Sulfonic acid derivatives of hydroxamic acids and their use as medicinal products

A sulfonic acid compound of hydroxamic acid selected from the group consisting of:

• 5-methyl-3(R)-[1 (S)-methylcarbamoyl-2-(4-sulfomethoxyphenyl1)ethylcarbamoyl]-2(R or S)-phthalimidomethylhexanohydroxamic acid,
• 5-methyl-3 (R)-{1(S)-methylcarbamoyl-2-[4-(2-sulfoethoxy)phenyl]ethylcarbamoyl}-2(R or S)-phthalimidomethylhexanohydroxamic acid,
• 5-methyl-3(R)-{1(S)-methylcarbamoyl-2-[4-(3-sulfopropoxy)phenyl]ethylcarbamoyl}-2(R or S)phthalimidomethylhexanohydroxamic acid,
• 5-methyl-3(R)-{1(S)-methylcarbamoyl-2-[4-(4-sulfobutoxy)phenyl]ethylcarbamoyl}-2(R or S)-phthalimidomethylhexanohydroxamic acid,
• 5-methyl-3(R)-{1(S)-methylcarbamoyl-2-[4-(5-sulfopentoxy)phenyl]ethylcarbamoyl}-2(R or S)-phthalimidomethylhexanohydroxamic acid, and
• 5-methyl-3(R)-{1(S)-phenylcarbamoyl-2-[4-(3-sulfopropoxy)phenyl]ethylcarbamoyl}-2(R or S)-phthalimidomethylhexanohydroxamic acid,
• or a pharmacologically acceptable salt thereof.

A method of preventing sepsis, which comprises administering an effective amount of a sulfonic acid compound of hydroxamic acid or a pharmacologically acceptable salt thereof to a mammal in need thereof, wherein the sulfonic acid compound has the formula (I):

• wherein
• X is hydrogen or a hydroxyl group-protecting group;
• R1is phthalimidomethyl;
• R2 is hydrogen, alkyl, arylalkyl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl or aryl;
• Y is O, NR7 wherein R7 is as defined for R2 or S;
• n is an integer of any of 1 to 6;
• R3 is hydrogen, halogen, hydroxyl group, trifluoromethyl, cyano, nitro, amino, alkyl, alkoxy, acyloxy, carbamoyl, lower alkylamino or dilower alkylamino group;
• R4 is OR8 wherein R8 is hydrogen, lower alkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl or NR10R11 wherein R10 and R11 are the same or different and each is hydrogen, lower alkyl, arylalkyl, heteroaryl, heteroarylalkyl or aryl, or R10 and R11 optionally form an optionally substituted hetero ring together with the adjacent nitrogen atom;
• and
• said arylalkyl, heteroarylalkyl, heteroarylalkylthioalkyl, heteroarylthioalkyl, arylthioalkyl, arylalkylthioalkyl, phthalimidomethyl, aryl and heteroaryl optionally have substituents, or a pharmacologically acceptable salt thereof.

A method of treating sepsis, MOF, chronic articular rheumatism, Crohn's disease, cachexia, or asthma, which comprises administering an effective amount of a sulfonic acid compound of hydroxamic acid or a pharmacologically acceptable salt thereof to a mammal in need thereof, wherein the sulfonic acid compound has the formula (I):

• wherein
• X is hydrogen or a hydroxyl group-protecting group;
• R1is phthalimidomethyl;
• R2 is hydrogen, alkyl, arylalkyl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl or aryl;
• Y is O, NR7 wherein R7 is as defined for R2 or S;
• n is an integer of any of 1 to6;
• R3 is hydrogen, halogen , hydroxyl group, trifluoromethyl, cyano, nitro, amino, alkyl, alkoxy, acyloxy, carbamoyl, lower alkenylamino or dilower alkylamino group;
• R4 is OR8 wherein R8 is hydrogen, lower alkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl or NR10R11 wherein R10 and R11 are the same or different and each is hydrogen, lower alkyl, arylalkyl, heteroaryl, heteroarylalkyl or aryl, or R10 and R11 optionally form an optionally substituted hetero ring together with the adjacent nitrogen atom;
• and
• said arylalkyl, heteroarylalkyl, heteroarylalkylthioalkyl, heteroarylthioalkyl, arylthioalkyl, arylalkylthioalkyl, phthalimidomethyl, aryl and heteroaryl optionally have substituents, or a pharmacologically acceptable salt thereof.