title: Optimization of CRF1R binding affinity of 2-(2,4,6-trichlorophenyl)-4-trifluoromethyl-5-aminomethylthiazoles through rapid and selective parallel synthesis.
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.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. dmitry.zuev@bms.com
authors.forename: Dmitry
authors.initials: D
authors.lastname: Zuev
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Michne
authors.forename: Sokhom S
authors.initials: SS
authors.lastname: Pin
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Taber
authors.forename: Gene M
authors.initials: GM
authors.lastname: Dubowchik
mesh_terms: D001665:Binding Sites; D006846:Hydrocarbons, Halogenated / Q000138:chemical synthesis* / Q000494:pharmacology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000494:pharmacology; D000099052:CRF Receptor, Type 1
chemical_list: D006846:Hydrocarbons, Halogenated; D018019:Receptors, Corticotropin-Releasing Hormone; D013844:Thiazoles; D000099052:CRF Receptor, Type 1