MXPA97006627A - Derivative of tiazolidinone optically act - Google Patents

Abstract

A thiazolidinonaptically active derivative having the general formula (I): wherein R represents a hydrogen atom, a C 1 -C 4 alkyl group, a phenyl group, a substituted phenyl group (said substituent represents C 1 -C 4 alkyl, C 1 alkoxy -C4 or halogen), a phenylalkyl group of C1-C2 or a substituted phenylalkyl group of C1-C2 (the substituent of said phenyl represents C1-C4 alkyl, C1-C4 alkoxy or halogen) R1 represents a C1-6 alkyl group C6; and n represents 1 or 2, the thiazolidinonaptically active derivative of the present invention having thiazolidinonaptically active of the present invention has excellent action against angina pectoris and is useful as a preventive agent or a therapeutic agent for angina pec

Description

DERIVATIVE OF OPTICAL ACTIVE TIAZOLIDINONE FIELD OF THE INVENTION The present invention relates to optically active thiazole thiazole derivatives having an excellent dilation action of collateral vessel and action against angina pectoris, a composition for prevention or therapy of angina which comprises them as an active ingredient, the use of the same to produce a pharmaceutical preparation for prevention or therapy of angina pectoris, a preventive or therapeutic method for angina which comprises administering a pharmacologically effective amount thereof to a mammal, or a method of preparing the same; or a composition for prevention or therapy of an ulcerative disease comprising thia- or oxazolidinone derivatives as an active ingredient, the use thereof to produce a pharmaceutical preparation for prevention or therapy of an ulcerative disease or a preventive or therapeutic method. for an ulcerative disease comprising administering a pharmacologically effective amount thereof to a mammal.

BACKGROUND OF THE INVENTION Currently, nitroglycerin is the most frequently used therapeutic agent for cardiovascular diseases, particularly angina pectoris. - However, nitroglycerin easily suffers the effect of the first step and has the defect that the duration of its action is short. Meanwhile, headache, vertigo and tachycardia appear as side effects due to the reduction in blood pressure. In view of this background, a therapeutic agent for angina pectoris has been required with prolonged actions that do not clinically suffer the first-pass effect. The present inventors have found, as a means to solve the above problem, a compound having a thia- or oxazolidinone backbone, for example, compound A having the following formula: compound A (wherein Ra, Rb, Re and Rd represent a hydrogen atom, etc., 0 represents an alkylene group of C2-C6 and Y represents an oxygen atom or a sulfur atom) (e.g., 25 Patent Publication No examined Japanese (KOKOI) No. Hei 5 ~ 213910). However, an anti-ulcerative action of these compounds has not been known at all.

BRIEF DESCRIPTION OF THE INVENTION The present inventors did additional study * - and have found that compounds having an optically active thiazolidone skeleton have an excellent collateral vessel dilation action which is prolonged and exhibits fewer side effects, the compounds being useful as a preventive agent or a therapeutic agent for angina pectoris (particularly a therapeutic agent for angina pectoris) and the compounds have excellent stability to achieve the present invention. In addition, the present inventors made studies on the pharmacological effects of the compounds having a skeleton of t a- or oxazolidinone and have found that these compounds have an excellent an ulcular ulcer action and the compounds are useful as a preventive or a therapeutic agent for an ulcerative disease (particularly a therapeutic agent for an ulcerative disease). The present invention provides optically active t-azole derivatives, a composition for prevention or therapy of angina which comprises them as an active ingredient, the use thereof to produce a pharmaceutical preparation for prevention or therapy of angina pectoris, a preventive or therapeutic method for angina which comprises administering a pharmacologically effective amount thereof to a mammal or a method of preparing the same; or a composition for prevention or therapy of an ulcerative disease comprising t a- or oxazolidinone derivatives as an active ingredient, the use thereof to produce a pharmaceutical preparation for prevention or therapy of an ulcerative disease or a preventive or therapeutic method for an ulcerative disease that involves administering a pharmacologically effective amount thereof to a mammal.

DETAILED DESCRIPTION OF THE INVENTION The optically active thiazolidone derivatives of the present invention have the general formula: In the above formula, R 1 represents a hydrogen atom, a C 1 -C 4 alkyl group, a femlo group, a substituted phenyl group (the substituent represents c_-C * alkyl, Ci-C alkoxy or halogen), a phenylalkyl group of Ci-C2 or a phenylalkyl group of substituted Ci-C2 (the femlo substituent represents a Ci-C4 alkyl, Ci-C4 alkoxy or halogen); R2 represents an alkyl group of Ci-Cβ; and refer to 1 or 2. A thia- or oxazolidmone derivatives which are an active ingredient of a preventive agent or a therapeutic agent for an ulcerative disease have the general formula: In the above formula, W represents a sulfur atom or an oxygen atom and X represents a group having the formula: -N (R3) - or X represents a sulfur atom or an oxygen atom and W represents a group that has the formula: ~ N (R3) -; R3 represents a hydrogen atom, an alkyl group of Ci-C or an arylalkyl group of C_-C "; R * and R5 may be the same or different and represent a hydrogen atom, an alkyl group of Ci-Cß, an arylalkyl group of Ci-C *, an aryl group, a 5- or 6-membered heterocyclic aromatic group containing from 1 to 3 heteroatoms selected from the group consisting of nitrogen atoms, oxygen atoms and sulfur atoms, which may optionally be fused with a benzene ring or a 5- or 6-membered heterocyclic aromatic group containing 1 to 3 heteroatoms selected from the group consisting of nitrogen atoms, oxygen atoms and sulfur atoms which may be optionally substituted and condensed with a benzene ring (the substituent represents C_ -Ce alkyl, arnino, Ci-C monoalkylaryn or dialkylamino of d -Ce). R6 represents a hydrogen atom, an Ci-Cß alkyl group or a C 1 -C 4 arylalkyl group; A represents an alkylene group of O 2 -Ce or a substituted alkylene group of C 2 -Ce (the substituent represents a carboxyl group, an alkoxycarbonyl group of Ci-Ce or a loxycarbonyl group); and the aforementioned aplo represents C 1 -C 0 or C 1 -C 1 substituted aryl (the substituent represents C 1 -Ce alkyl, C 1 -C e alkoxy, hydroxy, halogen, anino, C 1 -C e-nonoalkylamino, Ci dialkylanino- Ce or nitro). The alkyl group of Ci-A of Rl etc., or the alkyl entity of the Ci-C alkoxy group included in Rl can include, for example, a methyl, ethyl, propyl, isopropyl, butyl, s-butyl, isobutyl group and t-butyl, preferably an alkyl group of C1-C3, most preferably a C1-C2 alkyl group, and particularly preferably a methyl group. The hydrogen atom included in Rl can include, for example, a fluorine, chlorine, bromine and iodine atom, and preferably a fluorine atom or a chlorine atom. The phenylalkyl group of Ci-C2 of R1 may preferably include benzyl group or phenethyl group, and preferably benzyl group. The C 1 -C e alkyl group of R 2 may include, for example, a methyl, ethyl, propyl, isopropyl, butyl, single, isobuyl, t-butyl, pentyl and hexyl group, preferably an alkyl group of Ci-C4, most preferably a methyl, ethyl, propyl, sopropyl, butyl or isobutyl group, preferably a methyl, propyl, butyl or isobutyl group, and a methyl group is particularly preferred. The Ci-Ce alkyl group of R3, R *, RS, Rβ, etc., or the alkyl entity of the Ci-C alkoxy group or the Ci-C alkylating group included in R3, A, etc., may include the above group, preferably an Ci-C4 alkyl group, preferably an Ci-C2 alkyl group, and is particularly preferable a methyl group. The entity aplo of the aplaclime group of Ci-C > of R3, R *, R5 and R6 may include the group described below and the alkyl entity may include the above group; and may include, for example, a benzyl, phenethio, 2-phenylpropyl, 3-phenylpropyl, 4-phenylbutyl, diphenylmetyl, 1-naphthylphenyl, and 2-naphthylmethyl group, preferably phenylalkyl group. of C1-C4, most preferably a benzyl group or a phenethyl group, and a benzyl group is particularly preferred. The aryl group of R * and R5 or the aryl entity of the aryloxycarbon group included in fl may include the above group, and preferably a phenol group. The halogen of the substituent of the group aplo of R¿ and R5 may include the above group, and preferably a fluorine atom or a chlorine atom. The heterocyclic aromatic group of 5 or & members containing 1 to 3 heteroatoms selected from the group consisting of nitrogen atoms, oxygen atoms and sulfur atoms, which may optionally be fused to a benzene ring may include, for example, furyl, t-enyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isotylazole, irnidazolyl, pyrazolyl, pipdyl pyridazinyl, pyrimidinyl, indolyl, qumolyl and quimazolim, preferably functional, time, oxazolyl, isoxazolyl, isoxazolyl, thiazolyl, isothiazolyl or pyridyl, most preferably a furyl, thienyl or pipdoyl group, and a fuplo group or a thienyl group is par ticularly preferable. The alkylene group of the C 2 -Ce alkylene group of A may include, for example, ethylene, methylethylene, trirnethylene, tetraethylene, pentamethien and hexamethyl, preferably an alkylene group of C 2 -C *, and an ethylene group is particularly preferred. or a methylethylene group. In the compound (II), those containing a carboxyl or phenol entity can form salts with a base. Said salts can include, for example, a salt with an alkali metal such as lithium, sodium and potassium, a salt with a calcium metal such as barium and calcium, a salt with other metals such as magnesium and aluminum, a salt with a organic amine such as dicyclohexylamine and a salt with a basic amino acid such as lysine and arginine, and preferably a salt with an alkali metal. Meanwhile, the compound (II) containing amino or alkylammo groups can form salts with an acid. Said salts may include, for example, a salt with an inorganic acid such as hydrochloric acid, brornhydric acid, sulfuric acid, phosphoric acid and carbonic acid, a salt with a carboxylic acid such as acrylic acid, fumaric acid, oxalic acid, acid malonic acid, succinic acid, citric acid, malic acid and benzoic acid, a salt with a sulphonic acid such as methanesulphonic acid, ethanesulonic acid, benzenesulonic acid and toluensulonic acid and a salt with an acidic amino acid such as glutamic acid and acid aspartic acid, and preferably a salt with hydrochloric acid or a carboxylic acid co. In addition, the present invention includes hydrates of the compound (T) and in the case where there is an asymmetric carbon atom in a molecule of the compound (II), the present invention includes a racemic modification and an optically active substance and also includes the compound (II) or hydrates of a salt thereof. Meanwhile, the compound (I) included in the compound (II) also has an excellent ulcerative action. The compound having the general formula (I) can preferably include 1) A compound in which R 1 is a hydrogen atom, an C 1 -C 4 alkyl group, a femlo group, a substituted phenyl group (the substituent is methyl, rnetoxy) , fluorine or chlorine), a benzyl group, a substituted benzyl group (the substituent is methyl, methoxy, fluorine or chlorine), a phenethyl group or a substituted phenethyl group (the substituent is methyl, ethoxy, fluorine or chlorine). 2) A compound in which Rl is a hydrogen atom, a methyl group, a 4-rnetox? Fen? it or a benzyl group. 3) A compound in which Rl is a hydrogen atom. 4) A compound in which R2 is a C1-C4 alkyl group. 5) A compound in which R2 is a methyl group, an ethyl group, a propyl group, a sopropyl group, a butyl group or an isobutyl group. 6) A compound in which R2 is a methyl group, a propyl group, a butyl group or an isobutyl group. 7) A compound in which R2 is a methyl group, and?) A compound in which n is 1. Meanwhile, an optional combination of the compound arbitrarily selected from the group consisting of 1) - 3), 4) is preferred. - 7) and B), and may include, for example, the following compounds. 9) A compound in which R1 is a hydrogen atom, an alkyl group of CiC ", a phenyl group, a substituted phenyl group (the substituent is methyl, methoxy, fluorine or chlorine), a benzyl group, a substituted benzyl group (the substituent is methyl, methoxy, fluoro- or chloro), a phenethyl group or a substituted phenethyl group (the substituent is methyl, methoxy, fluoro or chloro); R2 is an alkyl group of C? ~ C "; and n is 1, 10) A compound in which R 1 is a hydrogen atom, a methyl group, a 4-methoxyphenyl group or a benzyl group; R 2 is a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group or an isobutyl group; and n is 1, 11) A compound in which R 1 is a hydrogen atom; R2 is a methyl group, a propyl group, a butyl group or an isobutyl group; and n is 1, and 12) A compound in which R 1 is a hydrogen atom; and R2 is a methyl group. Meanwhile, the compound having the above general formula (II) may preferably include 13) A compound in which R3 is a hydrogen atom, an alkyl group of C_-C, a benzyl group or a phenethyl group; 14) A compound in which R3 is a hydrogen atom, a methyl group or a benzyl group, 15) A compound in which U is a sulfur atom or? N oxygen atom and X is a group having the formula -N (R3) - (wherein R3 is a hydrogen atom) or X is a sulfur atom and U is a group having the formula: -N (R3) - (wherein R3 is a hydrogen atom) , 16) A compound in which U is a sulfur atom or an oxygen atom and X is a group having the formula: -NR3- (wherein R3 is a hydrogen atom), 17) A compound in which R * and R5 can be the same or different and each is a hydrogen atom, a C1-C4 alkyl group, a C1-C4 phenylalkyl group, a substituted C1-C4 phenylalkyl group (the phenyl substituent is alkyl) of C 1 -C 4, C 1 -C 4 alkoxy, hydroxy, halogen or nitro), a naphthylmethyl group, a phenyl group, a substituted phenyl group (the substituent is C 1 -C 6 alkyl, C 1 -C 4 alkoxy, hydroxy, halogen o nitro), a naphthyl group or a furyl, thienyl, pyridyl, oxazolyl, thiazolyl, isoxazolyl or isothiazolyl group unsubstituted or substituted by Ci-C4 alkyl, 18) A compound in which R * and RS may be the same or different and each is a "hydrogen atom, a methyl group, a benzyl group, a substituted benzyl group (the substituent is methyl, methoxy, hydroxy, fluorine or chlorine), a phenethyl group, a substituted phenethyl group (the substituent is methyl) , methoxy, hydroxy, fluorine or chlorine), a phenyl group, a substituted phenyl group (the substituent is methyl, rnetoxy, hydroxy, fluoro or chloro), a fuplo group, a t-enyl group or a pyridyl group, 19) A compound wherein R * is a hydrogen atom, a methyl group, a benzyl group, a substituted benzyl group (the substituent is methyl, methoxy or hydroxy), a phenol group or a substituted phenyl group (the substituent is methyl) , methoxy, or hydroxy); and RS is a hydrogen atom, 20) A compound in which * is a hydrogen atom, a methyl group, a benzyl group, a phenyl group or a methoxyphemelo group; and R5 is a hydrogen atom, 21) A compound in which * is a hydrogen atom, a methyl group, a benzyl group or a 4-methoxyphenyl group; and R5 is a hydrogen lathe, 22) A compound in which * is a hydrogen atom; and R5 is a hydrogen atom, 23) A compound in which R6 is a hydrogen atom, a C1-C4 alkyl group, a benzyl group or a phenethiium group, 24) A compound in which Rβ is a hydrogen, a methyl group or a benzyl group, 25) A compound in which R6 is a hydrogen atom, 26) A compound in which A is a C2-C4 alkyl ene group, a C2-C4 carboxyalkylene group or a group (C? ~ C4) -alcoxycarbonyl-alkylene of C2-C4, 27) A compound in which A is an alkylene group of C2-C ?,, 28) A compound in which A is a ethylene group or a 1-methyl-ethyl group. Meanwhile, an optional combination of the compound arbitrarily selected from the group consisting of 13) -16), 17) -22), 23) -25) and 26) -28), and may include, for example, the following compounds. 29) A compound in which R3 is a hydrogen atom, an alkyl group of Ci-C4, a benzyl group or a phenethio group; R * and R5 can be the same or different and each is a hydrogen atom, a C1-C4 alkyl group, a phenylalkyl group of Ci-C, a phenyl-substituted Ci-Ci group (the phenyl substituent) is Ci-C "alkyl, C 1 -C 4 -alkoxy, hydroxy, halogen or nitro), a naphthylmethyl group, a phenyl group, a substituted phenyl group (the substituent is C 1 -C 4 alkyl, Ci-C 4 alkoxy, hydroxy, halogen or nitro), a naphthyl group or a fuplo, timme, pyridyl, oxazolyl, thiazolyl, isoxazolyl or isothiazolyl group unsubstituted or substituted by Ci-C4 alkyl; Rβ is a hydrogen atom, an alkyl group of C? ~ C4, a benzyl group or a phenethyl group; and fl is an alkylene group of C2-C4, a carboxyalkylene group of C2-C "or a group (Ci-C4) -alcox-carbon-1-alkylene of C2-C, 30) A compound in which R3 is a hydrogen atom, a methyl group or a benzyl group; RA RS can be the same or different and each is a hydrogen atom, a methyl group, a benzyl group, a substituted benc group (the substituent is methyl, rnetoxy, hydroxy, fluorine or chlorine), a phenethyl group, a substituted phenetium (the substituent is methyl, rnetoxy, hydroxy, fluorine or chlorine), a femlo group, a substituted phenyl group (the substituent is methyl, methoxy, hydroxy, fluorine or chlorine), a fuplo group, a thienyl group or a pindyl group; R6 is a hydrogen atom, a methyl group or a benzyl group; and fl is an alkylene group of C2-C4, 31) A compound in which W is a sulfur atom or an oxygen atom and X is a group having the formula: -NR3- (wherein R3 is a hydrogen) or X is a sulfur atom and U is a group having the formula: -NR3- (wherein R3 is a hydrogen atom); R 4 is a hydrogen atom, a methyl group, a benzyl group, a substituted benzyl group (the substituent is methyl, rnetoxy or hydroxy), a femlo group or a substituted phenyl group (the substituent is methyl, methoxy or hydroxy); RS is a hydrogen atom; RS is a hydrogen atom; and fl is a C2-C4 alkylene group, 32) A compound in which U is a sulfur atom or an oxygen atom and X is a group having the formula: -NR3- (wherein R3 is a hydrogen); R * is a hydrogen atom, a methyl group, a benzyl group, a phenyl group or an ethoxyphenyl group; RS is a hydrogen atom, - RS is a hydrogen atom; and A is an alkylene group of C2-C4, 33) A compound in which U is a sulfur atom and X is a group having the formula: -NR- (wherein R3 is a hydrogen atom); R * is a hydrogen atom, a methyl group, a benzyl group or a 4-methoxyphenol group; RS is a volume of hydrogen; RS is a hydrogen atom; and A is a ethylene glycol or a l-methyl group < full, or 32) A compound in which U is a sulfur atom and X is a group having the formula: -NR3- (wherein R3 is a hydrogen atom); R * is a hydrogen atom! RS is a hydrogen atom? RS is a hydrogen atom; and fl is an ethylene group or a 1-methylethylene group. The preferred compound in general formula (I) can be specifically exemplified in Table 1.

