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.
E C Taylor  1 ,  D Kuhnt ,  C Shih ,  S M Rinzel ,  G B Grindey ,  J Barredo ,  M Jannatipour ,  R G Moran
Affiliations
  • 1. Department of Chemistry, Princeton University, New Jersey 08544.
PMID: 1447744 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.