title: Biphenyls as potent vitronectin receptor antagonists. Part 2: biphenylalanine ureas.
abstract: Vitronectin receptor (alpha(V)beta(3)) antagonism has been implicated in a variety of disease states, like restenosis, osteoporosis and cancer. In this work, we present the development of a novel class of biphenyl vitronectin receptor antagonists. Identified from a focused combinatorial library based on para-bromo phenylalanine, these compounds show nanomolar affinity to the vitronectin receptor and display unprecedented SAR. Their binding mode can be rationalized by computational docking studies using the X-ray structure of alpha(V)beta(3).
authors.affiliation: Institute of Medicinal Chemistry, Pharma Research Center, Bayer AG, D-42096 Wuppertal, Germany. klaus.urbahns.ku1@bayer.co.jp
authors.forename: Klaus
authors.initials: K
authors.lastname: Urbahns
authors.forename: Michael
authors.initials: M
authors.lastname: Härter
authors.forename: Andrea
authors.initials: A
authors.lastname: Vaupel
authors.forename: Markus
authors.initials: M
authors.lastname: Albers
authors.forename: Delf
authors.initials: D
authors.lastname: Schmidt
authors.forename: Ulf
authors.initials: U
authors.lastname: Brüggemeier
authors.forename: Beatrix
authors.initials: B
authors.lastname: Stelte-Ludwig
authors.forename: Christoph
authors.initials: C
authors.lastname: Gerdes
authors.forename: Hideki
authors.initials: H
authors.lastname: Tsujishita
mesh_terms: D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors; D008024:Ligands; D008958:Models, Molecular; D010649:Phenylalanine / Q000737:chemistry; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D001713:Biphenyl Compounds; D039302:Integrin alphaVbeta3; D008024:Ligands; D010649:Phenylalanine; D014508:Urea