10 g of hebutyloxybenzyl chloride, 2.0 Hg of potassium carbonate Heat to reflux in 15 ml of butanone overnight. Add water to the reaction mixture and dilute with ethyl acetate. Extract the product. The ethyl acetate layer was sequentially washed with water and saturated saline and dissolved in anhydrous magnesium sulfate. Dry on a rack. Volatile substances were removed under reduced pressure and the resulting residue was transferred to a silica gel column. Purification by chromatography (eluent: toluene-ethyl acetate (20:1)) Then ethyl 4-(p-hebutyloxybenzyloxy)indan-1-one 2.17 g of -2-acetate are obtained.

1) Oily substance 2) Nuclear magnetic resonance spectrum (CD C1, medium, TMS internal standard, ppm) 0 ．． 8-0.95 (3H), 1.21 (3H, t), 1.2-1.4 (8H), 1 ．． 7-1.9 (2), 2.3-3゜1 (41), L 44 (LH, dd) , 3.96 (2H, t), 4.14 (2H, q), 5.08 (2H , s), 6. 2L for X d),? ,'0~7.4 (5H) Reference example 44 Dissolve p-hebutyloxybenzoic acid 730D in 5 ml of methylene chloride, add N Add 10 μl of N-dimethylformamide and 410 μl of oxalyl chloride. Stir for 1 hour. The reaction mixture was concentrated under reduced pressure to yield crude p-hebutyloxybenzoylene. Luchloride is obtained. 3-(m-aminophenyl)propionitrile 380 mg of pyridine 1.5 ml. Add the above to 4 ml of methylene chloride solution at -30°C. A 2 ml solution of p-heptyloxybenzoyl chloride is added dropwise. gradually chamber Warm and stir for 3 hours. Add water and extract the product with ethyl acetate. Ethyl acetate layer Washed sequentially with 5% hydrochloric acid, saturated sodium bicarbonate, water, and saturated saline, and anhydrous sulfur. Dry over magnesium chloride and concentrate under reduced pressure. Silica gel column chromatography of the residue When purified by graphography (eluent: toluene-ethyl acetate (to: 1)), 3-　Cm　-((p-heptyloxy)benzamide]hue, =ru]propio 830 mg of nitrile are obtained.

1) Melting point: 129-131℃ 2) Nuclear magnetic resonance spectrum (CD in CI3, TMS internal standard, ppm) 0 ．． 8-1.0 (3H), 1.3-1.6 (8H), 1.7-1.9 (2H), 2 ．． 55-2.75 (2H), 2.90-3.10 (2H), 4.03 (2[(, t), 6.9-7.9 (8H) Example 53 5'-acetyl-2'-hydroxy-4-(4-phenylbutylene) obtained in Reference Example 40 xy)benzanilide 2.5g, ethyl bromoacetate 1.3g, carbonic anhydride Potassium 1.2 g, catalytic amount of tetra n-butylammonium bromide, 2 - Stir a mixture of 30 ml of butanone at 60-70° C. for 6 hours. Toluene in reaction solution Add 50ml, wash with dilute aqueous sodium hydroxide solution, rinse with water, and add anhydrous magnesium sulfate. Dry with a vacuum cleaner and concentrate under reduced pressure. The residue was recrystallized from isopropyl alcohol, Ethyl 4-acetyl-2-(p-(4-phenylbutoxy)benzamide) 2.4 g of noxyacetate was obtained.

1) Melting point: 105-107℃ 2) Elemental analysis value (C2s H31N Oe and shite) C (%) H (%) N (%) Calculated value ? 1.15 6J8 2.86 Experimental value 70.92 6,39 2.7 7 Compounds of Examples 54 to 63 were obtained by the same method.

Ethyl 4-bromo-2-(p-(4-phenylbutoxy)benzamidephenol) xyacetate physical and chemical properties 1) Melting point: 85-86℃ 2) Elemental analysis value (as Cx7H218N 05B r) C (%) H (% ) N (%), Br (%) Theory @ 61.60 5.36 2.66 15. 18 Experimental value 61.58 5.35 2.61 15.20 Raw material compound: Reference example Compound 28 + B r CHt COOCt Hs Example 55 physical and chemical properties 1) Melting point: 58-59℃ 2) Elemental analysis flow (as CzsH31N Os) C (%) H (%) N (% ) Theoretical value 73.24 6.99 2.95 Experimental value 73.14 6.85 2. 69 raw material compound: Compound of Reference Example 30 + B r CH * COOCt Hs implementation Example 56 Ethyl 2-(p-(4-phenylbutoxy)benzamide-4-propylph phenoxy acetate physical and chemical properties 1) Melting point: 57-586C 2) Elemental analysis value (as Cs o H2S NO7) C (%) H (%) N (%) Theoretical value 73,60 7.21 2.86 Experimental value 73.47 7.39. 2 ．． 84 Raw material compound: Reference example 31 compound ÷ BrCH, C00CtHs Example 57 CH(CH+)z Ethyl 4-isopropyl-2-(p-(4-phenylbutoxy)benzamide ]Phenoxy acetate physical and chemical properties l) Oily substance 2) Elemental analysis values (as C30HssN Os) C (%) H (%) N ( %) Theoretical value 73.60 7.21 2.86 Experimental value 73.64 7J1 2.8 2 Raw material compound: Reference example 35 Compound: BrCHzCOOCtHs Example 58 N Ethyl 4-cyano-2-(p-(4-phenylbutoxy)benzamide)phene Noxy acetate physical and chemical properties 1) Melting point: 115-116℃ 2) Elemental analysis value (as C*aHtsN tOs) C (%) H (%) N (%) Theoretical value 71.1? 5.97 5.93 Experimental value 71.15 6.01 5. 85 raw material compound: Compound B r CHt C00C* Hs implementation of Reference Example 32 Example 59 Ethyl 4-ethoxycarbonylmethoxy-3-(p-(4-phenylbutoxy) ) Benzamide] benzoate physicochemical properties l) Melting point: 93-94°C 2) Elemental analysis values (CS.HisNOt) C (%) H (%) N (% ) Theoretical value 69.35 6,40 2.70 Experimental value 694O6,452,63 Raw material compound: Compound of Reference Example 27 ÷ BrCHtCOOCtHs Example 60 Ethyl 4-ethoxycarbonylmethyl-2-(p-(4-phenylbutoxy) Benzamide] phenoxy acetate physical and chemical properties 1) Oily substance 2) Elemental analysis value (as C3tHaaNOt) N (%) Theoretical value 2.62 Experimental value 2.54 Raw material compound: Compound of Reference Example 33 + B r CH * COOCx Hs Example 6 1 Ethyl 3-ethoxycarbonylmethoxy-4-(p-(4-phenylbutoxy) ) Benzamide] benzoate physicochemical properties l) Melting point: 113-114℃ 2) Elemental analysis value (C,.Hs 3N OV) C (%) H (%) N (%) Theoretical value 89.35 6.40 2.70 Experimental value 69.19 6.53 2. 75 Raw material compound: Compound of Reference Example 34 + BrCHtCOOCzHs Example 62 Ethyl 5-(2-ethoxycarbonyl)ethyl-2-(p-(4-phenylbutylene) Toxi)benzamide] phenoxyacetate physical and chemical properties 1) Melting point: 86-88℃ 2) Elemental analysis values (as Cs*HsqN O7) C (%) H (%) N (% ) Theoretical value 70.18 6.81 2.56 Experimental value 70.19 6.87 2. 57 raw material compound: Compound of Reference Example 36 ÷ B r CHt C00Ct HsCI Ethyl 4-[4-chloro-2-(p-(4-phenylbutoxy)benzamide) ]Phenoxybutyrate physical and chemical properties l) Melting point: 87-88℃ 2) Elemental analysis value (C*sH3*N as OsC1) C (%) H (%) N (%) Theoretical value 68.29 6.32 2.75 Experimental value 68.09 64O2,75 Raw material compound: Example 64 Ethyl 4-(1,3-dioxan-2-yl)-2-(p- (4-phenylbutoxy)benzamide] 8.69 g of phenoxy acetate was added to the Dissolve in 200 ml of setone, add 6 ml of 6% hydrochloric acid, and stir at room temperature for 2 hours.

Add 30ml of water, cool, remove the precipitated crystals, wash with 50% acetone, and evaporate. Chil 4-formyl-2-(p-(4-phenylbutoxy)benzamide)phene 6.0 g of Noxyacetate was obtained.

l) Melting point 109-110℃ 2) Elemental analysis value (as C2sH29N Oa) C (%) ■ ((%) N ( %) Calculated value 70.72 6.13 2.93 Experimental (1"α 70.77 6.05 2.93 Ethyl 4-formyl-2-(p-(4-phenyl) obtained in Example 64 butoxy)benzamidocyphenoxy acetate 2.8g, ethanol 30ml Add 1.0.2 g of sodium borohydride to the mixed solution while cooling with water.

Stir at room temperature for 2 hours, add 50 ml of ethyl acetate, and acidify with dilute hydrochloric acid.

