| Literature DB >> 10585208 |
M G Russell1, V G Matassa, R R Pengilley, M B van Niel, B Sohal, A P Watt, L Hitzel, M S Beer, J A Stanton, H B Broughton, J L Castro.
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.Entities:
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Year: 1999 PMID： 10585208 DOI： 10.1021/jm9910021
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446