Structure-activity relationships of a novel class of endothelin receptor selective antagonists; 6-carboxy-2-isopropylamino-5,7-diarylcyclopenteno[1,2-b]pyridines.

Journal Article (Academic article)

The synthesis and structure-activity relationships of 6-carboxy-2-isopropylamino-5,7-diarylcyclopenteno[1,2-b]pyridine class of ET(A) receptor selective antagonists were described. These derivatives were prepared from the optically active key intermediates (3, 4, 10, and 13). Optimization of the substituent at the 2-position of the bottom 4-methoxyphenyl ring of the lead compound 1 led to identification of 2-hydroxy-1-methylethoxy (2g and h), hydroxyalkyl (2i, m, and p), 3-methoxy-2-methylpropyl (2t and u), N-acetyl-N-methylaminomethyl (2v), and 2-(dimethylcarbamoyl)propyl (2w) derivatives that showed greater than 1000-fold selectivity for the ET(A) receptor over the ET(B) receptor with excellent binding affinity (IC(50)

Full Text

Duke Authors

Cited Authors

  • Takahashi, H; Ohtake, N; Sakamoto, T; Iino, T; Kawanishi, N; Nakamura, M; Yoshizumi, T; Niiyama, K; Ozaki, S; Okada, H; Kano, A; Ishii, Y; Okada, M; Saito, M; Sawazaki, Y; Hayama, T; Nishikibe, M

Published Date

  • March 2004

Published In

Volume / Issue

  • 14 / 6

Start / End Page

  • 1503 - 1507

International Standard Serial Number (ISSN)

  • 0960-894X

Digital Object Identifier (DOI)

  • 10.1016/j.bmcl.2004.01.008


  • English