Preparation of spiro derivatives for the modulation of stearoyl-coa desaturase.

Abstract

The title compds. I [Q = pyridinediyl, pyrimidinediyl, pyrazinediyl, etc.; W = NR7CO, C(O)NR7, NR7C(O)NR7, etc.; Z = C(O), O, S, etc.; k = 0-1; m = 0-8; n = 0-4; p = 0-4; R1 = H, alkyl, alkoxy, etc.; R2 = H or alkyl; R3 = alkyl, halo, haloalkyl, etc.; R5 = alkyl, halo, haloalkyl, etc.; R6 = alkyl, alkoxy, cycloalkyl, etc.] that modulate the activity of stearoyl-CoA desaturase, were prepd. Thus, amidating 2-(7-fluoro-4-oxospiro[chroman-2,4'-piperidine]-1'-ylcarboxamido)isonicotinic acid (prepn. given) with methylamine hydrochloride afforded II which was subsequently converted to its HCl salt which showed microsomal IC50 of 0.524 μM when tested for SCD inhibition. Methods of using compds. I to modulate the activity of stearoyl-CoA desaturase and pharmaceutical compns. comprising such derivs. are also encompassed. [on SciFinder(R)]