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 Citations (Scopus)

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
StatePublished - 2002

Fingerprint

Thromboxane Receptors
Tetrahydroisoquinolines
Platelets
Platelet Aggregation
Tretoquinol
Substitution reactions
Nitrogen
Agglomeration
Prostaglandin H2 Receptors Thromboxane A2
Prostaglandin H2
Thromboxane A2
Platelet Aggregation Inhibitors
Derivatives
Oxidation
Molecules
In Vitro Techniques
isoquinoline

All Science Journal Classification (ASJC) codes

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

Cite this

Synthesis and in vitro platelet aggregation and TP receptor binding studies on bicyclic 5,8-ethanooctahydroisoquinolines and 5,8-ethanotetrahydroisoquinolines. / Saha, Shankar L.; Roche, Victoria F.; Pendola, Kathleen; Kearley, Mark; Lei, Longping; Romstedt, Karl J.; Herdman, Mark; Shams, Gamal; Kaisare, Vivek; Feller, Dennis R.

In: Bioorganic and Medicinal Chemistry, Vol. 10, No. 8, 2002, p. 2779-2793.

Research output: Contribution to journalArticle

Saha, Shankar L. ; Roche, Victoria F. ; Pendola, Kathleen ; Kearley, Mark ; Lei, Longping ; Romstedt, Karl J. ; Herdman, Mark ; Shams, Gamal ; Kaisare, Vivek ; Feller, Dennis R. / Synthesis and in vitro platelet aggregation and TP receptor binding studies on bicyclic 5,8-ethanooctahydroisoquinolines and 5,8-ethanotetrahydroisoquinolines. In: Bioorganic and Medicinal Chemistry. 2002 ; Vol. 10, No. 8. pp. 2779-2793.
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AU - Roche, Victoria F.

AU - Pendola, Kathleen

AU - Kearley, Mark

AU - Lei, Longping

AU - Romstedt, Karl J.

AU - Herdman, Mark

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AU - Kaisare, Vivek

AU - Feller, Dennis R.

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