Conformational considerations in the design of dual antagonists of platelet-activating factor (PAF) and histamine.

Journal Article (Journal Article)

Following the discovery of the first dual antagonist of platelet-activating factor (PAF) and histamine, 1-acetyl-4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin- 11-ylidene)piperidine, Sch 37370, 1, a related series of structures, exemplified by (+/-)-1-acetyl-4-(8-chloro-5,6-dihydro-11H-benzo[5,6]-cyclohepta[1,2-b] pyridin-11-yl)piperazine, Sch 40338, 2, were prepared. Interestingly, the compounds exhibited a parallel structure antiallergy activity relationship, suggesting that the two series may adopt a common conformation at the PAF receptor. Conformational analysis led to a proposal for this bioactive conformation accessible to both series. The synthesis of novel conformationally constrained analogues that might mimic the proposed bioactive conformation of these compounds, and the evaluation of their in vitro antiallergy activity form the subject matter of this report.

Full Text

Duke Authors

Cited Authors

  • Kaminski, JJ; Carruthers, NI; Wong, SC; Chan, TM; Billah, MM; Tozzi, S; McPhail, AT

Published Date

  • July 1999

Published In

Volume / Issue

  • 7 / 7

Start / End Page

  • 1413 - 1423

PubMed ID

  • 10465415

Electronic International Standard Serial Number (EISSN)

  • 1464-3391

International Standard Serial Number (ISSN)

  • 0968-0896

Digital Object Identifier (DOI)

  • 10.1016/s0968-0896(99)00075-9


  • eng