title: Identification of a butyrophenone analog as a potential atypical antipsychotic agent: 4-[4-(4-chlorophenyl)-1,4-diazepan-1-yl]-1-(4-fluorophenyl)butan-1-one.
abstract: The synthesis and exploration of novel butyrophenones have led to the identification of a diazepane analogue of haloperidol, 4-[4-(4-chlorophenyl)-1,4-diazepan-1-yl]-1-(4-fluorophenyl)butan-1-one (compound 13) with an interesting multireceptor binding profile. Compound 13 was evaluated for its binding affinities at DA subtype receptors, 5HT subtype receptors, H-1, M-1 receptors and at NET, DAT, and SERT transporters. At each of these receptors, compound 13 was equipotent or better than several of the standards currently in use. In in vivo mouse and rat models to evaluate its efficacy and propensity to elicit catalepsy and hence EPS in humans, compound 13 showed similar efficacy as clozapine and did not produce catalepsy at five times its ED(50) value.
authors.affiliation: Division of Basic Pharmaceutical Sciences, Florida A&M University, College of Pharmacy and Pharmaceutical Sciences, Tallahassee, FL 32307, USA. seth.ablordeppey@famu.edu
authors.forename: Seth Y
authors.initials: SY
authors.lastname: Ablordeppey
authors.forename: Ramazan
authors.initials: R
authors.lastname: Altundas
authors.forename: Barbara
authors.initials: B
authors.lastname: Bricker
authors.forename: Xue Y
authors.initials: XY
authors.lastname: Zhu
authors.forename: Eyunni V K Suresh
authors.initials: EV
authors.lastname: Kumar
authors.forename: Tanise
authors.initials: T
authors.lastname: Jackson
authors.forename: Abdul
authors.initials: A
authors.lastname: Khan
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Roth
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001381:Azepines / Q000737:chemistry* / Q000494:pharmacology*; D002090:Butyrophenones / Q000737:chemistry* / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: C532761:4-(4-(4-chlorophenyl)-1,4-diazepan-1-yl)-1-(4-fluuorophenyl)butan-1-one; D014150:Antipsychotic Agents; D001381:Azepines; D002090:Butyrophenones; D003024:Clozapine; D006220:Haloperidol; D001058:Apomorphine