Patent Number: 8,067,452

Title: 3-hydroxyisothiazole-4-carboxamidine derivatives as CHK2 inhibitors

Abstract: This invention provides compounds of Formula I which are inhibitors of Chk2 and are useful as a radiation protection agents in anticancer radiotherapy. A method of modulating Chk2 in vitro includes treating a substrate with Chk2 in the presence of compounds of formula I. A method of making a compound of formula I includes: a) forming a biaryl amine having an amino (NH.sub.2) group; b) converting the amino group to an isothiocyanate group; c) adding a cyanoacetamide to the isothiocyanate group to form a thioamide adduct; d) cyclizing the thioamide adduct to form an isothiazole having a cyano group; and e) adding an amine to the cyano group to form a carboxamidine group.

Inventors: Wu; Jim Zhen (Shanghai, CN), Chen; Huanming (Irvine, CA)

Assignee: Valeant Pharmaceuticals International

International Classification: A61K 31/425 (20060101); C07D 275/03 (20060101)

Expiration Date: 2020-11-29 0:00:00