The ethyl acetate layer is separated, washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The residue was recrystallized from ethanol to give ethyl 4-hydroxymethyl-2-(p-( Obtained 2.06 g of 4-phenylbutoxy)benzamidocyphenoxy acetate. .

■) Melting point: 101-104°C 2) Elemental analysis values (as C2a H31NOa) C (%) H (%) N ( %) Calculation (Direct 70.42 6.54 2.93 Experimental value 70.25 6.51 2 ．． 85 Example 6b -phenylbutoxy)benzamidocyphenoxy acetate 1 g.

Benzene 20ml1. Add 260 mg of salt to a solution of 20 ml of methylene chloride under water cooling. Add thionyl chloride. Stir for 30 minutes at room temperature, add 60ml of toluene, and rinse with cold water. Wash, dry over anhydrous magnesium sulfate, and concentrate under reduced pressure. The residue was dissolved in toluene-n- Recrystallize from hexane to give ethyl 4-chloromethyl-2-(p-(4-phenylbutylene) 0.76 g of benzamide siphenoxy acetate was obtained.

l) Melting point: 115-117℃ 2) Elemental analysis value (as C26H3゜N Os C!) C (%) H (%) N (%) CI (%) Calculated value 67.80 6.10 2.82 7.15 Actual Experimental value 67.87 6.13 2.797.27 Example 67 nylbutoxy)benzamidocyphenoxy acetate 200mg, ethyl thio Acetate 50mg, anhydrous potassium carbonate 60mg, N, N-dimethylphosate Stir a mixture of 5 ml of Lumamide at room temperature for 1 hour, add 20 ml of toluene, and add water. Wash, dry with anhydrous magnesium sulfate, and concentrate under reduced pressure (30 ffll of silica gel). ), eluted with a mixture of toluene and ethyl acetate (9:1), and ethyl 4-[(ethyl (cycarbonylthio)methyl)-2-(p-(4-phenylbutoxy)benzami Obtain 170 mg of dosiphenoxy acetate.

1) Melting point: 56-57°C 2) Elemental analysis value (as C32H!?N O?S) C (%) H (%) N (%) Calculated value 66.30 6.43 2.42 Experimental value 66.04 6.43 2. 31 Example 68 Zuamide] phenoxy acetate hydrochloride 200mg, pyridine 3ml mixture Add 1 ml of a mixture of formic acid and acetic anhydride (3:5 v/v) and stir at room temperature overnight.

Add 40 ml of ethyl acetate to the reaction solution, acidify with dilute hydrochloric acid, and separate the layers. Ethyl acetate layer The sample was washed with water, dried over anhydrous magnesium sulfate, and vacuumed. Isopropyl residue Recrystallize from alcohol to obtain ethyl 4-formylamide-2-(p-(4-phenylated) 130 mg of nylbutoxy)benzamide siphenoxy acetate are obtained.

1) Melting point: 112-114°C 2) Elemental analysis values (as C2aH3o\20+1) C (%) H (%) N (%) Calculated value 6g, 56 6.16 j, 71 Experimental value 68.43 6.31 5. 62 Example 69 Ethyl 4-amino-2-(p-(4-phenylbutoxy)benzamide) Noxyacetate Hydrochloride 200mg and pyridine 5ml mixed with acetic anhydride 1ml was added under water cooling and stirred at room temperature overnight. The reaction solution was treated in the same manner as in Example 68 to obtain Chil 4-acetamido-2-(p-(4-phenylbutoxy)benzamidosy) 150 mg of phenoxy acetate was obtained.

l) Melting point: 130-132°C 2) Elemental analysis value (as C2983□N20.) C (%) H (%) N ( %) Calculated value 69.03 6.39 5.55 Experimental value 68.89 6.37 5. 43 Example 70° Ethyl isocyanate in a mixture of 40, 5 mg, and 5 ml of methylene chloride) Add 30 mg and stir at room temperature overnight. The reaction solution was treated in the same manner as in Example 68. , ethyl 4-(3-ethylureido)-2-(p-(4-phenylbutoxy) 130 mg of benzamide]funinoxy acetate was obtained.

■) Melting point: 170-172℃ 2) Elemental analysis value (as C3o H3S Ns Oe) C (%) H (% ) N (%) Calculated value 67.53 6.61 7.87 Experimental value 67.59 6.63 7. 80 Example 71 Zuamide] phenoxy acetate hydrochloride 200mg, pyridine 5ml mixture Add a mixture of 200 mg of ethyl oxalyl chloride and 1 ml of methylene chloride. -Add at below 30°C and stir overnight at room temperature. The reaction solution was treated in the same manner as in Example 68. and oily ethyl 4-ethoxalylamide-2-(p-(4-phenylbutoxy) c) 200 mg of benzamide] phenoxy acetate was obtained.

1) Nuclear magnetic resonance spectrum (CD C1, 5 standards in TMS, ppm) 1, 1-1.6 (m, 6H), 1.6-2.0 (+n, 4H), 2.5 ~2.8 (m, 2H), 3.8~4.1 (m, 2Hj 4.1-4.5 (m, 4H), 4.58 (s, 2H), 6.6-7.8 (12H ) Example 72 Ethyl 4-amino-2-(p-(4-phenylbutoxy)benzamide)phene Nokizu! Cetate hydrochloride 200mg, mono-p-methoxybenzyl Maloney To a mixture of 107 mg of dicyclohexyl carbodiimide and 5 ml of pyridine, add 90 mg of dicyclohexylcarbodiimide. mg and stirred overnight at room temperature. After treating the reaction solution in the same manner as in Example 68, Toluene-ethyl acetate (4:1) was subjected to silica gel column chromatography. Elute with a mixture of caramelized ethyl 4-(p-methoxybenzyloxycarboxylate) nyl)acetamido-2-(p-(4-phenylbutoxy)benzamide]phene 1LOmg of noxyacetate was obtained.

l) Nuclear magnetic resonance spectrum (DMSO-d, TMS internal standard, ppm) L , if! (t, death), 1.5-2.0 (m, 41(), 2.5 ”-2,8 (m, 2H), 3.46 (s, 2H) @, 3.72 (s) .

3H), 4.9-4.2 (m, 2H), 4.16 (q, 2H), 4.82 (s, 2H), 5.06 (s, 2H)@, 6.8~8° 3 (16FI) Example 73 Ethyl 4-amino-2-(p-(4-phenylbutoxy)benzamide)phene Noxyacetate hydrochloride 200B, ethyl bromoacetate 70.4mg, 114 mg of anhydrous potassium carbonate, N,N-dimethylform. Silica gel residue Column: Subjected to chromatography and mixed with toluene-ethyl acetate (4:1) Elute with ethyl 4-ethoxycarbonylmethylamino-2-(p-(4-ph) 140 mg of phenylbutoxybenzamide]phenoxyacetate was obtained.

l) Melting point 61-63℃ 2) Elemental analysis value (as C31Hs *NtOma) C (%) H (% ) N (%) Calculated value 67.87 6.61 5.11 Experimental value 67.74 6.56 5. 11 Example 74 (rubutoxy)benzamide] phenoxy acetate 0.5 g, methanol 5 m 1. Add 1 ml of aqueous sodium hydroxide solution to a mixture of 5n+1 tetrahydrofuran. Add and stir at room temperature for 2 hours. Add 10ml of water to the reaction solution, concentrate under reduced pressure, and remove methane. Excluding alcohol and tetrahydrofuran.

Dilute hydrochloric acid is added to the residue to make it acidic, and the resulting crystals are collected in a furnace and mixed with isopropyl alcohol. to give 4-acetyl-2=(p-(4-phenylbutoxy)benzamide). 0.39 g of phenoxyacetic acid was obtained.

l) Melting point: 186-188℃ 2) Elemental analysis value (as Cx7H2?N Oe) C (%) H (%) N ( %) Calculated value 70,27 5.90 3.03 Experimental value 70.07 5.73 3. Compounds of Examples 75 to 92 were obtained by the same method below.

