On March 13, 2003, Kajino, Masahiro; Kawada, Akira; Nakayama, Yutaka; Kimura, Haruhide published a patent.Quality Control of Ethyl 6-cyanopicolinate The title of the patent was Preparation of 2-heterocyclyl-1,3-benzothiazinone derivatives as inhibitors of apoptosis or cytoprotective agents. And the patent contained the following:
Compounds represented by the following general formula (I) or salts thereof (wherein R1 represents hydrogen, halogeno, hydroxy, nitro, optionally halogenated alkyl, optionally substituted alkoxy, acyl or optionally substituted amino; R2 represents pyridyl, furyl, thienyl, pyrrolyl, quinolyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, tetrahydroquinolyl or thiazolyl, each optionally substituted; and n is 1 or 2), which and have a high safety and favorable effects of inhibiting cell death and binding to macrophage migration inhibitory factor (MIF), are prepared Also disclosed are apoptosis inhibitors, cytoprotective agents, or myocardial cell death inhibitors, or preventives/remedies for diseases caused by apoptosis or MIF which contain the compounds of the general formula (I), in particular for the prevention and/or treatment of circulatory diseases, bone or joint diseases, infectious diseases, inflammatory bowel diseases, or kidney. They are also useful for the prevention and/or treatment of heart diseases, heart failure syndromes, neurodegenerative diseases, brain vascular diseases, central nerve infections, traumatic diseases, demyelinating diseases, liver diseases, myelodysplastic syndrome, AIDS, cancer, etc. Thus, a mixture of 0.67 g thiosalicylic acid Me ester, 2-cyano-6-propylthiopyridine, and 0.84 mL Et3N in 50 mL toluene was refluxed for 48 h to give 37% 2-(6-propylthio-2-pyridyl)-4H-1,3-benzothiazin-4-one which was oxidized by m-chloroperbenzoic acid in EtOAc at room temperature for 18 h to give 2-(6-propylsulfinyl-2-pyridyl)-4H-1,3-benzothiazin-4-one (II). II was further oxidized by m-chloroperbenzoic acid in EtOAc at room temperature for 18 h to give 41% 2-(6-propylsulfonyl-2-pyridyl)-4H-1,3-benzothiazin-4-one (III). II and III showed the minium effective concentration of 0.019 and 0.010 μM, resp., for inhibiting apoptosis of new born rat’s first generation myocardial cells. A tablet and a capsule formulation containing 2-(6-methylsulfonyl-2-pyridyl)-4H-1,3-benzothiezin-4-one were described. The experimental process involved the reaction of Ethyl 6-cyanopicolinate(cas: 97483-79-9).Quality Control of Ethyl 6-cyanopicolinate
The Article related to heterocyclylbenzothiazinone preparation apoptosis inhibitor cytoprotective agent, myocardial cell death inhibitor heterocyclylbenzothiazinone preparation, circulatory disease prevention treatment heterocyclylbenzothiazinone preparation, bone joint disease prevention treatment heterocyclylbenzothiazinone preparation and other aspects.Quality Control of Ethyl 6-cyanopicolinate