Title of article :
8-Piperazinyl-2,3-dihydropyrrolo[3,2-g]isoquinolines: Potent, selective, orally bioavailable 5-HT1 receptor ligands
Author/Authors :
Tom D. Heightman، نويسنده , , Laramie M. Gaster، نويسنده , , Sarah L. Pardoe، نويسنده , , Jean-Pierre Pilleux، نويسنده , , Michael S. Hadley، نويسنده , , Derek N. Middlemiss، نويسنده , , Gary W. Price، نويسنده , , Claire Roberts، نويسنده , , Claire M. Scott، نويسنده , , Jeannette M. Watson، نويسنده , , Laurie J. Gordon، نويسنده , , Vicky A. Holland، نويسنده , , Jenifer Powles، نويسنده , , Graham J. Riley، نويسنده , , Tania O. Stean، نويسنده , , Brenda K. Trail، نويسنده , , Neil Upton، نويسنده , , Nigel E. Austin، نويسنده , , Andrew D. Ayrton، نويسنده , , Tanya Coleman، نويسنده , , et al.، نويسنده ,
Abstract :
The novel 8-piperazinyl-2,3-dihydropyrroloisoquinoline template was synthesized in nine steps. The template was N-substituted to give a series of compounds showing binding to human cloned 5-HT1A, 5-HT1B and 5-HT1D receptors with pKi’s greater than 9 and selectivities up to 1000-fold against other serotonin, dopamine and adrenergic receptors. Several compounds were shown to possess weak partial agonist activity in cloned receptors, which translated to antagonism in in vitro studies.
Keywords :
5-HT1A , 5-HT1D , 5-HT1B , Receptor antagonist