4-ethyl-2-Cp-(4-phenylbutoxy)benzamide] fenogyo vinegar acid physical and chemical properties 1) Melting point: 129-132℃ 2) Elemental analysis values (as Ct7H29N Os) C (%) H (%) N ( %) Theoretical value 72.46 6,53 3.13 Experimental value 72.33 6.65 3. 09 Raw material compound: Compound of Example 55 2-(p-(4-phenylbutoxy)benzamide to 4-propylphenoxy acetic acid physical and chemical properties 1) Melting point: 109-112°C 2) Elemental analysis value (as Ct a Hs lN Os) N (%) Theoretical value 3.03 Experimental value 3.01 3) Nuclear magnetic resonance spectrum (in CD C13, TMS internal standard, ppm) 0. 90 (t, 3) 1), 1.4-2.0 (6H), 2.4-2.8 (4H), 3. 8-4.1 (2H). 4.70 (s, 2tO, 6,7-7.0 (4H), 7. 0-7.4 (5tl), 7.8-8.0 (2H), 8.15 (d, IH) , 8.62 (s, LH), 8.91 (S, LH) Raw material compound; compound of Example 56 4-isopropyl-2-(p-(4-phenylbutoxy)benzamide)pheno xyacetic acid physical and chemical properties ■) Melting point 117 ~] 19°C 2) Elemental analysis values (as C28831N Os) C (%) H (%) N ( %) Theoretical value 72.83 6.77 3.03 Experimental value 73.05 6.91 3. 04 Raw material compound: Compound of Example 57 4-Hydroxy-2-[p-(4-phenylbutoxy)benzamide]phenoki cyanoacetic acid physical and chemical properties ■) Melting point: 198-199℃ 2) Elemental analysis values (as CzsHtsN Oa) C (%) H (%) S ( %) Theoretical value 6g, 95 5.79 3.22 Experimental value 69.01 5.99 3. 13 Raw material compound: Compound of Reference Example 42 4-formamide-2-(p-(4-phenylbutoxy)benzamide)pheno xyacetic acid physical and chemical properties l) Melting point: 78-80℃ 2) Elemental analysis value (as CzeHteNtOe) N (%) Theoretical value 6.06 Experimental value 5.99 Raw material compound: Compound of Example 68 4-acetamido-2-(p-(4-phenylbutoxy)benzamide)pheno xyacetic acid physical and chemical properties 1) Melting point: 184-186℃ 2) Elemental analysis value (as C2?H!8N 206) C (%) H (%) N (%) Theoretical value 6g, 05 5.92 5.88 Experimental value 67.77 5,96 5. 79 Raw material compound: Compound of Example 69 4-Oxaloamide-2-[p-(4-phenylbutoxy)benzamide]phene Noxyacetic acid physical and chemical properties l) Melting point: 206-207°C 2) Elemental analysis value (C2?818N *Os・18H, as O) C (%) H (%) N (%) Theoretical value 63.57 5.22 5.49 Experimental value 63.63 5.21 5. 44 Raw material compound: Compound of Example 71 Example 82 4-(2-carboxyacetamide)-2-(p-(4-phenylbutoxy)base Phenoxyacetic acid physical and chemical properties 1) Melting point: 179-181℃ (decomposition) 2) Elemental analysis value (C!aHtsNzO s) C (%) H (%) N (%) Theoretical value 64.61 5.42 5.38 Experimental value 64.67 5.39 5. 324-carboxy-2-(p-(4-phenylbutoxy)benzamide) Noxyacetic acid physical and chemical properties 1) Melting point: 244-246°C 2) Elemental analysis values (028825N as O7) C (%) H (%) N (% ) Theoretical value 67.38 5.44 3.02 Experimental value 67.33 5.48 3. 03 Raw material compound: Compound of Example 59 4-carboxymethyl-2-(p-(4-phenylbutoxy)benzamide Schiff Enoxyacetic acid physical and chemical properties l) Melting point: 210-2゛13℃ 2) Elemental analysis value (as C2, H*tN O?) Theoretical value 67.91 5. 70 2.93 Experimental value 87.45 5.69 2.92 Raw material compound: Example 6 0 compounds 4-formyl-2-(p-(4-phenylbutoxy)benzamidocyphenoxy) acetic acid physical and chemical properties ■) Melting point: 151-152℃ C (%) H (%) N (%) Theoretical value 69,79 5.63 3.13 Experimental value 69.79 5.54 3. 11 Raw material compound: Compound of Example 64 4-Hydroxymethyl-2-(p-(4-phenylbutoxy)benzamide Schiff Enoxyacetic acid physical and chemical properties l) Melting point: 138-139℃ 2) Elemental analysis value (as Cll81?N Oe) C (%) H (%) N (%) Theoretical value 69.47 6.05 3.12 Experimental value 69.34 5Jl 3.0 5 Raw material compound: Compound of Example 65 4-carboxymethylthiomethyl-2-(p=(4-phenylbutoxy)benz Physicochemical properties of amide] phenoxyacetic acid l) Melting point: 139-141°C 2) Elemental analysis value (as CtsHteN O?S) N (%) Theoretical value 2.68 Experimental value 2.57 Raw material compound: Compound of Example 67 4-cyano-2-(p-'(4-phenylbutoxy)benzamide]phenoxy acetic acid physical and chemical properties 1) Melting point: 148-149℃ 2) Elemental analysis value (as C26H24N 205) C (%) H (%) N (%) Theoretical value 70.26 5.44 6.30 Experimental value 70.14 5.44 6. 12 Starting compound: Compound of Example 58 4-Bromo-2-(p-(4-phenylbutoxy)benzamidesiphenoxy vinegar acid physical and chemical properties 1) Melting point: 163-165℃ 2) Elemental analysis values (as C25H24N O5) C (%) H (%) N (% ) Br (%) Theoretical value 60.25 4.8:) 2.81 16.03 Experimental value 60.15 4.99 2.75 16.02 Raw material compound: Compound of Example 54 thing 5-carboxy 2-[p-(4-phenylbutoxy)benzamide cyanoacetic acid physical and chemical properties ■) Melting point: 235-237.5°C 2) Elemental analysis value (as C28825N O?) C (%) H (%) N ( %) Theoretical value 67.385.44 3.02 Experimental value 87.06 5.53 3.1 0 raw material compound: Compound of Example 61 5-(2-carboxy)ethyl-2-(p-(4-phenylzo)xy)benz Amide] Phenoxyacetic acid physical and chemical properties ■) Melting point: 147-149℃ 2) Elemental analysis value (as C*sH2-sNO?・0JHtO)C (% ) H (%) N (%) Theoretical value 67.68 6.00 2.82 Experimental value 67.60 6.19 2. 64 raw material compound: compound of Example 62 Example 92 4-[4-chloro-2-(p-(4-phenylbutoxy)benzamide]pheno Butyric acid physical and chemical properties 1) Melting point: 118-119℃ 2) Elemental analysis value (as CxqHtsN OsC1) C (%) H (%) N (%) Theoretical value 67.28 5.86 2.91 Experimental value 67.13 5.77 2. 82 Raw material compound: Compound of Example 63 Example 93 c) Benzamide] Phenoxyacetic acid physical and chemical properties 1) Melting point: 129-132°C 2) Elemental analysis value (as CztHzaN 207・'/1Hto) C (%) H (%) N (%) Theoretical value 64.66 5.83 5.59 Experimental value 64.69 5.92 5. 46 Raw material compound: Compound of Example 73 4-(3-ethylureido)-2-(p-(4-phenylbutoxy)benzami Dosiphenoxyacetic acid physical and chemical properties ■) Melting point: 156℃ 2) Elemental analysis value (as C2e H31N s Oa) C (%) H (%) N (%) Theoretical value 66.52 6.18 8.3L Experimental value 66.18 6°15 8. 13 Raw material compound: Compound of Example 70 Example 95 4-hydroxy-2-(p-(4-phenylbutoxy)ben) obtained in Example 78 Zuamide] Phenoxyacetic acid 0.62g, anhydrous potassium carbonate 0.46g, iodide solution A catalytic amount of tetra-n bromide was added to a mixture of 2.47 g of chill and 10 ml of 2-butanone. -Add butylammonium and stir at 60°C for 20 hours. Dilute the reaction solution with ethyl acetate diluted with water and filtered to remove insoluble matter. Add f liquid to 0, 02. N aqueous sodium hydroxide solution, After successively washing with water and drying over anhydrous magnesium sulfate, the solvent was distilled off. solid obtained The product was recrystallized from ethanol to give methyl 4-methoxy-2-(p-(4-phenyl) 0.59 g of (rubutoxy)benzamide siphenoxy acetate was obtained.

1) Melting point: 91-93℃ 2) Elemental analysis value (as CayHteN Oe) N (%) Calculated value 3.02 Experimental value 2.98 Example 96 Toxy)benzamide] phenoxyacetic acid 0.64g, anhydrous potassium carbonate 0°50 g, in a mixture of 0.60 g of ethyl bromoacetate and 8 ml of 2-butanone, Add a catalytic amount of tetra-n-butylammonium bromide and stir at 60°C for 4 hours. . Dilute the reaction solution with ethyl acetate and remove the insoluble matter. pass Wash the f solution with water and add anhydrous sulfuric acid. After drying with magnesium, the solvent was distilled off. Recrystallize the obtained solid from ethanol Then, ethyl [[4-ethoxycarbonylmethoxy-2-(p-(4-phenyl) (rubutoxy)benzamide]phenoxy]acetoxy]acetate O, 83g I got it.

