RU2001107007A

RU2001107007A - Pyridinium derivatives for the treatment of age-related and diabetic vascular complications, the method of their production and their therapeutic applications

Info

Publication number: RU2001107007A
Application number: RU2001107007/04A
Authority: RU
Inventors: Алангуди САНКАРАНАРАЯНАН
Original assignee: Торрент Фармасьютикалз Лтд.
Priority date: 1999-10-06
Filing date: 1999-10-22
Publication date: 2003-04-20

Claims

1. The compound of the pyridinium series of General formula I and its pharmaceutically acceptable salts, useful for the treatment of vascular complications associated with diabetes and age-related disorders,

where R ₁ represents —R ₄ —R ₅ or —N (R ₇ ) N (R ₇ ) R ₉ ;
R _{4 is} selected from the group —N (R ₇ ) R ₆ O—, —N (R ₇ ) R ₆ N (R ₇ ), OR ₆ O, —OR ₆ N (R ₇ ) - wherein R ₆ is alkyl;
R _{5 is} selected from the group consisting of alkyl, aryl, including heteroaryl, —COR ₇ , SO ₂ R ₇ , —C (S) NHR ₇ , —C (NH) NHR ₇ , —COR ₁₀ , —C (O) NHR _7, and

where R ₇ selected from the group comprising H, alkyl or aryl, including heteroaryl;
R _{2 is} selected from the group consisting of F, Cl, Br, I, OR ₇ , NO ₂ , alkyl, aryl, including heteroaryl, formyl, acyl, C (O) NR ₇ R ₁₀ , C (O) OR ₇ , NR ₇ R ₁₀ , N = C (R ₇ ) (R ₁₀ ), SR ₇ , SO ₂ NH ₂ , SO ₂ alkyl and SO ₂ aryl, and m is 0, 1 or 2;
R _{3 is} selected from the group consisting of R ₇ , OR ₇ , N (R ₇ ) (R ₁₀ ), N = C (R ₇ ) (R ₁₀ ), N (R ₇ ) N (R ₇ ) (R ₁₀ ), N (R ₇ ) N = C (R ₇ ) (R ₁₀ ) and CH (R ₇ ) C (O) R ₈ , where R _{8 is} selected from the group consisting of R ₇ , OR ₇ and NR ₇ R ₁₀ ;
R _{9 is} selected from the group consisting of hydrogen, alkyl, aryl, including heteroaryl, C (O) R ₁₀ , —SO ₂ R ₁₀ , —C (S) NHR ₁₀ , —C (NH) NH (R ₁₀ ), —C (O) NHR ₁₀ , R ₁₀ are selected from the group consisting of H, alkyl or aryl, including heteroaryl, and in each case it is not necessarily different from the substituent R ₇ ;
X is selected from the group consisting of halogen ion, acetate ion, perchlorate ion, sulfonate ion, oxalate ion, citrate ion, tosylate ion, maleate ion, mesylate ion, carbonate ion, sulfite ion, hydrophosphoric ion, phosphonate ion, phosphate ion, BF ₄ ^- , PF ₆ ^- , provided that (i) if the two alkyl groups are on the same carbon or nitrogen, they are optionally linked together to form a cyclic structure, and (ii) the nitrogen of the heteroaryl ring R ₁₀ , if present, is optionally quaternized with such a compound as X-CH ₂ C (O) -R ₃ .

