Preparation of aminopyridine derivatives as selective Aurora-A inhibitors for treatment of cancer.

Abstract

The title compds. I [A1 is (RbjCRbj')m2; A2 is (RaiCRai')m1; A3 is (Y2Rc)n1CO(Y3Rd)n2R; m1 and m2 each is 1, 2, or 3; n1 and n2 each is 0 or 1; i is an integer of 1 to m1; j is an integer of 1 to m2; R is optionally substituted aryl, heteroaryl, or cycloalkyl; Rai and Rai' each is hydrogen, alkyl; Rbj and Rbj' each is hydrogen, alkyl; Rc, Rd, and R1 each is hydrogen, alkyl; X1 is CH, CX1a, N; X1a is (un)substituted alkyl; X2 is CH, N, etc.; X3 is CH, CX3a, N; X3a is (un)substituted alkyl; X4 is CH or N; Y1, Y2, and Y3 are the same or different and each is CH or N; Z1 and Z2 are the same or different and each is CH or N; and W is a 5-membered arom. heterocycle, e.g., pyrazole or thiazole] are prepd. Thus, (5-bromothiazol-2-yl)-(6-(4-benzoylpiperazin-1-ylmethyl)pyridin-2-yl)amine was prepd. in a multistep process from 2-aminothiazole and 2,6-dichloropyridine. Compds. of this invention showed IC50 values of 0.36 nM to 110 nM against Aurora-A; they showed IC50 values of 47 nM to 28000 nM against Aurora-B. [on SciFinder(R)]