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.
Pfizer Global Research and Development, Groton/New London Laboratories, Pfizer Inc., Eastern Point Road, Groton, CT 06340, USA.
Gayatri
G
Balan
Jonathan
J
Bauman
Samit
S
Bhattacharya
Mayda
M
Castrodad
David R
DR
Healy
Michael
M
Herr
Paul
P
Humphries
Sandra
S
Jennings
Amit S
AS
Kalgutkar
Brendon
B
Kapinos
Vishal
V
Khot
Kimberly
K
Lazarra
Mei
M
Li
Yan
Y
Li
Constantin
C
Neagu
Robert
R
Oliver
David W
DW
Piotrowski
David
D
Price
Hong
H
Qi
Holly A
HA
Simmons
James
J
Southers
Liuqing
L
Wei
Yan
Y
Zhang
Vishwas M
VM
Paralkar
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