Melting point: 64℃ 2) Elemental analysis value (033H39N O+. Closed) C (%) H (%) N (%) Calculated value 65.23 6.14 2J1 experimental value 6. ), 00 5.96 2. 23 Example 97 Methyl 4-methoxy-2-(p-(4-phenylbutoxy) obtained in Example 95 Add 0.54 g of benzamide siphenoxy acetate to 25 ml of 90% methanol. Suspend, add 10 ml of IN sodium hydroxide aqueous solution, and stir at 60°C for 2 hours. Stir. Dilute the reaction solution with 50ml of water and acidify by adding 7ml of 2N hydrochloric acid. , extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and then dissolved. The medium was distilled off. The obtained solid was recrystallized from isopropyl alcohol to give 4- Methoxy-2-(p-(4-phenylbutoxy)benzamide]phenoxyacetic acid 0.49g was obtained.

l) Melting point: 139-141"C 2) Elemental analysis values (as CiaH1?N Os) C (%) H (%) N ( %) Calculated value 69.47B, 05 3.12 Experimental value 69. :13 6.1'a 3. Q3 Example 98 -2-(p-(4-phenylbutoxy)benzamide]phenoxy]acetoxy ] Using 0.77 g of acetate as a raw material, it was treated in the same manner as in Example 97 to obtain (2-(p- (4-phenylbutoxy)benzamide)-1,4-phenylenedioxy] diacetic acid 0.57 g of acid was obtained.

l) Melting point: 211-214℃ 2) Elemental analysis values (as Ct7HtqN Os) C (%) H (%) N ( %) Calculated value 65.71 5.51 2.84 Experimental value 65.74 5.51 2. 77 Example 99 Add the ethyl 4-chloromethyl obtained in Example 66 to the methoxide-methanol solution. -2-(p-(4-phenylbutoxy)benzamide]phenoxyacetate) Add 200 mg and stir overnight at room temperature. Add 1 ml of water to the reaction solution and stir for 1 hour. , acidify with dilute hydrochloric acid, and then concentrate under reduced pressure. Add 10ml of water to the residue to form crystals? door 4-methoxymethyl-2-(p-( 100 mg of 4-phenylbutoxy)benzamide]phenoxyacetic acid was obtained.

1.) Melting point: 126-129°C 2) Elemental analysis values (as CiaHtsN Oa) C (%) H (%) N ( %) Calculated value 69.79 5.63 3.13 Experimental value 69.79 5.54 3. 11 Examples 100 Reference Example 43 was added to a methanol (8 ml) solution of 30 mg of cerous chloride heptahydrate. Ethyl 4-(p-hebutyloxyben,zyloxy)indan-1 obtained in 350 mg of -one-2-acetate was dissolved and cooled to -10°C. boron hydride Add 300 mg of sodium and stir for 30 minutes.

Add water and bring to room temperature and extract the product with ethyl acetate. The ethyl acetate layer was diluted with saturated saline. Washed twice, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to yield ethyl 1-hyperoxychloride. Droxy-4-(p-hebutyloxybenzyloxy)indan-2-acetate This yields 390 mg.

l) Oily substance 2) Nuclear magnetic resonance spectrum (iH quasi in CDC13, TMS, ppm) 0. 8 to 1.0 (2t(), 1.25, 1.2B (3H1 each t in total), 1. 2-1.45 (8H).

1.6-1, 9 (2H), 2, 3-4.4 ('+H), 3.96 (2 H, t), 4.15.4.21 (total of 2H1 each q, 7:4), 5.00 (2H, s), 5.20 (IH, to w = 111 (Z), 6.8 to 7, 4 (7) 1) Example 101 Ethyl 1-hydroxy-4-(p-hebutyloxybenzene) obtained in Example 100 Dissolve 380 mg of (indyloxy)-2-indane acetate in 10 ml of methanol. Add 2.5 ml of a 5% caustic soda aqueous solution and stir at room temperature for 8 hours. to 20% hydrochloric acid Make acidic and extract with ethyl acetate.

The ethyl acetate layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. , and concentrated to dryness under reduced pressure. Recrystallization of the crystalline residue from ethyl acetate-hexane yields 2 30 mg of 1-hydroxy-4-(p-heptyloxybenzyloxy)-2- Obtain indane acetic acid.

l) Melting point: 180℃ 2) Elemental analysis value (as CxsHs20s) C (%) H (%) Theoretical value 72', 79 7.82 Experimental value 72.66 7.98 Example 102 3-(m-((p-hebutyloxy)benzamide)phene obtained in Reference Example 44 Dissolve 630 mg of propionitrile in 5 ml of N,N-dimethylformamide. Dissolved, added 340 mg of sodium azide and 280 mg of ammonium chloride, and Heat to 0°C. After 4 hours and 16 hours, same amounts of sodium azide and ammonium chloride were added. Add monium and heat for 20 hours.

Water is added to the reaction mixture and the resulting crystalline solid is collected by suction. After washing the solid with water and drying it , recrystallized from methanol-ethyl acetate to give 4-heptyloxy-3°-(2-( 540 mg of 5-tetrazolyl)ethyl]benzanilide are obtained.

l) Melting point: 164-165℃ 2) Elemental analysis value (as C23Ht s N i O2) C (%) H (%) N (%) Theoretical value 67.79 7.17 17.19 Experimental value 67.96 7.13 1 6.91 Hades Example 103 (tablet) Compound of Example 40 [4-chloro-2-(p-(4-phenylbutoxy)benz Amide] phenoxyacetic acid) 30mg Lactose 1.04mg Cornstarch 57B Hydroxypropylcellulose 4mg Carboxymethylcellulose Calciu Magnesium stearate 1mg Compound of Example 40 (4-chloro-2-(p-(4-phenylbutoxy)benz) amido] phenoxyacetic acid), 4 g of lactose IQ, and 57 g of corn starch. Add 10% (w/v) hydroxypropyl cellulose dissolved in water to this mixture. 40 ml of liquid was added and granules were prepared by wet granulation. Carboxyme to this granule Add 4 g of chillulose calcium and 1 g of magnesium stearate and mix. This was then compressed into tablets (200 mg per tablet).

Example 104 (capsules) Compound of Example 4o (4-chloro-2'-(p-(4-phenylbutoxy)ben zamide) phenoxyacetic acid) 30J crystalline cellulose 40mg Crystal lactose 129mg Magnesium stearate 1mg Take 1,000 times the amount of each of the above ingredients, mix in a conventional manner, and then gelatin capsules. The mixture was filled into capsules (1 capsule 200 mg).

Example 105 Compound of Example 40 (4-chloro-2-(p-(4-phenylbutoxy)benz) Amide] phenoxy vinegar M) O, 1 g purified with ethanol-propylene glycol Dissolve in 90 ml of water (30 ml: 10 w: 60 min.) and add the same mixture to a colander. After adjusting the total volume to 100+nl, fill each 100ml into a designated container and seal it as an inhaler. did.

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Claims (1)

