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: ##STR00001## and including stereoisomers, solvates, and pharmaceutically acceptable salts thereof, wherein each of R.sup.1, R.sup.22 , R.sup.3 and R.sup.4 is independently selected from hydrogen, R.sup.5R.sup.6, and R.sup.7, R.sup.5 is selected from alkyl, heteroalkyl, aryl and heteroaryl; R.sup.6 is selected from (R.sup.5).sub.n-alkylene, (R.sup.5).sub.n-heteroalkylene, (R.sup.5).sub.n-arylene and (R.sup.5).sub.n-heteroarylene; R.sup.7 is selected from (R.sup.6).sub.n-alkylene, (R.sup.6).sub.n-heteroalkylene, (R.sup.6).sub.n-arylene, and (R.sup.6).sub.n-heteroarylene; and n is selected from 0, 1, 2, 3, 4 and 5, where R.sup.1 and R.sup.2 may together form a heterocyclic structure including the nitrogen to which they are both attached, and R.sup.3 and R.sup.4 may together form a heterocyclic structure including the nitrogen to which they are both attached; and each of L.sup.1 and L.sup.2 is 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.
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a Continuation-in-Part of U.S. Utility application Ser. No. 09/545,237, filed Apr. 7, 2000, now issued as U.S. Pat. No. 6,420,400, which is incorporated herein by reference in its entirety.
This invention is directed to methods of using compounds having the structure: ##STR00001## and including stereoisomers, solvates, and pharmaceutically acceptable salts thereof, wherein each of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 is independently selected from hydrogen, R.sup.5, R.sup.6, and R.sup.7; R.sup.5 is selected from alkyl, heteroalkyl, aryl and heteroaryl; R.sup.6 is selected from (R.sup.5).sub.n-alkylene, (R.sup.5).sub.n-heteroalkylene, (R.sup.5).sub.n-arylene and (R.sup.5).sub.n-heteroarylene; R.sup.7 is selected from (R.sup.6).sub.n-alkylene, (R.sup.6).sub.n-heteroalkylene, (R.sup.6).sub.n-arylene, and (R.sup.6).sub.n-heteroarylene; and n is selected from 0, 1, 2, 3, 4 and 5, where R.sup.1 and R.sup.2 may together form a heterocyclic structure including the nitrogen to which they are both attached, and R.sup.3 and R.sup.4 may together form a heterocyclic structure including the nitrogen to which they are both attached; and each of L.sup.1 and L.sup.2 is independently selected from -A1-A2-A3- where each of A1, A2, and A3 is independently selected from a direct bond, alkylene, heteroalkylene, arylene and heteroarylene. These compounds are useful in treating hyperproliferative disorders and inducing apoptosis.
