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 language | English |
|---|---|
| Pages (from-to) | 2779-2793 |
| Number of pages | 15 |
| Journal | Bioorganic and Medicinal Chemistry |
| Volume | 10 |
| Issue number | 8 |
| DOIs | |
| State | Published - 2002 |
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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 journal › Article
}
TY - JOUR
T1 - Synthesis and in vitro platelet aggregation and TP receptor binding studies on bicyclic 5,8-ethanooctahydroisoquinolines and 5,8-ethanotetrahydroisoquinolines
AU - Saha, Shankar L.
AU - Roche, Victoria F.
AU - Pendola, Kathleen
AU - Kearley, Mark
AU - Lei, Longping
AU - Romstedt, Karl J.
AU - Herdman, Mark
AU - Shams, Gamal
AU - Kaisare, Vivek
AU - Feller, Dennis R.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
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U2 - 10.1016/S0968-0896(02)00101-3
DO - 10.1016/S0968-0896(02)00101-3
M3 - Article
VL - 10
SP - 2779
EP - 2793
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 8
ER -