title: Synthesis and evaluation of azabicyclo[3.2.1]octane derivatives as potent mixed vasopressin antagonists.
abstract: A series of biaryl amides containing an azabicyclooctane amine headpiece were synthesized and evaluated as mixed arginine vasopressin (AVP) receptor antagonists. Several analogues, including 8g, 12g, 13d, and 13g, were shown to have excellent V(1a)- and good V(2)-receptor binding affinities. Compound 13d was further profiled for drug-like properties and for an in vitro comparison with conivaptan, the program's mixed V(1a)/V(2)-receptor antagonist standard.
authors.affiliation: Chemical Sciences, Pfizer Global Research and Development, Collegeville, PA 19335, USA. aimeecrombie@hotmail.com
authors.forename: Aimee L
authors.initials: AL
authors.lastname: Crombie
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Antrilli
authors.forename: Brandon A
authors.initials: BA
authors.lastname: Campbell
authors.forename: David L
authors.initials: DL
authors.lastname: Crandall
authors.forename: Amedeo A
authors.initials: AA
authors.lastname: Failli
authors.forename: Yanan
authors.initials: Y
authors.lastname: He
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Kern
authors.forename: William J
authors.initials: WJ
authors.lastname: Moore
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Nogle
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Trybulski
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors*; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D001552:Benzazepines; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D009795:Octanes / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001372:Aza Compounds; D001552:Benzazepines; D001643:Bridged Bicyclo Compounds; D009795:Octanes; C106389:conivaptan; D001127:Arginine Vasopressin