title: New potent calcimimetics: II. Discovery of benzothiazole trisubstituted ureas.
abstract: Following the identification of trisubstituted ureas as a promising new chemical series of allosteric modulators of the calcium sensing receptor (CaSR), we further explored the SAR around the urea substitution, leading to the discovery of benzothiazole urea compound 13. This compound is a potent calcimimetic with an EC50=20 nM (luciferase assay). Evaluated in an in vivo model of chronic renal failure (short term and long term in 5/6 nephrectomized rats), benzothiazole urea 13 significantly decreased PTH levels after oral administration while keeping calcemia within the normal range.
authors.affiliation: Galapagos SASU, 102 Avenue Gaston Roussel, 93230 Romainville, France. pierre.deprez@glpg.com
authors.forename: Pierre
authors.initials: P
authors.lastname: Deprez
authors.forename: Taoues
authors.initials: T
authors.lastname: Temal
authors.forename: Hélène
authors.initials: H
authors.lastname: Jary
authors.forename: Marielle
authors.initials: M
authors.lastname: Auberval
authors.forename: Sarah
authors.initials: S
authors.lastname: Lively
authors.forename: Denis
authors.initials: D
authors.lastname: Guédin
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Vevert
mesh_terms: D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002118:Calcium / Q000737:chemistry*; D044169:Receptors, Calcium-Sensing / Q000037:antagonists & inhibitors*; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D052160:Benzothiazoles; D044169:Receptors, Calcium-Sensing; D014508:Urea; C005465:benzothiazole; D002118:Calcium