MXPA99005770A - Sulfonamide and carboxamide derivatives and drugs containing the same as the active ingredient - Google Patents

Abstract

Sulfonamide and carboxamide derivatives represented by general formula (I) wherein the rings A and B represent each a carbocycle or a heterocycle;Z1 represents -COR1, -CH=CH-COR1, etc.;Z2 represents H, alkyl, etc.;Z3 represents a single bond or alkylene;Z4 represents SO2 or CO;Z5 represents alkyl, phenyl, a heterocycle, etc., R2 represents CONR8, O, S, NZ6, Z7-alkylene, alkylene, etc.;R3 represents H, alkyl, halogeno, CF3, etc.;R4 represents H, optionally substituted alkyl, etc., and n and t are each from 1 to 4. The compounds of general formula (I) bind to PGE2 receptors and exert an antagonism or agonism thereto. Thus, they are applicable to drugs having the effects of inhibiting uterine muscle contraction, analgesia, inhibiting digestive tract movement, hypnosis, enlarging vesical capacity, contracting the uterine, promoting the digestive tract movement, suppressing the secretion of gastric hydrochloric acid, lowering blood pressure, or diuresis.

Description

DERIVATIVES OF SULFONAMIDE AND CARBOXAMIDE AND DRUGS THAT CONTAIN THE SAME AS THE ACTIVE INGREDIENT FIELD OF THE INVENTION This invention relates to sulfonamide and carboamide derivatives. More particularly, this invention relates to (1) the compounds of the formula (1) (where all the symbols are as they will be defined here below). (2) process for preparing the same and (3) prostaglandin E2 antagonists or agonists (abbreviated as PGE2) which comprise them as an active ingredient.

BACKGROUND OF THE INVENTION PGE2 is known as a metabolite in the arachidonate cascade. It is well known that PGE2 causes uterine contraction, induction of pain, promotion of digestive peristalsis, effects upon awakening, vesicular contraction, suppression of gastric acid secretion, or reduction of blood pressure, etc. The PGE2 agonist or PGE2 antagonist is expected, show the following actions. To antagonize against PGE2 it is suggested to suppress the aforementioned effects, in such a way that an activity is linked for the inhibition of uterine contraction, analgesic action, inhibition of digestive peristalsis, induction of sleep or increase of vesicular capacity. Therefore, PGE2 antagonists are considered to be used for the prevention of abortions, as analgesics, as antidiarrheals, as inducers of sleep or as agents for the treatment of pollakiuria. To show the agonistic activity PGE2, it is suggested to promote the effects mentioned above, in such a way that an activity is linked to uterine contraction, promotion of digestive peristalsis, suppression of gastric acid secretion or reduction of blood pressure or diuresis. Therefore, the PGE agonists; they are considered to be used as antiabortion, cathartic, anti-ulcer, anti-gastritis, antihypertensive or diuretic agents. A batch of PGE2 agonists including PGE2 itself is known, but only a few compounds (PGE2 antagonists) which possess the inhibition of PGE2 activity by antagonism against PGE2 are known. For example, the patent applications that refer to PGE antagonists are the following: In the specification of WO-96/03380, it is described that the compounds of the formula (A) (wherein A is phenyl which can be substituted etc., B is a ring system which can be substituted, D is a ring system which can be substituted, R1A is carboxyl, etc., R2A is H, alkyl from 1 to 6 carbon atoms, etc., R3A is H, alkyl of 1 to 4 carbon atoms, R4A is alkyl (as ex.)) are active as PGE antagonists. In the specification of WO-96/06822, it is described that the compounds of the formula (B) (where A is a ring system which can be substituted, B to this, an aryl ring, which can be replaced or phenyl which can be substituted, D is a ring system which can be substituted, XB is (CHR4B) nB, O (CHR4B) nBO (CHR4B) pCR4B = CRB (CHR4B) q, R18 is carboxyl etc., R3B is H, alkyl of 1 to 4 carbon atoms, R4B is H, alkyl of 1 to 4 carbon atoms, (as extr.)). they are active as PGE antagonists. In the specification of WO-96/11902, it is described that the compounds of the formula (C) (wherein A, B and D are several ring systems, R1C is carboxyl etc., R3C is H, alkyl of 1 to 4 carbon atoms, Z is - (CH (R5c)) m, etc. (as extr. )) are active as PGE antagonists. Otherwise, some compounds having a structure similar to the compounds of the present invention are known. For example, the following compounds are described in Justus Liebigs Ann. Chem. (1909), 367, 133. (where RD is H or ethyl.) The following compounds are described in Khim. Geterotsikl. Soedin (1974), (6), 760. (wherein RE is phenethyl, benzyl, hexadecyl, decyl, nonyl, butyl, propyl, ethyl, methyl.) The following compounds are described in Khim. Geterotsikl. Soedin (1972), (10), 1341.

(F-2) (where R * is nitro or methoxy.) The following compounds are described in Khim. Geterotsikl. Soedin (1972), (5), 616.

The following compounds are described in Khim. Geterotsikl. Soedin (1976), (5), 641.

The following compounds are described in Khim. Geterotsikl. Soedin (1971), (7), 1028.

(J-2) The following compounds are described in Khim. Geterotsikl. Soedin (1970), (12), 1597. where each R? is Br or Cl.) The compounds of the formula (A), (B) and (C) in the related techniques possess the same pharmacological activity as the compounds of the present invention. But there is a difference in structure as follows: The compounds of the present invention have as an essential element in their structure sulfonamide or carboamide. On the other hand, the compounds described in such related techniques have either an ether or alkylene in the corresponding part. That is, it is not easy to predict the compounds of the present invention from the structure of these reported techniques. In addition, the compounds of the formula (D) to (K) refer to the study for synthesis only. In this literature, there is no description in pharmacological activity. The carboxyl group in such compounds is connected to the ortho position, so the compounds of the present invention are different from such compounds in structure. Therefore, it is not easy to predict the present invention from such compounds that possess the different activity and structure.

DESCRIPTION OF THE INVENTION The present invention relates to (1) sulfonamide or carboamide derivatives of the formula (I) (wherein each, independently, is a carbocyclic ring of 1 to 5 carbon atoms or a 5-7 membered heterocyclic ring containing one or two oxygen, sulfur or nitrogen atom (s) .Z1 is -COR1 -alkylene COR1 of 1 to 4 carbon atoms -CH = CH-COR1 -C = COR:, or -alkylene-COR ^ O- of 1 to 3 carbon atoms (wherein R1 is hydroxy, alkoxy of 1 to 4 carbon atoms or the formula NR_R7 (wherein R and R "" each, independently is H or alkyl of 1 to 4 atoms of carbon)), or alkylene-OH of 1 to 5 carbon atoms Z: is H, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, nitro, halogen, trifluoromethyl, trifluoromethoxy, hydroxy or COR1 (wherein R1 is as defined hereinabove) Z3 is a single bond or alkylene of 1 to 4 carbon atoms carbon Z4 is S02 or CO, Z5 is (1) alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, or alkynyl of 2 to 8 carbon atoms. (2) phenyl, cycloalkyl of 3 to 7 to carbon atoms, or a 5-7 membered heterocyclic ring containing one or two oxygen, sulfur or nitrogen atom (s), or (3) alkyl of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon atoms , or alkynyl of 2 to 4 carbon atoms, substituted by phenyl or cycloalkyl of 3 to 7 carbon atoms. (phenyl, cycloalkyl of 3 to 7 carbon atoms, and 5-7 membered heterocyclic ring containing one or more oxygen, sulfur or nitrogen atom (s), mentioned in (2) and (3) above) may be substituted by 1-5 of R 5 (wherein R 5 (if two or more R 5, each independently) is H, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkylthio of 1 to 6 carbon atoms , nitro, halogen, trifluoromethyl, trifluoromethoxy or hydroxy)). R1 is CONR8 NR8CO, CONR8- alkylene of 1 to 4 carbon atoms, alkylene of 1 to 4 carbon atoms CONR8, NR8CO-alkylene of 1 to 4 carbon atoms, alkylene of 1 to 4 carbon atoms-NR8CO, alkylene from 1 to 3 carbon atoms-CONR8-alkylene of 1 to 3 carbon atoms or, alkylene of 1 to 3 carbon atoms-NR8CO-alkylene of 1 to 3 carbon atoms (wherein each R8 is H, or 1 to 4 carbon atoms), 0, S, NZ6 (where Z6 is H or alkyl of 1 to 4 carbon atoms), Z7-alkylene of 1 to 4 carbon atoms, alkylene of 1 to 4 carbon atoms- Z7, or alkylene of 1 to 3 carbon atoms-Z7-alkylene of 1 to 3 carbon atoms (wherein each Z7 is O, S or NZ6 (where Z6 is as defined below)). C 1 -C 4 -alkylene CO-C 1 -C 3 -alkylene-CO-C 1 -C 3 -alkylene, C 2 -C 4 -alkenylene-2 -C 4 -alkenylene, or alkenylene-C 2 -C 4 -alkylene 2 to 4 carbon atoms R3 is H, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkylthio of 1 to 6 carbon atoms, nitro, halogen, trifluoromethyl, trifluoromethoxy, hydroxy or hydroxymethyl, R4 is (1) H, (2) alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, or alkynyl of 2 to 8 carbon atoms, (3) alkyl of 1 to 6 carbon atoms substituted by one or two substituent (s) selected from the group consisting of COOZ8, CONZ9Z10, and OZ8 (wherein Z8, Z9 and Z10 each independently is H or alkyl) 1 to 4 carbon atoms) and Cl-4 alkoxy-Cl-4 alkoxy, (4) cycloalkyl of 3 to 7 carbon atoms, or (5) alkyl of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon atoms carbon or alkynyl of 2 to 4 carbon atoms substituted by phenyl or cycloalkyl of 3 to 7 carbon atoms (phenyl and cycloalkyl of 3 to 7 carbon atoms mentioned in the above (4) and (5) can be substituted by 1- 5 of R5 (where R5 is as defined here)) ynyt each, independently is an integer of 1-4, with the provision that (1) R2 and Z3 should be connected to the position 1- or 2- of is a benzene ring and (Z2) is preferably COR1, Z: should be connected to the 3 or 4 position of the benzene ring) or a non-toxic salt thereof, (2) process for preparing them and (3) PGE2 antagonists or agonists which comprise them as an active ingredient.

DETAILED DESCRIPTION OF THE INVENTION In the formula (1), alkyl of 1 to 4 carbon atoms in Z5 and R4 and alkyl of 1 to 4 carbon atoms represented by Z2, Z6, Z8, Z9, Z10, R6, R7 and R8 suggest methyl, ethyl, propyl, butyl and isomers thereof. In the formula (I), alkyl of 1 to 6 carbon atoms in R 4 and alkyl of 1 to 6 carbon atoms represented by R 3 and R 5 suggest methyl, ethyl, propyl and butyl, pentyl, hexyl and isomers thereof. In the formula (I), alkyl of 1 to 8 carbon atoms, represented by Zb and R4 suggest methyl, ethyl, propyl, butyl, pentyl, hexyl, octyl and isomers thereof. In formula (1), alkenyl of 2 to 4 carbon atoms in Z5 and R4 suggests vinyl, propenyl, butenyl and isomers thereof. In formula (1), alkenyl of 2 to 8 carbon atoms represented by Z5 and R4 suggests alkyl of 2 to 8 carbon atoms having 1-3 double bonds and, for example, vinyl, propenyl, butenyl, pentenyl, hexenyl , heptenyl, octenyl etc. and isomers thereof.

In formula (1), alkynyl of 2 to 4 carbon atoms in Z5 and R4 suggests ethynyl, propynyl, butynyl and isomers thereof. In the formula (1), alkenyl of 2 to 8 carbon atoms represented by Z5 and R4 suggests alkyl of 2 to 8 carbon atoms having 1-3 triple bonds or triple bonds and, for example, ethynyl, propynyl, butynyl , pentinyl, hexinyl, heptinyl, octinyl etc. and isomers thereof. In formula (1), alkoxy of 1 to 4 carbon atoms in R 4 and alkoxy of 1 to 4 carbon atoms represented by Z 2 and R 1 suggest methoxy, ethoxy, propoxy, butoxy and isomers thereof. In formula (1), alkoxy of 1 to 6 carbon atoms represented by R3 and R5 suggests methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy and isomers thereof. In formula (1), alkylthio having from 1 to 6 carbon atoms represented by R 3 and R 5 suggests methylthio, ethylthio, propylthio, butylthio, pentthylthio, hexylthio and isomers thereof. In the formula (1), alkylene of 1 to 3 carbon atoms in Z1 and R2 suggests methylene, ethylene, trimethylene and isomers thereof. In formula (1), alkylene of 1 to 4 carbon atoms in Z1 and R2 and alkylene of 1 to 4 carbon atoms represented by Z3 suggests methylene, ethylene, trimethylene, tetramethylene and isomers thereof. In the formula (1), alkylene of 1 to 5 carbon atoms, in Z1, suggests methylene, ethylene, trimethylene, tetramethylene, pentamethylene and isomers thereof. In the formula (1), alkylene of 2 to 4 carbon atoms represented by R2 suggests ethylene, trimethylene, tetramethylene and isomers thereof. In formula (1), alkenylene of 2 to 4 carbon atoms represented by R2 suggests vinylene, propenylene, butenylene and isomers thereof. In the formula (1), alkynylene represented by R2 suggests ethynylene, propynylene, butynylene and isomers thereof. In formula (1), cycloalkyl of 3 to 7 carbon atoms in Z5 and R4 and cycloalkyl of 3 to 7 carbon atoms represented by Z5 and R4 suggests cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl.

In formula (1), the carbocyclic ring of 5 to carbon atoms, represented by suggests a mono, bi or tri carbocyclic aryl añilo of 5 to 15 carbon atoms, or partially or completely a saturated ring thereof. For example, carbocyclic aryl of 5 to 15 carbon atoms includes benzene, pentalene, indene, naphthalene, azulene, fluorene, anthracene etc. The partially or fully saturated ring thereof includes the ring mentioned above which is partially or completely saturated. Thus, for the carbocyclic ring of 5 to 15 carbon atoms, preferably mono or bi-carbocyclic aryl ring of 5 to 10 carbon atoms and the aforementioned cycloalkyl of 5 to 7 carbon atoms, and more preferably benzene, naphthalene, is listed. , cyclopentyl, cyclohexyl or cycloheptyl. In formula (1), the 5- to 7-membered heterocyclic ring containing one or two oxygen, sulfur or nitrogen atom (s) represented by, and z5 suggests a 5- to 7-membered heterocyclic aryl ring containing one or two atom (s) of oxygen, sulfur or nitrogen or partially or completely a saturated ring thereof. The 5- to 7-membered heterocyclic aryl ring containing one or two oxygen, sulfur or nitrogen atom (s) includes pyrrole, imidazole, pyrazole, pyridine, pyrazine, pyrimidine, pyridazine, azepine, diazepine, furan, pyran, oxepin, oxazepine, thiophene, tiain (thiopyran), tiepine, oxazole, isoxazole, thiazole, isothiazole, oxadiazole, oxadiazine, oxazepine, oxadiazepine, thiadiazole, thiadiazine, thiadiazepine etc. The 5- to 7-membered heterocyclic ring contains one or two oxygen, sulfur or nitrogen atoms which is partially or completely saturated, including pyrroline, pyrrolidine, imidazoline, imidazolidine, pyrazoline, pyrazolidine, piperidine, piperazine, tetrahydropyrimidine, tetrahydropyridazine, dihydrofuran, tetrahydrofuran, dihydropyran, tetrahydropyran, dihydrothiophene, tetrahydrothiophene, dihydrothiain (dihydrothiopyran), tetrahydrothiain (tetrahydrothiopyran), dihydroxazole, tetrahydroxazole, dihydroisoxazole, tetrahydroisoxazole, dihydrothiazole, tetrahydrothiazole, dihydroisothiazole, tetrahydroisothiazole, morpholine, thiomorpholine etc.

In the formula (1), halogen represented by Z2, R3 and R5 suggests chlorine, bromine, fluorine and iodine.

In the formula (1), so for Z3 which represents a single bond or alkylene of 1 to 4 carbon atoms, preferably, a single bond or more preferably, a single bond is listed.

In formula (1), so for Z4 which represents S02 or CO, S02 is preferably listed.

In formula (1), so for R4, preferably, each group is more preferably, a group preferably hydrogen.

Unless otherwise specified, all isomers are included in the invention. For example, alkyl, alkylene and alkenylene include straight chain or straight chain or branched chain. The double bond in alkenylene includes the structure of configurations E, Z and EZ mixtures. The isomers generated by the asymmetric carbon (s) eg branched alkyl are also included in the present invention.

In the compounds of the formula (I) of the present invention, compounds are preferred where is a carbocyclic ring of 5 to 15 carbon atoms and Z5 is alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, alkynyl of 2 to 8 carbon atoms or a group containing phenyl or cycloalkyl of 3 to 7 carbon atoms (each ring can be substituted).

Compounds where y is a mono or bi ring of carbocyclic aryl of 5 to 10 carbon atoms and cycloalkyl of 5 to 7 carbon atoms and Z5 is the group mentioned above are most preferable.

Also preferred are compounds wherein at least one of, and Z5 is a 5- to 7-membered heterocyclic ring containing one or two oxygen, sulfur or nitrogen atom (s) (each ring may be substituted). Such compounds include, for example, compounds where (1) and is a carbocyclic ring of 5 to 15 members and Z5 is a 5- to 7-membered heterocyclic ring containing one or (2) Oxygen, sulfur or nitrogen atom (s) of T- is a 5- to 7-membered heterocyclic ring containing a heterocyclic ring of one or two oxygen, sulfur or nitrogen atoms and the other is a carbocyclic ring of 5 to 15 carbon atoms. The compounds wherein the carbocyclic ring is represented by and / or in the case of the previous ones (1) and 2) is a mono or bi-aryl carbocyclic ring of 5-10 carbon atoms and cycloalkyls of 5 to 7 carbon atoms are more preferable. In the compounds of the formula (1) of the present invention, the concrete and preferable compounds include the compounds described in the Examples and corresponding esters and amides.

[Salt] The compounds of the present invention of the formula (I) can be converted into the corresponding salts by methods known per se. Water-soluble and non-toxic salts are preferable. Suitable salts, for example, are the following: alkali metal salts (potassium, sodium, etc.,) salts of alkaline earth metals (calcium, magnesium, etc.), ammonium salts, salts of pharmaceutically acceptable organic amines (tetramethylammonium, triethylamine, methylamine, diethylamine, cyclopentylamine, benzylamine, phenethylamine, piperidine, monoethanolamine, diethanolamine, tris (hydroxymethyl) aminomethane, lysine, arginine, N-methyl-D-glucamine etc.).

[The method of preparation for the compounds of the present invention] The compounds of the formula (I) of the present invention can be prepared by the method described in the following, the method described in the Examples as hereinbefore or known methods. (1) In the compounds of the formula (I) of the present invention, the carboxylic acid compounds of the formula (Ia) (wherein Zla and Za are as Z1 and Z2 respectively, with the proviso that at least one of them is COOH or a group containing COOH, and the other symbols are as defined hereinbefore) can be prepared from the ester compound of the formula (Ib) (wherein Zlb and Z2b are as Z1 and Z2 respectively, with the provision that at least one of them is CORlb or a group containing CORlb, (where Rlb is alkoxy of 1 to 4 carbon atoms or methoxymethoxy (abbreviated as OMOM).). R3, Rb and Z5b are like R3, R4 and R5 respectively, with the proviso that when R3, R4, or R5 in Z5 is COOH or hydroxy, or a group containing COOH or hydroxy, each COOH is hydroxy is protected by a protecting group which is removed under an acidic, neutral or alkaline condition, and the other symbols are as defined herein above). by hydrolysis under an alkaline, acidic or neutral condition, if necessary, followed by hydrolysis under the different condition.

The removal of a protecting group by hydrolysis under an alkaline, acidic or neutral condition is a well-known reaction as described hereinabove. (2) In the compounds of the formula (I) of the present invention, the ester compounds of the formula of) (wherein Zlc and Z2c are as Z1 and Z2 respectively, with the provision that at least one of them is CORlc or a group containing CORlc, (where Rlc is alkoxy) and the other symbols are as defined herein above) they can be prepared from the compound of the formula (la) by esterification.

Esterification in a well-known manner can be carried out, for example; (a) by the method using diazoalkane, (b) by the method using alkyl halide, (c) by the method using dimethylformamide (DMF) -acetal dialkyl, or (d) by the method of reacting the corresponding alkanol, etc. .

The specific description of the methods described above is as follows: (a) The method using diazoalkane can be carried out for example, using the corresponding diazoalkane in an organic solvent (diethyl ether, ethyl acetate, methylene chloride, acetone, methanol or ethanol, etc.) at -10 ~ 40 ° C. (b) The method using alkyl halide can be carried out for example in an organic solvent (acetone, DMF, dimethyl sulfoxide (DMSO), etc.) in the presence of a base (potassium carbonate, sodium carbonate, potassium hydrogen carbonate) , sodium hydrogen carbonate, calcium oxide, etc.) using the alkyl halide corresponding to -10 ~ 40 ° C. (c) The method using acetal dialkyl DMS can be carried out for example, in an organic solvent (benzene, toluene, etc.) using the dialkyl acetal DMF corresponding to -10 ~ 40 ° C. (d) The method by reacting the corresponding alkanol can be carried out for example in the corresponding alkanol (HRlc (Rlc is as defined above)) using aicdo (HCl, sulfuric acid, p-toluene sulfonic acid, hydrochloride gas, etc.). ) or condensing agents (DCC, pivaloyl halide, arylsulfonyl halide, alkylsulfonyl halide, etc.) at 0 ~ 40 ° C. Of course, an organic solvent (tetrahydrofuran, methylene chloride, etc.) which does not refer to the reaction can be added in this esterification. (3) In the compounds of the formula (I) of the present invention, the amide compounds of the formula (Id) (where Z1 and Z2d are like Z1 and Z respectively, with the provision that at least one of them is CORld or a group containing CORl, (where Rld is NR6R7 (where all symbols are as defined here above ), and the other symbols are as defined herein above.) can be prepared by reacting the compound of the formula (la) with the compound of the formula (III) HNR6R7 (III) (where all the symbols are as defined here above) to form the amide link.

The reaction to form an amide bond is known, for example, in an organic solvent (THF, methylene chloride, benzene, acetone, acetonitrile, etc.), in the presence or absence of a tertiary amine (dimethylaminopyridine, pyridine, triethylamine, etc.) using a condensing agent (EDC or DCC etc.) at 0 ~ 50 ° C. (4) In the compounds of the formula (I) of the present invention, the alcohol compounds of the formula of) (wherein Zle is alkylene of 1 to 5 carbon atoms-OH, and the other symbols are as defined herein above). can be prepared by the reduction of the compound of the formula (If) (wherein Zlf is COOYf or alkylene COOY of 1 to 4 carbon atoms (wherein Yf is alkyl of 1 to 4 carbon atoms), and the other symbols are as defined herein above).

The reductive reaction is known, and for example, this reaction can be carried out in the presence of an organic solvent (THF, methylene chloride, diethyl ether, lower alkanol, etc.), using lithium aluminum hydride (LAH) or aluminum hydride diisobutyl (DIBAL) at -78 ° C at room temperature. (5) In the compounds of the formula (Ib), wherein R2 is CONR8, Cl-4 alkylene-CONR8, CONR8-alkylene of 1 to 4 carbon atoms, Cl-3 alkylene-CONR8-alkylene of 1 to 3 atoms carbon, (where all the symbols are as defined herein above), ie, the compounds of the formula (Ib-1) (wherein R20 is CONR8, Cl-4 alkylene-CONR8, CONR8-Cl-4 alkylene, Cl-3 alkylene-CONR8-alkylene of 1 to 3 carbon atoms (wherein all symbols are as defined herein above), and the other symbols are as defined here above). they can be prepared by reacting the compound of the formula (IV) (wherein R200 is a single bond or alkylene of 1 to 4 carbon atoms, and the other symbols are as defined herein above). with the compound of the formula (V) (wherein R201 is a single bond or alkylene of 1 to 4 carbon atoms, and the other symbols are as defined herein above) to form an amide bond. The reaction to form an amide bond can be carried out as the method described in (3). (6) In the compounds of the formula (Ib), wherein R2 is NR8CO, Cl-4 alkylene-NR8CO, NR8CO-Cl-4 alkylene, Cl-3 alkylene-NR8CO-Cl-3 alkylene (wherein all the symbols they are as defined herein above), ie, the compounds of the formula (Ib-2). (wherein R21 is NR8CO, Cl-4 alkylene-NR8CO, NR8CO-Cl-4 alkylene, Cl-3 alkylene-NR8CO-alkylene of 1 to 3 carbon atoms (wherein all symbols are as defined herein above), and the other symbols are as defined here above). they can be prepared by reacting the compound of the formula (VI) (where all the symbols are as defined here above) with the compound of the formula (VII) (where all symbols are as defined here) to form an amide bond. The reaction to form an amide bond can be carried out as the method described in (3). (7) In the compounds of the formula (Ib), wherein R 2 is O, S, NZ 6, Z 7 -alkylene of 1 to 4 carbon atoms, alkylene of 1 to 4 carbon atoms-Z 7 or alkylene of 1 to 3 carbon atoms-Z7-alkylene of 1 to 3 carbon atoms (wherein all symbols are as defined above), ie, the compounds of the formula (Ib-3) (wherein R22 is 0, S, NZ6, Z7-alkylene of 1 to 4 carbon atoms, alkylene of 1 to 4 carbon atoms-Z7 or alkylene of 1 to 3 carbon atoms-Z7-alkylene of 1 to 3 atoms carbon (where all symbols are as defined hereinbefore).) can be prepared by reacting the compound of the formula (VIII) (where all the symbols are as defined hereinbefore) with the compound of the formula (IX) X-Z4-Z5 (IX) (wherein X is halogen and the other symbols are as defined hereinbefore) to form a sulfonamide bond or carboamide bond.

The reactions to form a carboamide or sulfonamide bond can be carried out for example in an organic solvent (THF, methylene chloride, benzene, acetone, acetonitrile, etc.), in the presence or absence of tertiary amines (dimethylaminopyridine, pyridine, triethylamine, etc.) at 0 ~ 50 ° C. (8) In the compounds of the formula (Ib), wherein R2 is NZ6 Cl-4 alkylene, Cl-4 alkylene-NZ6 or Cl-3 alkylene-NZ6-Cl-3 alkylene (wherein all symbols are as defined hereinbefore), ie, the compounds of the formula (Ib-4). (wherein R23 is NZ6 Cl-4 alkylene, Cl-4 alkylene-NZ6 or, Cl-3 alkylene-NZ6 alkylene of 1 to 3 carbon atoms (where all symbols are as defined herein above), and the others symbols are as defined here above). they can be prepared by (a) reacting (reductive amination) the compound of the formula (Vi-a) (wherein R230 is a single bond or alkylene of 1 to 4 carbon atoms, and the other symbols are as defined herein above.) with the compound of the formula (VII-a) (wherein R231 is a single bond or alkylene of 1 to 3 carbon atoms, and the other symbols are as defined hereinbefore) or (b) reacting (reductive amination) the compound of the formula (V1-b) (where all the symbols are as defined here above) with the compound of the formula (Vll-b) (where all symbols are as defined here above) The reaction of the reductive amination described in the above (a) and (b) can be carried out for example, in an organic solvent (methane, etc.) in an acidic condition, using a boron reagent such as sodium cyanoborohydride, etc. , at 0 ~ 50 ° C. (9) In the compounds of the formula (Ib), wherein R2 is alkenylene of 2 to 4 carbon atoms, ie, the compounds of the formula (Ib-5) (wherein R25 is alkenylene of 2 to 4 carbon atoms and the other symbols are as defined hereinbefore) can be prepared by reacting the compound of the formula (XI) (where all the symbols are as defined hereinbefore) with the compound of the formula (IX) X-Z4-Z5b (IX) (wherein all symbols are as defined above) to form a sulfonamide bond or a carboamide bond.

The reaction to form a sulfonamide bond or a carboamide bond can be carried out by the method described in (7). (10) In the compounds of the formula (Ib), wherein R 2 is alkylene of 2 to 4 carbon atoms, ie, the compounds of the formula (Ib-6) (wherein R26 is alkylene of 2 to 4 carbon atoms, Zl c, z5c and z4cc are as zlb, Z5b and Z4b, respectively, with the proviso that none of Zlcc, Z5cc and Z4cc are alkenylene, alkynylene, alkenylene containing a group and alkynylene containing a group, and the other symbols are as defined hereinbefore.) can be prepared by the catalytic reduction of the compound of the formula (Ib-5).

The catalytic reduction is known, and for example, this reaction can be carried out under the condition of hydrogen gas atmosphere, in an organic solvent (THF, alkanol or acetone, etc.) using a reductive catalyst (Pd, Pd-C, Pt - or platinum oxide, etc.) at 0 ~ 50 ° C. (11) In the compounds of the formula (Ib), wherein R 2 is alkynylene of 2 to 4 carbon atoms, ie, the compounds of the formula (Ib-7). (wherein R 27 is alkynylene, and the other symbols are as defined herein above.) can be prepared by reacting the compound of the formula (XII) (where all symbols are as defined hereinabove.) with the compound of the formula (IX) X-Z4-Z5b! IX) (where all the symbols with as defined above) to form a sulfonamide bond or a carboamide bond.

The reaction to form a sulfonamide bond or a carboamide bond can be carried out as the method described in (7). (12) In the compounds of the formula (Ib) wherein R2 is NZ6S02 (where all symbols are as defined herein above), ie, the compounds of the formula (Ib-8) (where R28 is NZ S02 (where all symbols are as defined herein above.) and the other symbols are as defined herein above.) can be prepared by reacting the compound of the formula (Z-1) (where all the symbols are as defined here above.), c with the compound of the formula (Z-2) (where all symbols are as defined herein above.) To form a sulfonamide bond.

The reaction to form a sulfonamide bond can be carried out as the method described in (7). (13) In the compounds of the formula (Ib), wherein R2 is CO, CO-alkylene of 1 to 4 carbon atoms, alkylene of 1 to 4 carbon atoms-CO or alkylene of 1 to 3 carbon atoms, that is, the compounds of the formula (Ib-9) (lb-9) (wherein R29 is CO, CO-alkylene of 1 to 4 carbon atoms, alkylene of 1 to 4 carbon atoms-CO or alkylene of 1 to 3 carbon atoms-CO-alkylene of 1 to 3 carbon atoms, and the other symbols are as defined hereinabove.) can be prepared by reacting the compound of the formula (Z-3) (where all the symbols are as defined here above.) with the compound of the formula (Z-4) (where all the symbols are as defined hereinabove.) This reaction can be carried out, for example, in an organic solvent (THF, methylene chloride, benzene, acetone, acetonitrile, etc.) in the presence of Zn or cyano copper at -78 ° C at room temperature. (14) In the compounds of the formula (Ib), wherein Rb is a group preferably H, ie, the compounds of the formula (Ib-10). (wherein R44 is as R4 preferably H, and the other symbols are as defined herein above.) can be prepared by reacting the compound of the formula (Ib-11) (where all the symbols are as defined here above.) and (a) the compound of the formula (Z-5) X-R44 (Z-5) (where all symbols are as defined here above.) or (b) the compound of the formula (Z-6) HO-R44 (Z-6) (where all symbols are as defined hereinbefore.) The above reaction is the N-alkylation reaction or the corresponding reaction. For example, this reaction (a) in case of using an alkyl halide of the formula (where all symbols are as defined herein above.) can be done in an organic solvent (acetone, THF or methylene chloride, etc.) in the presence of a base (potassium carbonate, etc.) at 0 ~ 50 ° C.

The reaction (b) in case of using an alcohol of the formula HO-R ' (where all symbols are as defined hereinbefore), it can be carried out in an organic solvent (acetone, THF or methylene chloride, etc.) in the presence of triphenylphosphine and diethyldiazocarboxylate (DEAD) at 0 ~ 50 ° C. (15) The compounds wherein R3 is hydroxymethyl can be prepared by the above-mentioned method or the method described in the following Examples. (16) Compounds wherein Z4 is S02 and Z5 is cyclopentyl, cyclohexyl (each ring can be substituted by 1-5 of R5 (R5 is as defined hereinbefore).) Or isopropyl can be prepared by the method mentioned above or the method described in the following Examples. (17) The compounds wherein the symbol (s) preferably Z1 is / are COOH, COOZa (where Za is alkyl of 1 to 4 carbon atoms) or hydroxy or a group containing COOH, COOZa (where Za is as defined herein above.) or hydroxy can be prepared by reacting under the condition of each of the above groups and Z1 if necessary, protected by a protecting group which is removed under an alkaline, acidic or neutral condition or combining the removal of protecting groups under different conditions (for example, removal of a protecting group under an acidic condition and removal of a protecting group under an alkaline condition can be carried out successively, either a reaction that is first initiated.) A COOH protecting group which is removable under an acidic condition, includes, for example, a silyl-containing group such as t-butyldimethylsilyl, etc. or t-butyl.

A COOH protecting group which is removable under an alkaline condition includes an alkyl group (e.g., methyl, etc.) preferably t-butyl.

A COOH protecting group which is removable under both an acidic condition and an alkaline condition includes, for example, methoxymethyl.

A protective group of COOH which is removable under a neutral condition includes benzyl, etc.

A hydroxy protecting group which is removable under an acidic condition includes, for example, tetrahydropyranyl, silyl which contains a group such as t-butyldimethylsilyl, etc. 1-ethoxyethyl or methoxymethyl, etc.

A hydroxy protecting group, which is removable under an alkaline condition includes an acyl group such as acetyl, etc.

A hydroxy protecting group which is removable under a neutral condition includes benzyl or silyl which contains a group such as t-butyldimethylsilyl, etc.

The removal of a protecting group under an alkaline condition is well known. For example, this reaction can be carried out in an organic solvent (methanol, THF, dioxane, etc.) using an alkali metal hydroxide (sodium hydroxide, potassium hydroxide, etc.), or a carbonate salt (sodium carbonate) , potassium carbonate, etc.) or an aqueous solution thereof, or a mixture thereof at 0 ~ 40 ° C.

The removal of a protecting group under an acidic condition is well known. For example, this reaction can be carried out in a solvent (methylene chloride, dioxane, ethyl acetate, water or a mixture thereof, etc.) using an organic acid (trifluoroacetic acid, etc.), or an inorganic acid (HCl, HBr etc.) at 0 ~ 120 ° C.

The removal of a protecting group under a neutral condition is well known. For example, this reaction using benzyl can be carried out in a solvent (ether, THF, dioxane, dimethoxyethane, diethyl ether, etc.) alcohol (methanol, ethanol, etc.), benzene (benzene, toluene, etc.), ketone (acetone) , methylethyl ketone, etc.), nitrile (acetonitriolo, etc.) amide (dimethylformamide etc.) water, ethyl acetate, acetic acid or mixture thereof, etc.) in the presence of a catalyst (Pd-C, palladium black , PdOH, Pt02, Raney nickel, etc.), at ordinary pressure or increased under the condition of atmosphere gas or hydrogen in the presence of aminium format at 0 ~ 200 ° C.

This reaction using silyl contains a group such as t-butyldimethylsilyl, can be carried out in a solvent such as ether (THF, etc.) using tetrabutylammonium fluoride at 0 ~ 50 ° C.

The compounds of the formula (III), (V), (VII), (IX), (Vil-a), (VH-b), (Z-2), (Z-4), (Z-5) or (Z-6) are acidic or can be easily prepared by well-known methods or the methods described in the preceding Examples. The compounds of the formula (IV), (VI), (VIII), (X), (XI), (XII) or (Z-3) can be prepared by the following reaction schemes (A) - (F).

In the reaction scheme, each symbol is as defined above, or as defined below: R200: a single bond or alkylene of 1-4 carbon atoms; R202: a single bond or alkylene of 1-4 carbon atoms; R203: a single bond or alkylene of 1-4 carbon atoms; R204: a single bond or alkylene of 1 or 2 carbon atoms; R205: alkylene of 1, 2 or 3 carbon atoms; R206: a single bond or alkylene of 1 or 2 carbon atoms; R207: alkylene of 1, 2 or 3 carbon atoms; R208: alkylene of 1, or 2 carbon atoms; R50: alkyl of 1, carbon atoms; R51: trifluoroacetyl; X1, X2, X3, X4: halogen -1 or cn or cp Reaction Scheme (A) (IV) (Z-3) cp or cp O cp Reaction Scheme IB) (XVIII) (VI) cp or cp cp Reaction scheme C (XXII) (VIII) cp or cp s cp Reaction Scheme (D) (XXVI) (VIII) ro cp or cp Cp Reaction Scheme ÍE) (XXX) (XI) ro ro Cp or Cp O Cp Reaction Scheme (R < XXXIV > (XXXII) (XXXIII) Reduction (XXXVH) (XII) In each reaction in the present specification, the products obtained can be purified by conventional techniques. For example, the purification may be carried out by distillation at atmospheric or reduced pressure, by high performance liquid chromatography, by thin layer chromatography or by column chromatography using silica gel or magnesium silicate, by washing or by recrystallization. The purification can be carried out after each reaction, or after series of reactions.

[Starting materials and reagents] The starting materials and reagents in the present invention are known per se or can be prepared by known methods.

Industrial availability [Pharmacological activity of the compounds of the present invention] The compounds of the present invention of the formula (I) can bind to the prostaglandin E2 receptors and show antagonistic activity against the action of this or agonist activity, thus they are useful as agonists or antagonists of PGE2. As mentioned above, antagonizing against PGE2 is linked to the inhibition of uterine contraction, analgesic action, inhibition of digestive peristalsis, induction of sleep or increase of bladder capacity. Therefore, PGE2 antagonists are considered to be useful for the prevention of abortion, as analgesics, as antidiarrheals, as sleep inducers or as agents for the treatment of frequency. As mentioned above, it is demonstrated that the PGE2 agonist activity is linked to uterine contraction, promotion of digestive peristalsis, suppression of gastric acid secretion or reduction of blood pressure or diuresis. Therefore, PGE2 agonists are considered useful as antiabortion, cathartic, antiulcer, antigastritis, antihypertensive or diuretic agents. For example, in the standard laboratory test, it was confirmed that the compounds of the formula (I) of the present invention can bind to the PGE2 receptor (EP, receptor) according to the assay using the prostanoid receptor subtype cell. . (i) Binding or binding assay using the prostanoid receptor subtype expression cell The preparation of the membrane fraction was carried out according to the method of Sugimoto et al (J. Biol. Chem. 267, 6463-6466 (1992)), using the CHO cell of expression of the prostanoid receptor subtype (mouse EP1) . The membrane fraction contained in the standard test mixture (0.5 mg / ml), 3H-PGE2 in a final volume of 200 μl, was incubated for 1 hour at room temperature. The reaction was determined by the addition of 3 ml of ice-cooled buffer. The mixture was filtered rapidly through a glass filter (GF / B). The radioactivity associated with the filter was measured by liquid scintillation counting. The Kd and Bmax values were determined from Scatchard portions (Ann. N.Y. Acad. Sci., 5_1, 660 (1949)). The non-specific binding or binding was calculated as the linkage in the presence of an excess (2.5 μM) of unlabelled PGE2. In the experiment for the binding competition of 3H-PGE2 specified by the compounds of the present invention, 3H-PGE2 was added at a concentration of 2.5 nM and the compound of the present invention was added at various concentrations. The following buffer was used throughout the reaction.

Shock absorber: potassium phosphate (pH 6.0, 10 mM), EDTA (1 mM), MgCl2 (10 mM), NaCl (0.1 M). The dissociation constant Ki (μM) of each compound was calculated by the following equation. Ki = IC50 / (l + ([C] / Kd)) The results are shown in Table 1.

Table 1 [Toxicity] The toxicity of the compounds of the present invention is very low and therefore, it is confirmed that these compounds are safe to use as medicaments.

