Discovery of a class of calcium sensing receptor positive allosteric modulators; 1-(benzothiazol-2-yl)-1-phenylethanols

Magnus Gustafsson; Jacob Jensen; Sine M Bertozzi; Erika A Currier; Jian-Nong Ma; Ethan S Burstein; Roger Olsson

doi:10.1016/j.bmcl.2010.07.077

Discovery of a class of calcium sensing receptor positive allosteric modulators; 1-(benzothiazol-2-yl)-1-phenylethanols

Bioorg Med Chem Lett. 2010 Oct 1;20(19):5918-21. doi: 10.1016/j.bmcl.2010.07.077. Epub 2010 Jul 23.

Authors

Magnus Gustafsson¹, Jacob Jensen, Sine M Bertozzi, Erika A Currier, Jian-Nong Ma, Ethan S Burstein, Roger Olsson

Affiliation

¹ ACADIA Pharmaceuticals AB, Medeon Science Park, Per Albin Hanssons väg 35, S-205 12 Malmö, Sweden.

PMID: 20727747
DOI: 10.1016/j.bmcl.2010.07.077

Abstract

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.

MeSH terms

Allosteric Regulation
Animals
Benzothiazoles / chemical synthesis
Benzothiazoles / chemistry*
Benzothiazoles / pharmacology
Benzyl Alcohols / chemistry*
Benzyl Alcohols / pharmacology
Cinacalcet
Drug Evaluation, Preclinical
Humans
Microsomes, Liver / metabolism
Naphthalenes / chemistry
Parathyroid Hormone / metabolism
Phenylethyl Alcohol / chemical synthesis
Phenylethyl Alcohol / chemistry*
Phenylethyl Alcohol / pharmacology
Rats
Receptors, Calcium-Sensing / chemistry*
Receptors, Calcium-Sensing / metabolism
Structure-Activity Relationship

Substances

Benzothiazoles
Benzyl Alcohols
Naphthalenes
Parathyroid Hormone
Receptors, Calcium-Sensing
Phenylethyl Alcohol
Cinacalcet