Synthesis and in vitro platelet aggregation and TP receptor binding studies on bicyclic 5,8-ethanooctahydroisoquinolines and 5,8-ethanotetrahydroisoquinolines

Shankar L. Saha, Victoria F. Roche, Kathleen Pendola, Mark Kearley, Longping Lei, Karl J. Romstedt, Mark Herdman, Gamal Shams, Vivek Kaisare, Dennis R. Feller

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Eighteen novel bicyclic 1-substituted benzyl octahydro- and tetrahydroisoquinolines were synthesized and evaluated for human thromboxane A2/prostaglandin H2 (TP) receptor affinity and antagonism of TP receptor-mediated platelet aggregation. In both cases, potency depended more on the presence of methoxy groups on the 1-benzyl moiety than on nitrogen substitution or extent of oxidation of the isoquinoline ring system. The most potent of the bicyclic compounds retained the 5,8-ethanooctahydroisoquinoline ring structure of the parent molecule (1) and required the 3,4,5-trimethoxybenzyl substitution pattern found in the well-characterized tetrahydroisoquinoline antiplatelet agent trimetoquinol. Differences in nitrogen substituent SAR were noted between the mono-methoxylated compounds and the 3,4,5-trimethoxybenzyl derivatives.

Original languageEnglish
Pages (from-to)2779-2793
Number of pages15
JournalBioorganic and Medicinal Chemistry
Volume10
Issue number8
DOIs
Publication statusPublished - 2002

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this