[Application for Pharmaceutical Products] The compounds of the present invention of the formula (I) can bind to the prostaglandin E2 receptors and show antagonistic activity against the action thereof or agonist activity, therefore they are useful as agonists or PGE2 antagonists As mentioned above, antagonizing against PGE2 is linked to the inhibition of uterine contraction, - analgesic action, inhibition of digestive peristalsis, induction of sleep or increase of bladder capacity. Therefore, PGE2 antagonists are considered useful for the prevention of abortion, as analgesics, as antidiarrheals, as inducers of sleep or as agents for the treatment of pollakiuria. As mentioned above, it is demonstrated that the PGE2 agonist activity is linked to uterine contraction, promotion of digestive peristalsis, suppression of gastric acid secretion or reduction of blood pressure or diuresis. Therefore, PGE2 agonists are considered useful as antiabortion, cathartic, antiulcer, antigastritis, antihypertensive or diuretic agents. The compounds of the present invention can bind to the prostaglandin E2 receptors in particular, strongly to the EP1 receptor, therefore they are expected to be useful as analgesics or as agents for the treatment of frequency. For the purposes described above, the compounds of the formula (I), nontoxic salts thereof and hydrates thereof, can normally be administered systemically or locally, usually by oral or parenteral administration. The doses to be administered are determined depending on the age, body weight, symptom, the desired therapeutic effect, the route of administration, and the duration of the treatment etc. In the human adult, the doses per person per dosage are generally between 1 μg and 100 mg, by oral administration, up to several times per day, and between 0.1 μg and 10 mg, by parenteral administration (preferred in the vein) to several times per day, or administration continues between 1 and 24 hours per day in the vein. As mentioned above, the doses to be used depend on several conditions. Therefore, there are cases in which doses lower than or greater than the ranges specified above can be used. In the administration of the compounds of the present invention, they are used as solid compositions, liquid compositions or other compositions for oral administration, such as injections, liniments or suppositories etc., for parenteral administration. Solid compositions for oral administration include compressed tablets, pills, capsules, dispersible powders, and granules etc. The capsules contain hard capsules and soft or soft capsules. In such solid compositions, one or more of the active compound (s) is or is, mixed with at least one inert diluent such as lactose, mannitol, mannitol, glucose, hydroxypropylcellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone. , magnesium metasilicate aluminate. The compositions may also comprise, as is normal practice, additional substances other than inert diluents: for example, lubricating agents such as magnesium stearate, disintegrating agents, such as calcium glycollate and cellulose, and adjuvants for dissolving, such as acid glutamic or asparaginic acid. Tablets or pills, if desired, may be coated with gastric or enteric film such as sugar, gelatin, hydroxypropylcellulose or hydroxypropylcellulose phthalate etc., or coated with two or more films. And in addition, the coating may include containment with capsules of absorbable materials such as gelatin. Liquid compositions for oral administration include pharmaceutically acceptable emulsions, solutions, syrups and elixirs etc. In such liquid compositions, one or more of the active compound (s) is or is comprised of inert diluent (s) commonly used in the art (e.g., purified water, ethanol, etc.). ). Except for inert diluents, such compositions may also comprise adjuvants such as wetting agents, suspending agents, sweetening agents, flavoring agents, flavoring agents and preserving agents. Other compositions for oral administration include spray compositions which can be prepared by known methods and which comprise one or more of the active compound (s). Spray compositions may comprise additional substances other than inert diluents: for example, stabilizing agents such as sodium acid sulfate, stabilizing agents to provide the isotonicity of the title compound, isotonic buffer such as sodium chloride, sodium citrate, citric acid . For the preparation of such spray compositions, for example, the method described in U.S. Patent No. 2868691 or 3095355 can be used. Injections for perenteral administration include aqueous or non-aqueous solutions, suspensions and sterile emulsions. Aqueous solutions or suspensions include distilled water for injection and physiological salt solution. Non-aqueous solutions or suspensions include propylene glycol, polyethylene glycol, plant oil such as olive oil, alcohol such as ethanol, POLYSORBATE80 (registered trademark) etc. Such compositions may comprise additional diluents, for example, preserving agents, wetting agents, emulsifying agents, dispersing agents, stabilizing agents, adjuvants such as adjuvants to dissolve (eg, glutamic acid, asparaginic acid). They can be sterilized, for example, by filtration through a bacterial generation retarding filter, by incorporation of sterilizing agents in the compositions or by irradiation. They are also manufactured in the form of sterile solid compositions and which can be dissolved in sterile water or some other sterile diluents by injection immediately before use. Other compositions for parenteral administration include liquids for external use, and endemic liniments, ointment, suppositories and pessaries which comprise one or more of the active compound (s) and can be prepared by known methods.

The best way to carry out the invention The following reference examples and examples are proposed to illustrate, but not limit, the present invention. The solvents in parentheses show the elution or development solvents and the ratios of the solvents used are by volume in chromatographic separations. Without special explanation, the NMR data were determined in CDC13 solution.

Reference Example 1 -Chloroanthranilic Acid Methyl Ester To a suspension of 5-chloroanthranilic acid (6.1 g) in AcOEt-MeOH (20 ml + 10 ml), a solution of an excess amount of diazomethane in ether (50 ml) was added at 0 ° C. After completion of the reaction, the reaction solvent was evaporated to dryness to give the title compound (6.6 g) having the following physical data. NMR: d 7.82 (ÍH, d), 7.21 (1H, dd), 6.60 (1H, d), 5.73 (2H, brs), 3.88 (3H, s).

Reference Example 2 Methyl 2-phenylsulfonylamino-5-chlorobenzoate To a solution of 5-chloroanthranilic acid methyl ester (400 mg, prepared in Reference Example 1) and pyridine (0.87 ml) in methylene chloride, benzenesulfonyl chloride (0.33 ml) was added at 0 ° C. The solution was stirred overnight at room temperature. The reaction mixture was poured into dilute HCl and extracted with ethyl acetate. The organic layer was washed, dried over and concentrated under reduced pressure. The residue was purified on silica gel column chromatography (hexane-AcOEt) to give the title compound (664 mg) having the following physical data. TLC: Rf 0.30 (hexane: AcOEt = 4: 1); NMR: 6 10.5 (HH, s), 7.90-7.79 (3H, m), 7.79 (HH, d), 7.60-7.37 (4H, m), 3.88 (3H, s).

Reference Example 3 2-Phenylsulfonylamino-5-chlorobenzoic acid Cl To a solution of methyl 2-phenylsulfonylamino-5-chlorobenzoate (600 mg, prepared in Reference Example 2) in the THF-MeOH mixture (6 ml + 3 ml), 2N of NaOH solution was added. The mixture was stirred for two days. INN of HCl (4.5 ml) was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed and dried overhead to give the title compound (575 mg) having the following physical data. NMR: d 10.31 (HH, s), 7.99 (1H, d), 7.92-7.83 (2H, m), 7.70 (HH, d), 7.63-7.42 (4H, m), 6.20 (HH, brs).

Example 1 Methyl 4- (2-phenylsulfonylamino-5-chlorobenzoylamino) benzoate To a suspension of 2-phenylsulfonylamino-5-chlorobenzoic acid (250 mg, prepared in Reference Example 3) and methyl p-aminobenzoate (133 mg) in methylene chloride (5 ml), EDC (168 mg) was added. and dimethylaminopyridine (20 mg). The mixture was stirred for 3 days at room temperature. The reaction mixture was poured into dilute HCl and extracted with ethyl acetate. The organic layer was washed, dried over and concentrated under reduced pressure. The residue was purified on silica gel column chromatography (AcOEt-benzene) to give the title compound (142 mg) having the following physical data. TLC: Rf 0.29 (AcOEt: benzene = 1: 9); NMR (CDC13 + DMSO-de): d 10.40 (HH, s), 9.90 (HH, m), 8.03 (2H, d), 7.82-7.70 (5H, m), 7.63 . { ÍH, d), 7.50-7.24 (4H, m), 3.93- (3H, s).

Example 2 4- (2-phenylsulfonylamino-5-chlorobenzoylamino) benzoic acid To a solution of methyl 4- (2-phenylsulfonylamino-5-chlorobenzoyl) benzoate (122 mg, prepared in Example 1.) in THF-MeOH (4 ml + 2 ml), an aqueous NaOH solution was added. of 2N (0.5 ml) at room temperature. The mixture was stirred overnight. To the reaction mixture, 2N of HC1 (0.6 ml) and water were extracted. The mixture was extracted with ethyl acetate. The organic layer was washed, dried over, and concentrated under reduced pressure. The residue was purified by recrystallization from the AcOEt-hexane mixture to give the title compound (80 mg) having the following data. TLC: Rf 0.32 (MeOH: CH2C12 = 15:85); NMR (DMSO-de): d 12.74 (HH, brs), 10.61 (HH, s), 10.40 (HH, s), 7.95 (2H, d), 7.85-7.71 (5H, m), 7.64-7.35 (5H , m).

Example 2 (a) -2 (bb) The title compounds having the following physical data were obtained by the same procedure as Reference Example l ~ Reference Example 3 and Examples 1 and 2.

Example 2 (a) 3- (2-phenylsulfonylaminobenzoylamino) benzoic acid TLC: Rf 0.57 (CHC13: MeOH: AcOH = 100: 10: 1); NMR (DMSO-de): d 13.01 (ÍH, brs), 10.66 (ÍH, brs), 10.50 (ÍH, brs), 8.32 (ÍH, brs), 7.89 (ÍH, d), 7.76 (4H, m), 7.51 (6H, m), 7.23 (ÍH,).

Example 2 (b) 3- (2-Phenylsulfonylamino-5-chlorobenzoylamino) benzoic acid TLC: Rf 0.26 (MeOH: CHC13 = 15: 85); NMR (CDC13: DMS0-d6 = l: l): d 12.70 (HH, brs), 10.69 (HH, s), 10.44 (HH, S), 8.27 (HH, t), 7.95-7.69 (5H, m) 7.59-7.36 (6H, m).

Example 2 (c) 4- (2-Phenylsulfonylaminobenzoylamino) benzoic acid TLC: Rf 0.50 (CHCl3: MeOH: AcOH = 100: 10: 1); NMR (DMSO-de): d 12.76 (HH, brs), 10.57 (HH, s), 10.49 (HH, s), 7.95 (2H, d), 7.77 (5H, m), 7.28-7.62 (5H, m ), 7.24 (ÍH,).

Example 2 (d) 4- [2- (4-Chlorophenyl) sulfonylamino-5-chlorobenzoylamino] benzoic acid TLC: Rf 0.27 (MeOH: CHC13 = 15:85); NMR (DMSO-de): d 12.70 (1H, brs), 10.59 (HH, s), 10.30 (HH, s), 7.59 (2H, d), 7.83-7.66 (5H, m), 7.62-7.47 (3H , m), 7.34 (ÍH, d).

Example 2 (e) 4- [2- (4-Chlorophenylsulfonylamino) -4-chlorobenzoylamino] benzoic acid TLC: Rf 0.69 (CHC13: MeOH: AcOH = 17: 2: 1); NMR (CDCI3 + DMSO-de): o 10.9-10.3 (ÍH, br), 10.3-9.9 (ÍH, br), 7.84 (2H, d), 7.7-7.5 (5H, m), 7.45 (1H, s- similar), 7.17 (2H, d), 7.0-6.9 (ÍH, m).

Example 2 (f) 4- [2- (4-Chlorophenylsulfonylamino) -6-chlorobenzoylamino] benzoic acid TLC: Rf 0.67 (CHC13: MeOH: AcOH = 17: 2: 1); NMR: d 9.64 (ÍH, s-similar), 7.8-7.7 (2H, m), 7.5-7.3 (4H, m), 7.1-6.9 (5H, m).

Example 2 (g) 4- [2- (4-Chlorophenylsulfonylamino) -3-chlorobenzoylamino] benzoic acid TLC: Rf 0.32 (CHC13: MeOH = 9: 1); NMR (DMSO-de): d 12.8-12.6 (ÍH, br), 10.7-10.5 (ÍH, br), 10.12 (ÍH, s), 7.89 (2H, d), 7.7-7.5 (6H, m), 7.5 -7.3 (3H, m),.

Example 2 (h) 4 [2- (2-Chlorophenylsulphonylamino) -5-chlorobenzoyl] -benzoic acid TLC: Rf 0.16 (CHC13: MeOH = 9: 1); NMR (DMSO-de): d 12.78 (HH, br), 10.80 (2H, br), 8.08-8.03 (HH, m), 7.95 (2H, d), 7.88 (HH, d), 7.80 (2H, d) ), 7.66-7.46 (4H, m), 7.38 (ÍH, d).

E p e 2 (i) 4- [2- (3-Chlorophenylsulfonylamino) -5-chlorobenzoylamino] benzoic acid TLC: Rf 0.15 (CHC13: MeOH = 9: 1); NMR (DMSO-de): d 12.76 (HH, br), 10.62 (HH, brs), 10.36 (HH, brs), 7.92 (2H, d), 7.77-7-73 (4H, m), 7.67-7.44 (4H,), 7.28 (ÍH, d).

Example 2 (j) 4- [2- (4-Chlorophenylsulfonylamino) -5-fluorobenzoyl] -benzoic acid TLC: Rf 0.28 (MeOH: CHC13 = 15: 85); NMR (DMSO-de): d 12.78 (HH, brs), 10.50 (HH, s), 10.09 (HH, s), 7.95 (2H, d), 7.75 (2H, d), 7.68-7.26 (7H, m ).

Example 2 (k) 4- [2- (4-Chlorophenylsulfonylamino) -5-bromobenzoylamino] benzoic acid TLC: Rf 0.28 (MeOH: CHC13 = 15: 85); NMR (DMSO-de): d 12.74 (ÍH, brs); 10.61 (HH, s), 10.33 (HH, s), 7.95 (2H, d), 7.89 (HH, d), 7.81-7.65 (5H,), 7.53 (2H, d), 7.29 (HH, d).

Example 2 (1) 4- [2- (4-Chlorophenylsulfonylamino) -5-ethoxybenzoylamino] benzoic acid TLC: Rf 0.30 (MeOH: CHC13 = 15: 85); NMR (DMSO-de): d 12.77 (HH, brs), 10.39 (HH, s), 9.79 (HH, s), 7.94 (2H, d), 7.73 (2H, d), 7.59 (2H, d), 7.43 (2H, d), 7.25-7.15 (2H, m), 7.09 (ÍH, dd).

Example 2 (m) 4- [2- (4-Bromophenylsulfonylamino) -5-chlorobenzoylamino] benzoic acid TLC: Rf 0.27 (CHC13: MeOH = 9: 1); NMR (DMSO-de): d 12.74 (HH, br), 10.55 (HH, brs), 10.27 (HH, brs), 7.92 (2H, d), 7.75-7.71 (3H, m), 7.66-7.51 (5H , m), 7.31 (ÍH, d).

Example 2 (n) 4- [2- (4-Methylphenylsulfonylamino) -5-chlorobenzoylamino] benzoic acid TLC: Rf 0.30 (CHCl3: MeOH = 9: 1); NMR (DMSO-d6): d 12.76 (HH, br), 10.56 (HH, brs), 10.23 (HH, brs), 7.93 (2H, d), 7.77-7.73 (3H, m), 7.60-7.51 (3H , m), 7.36 (ÍH, d), 7.23 (2H, d), 2.24 (3H, s).

Example 2 (o) 4- [2- (4-Methoxyphenylsulfonylamino) -5-chlorobenzoylamino] benzoic acid TLC: Rf 0.29 (CHC13: MeOH = 9: 1); NMR (DMSO-de): d 12.76 (HH, br), 10.57 (HH, brs), 10.16 (HH, brs), 7.93 (2H, d), 7.77-7.73 (3H, m), 7.62 (2H, d) ), 7.59-7.52 (HH, m), 7.37 (HH, d), 6.93 (2H, d), 3.70 (3H, s).

Example 2 (p) 4- [2- (4-Nitrophenylsulfonylamino) -5-chlorobenzoyl] benzoic acid TLC: Rf 0.10 (CHC13: MeOH = 9: 1); NMR (DMSO-de): d 12.71 (ÍH, br), 10.55-10.35 (2H, br), 8.19 (2H, d), 7.39-7.86 (4H, m), 7.71-7.64 (3H, m), 7.58 -7.52 (ÍH,), 7.32 (ÍH, d).

Example 2 (q) 4- [2- (2,4-Dichlorophenylsulfonylamino) -5-chlorobenzoylamino] benzoic acid TLC: Rf 0.22 (CHC13: MeOH = 9: 1); NMR (DMSO-de): d 12.50 (ÍH, br), 10.73 (2H, br), 7.99-7.91 (3H,), 7.85 (ÍH, d-similar), 7.79-7.71 (3H, m), 7.58- 7.51 (2H,), 7.36 (ÍH, d).

Example 2 (r) 4- [2- (4-Butylphenylsulfonylamino) -5-chlorobenzoylamino] benzoic acid TLC: Rf 0.33 (CHCl3: MeOH = 9: 1); NMR (DMSO-de): d 12.72 (HH, br), 10.55 (HH, brs), 10.24 (HH, s), 7.92 (2H, d), 7.78-7.72 (3H, m), 7.60 (2H, d) ), 7.57-7.51 (HH, m), 7.37 (HH, d), 7.24 (2H, d), 2.54-2.49 (2H, m), 1.48-1.33 (2H, m), 1.29-1.11 (2H,) , 0.82 (3H, t).

Example 2 (s) 4- [2- (4-Chlorophenylsulfonylamino) benzoylamino] benzoic acid TLC: Rf 0.30 (AcOEt: hexane: AcOH = 7: 16: 1); NMR (DMSO-de): d 13.00-12.60 (ÍH, brs), 10.55 (ÍH, brs), 10.38 (ÍH, brs), 7.59 (2H, d), 7.78 (2H, d), 7.74 (ÍH,) , 7.72 (2H, d), 7.51 (2H, d), 7.50 (H, m), 7.40-7.24 (2H, m).

Example 2 (t) 4- (2-Phenylsulfonyl-5-fluorobenzoylamino) benzoic acid TLC: Rf 0.23 (CHC13: MeOH = 9: 1); NMR (DMSO-de): d 12.70 (HH, br), 10.52 (HH, br), 10.13 (HH, br), 7.92 (2H, d), 7.74 (2H, d), 7.68-7.64 (2H, m ), 7.59-7.27 (6H,).

Example 2 (u) 4- (2-Phenylsulfonylamino-4-fluorobenzoylamino) benzoic acid TLC: Rf 0.20 (CHC13: MeOH = 9: 1); NMR (DMSO-de): d 12.81 (HH, br), 10.85 (HH, br), 10.60 (HH, br), 7.95-7.74 (7H, m), 7.63-7.46 (3H,), 7.19-7.02 ( 2H, m).

Example 2 (v) 4- [2- (4-Chlorophenylsulfonylamino) -4-fluorobenzoylamino] benzoic acid TLC: Rf 0.22 (CHC13: MeOH = 9: 1); NMR (DMSO-de): d 12.28 (HH, br), 10.75 (HH, br), 10.58 (HH, br), 7.95.7.72 (7H, m), 7.53 (2H, d), 7.19-708 (2H ,).

Example 2 (w) 4- [2- (4-Fluorophenylsulfonylamino) -5-chlorobenzoylamino] benzoic acid TLC: Rf 0.26 (CHC13: MeOH = 9: 1); NMR (DMSO-de): d 12.75 (HH, br), 10.58 (HH, br), 10.27 (HH, brs), 7.93 (2H, d), 7.80-7.72 (5H, m), 7.54 (HH, dd) ), 7.34-7.22 (3H m).

Example 2 (x) 4- [2- (4-Trifluoromethylphenylsulfonylamino) -5-chlorobenzoyl] benzoic acid TLC: Rf 0.26 (CHC13: MeOH = 9: 1); NMR (DMSO-de): d 12.70 (HH, br), 10.56 (HH, br), 10.41 (HH, br), 7.92-7.68 (9H, m), 7.54 (HH, dd-similar), 7.31 (HH) , d).

Example 2 (y) 4- (2-Phenylsulfonylamino-5-chlorobenzoylaminomethyl) benzoic acid TLC: Rf 0.45 (MeOH: CHC13 = 1: 4); NMR (DMSO-de): d 12.90 (HH, s), 11.47 (HH, s), 9.46 (HH, t), 7.94 (2H, d), 7.86 (HH, d), 7.77-7.36 (9H, m ), 4.48 (ÍH, d).

Example 2 (z) 4- [2- (2-Phenylvinyl) sulfonamino-5-chlorobenzoylamino] benzoic acid TLC: Rf 0.43 (CHCl3: MeOH = 9: 1); NMR (CD30D): d 7.98 (2H, d), 7.83 (ÍH, d), 7.72 (2H; d), 7. 63 (ÍH, d), 7.53 (ÍH; dd), 7.5-7.2 (6H,), 7.01 (ÍH, d).

Example 2 (aa) 4- [2- (2-Phenylethyl) sulfonylamino-5-chlorobenzoylamino] benzoic acid TLC: Rf 0.27 (CHC13: MeOH = 9: 1); NMR (DMSO-de): d 12.75 (HH, br), 10.78 (HH, brs), 10.05 (HH, s), 7.95-7.79 (5H, m), 7.63-7.53 (2H, m), 7.24-7.10 (5H, m), 3.53-3.45 (2H, m), 2.99-2.91 (2H, m).

Example 2 (bb) 4- [2- (4-Chlorophenylsulfonylamino) -5-nitrobenzoylamino] benzoic acid TLC: Rf 0.32 (AcOEt: hexane: AcOH = 4: 12: 1); NMR (DMSO-de): d 12.50-10.00 (2H, brs), 8.66 (ÍH, d), 8.36-8.24 (1H, dd), 8.05-7.87 (4H, m), 7.80 (2H, d), 7.68 -7.55 (3H,).

Example 3 4- [2- (4-Hydroxyphenylsulfonylamino) -5-chlorobenzoylamino] benzoic acid To a solution of the mixture of methyl 4- [2- (4-pivaroyloxyphenylsulfonyl-amino) -5-chlorobenzoylamino] benzoate (214 mg; prepared by the same procedure as Reference Examples 1, 2 and 3 and Example 1.) in MeOH-THF (8 ml + 3 ml), an aqueous 2N NaOH solution (2 ml) was added. The mixture was stirred for one day at 60 ° C. To the reaction solution, HCl was added. The mixture was extracted with ethyl acetate. The organic layer was washed, dried over and purified by recrystallization from the MeOH-AcOEt-hexane mixture solvent to give the title compound (105 mg) having the following physical data. TLC: Rf 0.42 (CHC13: MeOH: AcOH = 45: 4: 1); NMR (DMSO-de): d 13.0-12.6 (ÍH, br), 10.64 (ÍH, s-like), 10.50 (ÍH, s-like), 10.21 (ÍH, s), 7.95 (2H, d), 7.9 -7.7 (3H, m), 7.6-7.3 (4H, m), 6.76 (2H, d).

Reference Example 4 4- [2- (2-nitro-5-chlorophenyl) - (EZ) -vinyl] methyl benzoate To a solution of 4-methoxycarbonylphenylmethyltriphenylphosphine bromide (4.83 g) in THF (20 ml), potassium t-butoxide (600 mg) was added. The mixture was stirred for 1 hour at room temperature. To the reaction solution, 2-nitro-5-chlorobenzaldehyde (742 mg) was added at o ° C. The mixture was stirred for 30 minutes at room temperature. The reaction mixture was poured into dilute HCl. The mixture was extracted with hexane-AcOEt. The organic layer was washed, dried over and concentrated under reduced pressure. The residue was purified over silica gel column chromatography (hexane-AcOEt) and recrystallization from the solvent of the hexane-AcOEt mixture to give the title compound (680 mg) having the following physical data. TLC: Rf 0.44: AcOEt = 4: 1).

Reference Example 5 4- [2- (2-amino-5-chlorophenyl) - (E) -vinyl] methyl benzoate and methyl 4- [2- (2-amino-5-chlorophenyl) - (Z) -vinyl] benzoate To a solution of methyl 4- [2- (2-nitro-5-chlorophenyl) - (EZ) -vinyl] enzoate (525 mg, prepared in Reference Example 4.) in THF (4 ml), were added water (1.5 ml), 2N HCl and reduced iron (554 mg). The mixture was stirred overnight at room temperature. Additionally, to the mixture, 2N HCl (0.2 ml) and reduced iron powder (330 mg) were added. The mixture was stirred for 3 days. The reaction mixture was diluted with ethyl acetate and filtered. The filtrate was washed, dried over and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (ether-hexane-AcOEt) to give the title compound having the following physical data. (E) TLC-type compound: Rf 0.37 (AcOEt: benzene = 5: 95).

(Z) compound of TLC type: Rf 0.41 (AcOEt: benzene = 5: 95).

Example 4 4- [2- [2- (4-chlorophenylsulfonylamino) -5-chlorophenyl] - (E) vinyl] methyl benzoate To methyl 4- [2- (2-amino-5-chlorophenyl) - (E) -vinyl] enzoate (130 mg, prepared in Reference Example 5.) in methylene chloride (3 ml), pyridine was added (0.073 μl) and p-chlorobenzenesulfonyl chloride (114 mg). The mixture was stirred overnight at room temperature. The reaction mixture was poured into dilute HCl and extracted with ethyl acetate. The organic layer was washed, dried over and concentrated under reduced pressure. The residue was purified on silica gel column chromatography (AcOEt-hexane) to give the title compound (205 mg) having the following physical data. TLC: Rf 0.15 (AcOEt: benzene = 4: 96); NMR: d 8.02 (2H, d), 7.63 (2H, d), 7.51 (HH, s), 7.41-7.30 (4H, m), 7.26-7.22 (2H, m), 6.91 (HH, d), 6.81 (ÍH, d), 6.63 (ÍH, s), 3.95 (3H, s).

Example 4 (a) 4- [2- [2- (4-chlorophenylsulfonylamino) -5-chlorophenyl] - (Z] vinyl] methyl benzoate Using the type Z compound prepared in Reference Example 5, the title compound having the following physical data was obtained by the same procedure as in Example 4. TLC: Rf 0.23 (AcOEt: benzene = 4: 96); NMR: d 7.82 (2H, d), 7.57 (2H, d), 7.46 (lH, d), 7.33 (2H, d), 7.24 (lH, dd), 7.06 (lH, d), 6.99 (lH, d ), 6.72 (ÍH, d), 6.48 (ÍH, s), 6.20 (ÍH, d), 3.90 (3H, s).

Example 5 4- [2- [2- (4-chlorophenylsulfonylamino) -5-chlorophenii acid; (E) -vinyl] benzoic Using methyl 4- [2- [2- (4-chlorophenylsulfonylamino) -5-chlorophenyl] - (E) -vinyl] benzoate (190 mg, prepared in Example 4.), the title compound (168 mg) which has the following physical data was obtained by the same procedure as in Example 2. TLC: Rf 0.36 (MeOH: CHC13 = 15: 85); NMR (DMSO-de): d 10.11 (HH, brs), 7.96 (2H, d), 7.80 (HH, d), 7.59 (2H, d), 7.52-7.41 (4H, m), 7.36 (HH, dd) ), 7.20 (ÍH, d), 7.15 (ÍH, d), 7.08 (ÍH, d).

Example 5 (a) 4- [2- [2- (4-chlorophenylsulfonylamino) -5-chlorophenyl] (Z) -vinyl] benzoic acid Using the methyl 4- [2- [2- (4-chlorophenylsulfonylamino) -5-chlorophenyl] - (Z) -vinyl] benzoate prepared in Example 4 (a), the title compound having the following physical data is obtained by the same procedure as in Example 2. TLC: Rf 0.46 (MeOH: CHC13 = 15: 85); NMR (DMSO-de): d 10.05 (HH, brs), 7.79-7.67 (4H, m), 7.55 (2H, d), 7.30 (HH, dd), 7.15 (HH, d), 7.00 (HH, d ), 6.91 (ÍH, d), 6.64 (2H, s).

Example 6 4- [2- [2- (4-chlorophenyl) sulfonylamino-5-chlorophenyl] ethyl] benzoic acid To a solution of 4- [2- [2- (4-chlorophenyl) sulfonylamino-5-chlorophenyl] vinyl] benzoic acid (54 mg, prepared in Example 5) in THF (4 ml), hydrate oxide was added of platinum (3 mg). The mixture was stirred for 2 hours at room temperature in a stream of hydrogen. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. Methylene chloride was added to the residue. The mixture was stirred. The precipitate was collected by a filter to give the title compound (46 mg) having the following physical data. TLC: Rf 0.42 (MeOH: CHC13 = 15: 85); NMR (DMSO-de): d 12.75 (H, s), 9.88 (H, s), 7.84 (2H, d), 7.72-7.57 (4H, m), 7.32 (H, d), 7.23 (2H, d) ), 7.18 (ÍH, dd), 6.88 (ÍH, d).

Reference Example 6 Methyl 4- (2-trifluoroacetylamino-5-chlorophenoxymethyl) benzoate To a solution of 2-trifluoroacetylamino-5-chlorophenol (350 mg) and methyl 4-bromomethylbenzoate (435 mg) in DMF (3 ml), potassium carbonate (263 mg) was added at room temperature. The mixture was stirred for 1.5 hours at 60 ° C. After completion of the reaction, the reaction mixture was poured into dilute HCl and extracted with ethyl acetate. The organic layer was washed, dried over and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (AcOEt-benzene) to give the title compound (353 mg) having the following physical data. TLC: Rf 0.44 (AcOEt: benzene = 5: 95).

Reference Example 7 Methyl 4- (2-amino-5-chlorophenoxymethyl) benzoate To a solution of methyl 4- (2-trifluoroacetylamino-5-chlorophenoxymethyl) benzoate (300 mg, prepared in Reference Example 6.) in THF-MeOH mixture (4 ml + 10 ml), a Sodium carbonate solution (440 mg) in water (2 ml). The solution was stirred for 8 hours at 60 ° C and overnight at room temperature. The reaction mixture was poured into dilute HCl and extracted with ethyl acetate. The organic layer was washed, dried over and concentrated under reduced pressure. The residue was purified on silica gel column chromatography (AcOEt-benzene) to give the title compound (194 mg) having the following physical data. TLC: Rf 0.27 (AcOEt: benzene = 5: 95).

Example 7 4- [2- (4-chlorophenylsulfonylamino) -5-chlorophenoxymethyl] methyl benzoate Using methyl 4- (2-amino-5-chlorophenoxymethyl) benzoate (165 mg, prepared in Reference Example 7.), the title compound (259 mg) having the following physical data was obtained by the same procedure as in Example 4. TLC: Rf 0.30 (AcOEt: benzene = 5: 95); NMR: d 8.06 (2H, d), 7.59 (2H, d), 7.53 (H, d), 7.34 (2H, d), 7.18 (2H, d), 6.96 (H, dd), 6.82 (H, brs ), 6.76 (ÍH, d), 4.89 (2H, s), 3.96 (3H, s).

Example 7 (a) Methyl 4- (2-phenylsulfonylamino-4-chlorophenoxymethyl) benzoate OOMe Using 2-trifluoroacetylamino-4-chlorophenol, the title compound having the following physical data was obtained by the same procedure as in Reference Example 6? Reference Example 7- > Example 4-Example 2. TLC: Rf 0.37 (hexane: AcOEt = 2: 1); NMR: d 8.01 (2H, d, J = 8.4 Hz), 7.75 (2H, m), 7.63 (ÍH, d, J = 2.4 Hz), 7.56 (HI, m), 7.43 (2H, m), 7.15 (2H, d, J = 8. 4 Hz), 6.69 (ÍH, brs), 6.97 (ÍH, dd, J = 2.4, 8.8Hz), 6. 63 (ÍH, d, J = 8.8Hz), 4.92 (2H, s), 3.94 (3H, s).

Example 8 4- [2- (4-chlorophenylsulfonylamino) -5-chlorophenoxymethyl] benzoic acid Using methyl 4- [2- (4-chlorophenylsulfonylamino) -5-chlorophenoxymethyl] benzoate (210 mg, prepared in Example 7.), the title compound was obtained by the same procedure as in Example 2 (197). mg) that has the following physical data. TLC: Rf 0.43 (MeOH: CHC13 = 15: 85); NMR (DMSO-de): d 9.89 (HH, br s), 7.93 (2H, d), 7.60 (2H, d), 7.42 (2H, d), 7.34 (2H, d), 7.29 (HH, d) , 7.06 (1H, d), 7. 01 (ÍH, dd), 4.98 (2H, s).

Example 8 (a) -8 (c) The title compounds having the following physical data were obtained by the same procedure as in Reference Examples 6, 7 and Examples 7 and 8.

Example 8 (ai 4- (2-phenylsulfonylamino-5-chlorophenoxymethyl) benzoic acid TLC: Rf 0.39 (MeOH: CHC13 = 2: 8); NMR (DMSO-de): d 12.98 (HH, s), 9.78 (HH, s), 7.92 (2H, d), 7.65 (2H, d), 7.55 (HH, t), 7.41 (2H, t), 7.37 (2H, d), 7.28 (HH, d), 7.04 (HH, dz), 6.98 (HH, dd), 4.98 (2H, s).

Example 8 (b) 4- (2-phenylsulfonylamino-4-chlorophenoxymethyl) benzoic acid TLC: Rf 0.40 (MeOH: CHC13 = 2: 8); NMR (DMSO-de): d 12.98 (HH, brs), 9.94 (HH, s), 7.90 (2H, d), 7.70 (2H, d), 7.58 (HH, t), 7.44 (2H,), 7.36 (2H, d), 7.28 (HH, d), 7.15 (HH, dd), 6.94 (HH, d), 4.97 (2H, s).

Example 8 (c) 4- [2- (4-Chlorophenylsulfonylamino) -4-chlorophenoxymethyl] benzoic acid TLC: Rf 0.40 (MeOH: CHC13 = 2: 8); NMR (DMSO-de): d 12.93 (HH, s), 10.02 (HH, s), 7.88 (2H, d), 7.61 (2H, d), 7.42 (2H, d), 7.35-7.22 (3H, m ), 7.17 (ÍH, dd), 6.93 (ÍH, d), 4.94 (2H, s).

Reference Example 8 0-mesyl-2-nitro-5-chlorobenzyl alcohol A solution of 2-nitro-5-chlorobenzyl alcohol (400 mg) in methylene chloride (6 ml) was cooled by ice-salt. To this solution, triethylamine (0.6 ml) and mesyl chloride (0.25 ml) were added. The mixture was stirred for 15 minutes. Water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed, dried over and concentrated under reduced pressure to give the title compound (600 mg) having the following physical data. TLC: Rf 0.36 (hexane: AcOEt = 2: 1).

Reference Example 9 Methyl 4- (2-nitro-5-chlorophenylmethoxy) benzoate c, To a solution of 0-mesyl-2-nitro-5-chlorobenzyl alcohol (600 mg, prepared in Reference Example 8) in acetone (10 ml), methyl 4-hydroxy-benzoate (425 mg) and carbonate were added. of potassium (900 mg). The mixture was stirred for 1 hour. To the reaction mixture, acetone (10 ml) was added. The mixture was stirred for 22 hours and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane-AcOEt) to give the title compound (463 mg) having the following physical data. TLC: Rf 0.26 (hexane: AcOEt = 2: 1).

Reference example 10 Methyl 4- (2-amino-5-chlorophenylmethoxy) enzoate A mixture of methyl 4- (2-nitro-5-chlorophenylmethoxy) benzoate (640 mg, prepared in Reference Example 9), THF (10 ml), water (3 ml), IN HCl (0.4 ml) and powder of iron (500 mg) was stirred for 13 hours. The reaction mixture was filtered. The filtrate was washed, dried and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane-AcOEt) to give the title compound (419 mg) having the following physical data. TLC: Rf 0.23 (hexane: AcOEt = 4: 1).

Example 9 4- [2- (4-chlorophenylsulfonylamino) -5-chlorophenylmethoxy] methyl benzoate To a solution of methyl 4- (2-amino-5-chlorophenylmethoxy) benzoate (450 mg, prepared in Reference Example 10.) in methylene chloride (4 ml), pyridine (0.24 ml) and sodium chloride were added. 4-Chlorobenzenesulfonyl (380 mg). The mixture was stirred for 21 hours. Water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed, dried over and concentrated under reduced pressure. The residue was purified by recrystallization from a solvent of the hexane AcOEt mixture to give the title compound (310 mg) having the following physical data. TLC: Rf 0.45 (benzene: AcOEt = 9.: 1); NMR: d fl.01 (2H, d), 7.62 (2H, d), 7.40 (2H, d), 7.32-7.26 (3H, m), 7.11 (ÍH, brs), 6.90 (2H, d), 4.80 (2H, s), 3.90 (3H, s).

Example 10 4- [2- (4-chlorophenylsulfonylamino) -5-chlorophenylmethoxy] benzoic acid Using methyl 4- [2- (4-chlorophenylsulfonylamino) -5-chlorophenylmethoxy] enzoate (300 mg, prepared in Example 9.), the title compound was obtained by the same procedure as in Example 2 (187). mg) that has the following physical data. TLC: Rf 0.51 (AcOEt); NMR (DMSO-d6): d 10.2-10.0 (HH, br), 7.90 (2H, d), 7.69 (2H, d), 7.61 (2H, d), 7.49 (HH, d), 7.36 (HH, dd) ), 7.01 (ÍH, d), 6.92 (2H, d), 5.02 (2H, s).

Reference Example 11 2-Phenylsulfonylamino-5-chloro-l-nitrobenzene To a solution of 2-nitro-4-chloroaniline (500 mg) and pyridine (2.1 ml in methylene chloride (10 ml), benzenesulfonyl chloride (1.2 ml) was added dropwise at 0 ° C under an argon atmosphere The reaction mixture was stirred for 3 days at room temperature, water was added to the reaction mixture, the mixture was extracted with ethyl acetate, the organic layer was washed, dried over and concentrated under reduced pressure. The residue was recrystallized from the solvent of the AcOEt-hexane mixture to give the by-product.The mother liquor was concentrated under reduced pressure.The residue was purified by column chromatography on silica gel (AcOEt-hexane) and recrystallized from the Solvent of the AcOEt-hexane mixture to give the title compound (175 mg) having the following physical data: TLC: Rf 0.37 (AcOEt: hexane = 1: 5).

Reference Example 12 2-phenylsulfon! Lamino-5-chloroaniline To a solution of 2-phenylsulfonylamino-5-chloro-1-nitrobenzene (172 mg, prepared in Reference Example 11.) in acetic acid (4 ml), reduced iron powder (154 mg) was added at room temperature. under an argon atmosphere. The suspension was stirred for 2 hours at 120 ° C. The reaction suspension was diluted with ethyl acetate and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel. { AcOEt-hexane) to give the title compound (92 mg) having the following physical data. TLC: Rf 0.34 (AcOEt: hexane = 1: 2).

Example 11 Methyl 4- (2-phenylsulfonylamino-5-chlorophenylaminocarbonyl) benzoate To a solution of 2-phenylsulfonylamino-5-chloroaniline (90 mg, prepared in Reference Example 12.) and pyridine (0.05 ml) in methylene chloride (5 ml), 4-methoxycarbonylbenzoic acid chloride (70 mg) was added. mg) at room temperature under a stream of argon. The mixture was stirred for 6 hours. After the completion of the reaction, water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed, dried, and concentrated under reduced pressure. The residue was purified by recrystallization of the solvent from the AcOEt-hexane mixture to give the title compound (112 mg) having the following physical data. TLC: Rf 0.55 (AcOEt: hexane = 1: 1); NMR (CDCl 3 + DMSO-d 6): d 9.41 (HH, brs), 8.93 (HH, brs), 8.22 (HH, d), 8.15 (2H, d), 7.98 (2H, d), 7.72-7.62 (2H , m), 7.58-7.45 (HH, m), 7.44-7.32 (2H, m), 6.96 (HH, dd), 6.82 (HH, d).

Example 12 4- (2-Phenylsulfonylamino-5-chlorophenylamino-carbonyl) benzoic acid Using methyl 4- (2-phenylsulfonylamino-5-chlorophenyl-aminocarbonyl) benzoate (110 mg, prepared in Example 11), the title compound (107 mg) having the same procedure as in Example 2 was obtained the following physical data. TLC: Rf 0.36 (AcOEt: hexane: AcOH = 8: 10: 1); NMR (DMSO-de): d 13.00 (HH, brs), 9.80 (HH, brs), 9.65 (1H, s), 8.09 (2H, d), 7.87 (2H, d), 7.81 (HH, d), 7.65-7.50 (3H, m), 7.40 (2H, t), 7.22 (ÍH, dd), 7.14 (ÍH, d).

Reference Example 13 2-nitro-5-chlorobenzoic acid chloride A solution of 2-nitro-5-chlorobenzoic acid (200 mg) in sulfonyl chloride (20 ml) was stirred for 4 hours at 99 ° C in a stream of argon. After allowing to cool, the solution was concentrated under reduced pressure to give the title compound.

Reference Example 14 1- (2-nitro-5-chlorobenzoyl) -1- (4-methoxycarbonylphenyl) -methylidene triphenylphosphoran To a solution of 4-methoxycarbonylbenzyltriphenylphosphonium bromide (1.17 g) in THF (8 ml), potassium t-butoxide (246 mg) was added in a stream of argon. The mixture was stirred for 30 minutes. A solution of 2-nitro-5-chlorobenzoic acid chloride (prepared in Reference Example 13.) in THF (4 ml) was added dropwise to the reaction solution. The mixture was stirred for 3 hours at room temperature. The reaction mixture was cooled by adding saturated aqueous ammonium chloride and extracted with chloroform. The organic layer was washed, dried over and concentrated under reduced pressure. The residue was purified in column chromatography on silica gel (CHCl3-MeOH) to give the title compound (619 mg) having the following physical data. TLC: Rf 0.26 (CHC13: MeOH = 100: 1).

Reference Example 15 4- [2- (2-nitro-5-chlorophenyl) ethynyl] methyl benzoate A solution of 1- (2-nitro-5-chlorobenzoyl) -1- (4-methoxycarbonyl-phenyl) methylidene triphenylphosphoran (513 mg; prepared in Reference Example 14.) in o-dichlorobenzene (10 ml) was refluxed for 9 hours at 180 ° C in a stream of argon. The reaction mixture was concentrated under reduced pressure. The residue was purified in silica gel column chromatography (hexane-AcOEt) to give the title compound (189 mg) having the following physical data. TLC: Rf 0.39 (hexane: AcOEt = 7: 1).

Reference Example 16 4- [2- (2-amino-5-chlorophenyl) ethynyl] methyl benzoate To a solution of methyl 4- [2- (2-nitro-5-chlorophenyl) ethynyl) benzoate (180 mg, prepared in Reference Example 15.) in acetic acid (3.6 ml), reduced iron powder was added. (160 mg). The mixture was refluxed for 30 minutes and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane-AcOEt) to give the title compound (114 mg) having the following physical data. TLC: Rf 0.25 (hexane: AcOEt = 5: 1).

