Methotrexate analogues. 12. Synthesis and biological properties of some aza homologues

J Med Chem. 1979 Jul;22(7):869-74. doi: 10.1021/jm00193a022.

Abstract

Methotrexate analogues, in which an additional nitrogen 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 also less cytotoxic against human lymphoblastic leukemia cells (CCRF-CEM). In vivo against L-1210 leukemia in mice, the aza homologue of methotrexate showed significant antitumor activity (%ILS = 55%) compared to methotrexate (%ILS = 88%).

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / therapeutic use
  • Folic Acid Antagonists
  • Humans
  • In Vitro Techniques
  • Lactobacillus casei / drug effects
  • Lactobacillus casei / enzymology
  • Lactobacillus casei / growth & development
  • Leukemia L1210 / drug therapy
  • Leukemia, Lymphoid / drug therapy
  • Male
  • Methods
  • Methotrexate / analogs & derivatives*
  • Methotrexate / chemical synthesis
  • Methotrexate / pharmacology
  • Methotrexate / therapeutic use
  • Mice
  • Thymidylate Synthase / antagonists & inhibitors

Substances

  • Antineoplastic Agents
  • Folic Acid Antagonists
  • Thymidylate Synthase
  • Methotrexate