2. The compound of claim 1, wherein the group —C (O) R ₁ is at position 3 or 4.

3. The compound according to claim 1 or 2, where the group -C (O) R ₁ is in position 3.

4. Connection PP. 1, 2 or 3, where m is 0 or 1.

5. Connection PP. 1, or 4, where m is 0.

6. Connection PP. 1 or 2 where X represents a halogen ion.

7. The compound according to claim 1, which is selected from the group comprising the following compounds:
(a) N, N'-bis [3-carbonyl-1- (2-thien-2'-yl-2-oxoethyl) -3-pyridinium] hydrazine dibromide or its other pharmaceutically acceptable salts;
(b) 1- (2-ethoxy-2-oxoethyl) -3- (2- (2-pyridyl) hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(c) 1- (2-ethoxy-2-oxoethyl) -3- (2- (benzoyloxy) ethylaminocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(d) N, N'-bis [3-carbonyl-1- (2-phenyl-2-oxoethyl) pyridinium] hydrazine dibromide or its other pharmaceutically acceptable salts;
(e) 1- (2-phenyl-2-oxoethyl) -3- (hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(f) 1- (2-thien-2'-yl-2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(g) N, N'-bis [3-carbonyl-1- (2- (2,4-dichlorophenyl) -2-oxoethyl) pyridinium] hydrazine dibromide or its other pharmaceutically acceptable salts;
(h) 1- (2-phenyl-2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(i) 1- (2-ethoxy-2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(j) 1- (2-phenyl-2-oxoethyl) -3- (phenylsulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(k) 1- (2-phenyl-2-oxoethyl) -2-chloro-3- (phenylsulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(l) 1- (2-thien-2'-yl-2-oxoethyl) -4- (2- (benzoyloxy) ethylaminocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(m) 1- (2- (2,4-dichlorophenyl) -2-oxoethyl) -3- (2- (benzoyloxy) ethylaminocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(n) 1- (2-phenyl-2-oxoethyl) -3- (2- (acetoxy) ethyloxycarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(o) 1- (2-ethoxy-2-oxoethyl) -3- (2- (benzoyloxy) ethyloxycarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(aa) N, N'-bis [3-carbonyl-1- (2-thien-2'-yl-2-oxoethyl) pyridinium] hydrazine dichloride or its other pharmaceutically acceptable salts;
(ab) N, N'-bis- [3-carbonyl-1- (2-cyclopropylamino-2-oxoethyl) pyridinium] hydrazine dichloride or its other pharmaceutically acceptable salts;
(ac) 1- (2-phenylamino-2-oxoethyl) -4- (phenylsulfonyl hydrazino-carbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(ad) 1- (2- (2 ', 4'-dichlorophenyl) -2-oxoethyl) -3- (2 (methoxy) ethoxycarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(ae) 1- (2-phenylamino-2-oxoethyl) -3 - ((benzoyloxy) ethylaminocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(af) 1- (2-thien-2'-yl-2-oxoethyl) -3- (phenylaminocarbonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(ag) 1- (2-phenyl-2-oxoethyl) -3- (2- (acetoxy) ethylaminocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(ah) 1- (2-phenylamino-2-oxoethyl) -3- (phenylsulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(ai) 1- (2-phenylamino-2-oxoethyl) -3 - ((4-methylphenyl) sulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(aj) 1- (2-phenyl-2-oxoethyl) -3- (2- (benzoyloxy) ethyloxycarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(ak) 1- (2-thien-2'-yl-2-oxoethyl) -3- (phenylcarbonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(al) 1- (2-ethoxy-2-oxoethyl) -3 - ((phenylmethyl) sulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(am) 1- (2-phenyl-2-oxoethyl) -3 - ((phenylmethyl) sulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(an) N, N'-bis [3-carbonyl-1- (2-furan-2'-yl-2-oxoethyl) pyridinium] hydrazine dibromide or its other pharmaceutically acceptable salts;
(ao) 1- (2 ', 4'-dichloro-phenyl-2-oxoethyl) -3- (2-methoxyethylaminocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(ar) 1- (2-thien-2'-yl-2-oxoethyl) -3 - ((2-methoxyethyl) aminocarbonyl) -5-bromopyridinium chloride or its other pharmaceutically acceptable salts;
(aq) 1- (2-thien-2'-yl-2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(ar) 1- (2-thien-2'-yl-2-oxoethyl) -3- (2- (2-chloro-3-pyridoylhydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(as) 1- (2-cyclopropylamino-2-oxoethyl) -3- (2-methoxyethylaminocarbonyl) pyridinium chloride or other pharmaceutically acceptable salts thereof;
(at) 1- (2-isopropylamino-2-oxoethyl) -3- (2-methylsulfonyl hydrazinocarbonyl) pyridinium chloride or other pharmaceutically acceptable salts thereof;