Example 13 4- [2- [2- (4-chlorophenylsulfonylamino) -5-chlorophenyl] ethynyl] -benzoic acid methyl ester To a solution of methyl 4- [2- (2-amino-5-chlorophenyl) ethynyl] benzoate (136 mg, prepared in Reference Example 16.) in methylene chloride (2 ml), pyridine (77 mg) was added. μ 1) and 4-chlorobenzenesulfonyl chloride (106 mg) at 0 ° C under an argon atmosphere. The mixture was stirred for 24 hours at room temperature. The reaction mixture was diluted with ethyl acetate, washed, dried over and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane-AcOEt) to give the title compound (207 mg) having the following physical data. TLC: Rf 0.50 (hexane: AcOEt = 3: 1); NMR: d 8.07 (2H, d), 7.67 (2H, d), 7.58 (HH, d), 7.49 (2H, d), 7.39 (HH, d), 7.34 (2H, d), 7.32 (HH, dd) ), 7.07 (ÍH, brs), 3.96 (3H, s).

Example 14 4- [2- [2- (4-chlorophenylsulfonylamino) -5-chlorophenyl] ethynyl] benzoic acid COOH Using methyl 4- [2- [2- (4-chlorophenylsulfonylamino) -5-chlorophenyl] ethynyl] enzoate (199 mg, prepared in Example 13), the title compound (181 mg) having the following physical data was obtained by the same procedure as in Example 2. TLC: Rf 0.43 (CHC13: MeOH: AcOH = 100: 5: 1); NMR (DMSO-de): d 13.16 (ÍH brs), 10.32 (ÍH, brs), 8.00 (2H, d), 7.65 (2H, d), 7.59 (ÍH, d), 7.57 (2H, d), 7.50 (ÍH, dd), 7.43 (2H, d), 7.35 (ÍH, d).

Reference Example 17 Methyl 4- (2-amino-5-trifluoromethylphenoxymethyl) benzoate Using 2-nitro-5-trifluoromethylphenol, the title compound having the following physical data was obtained by the same procedure as in Reference Example 6 - »Reference Example 12. TLC: Rf 0.33 (hexane: AcOEt = 3: 1).

Example 15 Methyl 4- (2-phenylsulfonylamino-5-trifluoromethylphenoxymethyl) benzoate Using methyl 4- (2-amino-5-trifluoromethylphenoxymethyl) -benzoate (prepared in Reference Example 17.), the title compound having the following physical data was obtained by the same procedure as in Example 7. TLC : Rf 0.76 (benzene: acetone = 9: 1); NMR: d 8.05 (2H, d, J = 8.2 Hz), 7.77 (2H, m), 7.69 (HH, d, J = 8.6 Hz), 7.58 (HH, m), 7.45 (2H, m), 7.25 ( 3H, m), 7.18 (HH, m), 6.99 (HH, m), 5.02 (2H, s), 3.95 (3H, s).

Example 16 4- (2-Phenylsulfonylamino-5-trifluoromethylphenoxymethyl benzoic acid H Using methyl 4- (2-phenylsulfonylamino-5-trifluoromethyl-phenoxymethyl) enzoate (prepared in Example 15.), the title compound having the following physical data was obtained by the same procedure as in Example 2. TLC: Rf 0.52 (CHC13: MeOH: AcOH = 100: 5: 1); NMR (DMSO-de): d 12.95 (HH, brd), 10.10 (HH, brd), 7.93 (2H, d, J = 8.0 Hz), 7.75 (2H, m), -7.59 (HH, m), 7.40 -7.53 (5H, m), 7.27 (2H, m), 5.14 (2H, s).

Example 17 4- [2- (N-isopropyl-phenylsulfonylamino) -4-chlorophenoxymethyl] methyl benzoate OMe To a solution of methyl 4- (2-phenylsulfonylamino-4-chlorophenoxymethyl) benzoate (402 mg; prepared in Example 7 (a).) In DMF (4 ml) was added potassium carbonate (256 mg) and iodide of isopropyl (185 μl). The mixture was stirred overnight at room temperature and for 9 hours at 50 ° C. To the reaction solution, ice-cooled water and 2N HCl were added. The mixture was extracted with ethyl acetate. The organic layer was washed, dried, concentrated after filtration, solidified with ethanol and washed to give the title compound (411 mg) having the following physical data. TLC: Rf 0.59 (hexane: AcOEt = 2: 1); NMR: d 8.05 (2H, d, J = 8.8 Hz), 7.83-7.79 (2H, m), 7.55-7.26 (6H, m), 7.08 (H, d, J = 2.8 Hz), 6.89 (H, d) , J = 8.8 Hz), 5.04 (2H, s), 4.36 (ÍH, sept, J = 6.8 Hz), 3.93 (3H, s), 1.05 (6H, d, J = 6.8 Hz).

Example 17 (1) - (4) Using the corresponding compounds, the title compounds having the following physical data were obtained by the same procedure as in Reference Example 6- Example of Reference 7- »Example 7-» Example 17 or Reference Example d? Reference Example 9- »Reference Example 10-» Example 9- > Example 17 Example 17 (1) 4- [Methyl 2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethyl-phenoxymethyl] benzoate TLC: Rf 0.55 (hexane: AcOEt = 2: 1) NMR: d 8.07 (2H, d, J = 8.4 Hz), 7.79 (2H, m), 7.44-7.55 (3H, m), 7.32-7.43 (2H, m), 7.18-7.29 (3H, m), 5.10 (2H, s), 4.38 (ÍH, sept, J = 6.6 Hz), 3.94 (3H, s), 1.05 (6H, d, J = 6.6 Hz).

Example 17 (2) 4- [Methyl 2- (N-isopropyl-phenylsulfonylamino) -5-methylphenoxymethyl] benzoate TLC: Rf 0.48 (hexane: AcOEt = 2: 1); NMR: d 8.04 (2H, d, J = 8.4 Hz), 7.80 (2H, m), 7.41-7.52 (3H, m), 7.28-7.39 (2H, m), 6.97 (HH, d, J = 8.6 Hz), 6.73-6.80 (2H, m), 5.00 (2H, s), 4.38 (H, Sept, J) = 7.0Hz), 3. 93 (3H, s), 2.35 (3H, s), 1.05 (6H, d, J = 7.0 Hz).

Example 17 (3) 4- [Methyl 2- (N-isopropyl-phenylsulfonylamino) -5-chlorophenoxymethyl] benzoate Me TLC: Rf 0.30 (hexane: AcOEt = 4: 1); NMR: d 8.06 (2H, d, J = 8.2 Hz), 7.78 (2H, d, J = 7.2 Hz), 7.25-7.48 (5H, m), 6.85-7.05 (3H, m), 5.02 (2H, s ), 4.37 (ÍH, sept, J = 6.4 Hz), 3.94 (3H, s), 1.04 (6H, d, J = 6.4 Hz).

Example 17 (4; 4- [2- (N-isopropyl-2-furanylsulfonylamino) -5-trifluoromethyl-phenoxymethyl] cinnamate TLC: Rf 0.39 (benzene: AcOEt = 19: 1); NMR: d 7.71 (HH, d, J = 16 Hz), 7.59-7.45 (5H, m), 7.23-7.20 (3H, m), 6.94-6.92 (HH, m), 6.50-6.42 (2H, m) , 5.12 (2H, s), 4.5-4.4 (HH, m), 3.82 (3H, s), 1.09 (6H, dd, J = 6.5, 2Hz).

Example 18 4- [2- (N-isopropyl-phenylsulfonylamino) -4-chlorophenoxymethyl] benzoic acid OOH Using methyl 4- [2- (N-isopropyl-phenylsulfonylamino) -4-chloro-phenoxymethyl] benzoate (prepared in Example 17.), the title compound having the following physical data was obtained by the same procedure as in Example 2.

TLC: Rf 0.43 (CHC13: MeOH: H20 = 9: 1: 0.1); NMR (DMSO-de): d 12.90 (ÍH, br), 7.94 (2H, d, J = 8.4 Hz), 7.78 (2H, d, J = 8.4 Hz), 7.66-7.45 (6H, m), 7.23 ( HH, d, J = 8.4 Hz), 7.07 (HH, d, J = 2.4 Hz), 5.13 (2H, s), 4.20 (HH, sept, J = 6.6 Hz), 0. 99 and 0.96 (every 3H, every d, J = 6.6 Hz).

Example 18 (1) -18 (128) Using the corresponding compounds, the title compounds having the following physical data were obtained by the same procedure as in the Reference Example 6- »Reference Example 7- > Example 7- »Example 17-Example 2 or Reference Example 8- > Reference Example 9-Reference Example 10- > Example 9- > Example 17- > Example 2 Example 18 (1) 4- [2- (N-Carboxymethyl-phenylsulfonylamino) -4-chlorophenoxymethyl] benzoic acid TLC: Rf 0.20 (CHC13: MeOH: H20 = 7: 3: 0.3); NMR (DMSO-de): d 12.93 (2H, br), 7.88 (2H, d, J = 8.4 Hz), 7. 63-7.37 (7H, m), 7.16-7.06 (3H, m), 4.88 (2H, s), 4.31 (2H, s).

Example 18 (2) 4- [2- [N- (2-Hydriximethyl) -phenylsulphonyl] -4-chlorophenoxymethyl] -benzoic acid TLC: Rf 0.26 (CHC1: MeOH: H20 = 9: 1: 0.1); NMR (DMSO-de): d 12.71 (ÍH, br), 7.88 (2H, d, J = 8.4Hz), 7.63-7.32 (7H, m), 7.19-7.08 (3H, m), 4.89 (2H, brs ), 4.71 (ÍH, br), 3.86-3.40 (4H, m).

Example 18 (3) 4- [2- (N-Methyl-phenylsulfonylamino) -4-trifluoromethylphenoxymethyl] benzoic acid H TLC: Rf 0.31 (CHC13: MeOH: H20 = 9: 1: 0.1); NMR (DMSO-de): d 12.90 (ÍH, br), 7.90 (2H, d, J = 8.4Hz), 7.76-7.70 (ÍH, dd-similar), 7.64-7.43 (6H,), 7.31 (ÍH, d, J = 8.4Hz), 7.23 (2H, d, J = 8.4Hz), 5.05 (2H, s), 3.18 (3H, s).

Example 18 (4) 4- [2- (N- (2-Hydroxymethyl) -phenylsulfonylamino] -4-trifluoromethylphenoxymethyl] benzoic acid TLC: Rf 0.24 (CHC13: MeOH: H20 = 9: 1: 0.1); NMR (DMS0-d6): d 12.51 (HH, br), 7.89 (2H, d, J = 8.4Hz), 7.74 (HH, dd, J = 2.2 and 8.4Hz), 7.62-7.37 (6H, m), 7.28 (ÍH, d, J = 8.4Hz), 7.20 (2H, d, J = 8.4Hz), 5.00 (2H, brs), 4.70 (1H, br), 4.70 (ÍH, br), 3.66-3.28 (4H , m).

Example 18 (5) 4- [2- [N- (2-hydroxymethyl) -phenylsulfonylamino] -5-trifluoromethylphenoxymethyl] benzoic acid TLC: Rf 0.40 (CHC13: MeOH: AcOH = 100: 5: 1); NMR (DMSO-d6): d 12.96 (ÍH, brd), 7.89 (2H, d, J = 8.4Hz), 7. 61 (2H, m), 7.34-7.58 (6H, m), 7.20 (2H, d, J = 8.4Hz), . 05 (ÍH, brs), 4.67 (ÍH,), 3.60 (2H,), 3.42 (2H, m).

Example 18 (6) 4- [2- (N-Methyl-phenylsulfonylamino) -5-chlorophenoxymethyl] benzoic acid H TLC: Rf 0.36 (CHC13: MeOH: H20 = 9: 1: 0.1); NMR (DMSO-d6): d 12.63 (HH, br), 7.89 (2H, d, J = 8.4Hz), 7.64-7.41 (5H,), 7.25-7.19 (4H, m), 7.05 (HH, dd, J = 2.2 and 8.4Hz), 4.98 (2H, s), 3.12 (3H, s).

Example 18 (7) 4- [2- [N- (2-Hydroxymethyl) -phenylsulfonylamino] -5-chlorophenoxymethyl] benzoic acid H TLC: Rf 0.27 (CHC13: MeOH: H20 = 9: 1: 0.1); NMR (DMSO-de): d 12.88 (HH, br), 7.89 (2H, d, J = 8.4Hz), 7.62-7.36 (5H,), 7.29-7.17 (4H, m), 7.06 (HH, dd, J = 2.2 and 8.4Hz), 4.95 (2H, brs), 4.68 (ÍH, br), 3.66-3.24 (4H, br).

Example 18 (8) 4- [2- (N-Methyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid TLC: Rf 0.46 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 8.08 (2H, d, J = 8.0Hz), 7.68 (2H, m), 7.12-7.53 (8H, m), 4.93 (2H, s), 3.24 (3H, s).

Example 18 (9) 4- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid TLC: Rf 0.44 CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 8.15 (2H, d, J = 8.6Hz), 7.81 (2H, m), 7.52 (3H, m), 7.38 (2Hm), 7.24 (3H, m), 5.13 (2Hf s), 4.40 (ÍH, sept, J = 6.8Hz).

Example 18 (10) 4- [2- (N-isopropyl-phenylsulfonylamino) -5-chlorophenoxymethyl] benzoic acid OH TLC: Rf 0.35 (CHC13: MeOH: H20 = 9: 1: 0.1); NMR (DMSO-de): d 12.96 (ÍH, br), 7.95 (2H, d, J = 8.2Hz), 7.78-7.74 (2H, m), 7.65-7.43 (5H, m), 7.32 (ÍH, s ), 7.07 (2H, s), 5.21 and 5.07 (each HH, each d, J = 15.6Hz), 4.21 (HH, sept-like), 0.94 (6H, d, J = 6.8Hz).

Example 18 (11) 4- [2- (N-isopropyl-phenylsulfonylamino) -4-trifluoromethylphenoxymethyl] benzoic acid H TLC: Rf 0.30 (CHC13: MeOH: H20 = 9: 1: 0.1); NMR (DMSO-de): d 13.03 (ÍH, br), 7.95 (2H, d, J = 8.2Hz), 7.84.7.74 (3H, m), 7.67-7.39 (6H, m), 7.25 (ÍH, d , J = 2.4Hz), 5.28 and 5.21 (each ÍH, each d, J = 16.6Hz), 4.26 (ÍH, sept-similar), 0.98 and 0.97 (each 3H, each d, J = 6.6Hz).

Example 18 (12) 4- [2- [N- (2-Methoxyethoxymethyl) -phenylsulfonylamino] -4-chlorophenoxymethyl] benzoic acid H TLC: Rf 0.40 (CHC13: MeOH: H20 = 9: 1: 0.1); NMR (DMSO-de): d 12.98 (ÍH, br), 7.91 (2H, d, J = 8.2Hz), 7.66-7.52 (3H,), 7.45-7.38 (3H, m), 7.26-7.22 (3H, m), 7.10 (1H, d, J = 8.2Hz), 5.06 (2H, brs), 4.92 (2H, brs), 3.68-3.63 (2H, t-similar), 3.42-3.37 (2H, t-similar) , 3.21 (3H, s).

Example 18 (13) 4- [2- [N- (2-methoxyethyl) -phenylsulfonylamino] -4-chlorophenoxymethyl] benzoic acid TLC: Rf 0.25 (CHC13: MeOH: H20 = 9: 1: 0.1) NMR (DMSO-de): d 12.92 (OH, br), 7.88 (2H, d, J = 8.2Hz), 7.64-7.39 (6H, m), 7.22-7.10 (4H, m), 4.91 (2H, brs), 3.69 (2H, br), 3.38-3.33 (2H, m), 3.13 (3H, s).

Example 18 (14) 4- [2- [N- [2- (2-methoxyethoxy) ethyl] -phenylsulfonylamino acid] 4-chlorophenoxymethyl] benzoic acid TLC: Rf 0.29 (CHC13: MeOH: H20 = 9: 1: 0.1); NMR (DMSO-de): d 12.95 (ÍH, br), 7.89 (2H, d, J = 8.2Hz), 7. 65-7.39 (6H, m), 7.25 (HH, d, J = 2.6Hz) 7.20 (2H, d, J = 8.2Hz), 7.11 (HH, d, J = 8.2Hz), 4.92 (2H, brs) , 3.69 (2H, br), 3.47-3.28 (6H,), 3.19 (3H, s).

Example 18 (15) 4- [2- (N-Ethyl-phenylsulfonylamino) -4-chlorophenoxymethyl] benzoic acid H TLC: Rf 0.51 (CHC13: MeOH = 9: 1); NMR: d 8.08 (2H, d, J = 8.2Hz), 7.8-7.6 (2H, m), 7.5-7.2 (7H, m), 6.81 (ÍH, d, J = 9.4Hz), 4.88 (2H, s) ), 3.67 (2H, q, J = 7.0Hz), 1.11 (3H, t, J = 7.0Hz).

Example 18 (16) 4- [2- (N-Propyl-phenylsulfonylamino) -4-chlorophenoxymethyl] benzoic acid H TLC: Rf 0.50 (CHC13: MeOH = 9: 1); NMR: d 8.08 (2H, d, J = 8.4Hz), 7.7-7.6 (2H,), 7.5-7.2 (7H, m), 6.80 (ÍH, d, J = 9.6Hz), 4.85 (2H, s) , 3.6-3.5 (2H, m), 1.6-1.4 (2H, m), 0.89 (3H, t, J = 7.2Hz).

Example 18 (17) 4- [2- (N-Butyl-phenylsulfonylamino) -4-chlorophenoxymethyl] benzoic acid H TLC: Rf 0.53 (CHC13: MeOH = 9: 1); NMR: d 8.08 (2H, d, J = 8.4Hz), 7.7-7.6 (2H,), 7.5-7.2 (7H,), 6.80 (ÍH, d, J = 9.4Hz), 4.86 (2H, s), 3.7-3.5 (2H, m), 1.5-1.2 (4H, m), 0.85 (3H, t, J = 7.0Hz).

Example 18 (18) 4- [2- (N-Pentyl-phenylsulfonylamino) -4-chlorophenoxymethyl] benzoic acid TLC: Rf 0.56 (CHC13: MeOH: 9: 1); NMR: d 8.08 (2H, d, J = 8.2 Hz), 7.7-7.6 (2H, m), 7.5-7.2 (7H, m), 6.8-6.7 (HI, m), 4.86 (2H, s), 3.6 -3.5 (2H, m), 1.5-1.2 (6H, m), 0.9-0.8 (3H, m).

Example 18 (19) 4- [2- (N-hexyl-phenylsulfonylamino) -4-chlorophenoxymethyl] benzoic acid TLC: Rf 0.58 (CHC13: MeOH = 9: 1); NMR: d 8.08 (2H, d, J = 8.6Hz), 7.7-7.6 (2H, m), 7.5-7.2 (7H, m), 6.9-6.8 (HI, m), 4.86 (2H, s), 3.6 -3.5 (2H, m), 1.5-1.1 (8H, m), 0.9-0.8 (3H, m).

Example 18 (20) 4- [2- (N-Bznyl-phenylsulfonylamino) -4-chlorophenoxymethyl] benzoic acid H TLC: Rf 0.60 (CHC13: MeOH = 9: 1); NMR: d 8.09 (2H, d, J = 8.6Hz), 7.8-7.7 (2H, m), 7.6-7.3 (3H, m), 7.3-7.1 (9H, m), 6.71 (ÍH, d, J = 8.8Hz), 4.82 (2H, s), 4.78 (2H, s).

Example 18 (21) 4- [2- (N-isopropyl-phenylsulfonylamino) -5-methylphenoxymethyl] benzoic acid TLC: Rf 0.50 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 8.13 (2H, d, J = 8.2Hz), 7.82 (2H, m), 7.49 (3H, m), 7.36 (2H, m), 6.98 (ÍH, d, J = 8.6Hz), 6.77 ( 2H, m), 5.05 (2H, s), 4.40 (ÍH, sept, J = 6.6Hz), 2.36 (3H, s), 1.05 (6H, d, J = 6.6Hz).

Example 18 (22) 4- [2- (N-Methyl-phenylsulfonylamino) -5-methylphenoxymethyl] benzoic acid TLC: Rf 0.56 (AcOEt: hexane: AcOH = 9: 10: 1); NMR (DMSO-d6): d 12.96 (ÍH, brs), 7.89 (2H, d, J = 8.5Hz), 7. 67-7.40 (5H, m), 7.23 (2H, d, J = 8.0Hz), 7.06 (ÍH, d, J = 8.0Hz), 6.93 (lH, s), 6.78 (ÍH, d, J = 8.0Hz), 4.93 (2H, s), 3.12 (3H, s), 2.30 (3H, s).

Example 18 (23) 4- [2- [N- (2-Hydroxymethyl) -phenylsulfonylamino] -5-methylphenoxymethyl] benzoic acid H TLC: Rf 0.27 (AcOEt: hexane: AcOH = 9: 10: 1); NMR (DMSO-de): d 12.95 (ÍH, brs); 7.87 (2H, d, J = 8.5Hz), 7. 55-7.32 (5H, m), 7.20 (2H, d, J = 8.5Hz), 7.08 (HH, d, J = 8.0Hz), 6.91 (HH, s), 6.77 (HH, d, J = 8.0Hz ); 4.89 (2H, brs), 4.63 (HH, t, J = 4.0Hz), 3.50-3.20 (4H, m), 2.29 (3H, s).

Example 18 (24) 4- [2- [N- (prop-2-enyl) -phenylsulfonylamino] -4-chlorophenoxymethyl] benzoic acid H TLC: Rf 0.54 (CHC13: MeOH = 9: 1); Nmr: d 8.08 (2H, d, J = 8.0Hz), 7.8-7.6 (2H, m), 7.6-7.2 (7H, m), 6.78 (H, d, J = 9.4Hz), 5.9-5.6 (H) , m), 5.2-5.0 (2H, m), 4.86 (2H, s), 4.3-4.2 (2H, m).

Example 18 (25) 4- [2- (N-Cyclopentyl-phenylsulfonylamino) -4-chlorophenoxymethyl] benzoic acid TLC: Rf 0.47 (CHC13: MeOH = 9: 1); NMR: d 8.13 (2H, d, J = 8.4Hz), 7.9-7.8 (2H,), 7.6-7.2 (6H, m), 7.07 (ÍH, d, J = 2.6Hz), 6.88 (ÍH, d, J = 8.8Hz), 5.1-5.0 (2H, m), 4.5-4.3 (ÍH, m), 2.0-1.7 (2H, m), 1.6-1.2 (6H, m).

Example 18 (26) 4- [2- [N- (2-methoxyethyl) -phenylsulfonylamino] -5-trifluoromethylphenoxymethyl] benzoic acid H TLC: Rf 0.46 (CHC13: MeOH: AcOH = 100: 5: 1), NMR: d 8.07 (2H, d, J = 8.4Hz), 7.66 (2H, m), 7.18-7.53 (7H, m), 7.12 (lH, m), 4.90 (2H, s), 3.81 (2H, m), 3.51 (2H, t, J = 6.0Hz), 3.24 (3H, s).

Example 18 (27) 4- [2- (N-Ethyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid TLC: Rf 0.43 (CHC13: MeOH = 9: 1); NMR: d 8.09 (2H, d, J = 8.4Hz), 7.7-7.6 (2H, m), 7.5-7.2 (7H, m), 7.15 (H, d, J = 1.6Hz), 4.94 (2H, s) ), 3.69 (2H, q, J = 7.4Hz), 1.11 (3H, t, J = 7.4Hz).

Example 18 (28) 4- [2- (N-Propyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid TLC: Rf 0.5 (CHC13: MeOH = 9: 1); NMR: d 8.09 (2H, d, J = 8.2Hz), 7.7-7.6 (2H, m), 7.5-7.2 (7H, m), 7.14 (H, s), 4.92 (2H, s), 3.59 (2H) , t, J = 7.4Hz), 1.6-1.4 (2H, m), 0.88 (3H, t, J = 7.4HZ).

Example 18 (29) 4- [2- (N-Isobutyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid TLC: Rf 0.53 (CHC13: MeOH = 9: 1); NMR: d 8.10 (2H, d, J = 8.4Hz), 7.7-7.6 (2H, m), 7.5-7.2 (7H, m), 7.11 (ÍH, d, J = 1.6Hz), 5.0-4.8 (2H ,), 3.44 (2H, d, J = 7.4Hz), 1.7-1.5 (ÍH, m), 0.90 (6H, d, J = 6.4Hz).

Example 18 (30) 4- [2- (N-Cyclopentyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid TLC: Rf 0.54 (CHC13: MeOH = 9: 1); NMR: d 8.15 (2H, d, J = 8.0Hz), 7.8-7.7 (2H, m), 7.6-7.3 (5H, m), 7.3-7.2 (3H, m), 5.2-5.0 (2H,), 4.5-4.3 (ÍH, m), 4.5-4.3 (ÍH, m), 2.0-1.8 (2H, m), 1.6-1.2 (6H,).

Example 18 (31) 4- [2- [N- (prop-2-enyl) -phenylsulfonylamino] -5-trifluoromethylphenoxymethyl] benzoic acid H TLC: Rf 0.47 (CHC13: MeOH = 9: 1); NMR: d 8.10 (2H, d, J = 8.6Hz), 7.8-7.6 (2H,), 7.6-7.2 (7H, m), 7.12 (IH, s), 5.9-5.6 (IH, m), 5.1- 5.0 (2H, m), 4.93 (2H, s), 4.24 (2H, d, J = 6.2Hz).

Example 18 (32) 4- [2- [N- (2-methylprop-2-enyl) -phenylsulfonylamino] -5-trifluoromethylphenoxymethyl] benzoic acid TLC: Rf 0.48 (CHC13: MeOH = 9: 1); NMR: d 8.10 (2H, d, J = 8.4Hz), 7.7-7.6 (2H,), 7.5-7.2 (7H, m), 7.10 (IH, s), 4.89 (2H, s), 4.71 (2H, d, J = 12.0Hz), 4.20 (2H, s), 1.74 (3H, s).

Example 18 (33) 4- [2- (N-isopropyl-4-methylphenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid H TLC: Rf 0.60 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 8.14 (2H, d, J = 8.4Hz), 7.68 (2H, d, J = 8.2Hz), 7.52 (2H, d, J = 8.2Hz), 7.19 (5H, m, arom), 5.14 ( 2H, s), 4.38 (ÍH, sept., J = 6.8Hz), 2.38 (3H, s), 1.05 (6H, d, J = 6.8Hz).

Example 18 (34) 4- [2- (N-isopropyl-4-fluorophenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid TLC: Rf 0.60 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 8.16 (2H, d, J = 8.2Hz), 7.76 (2H, m, ring), 7.52 (2H, d, J = 8.2Hz), 7.26 (3H, m, arom), 7.01 (2H,, arom), 5.10 (2H, dd, J = 11.8, 14.6Hz), 4.38 (ÍH, sept., J = 6.4Hz), 1.09 (3H, d, J = 6.4Hz), 1.07 (3H, d, J = 6.4Hz).

Example 18 (35) 4- [2- (N-isopropyl-4-methoxyphenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid H TLC: Rf 0.60 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 8.15 (2H, d, J = 8.2Hz), 7.72 (2H, d, J = 8.8Hz), 7.53 (2H, d, J = 8.2Hz), 7.18 (3H, m, arom), 6.81 (2H, d, J = 9.2Hz), 5.14 (2H, s), 4.35 (ÍH, sept., J = 6.4Hz), 3.83 (3H, s), 1.08 (3H, d, J = 6.4Hz), 1.05 (3H, d, J = 6.4Hz).

Example 18 (36) 4- [2- (N-isopropyl-phenylsulfonylamino) -5-chlorophenoxy] benzoic acid TLC: Rf 0.36 (CHC13: MeOH = 9: 1); NMR: d 8.11 (2H, d, J = 8.6Hz), 7.8-7.7 (2H, m), 7.6-7.3 (3H, m), 7.2-7.1 (2H, m), 7.02 (2H, d, J = 8.6Hz), 6.92 (HH, d, J = 2.0Hz), 4.6-4.4 (HH, m), 1.14 (3H, d, J = 2.4Hz), 1.11 (3H, d, J = 2.4Hz).

Example 18 (37) 3- [2- (N-isopropyl-phenylsulfonylamino) -5-chlorophenoxy] cinnamic acid TLC: Rf 0.33 (CHC13: MeOH = 9: 1); NMR: d 7.9-7.8 (2H,), 7.73 (HH, d, J = 15.8Hz), 7.6-7.3 (5H, m), 7.2-7.0 (4H, m), 6.78 (HH, d, J = 2.2 Hz), 6.42 (HH, d, J = 15.8Hz), 4.6-4.4 (HH, m), 1.17 (3H, d, J = 6.8Hz), 1.13 (3H, d, J = 6.8Hz).

Example 18 (38) Trans-4- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] cyclohexanoic acid H TLC: Rf 0.53 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 7.81 (2H, m), 7.42-7.63 (3H, m), 7.10-7.24 (3H, m), 4.38 (HH, sept., J = 6.8Hz), 3.79 (2H, m), 2.33 (HH, tt, J = 3.8, 10.2Hz), 2.11 (2H, m), 1.93 (2H, m), 1.71 (HH, m), 1.50 (2H, m), 1.18 (2H, m), 1.07 ( 3H, d, J = 6.8Hz), 1.02 (3H, d, J = 6.8Hz).

Example 18 (39) 4- [2- (N-isopropyl-phenylsulfonylamino) -5-chlorophenoxy] phenylacetic acid TLC: Rf 0.43 (CHCl3: MeOH = 9: 1); NMR: d 7.9-7.8 (2H,), 7.6-7.4 (3H, m), 7.28 (2H, d, J = 7.4Hz), 7.13 (IH, d, J = 8.6Hz), 7.01 (IH, dd, J = 2.2, 8.6Hz), 6.89 (2H, d, J = 8.6Hz), 6.78 (HH, d, J = 2.2Hz), 4.6-4.4 (HH, m), 3.66 (2H, s), 1.15 (3H, s), 1.12 (3H, s).

Example 18 (40) 4- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid TLC: Rf 0.5 (CHCl 3: MeOH = 9: 1); NMR: d 7.9-7.8 (3H, m), 7.60 (2H, d, J = 8.0Hz), 7.5-7.3 (5H, m), 7.3-7.2 (3H,), 6.49 (ÍH, d, J = 15.8 Hz), 5.08 (2H, s), 4.4-4.3 (ÍH, m), 1.05 (6H, d, J = 6.6Hz).

Example 18 (41) 3- [4- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] phenyl] propionic acid TLC: Rf 0.59 (CHC13: MeOH = 9: 1); NMR: d 7.80 (2H, d, J = 7.4Hz), 7.5-7.4 (HH, m), 7.4-7.2 (9H,), 4.99 (2H, s), 4.4-4.2 (HH, m), 3.00 ( 2H, t, J = 7.6Hz), 2.72 (2H, t, J = 7.6Hz), 1.08 (3H, d, J = 6.8Hz), 1.02 (3H, d, J = 6.8Hz).

Example 18 (42) 3- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] phenylacetic acid TLC: Rf 0.50 (CHC13: MeOH = 9: 1); NMR: d 7.8-7.7 (2H, m), 7.6-7.2 (10H, m), 5.05 (IH, d, J = 11.0Hz), 4.98 (IH, d, J = 11.0Hz), 4.4-4.2 (lH , m), 3.68 (2H, s), 1.06 (3H, d, J = 6.6Hz), 1.03 (3H, d, J = 6.6Hz).

Example 18 (43) 4- [2- (N-isopropyl-4-ethoxyphenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid TLC: Rf 0.44 (CHC13: MeOH = 9: 1); NMR: d 8.15 (2H, d, J = 8.2Hz), 7.71 (2H, d, J = 8.8Hz), 7.54 (2H, d, J = 8.2Hz), 7.3-7.2 (3H, m), 6.78 ( 2H, d, J = 8.8Hz), 5.14 (2H, s), 4.4-4.2 (ÍH, m), 4.03 (2H, q, J = 7.0Hz), 1.44 (3H, t, J = 7.0Hz), 1.08 (3H, d, J = 7.0Hz), 1.04 (3H, d, J = 7.0Hz).

Example 18 (44) 4- [2- (N-Isobutyl-phenylsulfonylamino) -5-ethylphenoxymethyl] benzoic acid TLC: Rf 0.47 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 8.07 (2H, d, J = 8.2Hz), 7.63 (2H, m), 7.15-7.44 (6H, m), 6.79 (H, m), 6.65 (H, m), 4.80 (2H, m ), 3.40 (2H,), 2.33 (3H, s), 1.63 (ÍH, m), 0.90 (6H, d, J = 6.4Hz).

Example 18 (45) 4- [2- (N-isopropyl-phenylsulfonylamino) -5-fluorophenoxymethyl] benzoic acid TLC: Rf 0.33 (CHC13: MeOH = 20: 1); NMR (DMSO-de): d 7.95 (2H, d, J = 8.2Hz), 7.80 (2H, d, J = 7.2Hz), 7.46-7.65 (5H, m), 7.08 (2H, m), 6.82 ( ÍH, m), 5.14 (2H, bis), 4.20 (ÍH, sept., J = 6.6Hz), 0.94 (6H, d, J = 6.6Hz).

Example 18 (46) 4- [2- (N-isopropyl-phenylsulfonylamino) -5-methoxyphenoxymethyl] benzoic acid TLC: Rf 0.30 (CHC13: MeOH = 20: 1); NMR (DMSO-de): d 7.59 (2H, d, J = 8.2Hz), 7.73 (2H, d, J = 7.2Hz), 7.42-7.68 (3H, m), 6.93 (2H, d, J = 8.6 Hz), 7.21 (HH, m), 6.56 (2H, dd, J = 8.6Hz, J = 2.8Hz), 5.11 (2H, bis), 4.20 (HH, sept, J = 6.6Hz), 3.79 (3H, s), 0.94 (6H, d, J = 6.6Hz).

Example 18 (47) 4- [2- (N-Propyl-phenylsulfonylamino) -5-methylphenoxymethyl] benzoic acid OH TLC: Rf 0.38 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 8.07 (2H, d, J = 8.6Hz), 7.67 (2H, m), 7.15-7.45 (6H, m), 6.79 (H, m), 6.68 (H, m), 4.83 (2H, brs ), 3.57 (2H, m), 2.34 (3H, s), 1.48 (2H, m), 0.88 (3H, t, J = 7.4Hz).

Example 18 (48) 4- [2- [N- (prop-2-enyl) -phenylsulfonylamino] -5-methylphenoxymethyl] benzoic acid TLC: Rf 0.39 (CHC13: MeOH: AcOH = 100: 5: 1) NMR: d 8.07 (2H, d, J = 8.0Hz), 7.69 (2H,), 7.13-7.48 (6H, m), 6.78 (OH) , m), 6.66 (HH,), 5.80 (HH, tdd, J = 6.2, 10.2, 17.2Hz), 4.98-5.12 (2H, m), 4.84 (2H, brs), 4.23 (2H, m), 2.33 (3H, s).

Example 18 (49) 4- [2- [N- (2-methylprop-2-enyl) -phenylsulfonylamino] -5-methylphenoxymethyl] benzoic acid H TLC: Rf 0.37 (CHCl3: MeOH: AcOH = 100: 5: 1); NMR: d 8.07 (2H, d, J = 8.2Hz), 7.66 (2H, m), 7.16-7.47 (6H, m), 6.77 (H, m), 6.64 (H, m), 4.80 (2H, brs ), 4.71 (2H, m), 4.20 (ÍH, brs), 2.32 (3H, s), 1.77 (3H, S).

Example 18 (50) 4- [2- (N-Cyclopropylmethyl-phenylsulfonylamino) -5-methylphenoxymethyl] benzoic acid TLC: Rf 0.31 (CHC13: MeOH: AcOH = 100: 5: 1); NMR. d 8.06 (2H, d, J = 8.0Hz), 7.68 (2H, m), 7.18-7.44 (6H, m), 6.80 (H, m), 6.68 (H, m), 4.84 (2H, brs), 3.48 (2H, m), 2.34 (3H, s), 0.91 (HH, m), 0.38 (2H, m), 0.07 (2H, m).

Example 18 (51) 4- [2- (N-Propyl-phenylsulfonylamino) -5-chlorophenoxymethyl] benzoic acid TLC: Rf 0.32 (CHC13: MeOH = 20: 1); NMR: d 8.07 (2H, d, J = 7.8Hz), 7.64 (2H, d, J = 6.8Hz), 7.10-7.41 (6H, m), 6.85-6.99 (2H,), 4.82 (2H, bs) , 3.55 (2H, t, J = 6.8Hz), 1.35-1.52 (2H, m), 0.87 (3H, t, J = 7.6Hz).

Example 18 (52) 4- [2- (N-Isobutyl-phenylsulfonylamino) -5-chlorophenoxymethyl] benzoic acid TLC: Rf 0.32 (CHC13: MeOH = 20: 1); NMR: d 8.04 (2H, d, J = 7.8Hz), 7.54 (2H, d, J = 7.4Hz), 7.10-7.41 (6H, m), 6.80-7.01 (2H, m), 4.58-4.95 (2H , bs), 3.34 (2H, d, J = 7.0Hz), 1.46-1.65 (ÍH, m), 0.83 (6H, d, J = 6.4Hz).

Example 18 (53) 4- [2- [N-prop-2-enyl) -phenylsulfonylamino] -5-chlorophenoxymethyl] benzoic acid H TLC: Rf 0.30 (CHC13: MeOH = 20: 1); NMR: d 8.09 (2H, d, J = 8.2Hz), 7.68 (2H, d, J = 6.8Hz), 7.19-7.52 (6H, m), 6.87-7.01 (2H, m), 5.76 (H) , ddt, J = 17.2, 9.8Hz, 6.4Hz), 5.09 (HH, d, J = 17.2Hz), 5.07 (HH, d, J = 9.8Hz), 4.85 (2H, s), 4.21 (2H, d , J = 6.4Hz).

Example 18 (54) 4- [2- [N- (2-methylprop-2-enyl) -phenylsulfonylamino] -5-chlorophenoxymethyl] benzoic acid TLC: Rf 0.33 (CHC13: MeOH = 20: 1); NMR: d 8.09 (2H, d, J = 8.2Hz), 7.65 (2H, d, J = 6.8Hz), 7.21-7.51 (6H, m), 6.83-7.00 (2H, m), 4.81 (2H, s ), 4.74 (ÍH, s), 4.68 (ÍH, s), 4.18 (2H, s), 1.75 (3H, s).

Example 18 (55) 4- [2- (N-Cyclopropylmethyl-phenylsulfonylamino) -5-chlorophenoxymethyl] benzoic acid H TLC: Rf 0. 40 (CHC13: MeOH = 20: 1); NMR: d 8.07 (2H, d, J = 8.6Hz), 7.69 (2H, d, J = 7.0Hz), 7.20-7.48 (6H, m), 6.85-7.09 (2H,), 4.85 (2H, s) , 3.47 (2H, bs), 0.85 (HH, m), 0.38 (2H, m), 0.06 (2H,).

Example 18 (56) 5- [2- (N-isopropyl-phenylsulfonylamino) -5-methylphenoxymethyl] furan-2-carboxylic acid TLC: Rf 0.18 (CHC13: MeOH = 9: 1); NMR: d 7.82 (2H, m), 7.56-7.35 (3H, m), 7.31 (HH, d, J = 3.5Hz), 6.97 (HH, d, J = 8.5Hz), 6.83-6.75 (2H, m ), 6.63 (1H, d, J = 3.5Hz), 5.03 (IH, d, J = 14Hz), 4.98 (IH, d, J = 14Hz), 4.37 (IH, m), 2.37 (3H, s), 1.09-0.96 (6H, m).

Example 18 (57) 4- [2- (N-Methoxymethyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid OH TLC: Rf 0.45 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 8.09 (2H, d, J = 8.0Hz), 7.65 (2H, m), 7.43-7.53 (2H, m), 7.20-7.40 (5H, m), 7.11 (H, m), 5.09 (2H , s), 4.89 (2H, s), 3.44 (3H, s).

Example 18 (58) 4- [2- (N-isopropyl-2-thienylsulfonylamino) -5-chlorophenoxymethyl] benzoic acid TLC: Rf 0.34 (CHCl3: MeOH = 20: 1); NMR: d 8.14 (2H, d, J = 8.2Hz), 7.52-7.57 (4H, m), 6.98-7.03 (4H, m), 5.12 (2H, s), 4.55 (ÍH, sept, J = 6.4Hz ), 1.09 (6H, d, J = 6.6Hz).

Example 18 (59) 4- [2- (N-isopropyl-2-thienylsulfonylamino) -5-methylphenoxymethyl] benzoic acid TLC: Rf 0.39 (CHC13: MeOH = 20: 1); NMR: d 8.13 (2H, d, J = 8.2Hz), 7.43-7.58 (4H, m), 6.97 (HH, m), 6.80 (2H, m), 5.12 (2H, s), 4.45 (H, Sept. , J = 6.4Hz), 1.09 (6H, d, J = 6.6Hz).

Example 18 (60) 4- [2- (N-isopropyl-2-furanylsulfonylamino) -5-methylphenoxymethyl] benzoic acid TLC: Rf 0.42 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 8.14 (2H, d, J = 8.2Hz), 7.58 (2H, d, J = 8.2Hz), 7.44 (HH, dd, J = 0.8, 1.6Hz), 6.88-6.95 (2H, m), 6.72-6.82 (2H, m), 6.41 (HH, dd, J = 1.6, 3.4Hz), 5.12 (2H, s) ), 4.51 (ÍH, sept, J = 6.6Hz), 2.31 (3H, s), 1.12 (3H, d, J = 6.6Hz), 1.10 (3H, d, J = 6.6Hz).

