Browse by author
Lookup NU author(s): Professor Alan Calvert
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
The synthesis of nine new 2-methyl-10-propargylquinazoline antifolates with substituents in the p-aminobenzoyl ring is described. In general the synthetic route involved the coupling of the appropriate ring-substituted diethyl N-[4-(prop-2-ynylamino)benzoyl]-L-glutamate with 6-(bromomethyl)-3,4-dihydro-2-methyl-4-oxoquinazoline followed by deprotection using mild alkali. The compounds were tested as inhibitors of partially purified L1210 thymidylate synthase (TS). They were also examined for their inhibition of the growth L1210 cells in culture. Compared to the parent compound 1a the 2'-fluoro analogue 2a exhibited enhanced potency in both systems whereas the 3'-fluoro analogue 3a showed enhanced growth inhibitory properties against L1210 cells despite being a poorer inhibitor of the isolated enzyme. Chloro, hydroxy, methoxy, and nitro substituents in the 2'-position were also well tolerated by the enzyme but failed to give enhanced growth inhibition. The series was extended to cover analogues of the 2'-fluoro, 3'-fluoro, 2'-chloro, 2'-methyl, 2'-amino, 2'-methoxy, and 2'-nitro derivatives with modified alkyl substituents at N10.
Author(s): Marsham PR, Jackman AL, Oldfield J, Hughes LR, Thornton TJ, Bisset GMF, O'Connor BM, Bishop JAM, Calvert AH
Publication type: Article
Publication status: Published
Journal: Journal of Medicinal Chemistry
Year: 1990
Volume: 33
Issue: 11
Pages: 3072-3078
Print publication date: 01/11/1990
ISSN (print): 0022-2623
ISSN (electronic): 1520-4804
URL: http://dx.doi.org/10.1021/jm00173a026
DOI: 10.1021/jm00173a026
PubMed id: 2231608
Altmetrics provided by Altmetric
