Discovery of a class of calcium sensing receptor positive allosteric modulators; 1-(benzothiazol-2-yl)-1-phenylethanols.
1-(Benzothiazol-2-yl)-1-(4-chlorophenyl)ethanol (1) was identified as a positive allosteric modulator (PAM) of the CaSR in a functional cell-based assay. This compound belongs to a class of compounds that is structurally distinct from other known positive allosteric modulators, for example, the phenylalkylamines cinacalcet, a modified analog (13) potently suppressed parathyroid hormone (PTH) release in rats, consistent with its profile as a PAM of CaSRs.
Gustafsson
Magnus
M
ACADIA Pharmaceuticals AB, Medeon Science Park, Per Albin Hanssons väg 35, S-205 12 Malmö, Sweden.
Jensen
Jacob
J
Bertozzi
Sine M
SM
Currier
Erika A
EA
Ma
Jian-Nong
JN
Burstein
Ethan S
ES
Olsson
Roger
R
D000494:Allosteric Regulation; D000818:Animals; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001592:Benzyl Alcohols / Q000737:chemistry* / Q000494:pharmacology; D000069449:Cinacalcet; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D009281:Naphthalenes / Q000737:chemistry; D010281:Parathyroid Hormone / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D044169:Receptors, Calcium-Sensing / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
D052160:Benzothiazoles; D001592:Benzyl Alcohols; D009281:Naphthalenes; D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing; D010626:Phenylethyl Alcohol; D000069449:Cinacalcet