Patent HU-0101304-A2 (HU)
Title: New pyridinium compounds treating aging-related and diabetic vascular complications, process for their preparation and pharmaceutical compositions containing them
Inventor: SANKARANARAYANAN
IPC: C07D213/04
Filed: 2001-03-29
Abstract: Pyridinium compounds are new. The following 57 pyridinium compounds are new: (1) N,N'-bis(3-carbonyl-1-(2-thien-2'-yl-2-oxoethyl)pyridinium) hydrazine dichloride; (2) N,N'-bis(3-carbonyl-1 (2-cyclopropylamino-2-oxoethyl)pyridinium) hydrazine dichloride; (3) 1 (2-phenylamino-2-oxoethyl)-4-(phenylsulfonylhydrazinocarbonyl)pyridinium chloride; (4) 1-(2-(2',4' dichlorophenyl)-2-oxoethyl)-3-(2-(methoxy)ethyloxycarbonyl)pyridinium bromide; (5) 1-(2-phenylamino-2-oxoethyl)-3-((benzoyloxy)ethylaminocarbonyl)pyridinium chloride; (6) 1-(2-thien-2'-yl-2-oxoethyl)-3-(phenylaminocarbonylhydrazinocarbonyl)pyridinium bromide; (7) 1-(2 phenyl-2-oxoethyl)-3-(2-(acetoxy)ethylaminocarbonyl)pyridinium bromide; (8) 1-(2-phenylamino-2-oxoethyl)-3-(phenylsulfonylhydrazinocarbonyl)pyridinium chloride; (9) 1-(2 phenylamino-2-oxoethyl)-3-((4-methylphenyl)sulfonylhydrazinocarbonyl)pyridinium chloride; (10) 1-(2 phenyl-2-oxoethyl)-3-(2-(benzoyloxy)ethyloxycarbonyl)pyridinium bromide; (11) 1-(2-thien-2'-yl-2-oxoethyl)-3-(phenylcarbonylhydrazinocarbonyl)pyridinium bromide; (12) 1-(2-ethoxy-2-oxoethyl)-3-((phenylmethyl)sulfonylhydrazinocarbonyl)pyridinium bromide; (13) 1-(2-phenyl-2-oxoethyl)-3-((phenylmethyl)sulfonylhydrazinocarbonyl)pyridinium bromide; (14) N,N' bis(3-carbonyl-1-(2-furan-2'-yl-2-oxoethyl)pyridinium) hydrazine dibromide; (15) 1-(2',4'-dichloro-phenyl-2-oxoethyl)-3-(2-methoxyethylaminocarbonyl)pyridinium bromide; (16) 1-(2-thien-2'-yl-2 oxoethyl)-3-((2-methoxyethyl)aminocarbonyl)-5-bromopyridinium chloride; (17) 1-(2-thien-2'-yl-2-oxoethyl)-3-(methanesulfonylhydrazinocarbonyl)pyridinium chloride; (18) 1-(2-thien-2'-yl-2-oxoethyl)-3-(2-(2-chloro-3-pyridoylhydrazinocarbonyl)pyridinium chloride; (19) 1-(2 cyclopropylamino-2-oxoethyl)-3-(2-methoxyethylaminocarbonyl)pyridinium chloride; (20) 1-(2-isopropylamino-2-oxoethyl)-3-(2-methylsulfonylhydrazinocarbonyl)pyridinium chloride; (21) 1-(2-phenylamino-2-oxoethyl)-3-((2-(1-oxo-3-cyclohexyl)propyl)hydrazinocarbonyl)pyridinium bromide; (22) 1-(2-thien 2'-yl-2-oxoethyl)-3-(2-(benzoyloxy)ethylaminocarbonyl)pyridinium bromide; (23) 1-(4-ethoxy-2,4-dioxobutyl)-3-(2-(benzoxyloxy)ethylaminocarbonyl)pyridinium chloride; (24) 1-(2-thien-2-yl-2-oxoethyl)-3-(1-oxo-1-(2-methoxycarbonyl)pyridyl)hydrazinopyridinium chloride; (25) 1-(1-(2 thien-2'-yl-2-oxoethyl)-5-aminocarbonyl-3-carbonylpyridinium)-2(1-(2-thien-2'-yl-2-oxoethyl)-3-carbonylpyridinium)hydrazine dichloride; (26) 1-(2-thien-2'-yl-2-oxoethyl)-3-(trifluoromethanesulfonylhydrazinocarbonyl)pyridinium bromide; (27) 1 (1-(2-thien-2'-yl-2-oxoethyl)-6-methyl-3-carbonylpyridinium)-2-(1-(2-thien-2'-yl-2-oxoethyl)-3-carbonylpyridinium)hydrazine dichloride; (28) N,N'-bis(3-carbonyl-1-(2-(5-methyl-thien-2-yl)-2-oxoethyl)pyridinium)hydrazine dichloride; (29) N,N'-bis(3-carbonyl-1-(2-(5-chloro-thien-2-yl)-2-oxoethyl)pyridinium)hydrazine dichloride; (30) 1-(2-thien-2'-yl-2-oxoethyl)-3(methanesulfonylhydrazinocarbonyl)-6-methylpyridinium bromide; (31) N,N'-bis(3-carbonyl-1-(2-(4-nitrothien-2-yl)-2-oxoethyl)pyridinium)hydrazine dichloride; (32) 1-(2-phenylamino-2-oxoethyl)-3-(phenylhydrazinocarbonyl)pyridinium chloride; (33) 1-(2-(4-nitro-thien-2-yl)-2-oxoethyl)-3-(methanesulfonylhydrazinocarbonyl)pyridinium bromide; (34) 1-(2-(5-nitro-thien-2-yl)-2-oxoethyl)-3-(methanesulfonylhydrazinocarbonyl)pyridinium chloride; (35) 1-(2-(5-chloro-thien-2-yl)-2-oxoethyl)-3-(methanesulfonylhydrazinocarbonyl)pyridinium bromide; (36) 1-(2-thien-2'-yl-2-oxoethyl)-3-(ethoxycarbonyhydrazinocarbonyl)pyridinium bromide; (37) 1-(2-thien-2'-yl-2-oxoethyl)-3-(isopropylsulfonylhydrazinocarbonyl)pyridinium bromide; (38) 1-(2-thien-2'-yl-2-oxoethyl)-3-(methanesulfonylhydrazinocarbonyl)-5-bromopyridinium bromide; (39) 1-(2-(2-ethoxycarbonylpyrrolidin-1-yl)-2-oxoethyl)-3-(methanesulfonylhydrazinocarbonyl)pyridinium chloride; (40) 1-(2-(5-methyl-thien-2-yl)-2-oxoethyl)-3-(methanesulfonylhydrazinocarbonyl)pyridinium chloride; (41) 1-(2-(4-carbethoxy-thiazolidin-3-yl)-2-oxoethyl)-3-(methanesulfonylhydrazinocarbonyl)pyridinium chloride; (42) 1-(2-(4-benzylpiperidin-1-yl)-2-oxoethyl)-3-(methanesulfonylhydrazinocarbonyl)pyridinium chloride; (43) N,N'-bis(3-carbonyl-1-(2-(2-ethoxycarbonylpyrrolidin-1-yl)-2-oxoethyl)pyridinium)hydrazine dichloride; (44) 1-(2-phenylamino-2 oxoethyl)-4-(2-(benzyloxy)ethylaminocarbonyl)pyridinium chloride; (45) 1-(2-thien-2'-yl-2-oxoethyl)-3-(phenylhydrazinocarbonyl)pyridinium bromide; (46) 1-(2-thien-2'-yl-2-oxoethyl)-3-(p-methoxyphenylsulfonylhydrazinocarbonyl)pyridinium bromide; (47) 1-(2-ethoxy-2-oxoethyl)-3-(phenylaminocarbonylhydrazinocarbonyl)pyridinium bromide; (48) 1-(2-ethoxy-2-oxoethyl)-3-(p-toluenesulfonylhydrazinocarbonyl)pyridinium bromide; (49) 1-(2-phenyl-2-oxoethyl)-3-(phenylaminocarbonylhydrazinocarbonyl)pyridinium bromide; (50) 1-(2-phenylamino-2-oxoethyl)-3-(benzylsulfonylhydrazinocarbonyl)pyridinium chloride; (51) 1-(2-phenyl 2-oxoethyl)-4-(methanesulfonylhydrazinocarbonyl)pyridinium bromide; (52) 1-(2-phenyl-2-oxoethyl)-3-(phenylhydrazinocarbonyl)pyridinium bromide; (53) 1-(2-ethoxy-2 oxoethyl)-4-(2-(benzoyloxy)ethylaminocarbonyl)pyridinium bromide; (54) 1-(2-ethoxy-2-oxoethyl)-3-(phenylhydrazinocarbonyl)pyridinium bromide; (55) 1-(2-phenyl-2-oxoethyl)-3-(p-methoxyphenylsulfonylhydrazinocarbonyl)pyridinium bromide; (56) 1-(2-phenyl-2-oxoethyl)-4-(2-(benzoyloxy)ethylaminocarbonyl)pyridinium bromide; and (57) 1-(2-ethoxy-2-oxoethyl)-4-(p-methanesulfonylhydrazinocarbonyl)pyridinium bromide. An independent claim is included for the preparation of the compounds. ACTIVITY : Antidiabetic; nephrotropic; neuroprotective; ophthalmological. Tests were carried out to determine the effects of test compounds on diabetic neuropathy and nephropathy in a rat model of diabetes. Diabetes was induced in rats by injection of streptozotocin (60mg/kg). After 12 weeks of diabetes, rats were treated with test compound for 8 weeks, and at the end of treatment, creatinine clearances and nerve conduction velocities were estimated. Creatinine clearance in an untreated diabetic group was compared with the treated group, and using N,N'-bis(3 carbonyl-1-(2-thien-2'-yl-2-oxoethyl)pyridinium) hydrazine dichloride (7.5mg/kg bid), % increase in creatinine clearance was 103%. There was a 60% increase in nerve conduction velocities. MECHANISM OF ACTION : Advanced glycation end product (AGE) breakers.