Penta-substituted benzimidazoles as potent antagonists of the calcium-sensing receptor (CaSR-antagonists).
A series of novel benzimidazole derivatives has been designed via a scaffold morphing approach based on known calcilytics chemotypes. Subsequent lead optimisation led to the discovery of penta-substituted benzimidazoles that exhibit attractive in vitro and in vivo calcium-sensing receptor (CaSR) inhibitory profiles. In addition, synthesis and structure-activity relationship data are provided.
Gerspacher
Marc
M
Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland. marc.gerspacher@novartis.com
Altmann
Eva
E
Beerli
René
R
Buhl
Thomas
T
Endres
Ralf
R
Gamse
Rainer
R
Kameni-Tcheudji
Jacques
J
Kneissel
Michaela
M
Krawinkler
Karl Heinz
KH
Missbach
Martin
M
Schmidt
Alfred
A
Seuwen
Klaus
K
Weiler
Sven
S
Widler
Leo
L
D001562:Benzimidazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D008958:Models, Molecular; D044169:Receptors, Calcium-Sensing / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D001562:Benzimidazoles; D044169:Receptors, Calcium-Sensing