N-phenylphenylglycines as novel corticotropin releasing factor receptor antagonists.
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.
Molteni
Valentina
V
Bristol-Myers Squibb Pharma Research Laboratories, 4570 Executive Drive, Suite 400, San Diego, California 92121, USA.
Penzotti
Julie
J
Wilson
Dean M
DM
Termin
Andreas P
AP
Mao
Long
L
Crane
Christine M
CM
Hassman
Fred
F
Wang
Tao
T
Wong
Harvey
H
Miller
Keith J
KJ
Grossman
Scott
S
Grootenhuis
Peter D J
PD
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
D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D005998:Glycine