TABLE 1 Compound Rl R2 n No. 1-1 H Me 1 1-2 Me Me 1 1-3 Et Me 1 1-4 Ph Me 1 1-5 4-Me-Ph Me 1 1-6 4-MeO-Ph Me 1 1-7 4 ~ F-Ph Me 1 1-8 4-Cl ~ Ph Me 1 1-9 Bz Me 1 1-10 4-Me-Bz Me 1 1-11 4-MeO-Bz Me 1 1-12 4-F-Bz Me 1 1-13 4-Cl-Bz Me 1 1-14 CH2CH2Ph Me 1 1-15 H Et 1 1 ~ 16 Me Et 1 1-17 Ph Et 1 1-18 4-Me-Ph Et 1 1-19 4-MeO-Ph Et 1 1-20 4-F-Ph Et 1 1-21 4-Cl-Ph Et 1 1-22 Bz Et 1 1-23 4-Me-Bz E 1 1-24 4-MeO-Bz Et 1 1-25 4-F-Bz Et 1 1-26 4-Cl-Bz Et 1 1-27 H Pr 1 1-28 Me Pr 1 1-29 Ph Pr 1 1-30 4-Me-Ph Pr 1 1-3.1 4-MeO-Ph Pr 1 1-32 4-F-Ph Pr 1 1-33 4-Cl-Ph Pr 1 1-34 Bz Pr 1 1-35 4-Me-Bz Pr 1 1-36 4-MeO-Bz Pr 1 1-37 4-F-Bz Pr 1 1-38 4-Cl-Bz Pr 1 1-39 H Me 1-40 Me Me 1-41 Ph Me 1-42 4-Me-Ph Me 1-43 4-MeO-Ph Me 1-44 4-F-Ph Me 1-45 4-Cl-Ph Me 1-46 Bz Me 2 1-47 4-Me-Bz Me 2 1-48 4-MeO-Bz Me 1-49 4-F-Bz Me 1-50 4-Cl-Bz Me 2 1-51 H Et 1-52 Me Et 1-53 Ph Et 1-54 4-Me-Ph Et 2 1-55 4-MeO-Ph Et 2 1-56 Bz Et 2 1-57 4-Me-Bz Et 1-58 4-MeO-Bz Et 1-59 H Pr-1 1-60 Me Pri 1 1-61 Ph Pri 1 1-62 4-Me-Ph Pri 1 1-63 4-MeO-Ph P i 1 1-64 4-F-Ph Pri 1 1-65 4-Cl-Ph Pri 1 1-66 Bz Pri 1 1-67 4-Me-Bz Pri 1 1-68 4-MeO-Bz Pri 1 1-69 4-F-Bz Pri 1 1-70 4-Cl-Bz Pri 1 1-71 H Bu 1 1-72 Me Bu 1 1-73 Ph Bu 1 1-74 4-Me-Ph Bu 1 1-75 4-MeO-Ph Bu 1 1-76 4 ~ F-Ph Bu 1 1-77 4-C.l-Ph Bu 1 1-78 Bz Bu 1 1-79 4-Me ~ Bz Bu 1 1-80 4-MeO-Bz Bu 1 1-81 4-F-Bz Bu 1 1-82 4-Cl-Bz Bu 1 1-83 H Bui 1 1-84 Me Bui 1 1-85 Ph Bui 1 1-86 4-Me-Ph Bui 1 1-87 4-MeO-Ph Bui 1 1-88 4-F-Ph Bui 1 1-89 4-Cl-Ph Bui 1 1-90 Bz Bui 1 1-91 4-Me-Bz Bui 1 1-92 4-MeO-Bz Bui 1 1-93 4-F-Bz Bul 1 1-94 4-Cl-Bz Bui 1 1-95 H Bu «1 1-96 Me Bu «1 1-97 Ph Bu * 1 1-98 4-Me-Ph Bu «1 1-99 4-MeO-Ph Bu «1 1-100 Bz Bu »1 l -101 4-Me-Bz Bu« l 1-102 4-MeO-Bz Bu »l 1-103 H Bu * 1 1-104 Me Bu * 1 1-105 Ph Bu * 1 1-106 4-Me-Ph Bu * l 1-107 4-MeO-Ph Bu * 1 1-108 Bz Bu * l 1-109 4-Me-Bz Bu * l 1-110 4-MeO-Bz Bu * 1 1-111 H Pn 1 1-112 Me Pn 1 1-113 Ph Pn 1 1-114 4-Me-Ph Pn 1 1-115 4-MeO-Ph Pn 1 1-116 Bz Pn 1 1-117 4-Me-Bz Pn 1 1-118 4-MeO-Bz Pn 1 1-119 H Hx 1 1-120 Me Hx 1 1-121 Ph Hx 1 1-122 4-Me-Ph Hx 1 1-123 4-MeO-Ph Hx 1 1-124 Bz Hx 1 1-125 4 ~ Me-Bz Hx 1 1-126 4-MeO-Bz Hx 1 1-1.27 H Pr 2 1-128 Me Pr 1-129 Ph Pr 1-130 4-Me-Ph Pr 2 1-131 4-MeO-Ph Pr 2 1-132 Bz Pr 2 1-133 4-Me ~ Bz Pr 1-134 4-MeO-Bz Pr 1-135 H Pri 1-136 Me Pri 1-137 Ph Pri 1-138 4-Me-Ph Pri 1-139 4-MeO-Ph Pri 2 1-140 Bz Pri 7 1-141 4-Me-Bz Pri 1-142 4-MeO-Bz Pri 1-143 H Bu 2 1-144 Me Bu 1-145 Ph Bu 1-146 4-Me ~ Ph Bu 1-147 4-MeO-Ph Bu 1-148 Bz Bu 1-149 4-Me-Bz Bu 1-150 4-MeO-Bz Bu 1-151 H Bui 1-152 Me Bui 1-153 Ph Bui 2 1-154 4-Me-Ph Bui 2 1-155 4-MeO-Ph Bui 2 1-156 Bz Bui 2 1-157 4-Me- Bz Bui 2 1-158 4-MeO-Bz Bui 2 In Table 1 above, the abbreviation indicates the next group. Bz Benzyl Bu Butyl Bui Isobutyl Bu-s-Butyl Bu * t-Butyl Et Ethyl Hx Hexyl Me Methyl Ph Phenyl Pn Pentium Pr Propyl Isopropyl In table i above, compounds are preferred Nos. 1-1, 1-2, 1-3, 1-6, 1-7, 1-9, 1-10, 1-11, 1-12, 1-13, 1-14, 1-15, 1-27, 1-28, 1-29, 1-30, 1-31- 1-32, 1-33, 1-34, 1-36, 1-39, 1-40, 1-43, 1-59, 1-50, 1-71- 1-72, 1-73, 1-74, 1-75, 1-78, 1-80, 1- 83, 1-84, 1-85, 1-87, 1-90, 1-92, 1-95, 1-103, 1-111, 1-112, 1-116, 1-119, 1-120, 1-123, 1-124, 1-127, 1-143, and 1-151; The most preferred compounds are Nos. 1-1, 1-2, 1-3, 1-6, 1-9, 1-10, 1-12, 1-14, 1-27, 1-28, 1-29, 1-31- 3 32, 1-33, 1-34 , 1-36, 1-60, 1-71- 1-72, 1-73, 1-75, 1-78, 1-80, 1- 83, 1-84, 1-85, 1-87, 1 -90, 1-92, 1-95, 1-103, 1-111, 1-112, 1- 116, 1-119, 1-120, 1-123, 1-124, 1-127, 1-143 , and 1-151; and particularly preferred compounds are Compound No. 1-1: (4R) -N-C (l) ~ l-rnethyl-2-nitro-oxyethyl] -2-oxothiazoli dm-4-yl-1-carboxyaryl. Compound No. 1-2: (4R) -NC (1S) -1-me-il-2-nitro-oxyethyl] -5-methy-2-oxothiazolidin-4-carboxylane Compound No. 1-6: (4R) -NC (1S) -l-rnet? L-2-ni tro-o ori ti] -5- (4-methoxyphenyl) -2-oxothiazolidin-4-yl-carboxylamide. Compound No. 1-9: (4R) -N- (IS) -l-methyl-2 - ni tro-oxietii] -5-benzyl-2-oxothiazolidin-4-yl-carboxyamide. Compound No. 1-15: (4R) -N-C (IS) - -ethyl-2-nitro-ox? Et? L] -2-oxothiazolidin-4-yl-carboxiarnide. Compound No. 1-27: (4R) -N-C (lS) -l-propyl-2-nitro-oxyethyl] -2-oxot-azole and din-4-ylcarbonium. Compound No. 1-28: (4R) -N-C (1S) -l-propyl-2-nitro-oxyethylene-3-methyl-2-oxothiazolidin-4-yl-carboxiaryne. Compound No. 1-31: (4R) -N-C (1S) -l-propyl-2-nitro-oxyethyl] -5- (4-rnetoxyphenyl) -2-oxothiazolidin-4-yl-carboxyamide. Compound No. 1-34: (4R) -N- (1S) -l-propyl-2-n-tro-oxyethyl-1-5-benzyl-2-oxo-iazoli-din-4-i1-carboxyamide.

Compound No. 1-71: (4R) -N-C (lS) -l-butyl-2-n-tro-oxyethyl] -2-oxot? Azoi? D? N- 4- ll-c-iarnide. Compound No. l-? 2: (4R) -N- (1 S) -l-but? L-2-n? Tro-or iet 11] -5-rnet? L-2-oxot? Azole? Dan- 4-? L-carboxiarnide. Compound No. 1-75: (R) -N-C (1S) -1-but? L -2-n? t-oxy-t-i-] -5- (4-methoxy-phena-1) -2-oxot-azole-d-n-4-l-carboxamide. Compound No. 1-78: (4R) -N- (1S) -l ~ but? L-2-nitro-oxyeth? I] -5-benzyl-2-oxot? Aolol d? N ~ 4- ? l-carbox? am? da. Compound No. 1-83. (4R) -N-C (1S) -l-? Sobut? L-2-n? Tro-ox? Et l] -2-oxo? Azole? din -4- 11 -carboxa amide. Compound No. 1-84: (4R) -NC (lS) -l-? Sobut? L-2-mtro-ox et? L3 ~ 5-rnet? I- 2-oxot? Azole? 4-? ? l ~ carbox? arn? da. Compound No. 1-87: (4R) -N- (1S) -l-? Sobut? L-2-n? Tro-ox? Et? L] -5- (4-rnetox? Phen? L) -2 -oxot? azole-4-l-carboxyamide, and Compound No. 1-90: (4R) -N- (1 S) -l-? sobutyl -2-n? tro-ox? e The most preferred compounds of the general formula (II) can be specifically exemplified in Table 2 and can be used to determine the specific compounds of the general formula (II). Table 3. The compounds of Table 2 and Table 3 have the structural formulas of (II-1? and (II-?), respectively.

TABLE 2 Compound R3 R4 RS RS A XI Do not. 2-1 H H H H (CH2) 2 S 2-2 Me H H H HCH2) 2 s 2-3 Et H H H (CH) 2 s 2-4 PhCH2 H H H (CH2) 2 s 2-5 H Me H H (CH2) 2 s 2-6 H Et H H (CH) 2 s 2-7 H Ph H H (CH2) 2 s 2-8 H 2-Thi H H (CH 2) 2 s 2-9 H 3-Thi H H (CH2> 2 s 2-10 H 2-Fur H H (CH 2) 2 s 2-11 H 3-Fur H H (CH2) 2 s 2-12 H 3-N? 2-Ph H H (CH2) 2 s 2-13 H 4-Cl-Ph H H (CH) 2 s 2-14 H 4-MeO-Ph H H (CH 2) 2 s 2-15 H 4-Thiz H H (CH2) 2 s 2-16 H 3-Pyr H H (CH2) _ s 2-17 H Me Me H (CH2) 2 s 2-18 Me Me Me H (CH2) 2 s 2-19 Me Me Me Me (CH2) 2 s 2-20 Et Ph H H (CH2) 3 s 2-21 Et Et H Me (CH2 s 2-22 PhCH2 Me H Et (CH2) 2 s 2-23 PhCH2 Ph H Pr (CH2 U S 2-24 Bu H H H (CH2) 2 S 2-25 H 1-Naph H H (CH 2) 2 S 2-26 H H H Me (CH 2) 2 S 2-27 H H H PhCH 2 (CH 2> 2 S 2-28 H PhCH2 H H (CH2) 2 S 2-29 PhCH2 H H H (CH2) 3 S 2-30 HHHH CH (Me) CH2 S -31 HHHH CH2CH (Me) S 2-32 HHHH (CH2) 5 S -33 HHHH (CH2) e S -34 HHHH (CH2 to O -35 Me HHH (CH2) 2 OR 2-36 Et H H H (CH 2) 2 O 2-37 PhCH 2 H H (CH 2) 2 O 2-38 H Me H H (CH 2) 2 O -39 H Et H H (CH 2) 2 O 2-40 H Ph H H (CH2) 2 O 2-41 H 2-Thi H H (CH 2) 2 O 2-42 H 3-Thi H H (CH 2) 2 O 2-43 H 2-Fur H H (CH 2) 2 O 2-44 H 3-Fur H H (CH 2) 2 O 2-45 H 3-N02-Ph H H (CH 2) 2 O - 6 H 4-Cl-Ph H H (CH 2) 2 O 2-47 H 4-MeO-Ph H H (CH 2) 2 O 2-48 H 4-Thiz H H (CH) 2 O 2-49 H 3-Pyr H H (CH 2) 2 0 2-50 H Me Me H (CH2) 2 0 2-5.1 Me Me Me H (CH2) 2 0 2-52 Me Me Me Me (CH2 > 2 0 2-53 Et Ph H H (CH2) 3 0 2-54 Et Et H Me (CH2) «0 2-55 PhCH2 Me H Et (CH2) 2 0 2-56 PhCH2 Ph H Pr (CH2) «0 2-57 Bu H H H (CH2) 2 0 2-58 H 1-Naph H H (CH 2) 2 0 2-59 H H H Me (CH2) 2 0 2-60 H H H PhCH2 (CH2) 2 0 2-61 H PhCH2 H H (CH2) 2 0 2-62 H H H H (CH2) 3 0 2-63 H H H H CH (Me) CH2 0 2-64 H H H H CH2 CH (Me) 0 2-65 H H H H (CH2) s 0 2-66 H H H H (CH2) e 0 2-67 H H H H (CH2) «? 2-68 H H H H (CH2) 3 s 2-69 H 4-Me-CH2Ph H H (CH2) 2 s 2-70 H 4-MeO-CH2Ph H H (CH2) 2 s 2-71 H 4-F-CH2Ph H H (CH2) 2 s 2-72 H 4-Cl-CH2Ph H H (CH2) 2 s 2-73 H 4-OH-CH2Ph H H (CH2) 2 s 2-74 H 4-Me-Ph HH (CH2) 2 s 2-75 H 4-F-Ph HH (CH2) 2 2-76 H 4-OH-Ph HH (CH2) 2 2-77 H 4-Me -CH2Ph HH (CH2) 2 O 2-78 H 4-MeO-CH2Ph HH (CH2) 2 O 2-79 H 4-F-CH2Ph HH (CH2) 2 O 2-80 H 4-Cl-CH2Ph HH (CH2 ) 2 O 2-81 H 4-OH-CH2Ph HH (CH2) 2 O 2-82 H 4-Me-Ph HH (CH2) 2 O 2-83 H 4-F-Ph HH (CH2) 2 O 2- 84 H 4-OH-Ph HH (CH 2) 2 O 2-85 HHHH (CH 2 O 2-86 H Me HH CH (Me) CH 2 s 2-87 H 3-Fur HH CH (Me) CH 2 2-88 H 4 -MeO-Ph HH CH (Me) CH2 2-89 H PhCH2 HH CH (Me) CH2 2-90 H Me HH CH (Me) CH2 or 2-91 H 3-Fur HH CH (Me) CH2 or 2-92 H 4-MeO-Ph HH CH (Me) CH2 or 2-93 H PhCH2 HH CH (Me) CH2 or TABLE 3 Compound R3 R * RS RS fl? Do not. 3-1 H H H H (CH2) 2 S 3-2 Me H H H (CH2) 2 < s 3-3 Et H H H (CH 2) 2 3-4 PhCH 2 H H (CH 2) 2 3-5 H Me H H (CH) 2 5 3-6 H Et H H (CH2) 2 S 3-7 H Ph H H (CH) 2 s 3-8 H 2-Thi H H (CH 2) 2 s 3-9 H 3-Thi H H (CH2) 2 s 3-10 H 2-Fur H H (CH 2) 2 s 3-11 H 3-Fur H H (CH2) 2 s 3-12 H 3-N02-Ph H H (CH2) 2 s 3-13 H 4-Cl-Ph H H (CH 2) 2 s 3-14 H 4-MeO-Ph H H (CH 2) 2 s 3-15 H 4-Thiz H H (CH2) 2 s 3-16 H 3-Pyr H H (CH2) 2 s 3-17 H Me Me H (CH2) 2 3-18 Me Me Me H (CH2) 2 5 3-19 Me Me Me Me (CH2) 2 s 3-20 Et Ph H H (CH 2) 2 3-21 Et Et H Me (CH 2) A s 3-22 PhCH2 Me H Et (CH2) 2 s 3-23 PhCH2 Ph H Pr (CH2 U S 3-24 BU H H H (CH2) 2 S 3-25 H 1-Naph H H (CH 2) 2 S 3-26 H H H Me (CH2) 2 S 3-27 H H H PhCH2 (CH2) 2 s 3-28 H PhCH2 H H (CH2) 2 s 3-29 H H H H (CH2) 3 s 3-30 H H H H CH (Me) CH2 s 3-31 H H H H CH2 CH (Me) s 3-32 H H H H (CH2) 5 s 3-33 H H H H (CH2) e s 3-34 H H H H (CH2) 2 0 3-35 Me H H H (CH2) 2 0 3-36 Et H H H (CH2) 2 0 3-37 PhCH2 H H H (CH2) 2 0 3-38 H Me H H (CH2) _ 0 3-39 H Et H H (CH2) 2 0 3-40 H Ph H H (CH2) 2 0 3-41 H 2-Thi H H (CH2) 2 0 3-42 H 3-Thi H H (CH2) 2 0 3-43 H 2-Fur H H (CH2) 2 0 3-44 H 3-Fur H H (CH2) 2 0 3-45 H 3-N? 2-Ph H H (CH2) 2 0 3-46 H 4-Cl-Ph H H (CH2) 2 0 3-47 H 4-MeO-Ph H H (CH2) 2 0 3-48 H 4-Thiz H H (CH 2) 2 0 3-49 H 3-Pyr H H (CH 2) 2 0 3-50 H Me Me H (CH2) 2 0 3-51 Me Me Me H (CH2) 2 0 3-52 Me Me Me Me (CH2) 2 0 3-53 Et Ph H H (CH2) 3 0 3-54 Et Et H Me (CH2 0 3-55 PhCH2 Me H Et (CH2) 2 0 3-56 PhCH2 Ph H Pr (CH2 0 3-57 Bu H H H (CH2) 2 0 3-58 H 1-Naph H H (CH 2) 2 0 3-59 H H H Me (CH2) 2 0 3-60 H H H PhCH2 (CH2) 2 0 3-61 H PhCH2 H H (CH2) 2 0 3-62 H H H H (CH2) 3 0 3-63 H H H H CH (e) CH2 0 3-64 H H H H CH2CH (Me) 0 3-65 H 4-Me-Ph H H (CH 2) 2 0 3-66 H 4-Me-Ph H H (CH 2) 2 s 3-67 H 4-Me-CH2Ph H H (CH2) 2 s 3-68 H 4-MeO-CH_Ph H H (CH 2) 2 s 3-69 H 4-F-CH2Ph H H (CH2) 2 s 3-70 H 4-Cl-CH2Ph H H (CH2) 2 s 3-71 H 4-OH-CH2Ph H H (CH2) 2 s 3-72 H 4-F-Ph H H (CH 2) 2 s 3-73 H 4-OH-Ph H H (CH 2) 2 s 3-74 H 4-Me-CH2Ph HH (CH2) 2 0 3-75 H 4-M bIO-CHaPh HH (CH2) 2 0 3-76 H 4-F-CH2Ph HH (CH2) 2 0 3-77 H 4 -Cl-CH_Ph HH (CH2) 2 0 3-78 H 4-0H-CH2Ph HH (CH2) 2 0 3-79 H 4-F-Ph HH (CH2) 2 0 3-80 H 4-OH-Ph HH (CH2) 2 O 3-81 HHHH (CH2 US 3-82 HHHH (CH2) «O 3-83 H Me HH CH (Me) CH2 S 3-84 H 3-Fur HH CH (Me) CH2 S 3-85 H 4-MeO-Ph H H CH (Me) CH 2 S 3-86 H PhCH 2 H H CH (Me) CH 2 S 3-87 H Me H H CH (Me) CH 2 O 3-88 H 3-Fur HH CH (Me) CH 2 0 3-89 H 4-MeO-Ph HH CH (Me) CH2 O 3-90 H PhCH2 HH CH (Me) CH2 O In tables 2 and 3 above, the abbreviation indicates the. next group, Bu Butyl Et Ethyl Fur Furyl Me Methyl Naph Naphthyl Ph Phenyl Pr Propyl Prid Pyridyl Thi Thienyl Thiz Thiazolyl In the above tables, compounds Nos. 2-1, 2-2, 2-5, 2-7, 2-8, 2-9, 2-1.0, 2-11, 2-12, 2-13 are preferred. , 2-14, 2-16, 2-17, 2-25, 2-26, 2-28, 2-30, 2-3.1, 2-34, 2-35, 2-38, 2-40, 2 -41, 2-42, 2-43, 2-44, 2-47, 2-61, 2-63, 2-67, 2-68, 2-69, 2-70, 2-71, 2-72 , 2-73, 2-74, 2-75, 2-76, 2-77, 2-78, 2-79, 2-80, 2-81, 2-82, 2-83, 2-84, 2 -85, 2-86, 2-87, 2-88 2-89, 2-90, 2-91, 2-92, 2-93, 3-1, 3-5, 3-7, 3-14, 3-30, 3-34, 3-38, 3-40, 3-47, 3-6S, 3-66, 3-67, 3-68, 3-69, 3-70, 3-71, 3- 72, 3-73, 3-83, 3-84, 3-85, 3-86, 3-87, 3-88, 3-89, and 3-90; The most preferred compounds are Nos. 2-1, 2-2, 2-5, 2-7, 2-8, 2-14, 2-25, 2-28, 2-30, 2-34, 2-38, 2-41, 2-44, 2-47, 2- 61, 2-63, 2-69, 2-70, 2-74, 2-78, 2-86, 2-88, 2-89, 2-90, 2-91, 2-92, 2-93, 3-1, 3-7, 3-14, 3-30, 3-66, 3-67, 3-68, and 3-85; and particularly preferred compounds are Compound No. 2-1: N- (2-nitrooxyethyl) -2-oxothiazolidin-4-yl-carboxiarnide. Compound No. 2-5: N ~ (2-nitrooxyethyl) -5-rnethyl-2-oxothiazolidin-4-yl-carboxyamide. Compound No. 2-14: N- (2-nitrooxyethyl) -5- (4-rnetoxy phenyl) -2-oxothiazolidin-4-yl-carboxyamide. Compound No. 2-28: N- (2-nitrooxyethyl) ~ 5 ~ benzyl-2-oxothiazo1idin-4-y1-carboxyamy a.

Compound No. 2-30: N- (1-methyl-2-nitrooxyethyl) -2-oxothiazolidin-4-yl-carboxyamide. Compound No. 2-34: N- (2-nitrooxyethyl) -2-oxooxazolidin-4-i1-carboxyamide. Compound No. 2-44: N- (2-nitrooxyethyl) -5- (3-furyl) -2-oxooxazolidin-4-i1-carboxyamide. Compound No. 2-61: N- (2-nitrooxyethyl) -5-benzyl-2-oxooxazolidin-4-yl-carboxyamide. Compound No. 2-63: N- (l-Rethyl-2-nitrooxyethyl) -2-oxooxazolidin-4-yl-carboxyamide. Compound No. 2-86: N- (1-methyl-2-nitrooxyethyl) -5-methyl-2-oxothiazolidin-4-yl-carboxyamide. Compound No. 2-88: N- (1-rnetii-2-nitrooxyethyl) -5- (4-rnetoxy) phenyl) -2-oxothiazolidin-1-carboxyamide. Compound No. 2-89: N- (l-Rethyl-2-nitrooxyethyl) -5-benzyl-2-oxothiazolidin-4-yl-carboxyamide. Compound No. 2-91: N- (1-methyl-2-nitrooxyethyl) -5- (3-furyl) -2-oxooxazolidin-4-yl-carboxyamide. Compound No. 2-93: N- (1-methyl-2-nitrooxyethyl) -5-benzyl-2-oxooxazolidin-4-yl-carboxy.arnida. Compound No. 3-1: N- (2-nitrooxyethyl) -2-oxothiazolidin-5-yl-carboarylane. Compound No. 3-14: N- (2-nitrooxyethyl) -4- (-rnetoxy phenyl) -2-oxothiazolidin-5-yl-carboxyamide. Compound No. 3-30: N- (1-methyl-2-nitrooxyethyl) -2-oxothiazolidin-5-yl-carboxyamide, and Compound No. 3-85: N- (1-methyl-2-nitrooxyethyl) -4 - (4- rnetoxifen.il) -2-oxothiazolidin-5-yl-carboxyamide. The compounds of the present invention having the general formula (I) are easily prepared according to the following methods.

