Preparation of hydroxamic acid derivatives as gram-negative antibacterial agents.

Abstract

The invention relates to title compds. I [n = 0-2; M = divalent radical selected from CH2, C2-3 alkenyl, C2-4 alkynyl; X1 = N, CR1; X2 = N, CR2; X3 = N, CR3; X4 = N, CR4; R1 = H, OMe, Ph, OPh, etc.; or R1 and R2 taken together with the ring to which they are attached form a bicyclic ring contg. 0-3 heteroatoms; R2 = H, NH2, halo, alkyl, etc.; or R2 and R3 taken together with the ring to which they are attached form a bicyclic ring contg. 0-3 heteroatoms; R3 = H, heterocyclyl, NH2, etc.; R4 = H, halo, NH2, etc.; R5 = (un)substituted aryl, NHPh, heteroaryl] or a salt thereof. In some embodiments, the invention relates to inhibitors of UDP-3-0-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC). Over two-hundred-ninety compds. I were prepd. E.g., a 3-step synthesis of II, starting from 4-bromopyridine-2-carboxylic acid, was given. Exemplified compds. I were tested for P. aeruginosa LpxC (data provided). For example, II showed 95.01% inhibition at 0.5 micro M. The invention also relates to pharmaceutical compns. comprising compds. I and their use in the prevention and/or treatment of Gram-neg. bacterial infections. [on SciFinder (R)]