On August 26, 2003, Bizzarro, Fred Thomas; Corbett, Wendy Lea; Grippo, Joseph Francis; Haynes, Nancy-Ellen; Holland, George William; Kester, Robert Francis; Mahaney, Paige Erin; Sarabu, Ramakanth published a patent.Application In Synthesis of Methyl 2-(2-aminothiazol-4-yl)acetate The title of the patent was Preparation of cycloalkylheteroaryl propionamides as glucokinase activators for treatment of type II diabetes. And the patent contained the following:
Title compounds [I; R1, R2 = H, halo, amino, hydroxyamino, NO2, cyano, sulfonamido, perfluoroalkyl, alkylthio, alkylsulfonyl, alkylsulfinyl, etc.; R3 = alkyl, cycloalkyl; R4 = certain un- or monosubstituted 5- and 6-membered heteroaromatic rings connected by a ring C atom; R4 (claims) = un- or monosubstituted triazine, pyrazine, or pyridazine; and their pharmaceutical acceptable salts], were prepared via amidation, for use as glucokinase activators for treatment of type II diabetes. Thus, the invention compound N-(5-chlorothiazol-2-yl)-3-cyclopentyl-2(R)-[4-(methanesulfonyl)phenyl]propionamide (II) was prepared by addition of 3-cyclopentyl-2(R)-[4-(methanesulfonyl)phenyl]propionic acid (preparation given) to a stirred mixture of triphenylphosphine and N-bromosuccinimide in methylene chloride at 0°, followed by stirring at room temperature for 30 min, addition of a solution of 2-amino-5-chlorothiazole hydrochloride and pyridine in methylene chloride, and stirring at 25° overnight. All of the exemplified compounds I activated glucokinase in vitro, exhibiting an SC1.5 ≤ 30 μM. Selected invention compounds exhibited glucokinase activator activity in vivo when administered orally to mice. Thus, I are expected to increase insulin secretion in the treatment of type II diabetes. The experimental process involved the reaction of Methyl 2-(2-aminothiazol-4-yl)acetate(cas: 64987-16-2).Application In Synthesis of Methyl 2-(2-aminothiazol-4-yl)acetate
The Article related to cycloalkylheteroaryl propionamide preparation thiazolyl glucokinase activator diabetes, antidiabetic thiazole pyrazine pyridazine pyridine pyrimidine glucokinase activator preparation and other aspects.Application In Synthesis of Methyl 2-(2-aminothiazol-4-yl)acetate
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica