Abstract
Antagonists of the corticotropin-releasing factor (CRF) neuropeptide may prove effective in treating stress and anxiety related disorders. In an effort to identify antagonists with improved physico-chemical properties a new series of CRF(1) antagonists were designed to substitute the propyl groups at the C7 position of the pyrazolo[1,5-a]pyrimidine core of 1 with heterocycles. Compound (S)-8d was identified as a high affinity ligand with a pK(i) value of 8.2 and a functional CRF(1) antagonist with pIC(50) value of 7.0 in the in vitro CRF ACTH production assay.
Copyright © 2010 Elsevier Ltd. All rights reserved.
MeSH terms
-
Azabicyclo Compounds / chemical synthesis
-
Azabicyclo Compounds / chemistry*
-
Azabicyclo Compounds / pharmacokinetics
-
Humans
-
Microsomes, Liver / metabolism
-
Oxadiazoles / chemical synthesis
-
Oxadiazoles / chemistry*
-
Oxadiazoles / pharmacokinetics
-
Protein Binding
-
Pyrazoles / chemistry*
-
Pyridines / chemistry*
-
Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
-
Receptors, Corticotropin-Releasing Hormone / genetics
-
Receptors, Corticotropin-Releasing Hormone / metabolism
-
Recombinant Proteins / antagonists & inhibitors
-
Recombinant Proteins / genetics
-
Recombinant Proteins / metabolism
Substances
-
Azabicyclo Compounds
-
NBI 77860
-
Oxadiazoles
-
Pyrazoles
-
Pyridines
-
Receptors, Corticotropin-Releasing Hormone
-
Recombinant Proteins
-
pyrazolopyridine