Format

Send to

Choose Destination
Bioorg Med Chem Lett. 2011 Oct 15;21(20):6108-11. doi: 10.1016/j.bmcl.2011.08.040. Epub 2011 Aug 16.

Discovery of potent, metabolically stable purine CRF-1 antagonists with differentiated binding kinetic profiles.

Author information

1
Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK. duncan.miller@pfizer.com

Abstract

Optimisation of the potency of a bicyclic CRF antagonist whilst retaining metabolic stability is described. A core change and incorporation of metabolically stable lipophilic groups resulted in a further potency gain without increasing metabolic liability. Pharmacological investigation of binding kinetics led to the identification of compound 25, a sub-nanomolar CRF-1 antagonist with slow dissociation kinetics and an encouraging pharmacokinetic profile.

PMID:
21889333
DOI:
10.1016/j.bmcl.2011.08.040
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center