Method fl (D 15 Method B (D Method C In the above formulas, R, R- and n have the same meanings as defined above, R? represents a protecting group of a mercapto group and R8 represents a protecting group of an arnino group. The protecting group of the mercapto group is not particularly limited in that it is well known in the field of synthetic organic chemistry and preferably includes a trisubstituted silyl group having a substituent selected from the group consisting of a C1-C4 alkyl group, a phenyl group and a phenyl group substituted with C 1 -C 4 alkyl, C 1 -C 4 alkoxy or halogen, a benzyl group, a benzyl group substituted with C 1 -C alkyl, C 1 -C 4 alkoxy or halogen, a benzyloxycarboryl group , a benzyloxycarbomyl group substituted with C1-C4alkyl, C1-C4alkoxy or halogen, a -butyl group or a t-butoxycarbomyl group, most preferably a tri-ethylsilyl group, a t-butyl silyl group, a t-butyldirnethylsilyl group It is a phenyldimethylsilyl group, a methoxy benzyl group, a penthoxy benzyl group, an ethoxybenzene loxycarbonyl group, a di-ethoxybenzyloxycarbonyl group or a t-butoxycarbomyl group, and preferably a t-butyl dirnet isi group. lio, a 4-rnetoxibencilo group, a 4-rnetox? benc group? loxycarbonyl or a t-butoxycarbomyl group, and a t-butox 1carbonyl group is particularly preferred. The protecting group of the same group is not particularly limited insofar as it is well known in the field of synthetic organic chemistry and preferably includes a trisubstituted silyl group having a substituent selected from the group consisting of an alkyl group of Ci-C4, a phenyl group and a femlo group substituted with C 1 -C alkyl, Ci-C * alkoxy or halogen, a benzyl group, a C 1 -C 4 alkyl substituted benzyl group, C 1 -C 4 alkoxy or halogen, a -ophenyl benzyloxycarbonyl, a benzyloxycarbonyl group substituted with CI-CA alkyl, C'-C "alkoxy or halogen, a t-butyl group or a t-butoxycarbomyl group, most preferably a tprnethylsilyl group, a tipeiysilyl group, a group t-butyldirnethylsilyl, a phenyldidyl group, a methoxybenzyl group, a methoxybenzyl group, a methoxybenzyloxycarbomyl group, a dimethoxybenzyloxycarbomyl group or a t-butoxycarbonyl group, most preferably a t-butyldimethylsilyl group, a 4-rnetoxyl benzyl group, a 4-methoxyl benzylcarbonyl group or a t-butoxycarbomyl group, and a t-butoxycarbonyl group is particularly preferred. The method fl is a method for preparing ol compound (I). Step Al is to prepare a compound having the general formula (I) and is carried out by reacting * a compound having the general formula (III) or a reagent derived therefrom (acid halides, mixed acid anhydrides or esters) active) with a compound having the general formula (TV) or its acid addition salt (for example, salts of mineral acids such as hydrochlorides, nitrates and sulfates) in an inert solvent, and is carried out, for example, , by an acid halide method, a mixed acid anhydride method, an active ester method or a condensation method. The acid halide method is carried out by reacting the compound (III) with a halogenating agent (for example, thionyl chloride, oxalyl chloride, phosphorus pentachloride, etc.) in an inert solvent to prepare the halogenide of acid, and reacting the acid halide with the compound (TV) or an acid addition salt thereof in an inert solvent in the presence or absence of a base. The base employed in this case may include, for example, organic amines such as t-tetylamine, N-methylimorpholma, pyridine and 4-d-rn-β-larinopyridine; alkali metal bicarbonates such as sodium bicarbonate and potassium bicarbonate; and alkali metal carbonates such as sodium carbonate and potassium carbonate, and preferably organic amines. The inert solvent used in this case is not particularly limited so long as it does not affect the reaction and may include, for example, hydrocarbons such as hexane, cyclohexane, benzene, toluene and xylene; halogenated hydrocarbons such as dichloromethane, 1,2-d-chloroethane and carbon tetrachloride; ethers such as ether, tetrahydrofuran and dioxane; ketones such as acetone; amides such as N, N-d? met? lformamide, N, N-d? methylacetamide, N-metii-2-pyrrolidone and hexarnetyl phosphoran * ida; and sulfoxides such as dimethyl sulfoxide, and preferably hydrocarbons, halogenated hydrocarbons, ethers or amides. The reaction temperature varies depending on the starting compounds (III) and (IV), the type of solvent, etc., and the reaction temperatures for both the reaction of the halogenating agent with the compound (III) and the reaction of the Acid halide with the compound (IV) are usually from -20 ° C to 150 ° C. Preferably, the reaction temperature for the first reaction is from -10 ° C to 50 ° C and for the second reaction it is from 0 ° C to 100 ° C. The reaction time varies depending on the reaction temperature, etc., and the reaction time of both reactions is usually from 15 minutes to 24 hours (preferably 30 minutes to 16 hours). The mixed acid anhydride method is carried out by reacting a Ci-C alkylcarbonate, a dialkyl cyclophosphoc acid of Ci-C or a C 1 -C 6 dianlfosphorylazide with the compound (III) to prepare the mixed acid anhydride and by reacting the resulting mixed acid anhydride with the compound (TV) or its acid addition salt. The reaction for preparing the mixed acid anhydride is carried out by reacting a Ci-Ce alkyl halocarbonate such as methyl chlorocarbonate, ethyl chlorocarbonate, isobutyl chlorocarbonate and hexyl chlorocarbonate (preferably ethyl chlorocarbonate or isobutyl chlorocarbonate) , a dialkylcyanophosphoric acid of Ci-Cβ such as dimethyzothiophosphoric acid, diethyl cyanophospho-acid and di-hexyl-cyanophospho-acid (preferably diethyl-cyanophospho-acid) or a diarylphosphorylazide of Ce-Cyn such as diphenylphosphorylazide, d? (pn? trofen? 1) phosphoplazide and dmaphthylphosphoplaside (preferably diphenylphosphorylazide) with the compound (III), preferably in an inert solvent in the presence of a base. The base and the inert solvent used in this case are similar to those used in the acid halide method. The reaction temperature varies depending on the starting compound (III), the type of solvent, etc., and is usually from ~ 20 ° C to 50 ° C (preferably from 0 ° C to 30 ° C), the reaction time it varies depending on the reaction temperature, etc., and is usually from 15 minutes to 24 hours (preferably 30 minutes to 16 hours). The reaction of the mixed acid anhydride with the compound (IV) or its acid addition salt is preferably carried out in an inert solvent in the presence or absence of a base. The base and the inert solvent used in this case are similar to those used in the acid halide method. The reaction temperature varies depending on the starting compound (IV), the type of solvent, etc., and is usually from ~ 20 ° C to 100 ° C (preferably from -10 ° C to 50 ° C). The reaction time varies depending on the reaction temperature, etc., and is usually from 15 minutes to 24 hours (preferably 30 minutes to 16 hours). In the case where dialkylcyanophosphocid or diaplfosphorylazide acid is used, the present method can be carried out by reacting the compound (III) with the compound (IV) directly in the presence of a base. The active ester method can be carried out by reacting the compound (III) with an active esterification agent (for example, an N-hydroxy compound such as N-hydroxysuccinirnide and N-hydroxybenzotriazole and the like) in the presence of an condensation (for example, dicyclohexylcarbodi irnide, carbonyldiinidazole and the like) to prepare the active ester, and reacting the active ester with the compound (IV) or its acid addition salt. The reaction to prepare the active ester is preferably carried out in an inert solvent, and the inert solvent used in this case is similar to that used in the acid halide method. The reaction temperature varies depending on the starting compounds (III) and (IV), the type of solvent, etc., the reaction temperature for the active esterification reaction is usually from -20 ° C to 50 ° C (preferably from -10 ° C to 30 ° C), and the reaction temperature for the reaction of the active ester compound with the compound (IV) is usually from -20 ° C to 50 ° C (preferably from -10 ° C to 30 ° C). ° C). The reaction time varies depending on the reaction temperature, etc., and the reaction times for both reactions is usually 15 minutes to 24 hours (preferably 30 minutes to 16 hours). The condensation method can be carried out by reacting the compound (III) with the compound (IV) or an acid addition salt thereof directly in the presence of a condensing agent (for example, di-cyclohexylcarbodiirnide, carbonyl diimidazole, hydrochloride 1- (N, Nd? Rnetilam? No? Ro? Il) -3-ethylcarbodiimide and the like). This reaction is carried out in a manner similar to the reaction for preparing * the active ester. After completion of the reaction, the desired compound in each reaction is collected from the reaction mixture by means of conventional procedures. For example, the desired compound of each reaction can be obtained by appropriately separating the insoluble material by filtration and collecting the precipitated crystal by filtration.; or by appropriately separating the insoluble material by filtration, properly neutralizing, separating the solvent by distillation, adding water to the reaction mixture, extracting the mixture with a water-immiscible organic solvent such as ethyl acetate, drying the organic layer and evaporating and extracting the solvent. If necessary, the compound obtained in this manner can be further puri? ed by means of conventional procedures, for example, recrystallization, column chromatography and the like. The starting compound (III) of the fl method is known or easily prepared according to known methods or with methods that are similar to them. For example, Tetrahedron, 45, 7459 (1989), 3. Arn. Chem. Soc, 79, 5203 (1957), 3. Am. Chen. Soc., 111, 6354 (1989), etc.].Method B is another method for preparing compound (I). Step Bl is to prepare a compound having the general formula (VI) and is carried out by reacting the compound (III) or a reagent derived therefrom with a compound having the general formula (V) in an inert solvent. This step is carried out, for example, by means of the acid halide method, the mixed acid anhydride method, the active ester method or the condensation method, and is carried out in the same manner as step Al. Step B2 is for preparing a compound having the general formula (I) and is carried out by reacting the compound having the general formula (VI) with a neutralizing agent in the absence or presence of an inert solvent. The nitration agent employed in this case may include, for example, fuming nitric acid, tet raflourobor or nitrocolide, thionylchloruronitic acid, thionylnitic acid and nitronium tetrafluoroboron, and preferably fuming nitric acid, nitrocolidium tetr fluoroboro or thionylchloruronide acid co. The inert solvent employed in this case is not particularly limited so long as it does not affect the reaction and may include, for example, hydrocarbons such as hexane, cyclohexane, benzene, toluene and xylene; halogenated hydrocarbons such as dichloromethane, 1,2-d-chloroethane and carbon tetrachloride; ethers such as ether, tetrahydrofuran and dioxane; ketones such as acetone; nitriles such as acetonitrile; amides such as N, N-dimethyl formamide, N, N-dirnethiacetamide, N-methyl-2-pyrrolidone and hexarnetiifosforarnide; and sulfoxides such as dimethyl sulfoxide, preferably halogenated hydrocarbons, ethers or nitriles, and particularly preferably nitriles. The reaction temperature varies depending on the starting compound (VI), the type of nitrating agent, etc., and is usually -20 ° C to 50 ° C, and preferably about room temperature. The reaction time varies depending on the reaction temperature, etc., and is usually from 30 minutes to 24 hours (preferably 1 hour to 10 hours). The compound (I) is also prepared by reacting the compound (VI) with a sulfonylating agent (for example, Ci-C alkanesulfonyl halides, such as methanesulfonyl chloride, r-methanesulfonyl bromide, ethanesulfonyl chloride and butanesulfonyl chloride C 1 -C 1 aryl halides such as benzenesulfonyl chloride, p-toluenesulfonyl chloride, p-toluenesulfonyl bromide and naphthylsulfonyl chloride, or C1-C4 alkanesulphonic anhydrides such as methane sulphonic anhydride, ethanesulfonic anhydride and butanesulfonic anhydride, preferably methanesulfonic chloride, ethanesulphonic chloride, benzenesulfonyl chloride, p-toluenesulfonyl chloride or methanesulphonic anhydride, and rnetanosulfonyl chloride is particularly preferred) at -20 ° C to 50 ° C (preferably about room temperature) for 30 minutes at 24 hours (preferably 1 hour to 10 hours) in an inert solvent (for example, hydrocarbon such is hexane, cyclohexane, benzene, toluene and xylene; halogenated hydrocarbons such as dichloroethane, 1,2-dichloroethane and carbon tetrachloride; or ethers such as co-oter, tetrahydrofuran and dioxane; or mtryls such as ketone taryl, preferably nitriles, and acetonitrile is particularly preferred) in the presence or absence of a base (e.g., organic amines such as tettiiamine, N-rnetiimorfol ina, pipdma and 4 ~ d? net? lam? nop? pd? na, and preferably triethylamine) to prepare the sulfonyloxy compound, and then reacting the sulfomloxy compound with tetraalkylammonium nitrate of Ci -CA (for example, tetramethyl ammonium nitrate, tetraethylammonium nitrate or tetrabutylammonium nitrate, and preferably tetrabutylaronium nitrate) at 0 ° C to 200 ° C (preferably 50 ° C to 150 ° C) for 30 minutes to 24 hours (preferably 1 hour to 10 hours) in an inert solvent (for example, aromatic hydrocarbons such as benzene , toluene and xi log, and preferably toluene). After completion of the reaction, the desired compound of each reaction is collected from the reaction mixture according to conventional procedures. For example, the desired compound can be obtained by collecting the precipitated crystal by filtration; separating the solvent by distillation; or by appropriately separating the solvent by distillation, adding water to the reaction mixture, extracting the mixture with an organic solvent immiscible in water such as ethyl acetate, drying the organic layer and evaporating and extracting the solvent. If necessary, the compound obtained in this way can be further purified by means of conventional procedures, for example, recrystallization, column chromatography and the like. Method C is another method to prepare the compound (I) Step C is to prepare a compound having the general formula (VIII) and is carried out by reacting a compound having the general formula (VID or a reagent derived therefrom with the compound (V) in an inert solvent. step can be carried out, for example, by means of the acid halide method, the mixed acid anhydride method, the active ester method or the condensation method and is carried out in the same manner as in step Al of the above method Fl Step C2 is for preparing a compound having the general formula (IX) and is carried out by reacting a compound having the general formula (VIII) with a nitrating agent in the absence or presence of a solvent This step is carried out in the same way as step B2 of method B above.

Step C3 is to prepare the compound (I) and is carried out by removing the protecting group of the mercapto group and the protecting group from the group of the compound (IX) and then reacting the resulting composition with carbom as carboni ldurnidazole; phosgene derivatives such as phosgene and tp phosgene; C 1 -C 4 alkyl halocarbonates such as methyl chlorocarbonate, ethyl chlorocarbonate, ethyl bromocarbonate, propyl chlorocarbonate and butyl chlorocarbonate; and halogenocarbonat or phenyl derivatives such as femlo chlorocarbonate, phenyl bromocarbonate, tolyl chlorocarbonate, methoxyphenyl chlorocarbonate and chlorophenyl chlorocarbonate (preferably carbonyldiimidazole, phosgene, triphosgene, methyl chlorocarbonate, ethyl chlorocarbonate, ethyl bromocbonate or chlorocarbonate) of femlo, and carbonyldiimidazole is particularly preferred). The reaction to remove the protecting group of the rnercapto group and the protecting group of the amino group is carried out by the method well known in the field of synthetic organic chemistry. For example, the protecting group of the rnercapto group and the protecting group of the amino group are removed by reacting a corresponding compound with an acid in an inert solvent. The acid used in this case may include, for example, mineral acids such as hydrochloric acid, nitric acid and sulfuric acid; carboxylic acids such as acetic acid and trifluoroacetic acid; and sulphonic acids such as methanesulphonic acid, benzenesulonic acid and p-toluensulonic acid, preferably hydrochloric acid, tri-fluoroacetic acid or p-toluenesulfonic acid, and hydrochloric acid is particularly preferred. The inert solvent used in this case is not particularly limited as long as it does not affect the reaction and may include, for example, hydrocarbons such as hexane, cyclohexane, benzene, toluene and xylene; halogenated hydrocarbons such as diechloro-methane, 1,2-dichloroethane and carbon tetrachloride; ethers such as ether, tetrahydrofuran and dioxane; ketone such as acetone; and nitriles such as acetonitrile, preferably halogenated hydrocarbons or ethers, and ethers are particularly preferred. The reaction temperature varies depending on the starting compound, etc., and is usually -20 ° C to 50 ° C, and preferably about room temperature. The reaction time varies depending on the reaction temperature, etc., and is usually from 30 minutes to 24 hours (preferably 1 hour to 10 hours). In the case where the protecting group of the mercapto group and / or the protecting group of the anino group is a trisubstituted silyl group, the protective group is also removed by reacting the corresponding compound with a reagent which produces a fluorine anion such or tetrabutyl onium fluoride and potassium fluoride instead of acid.

The protecting group of the mercapto group and the protecting group * of the arn group can not be eliminated in order, and preferably are eliminated at the same time under the same condition. The reaction of the compound obtained by removing the protecting group of the mercapto group and the protecting group of the amino group, with the carbonyl compound, is preferably carried out in an inert solvent. The inert solvent used in this case is not particularly limited insofar as it does not affect the reaction and may include, for example, hydrocarbons such as hexane, cyclohexane, benzene, toluene and xylene; halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane, and carbon chromium chloride; ethers such as ether, tetrahydrofuran and dioxane; ketones such as acetone; and nitriles such as acetonitrile, preferably halogenated hydrocarbons or ethers, and halogenated hydrocarbons are particularly preferred. The reaction temperature varies depending on the starting compound, etc., and is usually at -20 ° C to 50 ° C, and preferably at about room temperature. The reaction time varies depending on the reaction temperature, etc., and is usually from 10 minutes to 10 hours (preferably 20 minutes to 5 hours). After completion of the reaction, the desired compound of each reaction is collected from the reaction mixture by conventional procedures. For example, the desired compound can be obtained by separating the solvent by distillation; or by appropriately separating the solvent by distillation, adding water to the reaction mixture, extracting the mixture with an organic solvent immiscible in water such as ethyl acetate, drying the organic layer and evaporating and extracting the solvent. If necessary, the compound obtained in this way can be further purified by conventional procedures, for example, recrystallization, column chromatography and the like. The starting compound (VID of method C is known or easily prepared according to known methods or methods that are similar to them [eg, Chem. Flbsts., 74., 100379b (1971)]. A compound having the same General formula (I ') also has an excellent antiulcerative action and is prepared in the same manner as in the above procedure using a compound having the general formula (IV) in place of the compound (IV) or a compound having the general formula (V) instead of the compound (V).

"W l_¡ CONHf (CH2) ñ-ON? 2 (O am (IV) In the above formulas, R1, R2 and n have the same meanings as defined above. The compound having the general formula (II) which is an active ingredient of a preventive agent or a therapeutic agent for an ulcerative disease of the present invention is a known compound or is easily prepared in accordance with conventional procedures (e.g. Unexamined Japanese Patent Application (KOKflD No. Hei 5-213910 etc.) The compound having the general formula (I) above of the present invention exhibits a potent collateral dilator action, slight toxicity and fewer side effects such as headache, dizziness, tachycardia or harmful effects on the digestive system, liver, bone, etc., and does not suffer the first-pass effect, and is useful as a preventive agent and a therapeutic agent (preferably a therapeutic agent) for angina pe ho.Meanwhile, the compound having the general formula (II) above, or a pharmacologically acceptable salt thereof, exhibits a potent anti-inflammatory action. ulcerative, slight toxicity and fewer side effects such as headache, dizziness, tachycardia or harmful effects on the digestive system, liver, bone, etc., and is useful as a preventive agent and a therapeutic agent (preferably a therapeutic agent ) for an ulcerative disease. The compound (I) has characteristics such that its storage stability is excellent and can be handled easily. In the case where the compound (I) of the present invention is used as a therapeutic agent or a preventive agent for angina pectoris; or the compound (II) and a pharmacologically acceptable salt thereof is used as a preventive agent or a therapeutic agent for an ulcerative disease, can be administered as such or as a mixture, for example, with a pharmaceutically acceptable excipient, diluent or the like in the form of a tablet, a capsule, a granule, a powder and a syrup for oral administration, and an injectable preparation for parenteral administration. These preparations are made by the known method using additives such as excipients (e.g., sugar derivatives such as lactose, sucrose, glucose, mannitol and sorbitol; starch derivatives such as corn starch, potato mash starch, starch , dextrin and carboxymethyl starch, cellulose derivatives such as microcrystalline cellulose, hydroxypropyl-substituted lower cellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, calcium carboxymethylcellulose and sodium carboxy ethylcellulose with internal bridges; gum arabic; dextran; Pullulan; silicate derivatives such as anhydride; of light silicic acid, synthetic aluminum silicate and magnesium rneta-silicic acid aluninate, phosphate derivatives such as calcium phosphate, carbonate derivatives such as calcium carbonate, and sulfate derivatives such as calcium sulfate), binders ( for example, the excipients mentioned above, gelatin, pol ivinilpirro lidona; and Macrogol); disintegrating agents (eg, the excipients mentioned above, chemically modified starch, cellulose derivatives, etc. such as Croscarmellose sodium, sodium carboxymethyl ester and bridged polyvinylpyrrolidone), lubricants (eg, talcum, stearic acid; metal such as calcium stearate and magnesium stearate; colloidal silica; waxes such as beeswax and whale wax; boric acid; glycol; carboxylic acids such as fumaric acid and adipic acid; sodium carboxylate such as sodium benzoate; sulfates such as sodium sulfate; leucine; lauryl sulfates such as sodium lauryl esters and magnesium lauryl sulfate; silicic acids such as silicic acid anhydride and hydrated silicic acid; and depilated starch in the above excipients), stabilizers ( example, p-hydroxybenzoates such as methylparaben and propylparaben; alcohols such as chloroblutanol, benzyl alcohol and phenylethyl alcohol; benzalkonium chloride; phenols such as phenol and cresol; tirnerosal; acetic anhydride; and sorbic acid); correctors (eg, sweeteners, acidulators and perfumes conventionally used), diluents and solvents for injectable agents (eg, water, ethanol and glycerin). The dose varies depending on the condition and age of the patient to be treated, and is conveniently administered 1 to 6 times a day depending on the condition: in the case of oral administration, the lower limit of 1 mg each time (preferably 5 rng) and the upper limit of 1000 rng (preferably 300 ng) for an adult; and in the case of intravenous administration, the lower limit of 0.1 g each time (preferably 0.5 mg) and the upper limit of 100 mg (preferably 50 mg) for an adult. The present invention will be described more specifically below by showing examples, reference examples, test examples and preparation examples, however, the invention is not limited thereto.

