Preparation of pyridazine derivatives as stearoyl-CoA desaturase inhibitors for treating skin disorders.

Abstract

Title compds. I [wherein x, y = 1-3; W = (un)substituted CONH, NHCO, NHCONH, etc.; V = C(O), C(S), CH2, monosubstituted CH2; R2, R3 = alk(en)yl, heterocyclyl, etc.; R4, R5 = H, F, Me, etc.; R6 - R9a = H, alkyl, etc., and isomers, pharmaceutically acceptable salts, pharmaceutical compns. or prodrugs thereof], which are useful as stearoyl-CoA desaturase (SCD) inhibitors and in the treatment of SCD-mediated diseases, such as skin disorders, were prepd. For example, acylation of 1-Boc-piperazine with 2-trifluoromethylbenzoyl chloride followed by deprotection with TFA in dichloromethane gave the corresponding benzoylated piperazine. This compd. underwent condensation with 3-amino-6-chloropyridazine, and the resultant 3-pyridazinamine was then coupled with 4-methylpentanoic acid to afford piperazinylpyridazine II. Exemplified compds. I were tested for SCD inhibition (data given for representative compds. I). [on SciFinder(R)]