Deconstruction of sulfonamide inhibitors of the urotensin receptor (UT) and design and synthesis of benzylamine and benzylsulfone antagonists

  • Bioorg Med Chem Lett. 2013 Apr 1;23(7):2177-80. doi: 10.1016/j.bmcl.2013.01.105.
Steven J Taylor  1 ,  Fariba Soleymanzadeh ,  Ingo Muegge ,  Isamu Akiba ,  Naoyuki Taki ,  Saisoku Ueda ,  Elizabeth Mainolfi ,  Anne B Eldrup
Affiliations
  • 1. Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Rd., PO Box 368, Ridgefield, CT 06877-036, USA. [email protected]
PMID: 23453841 DOI: 10.1016/j.bmcl.2013.01.105
Abstract

Potent small molecule antagonists of the Urotensin Receptor are described. These inhibitors were derived via systematically deconstructing a literature inhibitor to understand the basic pharmacophore and key molecular features required to inhibit the protein receptor. The series of benzylamine and benzylsulfone antagonists herein reported display a combination of nanomolar molecular and cellular potency as well as acceptable in vitro permeability and metabolic stability.