Example 18 (61) 4- [2- (N-isopropyl-2-furanylsulfonylamino) -5-chlorophenoxymethyl] benzoic acid TLC: Rf 0.43 (CHC13: MeOH: AcOH = 100: 5: 1); NMR; d 8.16 (2H, d, J = 8.4Hz), 7.57 (2H, d, J = 8.4Hz), 7.45 (ÍH, dd, J = 0.8, 1.6Hz), 6.95-7.04 (3H, m), 6.92 ( ÍH, d, J = 4.4Hz), 6.43 (ÍH, dd, J = 1.8, 3.4Hz), 5.13 (2H, s), 4.49 (ÍH, sept, J = 7.0Hz), 1.11 (3H, d, J = 7.0Hz), 1.09 (3H, d, J = 7.0Hz).

Example 18 (62) 4- [2- (N-Isobutyl-phenylsulfonylamino) -4-methylphenoxymethyl] benzoic acid TLC: Rf 0.23 (hexane: AcOEt = 1: 1); NMR: d 8.06 (2H, d, J = 8Hz), 7.65-7.61 (2H, m), 7.6-7.4 (7H, m), 6.71 (ÍH, d, J = 8Hz), 4.9-4.6 (2H, m ), 3.5-3.4 (2H, m), 2.29 (3H, s), 1.63 (ÍH, sept, J = 6.5Hz), 0-91 (6H, d, J = 6.5Hz).

Example 18 (63) 4- [2- (N-isopropyl-phenylsulfonylamino) -4-ethylphenoxymethyl] benzoic acid OH TLC: Rf 0.22 (hexane: AcOEt = 1: 1); NMR: d 8.12 (2H, d, J = 8Hz), 7.86-7.81 (2H, m), 7.52-7.30 (5H, m), 7.15-7.10 (HH, m), 6.94 (HH, d, J = 1.5 Hz), 6.84 (ÍH, d, J = 8Hz), 5.02 (2H, s), 4.37 (ÍH, sept., J = 6.5Hz), 2.28 (3H, s), 1.08 (6H, t, J = 6.5 Hz).

Example 18 (64) 4- [2- [N- (prop-2-enyl) phenylsulfonylamino] -4-methylphenoxymethyl] benzoic acid TLC: Rf 0.43 (CHC13: MeOH: AcOH = 100: 5: 1); NMR (DMSO-de): d 7.89 (2H, d, J = 8.2Hz), 7.63 (2H, m), 7.38-7.59 (3H, m), 7.23 (2H, d, J = 8.2Hz), 7.12 ( lH, dd, J = 1.8, 8.4Hz), 6.98 (IH, d, J = 1.8Hz), 6.94 (IH, d, J = 8.6Hz), 5.71 (IH, dd, J = 6.4, 10.0, 17.2Hz ), 4.97-5.13 (2H, m), 4.88 (2H, brs), 4.17 (2H, m), 2.22 (3H, s).

Example 18 (65) 4- [2- (N-isopropyl-4-ethoxyphenylsulfonylamino) -5-chlorophenoxymethyl] benzoic acid H TLC: Rf 0.33 (CHC13: MeOH = 20: 1); NMR: d 8.13 (2H, d, J = 8.2Hz), 7.69 (2H, d, J = 9.0Hz), 7.49 (2H, d, J = 8.6Hz), 6.97.7.09 (3H, m), 6.76 ( 2H, d, J = 9.0Hz), 5.06 (2H.s), 4.34 (ÍH, sept, J = 6.6Hz), 4.02 (2H, q, J = 7.2Hz), 1.43 (3H, t, J = 7.0 Hz), 1.06 (3H, d, J = 6.6Hz), 1.03 (3H, d, J = 6.6Hz).

Example 18 (66) 4- [2- (N-isopropyl-4-ethoxyphenylsulfonylamino) -5-methylphenoxymethyl] benzoic acid TLC'.Rf 0.29 (CHCl3: MeOH = 20: 1); NMR: d 8.12 (2H, d, J = 8.4Hz), 7.72 (2H, d, J = 8.6Hz), 7.50 (2H, d, J = 8.6Hz), 7.01 (ÍH, d, J = 8.8Hz) , 6.72-6.80 (4H, m), 5.07 (2H, s), 4.34 (ÍH, sept, J = 6.6Hz), 4.01 (2H, q, J = 7.0Hz), 2.36 (3H, s), 1.42 ( 3H, t, J = 6.8Hz), 1.07 (3H, d, J = 7.2Hz), 1.04 (3H, d, J = 6.8Hz).

Example 18 (67) 4- [2- (N-Ethyl-phenylsulfonylamino) -4-methylphenoxymethyl] benzoic acid TLC: Rf 0.33 (CHC13: MeOH = 9: 1); NMR: d 8.05 (2H, d, J = 8.4Hz), 7.8-7.6 (2H,), 7.4-7.2 (5H, m), 7.2-7.0 (2H, m), 6.75 (ΔH, d, J = 8.4 Hz), 4.82 (2H, s), 3.8-3.6 (2H, m), 2.30 (3H, s), 1.11 (3H, t, J = 7.0Hz).

Example 18 (68) 4- [2- (N-Propyl-phenylsulfonylamino) -4-methylphenoxymethyl] benzoic acid TLC: Rf 0.44 (CHC13: MeOH: AcOH = 9: 1); NMR: d 8.05 (2H, d, J = 8.0Hz), 7.7-7.6 (2H, m), 7.5-7.0 (7H, m), 6.74 (ÍH, d, J = 8.4Hz), 4.80 (2H, s) ), 3.7-3.5 (2H,), 2.29 (3H, s), 1.6-1.4 (2H, m), 0.89 (3H, t, J = 7.4Hz).

Example 18 (69) 4- [2- (N-Butyl-phenylsulfonylamino) -4-methylphenoxymethyl] benzoic acid TLC: Rf 0.49 (CHC13: MeOH = 9: 1); NMR: d 8.05 (2H, d, J = 8.2Hz), 7.7-7.6 (2H, m), 7.4-7.2 (5H, m), 7.2-7.0 (2H, m), 6.74 (ÍH, d, J = 8.4Hz), 4.80 (2H, s), 3.7-3.5 (2H, m), 2.30 (3H, s), 1.6-1.2 (4H,), 0.85 (3H, t, J = 7.0Hz).

Example 18 (70) 4- [2- [N- (2-methylprop-2-enyl) -phenylsulfonolamino] -4-methylphenoxymethyl] benzoic acid TLC: Rf 0.38 (CHC13: MeOH = 9: 1); NMR: d 8.06 (2H, d, J = 8Hz), 7.65 (2H, m), 7.47-7.25 (3H, m), 7.19 (2H, d, J = 8Hz), 7.13 (ÍH, d, J = 2Hz ), 7.04 (ÍH, dd, J = 8 and 2Hz), 6.70 (ÍH, d, J = 8Hz), 4.85-4.65 (4H, m), 4.21 (2H, s), 2.29 (3H, s), 1.78 (3H, s).

Example 18 (71) 4- [2- (N-Cyclopropylmethyl-phenylsulfonylamino) -4-methylphenoxymethyl] benzoic acid H TLC: Rf 0.40 (CHC13: MeOH: AcOH = 100: 5: 1); NMR (CD3COD3: d 7.99 (2H, d, J = 8.0Hz), 7.68 (2H, m), 7.26-7.57 (5H, m), 7.15 (2H, m), 6.96 (ΔH, d, J = 8.8Hz ), 4.93 (2H, brs), 3.52 (2H, brs), 3.52 (2H, brd, J = 7.0Hz), 2.28 (3H, s), 0.90 (ÍH,), 0.35 (2H, m), 0.06 ( 2H, m).

Example 18 (72) 4- [2- (N-isopropyl-propylsulfonylamino) -5-methylphenoxymethyl] benzoic acid TLC: Rf 0.24 (CHC13: MeOH = 19: .1); NMR: d 8.14 (2H, d, J = 8.2Hz), 7.57 (2H, d, J = 8.2Hz), 7.16 (ÍH, m), 6.82 (2H, m), 5.13 (2H, s), 4.33 ( ÍH, m), 2.97 (2H, m), 2.36 (3H, s), 1.79 (2H, m), 1.23 (3H, d, J = 6.6Hz), 1. 09 (3H, d, J = 6.6Hz), 0.85 (3H, t, J = 7.4Hz).

Example 18 (73) 4- [2- (N-isopropyl-pentylsulfonylamino) -5-methylphenoxymethyl] benzoic acid TLC: Rf 0.26 (CHC13: MeOH = 19: 1); NMR: d 8.15 (2H, d, J = 8.0Hz), 7.56 (2H, d, J = 8.0Hz), 7.14 (1H, m), 6.81 (2H, m), 5.12 (2H, s), 4.32 ( ÍH, m), 2.97 (2H, m), 2.36 (3H, s), 1.77 (2H, m), 1.24 (3H, d, J = 6.6Hz), 1.16 (4H, m), 1.09 (3H, d , J = 6.6Hz), 1.12 (3H, d, J = 6.6Hz), 0.83 (3H, t, J = 6.4Hz).

Example 18 (74) 4- [2- (N-Benzyl-methylsulfonylamino) -5-methylphenoxymethyl] benzoic acid H TLC: Rf 0.39 (CHC13: MeOH = 19: 1); NMR: d 8.17 (2H, d, J = 8.0Hz), 7.53 (2H, d, J = 8.0Hz), 7.25 (5H, s), 6.98 (HH, m), 6.77 (2H, m), 5.17 (2H, s), 4.70 (2H, bs), 2.89 (3H, s), 2.30 (3H, s).

Example 18 (75) 4- [2- (N-Benzyl-propylsulfonylamino) -5-methylphenoxymethyl] benzoic acid H TLC: Rf 0.40 (CHC13: MeOH = 19: 1); NMR: d 8.17 (2H, d, J = 8.2Hz), 7.55 (2H, d, J = 8.2Hz), 7.23 (5H, s), 6.98 (IH,), 6.78 (2H, m), 5.16 (2H) , s), 4.77 (2H, bs), 2.95 (2H, m), 2.29 (3H, s), 1.81 (2H, m), 0.85 (3H, t, J = 7.6Hz).

Example 18 (76) 4- [2- (N-isopropyl-cyclopentylsulfonylamino) -5-ethylphenoxymethyl] benzoic acid TLC: Rf 0.38 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 8.15 (2H, d, J = 8.0Hz), 7.59 (2H, d, J = 8.0Hz), 7.14 (ÍH, d, J = 8.6Hz), 6.81 (2H, m), 5.12 (2H, s), 4.35 (ÍH, sept, J = 6.6Hz), 3.51 (ÍH,), 2.36 (3H, s), 1.85-2.15 (3H, m), 1.61-1.85 (3H, m), 1.34-1.61 (2H, m), 1.22 (3H, d, J = 6.6Hz), 1.08 (3H, d, J = 6.6Hz) .

Example 18 (1-1) 4- [2- (N-Isobutyl-ethylsulfonylamino) -4-ethylphenoxymethyl] benzoic acid TLC: Rf 0.23 (hexane: AcOEt = 1: 1); NMR: d 8.15 (2H, d, J = 8Hz), 7.53 (2H, d, J = 8Hz), 7.21 (HH, d, J = 1.5Hz), 7.08 (HH.DD, J = 8.5), 6.86 ( ÍH, d, J = 8.5Hz), 5.17 (2H, s), 3.46 (2H, d, J = 7.5Hz), 2.97 (2H, q, J = 7.5Hz), 2.30 (3H, s), 1.7- 1.5 (1H, m), 1.25 (3H, t, J = 7.5Hz), 0.94-0.90 (6H, m).

Example 18 (78) 4- [2- (N-Isobutyl-propylsulfonylamino) -4-methylphenoxymethyl] benzoic acid H TLC: Rf 0.27 (hexane: AcOEt = 1: 1); NMR: d 8.15 (2H, d, J = 8Hz), 7.53 (2H, d, J = 8Hz), 7.20 (ÍH, d, J = 0.5Hz), 7.08 (ÍH, dd, J = 8, 0.5Hz) , 6.86 (ÍH, d, J = 8Hz), 5.17 (2H, s), 3.44 (2H, d, J = 7Hz), 2.94-2.86 (2H, m), 2.30 (3H, s), 1.9-1.6 ( 3H, m), 1.0-0.9 (6H, m), 0.85 (3H, t, J = 7Hz).

Example 18 (79) 4- [2- (N-Isobutyl-butylsulfonylamino) -4-methylphenoxymethyl] benzoic acid TLC: Rf 0.37 (hexane: AcOEt = 1: 1); NMR: d 8.15 (2H, d, J = 8Hz), 7.53 (2H, d, J = 8Hz), 7.20 (ÍH, d, J = 0.5Hz), 7.08 (ÍH, dd, J = 8.5 0.5Hz), 6.86 (ÍH, d, J = 8.5Hz), 5.16 (2H, s), 3.45 (2H, d, J = 7Hz), 2.97-2.89 (2H, m), 2.30 (3H, s), 1.8-1.5 ( 3H, m), 1.3-1.1 (2H, m), 1.0-0.9 (6H, m), 0.79 (3H, t, J = 7Hz).

Example 18 (80) 4- [2- (N-Isobutyl-propylsulfonolamino) -5-methylphenoxymethyl] benzoic acid H TLC: Rf 0.25 (CHC13: MeOH = 20: 1); NMR: d 8.16 (2H, d, J = 8.4Hz), 7.53 (2H, d, J = 8.4Hz), 7.28 (ÍH,), 6.82 (2H, m), 5.18 (2H, s), 3.41 (2H , d, J = 7.0Hz), 2.89 (2H, m), 2.35 (3H, s), 1.78 (2H, m), 1.60 (1H, m), 0.90 (6H, d, J = 7.0Hz), 0.84 (3H, t, 7.6Hz).

Example 18 (81) 4- [2- [N- (prop-2-enyl) -propylsulfonylamino] -5-methylphenoxymethyl] benzoic acid TLC: Rf 0.23 (CHC13: MeOH = 20: 1); NMR: d 8.16 (2H, d, J = 8.4Hz), 7.56 (2H, d, J = 8.4Hz), 7.21 (HH, m), 6.90 (2H, m), 5.80 (HH, m), 5.17 ( 2H, s), 5.07 (2H, m), 4.21 (2H, d, J = 6.2Hz), 2.94 (2H, m), 2.34 (3H, s), 1.81 (2H, m), 0.86 (3H, t , J = 7.4Hz).

Example 18 (82) 4- [2- [N- (2-methylprop-2-enyl) -propylsulfonylamino] -5-ethylphenoxymethyl] benzoic acid H TLC: Rf 0.28 (CHC13: MeOH = 20: 1); NMR: d 8.16 (2H, d, J = 8.2Hz), 7.54 (2H, d, J = 8.2Hz), 7.23 (ÍH, m), 6.78 (2H, m), 5.17 (2H, s), 4.75 ( 2H, s), 4.18 (2H, m), 2.34 (3H, s), 1.79 (2H, m), 1.78 (3H, s), 0.85 (3H, t, J = 7.6Hz).

Example 18 (83) 4- [2- (N-Isobutyl-phenylsulfonylamino) -4-chlorophenoxymethyl] benzoic acid TLC: Rf 0.29 (CHC13: MeOH = 19: 1); NMR: d 8.06 (2H, d, J = 8.0Hz), 7.64 (2H, d, J = 8.0Hz), 7.20-7.40 (7H, m), 6.78 (ÍH, m), 4.80 (2H, bs), 3.40 (2H, d, J = 7.0Hz), 1.61 (HH, m), 0.90 (6H, d, J = 7.0Hz).

Example 18 (84) 4- [2- (N-Propyl-propylsulfonylamino) -5-methylphenoxymethyl] benzoic acid TLC: Rf 0.52 (CHC13: MeOH = 9: 1); NMR: d 8.17 (2H, d, J = 8.4Hz), 7.55. (2H, d, J = 8.4Hz), 7.25 (ÍH, d, J = 8.2Hz), 6.9-6.8 (2H, m), 5.17 (2H, s), 3.56 (2H, t, J = 7.4Hz) , 3.0-2.8 (2H, m), 2.35 (3H, s), 1.9-1.7 (2H, m), 1.6-1.4 (2H, m), 0.89 (3H, t, J = 7.2Hz), 0.84 (3H , t, J = 7.4Hz).

Example 18 (85) 4- [2- (N-Isobutyl-hexylsulfonylamino) -4-ethylphenoxymethyl] benzoic acid TLC: Rf 0.49 (CHC13: MeOH = 9: 1); NMR: d 8.16 (2H, d, J = 8.4Hz), 7.53 (2H, d, J = 8.4Hz), 7.21 (ÍH, d, J = 2.0Hz), 7.09 (ÍH, dd, J = 2.0, 8.4Hz), 6.87 (1H, d, J = 8.4Hz), 5.16 (2H, s), 3.45 (2H, d, J = 7.0Hz), 3.0-2.8 (2H, m), 2.30 (3H, s), 1.8-1.5 (3H,), 1.3 -1.0 (6H, m), 1.0-0.8 (6H, m), 0.83 (3H, t, J = 7.0Hz).

Example 18 (86) 4- [2- (N-Isobutyl-pentylsulfonyl) -4-methylphenoxymethyl] benzoic acid TLC: Rf 0.38 (CHC13: MeOH: AcOH = 100: 5: 1): NMR: d 8.16 (2H, d, J = 8.4Hz), 7.53 (2H, d, J = 8.4Hz), 7.21 (1H, d , J = 2.2Hz), 7.09 (HH, dd, J = 2.2, 8.6Hz), 6.87 (HH, d, J = 8.6Hz), 5.16 (2H, s), 3.45 (2H, d, J = 7.2Hz ), 2.91 (2H, m), 2.30 (3H, s), 1.74 (2H, m), 1.60 (HI, m), 1.17 (4H, m), 0.92 (6H, m), 0.82 (3H, m) .

Example 18 (87) 4- [2- [N- (prop-2-enyl) -propylsulfonylamino] -5-trifluoromethylphenoxymethyl] benzoic acid H TLC: Rf 0.33 (hexane: AcOEt = 1: 1); NMR (200MHz, CDC13 + 1 drop of CD3OD): d 8.15-8.11 (2H, m), 7.54-7.44 (3H, m), 7.30-7.24 (2H, m), 5.88-5.68 (H, m), 5.20 (2H, s), 5.12-5.10 (HH, m), 5.04-5.03 (HH, m), 4.21 (2H, d, J = 6.5Hz), 2.95-2.87 (2H, m), 1.8-1.7 (HH) , m), 0.84 (3H, t, J = 7.5Hz).

Example 18 (88) 4- [2- [N- (2-methylprop-2-enyl) -propylsulfonylamino] -5-trifluoromethylphenoxymethyl] benzoic acid H TLC: Rf 0.41 (hexane: AcOEt = 1: 1); NMR: d 8.30 (2H, d, J = 8Hz), 7.71-7.67 (2H, m), 7.62-7.56 (HH, m), 7.40-7.35 (2H,), 5.34 (2H, s), 4.89-4.85 (2H, m), 4.31 (2H, s), 3.07-2.99 (2H, m), 2.0-1.8 (2H, m), 1.87 (3H, s), 1.00-0.93 (3H, m).

Example 18 (89) 4- [2- (N-Propyl-2-furanylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid TLC: Rf: d 0.38 (hexane: AcOEt = 1: 1); NMR: d 7.81 (HH, d, J = 16Hz), 7.59 (2H, d, J = 8Hz), 7.42-7.37 (3H, m), 7.28-7.24 (2H, m), 7.18 (HH, d, J = 1.5Hz), 6.85 (HH, dd, J = 3, 1Hz), 6.49 (HH, d, J = 16Hz), 6.35 (HH, dd, J = 3, 2Hz), 5.03 (2H, s), 3.71 -3.64 (2H, m), 1.6-1.4 (2H, m), 0.88 (3H, t, J = 7Hz).

Example 18 (90) 4- [2- (N-Propyl-propylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid H 02S \ / \ TLC: Rf 0.40 (CHC13: MeOH = 9: 1); NMR: d 8.17 (2H, d, J = 8.2Hz), 7.56 (2H, d, J = 8.2Hz), 7.49 (H, m), 7.27 (2H, m), 5.22 (2H, s), 3, 58 (2H, m), 2.91 (2H,), 1.79 (2H, m), 1.45 (2H, m), 0.89 (3H, t, J = 7.4Hz), 0.85 (3H, t, J = 7.6Hz) .

Example 18 (91) 4- [2- (N-Isobutyl-propylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid H TLC: Rf 0.45 (CHC13: MeOH = 9: 1); NMR: d 8.18 (2H, d, J = 8.2Hz), 7.56 (2H, d, J = 8.2Hz), 7.51 (ÍH,), 7.28 (2H,), 5.23 (2H, s), 3.45 (2H, d, J = 7.4Hz), 2.89 (2H, m), 1.75 (2H,), 1.58 (HH, m), 0.90 (6H, d, J = 6.8Hz), 0.84 (3H, t, J = 7.4Hz ).

Example 18 (92) 4- [2- (N-Propyl-2-furanylsulfonylamino) -5-methyphenoxymethyl] benzoic acid TLC: Rf 0.38 (hexane: AcOEt = 1: 1); NMR: d 8.13 (2H, d, J = 8Hz), 7.44 (2H, d, J = 8Hz), 7.25 (HH, m), 7.12 (HH, d, J = 8Hz), 6.83-6.73 (3H, m ), 6.33-6.30 (ÍH, m), 5.01 (2H, s), 3.7-3.6 (2H,), 2.33 (3H, s), 1.52 (2H, q, J = 7Hz), 0.90 (3H, t, J = 7Hz).

Example 18 (93) 4- [2- (N-Isobutyl-2-furanylsulfonylamino) -5-methylphenoxymethyl] benzoic acid TLC: Rf 0.41 (hexane: AcOEt = 1: 1); NMR: d 8.13 (2H, d, J = 8Hz), 7.44 (2H, d, J = 8Hz), 7.25 (HH, m), 7.15 (HH, d, J = 8Hz), 6.80-6.71 (3H, m ), 6.31 (HH, m), 5.0 (2H, m), 3.53 (2H, d, J = 7Hz), 1.75-1.60 (HH, m), 0.91 (6H, t, J = 7Hz).

Example 18 (94) 4- [2- (N-Isobutyl-2-furanylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid TLC: Rf 0.44 (hexane: AcOEt = 1: 1); NMR: d 7.81 (HH, d, J = 16Hz), 7.60 (2H, d, J = 8Hz), 7.41-7.37 (3H, m), 7.27-7.22 (2H, m), 7.17 (HH, m), 6.83 (ÍH, dd, J = 3.5, 1.5Hz), 6.49 (ÍH, d, J = 16Hz), 6.35 (ÍH, dd, J = 3.5, 1.5Hz), 5.02 (2H, s), 3.53 (2H, d, J = 7.5Hz), 1.74-1.50 (ÍH, m), 0.90 (6H, d, J = 6.5Hz).

Example 18 (95) 4- [2- (N-Propyl-phenylsulfonylamino) -5-methylphenoxymethyl] cinnamic acid TLC: Rf 0.33 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 7.79 (ÍH, d, J = 16.0Hz), 7.67 (2H, m), 7.51 (2H, d, J = 8.0Hz), 7.24-7.43 (3H, m), 7.17 (2H, d, J = 8.0Hz), 7.15 (IH, d, J = 8.0Hz), 6.78 (IH, m), 6.68 (IH, ), 6.47 (ÍH, d, J = 16.0Hz), 4.79 (2H, brs), 3.55 (2H, m), 2.34 (3H, s), 1.47 (2H, m), 0.87 (3H, t, J = 76.2Hz).

Example 18 (96) 4- [2- (N-Isobutyl-phenylsulfonylamino) -5-methylphenoxymethyl] cinnamic acid H TLC: Rf 0.37 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 7.79 (HH, d, J = 16.0Hz), 7.63 (2H, m), 7.51 (2H, d, J = 8.2Hz), 7.24-7.46 (3H, m), 7.18 (HH, d, J = 7.8Hz), 7.16 (2H, d, J = 8.2Hz), 6.78 (HH, m), 6.66 (HH,), 6.48 (HH, d, J = 16.0Hz), 4.74 (2H, m), 3.41 (2H, m), 2.33 (3H, s), 1.61 (HH, m), 0.89 (6H, d, J = 6.4Hz).

Example 18 (97) 4- [2- (N-Isobutyl-propylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid H TLC: Rf 0.36 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 7.80 (HH, d, J = 16.0Hz), 7.62 (2H, d, J = 8.4Hz), 7.44-7.56 (3H,), 7.24-7.33 (2H, m), 6.50 (HH, d, J = 16.0Hz), 5.17 (2H, s), 3.44 (2H, d, J = 7.4Hz), 2.87 (2H, m), 7.15 (2H, m), 7.15 (2H, m), 1.55 (1H, m), 0.90 (6H, d, J = 6.6Hz), 0.83 (3H, t, J = 7.4Hz).

Example 18 (98) 4- [2- (N-Methyl-phenylsulfonylamido) -5-trifluoromethylphenoxymethyl] cinnamic acid TLC: Rf 0.44 (CHC13: MeOH = 9: 1); NMR: d 7.79 (ÍH, d, J = 16.2Hz), 7.7-7.6 (2H, m), 7.6-7.2 (7H, m), 7.2-7.1 (3H,), 6.49 (ÍH, d, J = 16.2 Hz), 4.88 (2H, s), 3.23 (3H, s).

Example 18 (99) 4- [2- (N-Propyl-phenylsulfonylamino) -5-trifluoromethyl phenoxymethyl] cinnamic acid TLC: Rf 0.43 (CHC13: MeOH = 9: 1); NMR: d 7.80 (HH, d, J = 16.0Hz), 7.7-7.6 (2H, m), 7.6-7.1 (10H, m), 6.49 (HH, d, J = 16.0Hz), 4.86 (2H) , s), 3.57 (2H, t, J = 7.2Hz), 1.6-1.3 (2H, m), 0.87 (3H, t, J = 7.2Hz).

Example 18 (100) 4- [2- (N-Isobutyl-phenylsulfonolamino) -5-trifluoromethylphenoxymethyl] cinnamic acid TLC: Rf 0.47 (CHC13: MeOH = 9: 1); NMR: d 7.80 (HH, d, J = 16.0Hz), 7.7-7.1 (12H, m), 6.49 (HH, d, J = 16.0Hz), 4.9-4.7 (2H, br), 3.42 (2H, d , J = 7.6Hz), 1.7-1.5 (ÍH, m), 0.89 (6H, d, J = 6.6Hz).

Example 18 (101) 4- [2- (N-isopropyl-propylsulfonylamino) -5-methylphenoxymethyl] cinnamic acid TLC: Rf 0.44 (CHC13: MeOH = 9: 1); NNMR: d 7.79 (HH, d, J = 16.0Hz), 7.53 (4H, m), 7.14 (HH,), 6.80 (2H, m), 6.47 (HH, d, J = 16.0Hz), 5.07 (2H , s), 4.31 (ÍH, m), 2.94 (2H, m), 1.79 (2H, m), 1.23 (3H, d, J = 6.6Hz), 1.08 (3H, d, J = 6.6Hz), 0.83 (3H, t, J = 7.2Hz).

Example 18 (102) 4- [2- (N-Ethyl-phenylsulfonylamino) -5-trifluoromethyl-phenoxymethyl] cinnamic acid TLC: Rf 0.37 (CHC13: MeOH = 9: 1); NMR: d 7.79 (ÍH, d, J = 16.0Hz), 7.60-7.71 (2H, m), 7.15-7.55 (10H, m), 6.49 (ÍH, d, J = 16.0Hz), 4.89 (2H, s ), 3.67 (2H, q, J = 7.0Hz), 1.09 (3H, t, J = 7.0Hz).

Example 18 (103) 4- [2- (N-Cyclopropylmethyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid TLC: Rf 0.47 (CHC13: MeOH = 9: 1); NMR: d 7.80 (HH, d, J = 16.0Hz), 7.14-7.55 (10H, m), 7.67 (2H, m), 6.49 (HH, d, J = 16.0Hz), 4.88 (2H, s), 3.49 (2H, d, J = 7.0Hz), 0.87 (HH, m), 0.37 (2H,), 0.06 (2H,).

Example 18 (104) 4- [2- (N-isopropyl-methylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid TLC: Rf 0.47 (CHC13: MeOH = 9: 1); NMR: d 7.76 (ÍH, d, J = 16.0Hz), 7.61 (2H, d, J = 8.4Hz), 7.49 (2H, d, J = 8.4Hz), 7.37 (3H, m), 6.48 (ÍH, d, J = 16.0Hz), 5.14 (2H, s), 4.31 (HH, m), 2.89 (3H, s), 1.28 (3H, d, J = 6.6Hz), 1.09 (3H, d, J = 6.6 Hz).

Example 18 (105) 4- [2- (N-Benzyl-propylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid TLC: Rf 0.29 (CHC13: MeOH: AcOH = 100: 5: 1); NMR; d 7.82 (ÍH, d, J = 16.2Hz), 7.65 (2H, d, J = 8.4Hz), 7.51 (2H, d, J = 8.4Hz), 7.09-7.31 (8H, m), 6.52 (ÍH, d, J = 16.2Hz), 5.17 (2H, s), 4.78 (2H, s), 2.94 (2H, m), 1.80 (2H, m), 0.85 (2H, t, J = 7.4Hz).

Example 18 (106) 4- [2- (N-Propyl-phenylsulfonylamino) -4-methylphenoxymethyl] cinnamic acid H TLC: Rf 0.39 (CHCl3: MeOH = 9: 1); NMR: d 7.79 (HH, d, J = 16.0Hz), 7.70-7.65 (2H, m), 7.50 (2H, d, J = 8.0Hz), 7.42-7.38 (HH, m), 7.30 (2H, t , J = 8.0Hz), 7.16 (2H, d, J = 8.0Hz), 7.11 (HH, d, J = 1.5Hz), 7.07 (HH, dd, J = 1.5, 8.0Hz), 6.74 (HH, d , J = 8.0Hz), 6.47 (ÍH, d, J = 16.0Hz), 4.90-4.70 (2H, br), 3.70-3.50 (2H, br), 2.29 (3H, s), 1.55-1.45 (2H, m), 0.88 (3H, t, J = 7.0Hz).

Example 18 (107) 4- [2- [N- (prop-2-enyl) -phenylsulfonylamino] -5-trifluoromethylphenoxymethyl] cyanic acid TLC: Rf 0.35 (CHC13: MeOH = 9: 1); NMR: d 7.80 (ÍH, d, J = 16.0Hz), 7.71-7.68 (2H, m), 7.54 (2H, d, J = 8.0Hz), 7.49-7.45 (ÍH,), 7.40 (ÍH, d, J = 8.0Hz), 7.38-7.33 (2H, m), 7.25 (HH, dd, J = 2.0, 8.0Hz), 7.19 (2H, d, J = 8.0Hz), 7.12 (HH, d, J = 2.0 Hz), 6.49 (ÍH, d, J = 16.0Hz), 5.80-5.70 (1H, m), 5.07-5.02 (2H, m), 4.88 (2H, s), 4.5-4.3 (2H, m).

Example 18 (108) 4- [2- [N- (2-methylprop-2-enyl) -phenylsulfonylamino] -5-trifluoromethylphenoxymethyl] cinnamic acids TLC: Rf 0.39 (CHCl3: MeOH = 9 NMR: d 7.80 (ΔI, d, J = 16.0Hz), 7.68-7.63 (2H, m), 7.54 (2H, d, J = 8.0Hz), 7.48-7.44 ( ÍH, m), 7.41 (ÍH, d, J = 8.0Hz), 7. 35 (2H, t, J = 8.0Hz), 7.25 (HH, dd, J = 1.5, 8.0Hz), 7.17 (2H, d, J = 8.0Hz), 7.10 (HH, d, J = 1.5Hz), 6.50 (ÍH, d, J = 16.0Hz), 4.84 (2H, s), 4.73 (HH, s), 4.86 (HH, s), 4.20 (2H, s), 1.74 (3H, s).

Example 18 (109) 4- [2- [N- (prop-2-enyl) -2-furanylsulfonylamino] -5-ethylphenoxymethyl] benzoic acid TLC: Rf 0.21 (hexane: AcOEt = 1: 1); NMR: d 8.14-8.13 (2H, m), 7.45 (2H, d, J = 8.5Hz), 7.28 (HH, m), 7.10 (HH, d, J = 7.5Hz), 6.85 (HH, m), 6.84-6.76 (ÍH, m), 6.71 (ÍH, s), 6.34 (ÍH, m), 5.88-5.79 (ÍH, m), 5.11-5.02 (4H, m), 4.33 (2H, bs), 2.32 ( 3H, bs).

Example 18 (110) 4- [2- [N- (2-methylprop-2-enyl) -2-furanylsulfonylamino] -5-methylphenoxymethyl] benzoic acid TLC: Rf 0.24 (hexane: AcOEt = 1: 1); NMR: d 8.14-8.13 (2H, m), 7.44 (2H, d, J = 8Hz), 7.26 (HH, m), 7.13 (HH, d, J = 8Hz), 6.82 (HH, m), 6.78- 6.69 (ÍH, s), 6.69 (ÍH, s), 6.33 (ÍH, m), 5.00 (2H, s), 4.76 (ÍH, dd, J = 9.5), 1.5Hz), 4.30 (2H, bs), 2.32 (3H, s), 1.78 (3H, s), Example 18 (111) 4- [2- (N-Isobutyl-phenylsulfonylamino) -4-methylphenoxymethyl] cinnamic acid TLC: Rf 0.37 (CHC13: MeOH = 9: 1); NMR: d 7.79 (ÍH, d, J = 16.0Hz), 7.70-7.60 (2H, m), 7.50 (2H, d, J = 8.0Hz), 7.40-7.35 (HH, m), 7.30-7.20 (2H, m), 7. 20-7.10 (3H, m), 7.05 (HH, dd, J = 2.0, 8.0Hz), 6.72 (HH, d, J = 8.0Hz), 6.47 (HH, d, J = 16.0Hz), 4.9-4.5 (2H,), 3.5- 3.3 (2H, m), 2.29 (3H, s), 1.7-1.6 (ÍH,), 1.0-0.8 (6H, m).

Example 18 (112) 4- [2- (N-Benzyl-methylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid TLC: Rf 0.62 (CHC13: MeOH = 9: 1); NMR: d 7.80 (HH, d, J = 16.0Hz), 7.64 (2H, d, J = 8.4Hz), 7.48 (2H, d, J = 8.4Hz), 7.24 (8H, m), 6.50 (HH, d, J = 16.0Hz), 5.18 (2H, s), 4.77 (2H, s), 2.88 (3H, s).

Example 18 (113) 4- [2- (N-Isobutyl-2-furanylsulfonylamino) -4-methylphenoxymethyl] benzoic acid TLC: Rf 0.26 (AcOEt: hexane = 1: 1); NMR: d 8.11 (2H, d, J = 8Hz), 7.41 (2H, d, J = 8Hz), 7.25 (HH,), 7.09 (HH, d, J = 2Hz), 7.06 (HH, dt, J = 8.2Hz), 6.80 (ÍH, dd, J = 4, 1Hz), 6.76 (ÍH, d, J = 8Hz), 6.31 (ÍH, dd, J = 2, 2Hz), 5.20-4.80 (2H, brs), 3.53 (2H, brs), 2.28 (3H, s), 1.67 (ÍH, m), 0.92 (6H, brs).

Example 18 (114) 4- [2- (N-isopropyl-2-furanylsulfonylamino) -4-methylphenoxymethyl] benzoic acid TLC: Rf 0.194 (AcOEt: hexane = 1: 1); NMR: d 8.12 (2H, d, J = 8Hz), 7.55 (2H, d, J = 8Hz), 7.44 (ΔI, d, J = 2Hz), 7.11 (ΔI, dd, J = 8.2Hz), 6.91 ( ÍH, dd, J = 3, 1Hz), 6.87 (ÍH, d, J = 3Hz), 6.84 (ÍH, d, J = 8Hz), 6.42 (ÍH, dd, J = 3, 1Hz), 5.10 (2H, s), 4.48 (ÍH, m), 2.27 (3H, s), 1.12 (6H, d, J = 7Hz).

Example 18 (115) 4- [2- [N- (2-methylprop-2-enyl) -2-furanylsulfonylamino] acid] 4-methylphenoxymethyl] benzoic acid TLC: Rf 0.21 (AcOEt: hexane = 1: 1); NMR: d 8.12 (2H, d, J = 8Hz), 7.42 (2H, d, J = 8Hz), 7.26 (HH, m), 7.07 (HH, d, J = 2Hz), 7.06 (HH, dd, J = 8, 2Hz), 6.83 (HH, d, J = 3Hz), 6.75 (HH, d, J = 8Hz), 6.33 (HH, dd, J = 3, 2Hz), 4.97 (2H, s), 4.77 ( 2H, s), 4.30 (2H, s), 2.28 (3H, s), 1.79 (3H, s).

Example 18 (116) 4- [2- (N-isopropyl-2-furanylsulfonylamino) -5-methylphenoxymethyl] cinnamic acid TLC: Rf 0.20 (hexane: AcOEt = 1: 1); NMR: d 7.80 (HH, d, J = 16Hz), 7.61-7.45 (4H, m), 7.43 (HH, m), 6.93-6.88 (2H, m), 6.79-6.73 (2H, m), 6.47 ( ÍH, d, J = 16Hz), 6.41 (ÍH, dd, J = 3.5, 2Hz), 5.07 (2H, s), 4.56-4.43 (ÍH, m), 2.34 (3H, s), 1.10 (6H, dd , J = 6.5, 4Hz).

Example 18 (117) 4- [2- (N-isopropyl-2-furanylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid TLC: Rf 0.18 (hexane: AcOEt = 1: 1); NMR: d 7.80 (HH, d, J = 16Hz), 7.63-7.51 (4H, m), 7.46 (HH, dd, J = 1.5, 1Hz), 7.23-7.20 (3H, m), 6.94 (HH, dd) , J = 3.5, 1Hz), 6.52-6.43 (3H, m), 5.14 (2H, s), 4.51-4.41 (ÍH, m), 1.09 (6H, dd, J = 6.5, 1Hz).

Example 18 (118) 4- [2- (N-isopropyl-2-furanylsulfonylamino) -4-trifluoromethylphenoxymethyl] benzoic acid TLC: Rf 0.35 (AcOEt: hexane: AcOH = 50: 1); NMR: d 8.16 (2H, d, J = 8.5Hz), 7.60 (3H, m), 7.38 (HH, dd, J = 1.0, 2.0Hz), 7.26 (HH, m), 7.05 (HH, d, J = 9.0Hz), 6.95 (ÍH, d, J = 3.0Hz), 6.47 (ÍH, dd, J = 2.0, 3.5Hz), 5.22 (2H, s), 4.52 (2H, sept, J = 7.0Hz), 1.12 (3H, d, J = 7.0Hz), 1.10 (3H, d, J = 7.0Hz).

Example 18 (119) 4- [2- (N-Isobutyl-2-furanylsulfonylamino) -4-trifluoromethylphenoxymethyl] benzoic acid TLC: Rf 0.35 (AcOEt: hexane: AcOH = 50: 50: 1); NMR: d 8.15 (2H, d, J = 9.0Hz), 7.55 (HH, m), 7.48 (2H, d, J = 9.0Hz), 7.44 (HH, d, J = 2.0Hz), 7.35 (HH, dd, J = 1.0, 2.0Hz), 6.99 (HH, d, J = 9.0Hz), 6.86 (HH, dd, J = 1.0, 2.0Hz), 6.39 (HH, dd, J = 2.0, 4.0Hz), 5.12 (2H, br), 3.52 (2H, d, J = 7.0Hz), 1.64 (ÍH, m), 0.92 (6H, d, J = 6.5Hz).

Example 18 (120) 4- [2- (N-isopropyl-phenylsulfonylamino) -4-trifluoromethylphenoxymethyl] cinnamic acid TLC: Rf 0.35 (AcOEt: hexane: AcOH = 50: 50: 1); NMR: d 7.81 (3H, m), 7.58-7.62 (3H, m), 7.53 (H, m), 7.49 (2H, d, J = 8.0Hz), 7.41 (2H, m), 7.24 (H, d) , J = 2.0Hz), 7.07 (HH, d, J = 8.5Hz), 6.49 (HH, d, J = 16.5Hz), 5.13 (HH, d, J = 12.5Hz), 5.12 (HH, d, J = 12.5Hz), 4.40 (ÍH, sept, J = 6.5Hz), 4.07 (3H, d, J = 6.5Hz), 1.02 (3H, d, J = 6.5Hz).

Example 18 (121) 4- [2- (N-Isobutyl-2-furanylsulfonylamino) -5-chlorophenoxymethyl] benzoic acid TLC: Rf 0.36 (AcOEt: hexane: AcOH = 50: 50: 1); NMR: d 8.14 (2H, d, J = 8.5Hz), 7.44 (2H, d, J = 8.5Hz), 7.26 (HH, m), 7.21 (HH, d, J = 9.0Hz), 6.98 (HH, dd, J = 2.5, 8.0Hz), 6.91 (HH, dd, J = 2.5Hz), 6.82 (HH, d, J = 4.5Hz), 6.34 (HH, d, J = 2.0, 3.0Hz), 5.00 ( 2H, br), 3.51 (2H, brs), 1.65 (HH, m), 0.91 (6H, d, J = 6.5Hz).

