Optimization of CRF1R binding affinity of 2-(2,4,6-trichlorophenyl)-4-trifluoromethyl-5-aminomethylthiazoles through rapid and selective parallel synthesis

Dmitry Zuev; Jodi A Michne; Sokhom S Pin; Jie Zhang; Matthew T Taber; Gene M Dubowchik

doi:10.1016/j.bmcl.2004.10.055

Optimization of CRF1R binding affinity of 2-(2,4,6-trichlorophenyl)-4-trifluoromethyl-5-aminomethylthiazoles through rapid and selective parallel synthesis

Bioorg Med Chem Lett. 2005 Jan 17;15(2):431-4. doi: 10.1016/j.bmcl.2004.10.055.

Authors

Dmitry Zuev¹, Jodi A Michne, Sokhom S Pin, Jie Zhang, Matthew T Taber, Gene M Dubowchik

Affiliation

¹ Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. [email protected]

PMID: 15603967
DOI: 10.1016/j.bmcl.2004.10.055

Abstract

An efficient approach was developed to synthesize 2-(2,4,6-trichlorophenylamino)-4-trifluoromethyl-5-aminomethylthiazoles, corticotropin-releasing factor type 1 receptor (CRF(1)R) antagonists, by monoalkylation of amines with chloromethyl intermediate 5. The effect of variations in aminomethyl side chain of 6 on binding affinity is discussed.

MeSH terms

Binding Sites
Hydrocarbons, Halogenated / chemical synthesis*
Hydrocarbons, Halogenated / pharmacology
Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors
Receptors, Corticotropin-Releasing Hormone / metabolism*
Structure-Activity Relationship
Thiazoles / chemical synthesis
Thiazoles / pharmacology

Substances

Hydrocarbons, Halogenated
Receptors, Corticotropin-Releasing Hormone
Thiazoles
CRF receptor type 1