Preparation of triazole derivatives as Axl inhibitors.

Abstract

Triazole derivs. I and II [A = CO, CS, COO, CONH and derivs., etc.; R1 = (un)substituted (hetero)aryl, cycloalkyl, etc.; R2, R4, R5 = independently H, alkyl, aryl, aralkyl, etc.; R3 = (un)substituted aryl, alkyl, cycloalkyl, aralkyl; and their stereoisomers and tautomers, and their pharmaceutically acceptable salts, hydrates, solvates, N-oxides, and prodrugs; with provisos] and pharmaceutical compns. contg. them are disclosed as inhibitors of the activity of the receptor protein tyrosine kinase Axl. Methods of using triazoles I and II in treating diseases or conditions assocd. with Axl catalytic activity are also disclosed. Thus, reacting 4-[2-(pyrrolidin-1-yl)ethoxy]aniline with cyanocarbonimidic acid di-Ph ester, followed by cyclization with hydrazine, and acylation with 4-isopropoxybenzoic acid gave acylated triazole III. Selected triazoles I and II inhibited the activity of Axl with an IC50 < 1 μM. [on SciFinder(R)]