Substantial evidence has accumulated from basic science and clinical studies implicating Corticotropin-releasing factor (CRF) as a physiological or pathophysiological mediator of stress responses of stress-induced disorders. Therefore, it has been hypothesized that a centrally-active CRF antagonist would represent a novel approach for treating anxiety and affective disorders as well as a range of other diseases which are directly associated with or exacerbated by stress. Phase I efforts resulted in the identification of four structurally- distinct nonpeptide compounds exhibiting an in vitro profile indicative of selective CRF antagonism. In vivo evaluation of """"""""lead"""""""" compounds and close structural analogs evidence of blockade of actions of exogenously administered CRF. Several of these compounds had an anxiolytic profile in behavioral models. Based on these results, the Phase II proposal seeks to continue and expand upon Phase I efforts by (1) increasing synthetic chemistry effort with a goal of improving the pharmacological profile of the lead structures, (2) examining new compound libraries for additional chemical leads (3) employing receptor binding and in vivo testing approaches of Phase I for evaluation of new compounds and (4) developing additional animal models to further characterize the therapeutic potential of CRF antagonists. It is hoped that compounds will be identified during the Phase II period that would have substantial potential for clinical development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
2R44MH044411-02
Application #
3509000
Study Section
Small Business Research Review Committee (MHSB)
Project Start
1990-09-30
Project End
1992-08-31
Budget Start
1990-09-30
Budget End
1991-08-31
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Nova Pharmaceutical Corporation
Department
Type
DUNS #
City
Baltimore
State
MD
Country
United States
Zip Code
21224