Antiproliferative 1,2,3-thiadiazole compounds

Abstract

Pharmaceutical compositions and compounds are provided. The compounds of the invention have anti-proliferative activity, and may promote apoptosis in cells lacking normal regulation of cell cycle and death. In one embodiment of the invention, formulations of the compounds in combination with a physiologically acceptable carrier are provided. The pharmaceutical formulations are useful in the treatment of hyperproliferative disorders, which disorders include tumor growth, lymphoproliferative diseases, angiogenesis. The compounds of the invention are 1,2,3-thiadiazoles having the structure:and including stereoisomers, solvates, and pharmaceutically acceptable salts thereof, wherein each of R, R2 , Rand Ris independently selected from hydrogen, RR, and R, Ris selected from alkyl, heteroalkyl, aryl and heteroaryl; Ris selected from (R)-alkylene, (R)-heteroalkylene, (R)-arylene and (R)-heteroarylene; Ris selected from (R)-alkylene, (R)-heteroalkylene, (R)-arylene, and (R)-heteroarylene; and n is selected from 0, 1, 2, 3, 4 and 5, where Rand Rmay together form a heterocyclic structure including the nitrogen to which they are both attached, and Rand Rmay together form a heterocyclic structure including the nitrogen to which they are both attached; and each of Land Lis independently selected from -A1-A2-A3- where each of Al, A2, and A3 is independently selected from a direct bond, alkylene, heteroalkylene, arylene and heteroarylene.