Benzoquinazoline inhibitors of thymidylate synthase: enzyme inhibitory activity and cytotoxicity of some sulfonamidobenzoylglutamate and related deriv...

Basic Information

ID: ALA1126944

Journal: J Med Chem

Title: Benzoquinazoline inhibitors of thymidylate synthase: enzyme inhibitory activity and cytotoxicity of some sulfonamidobenzoylglutamate and related derivatives.

Authors: Pendergast W, Dickerson SH, Johnson JV, Dev IK, Ferone R, Duch DS, Smith GK.

Abstract: Several folate-like thymidylate synthase inhibitors are described in which the pteridine nucleus of the folic acid molecule is replaced by a benzoquinazoline moiety, which in turn is attached to the benzoylglutamate side chain by a sulfonamide link. The most potent compounds had Ki values as low as 2.5 nM against the human enzyme, were good substrates for the cellular reduced folate transport system and for folylpolyglutamate synthetase, and had IC50 values for growth inhibition of tumor cell lines as low as 70 nM.

CiteXplore: 8230138

DOI: 10.1021/jm00074a030

Patent ID: