Preparation of bicyclic heteroaryl inhibitors of PDE4.

Abstract

The title compds. I [X3 = C(O), (un)substituted NH or CH2; R1, R2 = H, acyl, alkoxy, etc.; R3, R4 = H, halo, alkoxy, alkyl; R5 = (CR8R9)mW(CR10R11)n, (CR12R13)p; W = O, NR7, CONR7, SOq; m, n, q = 0-2; p = 1-2; R6 = carboxy, alkylcarboxy, amido, etc.; R7-R13 = H or alkyl], useful as inhibitors of phosphodiesterase 4 (PDE4) for the treatment or prevention of inflammatory diseases and other diseases involving elevated levels of cytokines and proinflammatory mediators, were prepd. E.g., a multi-step synthesis of II, starting from 1-(2,3-dihydroxy-4-methoxyphenyl)ethanone and bromocyclopentanone, was described. Exemplified compds. I were tested as PDE4 inhibitors (data given). Pharmaceutical compn. comprising the compd. I is disclosed. [on SciFinder(R)]