(au) 1- (2-phenylamino-2-oxoethyl) -3 - ({2- (1-oxo-3-cyclohexyl) propyl} hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(av) 1- (2-thien-2'-yl-2-oxoethyl) -3- [2- (benzoyloxy) ethylaminocarbonyl] pyridinium bromide or its other pharmaceutically acceptable salts;
(aw) 1- (4-ethoxy-2,4-dioxobutyl) -3- (2- (benzoyloxy) ethylaminocarbonyl) pyridinium chloride or other pharmaceutically acceptable salts thereof;
(ah) 1- (2'-thien-2'-yl-2-oxoethyl) -3- [1-oxo-1- (2-methoxycarbonyl) pyridyl] hydrazinopyridinium chloride or its other pharmaceutically acceptable salts;
(ay) 1- [1- (2-thien-2'-yl-2-oxoethyl) -5-aminocarbonyl-3-carbonylpyridinium] -2- [1- (2-thien-2'-yl-2-oxoethyl ) -3-carbonylpyridinium] hydrazine dichloride or its other pharmaceutically acceptable salts;
(az) 1- (2-thien-2'-yl-2-oxoethyl) -3- (trifluoromethanesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(ba) 1- [1- (2-thien-2'-yl-2-oxoethyl) -6-methyl-3-carbonylpyridinium] -2- [1- (2-thien-2'-yl-2-oxoethyl ) -3-carbonylpyridinium] hydrazine dichloride or its other pharmaceutically acceptable salts;
(bb) N, N'-bis [3-carbonyl-1- (2- (5-methylthien-2-yl) -2-oxoethyl) pyridinium] hydrazine dichloride or other pharmaceutically acceptable salts thereof;
(bc) N, N'-bis [3-carbonyl-1- (2- (5-chloro-thien-2-yl) -2-oxoethyl) pyridinium] hydrazine dichloride or its other pharmaceutically acceptable salts;
(bd) 1- (2-thien-2'-yl-2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) -6-methylpyridinium bromide or its other pharmaceutically acceptable salts;
(be) N, N'-bis [3-carbonyl-1- (2- (4-nitro-thien-2-yl) -2-oxoethyl) pyridinium] hydrazine dichloride or other pharmaceutically acceptable salts thereof;
(bf) 1- (2-phenylamino-2-oxoethyl) -3- (phenylhydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(bg) 1- (2- (4-nitro-thien-2-yl) -2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bh) 1-2- (5-nitro-thien-2-yl) -2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(bi) 1- (2- (5-chloro-thien-2-yl) -2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bj) 1- (2-thien-2'-yl-2-oxoethyl) -3- (ethoxycarbonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bk) 1- (2-thien-2'-yl-2-oxoethyl) -3- (isopropylsulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bl) 1- (2-thien-2'-yl-2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) -5-bromopyridinium bromide or its other pharmaceutically acceptable salts;
(bm) 1- (2- (2-ethoxycarbonylpyrrolidin-1-yl) -2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(bn) 1- (2- (5-methylthien-2-yl) -2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(bo) 1- (2- (4-carbethoxy-thiazolidin-3-yl) -2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(bp) 1- (2- (4-benzylpiperidin-1-yl) -2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(bq) N, N'-bis [3-carbonyl-1- (2- (2-ethoxycarbonyl pyrrolidin-1-yl) -2-oxoethyl) pyridinium] hydrazine dichloride or its other pharmaceutically acceptable salts;
(br) 1- (2-phenylamino-2-oxoethyl) -4- [2- (benzoyloxy) ethylaminocarbonyl] pyridinium chloride or its other pharmaceutically acceptable salts;
(bs) 1- (2-thien-2'-yl-2-oxoethyl) -3- (phenylhydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bt) 1- (2-thien-2'-yl-2-oxoethyl) -3- (p-methoxyphenylsulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bu) 1- (2-ethoxy-2-oxoethyl) -3- (phenylaminocarbonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bv) 1- (2-ethoxy-2-oxoethyl) -3- (p-toluenesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bw) 1- (2-phenyl-2-oxoethyl) -3- (phenylaminocarbonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bx) 1- (2-phenylamino-2-oxoethyl) -3- (benzylsulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(by) 1- (2-phenyl-2-oxoethyl) -4- (methanesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bz) 1- (2-phenyl-2-oxoethyl) -3- (phenylhydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(ca) 1- (2-ethoxy-2-oxoethyl) -4- [2- (benzoyloxy) ethylaminocarbonyl] pyridinium bromide or its other pharmaceutically acceptable salts;
(cb) 1- (2-ethoxy-2-oxoethyl) -3- (phenylhydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(cc) 1- (2-phenyl-2-oxoethyl) -3- (p-methoxyphenylsulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(cd) 1- (2-phenyl-2-oxoethyl) -4- [2- (benzoyloxy) ethylaminocarbonyl] pyridinium bromide or its other pharmaceutically acceptable salts;
(ce) 1- (2-ethoxy-2-oxoethyl) -4- (p-methanesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts.

