Design and synthesis of novel pyrrolidine-containing bradykinin antagonists

Bioorg Med Chem Lett. 2003 Jun 2;13(11):1879-82. doi: 10.1016/s0960-894x(03)00309-3.

Abstract

The design and synthesis of novel pyrrolidine-containing bradykinin antagonists, II, are described. Conformational analysis suggested that a pyrrolidine moiety could substitute for the N-methyl cis-amide moiety of FR 173657. The in vitro binding data showed that the (S)-isomer of II was potent in the bradykinin B(2) receptor-binding assay with a K(i) of 33 nM. The opposite isomer, (R)-II, had a K(i) of 46 nM. The in vitro binding data confirmed our conformational hypothesis.

MeSH terms

  • Bradykinin / antagonists & inhibitors*
  • Drug Design
  • Isomerism
  • Models, Molecular
  • Molecular Conformation
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / pharmacology*
  • Receptors, Bradykinin / metabolism

Substances

  • Pyrrolidines
  • Receptors, Bradykinin
  • Bradykinin