title: Discovery of novel 1-arylmethyl pyrrolidin-2-yl ethanol amines as calcium-sensing receptor antagonists.
abstract: A 3D quantitative structure-activity relationship study for inhibition of calcium-sensing receptor in the aryloxypropanolamine series predicted that these molecules adopt a U-shaped conformation with pi-stacking between the two aromatic rings. This hypothesis led to the discovery of novel 1-arylmethyl pyrrolidin-2-yl ethanol amines capable of antagonizing the calcium-sensing receptor with potency comparable to that of NPS-2143.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA. ashvinikumar.gavai@bms.com
authors.forename: Ashvinikumar V
authors.initials: AV
authors.lastname: Gavai
authors.forename: Roy J
authors.initials: RJ
authors.lastname: Vaz
authors.forename: Amarendra B
authors.initials: AB
authors.lastname: Mikkilineni
authors.forename: Jacques Y
authors.initials: JY
authors.lastname: Roberge
authors.forename: Yalei
authors.initials: Y
authors.lastname: Liu
authors.forename: R Michael
authors.initials: RM
authors.lastname: Lawrence
authors.forename: James R
authors.initials: JR
authors.lastname: Corte
authors.forename: Wu
authors.initials: W
authors.lastname: Yang
authors.forename: Mark
authors.initials: M
authors.lastname: Bednarz
authors.forename: John K
authors.initials: JK
authors.lastname: Dickson
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Ma
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Seethala
authors.forename: Jean H M
authors.initials: JH
authors.lastname: Feyen
mesh_terms: D004983:Ethanolamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D010024:Osteoporosis / Q000188:drug therapy; D011487:Protein Conformation; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D044169:Receptors, Calcium-Sensing / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D004983:Ethanolamines; D011759:Pyrrolidines; D044169:Receptors, Calcium-Sensing