[Claims] 1. General formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼ {The symbols in the formula represent the following meanings. A: hydrogen atom, phenyl group or phenoxy group n: integer from 3 to 10 R1: hydrogen atom or lower alkoxy group X1: -CH2CH2-, -CH=CH-, -CH2-Y1- (in the formula Y1: -O - , -S- or -NH-), -Y1-CH2-, -CO-Y2- (in the formula Y2: -NH-, -CH2-Y1- or -Y1-CH2-) or -Y2-CO- Been ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [In the formula, R2: hydrogen atom, halogen atom, nitro group, hydroxyl group, lower alkoxy group, carboxy group, cyano group, oxalamide group (-NHCOCOOH), lower alkyl Koxycarbonyl group, lower alkyl group, hydroxy lower alkyl group, lower alkyl group xy-lower alkyl group, carboxy-lower alkyl group, lower alkoxycarbonyl group alkyl group, carboxy lower alkylthio lower alkyl group, lower alkoxy group Rubonyl lower alkylthio lower alkyl group, halo lower alkyl group, carboxy lower alkoxy group, lower alkoxycarbonyl lower alkoxy group, lower alkanoyl lower alkoxy group, lower alkoxycarbonyl lower alkoxycarbonyl lower alkoxy group, lower alkanoyl group or formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R4 and R are the same or different, hydrogen atom, lower alkyl group, carboxy Lower alkyl group, lower alkoxycarbonyl lower alkyl group, lower alkanoyl group, carboxy lower alkanoyl group, lower alkoxycarbonyl lower alkanoyl group, substituted or unsubstituted phenyl lower alkoxycarbonyl lower alkanoyl group, Bamoyl group, lower alkoxalyl group or mono- or di-lower alkylaminocarbonyl group -CH=CH-, -Y3-Y4- (in the formula, Y3: single bond, -O-, -S- or -NH-; Y4: A group represented by an alkylene group with 1 to 6 carbon atoms which may be interrupted by a sulfur atom, a carboxyl group, a lower alkoxycarbonyl group, or a ▲ mathematical formula, chemical formula, table, etc. A group represented by ▼ However, when A is a hydrogen atom, (B) is ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ Or D is ▲ Mathematical formulas, chemical formulas, tables, etc. Compounds indicated by ▼ or pharmaceutically acceptable salts thereof. 2. In the general formula described in claim 1, A is a hydrogen atom or a phenyl group, n is 4 to 7, R1 is a hydrogen atom, and X1 is -CO-Y2- (in the formula, Y2 is -XH-) (B) is ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R2 is a hydrogen atom, a halogen atom, or a nitrogen atom. thoro group, lower alkyl group, or carboxy lower alkyl group) or ▲ Numerical formula, chemical formula, table, etc. ▼ X2 is -CH=CH- or -Y3-Y4- (in the formula, Y3 is a single bond, -O- or -S -, Y4 is an alkylene group having 1 to 6 carbon atoms which may be interrupted by a sulfur atom), D is a carboxy group, or ▲ has a numerical formula, chemical formula, table, etc. ▼ described in claim 1 compound. 3.4-chloro-2-[p-(4-phenylbutoxy)benzamide]phenoki The compound according to claim 1, which is cyacetic acid. 4.3-[o-[p-(4-phenylbutoxy)benzamido]phenyl]pro The compound according to claim 1, which is pionic acid. 5. The compound according to claim 1, which is o-[p-(4-phenylbutoxy)benzamide]cinnamic acid. 6. The compound according to claim I, which is o-[p-(4-phenylbutoxy)benzamide]phenoxyacetic acid. 7.4-Nitro-2-[p-(4-phenylbutoxy)benzamide]phenoki The compound according to claim 1, which is cyacetic acid. 8.4-Methyl-2-[p-(4-phenylbutoxy)benzamide]phenoki The compound according to claim 1, which is cyacetic acid. 9. The compound according to claim 1, which is 4-hebutyloxy-2'-(5-tetrazolylmethoxy)benzanilide. 10. (a) General formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(II) [The symbols in the formula represent the following meanings. A: hydrogen atom, phenyl group or phenoxy group, n: integer from 3 to 10, R1: hydrogen atom or lower alkoxy group. ] Carboxylic acids or their reactive derivatives represented by general formula (III) ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ (III) {The symbols in the formula represent the following meanings. vinegar. (B): ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. [R2 in the formula: hydrogen atom, halogen atom, nitro group, hydroxyl group, lower alkoxy group, carboxy group, cyano group, oxaloamide group (-NHCOCOOH), lower alkoxycarbonyl group, lower alkyl group, hydroxy lower alkyl group, lower class a Rukoxy lower alkyl group, carboxy lower alkyl group, lower alkoxycarbonyl group lower alkyl group, carboxy lower alkylthio lower alkyl group, lower alkyl group cyclocarbonyl lower alkylthio lower alkyl group, halo lower alkyl group, carboxy lower alkoxy group, lower alkoxycarbonyl lower alkoxy group, lower alkyl Noyl lower alkoxy group, lower alkoxycarbonyl lower alkoxycarbonyl Lower alkoxy group, lower alkanoyl group or formula ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ (In the formula, R4 and R5 are the same or different, hydrogen atom, lower alkyl group, Carboxy lower alkyl group, lower alkoxycarbonyl lower alkyl group, lower alkanoyl group, carboxy lower alkanoyl group, lower alkoxycarbonyl lower alkanoyl group substituted or unsubstituted phenyl lower alkoxycarbonyl lower alkanoyl group, carbamoyl group, lower alkoxalyl group or mono- or di-lower alkylaminocarboxylic group; (Y3: single bond, -O-, -S- or -NH-;Y4: Aluminum having 1 to 6 carbon atoms, which may be interrupted by a sulfur atom kylene group), D: carboxy group, lower alkoxycarbonyl group, or A group represented by ▼ However, when A is a hydrogen atom in general formula (II), ▲ there are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ there are mathematical formulas, chemical formulas, tables, etc. ▼, or D is ▲ Contains mathematical formulas, chemical formulas, tables, etc. (b) General formula (IV) ▲ Numerical formula, chemical formula, table, etc. ▼ (IV) [In the formula, A, n and R1 are the same as above] Amino compounds and general formula (V) ▲Mathematical formulas, chemical formulas, tables, etc.▼(V) [In the formula, (B), X2 and D are the same as above. (c) General formula (VI) ▲ Numerical formula, chemical formula, table, etc. ▼ (VI) [In the formula, A, n and R1 are the above-mentioned Same as . Y1 is -O-, -S- or -NH-, M1 is a hydrogen atom or an alkali metal atom when Y1 is an oxygen atom or a sulfur atom, and a hydrogen atom when Y1 is an imino group. means child. ] Compounds represented by general formula (VII) ▲Mathematical formulas, chemical formulas, tables, etc.▼(VII) [In the formula, (B), X2 and D are the same as above. Z1 means a halogen atom or a sulfonate residue, and Y5 means a methylene group or a methylene carbonyl group (-CH2CO-). ] or (d) General formula (VIII) ▲ Numerical formula, chemical formula, table, etc. ▼ (VIII) [In the formula, A, n, R1 and Z1 are the same as above. Y6 means a methylene group or a carbonylmethylene group (-COCH2-). ] Compounds represented by general formula (IX) ▲Mathematical formulas, chemical formulas, tables, etc.▼(IX) [In the formula, M1, Y1, (B)X2 and D are the same as above. ] or (e) General formula (X) ▲ Numerical formula, chemical formula, table, etc. ▼ (X) [In the formula, A, n and R1 are the same as above. Z2 means a halogen atom. ] in the halogen compound shown in By reacting sphine or tributylphosphine, the general formula (XI) ▲ Numerical formula, chemical formula, table, etc. ▼ (XI) [In the formula, A, n, R1 and Z2 are the same as above. R6 means a phenyl group or a butyl group. ] and then with a base. The general formula (XII) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (XII) [In the formula, B, X2 and D are the same as above. character. ] or (f) General formula (If) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (If) [In the formula, A, n, R1 (B) and X2 are the same as above. X1 is -CH2CH2-, -CH=CH-, -CH2-Y1- (in the formula, Y1 is the same as above) -Y1-CH2-, CO-Y2- (in the formula, Y2 is -NH -, -CH2-Y1 - or -Y1-CH2-) or -Y2-CO-, and R7 means a lower alkyl group or a lower alkoxyphenyl lower alkyl group. ] or (g) General formula (XIII) ▲ There are numerical formulas, chemical formulas, tables, etc. ▼ [In the formula, A, n, R1, X1 and (B) are as shown above. same. Y7 is an oxygen atom or a sulfur source The child M2 means a hydrogen atom or an alkali metal atom. ] and the compound represented by the general formula (XIV) Z2-Y4-D (XIV) [wherein Z2, Y4 and D are the same as above. ] or (h) a carbonyl lower alkanoyl group, a carbamoyl group, a lower alkoxalyl group, or a compound represented by the general formula (XV). or di-lower alkylaminocarbonyl group), R3: hydrogen atom, hydroxyl group, or lower alkoxy group], -, -S- or -NH-; Y4: a group represented by an alkylene group having 1 to 6 carbon atoms which may be interrupted by a sulfur atom, D: a carboxy group, a lower alkoxycarbonyl group, or ▲ formula , chemical formulas, tables, etc. A group represented by ▼ However, when A is a hydrogen atom in general formula (II), ▲ there are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ there are mathematical formulas, chemical formulas, tables, etc. ▼ or D is ▲ mathematical formula , chemical formulas, tables, etc. (b) General formula (IV) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (IV) [In the formula, A, n and R1 are the same as above] Amino compounds and general formula (V) ▲Mathematical formulas, chemical formulas, tables, etc.