Example 18 (122) 4- [2- (N-isopropyl-2-furanylsulfonylamino) -5-chlorophenoxymethyl] cinnamic acid TLC: Rf 0.49 (CHC1: MeOH = 9: 1); NMR: d 7.80 (HH, d, J = 16.2Hz), 7.60 (2H, d, J = 8.4Hz), 7.50 (2H, d, J = 8.4Hz), 7.45-7.42 (HH, m), 7.02- 6.90 (4H, m), 6.35-6.40 (2H, m), 5.07 (2H, s), 4.60-4.40 (lH, m), 1.10 (3H, d, J = 6.6Hz), 1.07 (3H, d, J = 6.6Hz).

Example 18 (123) 4- [2- (N-Isobutyl-2-furanylsulfonylamino) -5-chlorophenoxymethyl] cinnamic acid TLC: Rf 0.49 (CHC13: MeOH = 9: 1); NMR: d 7.80 (HH, d, J = 15.8Hz), 7.58 (2H, d, J = 8.0Hz), 7.37 (2H, d, J = 8.0Hz), 7.25 (HH, dd, J = 1.0, 1.8 Hz), 7.20 (HH, d, J = 8.2Hz), 7.00-6.90 (2H, m), 6.81 (HH, dd, J = 1.0, 3.6Hz), 6.49 (HH, d, J = 15.8Hz), 6.33 (ÍH, dd, J = 1.8, 3.6Hz), 4.95 (2H, s), 3.60-3.40 (2H, m), 1.80-1.50 (ÍH,), 0.90 (6H, d, J = 6.6Hz).

Example 18 (124) 4- [2- (N-Isobutyl-2-furanylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid H TLC: Rf 0.20 (hexane: AcOEt = 1: 1); NMR: d 8.18-8.14 (2H, m), 7.48-7.40 (2H, m), 7.30-7.26 (2H, m), 7.16 (HH, m), 6.84 (HH, dd, J = 3.5, 1Hz), 6.35 (ÍH, dd, J = 3.5, 2Hz), 5.07 (2H, s), 3.54 (2H, d, J = 7Hz), 1.64 (1H, sept, J = 7Hz), 0.90 (6H, d, J = 7Hz).

Example 18 (125) 4- [2- (N-Isobutyl-2-furanylsulfonylamino) -4-chlorophenoxymethyl] benzoic acid TLC: Rf 0.36 (CHC13: MeOH = 9: 1); NMR: d 8.14 (2H, d, J = 8.4Hz), 7.44 (2H, d, J = 8.4Hz), 7.34-7.20 (3H, m), 6.90-6.80 (2H, m), 6.37 (ÍH, dd , J = 1.8, 3.0Hz), 5.03 (2H, s), 3.51 (2H, d, J = 7.2Hz), 1.80-1.50 (ÍH, m), 0.91 (6H, d, J = 6.6Hz).

Example 18 (126) '4- [2- (N-Isobutyl-2-furanylsulfonylamino) -4-methylphenoxymethyl] cinnamic acid TLC: Rf 0.33 (CHCl3: MeOH = 9: 1); NMR: d 7.80 (ÍH, d, J = 16.0Hz), 7.57 (2H, d, J = 8.0Hz), 7.36 (2H, d, J = 8.0Hz), 7.28-7.22 (ÍH, m), 7.12-7.02 (2H,), 6. 84-6.74 (2H, m), 6.48 (HH, d, J = 16.0Hz), 6.32 (HH, dd, J = 1.8, 3.6Hz), 4.92 (2H, s), 3.54 (2H, d, J = 7.0Hz), 2.28 (3H, s), 1.80-1.60 (ÍH,), 0.92 (6H, d, J = 6.6Hz).

Example 18 (127) 4- [2- (N-Isobutyl-4-ethoxyphenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid H TLC: Rf 0.35 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 8.09 (2H, d, J = 8.5Hz), 7.52 (2H, d, J = 8.5Hz), 7.46 (ÍH, d, J = 8.5Hz), 7.25-7.29 (3H, m), 7.13 ( ÍH, brd, J = 1.5Hz), 6.73 (2H, d, J = 9.0Hz), 4.92 (2H, br), 3.96 (2H, q, J = 7.5Hz), 3.40 (2H, brs), 1.59 ( ÍH, m), 1.42 (3H, t, J = 7.5Hz), 0.90 (6H, brd, J = 6.0Hz).

Example 18 (128) 4- [2- (N-Methyl-phenylsulfonylamino) -4-chlorophenoxymethyl] benzoic acid H TLC: Rf 0.43 (CHC13: MeOH: H20 = 9.1; NMR (DMSO-de): d 7.87 (2H, d, J = 8.6 Hz), 7.66-7.38 (6H, m), 7. 25-7.11 (4H,), 4.95 (2H, s), 3.15 (3H, s).

Example 19 4- [Methyl 2- (N-cyclopentylmethyl-phenylsulfonylamino) -5-trifluoromethyl-phenoxymethyl] benzoate To a solution of methyl 4- (2-phenylsulfonylamino-5-trifluoromethyl-phenoxymethyl) benzoate (250 mg, prepared in Example 15.), triphenylphosphine (142 mg) and cyclopentylmethanol (54 mg) were added at 0 ° C. in THF (2 ml), diethyl azodicarboxylate (89 μl, abbreviated as DEAD). The mixture was stirred overnight at room temperature. The reaction solution was purified on silica gel chromatography (hexane: AcOEt = 7.1) to give the title compound (333 mg) having the following physical data).

TLC: Rf 0.51 (hexane: AcOEt = 3.1); NMR: d 8.01 (2H, d, J = 8.4 Hz), 7.63-7.58 (2H,), 7.48-7.28 (5H, m), 7.17 (2H, d, J = 8.4 Hz) 7.09 (ÍH, d, J = 1.4 Hz), 4.83 (2H, br), 3.95 (3H, s), 3.55 (2H, d-similar), 1.92-1.09 (9H, m).

Example 20 4- [2- (N-Cyclopentylmethyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid By the use of methyl 4- [2- (N-cyclopentylmethyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoate (prepared in Example 19), the compounds having the following physical data were obtained by the same procedure as in Example 2.

TLC: Rf 0.40 (CHC13: MeOH: H20 = 9: 1: 0.1); NMR: d 8.09 (2H, d, J = 8.2 Hz), 7.65-7.61 (2H,), 7.47-7.20 (7H, m), 7.11 (ÍH, d, J = 1.8 Hz), 4.89 (2H, br), 3.59-3.51 (2H, m), 1.93-1.10 (9H,).

Example 20 (1) -20 (30) By using the corresponding compounds, the title compounds having the following physical data were obtained by the same procedures as Reference Example 6 - »Reference Example 7 -» Example 7 - > Example 19 - »Example 2 or Reference Example 8 -» Reference Example 9 - Reference Example 10 - > Example 9 Example 19 - »Example 2.

Example 20 (1) 4- [2- (N-Cyclopropylmethyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid TLC: Rf 0.43 (CHC13: MeOH: H20 = 9: 1: 0.1); NMR: d 8.09 (2H, d, J = 8.2 Hz), 7.70-7.65 (2H, m), 7.54-7.22 (7H,), 7.14 (ÍH, d, J = 1.8 Hz), 4.93 (2H, s) , 3.51 (2H, d, J = 7.2 Hz), 0.96-0.81 (HH, m), 0.44-0.35 (2H, m), 0.10-0.02 (2H, m).

Example 20 (2) 4- [2- (N-t-Buitylmethyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] -benzoic acid TLC: Rf 0.5 (CHC13: MeOH: 9: 1); NMR: d 8.12 (2H, d, J = 8.0 Hz), 7.6-7.4 (4H, m), 7.4-7.2 (5H, m), 7.09 (H, d, J = l.8 Hz), 5.02 (H) , d, J = 12.4 Hz), 4.72 (ΔH, d, J = 12.4 Hz), 3.53 (2H, s), 0.86 (9H, s).

Example 20 (3) Acid - [2- (N-isopropyl-phenylsulfonylamino) -5-trif luoromethyl-phenoxymethyl] -phenylacetic acid TLC: Rf 0.47 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 7.79 (2H, d, J = 7.6 Hz), 7.20-7.50 (10 H, m), 5.01 (2H, s), 4.28 (ÍH, Sept. J = 6.6 Hz), 3.71 (2H, s), 1.08 (3H, d = 6.6 Hz), 1.01 (3H, d, J = 6.6 Hz).

Example 20 (4) 4- [2- (N-isopropyl-propylsulfonylamino) -5-trifluoromethylphenoxymethyl] -benzoic acid TLC: Rf 0.33 (CHC13: MeOH = 20: 1); NMR (CD3C1): d 8.13 (2H, d J = 8.0 Hz), 7.54 (2H, d, J = 8.0 Hz), 7.30-7.46 (3H, m), 5.19 (2H, s), 4.32 (H, Sept. ., J = 6.2 Hz), 2.96 (2H, m), 1.78 (2H, m), 1.27 (2H, d, J = 6.4 Hz), 1.12 (2H, d, J = 6.4 Hz), 0.85 (3H, t, J = 7.4 Hz).

Example 20 (5) 4- [2- (N-isopropyl-pentylsulfonylamino) -5-trifluoromethylphenoxymethyl] -benzoic acid TLC: Rf 0.40 (CHC13: MeOH = 20: 1); NMR (CD3CI): d 8.17 (2H, d J = 8.4 Hz), 7.59 (2H, d, J = 8.4 Hz), 7.12-7.41 (3H, m), 5.18 (2H, s), 4.32 (1H, Sept. ., J = 6.2 Hz), 2.97 (2H, m), 1.74 (2H, m), 1.02-1.35 (8H, m), 0.82 (3H, t, J = 6.8 Hz).

Example 20 (6) 4- [2- (N-isopropyl-butylsulfonylamino) -5-trifluoromethylphenoxymethyl] -benzoic acid TLC: Rf 0.40 (CHCl3: MeOH = 9: 1); NMR: d 8.17 (2H, d J = 8.2 Hz), 7.59 (2H, d, J = 8.2 Hz), 7.40 (ÍH, d, J = 7.8 Hz), 7.3-7.2 (2H, m), 5.18 (2H , s), 4.4-4.2 (ÍH, m), 3.1-2.9 (2H, m), 1.8-1.6 (2H, m), 1.4-1.0 (8H, m), 0.92 (3H, t, J = 7.2 Hz ).

Example 20 (7) 4- [2- (N-isopropyl-hexylsulfonylamino) -5-trifluoromethylphenoxymethyl] -benzoic acid TLC: Rf 0.44 (CHCl3: MeOH = 9: 1); NMR: d 8.8 (2H, d, J = 8.0Hz), 7.59 (2H, dJ = 8.0Hz) .7.40 (1H, d, J «8.0Hz), 7.3-7.2 (2H, m) .5.18 (2H, s), 4.4-4.2 (1H.m), 3.0-2.9 (2H, m) .1.8-1.6 (2H, m), 1.3-1.0 (12H, m), 0.85 (3H, t, J «7.4Hz).

Example 20 (8) 4- [2- (N-isopropyl-heptylsulfonylamino) -5-trifluoromethylphenoxymethyl] -benzoic acid TLC: Rf 0.48 (CHCL,: MeOH = 9: 1); NMR: d 8.18 (2H. d, J-ß.OHz), 7.59 (2H, d, J = 8.0Hz), 7.40 (1H d.J. 8.0Hz). 7.3-7.2 (2H, m), 5.18 (2H, s), 4.4-4.2 (1H, m), 3.0-2.9 (2H, m), 1.9-1.6 (2H, m). 1.4-1.0 (14H,), 0.86 (3H.W = 6.2H2).

Example 20 (9) 4- [2- (N-isopropyl-4-hydroxyphenylsulfonylamino) -trifluoromethylphenoxymethyl] enzoic acid TLC: Rf 0.28 (CHCl3: MeOH = 9: 1); NMR: d 8.13 (2H. d.J = 8.2Hz), 7.66 (2H, d, J = 9.2Hz) (7.50 (2H, d.J-8.2Hz), 7.3-7.2 (3H, m) .6.72 ( 2H, d.J = 9.2Hz), 5.10 (2H, S) .4.4-4.2 (1H, m), 3.0-1.5 (2H, br) t 1.10 (3H, d, J = 6.6Hz), 1.03 (3H , d, J = 6.6Hz).

Example 20 (10) 4- [2- (N-isopropyl-butylsulfonylamino) -5- acid TLC: Rf 0.41 (CHCl3: MeOH = 9: 1); "NMR: d 8.15 (2H, d, J = 8.6Hz), 7.57 (2H, d, J = 8.6Hz) .7.15 (1H d.J = 8.4Hz), 6.9-6.8 (2H, m), 5.13 (2H, s), 4.4-4.2 (1H, m) .3.1-2.9 (2H,) .2.36 (3H, s), 1.8-1.6 (2H, m), 1.3-1.2 (5H, m) .1.10 (3H, d.J = 6.6Hz), 0.81 (3H, t, J-7.4Hz).

Example 20 (11) 4- [2- (N-isopropyl-hexylsulfonylamino) -5-ethylphenoxymethyl] benzoic acid TLC: Rf 0.47 (CHGI3: MeOH-9: 1); NMR: d 8.15 (2H, d.J = 8.4Hz), 7.57 (2H, d, J = 8.4Hz), 7.15 (1H, d, J-8.4HZ). 7.1-7.0 (2H.m), 5.13 (2H, s), 4.4-4.2 (1H.m), 3.0-2.9 (2H, m). 2.36 (3H. S). 1.8-1.6 (2H,), 1.3-1.0 (12H, m), 0.84 (3H, t, = 6.4Hz).

Example 20 (12) 4- [2- (N-isopropyl-eptylsulfonylamino) -5-methylphenoxymethyl] enzoic acid TLC: Rf 0.47 (CHCl3: MeOH = 9: 1); NMR: 58.15 (2H, d.J-8.0Hz) .7.57 (2H.D, J = 8.0Hz) .7.15 (1H.D, J = 8.4Hz), 6. 9-6.8 (2H, m), 5.13 (2H, s), 4.4-4.2 (1H,), 3.0-2.9 (2H, m), 2.36 (3H, s), 1.9-1.6 (2H, m), 1.3 -1.0 (14H, m), 0.85 (3H, t, J = 6.2Hz).

Example 20 (13) 4- [2- (N-isopropyl-methylsulfonylamino) -5-methylphenoxymethyl] enzoic acid TLC: Rf 0.13 (hexane? AcOEt * = 1: 1); NMR: d 8.17-8.13 (2H,), 7.58-7.53 (2H, m), 7.17-7.12. { 1H (m), 6.8 (2H, m), . 1 (2H,), 4.33 (1H, sept., J = 6.5Hz), 2.90 (3H, s) .2.36 (3H, s), 1.26 (3H, d .J «6.5Hz), 1.09 (3H, d, J = 6.5Hz).

Example 20 (14) 4- [2- (N-isopropyl-ethylsulfonylamine) -5-methyl acid TLC: Rf 0.20 (hexane: AcOEt = 1: 1); NMR: d 8.17-8.13. { 2H, m) .7.59-7.55 (2H. M | .7.17-7.13 (1H, m), 6.6 (2H,), 5.1 (2H, m) .4.33 (1H, sept., J »7Hz), 3.01 ( 2H, q, J = 7Hz), 2.36 (3H.s), 1.29-1.20 (6H, m), 1.09 (3H, d.J = 6.5Hz).

Example 20 (15) 4- [2- (N-isopropyl-2-phenylethylsulfonylamino) -5-methylphenoxymethyl] -benzoic acid TLC: Rf 0.24 (hexane: AcOEt «1: 1); NMR: d 8.00-7.96 (2H,), 7.44-7.40 (2H, m), 7.26-7.14 (4H, m), 7.05-7.01 (2H, m), 6.85-6.81 (2H,), 5.07 (2H. s), 4.42-4.27 (1H, m), 3.4-3.2 (2H.m), 3.2-3.0 (2H, m), 2.36 (3H, s), 1.25 (3H, d.J = 6.5Hz), 1.09 (3H, d, J = 6.5Hz).

Example 20 (16) 4- [2- (N-isopropyl-benzylsulfonylamino) -5-methylphenoxymethyl] benzoic acid H TLC: Rf 0.22 (hexane: AcOEt = 1: 1); NMR: d 8.15-8.11 (2H, m), 7.63-7.59. { 2H. m), 7.3 (2H, m). 6.92-6.88 (1 H, m), 6.81-6.70 (2H.m), 5.2 (2H, m), 4.29 (2H.s), 4.18-4.02 (1H, m). 2.35 (3H, s), 1.12 (3H, d, J = 6.5Hz), 1.04 (3H, d, J = 6.5Hz).

Example 20 (17) 4- [2- (N-t-Butylmethyl-phenylsulfonylamino) -4-methylphenoxymethyl] enzoic acid TLC: Rf 0.37 (CHC! 3: MeOH = 9: 1); NMR: d 8.08 (2H, d, J = 8Hz) .7.55 (2H, m), 7.39 (1H, m), 7.32-7.20 (4H, m), 7.17 (1H, d.J = 2Hz), 7.03 (1H, dd, J = 8 and 2Hz) .6.68 (1H, d.-HzHz) .4.90 (H, d, J-13Hz), 4.59 (1 H, d.J = 13Hz) .3.57 (1 H, d.1 J.14Hz), 3.50 (1 H, d J = 14Hz), 2.28 (3H, s), 0.88 (9H, S).

Example 20 (18) 4- [2- (N-isopropyl-methylsulfonylamino) -5- trifluoromethylphenoxymethyl] -benzoic acid TLC: Rf 0.32 (CHCl3: MeOH = 9: 1); NMR: d 8.17 (2H, d, J = 8.5Hz), 7.58 (2H, d, J = 8.5Hz), .7.43-7.23 (3H.) .5.20 (2H, s), 4.32 (1 H.m), 2.91. { 3H, s) .1.29 (3H, d, J-7HZ), 1.10 (3H, d, J = 7Hz).

Example 20 (19) 4- [2- (N-isopropyl-ethylsulfonamido) -5-trifluoromethylphenoxymethyl] benzoic acid TLC: Rf 0.36 (CHC13: MeOH = 9: 1); NMR: d 8.18 (2H, d = 8.5Hz), 7.59 (2H, d, J = 8.5Hz),, 7.43-7.23 (3H, m) .5.19 (2H, S), 4.33 (1H, m) , 3.03 (2H, q, J = 7.5Hz), 1.32-1.17 (6H, r?). 1.09 (3H, d.J = 7Hz).

Example 20 (20) 4- [2- (N-isopropyl-cyclopentylmethylsulfonylamino) -5-methylphenoxy-methyl] benzoic acid TLC: Rf 0.26 (hexane: AcOEt -1: 1); NMR: d 8.17-8.13 (2H,) .7.59-7.55 (2H, m), 7.16-7.12 (1H, m), 6.63-6.80 (2H, m), 5.13 (2H, s), 4.31 (1H, sept., J = 7Hz) .3.04-3.00 (2H, m), 2.36 (3H, s) .2.4-2.2 (1H, m), 2.0-1.8 (2H, m), 1.6-1.4 (4H, m) , 1.24 (3H, d.J = 7Hz) .1.3-1.1 (2H.m), 1.09 (3H, d, J-7Hz).

Example 20 (21) 4- [2- (N-Cyclohexylmethyl-propylsulfonylamino) -5-methylphenoxy] -benzoic acid TLC: Rf 0.43. { CHCl3: MeOH = 9: 1): NMR: d 8.16 (2H, d.J «8.6Hz), 7.54 (2H.D. J = 8.6Hz), 7.26 (1H, d, J = 8.6Hz), 6.9- 6.8 (2H, m), 5.17 (2H, s), 3.5-3.4 (2H.m), 2.9-2.8 (2H.m), 2.35 (3H, s), 2.0-1.0 (13H, m), 0.84 ( 3H, t, J = 8.0Hz), 4.0-1.0 (1H, br).

Example 20 (22) 4- [2- (N-Cyclopentylmethyl-propylsulfonylamino) -5-ethylphenoxymethyl] -benzoic acid TLC: Rf 0.38 (CHC! 3: MeOH = 9: 1); NMR: d 8.16 (2H. D, J »8.4Hz), 7.54 (2H, d.J = 8.4Hz), 7.26 (1H, d, J-8.4Hz), 6.9-6.8 (2H,), 5.17 ( 2H, s), 3.6-3.5 (2H, m), 2.9-2.8 (2H, m), 2.35 (3H, s), 2.0-1.0 (11H, m). 0.84 (3H, t, J = 7.6Hz), 6.0-4.0 (1 H, br).

Example 20 (23) 257 4- [2- (N-isopropyl-propylsulfonylamino) -5- trifluoromethylphenoxymethyl] -cinnamic acid TLC: Rf 0.32 (CHCl3: MeOH: AcOH = 100: 5: 1); NMR: d 7.80 (1 H, d, J = 16.2 Hz). 7.61 (2H, d, J = 8.6Hz), 7.51 (2H, d, J = 8.6Hz), 7.39 (1H, d, J = 8.8Hz). 7.24-7.33 (2H, m), 6.49 (1 H, d, J = 16.2Hz), 5.12 (2H. S). 4.31 (1H, m). 2.95 (2H, m), 1.77 (2H, m), 1.26 (3H, d = 6.6Hz). 1.09 (3H, d, J = 6.6Hz), 0.82 (3H.t, J-7.2Hz).

Example 20 (24) 4- [2- (N-isopropyl-pentylsulfonylamino) -5- trifluoromethylphenoxymethyl] -cinnamic acid TLC: Rf 0.27 (CHCl,: MeOH: AcOH = 100: 5: 1); NMR: d 7.80 (1H, d, J-16.0Hz). 7.61 (2H, d.J = 8.4Hz). 7.51 (2H, d, J = 8.4Hz). 7. 39 (1 H.m), 7.24-7.33 (2H, m), 6.48 (1 H, d, J-16.0Hz). "5.12 {2H, s) 4.31 (1 H, Sept, J-6.6HZ), 2.96 (2H.m) .1.72 (2H.m) .1.26 (3H, d.J = 6.6Hz) .1.05 -1.23 (7H.m), 0.83 (3H, t, J = 6.2Hz).

Example 20 (25) 4- [2- (N-isopropyl-2-furanylsulfonylamino) -5- trifluoromethylphenoxymethyl] -benzoic acid TLC: Rf 0.22. { Hexane: AcOEt -1: 1); NMR: d 8.15. { 2H, d, J-SHz), 7.59 (2H.D, J = 8Hz) .7.46 (1H, dd.J-2, 1 Hz) .7.23 (3H.m), 6.94 (1H, dd.J-3.5, 1Hz) .6.44 (1H, d.J.-3.5.2Hz), 5.18 (2H.s), 4.49 (1H, m), 1.10 (6H. dd, J = 7.2.5Hz).

Example 20 (26) 4- [2- (N-isopropyl-2-thienylsulfonylamino) -5-trifluoromethylphenoxymethyl] -benzoic acid TLC: Rf 0.24 (hexane: AcOEt = 1: 1); NMR: d 8.15 (2H, d, J «8.5Hz) .7.57 (2H.D. J = 8.5Hz), 7.54-7.51 (2H.m) .7.25 (3H, m), 7.01-6.99 (1H.m) .5.19 (2H.s), 4.49-4.44. { 1 HOUR. m), 1.10 (6H.D. J = 6.5Hz). Example 20 (27) 4- [2- (N-isopropyl-4-chlorophenylsulfonylamino) -5- trifluoromethylphenoxymethyl] enzoic acid TLC: Rf 0.43 (CHCl3: MeOH = 10: 1); NMR (DMSO-dβ): d 7.93 (2H, d.J = 8.4Hz), 7.73 (2H.D. J-8.4Hz), 7.56 (1H, s). 7.50-7.28 (6H, m), 5.22 (2H, s) .4.38 (1H, Sept.J = 6.6Hz) .1.00 (3H, d.J-6.6Hz). 0.93 (3H. d, J = 6.6Hz).

Example 20 (28) 4- [2- (N-isopropyl-4-ethylphenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid TLC: Rf 0.40 (CHCl3: MβOH = 10: 1); NMR (DMSO-d6): d7.94 (2H, d, J = 8.4Hz), 7.66 (2H, d, J = 8.4Hz) .7.55 (1H. D, J = 1HZ), 7.49 (2H, d, J = 8.4Hz) .7.39 (1H, dd, J = 8.4Hz.1Hz), 7.32. { 1 HOUR. d, J = 8.4Hz), 7.23 (2H, d.J = 8.4Hz) .5.25 (2H, s), 4.14 (1H, sept, J = 6.6Hz), 2.61 (2H, q, J = 7.4Hz) .1.14 (3H, t.J = 7.4Hz) .1.00 (3H.D, J = 6.6Hz), 0.93. { 3H, d, J = 6.6Hz).

Example 20 (29) 4- [2- (N-isopropyl-4-propylphenylsulfonylamino) -5- trifluoromethylphenoxymethyl] benzoic acid TLC: Rf0.41 (CHCl3: MeOH = 10: 1); NMR (DMSO-d "): d 7.94 (2H.D. J-8.4HZ), 7.65 (2H, D.J.-8.4HZ) .7.55 (1H.D, J = 1 Hz) .7.50 (2H. J = 8.4Hz), 7.39 (1H dd J = 8.4Hz, 1 Hz), 7.32 (1H, d J = 8.4Hz), 7.20 (2H, d, J = 8.4Hz) .5.25 ( 2H. S) .4.13 (1H.sept, J = 6.6Hz) .2.55 (2H, t.J = 7.4Hz), 1.54 (2H.tq, J = 7.4Hz.7.4Hz), 0.97 (3H, d. J = 6.6Hz), 0.90 (3H. d. J-6.6HZ), 0.84 (3H.t J-7.4Hz).

Example 20 (30) 4- [2- (N-isopropyl-4-butylphenylsulfonylamino) -5-trifluoromethylphenoxyethyl] benzoic acid TLC: Ftf0.41 (CHCJ3: MeOH-10: 1); NMR (DMSO-dβ): d7.94 (2H, d.J-8.4HZ), 7.65 (2H, d.J = ß.4Hz), 7.55. { 1 H,?, J-1HZ} , 7? 9 (2H, d, J = ß.4Hz) .7.38 (1H. dd, J = 8.4Hz, 1Hz), 7.33 (1H.D. J-8.4HZ), 7.20 (2H, d, J = 8.4Hz) .5.24 (2H, S) .4.14 (1H, Sept. J «6.6Hz) .2.57 (2H, t J» 7.4Hz), 1.49 (2H, m), 1.25 (2H.) .0.98 (3H d) J = ß.6Hz), 0.89 (3H. d J «6.BHz), 0.87 < 3H, t, J = 7.4Hz).

Example 21-21 (16) By using 2-nitrophenol or the corresponding compounds, was the title compound having the following physical data obtained by the same procedure as Reference Example 6? Example of Reference 12 - »Reference Example 2? Example 2 Example 21 4- (2-Phenylsulfonylamino-phenoxymethyl) enzoic acid TLC: Rf 0.35 (AcOEt: hexane * AcOH = 6: 13: 1); NMR (DMSO-dβ): d 12.86 (1H.brs) .9.53 (1H.brs) .7.91 (2H, d.J = 8.0Hz), 7.66 (2H, d, J = 8.0Hz), 7.52 (1H, t, J = 7.0Hz), 7.45-7.25 (5H.m), 7.08 (1H, t.J = 9.0Hz), 6.95-6.80 (2H.m), 4.91 (2H.s).

Example 21 (1) 4- [2- (4-Chlorophenylsulphonylamino) -nophenoxymethyl] benzoic acid TLC: Rf 0.39 (AcOEt: hexane; AcOH-6: 13: 1); NMR (DMSO-d6): d 12.85 (1H.brs) .9.68 (1H.brs) .7.93 (2H.d, J «8.5Hz). 7-60 (2H. d- J-ß-dHz) .7.36 (4H, d.J «8.5Hz), 7.35-7.25 (1H, m), 7.12 (1H. dt, J = 7.5.2.0Hz), 6.96-6.85 (2H, m) .4.92 (2H, s).

Example 21 (2) 4- (2-Phenylsulfonylamino-4-fluorophenoxymethyl) benzoic acid TLC: Rf 0.37 (AcOEt: hexane: AcOH = 6: 13: 1); NMR (DMSO-d6): d 12.95 (1 H. brs) .9.90 (1 H. brs) .7.90 (2H.D. J-8.5HZ), 7.72 (2H, d, J = 7.0Hz) .7.58 ( 1H, m), 7.46 (2H.t. J = 7.5Hz), 7.37 (2H.D. J = 8.5Hz) .7.10 (1H, d, J = 9.5Hz) .6.92 (2H, d.J = 7.0 Hz) .4.95 (2H, s).

Example 21 (3) 4- (2-Phenylsulfonylamino-5-fluorophenoxymethyl) enzoic acid TLC: Rf 0.42 (AcOEt: hexane: AcOH-6: 13: 1); NMR (DMSO-dβ): d 12.95 (XH, brs), 9.65 (1 H. brs) .7.91 (2H, d, J = 8.5Hz), 7.60 (2H, d, J-7.0HZ), 7.52 (1 H. t, J = 7.0Hz), 7.39 (2H.D. J = 7.5Hz), 7.35. { 2H, d, J = 7.5Hz), 7.26 (1H, dd, J = 7.0.6.5Hz) .6.84 (1H, dd, J-11.0.2.5Hz), 6.75 (1H, dt. J-8.5 , 2.5Hz), 4.90 (2H, s).

Example 21 (4) 4- (2-Phenylsulfonylamino-4-bromophenoxymethyl) benzoic acid TLC: Rf 0.25. { AcOEt: hexane: AcOH »6: 13: 1); NMR (DMSO-d: d 12.97 (1 H, brs), 9.97 (1 H brs), 7.90 (2 H, d J => 6.0 Hz), 7.69 (2 H, dd J = 7.5, 2 Hz), 7.58 (1 H, tt J-7.5, 2 Hz), 7.46 (2 H, d, J = 7.5 Hz), 7.39 (1H, d, J = 2.5Hz), 7.36 (2H.D, J = 8.0Hz). 7.27 (1 H, dd, J = 9.0, 2.5Hz), 6.89 (1H, J = 9Hz), 4.97 (2H, s).

Example 21 (5) 4- (2-Phenylsulfonylamino-5-chlorophenylthiomethyl) benzoic acid TLC: Rf 0.50 (CHO,: MeOH: AcOH-100: 5: 1); NMR: d 7.99 (2H, d, J = 8.4Hz). 7J8 (2H.m). 7.41 -7.62 (5H, m), 7.23 (1H. dd.

J-2.6. 8.8Hz). 7.08 (1H.D, J-2.6HZ). 7.05 (2H. D, J »8.6Hz). 3.71 (2H, s).

Example 21 (6) 4- (2-phenylsulfonylamino-4-methoxyphenoxymethyl) benzoic acid TLC: Rl 0.38 (CHCl3: MeOH = 17: 3); NMR (DMSO-dβ): d 7.90 (2H, d.J = 8.5Hz). 7J1 (2H, d, J = 8.0Hz). 7.64-7.35 (5H, m), 6.90-6.80 (2H.m), 6.44 (1H, d.J.-9.0 and 3.0Hz), 4.89 (2 H. s), 3.65 (3 H. m). Example 21 (7) 4- (2-f-enylsulfonylamino-4-trif luoromethylphenoxymethyl) benzoic acid TLC: Rf 0.32 (CHCl3: MeOH = 17: 3); NMR (DMSO-dβ): d 7.92 (2H d, J = 8.5Hz). 7.69 (2H, d.J-8.0Hz), 7.63-7.34 (7H, m), 7.11 (1H.D. J = 8.5Hz). 5.09 (2H, s).

Example 21 (8) 4- (2-Phenylsulfonylamino-4-methylphenoxymethyl) benzoic acid TLC: Rf 0.43 (AcOEt: hexane: AcOH = 7: 12: 1); NMR (DMSO-d5): d 7.89 (2H, d.J * 8.0Hz) .7.66 (2H, d.J = 7.0Hz), 7.60-7.48 (1H, m) .7.41 (2H, d, J = 8.0Hz) t 7.35 (2H, d.J = 8Hz) .7.11 (1H.D. J = 2.0Hz), 6.90 (1H, dd.J-ß.0, 2.0Hz), 6.76 (1H, d. , J = 8Hz), 4.88 (2H, s), 2.19 (3H, s).

Example 21 (9) 4- (2-Phenylsulfonylamino-5-methylphenoxymethyl) benzoic acid TLC: Rf 0.43 (AcOEt: hexane: AcOH »7: 12: 1); NMR (DMSO-d6): d 7.91 (2H, d.J = 8.5Hz). 7.62 (2H, d, J-7.0Hz). 7.57-7.45 (1H, m). 7.44-7.30. { 4H, m), 7.14 (1H d, J = 8.0Hz), 6J5 (1H s). 6.71 (1H d, J-ß.OHz), 4.88 (2H. S) .2.21 (3H.s).

Example 21 (10) 4- (2-Benzylsulfonylamino-5-chlorophenoxymethyl) benzoic acid TLC: Rf 0.52 (CHCl3: MeOH: AcOH-100: 5: 1); NMR (DMSO-dβ): d 7.96 (2H.D, J = 8.0Hz), 7.67 (2H.D, J = 8.0Hz), 7.29 (5H, s), 7. 21 (1 H, d, J-8.2HZ), 7.20 (1H d, J = 2.4Hz), 6.95 (1H, dd J-2.4, 8.2Hz), 5.31 (2H. S). 4.38 (2H. S).

Example 21 (11) 4- (2-Phenylsulfonylamino-5-methoxyphenoxymethyl) benzoic acid TLC: Rf 0.40 (CHClj: MeOH = 4: 1); NMR (DMSO-dβ): d 7.90 (2H, d.J = 8.5Hz), 7.59 (2H, d.J »8Hz). 7.51 (1 H, t.

J-8HZ), 7.44-7.28 (4H, m). 7.15 (1H. D, J «8.5Hz), 6.54-6.47 (2H, m), 4.86 (2H, s) .3.69 (3H.s).

Example 21 (12) 3- (2-Phenylsulfonylamino-5-chlorophenoxymethyl) benzoic acid TLC: Rf 0.48 (AcOEt: hexane: AcOH- 7: 12: 1); NMR (DMSO-dβ): d 13.03 (1H, brs) .9.80 (1H, brs), 7.98 (1H, s) .7.95-7.86 (1H, m), 7.66 (2H, d.J = 7.0Hz) .7.58-7.46 (3H.m) .7.40 (2H.t.J = 7.0Hz) .7.27 (iH, d.J = 8.5Hz), 7.07 (1H.D. J = 2.5Hz), 6.96 (1H. , dd., J-8.5, 2.5Hz), 4.96 (2H .S).

Example 21 (13) 4- (2-Phenylsulfonylamino-4-chloro-5-methylphenoxymethyl) benzoic acid TLC: Rf 0.44 (CHCl3: MeOH = 4: 1); NMR (DMSO-dβ): d 7.91 (2H.D.J = 8Hz), 7.66 (2H.D.J = 7Hz) .7.55 (1H, t, J-7.5HZ), 7.47-7.30 (4H, m ), 7.25 (1H, s), 6.98 (1H. S) .4.93. { 2H. s) .2.23 (3H. S) - Example 21 (14) 4- (2-Phenylsulfonylamino-4,5-dichlorophenoxymethyl: benzoic acid TLC: Rf 0.42 (CHCl3: MeOH -4: 1); NMR (DMSO-dβ): d 7.92 < 2H, d, J = 8Hz) .7.69 (2H.D, J = 7.5Hz) .7.58 (1H.T.J = 7.5Hz), 7.50-7.31 (5H, m), 7.26 (1H.s) , 5.01 (2H. S).

Example 21 (15) 4- (2-Phenylsulfonylamino-5-chlorophenoxymethyl) phthalic acid TLC: Rf 0.36. { CHCl 3: MeOH: AcOH-15: 4: 1); NMR (DMSO-d,): d 13.23 (2H.brs), 9.86 (1H, s), 7.74-7.58 (4H, m) .7.56-7.30 (4H,), 7.29 (ΔI, d, J = 8.5 Hz ), 7.06 (HH, d, J = 2.0 Hz, 6.98 (HH, dd, J = 8.5, 2Hz) Example 21 (16) 4- (2-Phenylsulfonylamino-5-chlorophenoxy) benzoic acid H TLC: Rf 0.46 (CHCl3: MeOH = 9: 1); NMR: d 7.99 (2H, d, J = 9.0 Hz), 7.8-7.7 (3H, m), 7.6-7.5 (HH, m), 7.5-7.3 (2H, m), 7.15 (HH, dd, J = 2.2, 8.8 Hz), 6.97 (HH, s), 6.77 (HH, d, J = 2.2 Hz), 6.65 (2H, d, J = 9.0 Hz).

Reference Example 18 4- [3- (2-nitro-5-chlorophenoxy) propyl] methyl benzoate (a) compound having OH Me Sodium boron hydride (85 mg) was added to a solution of methyl 4- (2-methoxycarbonylethyl) benzoate (1.0 g) in a mixture of THF-MeOH (12 ml; THF: MeOH = 5: 1). The mixture was stirred for 19 hours at room temperature. Ammonium chloride was added to the reaction mixture. After an excess of the reagent was decomposed, the mixture was extracted with ethyl acetate. The organic layer was washed, dried and concentrated under reduced pressure. The residue was purified over silica gel column chromatography (AcOEt: hexane = 2: 3) to give the compound having OH (692 mg) giving the following physical results. TLC: Rf 0.38 (hexane: AcOEt = 1: 1). (b) composed of the title To a solution of 2-nitro-5-chlorophenol (150 mg) in THF (2.0 ml), the compound having OH prepared above (a) (168 mg) and triphenylphosphine (227 mg) were added in a stream of argon. Then, DEAD (136 μl) was added by dripping thereto at 0 ° C. The reaction mixture was stirred for 24 hours at room temperature. After stirring, the mixture was cooled by adding ice water and extracted with ethyl acetate. After stirring, the mixture was cooled by adding ice water and extracted with ethyl acetate. The organic layer was washed, dried and concentrated under reduced pressure. The residue was purified on silica gel column chromatography (hexane: AcOEt = 10: 1 → 5: 1) to give the title compound (309 mg) giving the following physical results. TLC: Rf 0.24 (hexane: AcOEt = 5: 1).

Example 22 4- [3- (2-Phenylsulfonylamino-5-chlorophenoxy) propylbenzoic acid Using methyl 4- [3- (2-nitro-5-chlorophenoxy) propyl] benzoate (prepared in Reference Example 18). The title compound has the following physical results obtained by the same procedure as in Reference Example 12: Reference Example 2- > Example 2. TLC: Rf 0.41 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 8.04 (2H, d, J = 8.4 Hz), 7.73 (2H, m), 7.50 (2H, m), 7.40 (2H, m), 7.21 (2H, d, J = 8.2 Hz), 5.92 ( ÍH, brs), 6.91 (HH, dd, J = 2.2, 8.6 Hz), 6.67 (HH, d, J = 2.2 Hz), 3.75 (2H, t, J = 6.2 Hz), 2.70 (2H, t, J = 7.0 Hz), 1.98 (2H, na).

Example 22 (l) -22 (4) Using the corresponding diester, half ester or 4-acetylbenzoic acid, the title compounds have the following physical results obtained by the same procedure as in Example ld Example 12 Reference example 2- Example 2.

Example 22 (1) Trans-4- (2-phenylsulfonylamino-5-chlorophenoxymethyl) cyclohexane acid TLC: Rf 0.39 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 7.70 (2H, m), 7.36-7.59 (4H, m), 6.92 (1H, brs), 6.91 (H, d, J = 2.2, 8.4 Hz), 6.70 (H, d, J = 2.2 Hz ), 3.55 (2H, d, J = 6.2 Hz), 2.31 (ÍH, tt, J = 3.8 12.0 Hz), 2.00-2.19 (2H, m), 1.35-1.85 (5H, m), 0.95 (2H, m ).

Example 22 (2) Cis-4- (2-phenylsulfonylamino-5-chlorophenoxymethyl) cyclohexanoic acid TLC: Rf 0.53 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 7.70 (2H, m), 7.35-7.57 (4H, m), 6.89 (HH, dd, J = 2.2, 8.6 Hz), 6.84 (HH, brs), 6.69 (HH, d, J = 2.2 Hz ), 3.58 (2H,, J = 6.4 Hz), 2.70 (HH, m), 1.98-2.15 (2H, m), 1.43-1.80 (5H, m), 1.15-1.40 (2H, m).

Example 22 (3) 6- (2-phenylsulfonylamino-5-chlorophenoxymethyl) nicotinic acid TLC: Rf 0.40 (CHC13: MeOH: AcOH = 100: 10: 1); NMR (DMSO-de): d 9.90 (HH, brs), 9.02 (HH, d, J = 1.6 Hz), 8. 27 (HH, dd, J = 2.2, 8.4 Hz), 7.62 (2H, m), 7.49 (2H, m), 7.31-7.39 (2H, m), 7.31 (HH, d, J = 8.6 Hz), 7.08 (HH, d, J = 2.2 Hz), 7.02 (HH, dd J = 2.2, 8.6 Hz), 4.96 (2H, s).

