3-[3-(Piperidin-1-yl)propyl]indoles as highly selective h5-HT(1D) receptor agonists.
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Russell MG, Matassa VG, Pengilley RR, van Niel MB, Sohal B, Watt AP, Hitzel L, Beer MS, Stanton JA, Broughton HB, Castro JL
3-[3-(Piperidin-1-yl)propyl]indoles as highly selective h5-HT(1D) receptor agonists.
J Med Chem. 1999 Dec 2;42(24):4981-5001.
- PubMed ID
- 10585208 [ View in PubMed]
- Abstract
Several 5-HT(1D/1B) receptor agonists are now entering the marketplace as treatments for migraine. This paper describes the development of selective h5-HT(1D) receptor agonists as potential antimigraine agents which may produce fewer side effects. A series of 3-[3-(piperidin-1-yl)propyl]indoles has been synthesized which has led to the identification of 80 (L-772,405), a high-affinity h5-HT(1D) receptor full agonist having 170-fold selectivity for h5-HT(1D) receptors over h5-HT(1B) receptors. L-772,405 also shows very good selectivity over a range of other serotonin and nonserotonin receptors and has excellent bioavailability following subcutaneous administration in rats. It therefore constitutes a valuable tool to delineate the role of h5-HT(1D) receptors in migraine. Molecular modeling and physical properties have been utilized to postulate the binding conformation of these compounds in the receptor cavity.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Sumatriptan 5-hydroxytryptamine receptor 1B IC 50 (nM) 10 N/A N/A Details Sumatriptan 5-hydroxytryptamine receptor 1D IC 50 (nM) 6.8 N/A N/A Details Sumatriptan 5-hydroxytryptamine receptor 1D EC 50 (nM) 12 N/A N/A Details