8. A method for producing compounds of the pyridinium series according to claim 1, which comprises preparing a suitably substituted pyridine derivative in accordance with the desired end product, followed by quaternizing the substituted pyridine derivatives with an appropriate reagent by boiling in alcohol solvents and / or high boiling solvents for 6-48 h to obtain the desired compounds.

9. The compound of general formula I according to claim 1, for the manufacture of a medicament for the treatment of diabetic complications and diseases associated with age, including kidney disease, nervous system disorders, retinopathy, atherosclerosis, microangiopathy, endothelial dysfunctions, dermatological disorders, darkening of the teeth and dysfunctions other organs.

10. The compound according to claim 9, which represents:
(a) N, N'-bis [3-carbonyl-1- (2-thien-2'-yl-2-oxoethyl) -3-pyridinium] hydrazine dibromide or its other pharmaceutically acceptable salts;
(b) 1- (2-ethoxy-2-oxoethyl) -3- (2- (2-pyridyl) hydrazino-carbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(c) 1- (2-ethoxy-2-oxoethyl) -3- (2- (benzoyloxy) ethylamino-carbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(d) N, N'-bis [3-carbonyl-1- (2-phenyl-2-oxoethyl) pyridinium] hydrazine dibromide or its other pharmaceutically acceptable salts;
(e) 1- (2-phenyl-2-oxoethyl) -3- (hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(f) 1- (2-thien-2'-yl-2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(e) N, N'-bis [3-carbonyl-1- (2- (2,4-dichlorophenyl) -2-oxoethyl) pyridinium] hydrazine dibromide or its other pharmaceutically acceptable salts;
(h) 1- (2-phenyl-2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(i) 1- (2-ethoxy-2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(j) 1- (2-phenyl-2-oxoethyl) -3- (phenylsulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(k) 1- (2-phenyl-2-oxoethyl) -2-chloro-3- (phenylsulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(l) 1- (2-thien-2'-yl-2-oxoethyl) -4- (2- (benzoyloxy) ethylaminocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(m) 1- (2- (2,4-dichlorophenyl) -2-oxoethyl) -3- (2- (benzoyloxy) ethylaminocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(n) 1- (2-phenyl-2-oxoethyl) -3- (2- (acetoxy) ethyloxycarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(o) 1- (2-ethoxy-2-oxoethyl) -3- (2- (benzoyloxy) ethyloxycarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(aa) N, N'-bis [3-carbonyl-1- (2-thien-2'-yl-2-oxoethyl) pyridinium] hydrazine dichloride or its other pharmaceutically acceptable salts;
(ab) N, N'-bis- [3-carbonyl-1- (2-cyclopropylamino-2-oxoethyl) pyridinium] hydrazine dichloride or its other pharmaceutically acceptable salts;
(ac) 1- (2-phenylamino-2-oxoethyl) -4- (phenylsulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(ad) 1- (2- (2 ', 4'-dichlorophenyl) -2-oxoethyl) -3- (2 (methoxy) ethoxycarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(ae) 1- (2-phenylamino-2-oxoethyl) -3 - ((benzoyloxy) ethylaminocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(af) 1- (2-thien-2'-yl-2-oxoethyl) -3- (phenylaminocarbonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(ag) 1- (2-phenyl-2-oxoethyl) -3- (2- (acetoxy) ethylaminocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(ah) 1- (2-phenylamino-2-oxoethyl) -3- (phenylsulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(ai) 1- (2-phenylamino-2-oxoethyl) -3 - ((4-methylphenyl) sulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(aj) 1- (2-phenyl-2-oxoethyl) -3- (2- (benzoyloxy) ethyloxycarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(ak) 1- (2-thien-2'-yl-2-oxoethyl) -3- (phenylcarbonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(al) 1- (2-ethoxy-2-oxoethyl) -3 - ((phenylmethyl) sulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(am) 1- (2-phenyl-2-oxoethyl) -3 - ((phenylmethyl) sulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(an) N, N'-bis [3-carbonyl-1- (2-furan-2'-yl-2-oxoethyl) pyridinium] hydrazine dibromide or its other pharmaceutically acceptable salts;
(ao) 1- (2 ', 4'-dichloro-phenyl-2-oxoethyl) -3- (2-methoxyethylaminocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(ar) 1- (2-thien-2'-yl-2-oxoethyl) -3 - ((2-methoxyethyl) aminocarbonyl) -5-bromopyridinium chloride or its other pharmaceutically acceptable salts;
(aq) 1- (2-thien-2'-yl-2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(ar) 1- (2-thien-2'-yl-2-oxoethyl) -3- (2- (2-chloro-3-pyridoylhydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(as) 1- (2-cyclopropylamino-2-oxoethyl) -3- (2-methoxyethylaminocarbonyl) pyridinium chloride or other pharmaceutically acceptable salts thereof;