▼(V) [In the formula, (B), X2 and D are the same as above. (C) General formula (VI) ▲ Numerical formula, chemical formula, table, etc. ▼ (VI) [In the formula, A, n and R1 are the above-mentioned Same as . Y1 is -O-, -S- or -NH-, M1 is a hydrogen atom or an alkali metal atom when Y1 is an oxygen atom or a sulfur atom, and a hydrogen atom when Y1 is an imino group. means child. ] Compounds represented by general formula (VII) ▲Mathematical formulas, chemical formulas, tables, etc.▼(VII) [In the formula, (B), X2 and D are the same as above. Z1 means a halogen atom or a sulfonate residue, and Y5 means a methylene group or a methylene carbonyl group (-CH2CO-). ] or (d) General formula (VIII) ▲ Numerical formula, chemical formula, table, etc. ▼ (VIII) [In the formula, A, n, R1 and Z1 are the same as above. Y6 means a methylene group or a carbonylmethylene group (-COCH2-). ] and the general formula (IX) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (IX) [In the formula, MI, Y1, (B), X2, and and D are the same as above. ] or (e) General formula (X) ▲ Numerical formula, chemical formula, table, etc. ▼ (X) [In the formula, A, n and R1 are the same as above. Z2 means a halogen atom. ] in the halogen compound shown in By reacting sphine or tributylphosphine, the general formula (XI) ▲ Numerical formula, chemical formula, table, etc. ▼ (XI) [In the formula, A, n, R1 and Z2 are the same as above. R8 means a phenyl group or a butyl group. ] and then with a base. The general formula (XII) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (XII) [In the formula, B, X2 and D are the same as above. character. ] Or (f) General formula (If) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (If) [In the formula, A, n, R1, (B) and X 2 are the above Same as . X1 is -CH2CH2-, -CH=CH-, -CH2-Y1- (in the formula, Y1 is the same as above) -Y1-CH2-], -CO-Y2- (in the formula, Y2 is -NH-, -CH2 -Y1- or -Y1-CH2-) or -Y2-C O-, R7 is a lower alkyl group or a lower alkoxyphenyl lower alkyl group. means alkyl group. ] or (g) General formula (XIII) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (XIII) [In the formula, A, n, R1, X1 and (B) is the same as above. Y7 is oxygen atom or sulfur atom, M2 is hydrogen atom or alkali means a metal atom. ] A compound represented by the general formula (XIV) Z2-Y4-D (XIV) [wherein Z2, Y4 and D are the same as above. ] or (h) General formula (XV) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (XV) [In the formula, A, n, R1, X1, (B) and X2 are Same as above. ] or (i) General formula (XVII) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (XVII) [In the formula, M2, R1, X1, (B ) X2 and D is the same as above. ] and the general formula (XVIII) A-(CH2)n-Z2(XVIII) [wherein A, n and Z2 are the same as above. [In the formula, A, n, R1, X1, (B) Same as . ] is obtained, and then, if desired, (j) if compound (I) has a vinylene group, it is reduced by a conventional method to convert it into the corresponding compound (I) having an ethylene group. , (k) In compound (I), R2 is a If it is a mino group, it can be alkylated or acylated by a conventional method to convert it into the corresponding alkyl amino group or acylamino group, or (1) Compound (I) in which R2 is a hydroxy lower alkyl group. In some cases, halogenation by conventional methods (m) When R2 in compound (I) is a formyl group, it is converted to the corresponding halo-lower alkyl group by reduction by a conventional method. (n) When R2 in compound (I) is a halo-lower alkyl group, converting the compound (I) into a corresponding hydroxymethyl group, or (n) converting the compound (I) into a lower alkyl group by a conventional method. (o) When R2 in compound (I) is a halo-lower alkyl group, convert it into lower alkoxycarbonyl-lower alkylthio by a conventional method. low-level software that responds by A method for producing a phenylene derivative represented by the general formula (I) or a salt thereof, which comprises converting the compound into a compound (I) which is an alkoxycarbonyl lower alkylthio lower alkyl group. 12. General formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(II) [The symbols in the formula represent the following meanings. A: hydrogen atom, phenyl group or phenoxy group, n: integer from 3 to 10, R1: hydrogen atom or lower alkoxy group. ] Carboxylic acids or their reactive derivatives represented by general formula (III) ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ (III) {The symbols in the formula represent the following meanings. vinegar. (B): ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [R2 in the formula: hydrogen atom, halogen atom, nitro group, Hydroxyl group, lower alkoxy group, carboxy group, cyano group, oxaroa Mido group (-NHCOCOOH), lower alkoxycarbonyl group, lower alkyl group, hydroxy lower alkyl group, lower alkoxy lower alkyl group, carboxy lower alkyl group, lower alkoxycarbonyl lower alkyl group, carboxy lower alkyl group ruthio lower alkyl group, lower alkoxycarbonyl lower alkylthio lower alkyl group group, halo-lower alkyl group, carboxy-lower alkoxy group, lower alkoxyl group Bonyl lower alkoxy group, lower alkanoyl lower alkoxy group, lower alkoxy carbonyl lower alkoxycarbonyl lower alkoxy group, lower alkanoyl group or is a formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R4 and R5 are the same or different and are water Elementary atoms, lower alkyl groups. carboxy lower alkyl group, lower alkoxy carboni lower alkyl group, lower alkanoyl group, carboxy lower alkanoyl group, lower alkoxycarbonyl lower alkanoyl group, substituted or unsubstituted phenyl lower alkanoyl group oxycarbonyl lower alkanoyl group, carbamoyl group, lower alkoxalyl gomata R3: hydrogen atom, hydroxyl group or lower alkoxy group], X2: -CH=CH-, -Y3-Y4- (in the formula Y3: single bond, - O-, -S- or -NH-; Y4: a group represented by an alkylene group having 1 to 6 carbon atoms which may be interrupted with a sulfur atom; D: a carboxy group, a lower alkoxycarbonyl group, or ▲ Mathematical formulas, chemical formulas, tables, etc. A group represented by ▼ However, when A is a hydrogen atom in general formula (II), (B) is a group represented by ▲ ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, or D is ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ A general formula characterized by reacting with the amino compound shown in (Ia) ▲ Formula , chemical formulas, tables, etc. ▼ (Ia) [In the formula, A, n, R1, (B ), X2 and D are the same as above. ] A method for producing the compound shown in 13. General formula (IV) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (IV) [The symbols in the formula represent the following meanings. A: hydrogen atom, phenyl group or phenoxy group, n: integer from 3 to 10, R1: hydrogen atom or lower alkoxy group. ] and the general formula (V) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (V) {The symbols in the formula represent the following meanings. (B): ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [R2 in the formula: hydrogen atom, halogen atom, nitro group, Hydroxyl group, lower alkoxy group, carboxy group, cyano group, oxaroa Mido group (-NHCOCOOH), lower alkoxycarbonyl group, lower alkyl group, hydroxy lower alkyl group, lower alkoxy lower alkyl group, carboxy lower alkyl group, lower alkoxycarbonyl lower alkyl group, carboxy lower alkyl group ruthio lower alkyl group, lower alkoxycarbonyl lower alkylthio lower alkyl group group, halo-lower alkyl group, carboxy-lower alkoxy group, lower alkoxyl group Bonyl lower alkoxy group, lower alkanoyl lower alkoxy group, lower alkoxy carbonyl lower alkoxycarbonyl lower alkoxy group, lower alkanoyl group or is a formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R4 and R5 are the same or different and are water Elementary atom, lower alkyl group, carboxy lower alkyl group, lower alkoxycarbonyl group lower alkyl group, lower alkanoyl group, carboxy lower alkanoyl group, lower alkoxycarbonyl lower alkanoyl group, substituted or unsubstituted phenyl lower alkanoyl group xycarbonyl lower alkanoyl group, carbamoyl group, lower alkoxalyl group or is a mono- or di-lower alkylaminocarbonyl group), R3: a hydrogen atom, a hydroxyl group, or a lower alkoxy group], X2: -CH=CH-, -Y3-Y4- (in the formula Y3: single bond, -O -, -S- or -NH-; Y4: a group represented by an alkylene group having 1 to 6 carbon atoms which may be interrupted with a sulfur atom), D: a carboxy group, a lower alkoxycarbonyl group, or ▲ formula , chemical formulas, tables, etc. A group represented by ▼ However, when A is a hydrogen atom in general formula (IV), (B) is a group represented by ▲ ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or D is ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ A general formula characterized by reacting with a carboxylic acid or its reactive derivative ( Ib) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [In the formula, A, n, R1, (B), X2 and D are the same as above. ] (Ib) A method for producing a compound represented by: 14. General formula (VI) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (VI) {The symbols in the formula represent the following meanings. A: hydrogen atom, phenyl group or phenoxy group, n: integer from 3 to 10, R1: hydrogen atom or lower alkoxy group, Y1: -O-, -S- or -NH-, M1: Y1 is an oxygen atom or sulfur When it is an atom, it is a hydrogen atom or an alkali metal atom, and when Y1 is an imino group, it is a hydrogen atom. ] and general formula (VII) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (VII) {The symbols in the formula represent the following meanings. vinegar. Z1: halogen atom or sulfonate residue, Y5: methylene group or methylene carb Bonyl group (-CH2CO-), (B): ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula R2: Hydrogen atom, halogen atom, nitro group, hydroxyl group, lower alkoxy group, carbo Oxy group, cyano group, oxalamide group (-NHCOCOOH), lower alkoxy carbonyl group, lower alkyl group, hydroxy lower alkyl group, lower alkoxy group alkyl group, carboxy lower alkyl group, lower alkoxycarbonyl lower alkyl group Kyl group, carboxy lower alkylthio lower alkyl group, lower alkoxycarbonyl group halo-lower alkyl group, halo-lower alkyl group, carboxy-lower alkyl group, Koxy group, lower alkoxycarbonyl lower alkoxy group, lower alkanoyl lower alkoxy group, lower alkoxycarbonyl lower alkoxycarbonyl lower alkoxy xy group, lower alkanoyl group, or formula ▲ Numerical formula, chemical formula, table, etc. lower alkoxycarbonyl group, lower alkyl group, lower alkanoyl group, xy lower alkanoyl group, lower alkoxycarbonyl lower alkanoyl group, substituted or unsubstituted phenyl lower alkoxycarbonyl lower alkanoyl group, carbamoy group, lower alkoxalyl group, or mono- or di-lower alkylaminocarbonyl group), R3: hydrogen atom, hydroxyl group, or lower alkoxy group], : single bond, -O-, -S- or -NH-; Y4: group represented by (alkylene group having 1 to 6 carbon atoms which may be interrupted by a sulfur atom), D: carboxy group, lower Alkoxycarbonyl group or ▲Mathematical formula, chemical formula, table, etc. A group represented by ▼. However, when A is a hydrogen atom in general formula (VI), (B) is a group represented by ▲. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ Or D is ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ General formula (Ic) characterized by reacting with the compound shown in ▲ Mathematical formula, chemical formula , tables, etc. ▼ (Ic) [In the formula, A, n, R1, Y1, Y5, (B), X2 and D are the same as above. ] A method for producing the compound shown in 15. General formula (VIII) ▲ Contains mathematical formulas, chemical formulas, tables, etc. ▼ (VIII) [The symbols in the formula represent the following meanings. Was. A: hydrogen atom, phenyl group or phenoxy group, n: integer from 3 to 10, R1: hydrogen atom or lower alkoxy group, Y6: methylene group or carbonyl methylene (-COCH2-), Z1: halogen atom or sulfonate residue] Compounds and general formula (IX) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (IX) {The symbols in the formula represent the following meanings. M1: When Y1 is an oxygen atom or a sulfur atom, a hydrogen atom or an alkali metal atom, When Y1 is an imino group, a hydrogen atom, Y1: -O-, -S- or -XH-, (B):▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, R2: hydrogen atom, halogen atom, nitro group, hydroxyl group, lower alkoxy group , carboxy group, cyano group, oxaroa Mido group (-NHCOCOOH), lower alkoxycarbonyl group, lower alkyl group, hydroxy lower alkyl group, lower alkoxy lower alkyl group, carboxy lower alkyl group, lower alkoxycarbonyl lower alkyl group, carboxy lower alkyl group ruthio lower alkyl group, lower alkoxycarbonyl lower alkylthio lower alkyl group group, halo-lower alkyl group, carboxy-lower alkoxy group, lower alkoxyl group Bonyl lower alkoxy group, lower alkanoyl lower alkoxy group, lower alkoxy carbonyl lower alkoxycarbonyl lower alkoxy group, lower alkanoyl group or is a formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R4 and R5 are the same or different and are water Elementary atom, lower alkyl group, carboxy lower alkyl group, lower alkoxycarbonyl group lower alkyl group, lower alkanoyl group, carboxy lower alkanoyl group, lower alkoxycarbonyl lower alkanoyl group, substituted or unsubstituted phenyl lower alkanoyl group xycarbonyl lower alkanoyl group, carbamoyl group, lower alkoxalyl group or is a mono- or di-lower alkylaminocarbonyl group), R3: a hydrogen atom, a hydroxyl group, or a lower alkoxy group], X2: -CH=CH-, -Y3-Y4- (in the formula Y3: single bond, - O-, -S- or -NH-; Y4: a group represented by an alkylene group having 1 to 6 carbon atoms which may be interrupted with a sulfur atom; D: a carboxy group, a lower alkoxycarbonyl group, or ▲ Mathematical formulas, chemical formulas, tables, etc. A group represented by ▼ However, when A is a hydrogen atom in the general formula (VIII), (B) is ▲ has a mathematical formula, chemical formula, table, etc. ▼ or ▲ has a mathematical formula, chemical formula, table, etc. ▼, or D is ▲There are mathematical formulas, chemical formulas, tables, etc.▼General formula (Id) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(Id) , R1, Y6, Y1, (B) X2 and D are the same as above. ] A method for producing the compound shown in 16. General formula (X) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(X) [The symbols in the formula represent the following meanings. A: hydrogen atom, phenyl group or phenoxy group, n: integer from 3 to 10, R1: hydrogen atom or lower alkoxy group, Z2: halogen atom. ) is reacted with triphenylphosphine or tributylphosphine. General formula (XI) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(XI) [In the formula, A, n, R1 and Z3 are the same as above. R6 is a phenyl group or butyl group], and then a base is added. to substituted benzyltriphenyl (or tributyl) phosphorane, and to this General formula (XII) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(XII) [The symbols in the formula represent the following meanings. vinegar. (B): ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [R2 in the formula: hydrogen atom, halogen atom, nitro group, Hydroxyl group, lower alkoxy group, carboxy group, cyano group, oxaroa Mido group (-NHCOCOOH), lower alkoxycarbonyl group, lower alkyl group, hydroxy lower alkyl group, lower alkoxy lower alkyl group, carboxy lower alkyl group, lower alkoxycarbonyl lower alkyl group, carboxy lower alkyl group ruthio lower alkyl group, lower alkoxycarbonyl lower alkylthio lower alkyl group group, halo-lower alkyl group, carboxy-lower alkoxy group, lower alkoxyl group Bonyl lower alkoxy group, lower alkanoyl lower alkoxy group, lower alkoxy carbonyl lower alkoxycarbonyl lower alkoxy group, lower alkanoyl group or is a formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R4 and R5 are the same or different and are water Elementary atom, lower alkyl group, carboxy lower alkyl group, lower alkoxycarbonyl group lower alkyl group, lower alkanoyl group, carboxy lower alkanoyl group, lower alkoxycarbonyl lower alkanoyl group, substituted or unsubstituted phenyl lower alkanoyl group xycarbonyl lower alkanoyl group, carbamoyl group, lower alkoxalyl group or is a mono- or di-lower alkylaminocarbonyl group), R3: a hydrogen atom, a hydroxyl group, or a lower alkoxy group], X2: -CH=CH-, -Y3-Y4- (in the formula Y3: single bond, -O -, -S- or -NH-: Y4: a group represented by an alkylene group having 1 to 6 carbon atoms which may be interrupted with a sulfur atom), D: a carboxy group, a lower alkoxycarbonyl group, or ▲ formula , chemical formulas, tables, etc. A group represented by ▼ However, when A is a hydrogen atom in general formula (X), (B) has a ▲ mathematical formula, chemical formula, table, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or D is ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ General formula (Ie) ▲ Number There are formulas, chemical formulas, tables, etc.▼(Ie) [In the formula, A, n, R1, (B), X2 and D are the same as above. ] A method for producing a compound represented by. 17. General formula (If) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (If) {The symbols in the formula represent the following meanings. A: hydrogen atom, phenyl group or phenoxy group, n: integer from 3 to 10, R1: hydrogen atom or lower alkoxy group, X1: -CH2CH2-, -CH=CH -, -CH2-Y1- (in the formula Y1: -O-, -S- or -NH-), -Y1-C H2-, -CO-Y2- (in the formula Y2: -NH-, -CH2-Y1- or -Y1- CH2-) or -Y2- Group represented by CO-, (B): ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [R2 in the formula: hydrogen atom , halogen atom, nitro group, hydroxyl group, lower alkoxy group, carboxy group, cyano group, oxaroa Mido group (-NHCOCOOH), lower alkoxycarbonyl group, lower alkyl group, hydroxy lower alkyl group, lower alkoxy lower alkyl group, carboxy lower alkyl group, lower alkoxycarbonyl lower alkyl group, carboxy lower alkyl group ruthio lower alkyl group, lower alkoxycarbonyl lower alkylthio lower alkyl group group, halo-lower alkyl group, carboxy-lower alkoxy group, lower alkoxyl group Bonyl lower alkoxy group, lower alkanoyl lower alkoxy group, lower alkoxy carbonyl lower alkoxycarbonyl lower alkoxy group, lower alkanoyl group or is a formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R4 and R5 are the same or different and are water Elementary atom, lower alkyl group, carboxy lower alkyl group, lower alkoxycarbonyl group lower alkyl group, lower alkanoyl group, carboxy lower alkanoyl group, lower alkoxycarbonyl lower alkanoyl group, substituted or unsubstituted phenyl lower alkanoyl group xycarbonyl lower alkanoyl group, carbamoyl group, lower alkoxalyl group or is a mono- or di-lower alkylaminocarbonyl group), R3: a hydrogen atom, a hydroxyl group, or a lower alkoxy group], X2: -CH=CH-, -Y3-Y4- (in the formula Y3: single bond, -O -, -S- or -NH-; Y4: a group represented by an alkylene group having 1 to 6 carbon atoms which may be interrupted with a sulfur atom, R7: a lower alkyl group or a lower alkoxyphenyl lower alkyl group } General formula (Ig) characterized by removing ester residue from ester ▲There are mathematical formulas, chemical formulas, tables, etc.