The discovery of novel calcium sensing receptor negative allosteric modulators.
The design and profile of a series of zwitterionic calcium sensing receptor negative allosteric modulators is described. Evaluation of key analogues using a rat model demonstrate a robust response, significantly improved potency over ronacaleret and have the potential as an oral, anabolic treatment for osteoporosis.
Balan
Gayatri
G
Pfizer Global Research and Development, Groton/New London Laboratories, Pfizer Inc., Eastern Point Road, Groton, CT 06340, USA.
Bauman
Jonathan
J
Bhattacharya
Samit
S
Castrodad
Mayda
M
Healy
David R
DR
Herr
Michael
M
Humphries
Paul
P
Jennings
Sandra
S
Kalgutkar
Amit S
AS
Kapinos
Brendon
B
Khot
Vishal
V
Lazarra
Kimberly
K
Li
Mei
M
Li
Yan
Y
Neagu
Constantin
C
Oliver
Robert
R
Piotrowski
David W
DW
Price
David
D
Qi
Hong
H
Simmons
Holly A
HA
Southers
James
J
Wei
Liuqing
L
Zhang
Yan
Y
Paralkar
Vishwas M
VM
D000284:Administration, Oral; D000494:Allosteric Regulation / Q000187:drug effects*; D045930:Anabolic Agents; D000818:Animals; D002460:Cell Line; D003521:Cyclopropanes / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D055808:Drug Discovery; D006801:Humans; D007189:Indans / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D008862:Microsomes, Liver; D010024:Osteoporosis / Q000188:drug therapy; D010666:Phenylpropionates / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D044169:Receptors, Calcium-Sensing / Q000037:antagonists & inhibitors*
D045930:Anabolic Agents; D003521:Cyclopropanes; D007189:Indans; D010666:Phenylpropionates; D044169:Receptors, Calcium-Sensing; C015766:cyclopropanecarboxylic acid; C561716:ronacaleret