(at) 1- (2-isopropylamino-2-oxoethyl) -3- (2-methylsulfonyl hydrazinocarbonyl) pyridinium chloride or other pharmaceutically acceptable salts thereof;
(au) 1- (2-phenylamino-2-oxoethyl) -3 - ({2- (1-oxo-3-cyclohexyl) propyl} hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(av) 1- (2-thien-2'-yl-2-oxoethyl) -3- [2- (benzoyloxy) ethylaminocarbonyl] pyridinium bromide or its other pharmaceutically acceptable salts;
(aw) 1- (4-ethoxy-2,4-dioxobutyl) -3- (2- (benzoyloxy) ethylaminocarbonyl) pyridinium chloride or other pharmaceutically acceptable salts thereof;
(ah) 1- (2'-thien-2'-yl-2-oxoethyl) -3- [1-oxo-1- (2-methoxycarbonyl) pyridyl] hydrazinopyridinium chloride or its other pharmaceutically acceptable salts;
(ay) 1- [1- (2-thien-2'-yl-2-oxoethyl) -5-aminocarbonyl-3-carbonylpyridinium] -2- [1- (2-thien-2'-yl-2-oxoethyl ) -3-carbonylpyridinium] hydrazine dichloride or its other pharmaceutically acceptable salts;
(az) 1- (2-thien-2'-yl-2-oxoethyl) -3- (trifluoromethanesulfonyl hydrazinocarbonyl) pyridinium bromide or other pharmaceutically acceptable salts thereof;
(ba) 1- [1- (2-thien-2'-yl-2-oxoethyl) -6-methyl-3-carbonylpyridinium] -2- [1- (2-thien-2'-yl-2-oxoethyl ) -3-carbonylpyridinium] hydrazine dichloride or its other pharmaceutically acceptable salts;
(bb) N, N'-bis [3-carbonyl-1- (2- (5-methylthien-2-id) -2-oxoethyl) pyridinium] hydrazine dichloride or other pharmaceutically acceptable salts thereof;
(be) N, N'-bis [3-carbonyl-1- (2- (5-chloro-thien-2-yl) -2-oxoethyl) pyridinium] hydrazine dichloride or its other pharmaceutically acceptable salts;
(bd) 1- (2-thien-2'-yl-2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) -6-methylpyridinium bromide or its other pharmaceutically acceptable salts;
(be) N, N'-bis [3-carbonyl-1- (2- (4-nitro-thien-2-yl) -2-oxoethyl) pyridinium] hydrazine dichloride or other pharmaceutically acceptable salts thereof;
(bf) 1- (2-phenylamino-2-oxoethyl) -3- (phenylhydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(bg) 1- (2- (4-nitro-thien-2-yl) -2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bh) 1-2- (5-nitro-thien-2-yl) -2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(bi) 1- (2- (5-chloro-thien-2-yl) -2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bj) 1- (2-thien-2'-yl-2-oxoethyl) -3- (ethoxycarbonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bk) 1- (2-thien-2'-yl-2-oxoethyl) -3- (isopropylsulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bl) 1- (2-thien-2'-yl-2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) -5-bromopyridinium bromide or its other pharmaceutically acceptable salts;
(bm) 1- (2- (2-ethoxycarbonylpyrrolidin-1-yl) -2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(bn) 1- (2- (5-methylthien-2-yl) -2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(bo) 1- (2- (4-carbethoxy-thiazolidin-3-yl) -2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(bp) 1- (2- (4-benzylpiperidin-1-yl) -2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(bq) N, N'-bis [3-carbonyl-1- (2- (2-ethoxycarbonyl pyrrolidin-1-yl) -2-oxoethyl) pyridinium] hydrazine dichloride or its other pharmaceutically acceptable salts;
(br) 1- (2-phenylamino-2-oxoethyl) -4- [2- (benzoyloxy) ethylaminocarbonyl] pyridinium chloride or its other pharmaceutically acceptable salts;
(bs) 1- (2-thien-2'-yl-2-oxoethyl) -3- (phenylhydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bt) 1- (2-thien-2'-yl-2-oxoethyl) -3- (p-methoxyphenylsulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bu) 1- (2-ethoxy-2-oxoethyl) -3- (phenylaminocarbonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bv) 1- (2-ethoxy-2-oxoethyl) -3- (p-toluenesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bw) 1- (2-phenyl-2-oxoethyl) -3- (phenylaminocarbonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bx) 1- (2-phenylamino-2-oxoethyl) -3- (benzylsulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(by) 1- (2-phenyl-2-oxoethyl) -4- (methanesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bz) 1- (2-phenyl-2-oxoethyl) -3- (phenylhydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(ca) 1- (2-ethoxy-2-oxoethyl) -4- [2- (benzoyloxy) ethylaminocarbonyl] pyridinium bromide or its other pharmaceutically acceptable salts;
(cb) 1- (2-ethoxy-2-oxoethyl) -3- (phenylhydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(cc) 1- (2-phenyl-2-oxoethyl) -3- (p-methoxyphenylsulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(cd) 1- (2-phenyl-2-oxoethyl) -4- [2- (benzoyloxy) ethylaminocarbonyl] pyridinium bromide or its other pharmaceutically acceptable salts;
(ce) 1- (2-ethoxy-2-oxoethyl) -4- (p-methanesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts.

