title: Epiminocyclohepta[b]indole analogs as 5-HT6 antagonists.
abstract: A new series of epiminocyclohepta[b]indoles with potent 5-HT(6) antagonist activity were discovered and optimized using in vitro protocols. One compound from this series was progressed to advanced pharmacokinetic (PK) studies followed by 5-HT(6) receptor occupancy studies. The compound was found to have excellent oral absorption, a highly favorable PK profile and demonstrated pharmacodynamic interaction with the 5-HT(6) receptor as shown by ex vivo autoradiography.
authors.affiliation: AMRI, 26 Corporate Circle, Albany, NY 12212-5098, USA. alan.henderson@amriglobal.com
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Henderson
authors.forename: Peter R
authors.initials: PR
authors.lastname: Guzzo
authors.forename: Animesh
authors.initials: A
authors.lastname: Ghosh
authors.forename: Jagjit
authors.initials: J
authors.lastname: Kaur
authors.forename: Jia-Man
authors.initials: JM
authors.lastname: Koo
authors.forename: Kassoum
authors.initials: K
authors.lastname: Nacro
authors.forename: Shailaja
authors.initials: S
authors.lastname: Panduga
authors.forename: Rashmi
authors.initials: R
authors.lastname: Pathak
authors.forename: Bharat
authors.initials: B
authors.lastname: Shimpukade
authors.forename: Valentina
authors.initials: V
authors.lastname: Tan
authors.forename: Kai
authors.initials: K
authors.lastname: Xiang
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Wierschke
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Isherwood
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018938:Caco-2 Cells; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D058915:Purinergic P1 Receptor Antagonists; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C097216:serotonin 6 receptor