▼(Ig) X2 is the same as above.] 18. General formula (XIII) ▲ Numerical formula, chemical formula, table, etc. ▼ (XIII) {Symbols in the formula represent the following meanings. Was. A: hydrogen atom, phenyl group or phenoxy group, n: integer from 3 to 10, R1: hydrogen atom or lower alkoxy group, X1: -CH2CH2-, -CH=CH -, -CH2-Y1- (in the formula Y1: -O-, -S- or -NH- -Y1-CH2 -, -CO-Y2- (in the formula Y2: -NH-, -CH2-Y1- or -Y1-CH 2-) or -Y2-CO- A group represented by (B): ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [R2 in the formula: hydrogen atom, halogen Atom , nitro group, hydroxyl group, lower alkoxy group, carboxy group, cyano group, oxaloa Mido group (-NHCOCOOH), lower alkoxycarbonyl group, lower alkyl group, hydroxy lower alkyl group, lower alkoxy lower alkyl group, carboxy lower alkyl group, lower alkoxycarbonyl lower alkyl group, carboxy lower alkyl group ruthio lower alkyl group, lower alkoxycarbonyl lower alkylthio lower alkyl group group, halo-lower alkyl group, carboxy-lower alkoxy group, lower alkoxyl group Bonyl lower alkoxy group, lower alkanoyl lower alkoxy group, lower alkoxy carbonyl lower alkoxycarbonyl lower alkoxy group, lower alkanoyl group or is the same or different from the formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼ Kyl group, carboxy lower alkyl group, lower alkoxycarbonyl lower alkyl group, lower alkanoyl group, carboxy lower alkanoyl group, lower alkoxycarbo lower alkanoyl group, substituted or unsubstituted phenyl lower alkoxycarbonyl group alkanoyl group, carpamoyl group, lower alkoxalyl group, or mono- or di-lower alkylaminocarbonyl group), R3: hydrogen atom, hydroxyl group, or lower alkoxy group], Y7: oxygen atom or sulfur atom, M2: hydrogen atom or alkali metal atom} and the compound represented by the general formula (XIV) Z2-Y4-D(XIV) {The symbols in the formula represent the following meanings. Z2: Halogen atom, Y4: Alkylene group having 1 to 6 carbon atoms which may be interrupted by a sulfur atom, D: Carboxy group, lower alkoxycarbonyl group, or ▲ Numerical formula, chemical formula, table, etc. A group represented by ▼ However, when A is a hydrogen atom in general formula (XIII), (B) has ▲ a mathematical formula, chemical formula, table, etc. ▼ or ▲ has a mathematical formula, chemical formula, table, etc. ▼ or D is a general formula (I h) that is characterized by reacting with the compound shown in ▲ There are mathematical formulas, chemical formulas, tables, etc. , R1, X1, (B) Y7, Y4 and D are the same as above. ] A method for producing the compound shown in ．． General formula (XV) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (XV) {The symbols in the formula represent the following meanings. A: hydrogen atom, phenyl group or phenoxy group, n: integer from 3 to 10, R1: hydrogen atom or lower alkoxy group, X1: -CH2CH2-, -CH=CH -, -CH2-Y1- (in the formula Y1: -O-, -S- or -NH- -Y1-CH2 -, -CO-Y2- (in the formula Y2: -NH-, -CH2-Y1- or -Y1-CH 2-) or -Y2-CO- A group represented by (B): ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [R2 in the formula: hydrogen atom, halogen Atom , nitro group, hydroxyl group, lower alkoxy group, carboxy group, cyano group, oxaloa Mido group (-NHCOCOOH), lower alkoxycarbonyl group, lower alkyl group, hydroxy lower alkyl group, lower alkoxy lower alkyl group, carboxy lower alkyl group, lower alkoxycarbonyl lower alkyl group, carboxy lower alkyl group ruthio lower alkyl group, lower alkoxycarbonyl lower alkylthio lower alkyl group group, halo-lower alkyl group, carboxy-lower alkoxy group, lower alkoxyl group Bonyl lower alkoxy group, lower alkanoyl lower alkoxy group, lower alkoxy carboel lower alkoxycarbonyl lower alkoxy group, lower alkanoyl group or is a formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R4 and R5 are the same or different and are water system atoms, lower alkyl group, carboxy lower alkyl group, lower alkoxycarbonyl group lower alkyl group, lower alkanoyl group, carboxy lower alkanoyl group, lower alkoxycarbonyl lower alkanoyl group, substituted or unsubstituted phenyl lower alkanoyl group xycarbonyl lower alkanoyl group, carbamoyl group, lower alkoxalyl group or is a mono- or di-lower alkylaminocarbonyl group), R3: a hydrogen atom, a hydroxyl group, or a lower alkoxy group], X2: -CH=CH-, -Y3-Y4- (in the formula Y3: single bond, -O -, -S- or -NH-: Y4: a group represented by an alkylene group having 1 to 6 carbon atoms which may be interrupted with a sulfur atom) General formula (Ii) characterized by the action of sodium azide on a substance ▲There are mathematical formulas, chemical formulas, tables, etc.▼(Ii) [In the formula, A, n, R1, X1, (B) and X2 are as above. same. ] A method for producing the compound shown in 20. General formula (XVII) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (XVII) {The symbols in the formula represent the following meanings. Was. M2: hydrogen atom or alkali metal atom, R1: hydrogen atom or lower alkoxy group, X1: -CH2CH2-, -CH=CH-, -CH2-Y1- (in the formula Y1: -O -, -S- or -NH -), -Y1-CH2-, -CO-Y2- (in the formula Y2: -NH-, -CH2-Y1- or -Y1-CH2-) or -Y2-CO- (B): ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [R2 in the formula: hydrogen atom, halogen atom, Nitro group, hydroxyl group, lower alkoxy group, carboxy group, cyano group, oxaroa Mido group (-NHCOCOOH), lower alkoxycarbonyl group, lower alkyl group, hydroxy lower alkyl group, lower alkoxy lower alkyl group, carboxy lower alkyl group, lower alkoxycarbonyl lower alkyl group, carboxy lower alkyl group ruthio lower alkyl group, lower alkoxycarbonyl lower alkylthio lower alkyl group group, halo-lower alkyl group, carboxy-lower alkoxy group, lower alkoxyl group Bonyl lower alkoxy group, lower alkanoyl lower alkoxy group, lower alkoxy carbonyl lower alkoxycarbonyl lower alkoxy group, lower alkanoyl group or is a formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R4 and R5 are the same or different and are water Elementary atoms, lower alkyl groups. carboxy lower alkyl group, lower alkoxy carboni lower alkyl group, lower alkanoyl group, carboxy lower alkanoyl group, lower alkoxycarbonyl lower alkanoyl group, substituted or unsubstituted phenyl lower alkanoyl group xycarbonyl lower alkanoyl group, carbazoyl group, lower alkoxalyl group or R3: hydrogen atom, hydroxyl group or lower alkoxy group], X2: -CH=CH-, -Y3-Y4- (in the formula Y3: single bond, - O-, -S- or -NH-; Y4: a group represented by an alkylene group having 1 to 6 carbon atoms which may be interrupted with a sulfur atom; D: a carboxy group, a lower alkoxycarbonyl group, or ▲ Mathematical formulas, chemical formulas, tables, etc. A group represented by ▼ However, when A is a hydrogen atom in the following general formula (XVIII), (B) is ▲ has a mathematical formula, chemical formula, table, etc. ▼ or ▲ has a mathematical formula, chemical formula, table, etc. ▼ Compound and or D is ▲ Numerical formulas, chemical formulas, tables, etc. General formula (XVIII) shown by ▼ A-(CH2)n-Z2(XVIII) [Symbols in the formula represent the following meanings. A: hydrogen atom, phenyl group or phenoxy group, n: an integer of 3 to 10, Z2: halogen atom]. General formula (I) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (I) [In the formula, A, n, R1, X1, (B), X2 and D are the same as above. ] A method for producing a compound represented by. 21. A is a hydrogen atom or a phenyl group, n is 4 to 7, R1 is a hydrogen atom, X1 is -C O-Y2- (In the formula, Y2 is -NH-(B) In the formula, R2 is a hydrogen atom, a halogen atom, a nitro group, a lower alkyl group, or a carboxy lower alkyl group) or ▲ Numerical formula, chemical formula, table, etc. ▼, X2 is -CH=CH - or -Y3-Y4- (in the formula Y3 is a single bond, -O- or -S-, Y4 is an alkylene group with 1 to 6 carbon atoms which may be interrupted by a sulfur atom), and R7 is a lower atom. 9. The manufacturing method according to claim 8, which is an alkyl group. 22. A is a hydrogen atom or a phenyl group, n is 4 to 7, R1 is a hydrogen atom, is -CO- Y2- (in the formula, Y2 is -NH-), (B) ▲ Numerical formula, chemical formula, table, etc. ▼ (Formula R2 is a hydrogen atom, halogen atom, nitro group or lower alkyl group), X2 is -Y3-Y4- (in the formula, Y3 is a single bond, -O- or -S-, and Y4 is a sulfur group) (alkylene group having 1 to 6 carbon atoms, which may be interrupted by a yellow atom) The manufacturing method according to item 10. 23. The manufacturing method according to claim 8, wherein the compound of formula (If) is ethyl 4-chloro-2-[p-(4-phenylbutoxy)benzamide] phenoxy acetate. 24. Claim 8 provides that the compound of formula (If) is ethyl 3-[o-[p-(4-phenylbutoxy)benzamido]phenyl]propionate. Scope of Claim 8. The manufacturing method according to item 8. 25. The method according to claim 8, wherein the compound of formula (If) is ethyl o-[p-(4-phenylbutoxy)benzamide]cinnamate. 26. The manufacturing method according to claim 8, wherein the compound of formula (If) is ethyl o-[p-(4-phenylbutoxy)benzamide] phenoxy acetate. 27. The manufacturing method according to claim 8, wherein the compound of formula (If) is ethyl 4-nitro-2-[p-(4-phenylbutoxy)benzamide] phenoxy acetate. 28. Claim 8 provides that the compound of formula (If) is ethyl 4-methyl-2-[p-(4-phenylbutoxy)benzamide] phenoxy acetate. Scope of Claim 8. The manufacturing method according to item 8. 29. Claim 10, wherein the compound of formula (XV) is p-hebutyloxy-N-(o-cyanomethoxyphenyl)benzamide. Manufacturing method described.