The discovery of an orally efficacious positive allosteric modulator of the calcium sensing receptor containing a dibenzylamine core.
The discovery of a series of novel and orally efficacious type II calcimimetics, developed from the lead compound 1, is described herein. Compound 22 suppressed plasma PTH levels relative to vehicle when dosed orally in a rat pharmacodynamic model.
Harrington
Paul E
PE
Chemistry Research and Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA. pharring@amgen.com
St Jean
David J
DJ
Clarine
Jeffrey
J
Coulter
Thomas S
TS
Croghan
Michael
M
Davenport
Adam
A
Davis
James
J
Ghiron
Chiara
C
Hutchinson
Jonathan
J
Kelly
Michael G
MG
Lott
Fred
F
Lu
Jenny Ying-Lin
JY
Martin
David
D
Morony
Sean
S
Poon
Steve F
SF
Portero-Larragueta
Elena
E
Reagan
Jeff D
JD
Regal
Kelly A
KA
Tasker
Andrew
A
Wang
Minghan
M
Yang
Yuhua
Y
Yao
Guomin
G
Zeng
Qingping
Q
Henley
Charles
C
Fotsch
Christopher
C
D000284:Administration, Oral; D000818:Animals; D001596:Benzylamines / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors* / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D013329:Structure-Activity Relationship
D001596:Benzylamines; D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing; C005051:dibenzylamine