Preparation of pyrazolo[1,5-a]pyrimidine derivatives for use as inhibitors of stearoyl-CoA desaturase (SCD) activity.

Abstract

Title compds. represented by the formula I [wherein n = 0 or 1; W = a direct bond, CO2, O, etc.; one of R1-R3 is Y-R18, and the other two are independently selected from H or (fluoro)alkyl; Y = O, S or alkylene; Y18 = (un)substituted (hetero)aryl; R4 = H, alkyl, alkenyl, etc.; R5 = H or alkyl; and pharmaceutically acceptable salts, solvates, hydrates, geometrical isomers, tautomers, optical isomers, and N-oxides thereof] were prepd. as inhibitors of stearoyl-CoA desaturase (SCD) activity. For example, reaction of 6-benzyl-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxylic acid with 2-methoxyethylamine gave II in 78% yield. II showed SCD inhibition with an IC50 value of 1.0 μM. Thus, I and their pharmaceutical compns. are useful for the treatment of medical conditions in which the modulation of SCD activity is beneficial, such as cardiovascular diseases, obesity, non- insulin-dependent diabetes mellitus, hypertension, neurol. diseases, immune disorders, cancer, essential fatty acid deficiency, acne, psoriasis, rosacea or other skin conditions. [on SciFinder(R)]