EXAMPLE 1 (4R) -NC (15) -l-Methyl-2-nitrooxyethyl] -2-oxothiazolidin-4-yl-carboxiarnide (Exemplary Compound No. 1-1) In 2.0 ml of dry tetrahydrofuran, 2.06 g of the suspension were suspended. (4R) -2-oxothiazolidin-4-carboxylic acid and 2.00 g of (lS) -l-rnetyl-2-nitrooxyethylamine hydrochloride; 4.5 ml of triethylamine and 3.00 ml of di phenyl phosphorylazide were added with stirring under cooling with ice, and the mixture was stirred at room temperature for 5 hours. Then, the solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography using cyclohexane-ethyl acetate (1: 4) as eluent to obtain 3.00 g of colorless crystals. The crystals were recrystallized from ethyl acetate to obtain 0.964 g of the desired compound as colorless needle crystals. P.f .: 122-123 ° C (desconp.). NMR spectrum (CDC13 + DMS0-d6) d ppm: 1.27 (3H, d, 3 = 6.6Hz), 3.67 (2H, d, 3 = 6.6Hz), 4.10-4.57 (4H, n), 7.57 (1H, bs), 7.78 (1H, br.s) ,.

E3EMPL0 2 (4R) -N- (lS) -l-Methyl-2-nitrooxyethyl] -2-oxothiazolidin-4-yl-carboxyamide (Exemplary Compound No. 1.-1) (2a) (4R) -Np.lS ) -l-Metii-2 ~ hydroxyethyl-3-2-oxothiazolidin-4-yl-carboxycarnide In 20 ml of dry tetrahydrocanal, 1.0 g of (4R) -2-oxothiazolidin-4-carboxylic acid was dissolved and 0.56 g of L-alaninol, 2.8 ml of triethylamine and 1.8 ml of diphenylphosphorylazide with stirring under ice-cooling; The mixture was stirred at room temperature for 3 hours. Then, the solvent was distilled off under reduced pressure and the obtained residue was purified by silica gel column chromatography using ethyl acetate as eluent and further purified by silica gel column chromatography using as eluent dichloromethane-methane1 ( 95: 5) to obtain 0.92 g of the desired compound as colorless crystals. P.f. : 160-162 ° C.

NMR spectrum, (DMS0-d6), d ppm: 1.04 (3H, d, 3 = 6.7Hz), 3.20-3.40 (3H, rn) 3.63 (1H, dd, 3 = 8.6Hz, 3 = 11.2Hz), 3.70 -3.88 (1H, m), 4.16-4, 2 (1H, m), 4.73 (1H, t, 3 = 5.6Hz), 7.83 (1H, d, 3 = 7.9Hz), 8.24 (1H, bs ). (2b) (4R) -N - [(1S) -l-Metii-2-nitrooxyethyl-3-2-oxothiazolidin-4-yl-carboxyamide In 10 ml of dry acetonitrile, 478 mg of nitronium tetrafluoroboron were dissolved (85% content), 0.43 ml of 2,4,6-collidine was added with stirring under ice cooling and the mixture was stirred under ice cooling for 30 minutes. To the resulting mixture was added 500 rng of (4R) -NC (lS) -l-methyl-2-hydroxyethyi3-2-oxothiazolidin-4-yl-carboxyamide, and the mixture was stirred at room temperature for 1 hour and 45 minutes . Then, the solvent was distilled off under reduced pressure and the residue thus obtained was purified by silica gel column chromatography using cyclohexane-ethyl acetate (3: 7) as eluent to obtain 178 mg of the desired compound as colorless crystals. P.f .: ll_-122ßC. The NMR spectrum of. compound was identical to that of the compound of example 1.

EXAMPLE 3 (4R) -N - [(lS) -l-Met? L-2-n? Troox? Et? L-2-oxot? Aol? D? N-4-? L-carboxiarnide (Exemplary Compound No. 1-1) (3a) Nr (lS) -l-Met? L-2-h? Drox etH] - (2R) -2-t-butoxycarbom lam? No-3-t-buto? Carbon? Lt? Opr * Opanarn? da In 100 rnl of dry tetrahydrofuran, 5.0 g of N, Sd? -t-butox? carbon? lLc? stein was dissolved and 1.3 g of L-alamnol, 4.4 ml of triethylamine and 4.0 g of diffele were added. osfop lazide with stirring under ice-cooling; The mixture was stirred at room temperature for 4 hours.

The solvent was then removed by distillation under reduced pressure and the residue was purified by silica gel column chromatography using cyclohexane-ethyl acetate (1: 1) as eluent to obtain 3.55 g of the desired compound or colorless crystals. P.f .: 70-72 ° C. NMR spectrum (CDC13), d ppm: 1.19 (3H, d, 3 = 6, 9Hz), 1.45 (9H, s), 1.51 (9H, s), 2.65-2.90 (1H, bs), 3.03-3.30 (2H , n), 3.42-3.58 (1H, rn), 3.63-3.78 (1H, m), 3.95-4.04 (1H, rn), 4.20-4.35 (1H, m), 5.42-5.68 (1H, bm), 6.46 (IH, d, 3 = 7.8Hz). (3b) NC (iq) -l-Met? L-2-nitroo? Et? I] - (2R) -2-t-butox? Carbon? L-am? No-3-t-butox? Carbon? Lt lopropanami da In 25 ml of dry acetoni plo were dissolved 1.24 g of tetra fluo roboro de nitromo (content of 85%), were added 1. 12 g of 2,4,6-col? D? Na under stirring under ice cooling, and the mixture was stirred under ice cooling for 30 minutes. Then, a solution obtained by dissolving 2.5 g of N-C (1S) -l-met? L-2-h? Drox was added to the mixture? t? 1] - (2R) -2-t-butox? Carbomlarn? o-3-t-butoxycarbon was added to 25 ml of dry acetonitrile, and the resulting mixture was stirred at room temperature for 3 hours, then the solvent was removed by distillation under reduced pressure and the residue thus obtained was purified by silica gel column chromatography using as eluent cyclohexane-ethyl acetate (4: 1) to obtain 1.39 g of the desired compound as light yellow crystals, mp: 123-124 ° C (decomp. ) NMR spectrum, (CDC13), d ppm: 1.27 (3H, d, 3 = 6, 8Hz), 1.45 (9H, s), 1.51 (9H, s), 3.05-3.28 (2H, m), 4.20- 4.55 (4H, m), 5.42 (1H, d, 3 = 6, 3Hz), 6.45-6.65 (IH, bs). (3c) (4R) -NC (lS) -l-Met? L-2-n? Troox? Et? L] -2-oxot? Aolol? D? N-4-? L-carbo lamide In 10 ml of a solution of 4N hydrochloric acid in d-oxane was dissolved 1.0 g of Nr (15) -l-met? l-2-nit roox? et? l] - (2R) -2-t-butox? carbon? lam? no -3-t-buto-icarbonylthiopropanarnide, and the solution was stirred at room temperature for 2 hours. The solvent was removed by distillation under reduced pressure, benzene was added to the residue, and the solution was evaporated to dryness or reduced pressure. The residue thus obtained was suspended in 10 nl of dry dichloromethane, 0.46 g of carbodiimidazole was added, and the mixture was stirred at room temperature for 40 minutes. The reaction mixture was purified by silica gel column chromatography using ethyl acetate as eluent to obtain 0.45 g of pale yellow crystals. The crystals were recrystallized from ethyl acetate to obtain 84 mg of the desired compound as colorless crystals. P.f .: 125-126 ° C (dec.) The NMR spectrum of the compound was identical to that of. composed of example 1.

EXAMPLE 4 (4R) -N - [(lS) -l-Ethyl-2-nitrooxyethyl] -2-oxothiazolidin-4-yl-carboxycarnide (Exemplary Compound No. 1-15) In 10 ml of dry tetrahydrofuran were suspended 0. 50 g of (4R) -2-oxothiazolidin-4-carboxylic acid and 0.70 g of (lS) -l-ethyl-2-nitrooxothiazine hydrochloride; 1.40 ml of triethylamine and 0.62 ml of diethylcyanophosphoric acid were added, and the mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography using cyclohexane-ethyl acetate (1: 2) as eluent to obtain a light yellow oil. Isopropyl ether was added to the oil to obtain a light yellow powder. The powder was dissolved in 10 ml of acetone and then 5 ml of ethyl acetate was added. The acetone was removed by distillation under reduced pressure and the mixture was allowed to stand at room temperature to obtain 0.24 g of the desired compound as crystal is colorless colourants. P. f. : 106-107 ° C, (decomp.). NMR spectrum, (d6-DMS0), d ppm: 0.87 (3H, t, 3 = 7.4HZ), 1.30-1.68 (2H, rn), 3.32 (1H, dd, 3 = 5.0Hz, 3 = 11.2Hz), 3. 68 (1H, dd, 3 = 8.5Hz, 3 = 11.2Hz), 3.95-4.10 (1H, m), 4.25-4.35 (1H, n), 4.41 (1H, dd, 3 = 7.5Hz, J = 11.2Hz), 4.60 (1H, dd, 3 = 4.3Hz, 3 = 11.2Hz), 8.09 (1H, d, 3 = 8.5Hz ), 8.27 (1H, bs).

EXAMPLE 5 (4R) -Nf (15) -I-Prop l-2-nitroox? Etii] -2-oxot? Azole? Din-4-? L-carboxyamid (Exemplary Compound No. 1-27) 0.84 g was obtained of the desired compound as colorless crystals in procedures similar to those of Example 4 using 0.50 g of (4R) -2-oxot-azole-n-4-carboxylic acid and 0.75 g of (lS) -l-propyl-2- hydrochloride mtroox i etilarnma. Mp: 99-100 ° C (decornp.) NMR spectrum (dd-DMSO), d ppm: 0.87 (3H, t, 3 = 7.1Hz), 1.15-1.55 (4H, m), 3.32 (1H, dd, 3 = 4.8Hz, 3 = 11.2Hz), 3.68 (1, H, dd, 3 = 8.6Hz, 3 = 11.2Hz), 4.03-4.18 (1H,), 4.23-4.33 (1H, rn), 4.39 (1H, dd, 3 = 7.5Hz, 3 = 11.2Hz), 4.60 (1H, dd, 3 = 4.2Hz, 3 = 11.2HZ), 8.09 (1H, d, 3 = 8.5Hz), 8.27 (1H, bs).

EXAMPLE 6 (4R) -N-L ~ (I5) -l-But? L -? - n? Troox? Et? L] -2-oxot? Azole-4? 1 -carboxiarnide (Exemplary Compound No. 1-71) 570 rng of the desired compound co or colorless crystals were obtained in procedures similar to those of example 4 using 441 mg of acid (4R) -2-oxot? Azolid? N-4- carboxylic acid and 500 g of (15) -l-butyl-2-nitrooxide hydrochloride. P.f .: 110-112 ° C (descoinp,). NMR spectrum, (CDC13), d pprn: 0.91 (3H, t, 3 = 7.2Hz), 1. 20-1.43 (4H, m), 1.45-1.75 (2H, rn), 3.61, (1H, dd, 3 = 4.9Hz, 3 = 11. Hz), 3.83 (1H, dd, 3 = 8.6Hz, 3 = 11.2Hz), 4.23-4.45 (3H, rn), 4.60 (1H, dd, 3 = 3.3Hz, 3 = 11.2Hz), 6.65 (1H, bs), 6.81 (IH, d, 3 = 8.6Hz).

EXAMPLE 7 (4R) -NL ~ (lS) -l-Tsopropyl-2-n-tyl-ethyl] -2-oxot-azolidi-4-l -carboxiarnid (Exemplary Compound No. 1-59) 343 were obtained mg of the desired compound as colorless crystals in procedures similar to those of Example 4 using 333 mg of (4R) -2-oxothiazolid-4-carboxylic acid and 500 mg of (lS) -l-? o? rop l -2-mt roox leti lamí na. P.f .: 89- < U ° C. NMR spectrum (d6-DMS0), d pprn: 0.96 (3H, d, 3 = 7.3Hz), 1. 00 (3H, d, 3 = 6, 6Hz), 1.83-2.02 (1H, m), 3.64 (1H, dd, 3 = 4. OHz, 3 = 11 Hz), 3.84 (1H, dd, 3 = 8.6 Hz, 3 = 11.2Hz), 4.05-4.20 (1H, n), 4.35-4.52 (2H, n), 4.65 (1H, dd, 3 = 4. OHz, 3 = 11.2Hz), 6.80 (1H, bs) , 6.86 (1H, d, 3 = 9.2Hz).

EXAMPLE 8 (4R) -N ~ C (15) -l-lsobutyl-2-nitroxetane-2-oxot-azole-4-yl-carboxyamide (Exemplary Compound No. 1-83) obtained 636 rng of the desired compound as yellow oil in procedures similar to those of example 4 using 544 rng of acid (4R) -2-oxot? azolidm-4-carboxylic acid and 500 ng of hydrochloride of (1S) -1 -? sobut ? l-2-nitroox? et? iam? na. NMR spectrum (d6-DMSO), d ppm: 0.93 (3H, d, 3 = 6.6Hz), 0. 95 (3H, d, 3 = 7.9Hz), 1.30-1.80 (3H, m), 3.61 (1H, dd, 3 = 4 OHz, 3 = 11.2HZ), 3.82 (1H, dd, 3 = 8.6Hz, 3 = 11.2Hz), 4.30-4.50 (3H, rn), 4.59 (1H, dd, 3 = 3.3Hz, 3 = 11.2Hz) , 6.69 (1H, bs), 6.85 (1H, d, 3 = 7.9Hz).

REFERENCE EXAMPLE 1 (4R) ~ N-L ~ (lR) -l-Met l-2-n? rooxiet l 1-2-oxot-azole-4-α-carboxamide In 100 nl of dry benzene, 5.64 g of (4R) -2-oxothiazolidin-4-carboxylic acid were suspended and they added 6.7 ml of oxalyl chloride and a few drops of dimethylformamide; The mixture was stirred at room temperature for 3 hours. The solvent was removed by filtration under reduced pressure, then benzene was added and the suspension was azeotropically distilled to dryness to obtain the pale yellow acid chloride. In 1.50 ml of dry dichloromethane, 5.00 g of (lR) -l-methyl-2-nitrooxyethylamine hydrochloride was suspended and, with stirring and under reduced pressure, 1.4 ml of triethylamine and a solution of the chloride were added dropwise. of acid previously obtained in 70 ml of dry dichloromethane; the mixture was stirred under ice-cooling for 1 hour. Then, the solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography using cyclohexane-ethyl acetate (1: 4) as eluent to obtain light yellow crystals. The crystals were recrystallized from ethyl acetate to obtain 2.79 g of the desired compound as colorless crystals. P.f .: 101-102 ° C (decomp.). NMR spectrum (CDC13 + d6-DMSO), d ppm: 1.27 (3H, d, 3 = 6.9Hz), 3.55-3.75 (2H, m), 4.23-4.58 (4H, rn), 7.47 (1H, d, 3 = 7.1Hz), 7.61 (1H, s).

