177948-41-3Relevant articles and documents
3-[3-(piperidin-1-yl)propyl]indoles as highly selective h5-HT(1D) receptor agonists
Russell, Michael G. N.,Matassa, Victor G.,Pengilley, Roy R.,Van Niel, Monique B.,Sohal, Bindi,Watt, Alan P.,Hitzel, Laure,Beer, Margaret S.,Stanton, Josephine A.,Broughton, Howard B.,Castro, José L.
, p. 4981 - 5001 (2007/10/03)
Several 5-HT(ID/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.
