title: New potent calcimimetics: I. Discovery of a series of novel trisubstituted ureas.
abstract: Starting from Fendiline and R-568, we identified a novel series of urea compounds as positive allosteric modulators of the calcium sensing receptor (CaSR), as part of a program to identify novel therapeutics for secondary hyperparathyroidism. Initially identified disubstituted ureas were converted to trisubstituted urea lead 20e, which was further modified to increase in vivo potency. Replacing a carbomethoxy substituent by various bioisosteres led to compound 46 which exhibited potent in vitro and in vivo activity after oral administration.
authors: Galapagos SASU, 102 Avenue Gaston Roussel, 93230 Romainville, France.
authors: Taoues
authors: T
authors: Temal
authors: Hélène
authors: H
authors: Jary
authors: Marielle
authors: M
authors: Auberval
authors: Sarah
authors: S
authors: Lively
authors: Denis
authors: D
authors: Guédin
authors: Jean-Paul
authors: JP
authors: Vevert
authors: Pierre
authors: P
authors: Deprez
mesh_terms: D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002118:Calcium / Q000737:chemistry*; D044169:Receptors, Calcium-Sensing / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D044169:Receptors, Calcium-Sensing; D014508:Urea; D002118:Calcium