Discovery of novel 1-arylmethyl pyrrolidin-2-yl ethanol amines as calcium-sensing receptor antagonists.
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.
Gavai
Ashvinikumar V
AV
Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA. ashvinikumar.gavai@bms.com
Vaz
Roy J
RJ
Mikkilineni
Amarendra B
AB
Roberge
Jacques Y
JY
Liu
Yalei
Y
Lawrence
R Michael
RM
Corte
James R
JR
Yang
Wu
W
Bednarz
Mark
M
Dickson
John K
JK
Ma
Zhengping
Z
Seethala
Ramakrishna
R
Feyen
Jean H M
JH
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
D004983:Ethanolamines; D011759:Pyrrolidines; D044169:Receptors, Calcium-Sensing