REFERENCE EXAMPLE 2 (1S) -N- (t-Butoxycarbonyl) -l-methyl-2-nitroo ietilarni.na In 200 ml of dry acetonitrile, 17.9 g of nitronium tetrafluoroboron were suspended and added dropwise. 17. 5 ml of 2,4,6-collidine at -5 ° C at 0 ° C under a stream of nitrogen. The reaction mixture was stirred at 0 ° C for 30 minutes, 10.7 g of N-t-butoxycarbonyl-L-alaninol was added thereto, and the mixture was stirred at room temperature for 1 hour and 20 minutes. Then, the solvent was distilled off under reduced pressure and ethyl acetate was added to the residue. The insoluble part was filtered off and the filtrate was evaporated to dryness under reduced pressure. The yellow oil obtained in this way was purified by silica gel column chromatography using cyclohexane-ethyl acetate (9: 1) as eluent. to obtain 7.12 g of the desired compound as a colorless oil. NMR spectrum (CDC13), d ppm: 1.23 (3H, d, 3 = 7.3Hz), 1. 45 (9H, s), 3.90-4.15 (1H,), 4.27-4.75 (3H,) REFERENCE EXAMPLE 3 (lS) -l-Metii-2-nitrooxyethylamine hydrochloride In 80 ml of 4N-dioxane hydrochloric acid, 4.52 g of (lS) -N- (t-butoxycarbonyl) -l-methyl-2-nitroxyethylamine were dissolved. and the mixture was allowed to stand at room temperature for 1 hour and 50 minutes. 160 mL of ether was added to the mixture and the crystals were collected by filtration and dried to obtain 3.02 of the desired compound as colorless crystals. P.f. : 134-135 ° C NMR spectrum (CDC13 + d6-DMS0), d ppm: 1.47 (3H, d, 3 = 6.6Hz), 3.55-3.70 (1H, m), 4.65-4.80 (2H, m).

REFERENCE EXAMPLE 4 (IR) -N- (t-Buto? C rbon? L) -1-met i 1-2-nitrooxyethylamine 8.55 g of the desired compound were obtained as a colorless oil in procedures similar to those of reference example 2 using 13.09 g of tetr fluoroboro de i tronío and 7. 72 g of N-t-butoxycarbon l-D-alaninol. NMR spectrum (CDC13), d pprn: 1.23 (3H, d, 3 = 7.3Hz), 1. 45 (9H, s), 3.95-4.15 (1H, m), 4.28-4.75 (3H,).

REFERENCE EXAMPLE 5 (lR) -l-rnet? L-2-n? Troox? Et? Larna? Hydrochloride 1.60 g of the desired compound were obtained as colorless crystals in procedures similar to those of Reference Example 3 using 8.55 g of (lR) -N- (t-butoxycarboni 1) -l-met? 1- 2-n? Troox? Et? Lam? Na and 90 ml of 4N-d-oxano hydrochloric acid. P.f .: 133-135 ° C. NMR spectrum (CDC13 + DMSO-d6), d ppm: 1.47 (3H, d, 3 = 6.9Hz), 3.55-3.70 (1H, m), 4.65-4.78 (2H, m).

REFERENCE EXAMPLE 6 (lS) -N- (t-Butox? Carbon? L) -l-et? L-2-n? Troox? And ilamine 3.19 g of the desired compound were obtained as a light yellow oil in procedures similar to those of the reference example 2 using 4.00 g of nitrogium tetr fluoroboro and 4.03 g of (lS) -N- (t-butoxycarbonyl) -l-ethyl-2-hydroyethylaniline. NMR spectrum (CDC13), d ppm: 0.98 (3H, t, 3 = 7.3Hz), 1.40-1.70 (2H, m), 1.45 (9H, s), 3.70-3.95 (1H, m), 4.20-4.70 ( 3H, rn).

REFERENCE EXAMPLE 7 (lS) -l-Ethyl-2-nitrooxyethylarnine hydrochloride 2.10 g of the desired compound were obtained as colorless crystals in procedures similar to those of reference example 3 using 3.19 g of (lS) -N- (t- butoxycarbonyl) -l-ethyl-2-nitrooxyethylamine and 50 ml of hydrochloric acid 4N-dioxane. P.f .: 121-123 ° C (dec. P.). NMR spectrum (d6-DMS0), d ppm: 0.96 (3H, t, 3 = 7.2Hz), 1.50-1.80 (2H, n), 3.35-3.50 (1H, m), 4.66 (1H, dd, 3 = 6.6Hz, 3 = 11.9Hz), 4.81 (1H, dd, 3 = 4.0Hz, 3 = 9Hz), 8.49 (3H, bs).

REFERENCE EXAMPLE 8 (lS) -N- (t-Buto-icarbonyl) -l-propyl-2-nitrooxyethylamine 3.03 g of the desired compound were obtained as colorless crystals in procedures similar to those of Reference Example 2 using 8.60 g of tetrafluoroboron of nitronium and 7.49 g of (lS) -N- (t-butoxycarbonyl) -l-propyl-2-hydroxyethylaniline. P.f .: 57-58 ° C. NMR spectrum (CDC13), d ppm: 0.95 (3H, t, 3 = 7. OHz), 1.25-1.70 (4H, rn), 1.45 (9H, s), 3.80-4.05 (1H, n), 4.20-4.70 (3H, m).

REFERENCE EXAMPLE 9 (1S) -1-prop l-2-n? Troox? Et? Iarn? Na hydrochloride 2.77 g of the desired compound were obtained as colorless crystals in procedures similar to those of reference example 3 using 4.00 g of (IS) -N- (t-butox? Carbon? L) -l-prop? L-2-mtroox? Et? Iarn? Na and 40 ml hydrochloric acid 4N-d? Oxano. P.f .: 157-158 ° C (decomp.). NMR spectrum (d6-DMS0), d ppm: 0.89 (3H, t, 3 = 7.2Hz), 1.30-1.70 (4H, m), 3.40-3.55 (1H, m), 4.65 (1H, dd, 3 = 6.8 Hz, 3 = 11.9Hz), 4.81 (1H, dd, 3 = 3 Hz, 3 = 11.9Hz), 8.51 (3H, bs).

REFERENCE EXAMPLE 10 (1 S) -N- (t-Butoxycarboml) -l-but? 1-2-ni roox? E? Lamina 1.56 g of the desired compound were obtained as a yellow oil in procedures similar to those of reference example 2 using 1.87 g of nitronium trifluoroboron and 2. 09 g of (15) -N- (t-butox? Carbon? L) -l-but? L-2-h? Drox? Et? Larn? Na. NMR spectrum (CDC13), d ppm: 0.91 (3H, t, 3 = 7.3Hz), 1.25-1.65 (6H, n), 1.45 (9H, s), 3.83-3.98 (1H, m), 4.30-4.60 ( 3H, rn).

REFERENCE EXAMPLE 11 (1S) -l-Butyl-2-n-trooxyl-ethylamine hydrochloride 702 mg of the desired compound were obtained as colorless crystals in procedures similar to those of reference example 3 using 1.56 g of ( l) -N- (t-butoxycarbonyl) -l-butyl-2-nitrooxyethylamine and 15 rnl of 4N-d-oxane hydrochloric acid. P.f .: 133-135 ° C (decomp.). NMR spectrum (CDC13), d ppm: 0.94 (3H, t, 3 = 7.3Hz), 1.20-2.00 (6H, m), 3.55-3.70 (1H, m), 4.65-4.85 (2H, n).

REFERENCE EXAMPLE 12 (lS) -N- (t-Butoxycarbonyl) -l-isopropyl-2-nitrooxole-ylamine 3.07 g of the desired compound was obtained as a yellow oil in procedures similar to those of reference example 2 using 3.19 g of tetr Lu Roboro of nitronium and 3. 31 g of (lS) -N- (t-butoxycarbonyl) -l-isoprop 1-2-hydroxyethyl ina. NMR spectrum (CDC13), d ppm: 0.97 (3H, d, 3 = 5.9Hz), 0.99 (3H, d, 3 = 6.6Hz), 1.45 (9H, s), 3.65-3.80 (1H, m), 4.35 -4.63 (3H, m).

REFERENCE EXAMPLE 13 (15) -l-Isopyropil-2-nitrooxyethylamine Hydrochloride 1.97 g of the desired compound were obtained as colorless crystals in procedures similar to those of Reference Example 3 using 3.07 g of (IS) -N- ( t -butoxycarboni l) - 1 -? soprop? l-2- mtroox i eti iarnina and 30 rn l of ací do orhloric acid 4N-d? oxano. P.f .: 174-175 ° C (decornp.). NMR spectrum (CDC13), d ppm: 1.14 (3H, d, 3 = 7.3Hz), 1. 17 (3H, d, 3 = 6.6Hz), 2.10-2.30 (1H, m), 3.40-3.52 (1H, rn), 4.70-4.90 (? H, in).

REFERENCE EXAMPLE 14 (lS) -N- (t-Buto-carbon? I) -l-? Sobu? L-2- n trooxie i lami a 3.84 g of the desired compound was obtained as a yellow oil in procedures similar to those of the reference example 2 using 3.91 g of nitroglycerin and 4. 35 g of (lS) -N- (t-butoxycarbonyl) -l-isobutyl-2-hydroxyl ethanol. NMR spectrum (CDC13), d ppm: 0.93 (3H, d, 3 = 4.6Hz), 0.95 (3H, d, 3 = 6Hz), 1.20-1.50 (2H, m), 1.45 (9H, s), 1.60- 1.80 (IH, rn), 3.90-4.10 (1H, n), 4.25-4.65 (3H, rn).

REFERENCE EXAMPLE 15 (15) - l-Isobutyl-l-2-nitrooxyethylate hydrochloride 2.32 g of the desired compound were obtained as colorless crystals in procedures similar to those of reference example 3 using 3.84 g of (lS) -N- (t-butoxycarbonyl) -1-? -butbutu-2-nitrooxyethylamine and 40 ml hydrochloric acid 4N-d-oxane.

P.f .: 174-175 ° C (decornp.). Spectrum NMR (CDC13), d, ppm: 0.93-1.10 (6H, m), 1.50-1.70 (1H, rn), 1.72-2.00 (2H, m), 3.65-3.82 (1H, m), 4.63-4.85 (2H, m).

EXAMPLE OF TEST 1 ACTION OF COLLATERAL VESSEL DILATION BY ADMINISTRATION INTRAVENOSA Beagle dogs (males), weighing 9 to 13 kg, were anesthetized by intravenous injection of pentobarbital at a dose of 30 mg / kg and examined for artificial respiration. To measure the pressure of the left carotid artery, a polyethylene cannula (intravenous catheter fltorn 2F) was inserted antegradely into a branch of the left thyroid artery. The initial current of the left carotid artery from this pressure measurement site was occluded for 1 minute with an arterial clamp, and the pressure was measured immediately before the occlusion (P) and the decrease in peripheral pressure (deltaP). Then, the test drug was administered through another poly ethylene cannula inserted in the inguinal vein. The left carotid artery was occluded for 1 minute, then 5, 15, 30, 5 and 60 minutes, and the pressure was measured immediately before the occlusion (Pa) and the decrease in peripheral pressure (deltaPa). The effect of dilation of collateral vessel (Collateral index = Cl) of the test drug was determined according to the following formula: CT-100 - (deltaPa / Pa) x 100 / (deltaP / P) As a result of this test, the Compounds of the plos 1, 5, 6 and 8 axes exhibited an excellent action, being the CK60) of more than 10 wing doses of 0..3 g / l.

EXAMPLE OF TEST 2 COLLATERAL GLASS DILATOR ACTION BY ADMINISTRATION IN THE VENA PORTA While the test specimens were prepared according to the method of test example 1, the animal was laparotomized along the abdominal midline, and < - e removed and cut a branch of the mesenteric vein by way of administering the portal vein test. A polyethylene cannula (At oin? F intravenous catheter) was inserted in an anterograde fashion into this vein to reside in the portal vein, and then the test drug was administered through it. To test the effect of the first step of the test drug, it was administered first in raven (inguinal vein) to determine the dilator action of the side-glass of the drug dur-ante 60 minutes. Then, the same test drug was administered in the portal vein 2 or 3 hours later to determine * collateral vessel diiating action for 60 minutes, and those actions were compared with each other. As a result of this test, the compound of Example 1 exhibited an excellent collateral dilator action.

EXAMPLE OF TEST 3 INHIBITION OF ULCERA INDUCED BY ASPIRIN As a test animal, 10 male rats of the üonryu strain each weighing 200 g-250 g in a group were used. The rats were fasted before the experiment for 24 hours but were able to freely drink water. The test compounds were suspended in 0.5% carboxy and 1 cellulose (CMC) solution. Meanwhile, 0.5% CMC solution was used for a control group. The test compound was administered orally (0.1 L / g of body weight) to the rats and an aspirin solution (150 rng / L: suspended in 0.5% CMC solution) was administered to the rats 1 hour later ( 0.1 rnl / 100 gd body weight). Four hours after the administration of the aspirin solution, the rats were sacrificed using carbon dioxide gas and the stomach of each rat was excised. In the stomachs, 10 ml of a 1% formal-ina solution were drained to allow the stomachs to expand and the stomachs were immersed in a 1% formal solution in a flask for approximately 15 to 20 minutes. Then, each stomach was cut along the greater curvature thereof and an area of ulceration in the gastric mucosa was measured by means of an image analysis apparatus TLuzex-F: manufactured by Nireko Co., Ltd.] . The average value of the area of ulceration of each group was calculated from the area of ulceration of each rat and the inhibition rate was obtained by comparing the average value of the test group with that of the control group. The results are shown in table 4.

TABLE 4 Compound Dosage Rate of administered inhibition (mg / kg) (%) Compound of example 1 30 63.58 * 100 80.15 ** 300 93.17 *** * p < 0.05 ** p < 0.005 In accordance with this test, the compound of Example 1 exhibited excellent anti-ulcerative action. - EXAMPLE OF TEST 4 STABILITY OF THE COMPOUNDS Approximately 2 mg of the test compound were accurately weighed and placed in a brown bottle. The bottle was allowed to stand in a dark place at room temperature (24-26 ° C) for 4 weeks and a residual ratio (%) of the test compound was measured by high pressure liquid chromatography (column: Inertsil ODS-3, solvent eluent: regulator (pH = 7.0) of 10 mM / acetomitril phosphoric acid, 80/20). The results are displayed in cell 5.

TABLE 5 Compound Residual ratio (%) Compound of Example 1 101.2 Compound 0 * 49.8 ** * Mixture 1: 1 of the compound of Example 1 and the (4R), (1R) isomer of the same. ** Compound of example 1 /? Sórnero (4R), (1R) of the same - 2/1 According to this test, the compound of Example 1 exhibited excellent storage stability compared to the 1: 1 mixture of the example compound and the (4R), (IR) isomer thereof. Meanwhile, the compound of Example 1 exhibited excellent storage stability as compared to the (4R), (1R) isomer.

EXAMPLE OF PREPARATION 1 Capsules Compound of example 1 50.0 rng Lactose 128.7 Corn starch 70, .0 Magnesium stearate 1.3 250 mg The powder formulated in this way is mixed and passed through a 60 mesh screen, and then the powder It is filled into 250 mg No. 3 gelatin capsule to prepare a capsule.

EXAMPLE OF PREPARATION 2 Tablets Compound of example 1 50.0 rng Lactose 124.0 Corn starch 25.0 Magnesium stearate 1.0 200 rng The powder formulated in this manner is mixed and made into a 200 mg tablet by means of a tabletting machine. If necessary, sugar coating can be applied to the tablet.