Example 22 (4) 4- [1RS- (2-phenylsulfonylamino-5-chlorophenoxy) ethyl] benzoic acid TLC: Rf 0.48 (CHC13: MeOH = 9: 1); NMR: d 12.00-10.0 (ÍH, br), 8.00 (2H, d, J = 8.4 Hz), 7.78 (2H, d, J = 7.8 Hz), 7.7-7.4 (4H, m), 7.1-7.0 (3H , m), 6.88 (HH, dd, J = 2.2, 8.8 Hz), 6.45 (HH, s), 5.14 (HH, s), 5.14 (HH, q, J = 6.4 Hz), 1.50 (3H, d, J = 6.4 Hz).

Reference Example 19 2-nitro-5-trifluoromethylphenyl methoxymethyl ether To a solution of 2-nitro-5-trifluoromethylphenol (400 mg) in DMF (4.0 ml), sodium hydride (77 mg) was added at 0 ° C in a stream of argon. The mixture was stirred for 30 minutes. After stirring, methoxymethyl chloride (147 μl) was added dropwise thereto at 0 ° C. The reaction mixture was stirred for 20 minutes. The reaction mixture was cooled by adding ice water and extracted with ethyl acetate. The layer containing ethyl acetate was washed, dried and concentrated under reduced pressure. The residue was purified over silica gel column chromatography (hexane: AcOEt = 20: 1) to give the title compound (353 mg) giving the following physical results. TLC: Rf 0.44 (hexane: AcOET = 10: 1); Reference Example 20 2-Amino-5-trifluoromethylphenyl methoxymethyl ether To a solution of 2-nitro-5-trifluoromethylphenyl methoxymethyl ether (353 mg, prepared in Reference Example 19) in MeOH (3.5 ml), 10% Pd-C (30 mg) was added in an argon stream. . The mixture was stirred vigorously at room temperature under a hydrogen atmosphere. The reaction mixture was filtered through celite and concentrated under reduced pressure to give the title compound (313 mg) giving the following physical results. TLC: Rf 0.44 (hexane: AcOET = 3: 1); Reference Example 21 N- (2-methoxymethoxy-4-trifluoromethyl-phenyl) -phenylsulfonylamino methyl acetate Using the methoxymethyl ether of 2-amino-5-trifluoromethylphenyl (313 mg, prepared in Reference Example 20). The title compound has the following physical results obtained by the same procedure as in Reference Example 2- Example 17. TLC: Rf 0.66 (benzene: acetone = 9: 1).

Reference Example 22 1, l-dimethyl-2- [N- (2-methoxymethoxy-4-trifluoromethyphenyl) phenylsulfonyl-amino] ethanol To a solution of N- (2-methoxymethoxy-4-trifluoromethylphenyl) phenylsulfonylamino methyl acetate (525 mg, prepared in Reference Example 21). In THF (6.0 ml), methylmagnesium bromide (2.67 ml) was added dropwise in an argon stream at 0 ° C. The mixture was stirred for 30 minutes. The reaction mixture was cooled with ice water, extracted with ethyl acetate, washed, dried and concentrated under reduced pressure. The residue was purified over silica gel column chromatography (hexane: AcOEt = 2: 1) to give the title compound (380 mg) giving the following physical results. TLC: Rf 0.26 (hexane: AcOET = 2: 1).

Reference Example 23 1, l-dimethyl-2- [N- (2-hydroxy-4-trifluoromethyl-phenyl) -phenylsulfonylamino] ethanol To a solution of 1,1-dimethyl-2- [N- (2-methoxymethoxy-4-trifluoromethyphenyl) -phenylsulfonylamino] -ethanol (380 mg, prepared in Reference Example 22) in THF (4.0 ml) was added 6N HCl (0.8 ml). The mixture was stirred for 2 days at room temperature. The reaction mixture was diluted with ethyl acetate, washed, dried and concentrated under reduced pressure. The residue was purified over silica gel column chromatography (hexane: AcOEt = 2: 1) to give the title compound (291 mg) giving the following physical results.

TLC: Rf 0.29 (benzene: acetone = 9: 1) Reference Example 24 2- (N-isopropyl-phenylsulfonylamino) -5-trif luoromethylphenol Using the methoxymethyl ether of 2-amino-5-trifluoromethylphenyl (prepared in Reference Example 20). The title compound has the following physical results obtained by the same procedure as in Reference Example 2-Example 17: Reference Example 23. TLC: Rf 0.57 (hexane: AcOEt = 5: 2).

EXAMPLE 23 4- [2- [N- (2-Hydroxy-2-methylpropyl) phenylsulfonylamino] -5-trifluoromethyl-phenoxymethyl] enzoic acid Using 1, 1-dimethyl-2- [N- (2-hydroxy-4-trifluoromethylphenyl) -phenylsulfonylamino] ethanol (prepared in Reference Example 23), the title compound has the following physical results obtained by the same procedure as in Reference Example 6-Example 2. TLC: Rf 0.48 (CHC13: MeOH: AcOH = 100: 5: 1); NMR (CD3COCD3): or 8.03 (2H, brd, J = 8.2 Hz), 7.47-7.66 (4H, m), 7.30-7.47 (6H, m), 5.21 (HH, m), 4.89 (HH, m), 3.79 (2H, s), 1.20 (6H, s).

Example 23 (1) -23 (3) Using 2- [N- (2-hydroxy-2-methylpropyl) -phenylsulfonylamino] -5-trifluoromethylphenol (prepared in Reference Example 23). The title compounds have the following physical results obtained by the same procedure as in Reference Example 6-Example 2.

Example 23 (1) 4- [2- [N- (2-Hydroxy-2-methylpropyl) phenylsulfonylamino] -5-trifluoromethylphenoxymethyl] cinnamic acid.

H TLC: Rf 0.53 (CHC13: MeOH: 9: 1); NMR: d 7.80 (HH, d, J = 16.0 Hz), 7.54 (6H, m), 7.35 (6H, m), 6.49 (HH, d, J = 16.0 Hz), 4.99 (HH, m), 4.81 ( ÍH, m), 3.63 (2H, m), 1.21 (6H, s).

Example 23 (2) 4- [2- [N- (2-hydroxy-2-methylpropii; phenylsulfonylamino] -5-methylphenoxymethyl] benzoic acid TLC: Rf 0.45 (CHC13: MeOH 9: 1); NMR: d 8.09 (2H, d, J = 8.4 Hz), 7.60 (2H, m), 7.28-7.44 (5H, m), 7.06 (H, m), 6.71 (2H, m), 5.00 (H, d) , J = 12.8 Hz), 4.74 (HH, d, J = 12.8 Hz), 3.69 (HH, d, J = 14.2 Hz), 3.57 (HH, d, J = 14.2 Hz), 2.33 (3H, s), 2.13 (ÍH, s), 1.25 (3H, bs), 1.19 (3H, bs).

Example 23 (3] 4- [2- [N- (2-Hydroxy-2-methylpropyl) -2-furanylsulfonylamino] -5-trifluoromethylphenoxymethyl] benzoic acid OH TLC: Rf 0.42 (CHC13: MeOH = 9: 1); NMR: d 8.15 (2H, d, J = 8.4 Hz), 7.52 (2H, d, J = 8.4 Hz), 7.21-7.34 (4H, m), 6.82 (HH, m), 6.38 (HH, m), 5.12 (2H, m), 3.76 (2H, m), 2.12 (ÍH, s), 1.23 (6H, bs).

Example 24 4- [2- (N-isopropyl-phenylsulfonylamino) -5-trif luoromethyl-phenoxymethyl] -phenoxy-acetic acid OOH Using 2- (N-isopropyl-phenylsulfonylamino] -5-trifluoromethylphenol (prepared in Reference Example 24), the title compound has the following physical results obtained by the same procedure as in Reference Example 18 (b) - Example 2. TLC: Rf 0.39 (AcOEt: hexane: AcOH = 9: 10: 1); NMR: d 7.80 (2H, d, J = 7.5 Hz), 7.49 (ΔH, t, J = 7.5 Hz), 7.40 -7.20 (7H, m), 6.95 (2H, d, J = 8.2 Hz), 4.98 (2H, s), 4.72 (2H, s), 4.28 (ÍH, qn, J = 6.5 Hz), 1.06 (3H, d, J = 6.5 Hz), 1.01 (3H, d, J = 6.5 Hz).

Example 24 (1) -24 (10) Using the corresponding compounds, the title compounds have the following physical results obtained by the same procedure as in Reference Example 18 (b) - »Example 2.

Example 24 (1) - [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] -thiophene-2-carboxylic acid TLC: Rf 0.54 (CHC13: MeOH: AcOH = 90: 9: 1); NMR: d 7.9-7.7 (3H, m), 7.6-7.3 (3H, m), 7.3-7.2 (3H, m), 7.16 (IH, d, J = 4.0 Hz), 5.20 (2H, s), 4.5 -4.3 (ÍH, m), 1.10 (3H, d, J = 3.8 Hz), 1.32 (3H, d, J = 3.8 Hz).

Example 24 (2) - [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] furan-2-carboxylic acid TLC: Rf 0.17 (CHC13: MeOH = 5: 1); NMR: d 7.76 (2H, d, J = 8.4 Hz), 7.54-7.29 (3H, m), 7.29-7.13 (4H, m), 6.52 (H, m), 5.00 (2H, s), 4.31 (H) , m), 0.98 (6H, m).

Example 24 (3) 4- [2- (N-isopropyl-phenylsulfonylamino) -5-methylphenoxymethyl] phenoxy-acetic acid TLC: Rf 0.09 (AcOEt); NMR: d 7.81 (2H, d, J = 7.5 Hz), 7.50-7.30 (5H, m), 7.00-6.91 (3H, m), 6.82-6.73 (2H, m), 4.91 (2H, s), 4.71 (2H, s), 4.27 (ÍH, sept., J = 7 Hz), 2.36 (3H, s), 1.05 (3H, d, J = 7 Hz), 1.01 (3H, d, J = 7 Hz).

Example 24 (4) 5- [2- (N-isopropyl-phenylsulfonylamino) -5-methylphenoxymethyl] thiophene-2-carboxylic acid TLC: Rf 0.30 (CHC13: MeOH = 9: 1); NMR: d 7.9-7.7 (3H, m), 7.5-7.4 (HH, m), 7.4-7.3 (2H, m), 7.12 (HH, d, J = 3.6 Hz), 7.01 (HH, d, J = 8.2 Hz), 6.9-6.7 (2H, m), 5.12 (2H, s), 4.5-4.3 (ÍH, m), 2.38 (3H, s), 1.51 (3H, d, J = 2.4 Hz), 1.05 ( 3H, d, J = 2.4 Hz).

Example 24 (5) 4- [2- (N-isopropyl-phenylsulfonylamino) -5-methylphenoxymethyl] cinnamic acid TLC: Rf 0.39 (hexane AcOEt = 1: 2); NMR: d 7.86-7.78 (3H, m), 7.60-7.26 (7H, m), 6.97 (H, d, J = 8 Hz), 6.80-6.74 (2H, m), 6.48 (H, d, J = 16 Hz), 5.01 (2H, s), 4.36 (ÍH, sept., J = 6.5 Hz), 1.05 (6H, d, J = 6.5 Hz).

Example 24 (6) 4- [2- (N-isopropyl-phenylsulfonylamino) -5-chlorophenoxymethyl] phenoxy-acetic acid H TLC: Rf 0.10 (CHC13: MeOH = 10: 1); NMR: d 7.80-7.76 (2H, m), 7.52-7.44 (HH, m), 7.35-7.26 (4H, m), 7.05-6.91 (5H, m), 4.91 (2H, s), 4.72 (2H, s), 4.28 (ÍH, sept., J = 7 Hz), 1.05 (3H, d, J = 7 Hz), 1.00 (2H, d J = 7 Hz).

Example 24 (7) 4- [2- (N-isopropyl-phenylsulfonylamino) -5-chlorophenoxymethyl] cinnamic acid OH TLC: Rf 0.31 (hexane: AcOEt = 1: 1); NMR: d 7.85-7.77 (2H, m), 7.60-7.35 (7H, m), 7.05-6.90 (3H, m), 6.48 (H, d, J = 16 Hz), 5.01 (2H, s), 4.36 (ÍH, step., J = 6.5 Hz), 1.04 (6H, d, J = 7 Hz).

Example 24 (8) 5- [2- (N-isopropyl-phenylsulfonylamino) -5-chlorophenoxymethyl] thiophene-2-carboxylic acid TLC: Rf 0.42 (CHC13: MeOH = 9: 1); NMR: d 7.8-7.7 (3H, m), 7.5-7.3 (3H, m), 7.2-6.9 (4H, m), 5.15 (IH, d, J = 13.2 Hz), 5.08 (IH, d, J = 13.2 Hz), 4.5-4.3 (HH, m), 5.5-4.0 (HH, br), 1.08 (3H, d, J = 2.6 Hz), 1.05 (3H, d, J = 2.6 Hz).

Example 24 (9) - [2- (N-isopropyl-phenylsulfonylamino) -5-chloromethylphenoxymethyl] furan-2-carboxylic acid TLC: Rf 0.37 (CHC13: MeOH = 9: 1); NMR: d 7.9-7.7 (2H, m), 7.6-7.4 (3H, m), 7.31 (ΔH, d, J = 3.4 Hz), 7.0-6.9 (3H, m), 6.63 (ΔI, d, J = 3.4 Hz), 5.03 (HH, d, J = 13.2 Hz), 4.96 (HH, d, J = 13.2 Hz), 5.5-4.5 (HH, br), 4.4-4.2 (HH, m), 1.03 (6H, d, J = 6.6 Hz).

Example 24 (10) 4- [2- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenoxy] -ethyl] benzoic acid TLC: Rf 0.40 (CHC13: MeOH = 9: 1); NMR: d 8.07 (2H,, d, J = 8.5 Hz), 7.83 (2H, d, J = 7 Hz), 7.65-7.45 (5H, m), 7.39 (2H, d, J = 8.5 Hz), 7.25 -7.08 (3H, m), 4.37 (HH, m), 4.25-4.05 (2H, m), 3.08 (2H, d, J = 7 Hz), 0.99 (3H, d, J = 6.5 Hz), 0.84 ( 3H, d, J = 6.5 Hz).

Example 25 2-Methoxy-4- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid Using 2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenol (prepared in Reference Example 24). The title compound has the following physical results obtained by the same procedure as in Reference Example 6- > Example 2. TLC: Rf 0.49 (CHC13: MeOH = 9: 1); NMR: d 11.0-10.6 (ÍH, br), 8.21 (ÍH, d, J = 7.8 Hz), 7.9-7.8 (2H, m), 7.71 (ÍH, d, J = 0.6 Hz), 7.7-7.4 (3H , m), 7.3-7.2 (2H, m), 7.2-7.1 (HH, m), 7.00 (1H, d, J = 7.8 Hz), 5.22 (2H, s), 4.6-4.4 (HH, m), 4.18 (3H, s), 1.08 (3H, d, J = 6.6 Hz), 0.92 (3H, d J = 6.6 Hz).

Example 26 2-Hydroxy-4- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid Using 2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenol (prepared in the Reference Example 24). The title compound has the following physical results obtained by the same procedure as in Reference Example 6: Reference Example 23 Example 2. TLC: Rf 0.56 (CHC13: MeOH: AcOH = 90: 9: 1); NMR: d 1051 (ÍH, s), 7.95 (ÍH, d, J = 8.0 Hz), 7.9-7.8 (2H, m), 7.6-7.4 (3H, m), 7.3-7.2 (3H, m), 7.1-7.0 (2H, m), 5.05 (2H, s), 4.5-4.3 (HI, m), 1.09 (3H, d, J = 5.0 Hz), 1.06 (3H, d J = 5.0 Hz).

Example 26 (l) -26 (2) Using the corresponding compounds, the title compounds have the following physical results obtained by the same procedure as in Reference Example 6- »Reference Example 23-? Example 2.

Example 26 (1) 2-Hydroxy-4- [2- (N-isopropyl-phenylsulfonylamino) -5-methylphenoxymethyl] benzoic acid TLC: Rf 0.20 (CHC13: MeOH = 17: 3); NMR: d 10.50 (HH, s), 7.92 (HH, d, J = 8.5 Hz), 7.83 (2H, m), 7.54-7.32 (3H, m), 7.05-6.93 (3H, m), 6.81-6.72 (2H, m), 4.97 (2H, s), 4.42 (HH, m), 2.35 (3H, s), 1.13-0.98 (6H, m).

Example 26 (2) 2-Hydroxy-4- [2- (N-isopropyl-phenylsulfonylamino) -5-chlorophenoxymethyl] benzoic acid TLC: Rf 0.21 (CHC13: MeOH = 9: 1); NMR: d 7.93 (ÍH, d, J = 8.0 Hz), 7.9-7.7 (2H, m), 7.6-7.3 (3H, m), 7.1-6.9 (5H, m), 4.97 (2H, s), 4.5 -4.3 (ÍH, m), 3.0-2.0 (2H, br), 1.07 (3H, d, J = 6.2 Hz), 1.04 (3H, d, J = 6.2 Hz).

Reference Example 25 4-Phenylsulfonylamino-3-nitrobenzotrifluoride To a solution of 4-amino-3-nitrobenzotrifluoride (3.09 g) was added sodium hydride THF (660 g). The mixture was stirred for 30 minutes at room temperature. After stirring, benzenesulfonyl chloride (3.18 g) was added thereto. The mixture was stirred for 2 hours at room temperature. In addition, sodium hydride (420 mg) was added thereto. The reaction mixture was stirred for 1 hour. The reaction mixture was acidified by adding an aqueous solution of ammonium chloride and extracted with ethyl acetate. ethyl. The organic layer was washed, dried, filtered and concentrated to give the title compound (4.86 mg) giving the following physical results. TLC: Rf 0.31 (hexane: AcOET = 3: 1); Reference Example 26 4-Phenylsulfonylamino-3-aminobenzotrifluoride Using the 4-phenylsulfonylamino-3-nitrobenzotrifluoride (2.4 g, prepared in Reference Example 25), the title compound (1.7 g) has the following physical results obtained by the same procedure as in Reference Example 12. TLC: Rf 0.17 (hexane: AcOEt = 3: 1).

Example 27 Methyl 4- (2-phenylsulfonylamino-5-trifluoromethylphenylaminomethyl) benzoate To a solution of 4-phenylsulfonylamino-3-aminobenzotriafluoride (100 mg, prepared in Reference Example 26) and methyl ester of terephthalic acid aldehyde (78 mg) in MeOH (2 ml), acetic acid (1.5 ml) was added. The mixture was stirred for 2 hours at room temperature. After stirring, a solution of sodium cyanoborohydride (30 mg) in MeOH (2 ml) was added. The mixture was stirred for 2 hours at room temperature. The reaction solution was extracted with H20-AcOEt, washed, dried, filtered and concentrated. The precipitate was washed with hexane to give the title compound (146 mg) giving the following physical results. TLC: Rf 0.27 (hexane: AcOET = 2: 1); NMR: d 8.02 (2H, m), 7.76 (2H, m), 7.6-7.4 (5H, m), 6.74-6.70 (2H, m), 6.55-6.50 (HH, m), 6.02 (HH, bs) , 5.35 (ÍH, m), 4.40 (2H, m), 3.92 (3H, s).

Example 28 4- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenylaminomethyl] -benzoic acid Using methyl 4- (2-phenylsulfonylamino-5-trifluoromethylphenylaminomethyl) -benzoate (prepared in Example 27). The title compound has the following physical results obtained by the same procedure as in Example 17- »Example 2.

TLC: Rf 0.45 (hexane: AcOEt = 1: 1). NMR: d 8.10 (2H, d, J = 8.5 Hz), 7.8-7.7 (2H, m), 7.6-7.4 (5H, m), 6.8-6.7 (2H, m), 6.7-6.6 (ÍH, m) , 5.34 (ÍH, m), 4. 69 (ÍH, sept., J = 7 Hz), 4.45 (2H, d, J = 6 Hz), 1.15 (3H, d, J = 7 Hz), 1.01 (3H, d, J = 7 Hz).

Example 29 4- [N-Methyl- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenyl] aminomethyl] benzoate methyl 4- [Methyl-methyl- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenylaminomethyl] benzoate (200 mg) was prepared by the same procedure as in Example 17, using 4- (2-phenylsulfonylamino) -5-trifluoromethylphenylaminomethyl) benzoate (prepared in Example 27). It was dissolved in DMF (5 ml). Sodium hydride (64 mg) and methyl iodide (200 μl) were added thereto. The mixture was stirred for 24 hours at 60 ° C. The reaction mixture was extracted with H20-AcOEt, washed, dried, filtered and concentrated under reduced pressure. The residue was purified in silica gel column chromatography (hexane: AcOEt = 5: 1) to give the title compound (105 mg) giving the following physical results. TLC: Rf 0.54 (CH2C12); NMR: d 8.0 (2H, m), 7.9 (2H, m), 7.6-7.5 (3H, m), 7.4 (2H, m), 7.4-7.2 (2H, m), 7.0 (1H,), 4.6- 4.3 (2H, m), 3.92 (3H, m), 2.72 (3H, s), 1.2 (3H, m), 0.8 (3H, m).

Example 30 4- [N-Methyl- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenyl] aminomethyl] benzoic acid Using methyl 4- [N-methyl- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenyl] aminomethyl] -benzoate (prepared in Example 29), the title compound has the following physical results obtained by the same procedure as in Example 2. TLC: Rf 0.45 (hexane: AcOEt = 1: 1).

NMR: d 8.09 (2H, d, J = 8 Hz), 7.9 (2H, m), 7.7-7.4 (5H, m), 7.2 (2H, m), 7.0 (HI, m), 4.6-4.4 (3H , m), 2.75 (3H, s), 1.26 (3H, d, J = 7 Hz), 0.85 (3H, d, J = 7 Hz).

Reference Example 27 Methyl 2-t-butoxycarbonylamino-5-trifluoromethylbenzoate 4-t-Butoxycarbonylaminobenzotrifluoride (3.90 g) was dissolved in THF. At 50 ° C, tert-butyl lithium (30 ml) was added dropwise thereto. The mixture was stirred for 3 hours while maintaining it at 50 ° C. Carbon dioxide gas was bubbled into this mixture under stirring (the temperature was increased to about -30 ° C). The solvent was removed by distillation. The extraction of the residue was carried out again with a solution of the 2N NaOH-ether mixture. The aqueous layer was acidified by adding 2N HCl, extracted with ether, washed, dried, filtered and concentrated after the combination of said ether-containing layer to give the crude compound. Such a crude compound was dissolved in ether. A solution of diazomethane in ether was added thereto until the reaction solution became yellow. The reaction solution was concentrated and purified by column chromatography on silica gel hexane: AcOEt = 20: 1: 1: 1) to give the title compound (3.80 g) giving the following physical results. TLC: Rf 0.70 (hexane: AcOET = 3: 1).

Reference Example 28 Methyl 2-amino-5-trifluoromethylbenzoate To a solution of methyl 2-t-5-butoxycarbonylamino-5-trifluoromethylbenzoate (3.80 g, prepared in Reference Example 27) in methylene chloride (30 ml), trifluoroacetic acid (6 ml) was added. The mixture was stirred for 8 hours at room temperature. The solvent was distilled off azeotropically three times with toluene. An aqueous sodium hydrogen carbonate solution was added to the reaction mixture to neutralize. The mixture was extracted with ethyl acetate, washed, dried, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane: AcOEt = 5: 1) to give the title compound (2.35 mg) giving the following physical results. TLC: Rf 0.20 (hexane: AcOET = 5: 1).

Example 31 4- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylbenzoylamino] benzoic acid Using the 2-amino-5-trifluoromethylbenzoate (prepared in Reference Example 28), the title compound has the following physical results obtained by the same procedure as in Reference Example 2 - »Example of reference 3? Example 2 . TLC: Rf 0.25 (hexane: AcOEt = 1: 2); NMR: d 10.01 (ÍH, s), 8.18-8.14 (3H, m), 7.93 (8H, m), 6. 64 (ÍH, d, J = 8 Hz), 4.67 (ÍH, sept., J = 6.5 Hz), 1.09 (3H, d, J = 6.5 Hz), 0.86 (3H, d, J = 6.5 Hz).

Reference Example 29 4- [2- [N- [1, 3-bis (t-butyldimethylsilyloxy) prop-2-yl] -phenylsulfonylamino] -5-trifluoromethylphenoxymethyl] methylbenzoate (a) compound (intermediate) that has 1,3-diOTBs OH TBsO OTBs To a solution of glycerol (2 g) in DMF (15 ml), a solution of t-butyl-dimethylsilyl chloride (6.5 g) and imidazole (3.3 g) in DMF (8 ml) was slowly added dropwise at 0 ° C. ). The reaction mixture was stirred for 3 hours at room temperature. The reaction mixture was poured into water, extracted with a solution of the AcOEt-hexane mixture (AcOEt: hexane = 1: 1) and purified by column chromatography on silica gel to give the compound having 1.3- diOTBs (5.8 g) giving the following physical results. TLC: Rf 0.5 (hexane: AcOET = 9: 1). (b) composed of the title Using methyl 4- (2-phenylsulfonylamino-5-trifluoromethylphenoxymethyl) benzoate (180 mg, prepared in Example 15) and the compound having 1,3-diOTBs prepared above in (a) (247 mg), the title compound (200 mg) gives the following physical results obtained by the same procedure as in Example 19. TLC: Rf 0.28 (hexane: AcOEt = 9: 1).

Example 32 4- [2- [N- (1, 3-dihydroxyprop-2-yl] -phenylsulfonylamino] -5-trifluoromethylphenoxymethyl] methylbenzoate To a solution of methyl 4- [2- [N- [1,3-bis (t-butyldimethylsilyloxy) prop-2-yl] -phenylsulfonylamino] -5-trifluoromethylphenoxymethyl] benzoate (200 mg, prepared in Example 29) in THF (3 ml), a solution of tetrabutylammonium fluoride (0.57 ml) in THF (IM) was added. The solution was stirred for 3 hours at room temperature. Water was added to the reaction compound. The mixture was extracted with ethyl acetate, washed, dried and purified by column chromatography on silica gel (110 mg) giving the following physical results. TLC: Rf 0.50 (CH2C12: MeOH = 9: 1); NMR: d 8.08 (2H, d, J = 8.2 Hz), 7.78 (2H, d, J = 7.2 Hz), 7.70-7.24 (8H, m), 5.14 (ÍH, d, J = 12.0 Hz), 5.06 ( HH, d, J = 12.0 Hz), 4.50-4.30 (HH, m), 3.93 (3H, s), 3.80-3.20 (4H, m), 2.72 (HH, dd, J = 3.6, 18.2 Hz).

Example 33 4- [2- [N- (1, 3-dihydroxyprop-2-ii; phenylsulfonylamino] -5-trifluoromethylphenoxymethyl] benzoic acid Using methyl 4- [2- [N- (1, 3-dihydroxyprop-2-yl) -phenylsulfonylamino] -5-trifluoromethylphenoxymethyl] benzoate (prepared in Example 32), the title compound has the following physical results obtained by the same procedure as in Example 2. TLC: Rf 0.51 (AcOEt: AcOH = 99: 1); NMR: d 8.13 (2H, d, J = 8.4 Hz), 7.8-7.7 (2H, m), 7.6-7.2 (8H, m), 5.17 (HI, d, J = 11.4 Hz), 5.08 (HI, d) , J = 11.4 Hz), 4.5-4.3 (HH, m), 3.6-3.5 (2H, m), 3.4-3.2 (2H, m).

Example 34 4- [2- [N- (1, 3-dimethoxyprop-2-yl) -phenylsulfonylamino] 5-trifluoromethylphenoxymethyl] benzoic acid Using methyl 4- [2- [N- (1, 3-dihydroxyprop-2-yl) -phenylsulfonylamino] -5-trifluoromethylphenoxymethyl] benzoate (prepared in Example 32), the title compound has the following physical results obtained by the same procedure as in Reference Example 19 Example 2. TLC: Rf 0.57 (CHC13: MeOH = 9: 1); NMR: d 8.18 (2H, d, J = 8.2 Hz), 7.8-7.7 (2H, m), 7.63 (2H, d, J = 8.2 Hz), 7.6-7.4 (3H, m), 7.3-7.2 (3H , m), 5.18 (2H, s), 4.5-4.4 (1H, m), 3.7-3.6 (HI, m), 3.5-3.0 (3H, m), 3.09 (3H, s), 3.04 (3H, s) ).

Reference example 30 2- (N- (isopropyl-methylsulfonylamino) -5-trifluoromethylphenyl methoxymethyl ether Using the methoxymethyl ether of 2-amino-5-trifluoromethylphenyl and mesyl chloride, the title compound has the following physical results obtained by the same procedure as in Reference Example 2 Example 17.

TLC: Rf 0.40 (hexane: AcOEt = 2: 1).

Reference Example 31 2- (N- (isopropyl-2-hydroxyhexylsulfonylamino) -5-trifluoromethylphenyl methoxymethyl ether To a solution of 2- (N- (isopropyl-methylsulfonylamino) -5-trifluoromethylphenyl methoxymethyl ether (135 mg; prepared in Reference Example 30) in THF (3.0 ml), hexamethylphosphoramide (420 μl) was added in a stream of argon, n-butyl lithium (742 μl) was added dropwise thereto at -78 ° C. The mixture was stirred for 1.5 hours, a solution of valeraldehyde (102 mg) was added dropwise to the mixture. in THF (1.0 ml) The mixture was stirred for 30 minutes The mixture was extracted with ethyl acetate, washed, dried and concentrated under reduced pressure The residue was purified on silica gel column chromatography (hexane: AcOEt = 4: 1) to give the title compound (69 mg) giving the following physical results.

TLC: Rf 0.49 (hexane: AcOET = 2: 1).

Reference Example 32 2- (N-isopropyl-1-hexenylsulfonylamino) -5-trifluoromethylphenyl methoxymethyl ether To a solution of 2- (N-isopropy1-2-hydroxyhexylsulfonylamino) -5-trifluoromethylphenyl methoxymethyl ether (160 mg, prepared in Reference Example 31) in methylene chloride (2.0 ml), triethylamine (104 μl) was added. and mesyl chloride (35 μl) in a stream of argon at 0 ° C. The mixture was stirred for 10 minutes. 1-5-diazabicyclo [5, 4, 0] undecene (134 μl) was added to the mixture. The mixture was stirred for 2 hours at room temperature. To the reaction mixture, diluted HCl was added. The mixture was extracted with ethyl acetate, washed, dried and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane: AcOEt = 8: 1) to give the title compound (140 mg) giving the following physical results.

TLC: Rf 0.37 (hexane: AcOET = 3: 1) Example 35 4- [2- (N-isopropyl-1-hexenylsulfonylamino) -5-trifluoromethylphenoxymethyl] -benzoic acid Using the methoxymethyl ether 2- (N-isopropyl-1-hexenylsulfonylamino) -5-trifluoromethylphenyl (prepared in Reference Example 32), the title compound has the following physical results obtained by the same procedure as in Reference Example 23 - > Reference Example 6- > Example 2. TLC: Rf 0.44 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 8.19 (2H, d, J = 8.2 Hz), 7.62 (2H, d, J = 8.2 Hz), 7.22-7.45 (3H, m), 6.68 (ÍH, td, J = 7.0, 15.0 Hz), 6.09 (HH, td, J = 1.4, 15.0 Hz), 5.19 (2H, s), 4.15 (HH, m), 1.97 (2H, m), 1.16-1.40 (7H, m), 1.03 (3H, d, J = 6.8 Hz), 0.86 (3H, m).

Reference Example 33 4- (2-Cyclopentylsulfinylamino-5-trifluoromethylphenoxymethyl) -methylbenzoate To a solution of methyl 4- (2-amino-5-trifluoromethylphenoxymethyl) benzoate (300 mg) in methylene chloride (3.0 ml), pyridine (187 μl) and triphenylphosphine (315 mg) were added in a stream of argon. Cyclopentylsulfonyl chloride (202 mg) was added dropwise thereto at 0 ° C. The mixture was stirred for 6 hours at room temperature. Water was added. The mixture was extracted with ethyl acetate, washed, dried and concentrated under reduced pressure. The residue was purified on silica gel column chromatography (hexane: AcOEt = 2: 1: 1: 1) to give the title compound (309 mg) having the following physical results. TLC: Rf 0.23 (hexane: AcOET = 2: 1).

Example 36 Methyl 4- (2-cyclopentylsulfonylamino-5-trifluoromethylphenoxymethyl) benzoate OOMe To a solution of methyl 4- (2-cyclopentylsulfinylamino-5-trifluoromethylphenoxymethyl) benzoate (305 mg, prepared in Reference Example 33.) in methylene chloride (4.0 ml), meta-chloroperbenzoic acid (456 mg) was added. at 0 ° C. The mixture was stirred for 1 hour. The reaction mixture was diluted with ethyl acetate, washed, dried over and concentrated under reduced pressure to give the title compound (317 mg) having the following physical data. TLC: Rf 0.56 (hexane: AcOEt = 2: 1); NMR: d 8.11 (2H, d, J = 8.6 Hz), 7.73 (HH, brd, J = 9.0 Hz9, 7.47 (2H, d, J = 8.6 Hz), 7.25 (HH,), 7.15 (HH, d, J = 1.4Hz), 6.95 (ÍH, brs), 5.21 (2H, s), 3.95 (3H, s), 3. 54 (ÍH, m), 1.53-2.16 (8H, m).

Example 37 4- [2- (N-isopropyl-cyclopentylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid H Using methyl 4- (2-cyclopentylsulfonylamino-5-trifluoromethylphenoxymethyl) benzoate (prepared in Example 36), the title compound (317 mg) having the following physical data was obtained by the same procedure as in Example 17 Example 2. TLC: Rf 0.40 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 8.17 (2H, d, J = 8.4Hz), 7.61 (2H, d, J = 8.4Hz), 7.38 (ÍH, d, J = 8.0Hz), 7.28 (2H, m), 5.17 (2H, s), 4.36 (ÍH, sept, J = 6.6Hz), 3.51 (ÍH, m), 1.84-2.10 (3H, m), 1.61-1.84 (3H, m), 1.30-1.56 (2H, m), 1.24 (3H, d, J = 6.6 Hz), 1.08 (3H, d, J = 6.6Hz).

Example 37 (1) -37 (7) Using the corresponding compounds, the title compounds having the following physical data were obtained by the same procedure as in Reference Example 33- > Example 36- »Example 17-» Example 2.

Example 37 (1) 4- [2- (N-isopropyl-cyclohexylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid TLC: Rf 0.27 (AcOEt: hexane = 1: 1); NMR: d 8.17 (2H, d, J = 8Hz), 7.61 (2H, d, J = 8Hz), 7.42 (IH, d, J = 8Hz), 7.28 (IH, d, J = 8Hz), 7.26 (IH) , s), 5.19 (2H, s), 4.32 (HH, m), 2.88 (HH, m), 2.25-2.04 (2H, m), 1.92-1.35 (5H, m), 1.30-0.60 (9H, m ).

Example 37 (2) 4- [2- (N-isopropyl-cyclohexylsulfonylamino) -5-methylphenoxymethyl] benzoic acid TLC: Rf 0.37 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 8.15 (2H, d, J = 8.6Hz), 7.59 (2H, d, J = 8.6Hz), 7.17 (HH, d, J = 8.4Hz), 6.82 (2H, m), 5.13 (2H, s), 4.32 (HH, m), 2.88 (HH, tt, J = 3.2, 12.0Hz), 2.35 (3H, s), 2.15 (2H, m), 1.36-1.90 (5H, m), 1.23 (3H , d, J = 6.6Hz), 1.12 (3H, d, J = 6.6Hz), 0.82 (ÍH, m).

Example 37 (3j 4- [2- (N-isopropyl-isopropylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid TLC: Rf 0.34 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 8.18 (2H, d, J = 8.4Hz), 7.60 (2H, d, J = 8.4 Hz), 7.42 (1H, d, J = 8.0Hz), 7.23-7.33 (2H, m), 5.17 ( 2H, s), 4.32 (ÍH, sept, J = 6.6Hz), 3.17 (ÍH, sept, J = 7.0Hz), 1.32 (3H, d, J = 7.0Hz), 1.25 (3H, d, J = 6.6 Hz), 1.19 (3H, d, J = 7.0Hz), 1.09 (3H, d, J = 6.6Hz).

Example 37 (4) 4- [2- (N-isopropyl-isopropylsulfonylamino) -5-methylphenoxymethyl] benzoic acid TLC: Rf 0.46 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 8.15 (2H, d, J = 8.2Hz), 7.57 (2H, d, J = 8.2Hz), 7.16 (ÍH, d, J = 8.4Hz), 6.81 (2H, m), 5.11 (2H, s), 4.31 (ÍH, sept, J = 6.6Hz), 3.16 (ÍH, sept, J = 6.8 Hz), 2.36 (3H, s), 1.31 (3H, d, J = 6.8Hz), 1.23 (3H, d, J = 6.6Hz), 1.18 (3H, d, J = 6.6Hz), 1.08 (3H, d, J = 6.8Hz).

Example 37 (5) 4- [2- (N-isopropyl-isopropylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid TLC: Rf 0.20 (AcOEt: hexane = 1: 1); NMR: d 7.79 (HH, d, J = 15Hz), 7.61 (2H, d, J = 8Hz), 7.50 (2H, d, J = 8Hz), 7.40 (HH, d, J = 8Hz), 7.34-7.20 (2H, m), 6.48 (HH, d, J = 15Hz), 5.12 (2H, s), 4.31 (HH, m), 3.14 (HH, m), 1.31 (3H, d, J = 7Hz), 1.25 (3H, d, J = 7Hz), 1.15 (3H, d, J = 7Hz), 1.07 (3H, d, J = 7Hz).

Example 37 (6) 4- [2- (N-isopropyl-cyclopentylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid TLC: Rf 0.24 (AcOEt: hexane = 1: 1); NMR: d 7.80 (HH, d, J = 15Hz), 7.61 (2H, d, J = 8Hz), 7.53 (2H, d, J = 8Hz), 7.38 (HH, d, J = 8Hz), 7.30-7.22 (2H, m), 6.48 (HH, d, J = 15Hz), 5.13 (2H, s), 4.35 (HH, m), 3.49 (HH, m), 2.20-1.16 (11H, m), 1.07 (3H , d, J = 7Hz).

Example 37 (7) 4- [2- (N-isopropyl-cyclohexylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid TLC: Rf 0.27 (AcOEt: hexane = 1: 1); NMR: d 7.80 (HH, d, J = 15Hz), 7.61 (2H, d, J = 8Hz), 7.52 (2H, d, J = 8Hz), 7.41 (HH, d, J = 8Hz), 7.34-7.20 (2H, m), 6.48 (HH, d, J = 15Hz), 5.13 (2H, s), 4.32 (HH, m), 2.87 (HH, m), 2.21-2.00 (2H, m), 1.90-1.34 (5H, m), 1.26 (3H, d, J = 7Hz), 1.18-0.61 (6H, m).

Reference Example 34 4- (3-nitro-5-t rif luoromet il? Iridin-2-yloxymethyl) methyl benzoate To a solution of 2-hydroxy-3-nitro-5-trifluoromethylpyridine (1.0 g) in toluene (10 ml), methyl 4-chloromethylbenzoate (1.32 g) and silver oxide (1.23 g) were added in a stream of argon. ). The mixture was refluxed for 18 hours with heating. The reaction mixture was filtered. The filtrate was concentrated. The residue was recrystallized from ethyl acetate to give the title compound (982 mg) having the following physical data. TLC: Rf 0.34 (hexane: AcOEt = 3: 1); Example 38 4- (3-Phenylsulfonylamino-5-trifluoromethylpyridin-2-yloxymethyl) benzoic acid Using methyl 4- (3-nitro-5-trifluoromethylpyridin-2-yloxymethyl) benzoate (prepared in Reference Example 34.), the title compound having the following physical data was obtained by the same procedure as in Example Reference 12- »Reference Example 2- > Example 2. TLC: Rf 0.50 (CHC13: MeOH: AcOH = 100: 5: 1); NMR (DMSO-de): d 12.94 (HH, m), 10.46 (HH, m), 8.33 (HH, m), 7.89 (HH, d, J = 8.4Hz), 7.85 (HH, d, J = 2.2 Hz), 7.73 (2H, m), 7.43-7.65 (3H, m), 7.36 (2H, d, J = 8.4 hz), 5.33 (2H, s).

Reference Example 35 4- [2- (N-Methoxymethoxyonylmethyl-phenylsulfonyl-amino) -5-trifluoromethylphenoxymethyl] benzoic acid "methoxymethyl ester 4- [2- (N-oxymethyl-phenylsulfonylamino) -5-trifluoromethyl-phenoxymethyl] benzoic acid (446 mg) was prepared by the same procedure as in Example 17- »Example 2 using 4- (2-phenylsulfonylamino-5) methyl -trifluoromethylphenoxymethyl) benzoate (prepared in Example 15.) was dissolved in DMF (5 ml). To the solution, methoxymethyl chloride (160 μl) and triethylamine (300 μl) were added dropwise. The mixture was stirred for 2 hours at room temperature. Water was added to it. The mixture was extracted with ethyl acetate, washed, dried over, filtered and concentrated to give the title compound (476 mg) having the following physical data. TLC: Rf 0.20 (hexane: AcOEt = 3: 1).

