title: Deconstruction of sulfonamide inhibitors of the urotensin receptor (UT) and design and synthesis of benzylamine and benzylsulfone antagonists.
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.
authors: Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Rd., PO Box 368, Ridgefield, CT 06877-036, USA. steven.taylor@boehringer-ingelheim.com
authors: Steven J
authors: SJ
authors: Taylor
authors: Fariba
authors: F
authors: Soleymanzadeh
authors: Ingo
authors: I
authors: Muegge
authors: Isamu
authors: I
authors: Akiba
authors: Naoyuki
authors: N
authors: Taki
authors: Saisoku
authors: S
authors: Ueda
authors: Elizabeth
authors: E
authors: Mainolfi
authors: Anne B
authors: AB
authors: Eldrup
mesh_terms: D001596:Benzylamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001596:Benzylamines; D043562:Receptors, G-Protein-Coupled; D013449:Sulfonamides; D013450:Sulfones; C121697:UTS2R protein, human; C030796:benzylamine