Claims (67)

1. NOVELTY OF THE INVENTION
2. CLAIMS 1"- A denuded de ti zoli dinona optically active that has the formula: where R 1 represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a female group which is unsubstituted or substituted with a radical selected from the group consisting of alkyl groups having 1 to 4 carbon atoms, alkoxy groups having 4 carbon atoms and halogen atoms, or a phenyl alkyl group wherein the alkyl group has 2 carbon atoms and the phenyl group is unsubstituted or substituted with a selected substituent of the group consisting of alkyl groups having from L to 4 carbon atoms, alkoxy groups having from 1 to 4 carbon atoms and halogen atoms; R2 represents an alkyl group having from 1 to 6 carbon atoms; and n represents L or 2. 2.- The optically active thiazolidinone derivative does not according to claim 1, further characterized in that Ri is a hydrogen atom, an alkyl group having 14 carbon atoms, a phenyl group which is unsubstituted or substituted with a substituent selected from methyl groups, methoxyl groups, fluorine atoms, chlorine atoms, a benzyl group which is unsubstituted or substituted by a substituent selected from methyl groups, methoxyl groups, fluorine atoms and chlorine atoms, or a fenetium group which is not substituted or it is substituted with a substituent selected from ethyl groups, ethoxy groups, fluorine atoms and chlorine atoms.
3. 3. The optically active thiazolidone derivative according to claim 1, further characterized in that R1 is a hydrogen atom, a methyl group, a 4-? Neox? Femlo group or a benzyl group.
4. 4. The optically active thiazolidinone derivative according to claim 1, further characterized in that l is a hydrogen atom.
5. 5. The optically active thiazolidinone derivative according to claim 1, further characterized in that R2 is an alkyl group having 1 to 4 carbon atoms.
6. 6. The optically active thiazolidone none derivative according to claim 1, further characterized in that R2 is a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group or an isobutyl group.
7. 7. The optically active tlazole dihydone derivative according to claim 1, further characterized in that R 2 is a methyl group, a propyl group, a butyl group or an isobutyl group.
8. 8. The optically active t-azolidone derivative according to claim 1, further characterized in that R2 is a methyl group.
9. 9. The optically active thiazolidone derivative according to claim 1, further characterized in that n is 1.
10. 10. The optically active thiazolidone derivative according to claim 1, further characterized in that R is a hydrogen atom, a alkyl group having from 1 to 4 carbon atoms, a femlo group which is unsubstituted or substituted with an eubstituyen e selected from methyl groups, ethoxy groups, fluorine atoms and chlorine atoms, a benzyl group which is unsubstituted or is substituted with a substituent selected from methyl groups, nitroxyl groups, fluorine atoms and chlorine atoms, or a phenethio group which is unsubstituted or substituted with a substituent selected from methyl groups, methoxyl groups, fluorine atoms and chlorine atoms; R2 is an alkyl group having from 1 to 4 carbon atoms; and n is 1.
11. 11. The optically active dyadol tlazole derivative according to claim 1, further characterized in that R1 is a hydrogen atom, a methyl group, a 02 group. 4-methox ifemlo or a benzyl group; R 2 is a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group or an isobutyl group; and n is 1.
12. 12. The optically active t-lazolidone derivative according to claim 1, further characterized in that R1 is a hydrogen atom; R 2 is a methyl group, a non-propyl group, a butyl group or an isobutyl group; and n is 1.
13. 13. The optically active thiazolidone derivative according to claim 1, further characterized in that R1 is a hydrogen atom and R2 is a methyl group.
14. 14. The optically active thiazolidone derivative according to claim 1, selected from the group consisting of: (4R) -N-E (IS) -1-met l -2-n? trooxiet i Ll-2-oxo-t-azozolidin-4-l-carboxamide; (4R) -N- (1 S) -l-met? L-2-n? Troox? -et? L] -5-met 1-2-oxo? Azole d? N-4-? l ~ carbox? am? da; (4R) -NC (1S) -l-rnet? L-2-n? Troox? Et? L] -5- (4-methox? Phen?) -2-oxot? Azole? D? N ~ 4- ? l-carboxyamide; (4R) -N- (15) -l-met? L-2-n? Troox? t l] -5-benc? 1-2-oxotamol-d-n-4-? L-carboxamide; (4R) -N-C (1S) -l-et? L-2 ~ n? Tro-ox? E? I] -2-oxot lazoli dm-4-? L -carboxyamide; (4R) -N-C (1S) -1-propyl-2-n? T roox? Et? I] -2-oxot? Azole? 4-? L-carbo? -amide; (4R) -N-C (lS) -l-propyl-2-n? Tro-ox? Et? P-5-met?] - 2-oxo-t? zol? d? n-4-? l-carbox? amide; (4R) -N- (lS) -l-prop? L -2-n? Tro-ox? Et? I] -5- (4-methox? Phen?) -2-oxo? Azole? D? N -4-? L-carbox? Am? Da; (4R) -N- (lS) -l-pro? -2-n? ro-oxieti-l-5-benzyl-2-oxo-tlazol idin-4-l -carbo-iamide; (4R) -N-C (15) -l-but? L- 2-n? T r * o -ox? Et? L] -2-oxot link]? D? N-4-? 1-carboxamide; (4R) -N- (15) -1- buti 1-2-n? Troox? Et? L] ~ 5-rnet? I-2-oxot? Azole? Din-4-? L-carbox? - ini da; (4 R) -NC (1S) -1 -buti 1-2 -n? Troox? Et? Ll-5- (4-rneto? Fem 1) -2 -oxo tlazol? Dm-4-? L-carboxamide; (4R) -N-C (1S) -l-butyl-2-mt-rooxiethi-5-benzyl-1-2-oxot-azol-dm-4- 11 -carbo-lamide; (4) ~ N-C (lS) -l- obut? I-2-itrooxietill--oxo? Azol L? -4 -i 1 -carbox i mi a; (4R) -N-C (1S) -1-isobuty 1-2 -tropoxyethyl 1-5 -methyl? -2-oxot? Azole? -4? 1-carbox? ami a; (4R) -N- (15) -1- isobu? L-2-n? Troox? Et? Ll-5- (4-methox? Phen? L) -2-oxot aiazolidi n-4-.?l- carbox? -ai gives, and (4R) -Nr (lS) -l-? sobuti 1- nit rooxieti l] -5-benzl-l-2-oxot lazol d-n-4-l-carboxyanide.
15. 15. A composition for preventing or treating angina pectoris comprising an effective amount of an active compound in admixture with a pharmacologically acceptable carrier or diluent; said active compound is an optically active idiane thiazole derivative according to the rei indication 1.
16. 16. The use of an optically active thiazole derivative thiazole derivative according to claim 1, to produce a medicament.
17. 17. The use of an effective amount of an optically active thiazolidinone derivative according to claim 1, in admixture with a pharmacologically acceptable carrier or diluent, to produce a medicament for the treatment or prophylaxis of angina pectoris.
18. 18. A process for the preparation of an optically active thiazolidinone derivative according to claim 1, which comprises reacting a carboxylic acid having the formula: (TGD wherein R1 is as defined in claim 1, or a reagent derived therefrom, with an amine having the formula: (TV) wherein R2 is as defined in claim 1, or a salt. of acid addition thereof.
19. 19. A process for preparing an optically active thiazolidinone derivative according to claim 1, which comprises reacting a carboxylic acid having the formula: wherein R 1 is as defined in claim 1, or a reagent derived therefrom, with an amine compound having the formula: 2 2 H 2 -NNT _S > pCH2) f? H (V) wherein R2 is as defined in claim 1, or an acid addition salt thereof and then the compound thus obtained.
20. 20. The use of a thia- or oxazolidone derivative of formula (II) as defined below or a pharmacologically acceptable salt thereof: wherein, U represents a sulfur atom or an oxygen atom and X represents a group having the formula: -N (R3) -, or X represents a sulfur atom or an oxygen atom and U represents a group having the formula: -N (R3) -; 3 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms or an aralkyl group in which the alkyl group has 1 to 4 carbon atoms and the aryl group is as defined below; R * and R5 are the same or different and each represents a hydrogen atom, an alkyl group having from 1 to 6 carbon atoms, an aralkyl group wherein the alkyl group has from 4 carbon atoms and the group ap is co or defined below, an aplo group as defined below, a 5- or 6-membered heterocyclic aromatic group containing from 1 to 3 heteroatoms selected from the group consisting of nitrogen atoms, oxygen atoms and sulfur atoms, which may be optionally condensed with a benzene ring or a 5- or 6-membered heterocyclic aromatic group containing 1 to 3 heteroatoms selected from the group consisting of nitrogen atoms, oxygen atoms and sulfur atoms which may be optionally substituted and optionally condensed with a benzene ring, said optional substitutes are selected from the group consisting of alkyl groups having from 1 to 6 carbon atoms, groups arn and mono- and dialkyl-lamino groups wherein each alkyl group has from 1 to 6 carbon atoms; R6 represents a hydrogen atom, an alkyl group having from 1 to 6 carbon atoms or an aralkyl group in which the alkyl group has from 1 to 4 carbon atoms and the aryl group is as defined below; fl represents an alkyl group having 2 to 6 carbon atoms and which is not substituted or substituted with a substituent selected from the group consisting of carboxyl groups, alkoxycarbomyl groups wherein the alkoxy groups have from 1 to 6 volumes of carbon carbon and loxycarbonyl groups wherein 1 aplo group is as defined above; the aforementioned aplo groups have from 6 to 10 carbon atoms and may be unsubstituted or may be substituted with a substituent selected from the group consisting of alkyl groups having 1 to 6 carbon atoms, alkoxy groups having 1 to 6 carbon atoms, to 6 carbon atoms, hydroxyl groups, halogen atoms, ammo groups, ono- and dialkylanino groups wherein each alkyl group has from L to 6 carbon atoms and nitro groups; in admixture with a pharmacologically acceptable carrier or diluent, to produce * a medicament for the treatment or prevention of ulcerative disease.
21. 21. The use according to claim 20, further characterized in that, in the derivative of formula (II), R3 is a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms, a benzyl group or a phenetyl group.
22. 22. The use according to claim 20, further characterized in that, in the derivative of formula (TI), R3 is a hydrogen atom, a methyl group or a benzyl group.
23. 23. The use according to claim 20, further characterized in that, in the derivative of formula (IT), it is either sulfur atom or an oxygen atom and X is a group having the formula -NR3-, where R3 is a hydrogen atom; or X is a sulfur atom and U is a group having the formula -NR3-, wherein R3 is a hydrogen atom.
24. 24. The use according to claim 20, further characterized in that, in the derivative of formula (II), W is a sulfur atom or an oxygen atom and X is a group having the formula -NR3-, in where R3 is a hydrogen atom.
25. 25. The use according to claim 20, further characterized in that, on the derivative of formula (TT), R4 and RS are the same or different and each is a hydrogen atom, an alkyl group having from 4 to carbon atoms, a phenylalkyl group wherein the alkyl group has from 1 to 4 carbon atoms and the femlo group is unsubstituted or substituted with a substituent selected from the group consisting of alkyl groups having from 1 to 4 carbon atoms , alkoxy groups having from 1 to 4 carbon atoms, hydroxyl groups, halogen atoms and nitro groups, a naphthylmethyl group, a femlo group which is unsubstituted or substituted with a substituent selected from the group consisting of alkyl groups which have from 1 to 4 carbon atoms, alkoxy groups having from L to 4 carbon atoms, hydroxyl groups, halogen atoms and nitro groups, a naphthyl group or a heterocyclic group selected from furyl, thienyl, phenyl groups iridyl, oxazolium, thiazolyl, isoxazolyl and isothiazolyl, said group is not substituted or is substituted with an alkyl group having from 1 to 4 carbon atoms.
26. 26. The use according to claim 20, further characterized in that, in the derivative of formula (II), R * and R5 are the same or different and each is a hydrogen atom, a methyl group, a benzyl group which is not substituted or substituted with a substituent selected from the group consisting of methyl groups, nitroxyl groups, hydroxyl groups, fluorine atoms, chlorine atoms, a phenethyl group which is not substituted or substituted with a selected substituent of the group consisting of methyl groups, methoxyl groups, hydroxyl groups, fluorine atoms and chlorine atoms, a phenyl group which is unsubstituted or substituted with a substituent selected from the group consisting of methyl groups, methoxyl groups, hydroxyl groups, atoms of fluorine and chlorine atoms, a fuplo group, a thienyl group or a pipdoyl group.
27. 27. The use according to claim 20, further characterized in that, in the derivative of formula (TI), R * is a hydrogen atom, a methyl group, a benzyl group which is not substituted or is substituted with a substuent selected from the group consisting of methyl groups, rnetoxyl groups and hydroxyl groups, or? phen group which is unsubstituted or substituted with a substituent selected from the group consisting of methyl groups, rnetoxyl groups and hydroxyl groups; and R5 is a hydrogen atom.
28. 28. The use according to claim 20, further characterized in that, in the derivative of formula (II), R * is a hydrogen atom, a methyl group, a benzyl group, a phenyl group or a methoxyphenyl group.; and R5 is a hydrogen atom.
29. 29. The use according to the indication rei 20, characterized adornas because, in the derivative of formula (II), R * is? N hydrogen atom, a methyl group, a benzyl group or a group 4-rnetoxifemlo; and R5 is a hydrogen atom.
30. 30. The use according to claim 20, further characterized in that, in the derivative of formula (TI), R * is a hydrogen atom, and R5 is a hydrogen atom.
31. 31. The use according to claim 20, further characterized in that, in the derivative of formula (II), R * is a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms, a group bencí lo or a phenetilo group.
32. 32. The use according to claim 20, further characterized in that, in the derivative of formula (II), Rβ is a hydrogen atom, a methyl group or a benzyl group.
33. 33.- The use in accordance with Claim 20, further characterized in that, in the derivative of formula (TT), P is a hydrogen atom.
34. 34. The use according to claim 20, further characterized in that, in the derivative of formula (TI), fl is an alkylene glycogen having from 2 to 4 atoms of carbon which is not substituted or is substituted with a carboxyl group or an alkoxycarbonyl group wherein the alkoxy group has from 1 to 4 carbon atoms.