Reference Example 36 4- [2- [N- (N, N-dimethylaminoonylmethyl) -phenylsulfonylamino] -5-trifluoromethylphenoxymethyl] benzoic acid "methoxymethyl ester To a solution of 4- [2- (N-methoxymethoxyonylmethy1-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic ester methoxymethyl ester (476 mg, prepared in Reference Example 35.) in THF (2 ml), dimethylamine ( 0.8 ml). The mixture was stirred for 3 days at room temperature. The solvent was removed by distillation. The residue was purified on silica gel column chromatography (hexane: AcOEt = 2: 1? -1: 1) to give the title compound (290 mg) having the following physical data. TLC: Rf 0.26 (hexane: AcOEt = 1: 1).

Example 39 4- [2- [N- (N, N-dimethylaminoonylmethyl) phenylsulfonylamino] -5-trifluoromethylphenoxymethyl] benzoic acid H Using 4- [2- [N- (N, N-dimethylaminoonylmethyl) -phenylsulfonylamino] -5-trifluoromethylphenoxymethyl] enoxy 'methoxymethyl ester (prepared in Example 36.), the title compound having the following physical data is obtained by the same procedure as in Reference Example 23 .. TLC: Rf 0.24 (AcOEt); NMR: d 8.10-8.06 (2H, m), 7.71-6.64 (3H, m), 7.55-7.47 (HH, m), 7/42-7.10 (6H, m), 4.94 (2H, s), 4.56 ( 2H, s), 3.04 (3H, s), 2.86 (3H, s).

Reference Example 37 Methyl 4-phenylsulfonylamino-3-methoxybenzoate Using 4-nitro-3-hydroxybenzoic acid, the title compound having the following physical data was obtained by the same procedure as in Reference Example 6 > Reference Example 12- * Reference example 2. TLC: Rf 0.12 (hexane: AcOEt = 3: 1).

Reference Example 38 1-Methyl-1- (4-phenylsulfonylamino-3-methoxyphenyl) ethanol To a suspension of methyl 4-phenylsulfonylamino-3-methoxybenzoate (3: 2 g, prepared in Reference Example 37.) in THF (50 ml), methyl lithium in ester was added dropwise at -65 ° C. The mixture was slowly heated to 5 ° C over a period of 3 hours under stirring. The reaction mixture was neutralized by adding dilute HCl and extracted with ethyl acetate. The organic layer was washed, dried over and concentrated to give the title compound having the following physical data. TLC: Rf 0.18 (hexane: AcOEt = 1: 1).

Reference Example 39 1-methyl-1- [4- (N-acetyl-phenylsulfonylamino) -3-methoxyphenyl] ethanol To a solution of 1-methyl-1- (4-phenylsulfonylamino-3-methoxyphenyl) -ethanol (2.65 g, prepared in Reference Example 38.) in methylene chloride (15 ml), acetic anhydride (3.05 ml) was added. ) and triethylamine (4.60 ml). The mixture was stirred overnight at room temperature. The solvent was distilled off. The residue was purified by column chromatography on silica gel (hexane: AcOEt = 3: 4) to give the title compound (2.33 g) having the following physical data. TLC: Rf 0.19 (hexane: AcOEt = 1: 1).

Reference Example 40 2- (N-Acetyl-phenylsulfonylamino) -5-isopropylphenyl methyl ester To a solution of 1-methyl-1- [4- (N-acetyl-phenylsulfonylamino) -3-methoxyphenyl] ethanol (2.50 g, prepared in Reference Example 39.) in methylene chloride (10 ml) were added to 0 ° C trifluoroacetic acid (10 ml) and triethylsilane (3.3 ml). The mixture was stirred for 1 hour at room temperature. The reaction mixture was added to saturated sodium hydrogen carbonate. The mixture was extracted with ethyl acetate. The organic layer was washed, dried over and concentrated. The residue was purified by column chromatography on silica gel (hexane: AcOEt = 3: 1) to give the title compound (2.33 g) having the following physical data. TLC: Rf 0.24 (hexane: AcOEt = 1: 1).

Reference Example 41 2- (N-acetyl-phenylsulfonylamino) -5-isopropylphenol To a solution of 2- (N-acetyl-phenylsulfonylamino) -5-isopropylphenyl methyl ester (2.28 g, prepared in Reference Example 40.) in methylene chloride (15 ml) was added at 0 ° C boron tribromide. (1.36 ml). The mixture was stirred for 5 hours at 10 ° C. The reaction mixture was poured, extracted with ethyl acetate. The organic layer was washed, dried over and concentrated. The residue was purified by column chromatography on silica gel (benzene: AcOEt = 23: 2) and recrystallized from the AcOEt-hexane mixture solution to give the title compound (1.55 g) having the following physical data. TLC: Rf 0.24 (benzene: AcOEt = 9: 1).

Reference Example 42 4- [2- (N-acetyl-phenylsulfonylamino) -5-isopropyl-phenoxymethyl] -benzoic acid methyl ester Using 2- (N-acetyl-phenylsulfonylamino) -5-isopropylphenol (1.50 g, prepared in Reference Example 41.), the title compound (2.22 g) having the following physical data was obtained by the same procedure as in Reference Example 6. TLC: Rf 0.24 (hexane: AcOEt = 7: 3).

Reference Example 43 4- (Phenylsulfonylamino) -3-methoxybenzyl alcohol A solution of methyl 4-phenylsulfonylamino-3-methoxybenzoate (1.5 g, prepared in Reference Example 37.) in THF (90 ml) was cooled to -78 ° C in a stream of argon. The solution of diisobutylaluminum hydride (1.0 M) in hexane (22 ml) was added by dripping thereto. The mixture was stirred for 4 hours at -78 ° C. After the temperature was increased to room temperature, the mixture was diluted with ether (100 ml). A saturated aqueous sodium sulfate (1.5 ml) was added thereto slowly. The mixture was stirred for 30 minutes, dried, filtered and concentrated to give the title compound (1.5 g). TLC: Rf 0.31 (AcOEt: hexane = 2: 1).

Reference Example 44 4-phenylsulfonylamino-3-methoxybenzaldehyde To a solution of 4-phenylsulfonylamino-3-methoxybenzyl alcohol (522 mg, prepared in Reference Example 43.) in methylene chloride (15 ml), manganese dioxide (3 g) was added in a stream of argon. The solution was stirred for one hour at room temperature. After the completion of the reaction, the reaction mixture was filtered. The filtrate was concentrated to give the title compound (404 mg) having the following physical data. TLC: Rf 0.57 (AcOEt: hexane = 3: 2).

Reference Example 45 1- (4-phenylsulfonylamino-3-methoxyphenyl) ethanol A solution of 4-phenylsulfonylamino-3-methoxybenzaldehyde (400 mg; prepared in Reference Example 44.) in THF (10 ml), cooled to -78 ° C in a stream of argon. A solution of methyl lithium (1.0M) in diethyl ether (3.4 ml) was added dropwise. The mixture was stirred for 20 minutes. After the completion of the reaction, a mixture of H20 + HC1 IN was added thereto to stop the reaction. The mixture was extracted with ethyl acetate three times. The organic layer was washed, dried above and purified by column chromatography on silica gel (AcOEt: hexane = 1: 1) to give the title compound (421 mg) having the following physical data. TLC: Rf 0.34 (AcOEt: hexane = 3: 2).

Example 40 4- (2-Phenylsulfonylamino-5-isopropylphenoxymethyl) benzoic acid Using methyl 4- [2- (N-acetyl-phenylsulfonylamino) -5-isopropyl-phenoxymethyl] benzoate (2.00 g, prepared in Reference Example 42.), the title compound (1.66 g) having the following data Physical data was obtained by the same procedure as in Example 2. TLC: Rf 0.49 (CHC13: MeOH = 4: 1); NMR (DMSO-de): d 7.84 (2H, d, J = 8.5Hz), 7.79-7.53 (5H, m), 7.41 (2H, d, J = 8.5Hz), 6.90 (ÍH, d, J = 8Hz ), 6.63 (ÍH, d, J = 2Hz), 6.55 (ÍH, dd, J = 8 and 2Hz), 4.82 (2H, s), 2.72 (ÍH, m), 1.10 (6H, d, J = 7Hz).

Example 41 Using 1- (4-phenylsulfonylamino-3-methoxyphenyl) ethanol (prepared in Reference Example 45.), the title compound having the following physical data was obtained by the same procedure as in Reference Example 40- * Example Reference 39 Example Reference 41- »Reference Example 6-Example 2. TLC: Rf 0.29 (AcOEt: hexane: AcOH = 5: 14: 1); NMR (DMSO-de): d 12.87 (HH, brs), 9.53 (HH, brs), 7.83 (2H, d, J = 8.5Hz), 7.78-7.50 (5H, m), 7.39 (2H, d, J = 8.0Hz), 6.86 (2H, d, J = 8.0Hz), 6.57 (HH, d, J = 2.0 Hz), 6.50 (HH, dd, J = 8.2Hz), 4.82 (2H, brs), 2.44 ( 2H, q, J = 7.5Hz), 1.08 (3H, t, J = 7.5 Hz).

Example 42 4- (2-Phenylsulfonylamino-5-hydroxymethylphenoxymethyl) benzoic acid Using the methyl 4-nitro-3-hydroxybenzoate, the title compound having the following physical data was obtained by the same procedure as in Reference Example 19: Reference Example 20-Reference Example 2- »Reference Example 43- > Reference Example 39: Reference Example 23- »Reference Example 6-Example 2. TLC: Rf 0.39 (AcOEt: hexane: AcOH = 13: 6: 1); NMR (DMSO-de): d 12.83 (HH, brs), 9.56 (HH, s), 7.83 (2H, d, J = 8.5Hz), 7.78-7.50 (5H, m), 7.38 (2H, d, J = 8. 5Hz), 6.88 (HH, d, J = 8.0Hz), 6.74 (HH, s), 6.56 (HH, d, J = 8.0Hz), 5.10 (HH, brt, J = 5.5Hz), 4.83 (2H, s), 4.34 (2H, d, J = 5.5Hz).

Reference Example 46 Methyl 4-chloro-2-hydroxybenzoate To a solution of 4-chloro-2-hydroxybenzoic acid (5.0 g) in ether (50 ml), diazomethane in ether was added until the reaction was complete at 0 ° C. The reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane: AcOEt = 4: 1) to give the title compound (5.4 g) having the following physical data. TLC: Rf 0.60 (hexane: AcOEt = 2.1).

Reference Example 47 2-hydroxymethyl-5-chlorophenol To a solution of lithium aluminum hydride (1.1 g) in THF (50 ml), methyl 4-chloro-2-hydroxybenzoate (5.38 g, prepared in Example) was added dropwise under a stream of argon at 0 ° C. Reference 46.) in THF (50 ml). After the solution was warmed to room temperature, the solution was stirred for 30 minutes. Water was added to the reaction mixture. The mixture was extracted with ether-AcOEt mixture solution, washed, dried over and concentrated under reduced pressure. The residue was recrystallized from a solution of hexane-AcOEt mixture to give the title compound (3.92 g) having the following physical data. TLC: Rf 0.60 (hexane: AcOEt = 1: 1).

Reference Example 48 Methyl 4- (2-mesyloxymethyl-5-chlorophenoxymethyl) benzoate Using 2-hydroxymethyl-5-chlorophenol (prepared in Reference Example 47.), the title compound having the following physical data was obtained by the same procedure as in Reference Example 6 > Reference Example 8. TLC: Rf 0.60 (benzene: acetone = 9: 1).

Reference Example 49 Methyl 4- (2-azidomethyl-5-chlorophenoxymethyl) benzoate To a solution of methyl 4- (2-mesyloxymethyl-5-chlorophenoxymethyl) benzoate (628 mg, prepared in Reference Example 48.) in DMF (5.0 ml) was added in a stream of sodium argon azide (530 mg. ). The mixture was stirred for 40 minutes at 60 ° C. The reaction mixture was diluted with ethyl acetate. The impurities were filtered with celite. The filtrate was washed, dried over and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane: AcOEt = 10: 1) to give the title compound (404 mg) having the following physical data. TLC: Rf 0.56 (hexane: AcOEt = 4: 1).

Reference Example 50 Methyl 4- (2-aminomethyl-5-chlorophenoxymethyl) benzoate To a solution of methyl 4- (2-azidomethyl-5-chlorophenoxymethyl) benzoate (389 mg, prepared in Reference Example 49.) in THF (4.0 ml), triphenylphosphine (462 mg) was added at room temperature. The mixture was stirred for 3 hours. After agitation, water was added thereto. The mixture was stirred for 15 hours. The reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (CHC13: MeOH = 50: 1 → 10: 1) to give the title compound (339 mg) having the following physical data. TLC: Rf 0.22 (CHC13: MeOH = 10: 1).

Example 43 4- (2-Phenylsulfonylaminomethyl-5-chlorophenoxymethyl) benzoic acid Using methyl 4- (2-aminomethyl-5-chlorophenoxymethyl) -benzoate (prepared in Reference Example 50.), the title compound having the following physical data was obtained by the same procedure as in Reference Example 2 - * Example 2. TLC: Rf 0.49 (CHC13: MeOH: AcOH = 100: 5: 1); NMR (DMSO-de): d 7.94 (2H, d, J = 8.0Hz), 7.77 (2H, m), 7. 45-7.70 (5H, m), 7.25 (HH, d, J = 8.2Hz), 7.05 (HH, d, J = 1.8Hz), 6.94 (ÍH, dd, J = 1.8, 8.2Hz), 5.20 (2H, s), 4. 00 (2H, s).

Example 44 4- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] phenylpropiolyl acid Using 4- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethyl-phenoxymethyl] benzoic acid (prepared in Example 18 (9).), The title compound having the following physical data was obtained by the same procedure than in the Reference Example 13? Reference Example 14- »Reference Example - »Example 2. TLC: Rf 0.32 (CHC13: MeOH = 8: 2); NMR: d 7.80 (2H, d, J = 8Hz), 7.64 (2H, d, J = 8Hz), 7. 68-7.26 (8H, m), 5.09 (2H, s), 4.38 (ÍH, sept, J = 6. 5Hz), 1.04 (6H, d, J = 6.5Hz).

Example 45 4- [2- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenyl] ethyl] benzoic acid Using methyl 4- [2- (2-t-butoxycarbonylamino-5-trifluoromethylphenyl) - (EZ) -vinyl] benzoate, the title compound has the following physical results obtained by the same procedure as in the Reference Example 23- > Reference Example 2? Example 17 -? - Example 2. TLC: Rf 0.45 (CHC13: MeOH = 9: 1); NMR: d 8.2-8.0 (3H, m), 7.9-7.7 (2H, m), 7.6-7.4 (7H, m), 7. 2-7.0 (2H, m), 4.8-4.6 (HH, m), 1.08 (3H, d, J = 5.0 Hz), 1.05 (3H, d, J = 5.0 Hz).

Example 46 4- (2-Phenylsulfonylamino-4-chloromethylphenoxymethyl) benzyl alcohol Using methyl 4- (2-phenylsulfonylamino-4-chlorophenoxymethyl) -benzoate (prepared in Example 7 (a)), the title compound has the following physical results obtained by the same procedure as in Reference Example 43. TLC: Rf 0.24 (hexane: AcOEt = 1: 1); NMR: d 7.75 (2H, m), 7.60 (ΔI, d, J = 2.4 Hz), 7.55 (ΔI, m), 7.45 (2H, m), 7.36 (2H, d, J = 8.0 Hz), 7.13 ( 2H, d, J = 8.0 Hz), 7.03 (HH, brs), 6.96 (HH, dd, J = 2.4, 8.8 Hz), 6.68 (HH, d, J = 8.8 Hz), 4.86 (2H, s), 4.73 (2H, t, J = 5.8 Hz), 1.74 (ÍH, t, J = 5.8 Hz).

Example 47 4- [N- [2- (4-chlorophenylsulfonylamino) -5-chlorophenyl] aminosulfonyl) benzoic acid Using the 2-nitro-4-chloroaniline, the title compound has the following physical results obtained by the same procedure as in Reference Example 2? Reference Example 12- > Example of Reference 2 Example 2. TLC: Rf 0.22 (CHC13: MeOH: H20 = 8: 2: 0.2); NMR (DMSO-de): d 9.68 (ÍH, br), 8.11 (2H, d, J = 8.4 Hz), 7. 84 (2H, d, J = 8.4 Hz), 7.69 (2H, d, J = 8.8 Hz), 7.62 (2H, d, J = 8.8 Hz), 7.12 (ÍH, dd, J = 2.4 and 8.4 Hz), 7.02 (ÍH, d, J = 2.4 ni, 6.97 (ÍH, d, J = 8.4 Hz).

Example 48 4- [2- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenyl] - (E) -vinyl] benzoic acid Using methyl 4- [2- (2-t-butoxycarbonylamino-5-trifluoromethylphenyl) - (E) -vinyl] benzoate, the title compound has the following physical results obtained by the same procedure as in Reference Example 23-? Reference Example 2? Example 17 - Example 2. TLC: Rf 0.45 (CHC13: MeOH = 9: 1); NMR: d 8.2-8.0 (3H, m), 7.9-7.7 (2H, m), 7.6-7.4 (7H, m), 7. 2-7.0 (2H, m), 4.8-4.6 (HH, m), 1.08 (3H, d, J = 5.0 Hz), 1.05 (3H, d, J = 5.0 Hz).

Example 48 (1) 4- [2- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenyl] - (Z) -vinyl] benzoic acid OH Using methyl 4- [2- (2-t-butoxycarbonylamino-5-trifluoromethylphenyl) - (Z) -vinyl] benzoate, the title compound has the following physical results obtained by the same procedure as in Reference Example 23 - »Reference Example 2- > Example 17- »Example 2.

TLC: Rf 0.51 (CHC13: MeOH = 9: 1); NMR: d 7.97 (2H, d, J = 8.4 Hz), 7.9-7.7 (2H, m), 7.7-7.4 (5H, m), 7.31 (2H, d, J = 8.4 Hz), 7.1-6.9 (2H , m), 6.77 (HH, d, J = 12.4 Hz), 4.7-4.5 (HH, m), 1.19 (3H, d, J = 6.6 Hz), 1.04 (3H, d, J = 6.6 Hz).

Example 49 4- (2-Benzoylamino-5-chlorophenoxymethyl) benzoic acid H Using the 2-nitro-5-chlorophenol, the title compound has the following physical results obtained by the same procedure as in the Example of Reference 6- > Reference Example 12- > Example ll- »Example 2. TLC: Rf 0.51 (CHC13: MeOH: AcOH = 100: 5: 1); NMR (DMSO-de): d 12.92 (HH, brs), 9.64 (HH, s), 7.94 (4H, m), 7.75 (HH, d, J = 8.6 Hz), 7.47-7.68 (5H, m), 7.23 (HH, d, J = 2.2 Hz), 7.05 (HH, dd, J = 2.2, 8.6 Hz).

Example 50-50 (2) Using 4- (2-phenylsulfonylamino-5-isopropylphenoxymethyl) -benzoic acid (prepared in Example 40) or 4- (2-phenylsulfonylamino-5-ethylphenoxymethyl) benzoic acid (prepared in Example 41), the title compound has the following physical results obtained by the same procedure as in Reference Example l Example 17-? Example 2.

Example 50 4- [2- (N-isopropyl-phenylsulfonylamino-5-isopropyl-phenoxymethyl] benzoic acid] TLC: Rf 0.13 (CHC13: MeOH = 19: 1); NMR (DMSO-d6): d 7.85 (2H, d, J = 8 Hz), 7.79-7.52 (5H, m) 7.40 (2H, d, J = 8 Hz), 7.01 (ÍH, d, J = 8 Hz ), 6.73 (H, d, J = 2 Hz), 6.65 (H, d, J = 8 and 2 Hz), 4.83 (H, m), (6H, d, J = 7 Hz), 0.95 (6H, d, J = 7 Hz).

Example 50 (i; 4- [2- (N-Methyl-phenylsulfonylamino) -5-isopropyl-phenoxymethyl] benzoic acid TLC: Rf 0.13 (CHC13: MeOH = 19: 1); NMR (DMSO-de): d 7.85 (2H, d, J = 8 Hz), 7.76-7.53 (5H, m) 7.39 (2H, d, J = 8 Hz), 6.98 (ÍH, d, J = 8 Hz ), 6.77 (HH, d, J = 2 Hz), 6.70 (HH, dd, J = 8 and 2 Hz), 4.78 (2H, brs), 3.33 (3H, s), 2.82 (HH, m), 1.15 (6H, d, J = 7 Hz).

Example 50 (2) 4- [2- (N-isopropyl-phenylsulfonylamino) -5-ethylphenoxymethyl] benzoic acid H TLC: Rf 0.40 (AcOEt: hexane: AcOH = 5: 14: 1); NMR: d 7.97 (2H, d, J = 8.0 Hz), 7.82-7.70 (2H, m), 7.62-7.32 (5H, m), 7.05 (ΔI, d, J = 8.0 Hz), 6.60 (ΔI, dd) , J = 8, 1.5 Hz), 6.53 (HH, d, J = 1.5 Hz), 4.86 (2H, br), 4.36 (HH, qn, J = 6.0 Hz), 2.55 (2H, q, J = 7.5H ), 1.18 (3H, t, J = 7.5Hz), 1.02 (6H, brd, J = 6.0 Hz).

Example 51 Sodium salt of 4- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] -cinnamic acid Na To a solution of 4- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid (425 mg, prepared in Example 18 (49).) In MeOH (5 ml), NaOH (0.41 ml) 2N was added. The mixture was stirred at room temperature. The mixture was azeotropically distilled with benzene three times, to give the title compound (430 mg) having the following physical data. TLC: Rf 0.19 (hexane: AcOEt = 1: 1); NMR: d 7.60 (2H, d, J = 7Hz), 7.40-6.97 (11H, m), 6.47 (ÍH, d = 16 Hz), 4.62 (2H, bs), 4.20-4.08 (ÍH, m), 0.77 (6H, d, J = 5 Hz).

Example 52 (1) -52 (5) Through the use of methyl 4- (2-amino-5-trifluoromethylphenoxymethyl) benzoate (prepared in Reference Example 17) and the corresponding benzenesulfonyl chloride derivatives, the compounds were obtained of the title that have the following physical data by the same procedure as in Example 4 - > Example 19 - > (it was used preferably in place of cyclopentyl ethanol). - »Example 2.

Example 52 (1) 4- [2- (N-isopropyl-4-propoxyphenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid TLC: Rf 0. 55 (CHC13: MeOH = 9. 1) NMR: d 8.16 (2H, d, J = 8.8 Hz), 7.71 (2H, d, J = 8.8 Hz), 7.54 (2H, d, J = 8.8 Hz), 7.30-7.22 (3H, m), 6.80 (2H, d, J = 8.8 Hz), 5.14 (2H, s), 4.44-4.24 (ÍH,), 3.92 (2H, t, J = 6.6 Hz), 1.91-1.72 (2H, m), 1.14-0.98 (9H, m).

Example 52 (2) 4- [2- (N-isopropyl-4-ethylthiophenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid TLC: Rf 0.64 (CHC13: MeOH = 9.1); NMR: d 8.17 (2H, d, J = 8.4 Hz), 7.66 (2H, d, J = 8.4 Hz), 7.53 (2H, d, J = 8.4 Hz), .30-7.20 (3H, m), 7.16 (2H, d, J = 8.4 Hz), 5.12 (2H, s), 4.44-4.22 (ÍH, m), 2.98 (2H, q, J = 7.6 Hz), 1.36 (3H, t, J = 7.6 Hz), 1.09 (3H, d, J = 6.6 Hz), 1.05 (3H, d, J = 6.6 Hz) Example 52 (3) 4- [2- (N-isopropyl-4-methylthiophenylsulphonylamino) -5-trilfluoromethylphenoxymethyl] benzoic acid TLC: Rf 0.56 (CHC13: MeOH = 9: 1); NMR: d 8.16 (2H, d, J = 8.4 Hz), 7.67 (2H, d, J = 8.4 Hz), 7.52 (2H, d, J = 8.4 Hz), 7.30-7.20 (3H, m), 7.12 (2H, d, J = 8.4 Hz), 5.12 (2H, s), 4.46-4.24 (ÍH, m), 2.48 (3H, s), 1.09 (3H, d, J = 7.0 Hz), 1.05 (3H, d, J = 7.0 Hz).

Example 52 (4) 4 [2- (N-isopropyl-4-butoxyphenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid TLC: Rf 0.51 (CHC13: MeOH = 9: 1); NMR: d 8.16 (2H, d, J = 8.4 Hz), 7.71 (2H, d, J = 8.8 Hz), 7.54 (2H, d, J = 8.4 Hz), 7.30-7.22 (3H,), 6.79 (2H , d, J = 8.8 Hz), 5.14 (2H, s), 4.42-4.27 (ÍH, m), 3.96 (2H, t, J = 6.2 Hz), 1.87-1.70 (2H, m), 1.60-1.40 (2H, m), 1.14-0.92 (9H, m).

Example 52 (5) 4- [2- (N-isopropyl-4-isopropoxyphenylsulfonylamino) -5-trifluoromethyl-phenoxymethyl] benzoic acid TLC: Rf 0.68 (CHC13: MeOH = 9: 1); NMR: d 8.17 (2H, d, J = 8.4 Hz), 7.71 (2H, d, J = 8.8 Hz), 7.56 (2H, d, J = 8.0 Hz), 7.30-7.22 (3H, m), 6.78 ( 2H, d, J = 8.8 Hz), 5.15 (2H, s), 4.62-4.50 (HH, m), 4.40-4.23 (HH, m), 1.35 (6H, d, J = 5.8 Hz), 1.08 (3H , d, J = 7.4 Hz), 1.04 (3H, d, J = 7.4 Hz).

Example 53 (1) -53 (3) By the use of methyl 4- (2-amino-5-chlorophenoxymethyl) benzoate (prepared in Reference Example 7), or 4- (2-amino-5-trifluoromethyl) methyl phenoxymethyl) benzoate (prepared in Reference Example 17), the compounds having the following physical data were obtained, by the same procedure as in Example 27 (the corresponding aldehyde was used) - Example 11 - Example 2.

Example 53 (1) 4- [2- (N-Isobutyl-benzoylamino) -5-chlorophenoxymethyl] benzoic acid H TLC: Rf 0.53 (CHC13: MeOH = 5: 1); NMR (CDC13 + 1 gora of CD3OD): d 8.08 (2H, d, J = 8 Hz), 7. 44-7.04 (8H, m), 6.94-6.80 (H, m), 6.73 (H, s), 5.03 (ÍH, d, J = 13 Hz), 4.82 (ÍH, d, J = 13 Hz), 3.91 (ÍH, dd, J = 15, 7Hz), 3.49 (ÍH, dd, J = 15, 7Hz), 2.10-1.60 (ÍH,), 0.98 (6H, d, J = 7Hz).

Example 53 (2) 4- [2- (N-isopropyl-benzoylamino) -5-trifluoromethylphenoxymethyl] benzoic acid TLC: Rf 0.49 (CHC13: MeOH = 9: 1); NMR: d 8.18 (2H, d, J = 8.4 Hz), 7.52-7.35 (3H, m), 7.30-7.03 (6H,), 7.02-6.92 (ÍH, m), 5.20-4.90 (2H, m), 4.90-4.70 (ÍH, m), 1.50-1.00 (6H, m).

Example 53 (3) 4- [2- (N-isopropyl-2-furoylamino) -5-trifluorophenoxymethyl] benzoic acid TLC: Rf 0.43 (CHC13: MeOH = 9: 1); NMR: d 8.09 (2H, d, J = 7.8 Hz, 7.43-7.22 (5H, m), 7.15 (HH, s), 6.25-6.20 (HH, m), 6.16-6.08 (HH, br), 5.20- 4.84 (3H, m), 1.40-1.00 (6H, m).

Example 54 4- (2-Benzoylamino-5-chlorobenzoylamino) benzoic acid By using 2-nitro-5-chlorobenzoic acid chloride (prepared in Reference Example 13), the title compound having the following physical data was obtained, by the same procedure as in Example 11 - »Example of reference 10 - »Example 11 - > Example 2 TLC: Rf 0.52 (AcOEt: hexane: AcOH = 7: 12: 1); NMR (DMSO-d6): d 12.77 (HH, brs), 11.33 (HH, s), 10.85 (HH, s), 8.36 (HH, d, J = 9.0 Hz), 8.02-7.78 (7H, m), 7.69 (ÍH, dd, J = 9.0, 2.5 Hz), 7.64-7.48 (3H, m).

Example 55 (l) -55 (2) By using the 2-nitro-5-chlorobenzoic acid chloride (prepared in Reference Example 13), the compounds having the following physical data were obtained, by the same procedure as in Example 11 - > Reference Example 10 - »Reference example 2 - > Example 2 Example 55 (1) 4- [2- (2-Thienylsulfonylamino) -5-chlorobenzoylamino] benzoic acid TLC: Rf 0.18 (CHC13: MeOH = 9: 1); - NMR (DMSO-d6): d 12.73 (HH, br), 10.68 (HH, brs), 10.48 (HH, brs), 7.93 (2H, d, J = 8.8 Hz), 7.87 (HH, dd, J = 1.2 and 3.6 Hz), 7.81 (HH, d, J = 2.2 Hz), 7.76 (2H, d, J = 8.8 Hz), 7.61-7.53 (2H, m), 7.41 (HH, d, J = 8.8Hz) , 7.05 (ÍH, dd, J = 3.8 and 4.0Hz).

Example 55 (2) 4- (2-Butylsulfonylamino-5-chlorobenzoylamino) benzoic acid OOH TLC: Rf 0.26 (CHC13: MeOH = 9: 1); NMR (DMSO-de): d 12.77 (ÍH, brs), 10.80 (ÍH, brs), 9.94 (ÍH, s), 7.93 (2H, d, J = 8.8Hz), 7.88 (ÍH, d, J = 2.2Hz), 7.82 (2H, d, J = 8.8Hz), 7.61 (HH, dd, J = 2.2 and 8.8 Hz), 7.54 (HH, d, J = 8.8Hz), 3.18 (2H, t-similar), 1.66-1.51 ( 2H, m), 1.37-1.19 (2H, m), 0.74 (3M, t, J = 7.2 Hz).

Reference Example 51 Methyl 4- (2-nitro-5-methylphenylthiomethyl) benzoate To a solution of methyl 4-acetylthiomethylbenzoate (794 mg) in MeOH (5.0 ml), sodium methoxide (191 mg) and 3-fluoro-4-nitrotoluene (500 mg) were subsequently added in a stream of argon at 0 ° C. mg). The mixture was slowly heated to room temperature. The mixture was stirred for 4 hours. Saturated aqueous ammonium chloride was added to the reaction mixture. The mixture was extracted with ethyl acetate, washed, dried over and concentrated under reduced pressure. The residue was recrystallized from ethanol to give the title compound (646 mg) having the following physical data. TLC: Rf 0.49 (CHC13: MeOH = 8: 4: 1); Example 56 4- [2- (N-isopropyl-2-furanylsulfonylamino) -5-methylphenylthioethyl] benzoic acid H By the use of methyl 4- (2-nitro-5-methylphenylthiomethyl) benzoate (prepared in Reference Example 51), the title compound having the following physical data was obtained, by the same procedure as in the Example of Reference 11 - > Reference Example 2 - »Example 17 - Example 2.

TLC: Rf 0.45 (CHC13: MeOH = AcOH = 100: 5: 1); NMR: d 8.04 (2H, d, J = 8.4 Hz), 7.58 (HH, dd, J = 0.8, 1.8 Hz), 7.48 (2H, d, J = 8.4 Hz), 7.08 (HH, m), 6.91- 6.98 (2H, m), 6.84 (HH, d, J = 8.0 Hz), 6.50 (HH, d, J = 6.8 Hz), 1.06 (d, J = 6.8 Hz).

Example 57 Acid 4- [2- (N-isobutyl-2-thienylsulfonylamino) -5-trif luoromethyl-phenoxymethyl] -cinnamic acid By using 2-nitro-5-trifluoromethylphene, the title compound having the following physical data was obtained, by the same procedure as in Reference Example 18 (b) - »Reference Example 12 -» Reference example 2 - »Example 17 - > • Example 2.

TLC: Rf 0.51 (CHC13: MeOH = AcOH = 100: 5: 1); NMR: d 7.80 (HH, d, J = 16.2 Hz) 7.57 (2H, d, J = 8.0 Hz), 7.22-7.46 (6H, m), 7.16 (HH,), 6.93 (HH, dd, J = 4.0 , 5.2 Hz), 6.49 (HH, d, J = 16.2 Hz), 4.94 (2H, brs), 3.45 (2H, d, J = 7.2 Hz), 1.62 (HH, m), 0.91 (6H, d, J = 6.6 Hz).

Example 58 6- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] -2-naphthalic acid.

By using 2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenol (prepared in Reference Example 24), and methyl 6-hydroxymethyl-2-naphtate, the title compound having the following physical data was obtained , by the same procedure as in Reference Example 18 - > Example 2 TLC: Rf 0.55 (CHC13: MeOH: AcOH = 100: 5: 1); NMR: d 8.74 (HH, s), 8.17 (HH, dd, J = 1.8, 8.8Hz), 8.03 (HH, d, J = 8.4 Hz), 8.3 (HH, brs), 7.95 (HH, d, J = 8.8 Hz), 7.79-7.87 (2H,), 7.61 (HH, dd, J = 1.4, 8.4 Hz), 7.43 (HH,), 7.32 (3H, m), 7.26 (2H, m), 5.26 (2H) , s), 4.39 (HH, m), 1.08 (3H, d, J = 6.6 Hz), 1.06 (3H, d, J = 6.6 Hz).

Example 59 (l) -59 (3) By using 2-nitro-5-trifluoromethylphenol, the title compounds having the following physical data were obtained, by the same procedure as in Reference Example 18 (b) - > Reference Example 12 - Example 27 - Example 11 - > Example 2 Example 59 (i; 4- [2- (N-isopropyl-2-f luorylamino) -5-trif luoromethylphenoxymethyl] cinnamic acid H TLC: Rf 0.44 (CHC13: MeOH = 9: 1); NMR: d 7.76 (ΔI, d, J = 16.2 Hz), 7.52 (2H, d, J = 8.4 Hz), 7.38 (ΔI, d, J = 8.4 Hz), 7.32 (ΔI, d, J = 8.4 Hz) , 7.28-7.20 (3H, m), 7.17 (HH, s), 6.45 (HH, d, J = 16.2 Hz), 6.24-6.19 (HH, m), 6.11-6.00 (HH, br), 5.20-4.80 (3H, m), 1.40-1.00 (6H, m).

Example 59 (2) 4- [2- (N-Isobutyl-2-fluorylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid TLC: Rf 0.49 (CHC13: MeOH = 9: 1); NMR: d 7.76 (ΔI, d, J = 15.9 Hz), 7.52 (2H, d, J = 8.4 Hz), 7.39 (ΔI, d, J = 8.1 Hz), 7.33-7.15 (5H, m), 6.45 ( ÍH, d, J = 15.9 Hz), 6.28-6.10 (2H, m), 5.20-4.90 (2H, m), 4.00-3.80 (ÍH, br), 3.60-3.30 (ÍH, br), 2.00-1.80 ( 1H, m), 0.95 (6H, d, J = 6.6 Hz).

Example 59 (3) 4- [2- (N-isopropyl-butyrylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid TLC: Rf 0.42 (CHC13: MeOH = 9: 1); NMR: d 7.78 (ΔI, d, J = 15.9 Hz), 7.58 (2H, d, J = 8.1 Hz), 7.42 (2H, d, J = 8.1 Hz), 7.35-7.20 (3H, m), 6.48 ( ÍH, d, J = 15.9 Hz), 5.20-4.93 (3H, m), 1.90 (2H, dt, J = 2.7, 7.5 Hz), 1.64-1.50 (2H, m), 1.17 (3H, d, J = 6.6 Hz), 0.94 (3H, d, J = 6.6 Hz), 0.79 (3H, t, J = 7.2 Hz).

Example 60 (1) -60 (2) By using 2-nitro-5-trifluoromethylphenol, the title compounds having the following physical data were obtained, by the same procedure as in Reference Example 18 (b) - > Reference Example 12 - »Reference Example 2 - > Example 19? Example 2 Example 60 (1) 4- [2- (N-isopropyl-4-ethoxyphenylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid TLC: Rf 0.51 (CHC13: MeOH = 9: 1); NMR: d 7.82 (ÍH, d, J = 16.0 Hz), 7.72 (2H, d, J = 8.8 Hz), 7. 61 (2H, d, J = 8.6 Hz), 7.48 (2H, d, J = 8.6 Hz), '7.28-7.22 (3H, m), 6.77 (2H, d, J = 8.8 Hz), 6.50 (ÍH, d, J = 16.0Hz), . 10 (2H, s), 4.40-4.20 (HH, m), 4.01 (2H, q, J = 6.8 Hz), 1. 43 (3H, t, J = 6.8 Hz), 1.07 (3H, d, J = 6.6 Hz), 1.03 (3H, d, J = 6.6 Hz).

Example 60 (2) 4- [2- (N-Isobutyl-4-ethoxyphenylsulfonylamino) -5-trifluoromethyl-enoxy-methyl acid} cinnamic H TLC: Rf 0.57 (CHC13: MeOH = 9: 1); Nmr: d 7.81 (ÍH, d, J = 15.6 Hz), 7.60-7.47 (3H,), 7.44 (1H, d, J = 8.2 Hz), 7.30-7.10 (5H, m), 6.73 (2H, d, J = 8.8 Hz), 6.50 (HH, d, J = 15.6 Hz), 5.00-4.80 (2H, br), 3.95 (2H, q, J = 7.0 Hz), 3.39 (2H, d, J = 6.8 Hz) , 1.70-1.50 (ÍH, m), 1.41 (3H, t, J = 6.8 Hz), 0.88 (6H, d, J = 6.6 Hz).

Example 61 4- [2- (N-isopropyl-3-ethoxyphenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid By the use of methyl 4- (2-amino-5-trifluoromethylphenoxymethyl) benzoate (prepared in Reference Example 17), the title compound having the following physical data was obtained, by the same procedure as in Example 4 - »Example 19 - Example 2.

TLC: Rf 0.63 (CHC13: MeOH = 9: 1); NMR: d 8.15 (2H, d, J = 8.4 Hz), 7.53 (2H, d, J = 8.4 Hz), 7.40-7.20 (6H, m), 7.02 (ÍH, ddd, J = 1.2, 2.4, 8.0Hz ), 5.13 (2H, s), 4.52-4.36 (ÍH, m), 3.98 (2H, q, J = 6.8 Hz), 1.40 (3H, t, J = 6.8 Hz), 1.08 (3H, d, J = 6.6 Hz), 1.06 (3H, d, J = 6.6 Hz).

Example 62 (l) -62 (2 By using 2-nitrobenzoic acid chloride, the title compounds having the following physical data were obtained, by the same procedure as in Example 11 - »Example of Reference 20 - > Reference Example 2 - > Example 2 Example 62 (1) 4- [2- (3-Chlorophenylsulfonylamino) benzoylamino] benzoic acid TLC: Rf 0.38 (CHC13: MeOH = 9: 1); NMR (DMSO-de): 6 10.59 (HH, s), 10.44 (HH, s), 7.95 (2H, d, J = 8.4 Hz), 7.86-7.60 (6H, m), 7.58-7.45 (2H, m ), 7.38-7.25 (2H,).

Example 62 (2) 4- [2- (4-Bromophenylsulfonylamino) benzoylamino] benzoic acid TLC: Rf 0.39 (CHC13: MeOH = 9: 1); NMR (DMSO-de); d 10.55 (HH, s), 10.38 (HH, s), 7.96 (2H, d, J = 8.8 Hz), 7.90-7.45 (8H, m), 7.44-7.25 (2H, m).

Formulation of Example 1 The following compounds were mixed in a conventional method and chopped to obtain 100 tablets, each containing 5 mg of the active ingredient. • 4- (2-phenyl-sulfonylamino-5-chlorobenzoylamino) benzoic acid (prepared in Example 2) 500 mg • Calcium glycolate (disintegrating agent) 200 mg • Magnesium stearate (lubricating agent) 100 mg • Microcrystalline cellulose 9.2 g It is noted that, in relation to this date, the best method known by the applicant to carry out the aforementioned invention is that which is clear from the present description of the invention.

Having described the invention as above, the content of the following is claimed as property.

