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-CRF1) antagonists. Several NPPGs with greater potency than the original hit 1 were rapidly identified, and resolution of th...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2004-05, Vol.47 (10), p.2426-2429
Main Authors: Molteni, Valentina, Penzotti, Julie, Wilson, Dean M, Termin, Andreas P, Mao, Long, Crane, Christine M, Hassman, Fred, Wang, Tao, Wong, Harvey, Miller, Keith J, Grossman, Scott, Grootenhuis, Peter D. J
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Combinatorial Chemistry Techniques
Dogs
Drug Design
Glycine - analogs & derivatives
Glycine - chemical synthesis
Glycine - chemistry
Glycine - pharmacokinetics
Humans
Medical sciences
Models, Molecular
Molecular Conformation
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems
Pharmacology. Drug treatments
Receptors, Corticotropin-Releasing Hormone - antagonists & inhibitors
Stereoisomerism
Structure-Activity Relationship
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Summary: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-CRF1) 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 CRF1 antagonist with a stereochemically distinct receptor binding affinity.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm049974i