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
Citation
W. Pendergast et al., BENZOQUINAZOLINE INHIBITORS OF THYMIDYLATE SYNTHASE - ENZYME-INHIBITORY ACTIVITY AND CYTOTOXICITY OF SOME SULFONAMIDOBENZOYLGLUTAMATE AND RELATED DERIVATIVES, Journal of medicinal chemistry, 36(22), 1993, pp. 3464-3471
Citations number
36
Categorie Soggetti
Chemistry Medicinal
Journal title
Journal of medicinal chemistry → ACNP
ISSN journal
00222623
Volume
36
Issue
22
Year of publication
1993
Pages
3464 - 3471
Database
ISI
SICI code
0022-2623(1993)36:22<3464:BIOTS->2.0.ZU;2-P
Abstract
Several folate-like thymidylate synthase inhibitors are described in w hich the pteridine nucleus of the folic acid molecule is replaced by a benzoquinazoline moiety, which in turn is attached to the benzoylglut amate side chain by a sulfonamide link. The most potent compounds had K(i) values as low as 2.5 nM against the human enzyme, were good subst ates for the cellular reduced folate transport system and for folylpol yglutamate synthetase, and had IC50 values for growth inhibition of tu mor cell lines as low as 70 nM.