Send to

Choose Destination
See comment in PubMed Commons below
Eur J Med Chem. 2014 May 6;78:1-9. doi: 10.1016/j.ejmech.2014.03.040. Epub 2014 Mar 15.

Synthesis of substituted pyrimidines as corticotropin releasing factor (CRF) receptor ligands.

Author information

  • 1Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007, USA.
  • 2Department of Pharmacology, Faculty of Medicine, University of Crete, Voutes, Heraklion 71003, Crete, Greece.
  • 3Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007, USA. Electronic address:


Corticotropin releasing factor (CRF) is a neuropeptide hormone produced from the hypothalamus that controls the secretion of corticotropin (ACTH) from the anterior pituitary gland that, in turn, prompts the adrenal glands to secrete glucocorticoids. This involvement in the hypothalamic-pituitary-adrenal axis (HPA) in response to stress and also playing a key role in behavioral, cardiovascular, immune and gastrointestinal systems made CRF binding to its receptors an important target in drug discovery aiming to develop lead compounds with the potential to treat various stress-related disorders including depression, anxiety and addictive disorders. Several non-peptide CRF1 receptor antagonists were developed by pharmaceutical companies and are currently in clinical trials with the aim of improving the health consequences of chronic stress and for use in the clinical management of anxiety and stress. Many showed promising results not only in treatment of anxiety and depression but also in treatment of CRF-induced hypertension, as well as in treatment of arthritis, irritable bowel syndrome and peptic ulcers. In this manuscript, we describe the synthesis of substituted pyrimidines with close structural similarities to reported lead compounds with promising CRF1 receptor affinities and carrying groups known to be associated with optimum affinity to CRF1 receptors. The affinity of the newly prepared compounds in comparison to antalarmin, a potent CRF1 receptor antagonist in clinical trials as a standard, is also described. Four compounds from the new series showed promising CRF1 receptor affinity.

Copyright © 2014 Elsevier Masson SAS. All rights reserved.


CRF; Corticotropin releasing factor receptor ligands; Pyrimidines; Thiazolo[4,5-d]pyrimidines

[PubMed - indexed for MEDLINE]

LinkOut - more resources

Full Text Sources

Chemical Information

PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk