title: N-phenylphenylglycines as novel corticotropin releasing factor receptor antagonists.
abstract: Screening of a computationally designed synthetic library led to the discovery of the N-phenylphenylglycines (NPPGs) as a novel class of human corticotropin releasing factor (h-CRF(1)) antagonists. Several NPPGs with greater potency than the original hit 1 were rapidly identified, and resolution of the racemate demonstrated that only the R-enantiomer displays activity. This structural class represents the first example of a non-peptide CRF(1) antagonist with a stereochemically distinct receptor binding affinity.
authors.affiliation: Bristol-Myers Squibb Pharma Research Laboratories, 4570 Executive Drive, Suite 400, San Diego, California 92121, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Molteni
authors.forename: Julie
authors.initials: J
authors.lastname: Penzotti
authors.forename: Dean M
authors.initials: DM
authors.lastname: Wilson
authors.forename: Andreas P
authors.initials: AP
authors.lastname: Termin
authors.forename: Long
authors.initials: L
authors.lastname: Mao
authors.forename: Christine M
authors.initials: CM
authors.lastname: Crane
authors.forename: Fred
authors.initials: F
authors.lastname: Hassman
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Harvey
authors.initials: H
authors.lastname: Wong
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Miller
authors.forename: Scott
authors.initials: S
authors.lastname: Grossman
authors.forename: Peter D J
authors.initials: PD
authors.lastname: Grootenhuis
mesh_terms: D000818:Animals; D020650:Combinatorial Chemistry Techniques; D004285:Dogs; D015195:Drug Design; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000099052:CRF Receptor, Type 1
chemical_list: D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D005998:Glycine