title: An orally active corticotropin releasing factor 1 receptor antagonist from 8-aryl-1,3a,7,8-tetraaza-cyclopenta[a]indenes.
abstract: 8-Aryl-1,3a,7,8-tetraaza-cyclopenta[a]indenes represent a novel series of high-affinity corticotropin-releasing factor-1 receptor (CRF1R) antagonists. Herein we report the synthesis and SAR around the tricyclic core and the anxiolytic activity of an orally dosed exemplary compound 9d (K(i)=8.0 nM) in a mouse canopy model.
authors.affiliation: Pharmaceutical Research Institute, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA. xiaojun.han@bms.com
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Han
authors.forename: Rita
authors.initials: R
authors.lastname: Civiello
authors.forename: Sokhom S
authors.initials: SS
authors.lastname: Pin
authors.forename: Kevin
authors.initials: K
authors.lastname: Burris
authors.forename: Lynn A
authors.initials: LA
authors.lastname: Balanda
authors.forename: Jay
authors.initials: J
authors.lastname: Knipe
authors.forename: Shelly
authors.initials: S
authors.lastname: Ren
authors.forename: Tracey
authors.initials: T
authors.lastname: Fiedler
authors.forename: Kaitlin E
authors.initials: KE
authors.lastname: Browman
authors.forename: Robert
authors.initials: R
authors.lastname: Macci
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Taber
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Gene M
authors.initials: GM
authors.lastname: Dubowchik
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001372:Aza Compounds / Q000737:chemistry; D003863:Depression / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D007192:Indenes / Q000737:chemistry; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008956:Models, Chemical; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D012995:Solubility; D013329:Structure-Activity Relationship; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D000928:Antidepressive Agents; D001372:Aza Compounds; D007192:Indenes; D018019:Receptors, Corticotropin-Releasing Hormone; D014867:Water