3-[3-(Piperidin-1-yl)propyl]indoles as highly selective h5-HT(1D) receptor agonists.

Article Details

Citation

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
DrugTargetPropertyMeasurementpHTemperature (°C)
Sumatriptan5-hydroxytryptamine receptor 1BIC 50 (nM)10N/AN/ADetails
Sumatriptan5-hydroxytryptamine receptor 1DIC 50 (nM)6.8N/AN/ADetails
Sumatriptan5-hydroxytryptamine receptor 1DEC 50 (nM)12N/AN/ADetails