11. A pharmaceutical composition for treating diabetic complications and age-related diseases, which comprises a pharmaceutically effective amount of one or more compounds of the general formula I, as defined in claim 1, or a pharmaceutically acceptable salt (s) thereof, in admixture with a pharmaceutically acceptable carrier, diluent , solvent, or excipient.

12. The pharmaceutical composition according to claim 11 in a form intended for oral administration.

13. The pharmaceutical composition of claim 12, wherein said pharmaceutically acceptable carrier is selected from one or more compounds: starch, lactose, polyvinylpyrrolidone (K-30), talc and magnesium stearate.

14. The pharmaceutical composition according to claim 11 in the form of a composition for parenteral administration.

15. The pharmaceutical composition according to claim 11 in the form of lotions, rinses for the mouth and toothpaste.

16. The pharmaceutical composition according to p. 11-14, where the specified compound or compounds selected from the group including:
(a) N, N'-bis [3-carbonyl-1- (2-thien-2'-yl-2-oxoethyl) -3-pyridinium] hydrazine dibromide or its other pharmaceutically acceptable salts;
(b) 1- (2-ethoxy-2-oxoethyl) -3- (2- (2-pyridyl) hydrazino-carbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(c) 1- (2-ethoxy-2-oxoethyl) -3- (2- (benzoyloxy) ethylamino-carbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(d) N, N'-bis [3-carbonyl-1- (2-phenyl-2-oxoethyl) pyridinium] hydrazine dibromide or its other pharmaceutically acceptable salts;
(e) 1- (2-phenyl-2-oxoethyl) -3- (hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(f) 1- (2-thien-2'-yl-2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(g) N, N'-bis [3-carbonyl-1- (2- (2,4-dichlorophenyl) -2-oxoethyl) pyridinium] hydrazine dibromide or its other pharmaceutically acceptable salts;
(h) 1- (2-phenyl-2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(i) 1- (2-ethoxy-2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(j) 1- (2-phenyl-2-oxoethyl) -3- (phenylsulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(k) 1- (2-phenyl-2-oxoethyl) -2-chloro-3- (phenylsulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(l) 1- (2-thien-2'-yl-2-oxoethyl) -4- (2- (benzoyloxy) ethylaminocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(m) 1- (2- (2,4-dichlorophenyl) -2-oxoethyl) -3- (2- (benzoyloxy) ethylaminocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(n) 1- (2-phenyl-2-oxoethyl) -3- (2- (acetoxy) ethyloxycarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(o) 1- (2-ethoxy-2-oxoethyl) -3- (2- (benzoyloxy) ethyloxycarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(aa) N, N'-bis [3-carbonyl-1- (2-thien-2'-yl-2-oxoethyl) pyridinium] hydrazine dichloride or its other pharmaceutically acceptable salts;
(ab) N, N'-bis- [3-carbonyl-1- (2-cyclopropylamino-2-oxoethyl) pyridinium] hydrazine dichloride or its other pharmaceutically acceptable salts;
(ac) 1- (2-phenylamino-2-oxoethyl) -4- (phenylsulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(ad) 1- (2- (2 ', 4'-dichlorophenyl) -2-oxoethyl) -3- (2 (methoxy) ethoxy-carbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(ae) 1- (2-phenylamino-2-oxoethyl) -3 - ((benzoyloxy) ethylaminocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(af) 1- (2-thien-2'-yl-2-oxoethyl) -3- (phenylaminocarbonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(ag) 1- (2-phenyl-2-oxoethyl) -3- (2- (acetoxy) ethylaminocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(ah) 1- (2-phenylamino-2-oxoethyl) -3- (phenylsulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(ai) 1- (2-phenylamino-2-oxoethyl) -3 - ((4-methylphenyl) sulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(aj) 1- (2-phenyl-2-oxoethyl) -3- (2- (benzoyloxy) ethyloxycarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(ak) 1- (2-thien-2'-yl-2-oxoethyl) -3- (phenylcarbonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(al) 1- (2-ethoxy-2-oxoethyl) -3 - ((phenylmethyl) sulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(am) 1- (2-phenyl-2-oxoethyl) -3 - ((phenylmethyl) sulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(an) N, N'-bis [3-carbonyl-1- (2-furan-2'-yl-2-oxoethyl) pyridinium] hydrazine dibromide or its other pharmaceutically acceptable salts;
(ao) 1- (2 ', 4'-dichloro-phenyl-2-oxoethyl) -3- (2-methoxyethylaminocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(ar) 1- (2-thien-2'-yl-2-oxoethyl) -3 - ((2-methoxyethyl) aminocarbonyl) -5-bromopyridinium chloride or its other pharmaceutically acceptable salts;
(aq) 1- (2-thien-2'-yl-2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(ar) 1- (2-thien-2'-yl-2-oxoethyl) -3- (2- (2-chloro-3-pyridoylhydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(as) 1- (2-cyclopropylamino-2-oxoethyl) -3- (2-methoxyethylaminocarbonyl) pyridinium chloride or other pharmaceutically acceptable salts thereof;
(at) 1- (2-isopropylamino-2-oxoethyl) -3- (2-methylsulfonyl hydrazinocarbonyl) pyridinium chloride or other pharmaceutically acceptable salts thereof;
(au) 1- (2-phenylamino-2-oxoethyl) -3 - ({2- (1-oxo-3-cyclohexyl) propyl} hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(av) 1- (2-thien-2'-yl-2-oxoethyl) -3- [2- (benzoyloxy) ethylaminocarbonyl] pyridinium bromide or its other pharmaceutically acceptable salts;
(aw) 1- (4-ethoxy-2,4-dioxobutyl) -3- (2- (benzoyloxy) ethylaminocarbonyl) pyridinium chloride or other pharmaceutically acceptable salts thereof;
(ah) 1- (2'-thien-2'-yl-2-oxoethyl) -3- [1-oxo-1- (2-methoxycarbonyl) pyridyl] hydrazinopyridinium chloride or its other pharmaceutically acceptable salts;
(ay) 1- [1- (2-thien-2'-yl-2-oxoethyl) -5-aminocarbonyl-3-carbonylpyridinium] -2- [1- (2-thien-2'-yl-2-oxoethyl ) -3-carbonylpyridinium] hydrazine dichloride or its other pharmaceutically acceptable salts;
(az) 1- (2-thien-2'-yl-2-oxoethyl) -3- (trifluoromethanesulfonyl hydrazinocarbonyl) pyridinium bromide or other pharmaceutically acceptable salts thereof;
(ba) 1- [1- (2-thien-2'-yl-2-oxoethyl) -6-methyl-3-carbonylpyridinium] -2- [1- (2-thien-2'-yl-2-oxoethyl ) -3-carbonylpyridinium] hydrazine dichloride or its other pharmaceutically acceptable salts;
(bb) N, N'-bis [3-carbonyl-1- (2- (5-methylthien-2-yl) -2-oxoethyl) pyridinium] hydrazine dichloride or other pharmaceutically acceptable salts thereof;
(bc) N, N'-bis [3-carbonyl-1- (2- (5-chloro-thien-2-yl) -2-oxoethyl) pyridinium] hydrazine dichloride or its other pharmaceutically acceptable salts;
(bd) 1- (2-thien-2'-yl-2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) -6-methylpyridinium bromide or its other pharmaceutically acceptable salts;
(be) N, N'-bis [3-carbonyl-1- (2- (4-nitro-thien-2-yl) -2-oxoethyl) pyridinium] hydrazine dichloride or other pharmaceutically acceptable salts thereof;
(bf) 1- (2-phenylamino-2-oxoethyl) -3- (phenylhydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(bg) 1- (2- (4-nitro-thien-2-yl) -2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bh) 1-2- (5-nitro-thien-2-yl) -2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(bi) 1- (2- (5-chloro-thien-2-yl) -2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bj) 1- (2-thien-2'-yl-2-oxoethyl) -3- (ethoxycarbonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bk) 1- (2-thien-2'-yl-2-oxoethyl) -3- (isopropylsulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bl) 1- (2-thien-2'-yl-2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) -5-bromopyridinium bromide or its other pharmaceutically acceptable salts;
