8-Piperazinyl-2,3-dihydropyrrolo[3,2-g]isoquinolines: potent, selective, orally bioavailable 5-HT1 receptor ligands.

Journal article

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.

Authors: Heightman, T; Gaster, L; Pardoe, S; Pilleux, J; Hadley, MS

• Publication status: Published
• Journal: Bioorganic and medicinal chemistry letters
• Volume: 15
• Issue: 19
• Pages: 4370-4374
• Publication date: 2005-10-01
• DOI: 10.1016/j.bmcl.2005.06.042
• EISSN: 1464-3405
• ISSN: 0960-894X
• Language: English
• Keywords: Administration, Oral; Isoquinolines; Receptor, Serotonin, 5-HT1B; Brain Chemistry; Animals; Serotonin Receptor Agonists; Ligands; Receptors, Serotonin; Receptor, Serotonin, 5-HT1A; Structure-Activity Relationship; Rats; Biological Availability; Receptor, Serotonin, 5-HT1D; Serotonin Antagonists