Methotrexate analogs. 12. Synthesis and biological properties of some aza homologs
- 1 July 1979
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 22 (7) , 869-874
- https://doi.org/10.1021/jm00193a022
Abstract
Methotrexate analogs, in which an additional N atom is inserted between the phenyl ring and the carbonyl group of the side chain were prepared by photochemical methods. The compounds were less inhibitory toward dihydrofolate reductase and thymidylate synthetase derived from Lactobacillus casei than was methotrexate. They were less cytotoxic against human lymphoblastic leukemia cells (CCRF-CEM). In vivo against L-1210 leukemia in mice the aza homolog of methotrexate showed significant antitumor activity (% ILS [100 times median survival time treated per median survival time control minus 1] = 55%) compared to methotrexate (%ILS = 88%).This publication has 7 references indexed in Scilit:
- Folate analogs altered in the C9-N10 bridge region: N10-tosylisohomofolic acid and N10-tosylisohomoaminopterinJournal of Medicinal Chemistry, 1978
- Methotrexate analogs. 11. Unambiguous chemical synthesis and in vitro biological evaluation of .alpha.- and .gamma.-monoesters as potential prodrugsJournal of Medicinal Chemistry, 1978
- Methotrexate analogs. 9. Synthesis and biological properties of some 8-alkyl-7,8-dihydro analogsJournal of Medicinal Chemistry, 1977
- Methotrexate analogs. 6. Replacement of glutamic acid by various amino acid esters and aminesJournal of Medicinal Chemistry, 1975
- Enzyme Studies with New Analogues of Folic Acid and Homofolic AcidJournal of Biological Chemistry, 1967
- The response in vitro, of continuous cultures of human lymphoblasts (CCRF-CEM cells) to chemotherapeutic agentsBiochemical Pharmacology, 1967
- PHARMACOLOGIC ASPECTS OF HOMOFOLATE DERIVATIVES IN RELATION TO AMETHOPTERIN-RESISTANT MURINE LEUKEMIA1966