title: New bicyclic cannabinoid receptor-1 (CB1-R) antagonists.
abstract: A series of conformationally constrained bicyclic derivatives derived from SR141716 was prepared and evaluated as hCB(1)-R antagonists and inverse agonists. Optimization of the structure-activity relationships around the 2,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one derivative 2a led to the identification of two compounds with oral activity in rodent feeding models (2h and 4a). Replacement of the PP group in 2h with other bicyclic groups resulted in a loss of binding affinity.
authors.affiliation: Pfizer Global Research and Development-Groton Laboratories, Groton, CT 06340, USA. philip.a.carpino@pfizer.com
authors.forename: Philip A
authors.initials: PA
authors.lastname: Carpino
authors.forename: David A
authors.initials: DA
authors.lastname: Griffith
authors.forename: Subas
authors.initials: S
authors.lastname: Sakya
authors.forename: Robert L
authors.initials: RL
authors.lastname: Dow
authors.forename: Shawn C
authors.initials: SC
authors.lastname: Black
authors.forename: John R
authors.initials: JR
authors.lastname: Hadcock
authors.forename: Philip A
authors.initials: PA
authors.lastname: Iredale
authors.forename: Dennis O
authors.initials: DO
authors.lastname: Scott
authors.forename: Michael W
authors.initials: MW
authors.lastname: Fichtner
authors.forename: Colin R
authors.initials: CR
authors.lastname: Rose
authors.forename: Robert
authors.initials: R
authors.lastname: Day
authors.forename: Joseph
authors.initials: J
authors.lastname: Dibrino
authors.forename: Mary
authors.initials: M
authors.lastname: Butler
authors.forename: Demetria B
authors.initials: DB
authors.lastname: Debartolo
authors.forename: Darrin
authors.initials: D
authors.lastname: Dutcher
authors.forename: Denise
authors.initials: D
authors.lastname: Gautreau
authors.forename: Jeff S
authors.initials: JS
authors.lastname: Lizano
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: O'connor
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Sands
authors.forename: Dawn
authors.initials: D
authors.lastname: Kelly-Sullivan
authors.forename: Karen M
authors.initials: KM
authors.lastname: Ward
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D005247:Feeding Behavior / Q000187:drug effects* / Q000502:physiology; D008954:Models, Biological; D010880:Piperidines / Q000737:chemistry; D011720:Pyrazoles / Q000737:chemistry; D047069:Pyrazolones / Q000737:chemistry; D011744:Pyrimidinones / Q000737:chemistry; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors*; D000077285:Rimonabant; D012377:Rodentia; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D019086:Bridged Bicyclo Compounds, Heterocyclic; D010880:Piperidines; D011720:Pyrazoles; D047069:Pyrazolones; D011744:Pyrimidinones; D043884:Receptor, Cannabinoid, CB1; C038362:pyrazolone; D000077285:Rimonabant