Patent TW-338041-B (TW)
Title: Thiazole and imidazole derivatives and their use as a millard reaction inhibitor
Inventor: YASUMURA KOICHI
IPC: A61P3/10
Filed: 1994-02-26
Granted: 1998-08-11
Abstract: A kind of compound or its medically acceptable salt represented by the following formula: where R1 represents hydrogen atom, C1~4, alkoxyl carbonyl-C1~4, alkyl, phenyl-C1~4 alkyl (its phenyl ring can have one C1~4 alkoxyl), or phenyl; R2 represents amino, phenyl sulfonamide group (its phenyl ring can contain a substitution group selected from halogen atom and C1~4 alkyl amide), or -N=R4 (where R4 represents C1~4 alkylene, C1~4 alkylene or C5-6 cycloalkylene having 1 or 2 C3~6 cycloalkyl group); R3 represents: hydrogen atom, C1~4 alkyl, phenyl-C1~4 alkoxyl-C1~4 alkyl, phenyl (may have one hydroxyl group), 5-member unsaturated heterocyclic-C1~4 alkyl containing 1 or 2 nitrogen atoms (wherein the heterocyclic group can stick to the phenyl ring and one hydroxyl can be positioned on the phenyl ring as a substitution group), -W-(NH)b-CO-OR5 (wherein W represents C1~4 alkylene, R5 represents hydrogen atom, C1~4 alkyl or phenyl-C1~4 alkyl, while b is 0 or 1), -Z-CORa {wherein Z represents C1~4 alkylene, Ra represents -Tyr-(ORa1)-ORb1, -Leu-ORb2, -Trp-ORb3, -Asp(ORa2)-ORb4, -Ph-Gly-ORb5 (where Ra1 and Ra2 represent respectively hydrogen atom or naphthyl, while Rb1, Rb2, Rb3, Rb4 and Rb5 representively respectively hydrogen atom or C1~4 alkyl) or -N(R6)-R7[where R6 represents C1~4, alkyl, carboxyl-C1~5 alkyl, C1~4 alkoxyl carbenyl-C1~5 alkyl, phenyl-C1~4 alkyl, C3~6 cycloalkyl, phenyl (which may contain 1-3 substitution groups selected from halogen atom, hydroxyl, C1~4, alkyl, C1~4 alkoxyl, C1~4 alkylthio, carboxyl, C1~4 alkoxyl carbenyl, phenyl-C1~4 alkoxyl, C1~2 dioxy alkylene, morphiline, halogenated C1~4 alkyl, carboxyl-C1-4 alkyl, C1~4 alkoxyl carbenyl-C1~4 alkyl, 6-carboxyl-2,5,7,8-tetramethyl-2-methoxyl, and 6-C1~4 alkanoxy-2,5,7,8-tetramethyl-2-methoxyl), naphthyl, 3,4-di-hydrobarbon-fornyl vinyl, morphiline, or 1 or 2 unsaturated heterocyclic-C1~4 alkyl selected from nitrogen atom, oxygen atom and sulfur atom, and R7 represents hydrogen atom or C1~4 alkyl]}, or a group represented by a formula below, {wherein B represents C1~4, alkylene; R8 represents carboxyl, nitro, phenyl-C1~4 alkyl, C1~4 alkylthio, and may contain phenylthio having 1 halogen atom, may contain phenyl-methyl-amide having 1 halogen atom, or O-D-R9 (wherein D represents C1~4 alkylene, R9 represents phenyl (the phenyl ring may contain 1 to 2 halogen atoms), having saturated or unsatured heterocyclic group or C3~6 cycloalkyl group selected from heteroatoms of nitrogen and sulfur]; and n denotes 0 or 1}; X represents -S- or -N (R10) - (where R10 represents hydrogen atom); (symbol) represents single bond or double bond; when (symbol) is single bond, A represents carbenyl, or when (symbol) is double bond, A represents = C(R11)-, {wherein R11 represents C1~4 which may contain 1 to 3 halogen atoms, carboxyl-C1~4 alkyl, pyrrole, thiazole, phenyl-amino-formyl-C1~4 alkyl (its phenyl ring may have 1 or 2 C1~4 alkoxyl) or (formula) group, (where R12 represents halogen atom, hydroxyl, carboxyl, phenyl thio or phenyl-C1~4 alkoxyl (its phenyl ring may have 1 halogen atom), and m denotes 0, 1, or 2)}; and one 6-member ring generated from the union of R4 and R10 described above, but in this example, A represents carbonyl; whereas R3 cannot be hydrogen atom; the restrictive conditions are: when R3 represents oxygen and A represents carbenyl, R1 cannot denote hydrogen atom or C1~4, alkoxyl carbenyl-C1~4 alkyl; when R3 represents C1~4 alkyl or -W-CO-OR5, X cannot represent -S-; and when R11 represents (formula) group, R2 cannot represent amino group.