(bm) 1- (2- (2-ethoxycarbonylpyrrolidin-1-yl) -2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(bn) 1- (2- (5-methylthien-2-yl) -2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(bo) 1- (2- (4-carbethoxy-thiazolidin-3-yl) -2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(bp) 1- (2- (4-benzylpiperidin-1-yl) -2-oxoethyl) -3- (methanesulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(bq) N, N'-bis [3-carbonyl-1- (2- (2-ethoxycarbonyl pyrrolidin-1-yl) -2-oxoethyl) pyridinium] hydrazine dichloride or its other pharmaceutically acceptable salts;
(br) 1- (2-phenylamino-2-oxoethyl) -4- [2- (benzoyloxy) ethylaminocarbonyl] pyridinium chloride or its other pharmaceutically acceptable salts;
(bs) 1- (2-thien-2'-yl-2-oxoethyl) -3- (phenylhydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bt) 1- (2-thien-2'-yl-2-oxoethyl) -3- (p-methoxyphenylsulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bu) 1- (2-ethoxy-2-oxoethyl) -3- (phenylaminocarbonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bv) 1- (2-ethoxy-2-oxoethyl) -3- (p-toluenesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bw) 1- (2-phenyl-2-oxoethyl) -3- (phenylaminocarbonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bx) 1- (2-phenylamino-2-oxoethyl) -3- (benzylsulfonyl hydrazinocarbonyl) pyridinium chloride or its other pharmaceutically acceptable salts;
(by) 1- (2-phenyl-2-oxoethyl) -4- (methanesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(bz) 1- (2-phenyl-2-oxoethyl) -3- (phenylhydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(ca) 1- (2-ethoxy-2-oxoethyl) -4- [2- (benzoyloxy) ethylaminocarbonyl] pyridinium bromide or its other pharmaceutically acceptable salts;
(cb) 1- (2-ethoxy-2-oxoethyl) -3- (phenylhydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(cc) 1- (2-phenyl-2-oxoethyl) -3- (p-methoxyphenylsulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts;
(cd) 1- (2-phenyl-2-oxoethyl) -4- [2- (benzoyloxy) ethylaminocarbonyl] pyridinium bromide or its other pharmaceutically acceptable salts;
(se) 1- (2-ethoxy-2-oxoethyl) -4- (p-methanesulfonyl hydrazinocarbonyl) pyridinium bromide or its other pharmaceutically acceptable salts.

17. A method for preparing a composition for parenteral administration according to claim 14, wherein said method comprises dissolving the active ingredient of general formula I, according to claim 1, in polyethylene glycol 400 and diluting the solution thus obtained with isotonic solution or water to the desired concentration.

18. A method for treating patients with diabetes by destroying a preformed AGE in said patient, which comprises administering an effective amount of a compound according to claim 1, either alone or in combination with other drugs for antidiabetic therapy.

19. A method for the prevention or treatment of diseases caused by diabetes and age-related complications, which comprises administering to a patient in need of such treatment an effective amount of a compound of formula I according to claim 1, either alone or in combination with a pharmaceutically acceptable carrier, diluent or excipient .

20. The method of claim 18, wherein the disease that is prevented or treated is a nephrological disease, a neurological disease, atherosclerosis, retinal disorders, dermatological disease, non-enzymatic browning of the oral cavity, endothelial dysfunctions or dysfunctions of other organs and growth disorders.