A NOVEL HYDROXAMIC ACID DERIVATIVE AS PEPTIDE DEFORMYLASE INHIBITOR AND MANUFACTURING METHOD THEREOF

• Main Authors: KANG, JAE HOON, YU, SEUNG WOO, LEE, HEE YEOL, CHO, BONG HWAN, AN, KYUNG MI
• Format: Patent
• Language: English
• Published: 30.10.2006
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

A novel hydroxamic acid derivative as a peptide deformylase inhibitor and a manufacturing method thereof are provided to inhibit proliferation of pathogenic bacteria by inhibiting their protein biosynthesis and polypeptide maturation catalyzed by the peptide deformylase. The hydroxamic acid derivative represented by the formula(I) or its pharmaceutically acceptable salt is provided, wherein A is -C(=O)NHOH or -N(CHO)OH; R1 is hydrogen, C1-3 alkyl, C4-6 cycloalkyl, halogen or hydroxy; R2 is hydrogen, linear or branched C1-6 alkyl, linear or branched C1-6 alkene, C4-6 cycloalkyl, C4-6 heterocycle containing N or O, or benzyl; R3 is hydrogen, methyl, linear or branched C1-6 alkyl, linear or branched C1-6 alkene, C4-6 cycloalkyl, phenyl or benzyl; R4 is hydrogen, linear or branched C1-4 alkyl, C1-4 alkene, or hydroxy substituted C1-4 alkyl; Y is represented by the formula(IIa), formula(IIb) or formula(IIc); n is 0 or 1; and R5, R6, R7, R8 and R9 are each independently hydrogen, linear or branched C1-3 alkyl, hydroxy, alkoxy, acyl, acyloxy, halogen, cyano, nitro, amino, N,N-dimethylamino, phenyl, morpholine or formyl. The hydroxamic acid derivative represented by the formula(I) or its pharmaceutically acceptable salt is prepared by reacting compounds of the formula(III) with hydroxylamine or N- or O-protected hydroxylamine, and removing the protecting group.