35. 35. The use according to claim 20, further characterized in that, in the derivative of formula (ID, fl is an alkylene group having 2 to 4 carbon atoms. with claim 20, characterized by adornments because, in the formula derivative (TT), fl is an ethylene group or a group 1 -metí le i Leño 37. The use according to claim 20, further characterized in that, in the derivative of formula (TT), R3 is a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a benzyl group or a phenethyl group; R * and Rd are the same or different and each is a hydrogen atom, an alkyl group having 4 carbon atoms, a phenol alkyl group wherein the alkyl group has from 1 to 4 carbon atoms and the femlo group is not substituted or is substituted with a substituent selected from the group consisting of alkyl groups having from 1 to 4 carbon atoms, alkoxy groups having from 1 to 4 carbon atoms, hydroxyl groups, halogen atoms and groups nitro, a naphthylmethio group, a phenyl group which is unsubstituted or substituted with a substituent selected from the group consisting of alkyl groups having from 1 to 4 carbon atoms, alkoxy groups having from 1 to 4 carbon atoms, groups hydroxyl, halogen atoms and nitro groups, a naphthyl group or a heterocyclic group selected from furyl, thienyl, pipdoyl, oxazolyl, thiazolyl, isoxazoyl and isothiazolyl groups, said group is unsubstituted or substituted an alkyl group having 1 to 4 carbon atoms; β is a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms, a benzyl group or a phenethiium group; and A is an alkylene group that p? it has from 2 to 4 carbon atoms which is unsubstituted or substituted with a carboxyl group or an alkoxycarbonyl group in which the alkoxy group has from 1 to 4 carbon atoms. 38. The use according to claim 20, further characterized in that, in the derivative of formula (ID, R3 is? N hydrogen atom, a methyl group or a benzyl group, R4 and R5 are the same or different and each one is a hydrogen atom, a methyl group, a benzyl group which is unsubstituted or substituted with a substiuent selected from the group consisting of methyl groups, inetoxyl groups, hydroxyl groups, fluorine atoms and chlorine atoms, a phenetium group which is unsubstituted or substituted by a substituent selected from the group consisting of methyl groups, nitroxyl groups, hydroxyl groups, fluorine atoms and chlorine atoms, a phenyl group which is unsubstituted or substituted by a substituent selected from the group consisting of methyl groups, netoxyl groups, hydroxyl groups, fluorine atoms and chlorine atoms, a fuplo group, a thienyl group or a pipdoyl group, R6 is a hydrogen atom, a methyl group or or a benzyl group; and fl is an alkylene group having 2 to 4 carbon atoms. 39. The use according to claim 20, further characterized in that, in the derivative of formula (TI), U is a sulfur atom or an oxygen atom and X is a group having the formula -NR3- , wherein R3 is a hydrogen atom; or X is a sulfur atom and Ul is a group having the formula -NR3-, wherein R3 is? n hydrogen atom; R * is a hydrogen atom, a methyl group, a benzyl group which is unsubstituted or substituted with a substitute e selected from the group consisting of methyl groups, methoxyl groups and hydroxyl groups, or a phenyl group which is not substituted or is substituted with a substituent selected from the group consisting of methyl groups, netoxyl groups and hydroxyl groups; R5 is a hydrogen atom; R6 is a hydrogen atom; and fl is an alkaline group that has de? to 4 carbon atoms. 40. The use according to claim 20, further characterized in that, in the derivative of formula (TI), U is a sulfur atom or an oxygen atom and X is a group having the formula -NR3- , wherein R3 is a hydrogen atom; R * is a hydrogen atom, a methyl group, a benzyl group, a femlo group or an ethoxypheme group; RS is a hydrogen atom; R6 is a hydrogen atom; and fl is an alkylene group having 2 to 4 carbon atoms. 41. The use according to claim 20, further characterized in that, in the derivative of formula (TT), U is a sulfur atom and X is a group having the formula -NR3-, wherein R3 is an atom of hydrogen; R * is a hydrogen atom, a methyl group, a benzyl group or a 4-rnetox ifenyl group; R5 is a hydrogen atom; R6 is a hydrogen atom; and fl is an ethylene group or a linear group. 42. The use according to claim 20, further characterized in that, in the derivative of formula (II), U is a sulfur atom and X is a group having the formula -NH-; R4 is a hydrogen atom; R5 is a hydrogen atom; R6 is a hydrogen atom; and fl is an ethylene group or a 1 -methyl group. 43. The use according to claim 20, further characterized in that the thia- or oxazole dinone derivative or pharmacologically acceptable salt thereof is selected from the group consisting of: N- (2-n? Troox? Et ?) 1-oxothiazolidi n-4-l-carboxiarnide; N- (2-n? Troox? Et? L) -5-met? L-2-oxothiazole? D? N-4-yl-carboxy amide; N- (2-mtroox? Et ii) -5- (-rnetoxifeni l) -2-oxo-thiazolidm-4? L-carboxyamide; N- (2-nitrooxidyl) -5-benzyl-2-oxothiazole? D? N-4-? L-carboxamide; N- (1-rnet? I-2- mtroo ietii) -2-oxot lazol? D? N-4-? L-carboxy amide; N- (2-nit roox? Et? L) -2-oxooxazole? D? N-4-? L ~ carbox? Arn? gives; N- (2- nor tro -ox? Et? L) -5- (3-fur? L) -2-oxooxazole? D? N-4-? L-carbox? Am? gives; N- (2-nitrooxyethyl) -5-benzyl-2-oxooxazole d-n-4-carboxycarnide; N- (1 -? Net? L-2-n? Troox? Et? L) -2-oxooxazole? D? N-4-yl-carbox? Am? Da; N- (1-rnenyl-2-n? Troox? Et? L) -5-met? L-2-oxot? Azole? -ne? 4-? L-carbox? -amide; N- (l ~ rnet? 1-2 ~ nitrooxiet.il) -5- (4-rnetox? Phen l) -2 ~ oxo-thiazole? D? N-4-? L-carboxamide; N- (l ~ rnet? L-2-mtroox? Ethyl) -5-benzyl-2-oxot? Azole? din-4-carboxyamide; N- (1-met? L-2-n? T ro-o? Et? L) -5- (3-fur? 1) -2 -oxooxazole? Dm-4-l-carboxamide; N- (l-rnet? I-2-nitrooxyethyl) -5- benzyl-2-oxooxazole? D? N ~ 4-? L-carboxamide; N- (2-n? Troox? Et? L) -2 ~ oxot? Aol? D? N ~ 5-? ~ Cbox? m? gives; N- (2-n? Troox? E? I) -4- (4-methox? Fon? L) -2-oxo-t? Azol? D? N-5-? 1-carboxiarnide; N- (l-rne? L-2-nitroox? E? L) -2-oxo-thiazole? din-5-? l -carboxiami da, and N- (l ~ met? l ~ 2-n? troox? et? l) -4- (4-rn tox? phen?) -2-oxot? azole? din-5-? l-carboxyiam? da; and pharmacologically acceptable salts of the same. 44. A composition for preventing or treating an ulcerative disease comprising an effective amount of an active compound in admixture with a pharmacologically acceptable carrier or diluent, characterized in that said active compound is a thia- or oxazolidinone derivative of formula (TI) as further defined, or a pharmacologically acceptable salt thereof: wherein Ul r-represents a sulfur atom or an oxygen atom and X represents a group having the formula: -N (R 3) -, or X r-e represents a sulfur atom or an oxygen atom and U represents a group that has the formula: -N (R3) ~; R3 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms or an aralkyl group in which the alkyl group has 1 to 4 carbon atoms and the aryl group is as defined above ahead; R * and R5 are the same or different and each represents a hydrogen atom, an alkyl group having from 1 to 6 carbon atoms, an aralkyl group wherein the alkyl group has from 4 carbon atoms and the aplo group is as defined below, an analogous group as defined below, a 5- or 6-membered heterocicc aromatic group containing from 1 to 3 heteroatoms selected from the group consisting of nitrogen atoms, Oxygen and sulfur atoms, which may be optionally condensed with a benzene ring or a 5- or 6-membered heterocyclic aromatic group containing 1 to 3 heteroatoms selected from the group consisting of nitrogen atoms, oxygen atoms and sulfur atoms which may be optionally substituted and optionally condensed with a benzene ring, said optional substituents are selected from the group consisting of alkyl groups having from 1 to 6 carbon atoms, arnine atoms and mono- and dialkylamino groups wherein each alkyl group has from 1 to 6 carbon atoms; R6 represents a hydrogen atom, an alkyl group having from 1 to 6 carbon atoms or an aralkyl group in which the alkyl group has from 1 to 4 carbon atoms and the aryl group is as defined below; A represents an alkylene group having 2 to 6 carbon atoms and which is unsubstituted or substituted with a substituent selected from the group consisting of carboxyl groups, alkoxycarbonyl groups wherein the alkoxy groups have from 1 to 6 carbon atoms and aryloxycarbomyl groups wherein 1 aryl group is as defined below; the aforementioned aryl groups have from 6 to 10 carbon atoms and can be unsubstituted or can be substituted with a substituent selected from the group consisting of alkyl groups having 1 to 6 carbon atoms, alkoxy groups having 1 to 6 carbon atoms, to 6 carbon atoms, hydroxyl groups, halogen atoms, ani groups, mono- and dialkylamino groups wherein each alkyl group has from 1 to 6 carbon atoms and nitro groups. 45. The composition according to claim 44, further characterized in that R3 is a hydrogen atom, an alkyl group having from L to 4 carbon atoms, a benzyl group or a phenethium group. 46. The composition according to claim 44, further characterized in that R3 is a hydrogen atom, a methyl group or a benzyl group. 47. The composition according to claim 44, further characterized in that U) is a sulfur atom or an oxygen atom and X is a group having the formula -NR3-, wherein R3 is a hydrogen atom; or X is a sulfur atom and U is a group having the formula -NR3-, wherein R3 is a hydrogen atom. 48. The composition according to claim 44, further characterized in that U is a sulfur atom or an oxygen atom and X is a group having the formula -NR3-, wherein R3 is a hydrogen atom. 49.- The composition according to claim 44, further characterized in that R * and R5 are 90 same or different and each is a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms, a femlalkyl group wherein the alkyl group has from 1 to 4 carbon atoms and the femlo group is not substituted or osta substituted with a substituent selected from the group consisting of alkyl groups having 1 to 4 carbon atoms, alkoxy groups having from 1 to 4 carbon atoms, hydroxyl groups, halogen atoms and nitro groups, a naphthyl group, a phenyl group which is unsubstituted or substituted by a substituent selected from the group consisting of alkyl groups having 1 to 4 carbon atoms, alkoxy groups having from 4 carbon atoms, hydroxyl groups, halogen atoms and nitro groups, a naphthyl group or a heterocyclic group selected from fuplo, thienyl, pipdoyl, oxazolyl, thiazolyl, isoxazolyl and isothiazolyl groups, said group is not substituted or is substituted with an alkyl group having from 1 to 4 carbon atoms. 50.- The composition according to claim 44, further characterized in that R * and R5 are the same or different and each is a hydrogen atom, a methyl group, a benzyl group that is unsubstituted or substituted with a substituent selected from the group consisting of methyl groups, methoxyl groups, hydroxyl groups, fluorine atoms, chlorine atoms, a phenothion group which is unsubstituted or substituted with a substituent selected from the group consisting of methyl groups, ethoxy groups, groups hydroxyl, fluorine atoms, and chlorine atoms, a phenyl group that is unsubstituted or substituted with a substituent selected from the group consisting of methyl groups, nitroxyl groups, hydroxyl groups, fluorine atoms, and chlorine atoms , a fuplo group, a thienyl group or a pyridyl group. 51.- The composition in accordance with claim 44, also characterized because R4 is an environment The hydrogen atom, a methyl group, a benzyl group which is unsubstituted or is substituted with a substituent selected from the group consisting of methyl groups, methoxyl groups and hydroxyl groups, or a femlo group which is unsubstituted or substituted by a its owner L5 selected from the group consisting of methyl groups, nitroxyl groups and hydroxyl groups; and RS is a hydrogen atom. 52.- The composition according to claim 44, characterized by adornas because R is a hydrogen atom, a methyl group, a benzyl group, a group Phenyl or a methoxyphenyl group; and R5 is a hydrogen atom. 53. The composition according to claim 44, further characterized in that R * is a hydrogen atom, a methyl group, a benzyl group or a 4- rnetoxy phenol group; and RS is a hydrogen atom. 54. The composition according to claim 44, further characterized in that R4 is a hydrogen atom, and R5 is a hydrogen atom. 55.- The composition according to claim 44, further characterized in that Rβ is a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a benzyl group or a phenethyl group. 56. The composition according to claim 44, further characterized in that R6 is a hydrogen atom, a methyl group or a benzyl group. 57.- The composition according to claim 44, further characterized in that R6 is a hydrogen atom. 58.- The composition according to claim 44, further characterized in that A is an alkylene group having 2 to 4 carbon atoms that is not substituted or is substituted with a carboxyl group or an alkoxycarbonyl group, wherein the group Alkoxy has 1 to 4 carbon atoms. 59. The composition according to claim 44, further characterized in that A is an alkylene group having 2 to k carbon atoms. 60. The composition according to claim 44, further characterized in that fl is an ethylene group or a 1-methylkene group. 61.- The composition according to claim 44, further characterized in that R3 is a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a benzyl group or a phenethyl group; R * and R5 are the same or different and each is a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms, a phenylalkyl group wherein the alkyl group has from 4 carbon atoms and the phenyl group is unsubstituted or substituted with a substituent selected from the group consisting of alkyl groups having from 1 to 4 carbon atoms, alkoxy groups having from 1 to 4 carbon atoms, hydroxyl groups, halogen atoms and nitro groups, a naphthylmethio group, a phenyl group which is unsubstituted or substituted with a substituent selected from the group consisting of alkyl groups having 1 to 4 carbon atoms, alkoxy groups having from 1 to 4 carbon atoms, hydroxyl groups, halogen atoms and nitro groups, a naphthyl group or a heterocyclic group selected from groups fuplo, timme, piphod, oxazolyl, thiazolyl, isoxazolyl and sothiazolyl, said group is unsubstituted or substituted by a alkyl group having from 1 to 4 carbon atoms; R * is a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a benzyl group or a phenethyl group; and A is an alkylene group having 2 to 4 carbon atoms which is unsubstituted or substituted with a carboxyl group or an alkoxycarbonyl group wherein the alkoxy group has from 1 to 4 carbon atoms. 62. The composition according to claim 44, further characterized in that R3 is a 10? of hydrogen, a methyl group or a benzyl group; R * and RS are the same or different and each is hydrogen atom, a methyl group, a benzyl group which is not substituted or substituted by a substitute selected from the group consisting of methyl groups, ethoxyl groups, hydroxyl groups, fluorine atoms and chlorine atoms, a phenethyl group which is unsubstituted or substituted with a substituent selected from the group consisting of methyl groups, nitroxyl groups, hydroxyl groups, fluorine atoms and chlorine atoms , a phenyl group which is unsubstituted or substituted with a substituent selected from the group consisting of methyl groups, methoxyl groups, hydroxyl groups, fluorine atoms and chlorine atoms, a furyl group, a thienyl group or a pyridyl group; R * is a hydrogen atom, a methyl group or a benzyl group; and fl is an alkylene group having 2 4 carbon atoms. 63.- The composition according to claim 44, further characterized in that W is a sulfur atom or an oxygen atom and X is a group having the formula -NR3-, wherein R3 is a hydrogen atom; or X is a sulfur atom and U is a group having the formula -NR3-, wherein R3 is a hydrogen atom; R * is a hydrogen atom, a methyl group, a benzyl group which is unsubstituted or substituted with a substituent selected from the group consisting of methyl groups, methoxyl groups and hydroxyl groups, or a phenyl group which is unsubstituted or is substituted with a substituent selected from the group consisting of methyl groups, rnetoxyl groups and hydroxyl groups; RS is a hydrogen atom; RS is a hydrogen atom; and fl is an alkylene group having 2 to 4 carbon atoms. 64.- The composition according to claim 44, further characterized in that U is a sulfur atom or an oxygen atom and X is a group having the formula -NR3-, wherein R3 is a hydrogen atom; R 4 is a hydrogen atom, a methyl group, a benzyl group, a phenyl group or a methoxyphenyl group; RS is a hydrogen atom; R * is a hydrogen atom; and fl ee an alkylene group having from 2 to 4 carbon atoms. The composition according to claim 44, further characterized in that W is a sulfur atom and X is a group having the formula -NR3-, wherein R3 is a hydrogen atom; 4 is a hydrogen atom, a methyl group, a benzyl group or a 4-methox-femlo group; R5 is a hydrogen atom; Rβ is a hydrogen atom; and fl is an ethylene group or a 1-methylethylene group. 66. The composition according to claim 44, further characterized in that U is a sulfur atom and X is a group having the formula -NH-; R * is a hydrogen atom; Re is a hydrogen atom; R is a hydrogen atom; and fl is an ethylene group or an L-methylene group. 67.- The composition according to claim 44, further characterized in that the a thia- or oxazolidinone derivative or the pharmacologically acceptable salt of the same is selected from the group consisting of: N- (2-nitrooxylethyl) -2- oxotol jazol i di n-4-? l-carboxamide; N- (2-n? Tro-o ie il) -5-rnet? 1 -2-oxot? Azole? din-A-11-carboxiarnide; N- (2-nit r-ooxietii) -5- (4-methox? Phen? L) -2-oxot? Azole? Dm-4-? L -carboxy-arm da; N- (2 ~ nitroxyethyl) ~ 5- has 11 -2-oxo < lazol idi n-4 -i I -carbo lamida; N- (l-met? L-2-mtroox? Et? I) -2-oxot? Aolol d? N-4-Ll-carbox lamide; N- (? -n? T rooxiet il) -? -oxoxoxazole -d-I -carbox i-Lda; N- (2-nor trooxiethyl) -5- (3-fur? 1) - -oxooxazole? ? n-4 - 11 -car-box lick; N- (2-n? Troox? Et? L) -5-benzyl-2-oxooxazole? D? N-4? -carboxyl lamide; N- (l-met? I-2-mtroox? Et? I) -2-oxooxazole? D? n-4-? l-carboxiarnide; N- (l-met? L-2-nitroox? Et? L) -5-met l-2-oxo-t? Aolol? D? N-4-? L-carboxyamide; N- (l-met? L-2-mtroox? Et i l) ~ 5 - (4-rnetox? Phen? L) -2-oxot? Aolol d? N ~ 4- ll -carboxyamide; N- (i-rnet? L-2-nitroxyethyl) -5-benzyl-2-oxot? Aolol? D? N-4-? L-carbox? Arn? Da; N- (1-rnet? I-2-mtroox? Et? L) - 5- (3-f? P 1) -2-oxooxazole idin- 4-? L-carhoxy -amide; N- (l-methyl-2-n? Troo? Et? I) -5-benzyl 1-2 -oxooxazole? D? N-4-? L-earbox lick; N- (2-n? Troox? Et? I) ~ 2-oxot? zol? d? n-5-? l-carboxamide; N- (2-n? Troox? Et? I) ~ 4- (4-methox? Phen? L) ~ 2-oxo-thiazole? D? N-5? -carboxylamide; N- (1-methyl-2-methyl-ethyl) -2-oxot-azole-d-n-5-l-carbo-lide, and N- (1 -methyl-2-nor rooxiet ii) -4- (4 ~? Netox? Phenyl) -2-oxothiazole? D? N-5? -carboxyamide; and pharmacologically acceptable salts of misnoe.