1. Academic Validation
  2. New potent calcimimetics: I. Discovery of a series of novel trisubstituted ureas

New potent calcimimetics: I. Discovery of a series of novel trisubstituted ureas

  • Bioorg Med Chem Lett. 2013 Apr 15;23(8):2451-4. doi: 10.1016/j.bmcl.2013.01.078.
Taoues Temal 1 Hélène Jary Marielle Auberval Sarah Lively Denis Guédin Jean-Paul Vevert Pierre Deprez
Affiliations

Affiliation

  • 1 Galapagos SASU, 102 Avenue Gaston Roussel, 93230 Romainville, France.
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.

Figures