Claims (15)

1. A sulfonamide or carboamide derivative of the formula (I) (wherein and each, independently, is a carbocyclic ring of 1 to 5 carbon atoms or a 5-7 membered heterocyclic ring containing one or two oxygen, sulfur or nitrogen atom (s) .ZL is -alkylene COR1 from 1 to 4 carbon atoms -CH = CH-COR1 or O-alkylene- of 1 to 3 carbon atoms -COR1 (wherein R1 is hydroxy, alkoxy of 1 to 4 carbon atoms or the formula NR6R7 (wherein R6 and R7 each, independently is H or alkyl of 1 to 4 carbon atoms)), or alkylene- of 1 to 5 carbon atoms -OH Z2 is H, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon, nitro, halogen, trifluoromethyl, trifluoromethoxy, hydroxy or COR1 atoms (wherein R1 is as defined hereinbefore) ZJ is a single bond or alkylene of 1 to 4 carbon atoms Z4 is S02 or CO, Z5 is (1 ) alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, or alkynyl of 2 to 8 carbon atoms. (2) phenyl, cycloalkyl of 3 to 7 carbon atoms, or a 5-7 membered heterocyclic ring containing one or two oxygen, sulfur or nitrogen atom (s), or (3) alkyl of 1 to 4 carbon atoms carbon, alkenyl of 2 to 4 carbon atoms, or alkynyl of 2 to 4 carbon atoms, substituted by phenyl or cycloalkyl of 3 to 7 carbon atoms. (phenyl, cycloalkyl of 3 to 7 carbon atoms, and 5-7 membered heterocyclic ring containing one or two oxygen, sulfur or nitrogen atom (s), mentioned in (2) and (3) above) may be substituted by 1-5 of R 5 (wherein R 5 (if two or more R 5, each independently) is H, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkylthio of 1 to 6 carbon atoms , nitro, halogen, trifluoromethyl, trifluoromethoxy or hydroxy)). R2 is CONR8 N RECO, CONR8- alkylene of 1 to 4 carbon atoms, alkylene of 1 to 4 carbon atoms-CONR8, NR8CO-alkylene of 1 to 4 carbon atoms, alkylene of 1 to 4 carbon atoms-NR8CO, alkylene from 1 to 3 carbon atoms-CONR8-alkylene of 1 to 3 carbon atoms or, alkylene of 1 to 3 carbon atoms-NR8CO-alkylene of 1 to 3 carbon atoms (wherein each R8 is H, or 1 to 4 carbon atoms), 0, S, NZ6 (where Z6 is H or alkyl of 1 to 4 carbon atoms), Z7-alkylene of 1 to 4 carbon atoms, alkylene of 1 to 4 carbon atoms- Z7, or alkylene of 1 to 3 carbon atoms-Z7-alkylene of 1 to 3 carbon atoms (wherein each Z7 is 0, S or NZ6 (wherein Z6 is as defined below)). C 1 -C 4 -alkylene-C 1 -C 3 -alkylene-C-C 1 -C 3 -alkylene, C 2 -C 4 -alkenylene-2 -C 4 -alkenylene, or alkenylene from 2 to 4 carbon atoms R3 is H, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkylthio of 1 to 6 carbon atoms, nitro, halogen, trifluoromethyl, trifluoromethoxy, hydroxy or hydroxymethyl, R 4 is (1) H, (2) alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, or alkynyl of 2 to 8 carbon atoms, (3) alkyl of 1 to 6 carbon atoms substituted by one or two substituent (s) selected from the group consisting of COOZ8, CONZ9Z10, and OZ8 (wherein Z8, Z9 and Z10 each independently is H or alkyl) 1 to 4 carbon atoms) and Cl-4 alkoxy-Cl-4 alkoxy, (4) cycloalkyl of 3 to 7 carbon atoms, or (5) alkyl of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon atoms carbon or alkynyl of 2 to 4 carbon atoms substituted by phenyl or cycloalkyl of 3 to 7 carbon atoms (phenyl and cycloalkyl of 3 to 7 carbon atoms mentioned in the above (4) and (5) can be substituted by 1- 5 of R5 (where R5 is as defined here)) ynyt each, independently is an integer of 1-4, with the proviso that (1) R2 and Z3 must be connected to the position 1- or 2- of is a benzene ring and (Z2) is preferably COR1, Z1 should be connected to the 3 or 4 position of the benzene ring *) or a non-toxic salt thereof, Z1 and (3) the compounds where 1 is COOH excluded COOH

2. A compound in accordance with claim 1, characterized in that y is a carbocyclic ring of 5 to 15 carbon atoms, and Z5 is alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, alkynyl of 2 to 8 carbon atoms or a group containing phenyl or cycloalkyl of 3-7 carbon atoms.

3. A compound according to claim 1, characterized in that at least one of y and Z5 is a 5- to 7-membered heterocyclic ring containing one or two oxygen, sulfur or nitrogen atom (s).

4. A compound in accordance with claim 1 or 3, characterized in that is a carbocyclic ring and Z5 is a 5- to 7-membered heterocyclic ring containing one or more oxygen, sulfur or nitrogen atoms.

5. A compound in accordance with claim 1 or 3, characterized in that one of is a 5- to 7-membered heterocyclic ring containing one or two oxygen, sulfur or nitrogen atoms, and the other is a carbocyclic ring of 5 to 15 carbon atoms.

6. A compound according to claim 1, 2 or 3, characterized in that R2 is CONR8 NR8CO, CONR8- alkylene of 1 to 4 carbon atoms, alkylene of 1 to 4 carbon atoms CONR8, NR8CO-alkylene of 1 to 4 carbon atoms carbon, alkylene of 1 to 4 carbon atoms-NR8CO, alkylene of 1 to 3 carbon atoms-CONR8-alkylene of 1 to 3 carbon atoms or, alkylene of 1 to 3 carbon atoms-NR8CO-alkylene of 1 to 3 carbon atoms (wherein each R8 is H, or alkyl of 1 to 4 carbon atoms).

7. A compound according to claim 1, 2 or 3, characterized in that R2 is O, S, NZfc; wherein Z6 is H or alkyl of 1 to 4 carbon atoms), Z7-alkylene of 1 to 4 carbon atoms, alkylene of 1 to 4 carbon atoms-Z7, or alkylene of 1 to 3 carbon atoms- Z7-alkylene of 1 to 3 carbon atoms (where each Z7 is O, S or NZ6 (where Z6 is as defined below)).

8. A compound according to claim 1, 2 or 3, characterized in that R: is alkylene of 2 to 4 carbon atoms, alkenylene of 2 to 4 carbon atoms or alkynylene of 2 to 4 carbon atoms.

9. A compound according to claim 1, 2 or 3, characterized in that R2 is CO, CO-alkylene of 1 to 4 carbon atoms, alkylene of 1 to 4 carbon atoms-CO or, alkylene of 1 to 3 carbon atoms-CO-alkylene of 3 carbon atoms.

10. A compound according to claim 1, characterized in that it is selected from (1) 4- (2-phenylsulfonylamino-5-chlorobenzoylamino) benzoic acid (2) 3- (2-phenylsulfonylaminobenzoylamino) benzoic acid (3) 3- (2-phenylsulfonylaminobenzoylamino) benzoic acid (4) 4- (2-phenylsulfonylaminobenzoylamino) benzoic acid (5) 4- [2- (4-chlorophenyl) sulfonylamino-5-chlorobenzoylamino] benzoic acid (6) 4- [2- (4-chlorophenylsulfonylamino) -4- chlorobenzoylamino] benzoic acid (7) 4- [2- (4-chlorophenylsulfonylamino) -6-chlorobenzoylamino] benzoic acid (8) 4- [2- (4-chlorophenylsulfonylamino) -3- chlorobenzoylamino] benzoic acid (9) acid 4- [ 2- (2-chlorophenylsulfonylamino) -5-chlorobenzoylamino] benzoic acid (10) 4- [2- (3-chlorophenylsulfonylamino) -5- chlorobenzoylamino] benzoic acid (11) 4- [2- (4-chlorophenylsulfonylamino) -5- fluorobenzoylamino] benzoic acid (12) 4- [2- (4-chlorophenylsulfonylamino) -5-bromobenzoylamino] benzoic acid (13) 4- [2- (4-chlorophenylsulfonylamino) -5-methoxybenzoylamino] benzoic acid (14) 4- [ 2- (4-Bromophenylsulfonylamino) -5-chlorobenzoylamino] benzoic acid (15) 4- [2- (4-Methylphenylsulfonylamino) -5- chlorobenzoylamino] benzoic acid (16) 4- [2- (4-methoxyphenylsulfonylamino) -5- chlorobenzoylamino] ben zoic (17) 4- [2- (4-nitrophenylsulfonylamino) -5- chlorobenzoylamino] benzoic acid (18) 4- [2- (2,4-dichlorophenylsulfonylamino) -5- chlorobenzoylamino] benzoic acid (19) 4- [ 2- (4-n-Butylphenylsulfonylamino) -5- chlorobenzoylamino] benzoic acid (20) 4- [2- (4-chlorophenylsulfonylamino) benzoylamino] benzoic acid(21) 4- (2-phenylsulfonylamino-5-fluorobenzoylamino) benzoic acid (22) 4- (2-phenylsulfonylamino-4-fluorobenzoylamino) benzoic acid (23) 4- [2 (4-chlorophenylsulfonylamino-4-fluorobenzoylamino) acid) benzoic acid (24) 4- [2-fluorophenylsulfonylamino-5-chlorobenzoylamino) benzoic acid (25) 4- [2- (4-trifluoromethylphenylsulfonylamino-5-chlorobenzoylamino) benzoic acid (26) 4- (2-phenylsulfonylamino-5-chlorobenzoylaminomethyl) acid ) benzoic acid (27) 4- [2- (2-phenylvinyl) sulfonylamino-5-chlorobenzoylamino] benzoic acid (28) 4- [2- (2-phenylethyl) sulfonylamino-5-chlorobenzoylamino) benzoic acid (29) 4- acid [2 (2-chlorophenylsulfonylamino-5-nitrobenzoylamino) benzoic acid (30) 4- [2- (4-hydroxyphenylsulfonylamino-5-chlorobenzoylamino) benzoic acid (31) 4- (2-phenylsulfonylamino-5-chlorobenzoylaminocarbonyl) benzoic acid (32) 4- [2- (N-isopropyl-phenylsulfonylamino) -5- tri-fluoro-methyl-benzoic acid) benzoic acid (33) 4- [N- [2- (4-chlorophenylsulfonylamino-5-chloro ofhenyl] aminosulfonyl] -benzoic acid (34) 4- (2-benzoylamino-5-chlorobenzoylamino) benzoic acid (35) 4- (2-Butylsulfonylamino-5-chlorobenzoylamino) benzoic acid (36) 4- [2 (3-chlorophenylsulfonylamino benzoylamino] benzoic acid and (37) 4- [2- (4-bromophenylsulphonylamino) benzoylamino] benzoic acid and methyl esters thereof.

11. A compound according to claim, characterized in that it is selected from (1) 4- [2- (4-chlorophenylsulfonylamino) -5- chlorophenoxymethyl] benzoic acid (2) 4- (2-phenylsulfonylamino-5-chlorophenoxymethyl) acid benzoic acid (3) 4- (2-phenylsulfonylamino-4-chlorophenoxymethyl) benzoic acid (4) 4- [2- (4-chlorophenyl-sulfonamino) -4- chlorophenoxymethyl] benzoic acid (5) 4- [2- (4-chlorophenylsulfonylamino ) -5- chlorophenylmethoxy] benzoic acid (6) 4- (2-phenylsulfonylamino-5-trifluoromethylphenoxymethyl) benzoic acid, (7) 4- [2- (N-isopropyl-phenylsulfonylamino) -4- chlorophenoxymethyl] benzoic acid (8) acid 4- [2- (N-carboxymethyl-phenylsulfonylamino) -4- chlorophenoxymethyl] -benzoic acid (9) 4- [2- (N- (2-hydroxyethyl) -phenylsulfonylamino] -4- chlorophenoxymethyl] -benzoic acid (10) acid 4- [2- (N-Methyl-phenylsulfonylamino) -4-trifluoromethylphenoxymethyl] -benzoic acid (11) 4- [2- [N- (2-hydroxyethyl) -phenylsulfonylamino] -4- trifluoromethylphenoxymethyl] -benzoic acid (12) 4- [2- [N- (2-hydroxyethyl) -phenylsulfonylamino] -5-trifluoromethylphenoxymethyl] -benzoic acid (13) 4- [2- (N-Methyl-phenylsulfonylamino) -5- chlorophenoxymethyl] -benzoic acid (14) 4- [2- [N- (2-hydroxyethyl) -phenylsulfonylamino] -5- chlorophenoxymethyl] -benzoic acid (15) 4- [2- (N-Methyl-phenylsulfonylamino) -5- trifluoromethoxyphenoxymethyl] -benzoic acid (16) 4- [2- (N-isopropyl-phenylsulfonylamino) -5- trifluorophenoxymethyl] -benzoic acid (17) 4- [2- (N-isopropyl-phenylsulfonylamino) -5- chlorophenoxymethyl] -benzoic acid (18) acid 4- [ 2- (N-isopropyl-phenylsulfonylamino) -4-trifluoromethylphenoxymethyl] -benzoic acid (19) 4- [2- [N- (2-methoxyethoxymethyl) -phenylsulfonylamino] -4-chlorophenoxymethyl] -benzoic acid (20) acid 4- [ 2- [N- (2-methoxyethyl) -phenylsulfonylamino] -4- chlorophenoxymethyl] -benzoic acid (21) 4- [2- [N- [2- (2-methoxyethoxy) ethyl] -phenylsulfonylamino) -4-chlorophenoxymethyl] -benzoic acid (22) 4- [2- (N-Ethyl-phenylsulfonylamino) -4- chlorophenoxymethyl] -benzoic acid (23! 4- [2- (N-propyl-phenylsulfonylamino) -4- chlorophenoxymethyl] benzoic acid (24! 4- [2- (N-butyl-phenylsulfonylamino) -4- chlorophenoxymethyl] benzoic acid! 25: 4- [2- (N-pentill-phenylsulfonylamino) -4- chlorophenoxymethyl] benzoic acid (26; 4- [2- (N-hexyl-phenylsulfonylamino) -4- chlorophenoxymethyl] benzoic acid (27; 4- [2- (N-benzyl-phenylsulfonylamino ) -4- chlorophenoxymethyl] benzoic acid (28; 4- [2- (N-isopropyl-phenylsulfonylamino) -5-methylphenoxymethyl] benzoic acid (29) 4- [2- (N-methyl-phenylsulfonylamino) -5-methylphenoxymethyl] benzoic acid (30; 4- [2- [N- (2-hydroxyethyl) -phenylsulfonylamino] -5-methylphenoxymethyl] benzoic acid: 3i: 4- [2- [N- (prop-2-enyl) -phenylsulfonylamino) - 4- cyclophenoxymethyl] benzoic acid (32, 4- [2- (N-cyclopentyl-phenylsulfonylamino) -4-chlorophenoxymethyl] benzoic acid (33) 4- [2- [N- (2-methoxyethyl) -phenylsulfonylamino] - 5- trifluoromethylphenoxymethyl] benzoic acid (34) 4- [2- (N-Ethyl-phenylsulfonylamino) -5- trifluoromethylphene ximethyl] benzoic acid (35) 4- [2- (N-propyl-phenylsulfonylamino) -5- trifluoromethylphenoxymethyl] benzoic acid (36) 4- [2- (N-Isobutyl-phenylsulfonylamino) -5- trifluoromethylphenoxymethyl] benzoic acid (37) 4- [2- (N-cyclopentyl-phenylsulfonylamino) -5- trifluoromethylphenoxymethylene benzoic acid (38) 4- [2- [N- (prop-2-enyl) -phenylsulfonylamino] -5- trifluoromethylphenoxymethyl] benzoic acid (39) acid 4- [2 [N- (2-methylprop-2-enyl) -phenylsulfonylamino] -5-trifluoromethylphenoxymethyl] benzoic acid (40) 4- [2- (N-isopropyl-4-methylphenylsulfonylamino) -5- trifluoromethyl-phenoxymethyl] benzoic acid (41) 4- [2- (N-isopropyl-4-fluorophenylsulfonylamino) -5- trifluoromethylphenoxymethylbenzoic acid (42) 4- [2- (N-isopropyl-4-methoxyphenylsulfonylamino) -5- trifluoromethyl-phenoxymethyl acid ] benzoic acid (43) 4- [2- (N-isopropyl-phenylsulfonylamino) -5- chlorophenoxy] benzoic acid (44) 3- [2- (N-isopropyl-phenylsulfonylamino) -5- chlorophenoxy] cinnamic acid (45) acid trans-4- [2- (N-isopropyl-fe n-sulphonylamino) -5- trifluoromethylphenoxymethyl] cyclohexanoic acid (46) 4- [2- (N-isopropyl-phenylsulfonylamino) -5- chlorophenoxy] phenylacetic acid (47) 4- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid (48) 3- acid [4- [2- (N-isopropyl-phenylsulfonylamino) -5- trifluoromethylphenoxymethylpheniol isopropionic acid (49) 3- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] -phenylacetic acid (50) 4- acid [2- (N-isopropyl-4-ethoxyphenylsulfonylamino) -5-trifluoromethyl-1-phenoxymethyl] benzoic acid (51) 4- [2- (N-Isobutyl-phenylsulfonylamino) -5-methylphenoxymethyl] benzoic acid (52) 4- [2] acid - (N-isopropyl-phenylsulfonylamino) -5- fluorotenoxymethiij benzoic acid (53) 4- [2- (N-isopropyl-phenylsulfonylamino) -5-methoxyphenoxymethyl] -benzoic acid (54) 4- [2- (N-propyl) acid phenylsulfonylamino) -5-methylphenoxymethyl] benzoic acid (55) 4- [2- [N- (2-methylprop-2-enyl) -phenylsulfonylamino] -5-methylphenoxy-methyl] benzoic acid (56) 4- [2- [ N- (2-methylprop-2-enyl) -phenylsulfonylamino] -5-methylphenoxymethyl} benzoic (57) 4- [2- (N-cyclopropylmethyl-phenylsulfonylamino) -5-methylphenoxy-methyl] benzoic acid, (58) 4- [2- (N-Propyl-phenylsulfonylamino) -5-chlorophenoxymethyl] benzoic acid, (59) 4- [2- (N-Isobutyl-phenylsulfonylamino) -5-chlorophenoxymethyl] benzoic acid, (60) 4- [2- [N- (prop-2-enyl) -phenylsulfonylamino] -5-chlorophenoxymethyl] -benzoic acid, (61) 4- [2- [N- (2-methylprop-2-enyl) -phenylsulfonylamino] ] -5-chlorophenoxy-methyl] benzoic acid, (62) 4- [2- (N-cyclopropylmethyl-phenylsulfonylamino) -5-chlorophenoxymethyl] -benzoic acid, (63) 4- [2- (N-methoxymethyl-phenylsulfonylamino) -5-trifluoromethylphenoxy-methyl] benzoic acid, (64) 4- [2- (N-Isobutyl-phenylsulfonylamino) -4-methylphenoxymethyl] benzoic acid, (65) 4- [2- (N-isopropyl-phenylsulfonylamino) -4 -methylphenoxymethyl] benzoic acid, (66) 4- [2- [N- (prop-2-enyl) -phenylsulfonylamino] -4-methylphenoxymethyl] -benzoic acid, (67) 4- [2- (N-isopropyl-4 -ethoxyphenylsulfonylamino) -5-chlorophenoxymethyl] benzoic acid, (68) 4- [2- (N-isopropyl-4-ethoxyphenylsulfonylamino) -5-methylphenoxy-methyl] benzoic acid, (69) 4- [2- (N) acid -ethyl-phenylsulfonylamino) -4-methylphenoxymethyl] benzoic acid, (70) 4- [2- (N-propyl-phenylsulfonylamino) -4-methylphenoxymethyl] benzoic acid, (71) 4- [2- (N-butyl-phenylsulfonylamino ) -4-methylphenoxymethyl] benzoic acid, (72) 4- [2- [N- (2-methylprop-2-enyl) -phensulfonylamino] -4-methylphenoxy-methyl] benzoic acid, (73) 4- [2- (N-cyclopropylmethyl-phenylsulfonylamino) -4-methylphenoxymethyl] benzoic acid, (74) 4- [2- (N-isopropyl-propylsulfonylamino) -5-methylphenoxymethyl] benzoic acid, (75) 4- [2- (N-isopropyl -pentylsulfonylamino) -5-methylphenoxymethyl] benzoic acid, (76) 4- [2- (N-benzyl-methylsulfonylamino) -5-methylphenoxymethyl] benzoic acid, (77) 4- [2- (N-benzyl-propylsulfonylamino) - 5-methylphenoxymethyl] benzoic acid, (78) 4- [2- (N-isopropyl-cyclopentylsulfonylamino) -5-methylphenoxymethyl] benzoic acid, (79) 4- [2- (N-Isobutyl-ethylsulfonylamino) -4-methylphenoxymethyl] benzoic, (80) 4- [2- (N-Isobutyl-propylsulfonylamino) -4-methylphenoxymethyl] benzoic acid, (81) acid 4- [2- (N-Isobutyl-butylsulfonylamino) -4-methylphenoxymethyl] enzoic acid, (82) 4- [2- (N-Isobutyl-propylsulfonylamino) -5-methylphenoxymethyl] benzoic acid, (83) 4- [ 2- [N- (prop-2-enyl) -propylsulfonylamino] -5-methylphenoxymethyl] enzoic, (84) 4- [2- [N- (2-methylprop-2-enyl) -propylsulfonylamino] -5-methylphenoxymethyl acid ] benzoium, (85) 4- (2- (N-Isobutyl-phenylsulfonylamino) -4-chlorophenoxymethyl] enzoic acid, (86) 4- [2- (N-Propyl-propylsulfonylamino) -5-methylphenoxymethyl] benzoic acid, ( 87) 4- [2- (N-Isobutyl-hexylsulfonylamino) 4-methylphenoxymethyl] benzoic acid, (88) 4- [2- (N-Isobutyl-pentylsulfonylamino) -4-methylphenoxymethyl] benzoic acid, (89) 4- acid [2- [N- (prop-2-enyl) -propylsulfonylamino] -5-trifluoromethylphenoxymethyl] benzoic acid, (90) 4- [2- (N- (2-methyl-rop-2-enyl) -propylsulfonylamino] ] -5-trifluoromethyl-phenoxymethyl] benzoic acid, (91) 4- [2- (N-propyl-propylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid, (92) 4- [2- (N-isobutyl-propyl) sulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid, (93) 4- [2- (N-propyl-phenylsulfonylamino) -5-methylphenoxymethyl] enzoic acid, (94) 4- [2- (N-isobutyl-phenylsulfonylamino) -5 -methylphenoxymethyl] cinnamic, (95) 4- [2- (N-Isobutyl-propylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid, (96) 4- [2- (N-Methyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid (97) 4- [2- (N-Propyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid, (98) 4- [2- (N-Isobutyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid, (99) 4- [2- (N-isopropyl-propylsulfonylamino) -5-methylphenoxymethyl] cinnamic acid, (100) 4- [2- (N-Ethyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid, (101) 4- [ 2- (N-cyclopropylmethyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid, (102) 4- [2- (N-isopropyl-methylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid, (103) 4- [2- (N) acid -benzyl-propylsulfonyl no) -5-trifluoromethylphenoxy-ethyl] cinnamic, (104) 4- [2- (N-Propyl-phenylsulfonylamino) -4-methylphenoxymethyl] cinnamic acid(105) 4- [2- [N- (prop-2-enyl) -phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid, (106) 4- [2- [N- (2-methyl? Rop-2) acid -enyl) -phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic,(107) 4- [2- (N-Isobutyl-phenylsulfonylamino) -4-methylphenoxymethyl] cinnamic acid, (108) 4- [2- (N-Benzyl-methylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid, (109) acid 4- [2- (N-isopropyl-phenylsulfonylamino) -4-trifluoromethylphenoxymethyl] cinnamic acid, (110) 4- [2- (N-Isobutyl-ethoxyphenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid, (11) 4- [2 - (N-methyl-phenylsulfonylamino) -4-chlorophenoxymethyl] benzoic acid, (112) 4- [2- (N-cyclopentylmethyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid, (113) 4- [2- (N-) acid cyclopropylmethyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid, (114) 4- [2- (Nt-Butylmethyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid, (115) 4- [2- (N-isopropyl-phenylsulfonylamino)} -5-trifluoromethylphenoxymethyl] phenylacetic acid, (116) 4- [2- (N-isopropyl-propylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid, (117) 4- [2- (N-isopropyl-pentylsulfonylamino) -5- acid trifluoromethylphenoxymethyl] benzoic acid, (118) 4- [2- (N-isopropyl-butylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid (119) 4- [2- (N-isopropyl-hexylsulfonylamino) -5-trifluoromethylphenoxy acid (120) Acid 4- [2- (N-isopropyl-heptylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid, (121) 4- [2- (N-isopropyl-4-hydroxyphenylsulfonylamino) -5-trifluoromethylphenoxymethyl) -benzoic acid, (122) Acid 4 - [2- (N-isopropyl-butylsulfonylamino) -5-methylphenoxymethyl] benzoic acid (123) 4- [2- (N-isopropyl-hexylsulfonylamino) -5-ethylphenoxymethyl] benzoic acid (124) 4- [2- (N) acid -isopropyl-heptylsulfonylamino) -5-methylphenoxymethyl] benzoic acid (125) 4- [2- (N-isopropyl-methylsulfonylamino) -5-methylphenoxymethyl] benzoic acid (126) 4- [2- (N-isopropyl-ethylsuiphenylamino) - 5-methylphenoxymethyl] benzoic acid (127) 4- [2- (N-isopropyl-2-phenylethylsulfonylamino) -5-methylphenoxymethyl] benzoic acid (128) 4- [2- (N-isopropyl-benzylsulfonylamino) -5-ethylphenoxymethyl] acid] Benzoic (129) Acid or 4- [2- (Nt-Butylmethyl-phenylsulfonylamino) -4-methylphenoxymethyl] benzoic acid (130) 4- [2- (N-isopropyl-methylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid (131) 4- [2- (N-isopropyl-ethylsulfonyalmino) -5-trifluoromethylphenoxymethyl] benzoic acid (132) 4- [2- (N-isopropyl-cyclopentylmethylsulfonylamino) -5-methylphenoxymethyl] benzoic acid (133) 4- [2- (N-Cyclohexylmethyl-propylsulfonylamino) -5-methylphenoxymethyl] benzoic acid (134) 4- [2- (N-Cyclopentylmethyl-propylsulfonylamino) -5-methylphenoxymethyl] benzoic acid (135) Acid 4- [2- (N-isopropyl-propylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid (136) 4- [2- (N-isopropyl-pentylsulfonolamino) -5-trifluoromethylphenoxymethyl] cinnamic acid acid (137) 4- [2- (N- isopropyl-4-chlorophenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid (138) 4- [2- (N-isopropyl-4-ethylphenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid (139) 4- [2- (N-isopropyl- 4-propylphenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid (140) 4- [2- (N-isopropyl-4-buylphenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid (141) 4- (2-phenylsulfonylamino-phenoxymethyl) benzoic acid (142) 4- [2- (4-Chlorophenylsulfonylamino) phenoxymethyl) benzoic acid (143) 4- (2-Phenylsulfonylamino-4-fluorophenoxymethyl) benzoic acid (144) 4- (2-Phenylsulfonylamino-5-fluorophenoxymethyl) benzoic acid (145) 4- (2-Phenylsulfonylamino-4-bromophenoxymethyl) benzoic acid (146) 4- (2-phenylsulfonylamino-5-chlorophenylthiomethyl) benzoic acid (147) 4- (2-phenylsulfonylamino-4-methoxyphenoxymethyl) benzoic acid (148) ) 4- (2-Phenylsulfonylamino-4-trifluoromethylphenoxymethyl) benzoic acid (149) 4- (2-phenylsulfonylamino-4-methylphenoxymethyl) benzoic acid (150) 4- (2-phenylsulfonylamino-5-methylphenoxymethyl) benzoic acid (151) Acid 4- (2-Benzylsulfonylamino-5-chlorophenoxymethyl) benzoic acid (152) 4- (2-Phenylsulfonylamino-5-methoxyphenoxymethyl) benzoic acid (153) 3- (2-phenylsulfonylamino-5-chlorophenoxymethyl) benzoic acid (154) Acid 4- (2-phenylsulfonylamino-4-chloro-5-methylphenoxymethyl) benzoic acid (155) 4- (2-phenylsulfonylamino-4), 5-dichlorophenoxymethyl) benzoic acid (156) 4- (2-phenylsulfonylamino-5-chlorophenoxymethyl) phthalic acid (157) 4- (2-phenylsulfonylamino-5-chlorophenoxy) benzoic acid (158) 4- [3- (2- phenylsulfonylamino-5-chlorophenoxy) propyl] benzoic acid (159) trans-4- (2-phenylsulfonylamino-5-chlorophenoxymethyl) cyclohexane acid (160) cis-4- (2-phenylsulfonylamino-5-chlorophenoxymethyl) cyclohexane acid (161) Acid 4 - [1RS- (2-phenylsulfonylamino-5-chlorophenoxy) ethyl] benzoic acid (162) 4- [2- [N- (2-hydroxy-2-methylpropyl) -phenylsulfonylamino] -5-trifluoromethylphenoxymethyl] benzoic acid (163) 4- [2- [N- (2-Hydroxy-2-methylpropyl) -phenylsulfonylamino] -5-trifluoromethylphenoxymethyl] -iami acid (164) 4- [2- [N- (2-Hydroxy-2-methylpropyl) -phenylsulfonylamino] -5-methylphenoxymethyl] benzoic acid (165) 4- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl acid ] phenoxyacetic (166) 4- [2- (N-isopropyl-phenylsulfonylamino) -5-methylphenoxymethyl] phenoxyacetic acid (167) 4- [2- (N-isopropyl-phenylsulfonylamino) -5-methylphenoxymethyl] cinnamic acid (168) Acid 4- [2- (N-isopropyl-phenylsulfonylamino) -5-chlorophenoxymethyl] phenoxyacetic acid (169) 4- [2- (N-isopropyl-phenylsulfonylamino) -5-chlorophenoxymethyl] cinnamic acid (170) 4- [2- [ 2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenoxy] ethyl] benzoic acid (171) 2-Methoxy-4- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethyl-phenoxymethyl] benzoic acid (172) Acid 2 -hydroxy-4- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid (173) 2-Hydroxy-4- [2- (N-isopropyl-phenylsulfonylamino) -5-methylphenoxymethyl] benzoic acid (174) 2-Hydroxy-4- [2- (N-isopropyl-phenylsulfonylamino) -5-chlorophenoxymethyl acid ] benzoic acid (175) 4- [2- (N-isopropyl-phenylsulfonylamino) -5- triufluoromethylphenylamino-methyl] benzoic acid (176) 4- [N-methyl- [2- (N-isopropyl-phenylsulfonylamino) -5- trifluoromethyl-phenyl] aminomethyl] benzoic acid (177) 4- [2- [N- (1, 3-dihydroxyprop-2-yl) -phenylsulfonylamino] -5-trifluoromethyl-phenoxymethyl] benzoic acid (178) 4- [2- [N- (1, 3-dimethoxyprop-2-yl) -phenylsulfonylamino] -5-trifluoromethyl-phenoxymethyl] benzoic acid (179) 4- [2- (N-isopropyl-1-hexenosulfonylamino) -5- trifluoromethylphenoxymethyl] benzoic acid (180) 4- [2- (N-isopropyl-cyclopentylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid (181) 4- [2- (N-isopropyl-cyclohexylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid ( 182) 4- [2- (N-isopropyl-cyclohexylsulfonylamino) -5-methylphenoxymethyl-J -benzoic acid (1) 83) 4- [2- (N-isopropyl-isopropylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid (184) 4- [2- (N-isopropyl-isopropylsulfonylamino) -5-methylphenoxymethyl] -benzoic acid (185) 4- [2- (N-isopropyl-isopropylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid (186) 4- [2- (N-isopropyl-cyclopentylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid (187) ) 4- [2- (N-isopropyl-cyclohexylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid (188) 4- [2- [N- (N, N-dimethylaminocarbonylmethyl) -phenylsulfonylamino] -5- trifluoromethylphenoxymethyl] benzoic acid (189) 4- [(2-phenylsulfonylamino-5-isopropylphenoxymethyl) benzoic acid (190) 4- (2-phenylsulfonylamino-5-hydroxymethylphenoxymethyl) benzoic acid (191) 4- (2-phenylsulfonylamino-5-hydroxymethylphenoxymethyl) benzoic acid ( 192) 4- (2-phenylsulphonylaminomethyl-5-chlorophenoxymethyl) benzoic acid (193) 4- [2- (N-isopropyl-phenylsulfonylamino) -5- tri-lorubomethyl-methyphenyloxy-methyl-tert-propionic acid (194) 4- (2-phenylsulfonylamino) -4- chlorophenoxymethylmethyl) benzyl (195) 4- (2-benzoylamino-5-chlorophenoxymethyl) benzoic acid (196) 4- [2- (N-isopropyl-phenylsulfonylamino) -5- isopropylphenoxymethyl] benzoic acid (197) 4- [2- (N-methyl-phenylsulfonylamino) -5- isopropylphenoxymethyl] benzoic acid (198) 4- acid [2- (N-isopropyl-phenylsulfonylamino) -5-ethylphenoxymethyl] enzoic acid (199) 4- [2- (N-isopropyl-4-propoxyphenylsulfonylamino) -5-trifluoromethyl-phenoxymethyl] benzoic acid (200) 4- [2 - (N-isopropyl-4-ethylthiophenylsulfonylamino) -5-trifluoromethyl-1-phenoxymethyl] benzoic acid (201) 4- [2- (N-isopropyl-4-methylthiophenylsulphonylamino) -5-trifluoromethyl-1-phenoxymethyl] benzoic acid (202) 4- acid [2- (N-isopropyl-4-butoxyphenylsulfonylamino) -5-trifluoromethyl-phenoxymethyl] benzoic acid (203) 4- [2- (N-isopropyl-4-isopropoxyphenylsulfonylamino) -5-trifluoromethyl-phenoxymethyl] benzoic acid (204) 4- [2- (N-Isobutyl-benzoylamino) -5- chlorophenoxymethyl] benzoic acid (205) 4- [2- (N-isopropyl-benzoylamino) -5-trifluoromethylphenoxymethyl] -benzoic acid (206) 6- [2- (N-isopropyl-phenylsulfonylamino) -5- trifluoromethylphenoxy-methyl] -naphthalic acid (207) 4- [2- (N-isopropyl-butyrylamino) -5-trifluoromethylphenoxymethyl] -cinnamic acid (208) 4- [2- (N-isopropyl-4-ethoxyphenylsulfonylamino) -5-trifluoromethylphenoxymethyl] -cinnamic acid (209) 4- [2- (N-Isobutyl-4-ethoxyphenylsulfonylamino) -5-trifluoromethyl-phenoxymethyl] cinnamic acid and (210) 4- [2- (N-isopropyl-3-ethoxyphenylsulfonylamino) -5-trifluoromethyl- acid phenoxymethyl] benzoic acid and esters thereof.

12. A compound according to claim 1, characterized in that it is selected from (1) 4- [2- [2- (4-chlorophenylsulfonylamino) -5-chlorophenyl] - (E) -vinyl] benzoic acid, (2) 4 - [2- [2- (4-chlorophenylsulfonylamino) -5-chlorophenyl] - (Z) -vinyl] benzoic acid, (3) 4- [2- [2- (4-chlorophenyl) sulfonylamino-5-chlorophenyl] ethyl ] benzoic acid, (4) 4- [2- [2- (4-chlorophenylsulfonylamino) -5-chlorophenyl] ethynyl] benzoic acid, (5) 4- [2- [2- (N-isopropyl-phenylsulfonylamino) -5 acid -trifluoromethylphenyl] ethyl] benzoic acid, (6) 4- [2- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenyl] - (E) -vinyl] benzoic acid, (7) 4- [2- [ 2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenyl] - (Z) -vinyl] benzoic acid, and methyl esters thereof.

13. A compound according to claim 1 characterized in that it is selected from (1) 4- [2- (N-isopropyl-2-thienylsulfonylamino) -5-chlorophenoxymethyl] benzoic acid, (2) 4- [2- ( N-isopropyl-2-thienylsulfonylamino) -5-methylphenoxymethyl] benzoic acid, (3) 4- [2- (N-isopropyl-2-furanylsulfonylamino) -5-methylphenoxymethyl] benzoic acid, (4) 4- [2- ( N-isopropyl-2-furanylsulfonylamino) -5-chlorophenoxymethyl] benzoic acid, (5) 4- [2- (N-propyl-2-furanylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid, (6) 4- [2- ( N-propyl-2-furanylsulfonylamino) -5-methylphenoxymethyl] benzoic acid, (7) 4- [2- (N-Isobutyl-2-furanylsulfonylamino) -5-methylphenoxymethyl] benzoic acid, (8) 4- [2- ( N-isobutyl-2-furanylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid, (9) 4- [2- [N- (prop-2-enyl) -2-furanylsulfonyl-amino] -5-methylphenoxymethyl] benzoic acid, (10) ) 4- [2- [N- (2-methylprop-2-enyl) -2-furanylsulfonylamino] -5-methylphenoxymethyl] benzoic acid, (11) 4- [2- (N-Isobutyl-2-furanylsulfonylamino) -4-methylphenoxymethyl] benzoic acid, (12) 4- [2- (N-isopropyl-2-furanylsulfonylamino) -4-methylphenoxymethyl] benzoic acid, (13) 4- [2- [N- (2-methylprop-2-enyl) -2-furanylsulfonylamino] -4-methylphenoxymethyl] benzoic acid, (14) 4- [2- (N-isopropyl-2-furanylsulfonylamino) -5 acid -methylphenoxymethyl] cinnamic, (15) 4- [2- (N-isopropyl-2-furanylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid, (16) 4- [2- (N-isopropyl-2-furanylsulfonylamino) -4 -trifluoromethylphenoxymethyl] benzoic acid, (17) 4- [2- (N-Isobutyl-2-furanylsulfonylamino) -4-trifluoromethylphenoxymethyl] benzoic acid,. (18) 4- [2- (N-Isobutyl-2-furanylsulfonylamino) -5-chlorophenoxymethyl] benzoic acid, (19) 4- [2- (N-isopropyl-2-furanylsulfonylamino) -5-chlorophenoxymethyl] cinnamic acid, (20) 4- [2- (N-Isobutyl-2-furanylsulfonylamino) -5-chlorophenoxymethyl] cinnamic acid, (21) 4- [2- (N-Isobutyl-2-furanylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid, (22) 4- [2- (N-Isobutyl-2-furanylsulfonylamino) -4-chlorophenoxymethyl] benzoic acid, (23) 4- [2- (N-Isobutyl-2-furanylsulfonylamino) -4-methylphenoxymethyl] cinnamic acid, (24) 4- [2- (N-isopropyl-2-furanylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid, (25) 4- [2- (N-isopropyl-2-thienylsulfonylamino) -5-trifluoromethylphenoxymethyl] benzoic acid, (26) 4- [2- [N-Hydroxy-2-methylpro? Il) -2-thienylsulfonylamino] -5-trifluoromethylphenoxymethyl] benzoic acid, (27) 4- [2- (N-isopropyl-2-furoylamino) -5-trifluoromethylphenoxymethyl] benzoic acid, (28) 4- [2- (2-thienylsulfonylamino) -5-chlorobenzoylamino] benzoic acid, (29) acid 4- [2- (N-isopropyl-2-furanylsulfonylamino) -5-methylphenylthiomethyl] benzoic acid, (30) 4- [2- (N-Isobutyl-2-thienylsulfonylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid, (31) acid 4- [2- (N-isopropyl-2-furoylamino) -5-trifluoromethylphenoxymethyl] cinnamic, and (32) 4- [2- (N-isobutyl-2-furoylamino) -5-trifluoromethylphenoxymethyl] cinnamic acid, and methyl esters thereof.

14. A compound according to claim 1, characterized in that it is selected from (1) 5- [2- (N-isopropyl-phenylsulfonylamino) -5-methylphenoxymethyl] furan-2-carboxylic acid, (2) 6- ( 2-phenylsulfonylamino-5-chlorophenoxymethyl) -nicotinic acid, (3) 5- [2- (N-isopropyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] thiophene-2-carboxylic acid, (4) 5- [2- (N- isopropyl-phenylsulfonylamino) -5-trifluoromethylphenoxymethyl] furan-2-carboxylic acid, (5) 5- [2- (N-isopropyl-phenylsulfonylamino) -5-methylphenoxymethyl] thiophene-2-carboxylic acid, (6) 5- [2-acid] - (N-isopropyl-phenylsulfonylamino) -5-chlorophenoxymethyl] thiophene-2-carboxylic acid, (7) 5- [2- (N-isopropyl-phenylsulfonylamino) -5-chlorophenoxymethyl] furan-2-carboxylic acid, and (8) 4- (3-phenylsulfonylamino-5-trifluoromethylpyridin-2-yloxymethyl) benzoic acid, and methyl esters thereof.

15. An E2 agonist or antagonist of prostaglandin, characterized in that it comprises the sulfonamide or carbonamide derivative of the formula (I) shown in claim 1, or a non-toxic salt thereof as an active ingredient. SUMMARY OF THE INVENTION The sulfonamide or carboamide derivatives of the formula (I) and a pharmaceutical composition which comprises the same as an active ingredient: (where in ring A, ring B is a carbocyclic ring, a heterocyclic ring, Z1 is -COR1, -CH = CH-COR1, etc., Z2 is H, alkyl, etc., Z3 is a double bond, alkylene Z4 is S02, CO; Z5 is alkyl, phenyl, a heterocyclic ring, etc., R2 is CONR8, O, S, NZ6, Z7-alkylene, alkylene, etc. R3 is H, alkyl, halogen, CF3 etc .; R 4 is H, (substituted) alkyl, etc., n, t is 1-4). The compounds of the formula (I) can bind to the PGE2 receptors, and display aantagonist activity against the action thereof, or an agonistic activity. Therefore, they are considered to be used as medicine for the inhibition of uterine contraction, analgesics, antidiarrheals, sleep inducers, medicine to increase bladder capacity or medicine for uterine contraction, cathartic, suppression of gastric acid secretion, antihypertensive or diuretic agents.