A Dideazatetrahydrofolate Analogue Lacking a Chiral Center at C-6, N-[4-[2-(2-amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5- yl)ethyl]benzoyl]-L-glutamic Acid, Is an Inhibitor of Thymidylate Synthase

J Med Chem. 1992 Nov 13;35(23):4450-4. doi: 10.1021/jm00101a023.

Abstract

N-[4-[2-(2-Amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5- yl)ethyl]benzoyl]-L-glutamic acid (15), prepared in five steps from 2-pivaloyl-7-deazaguanine, has been found to be an antitumor agent with its primary site of action at thymidylate synthase rather than purine synthesis. This compound appears to be a promising candidate for clinical evaluation.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use
  • Glutamates / chemical synthesis*
  • Glutamates / chemistry
  • Glutamates / therapeutic use
  • Guanine / analogs & derivatives*
  • Guanine / chemical synthesis
  • Guanine / therapeutic use
  • Humans
  • Leukemia L1210 / drug therapy
  • Leukemia, Lymphoid / drug therapy
  • Mice
  • Pemetrexed
  • Structure-Activity Relationship
  • Thymidylate Synthase / antagonists & inhibitors*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Glutamates
  • Pemetrexed
  • Guanine
  • Thymidylate Synthase