Derivatives of pyridinium salts, the method of production thereof, pharmaceutical compositions and methods of treatment

 

The invention relates to new salts of pyridinium General formula (I) or their pharmaceutically acceptable salts, where R1is-R4- R5or-N(R7)N(R7R9, R4choose from the group of-N(R7R6O-, N(R7R6N(R7), -OR6O-, -or SIG6N(R7)-, where R6- alkyl, R5choose from the group of alkyl, aryl, including heteroaryl, -COR7, -SO2R7and-COR10where R7Is H, alkyl or aryl, including heteroaryl, R2Is F, Cl, Br, J, alkyl, aryl, including heteroaryl, formyl, acyl, C(O)NR7R10or C(O)or SIG7, m = 0, 1, or 2, R3selected from the group comprising R7OR7N(R7)(R10) and CH(R7)C(O)R8, R8is R7OR7and NR7R10, R9is hydrogen, alkyl, aryl, including heteroaryl, -C(O)R10, -SO2R10, -C(S)other10, -C(NH)NH(R10), -C(O)other10, R10- H, alkyl, or aryl, including heteroaryl, and in each case, it is not necessarily different from R7X represents an ion halogen provided that 1) when two alkyl groups are the same carbon or nitrogen, they are not necessarily linked together with the formation of a cyclic structure, and (2) nitrogen heteroaryl ring the unity of formula (I) possess destructive AGE activity and can be used to treat diabetes, Nephrology, neurological diseases, atherosclerosis, disorders of the retina and dermatological diseases. 8 C. and 16 h.p. f-crystals, 5 PL.

Description text in facsimile form (see graphic part).

Claims

1. Connection pyridinium number of General formula (I) and its pharmaceutically acceptable saltswhere R1is-R4-R5or-N(R7)N(R7R9; R4choose from the group of-N(R7R6O-, -N(R7R6N(R7), -OR6O;- -OR6N(R7)-, where R6is alkyl; R5selected from the group including alkyl, aryl, including heteroaryl, -COR7, -SO2R7and-COR10where R7selected from the group comprising H, alkyl or aryl, including heteroaryl; R2selected from the group comprising F, Cl, Br, I, alkyl, aryl, including heteroaryl, formyl, acyl, C(O)NR7R10and C(O)OR7;
m = 0,1 or 2,
R3selected from the group comprising R7OR7N(R7)(R10) and CH(R7)C(O)R8,
where R8selected from the group comprising R7OR7and NR7R10;
R10, -C(NH)NH(R10), -C(O)other10,
R10selected from the group comprising H, alkyl or aryl, including heteroaryl, and in each case, it is not necessarily different from the substituent R7;
X represents a halogen ion,
provided that (i) if the two alkyl groups are the same carbon or nitrogen, they are not necessarily linked together with the formation of a cyclic structure, and (ii) the nitrogen heteroaryl ring R10if present, optional quaternity in this connection, as X-CH2C(O)-R3.

2. Connection on p. 1, where the group-C(O)R1is in position 3 or 4.

3. Connection under item 1 or 2, where the group-C(O)R1is in position 3.

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

5. Connection on p. 1 or 4, where m = 0.

6. Connection on p. 1, which is chosen from the group comprising the following compounds:
(a) N,N'-bis[3-carbonyl-1-(2-Tien-2'-yl-2-oxoethyl)-3-pyridine]gidrazzingidrate or other pharmaceutically acceptable salts;
(b) 1-(2-ethoxy-2-oxoethyl)-3-(2-(2-pyridyl)hydrazinophenyl)pyridineboronic or other pharmaceutically acceptable salts;
(c) 1-(2-ethoxy-2-oxoethyl)-3-(2-(benzoyloxy)ethylaminomethyl)pyridineboronic or other farmatsevticheskii acceptable salts;
(e) 1-(2-phenyl-2-oxoethyl)-3-(hydrazinophenyl)pyridineboronic or other pharmaceutically acceptable salts;
(f) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridineboronic or other pharmaceutically acceptable salts;
(g) N,N'-bis[3-carbonyl-1-(2-(2,4-dichlorophenyl)-2-oxoethyl)pyridine]gidrazzingidrate or other pharmaceutically acceptable salts;
(h) 1-(2-phenyl-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridineboronic or other pharmaceutically acceptable salts;
(i) 1-(2-ethoxy-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridineboronic or other pharmaceutically acceptable salts;
(j) 1-(2-phenyl-2-oxoethyl)-3-(vinylsulfonylacetamido)pyridineboronic or other pharmaceutically acceptable salts;
(k) 1-(2-phenyl-2-oxoethyl)-2-chloro-3-(vinylsulfonylacetamido) pyridineboronic or other pharmaceutically acceptable salts;
(l) 1-(2-Tien-2'-yl-2-oxoethyl)-4-(2-(benzoyloxy)ethylaminomethyl)pyridineboronic or other pharmaceutically acceptable salts;
(m) 1-(2-(2,4-dichlorophenyl)-2-oxoethyl)-3-(2-(benzoyloxy)ethylaminomethyl)pyridineboronic or other pharmaceutically acceptable salts;
(n) 1-(2-phenyl-2-oxoethyl)-3-(2-(methoxy)carbonylethyl is benzoyloxy)ethoxycarbonyl)pyridineboronic or other pharmaceutically acceptable salts;
(aa) N,N'-bis[3-carbonyl-1-(2-Tien-2'-yl-2-oxoethyl)pyridine]hereinbefore or other pharmaceutically acceptable salts;
(ab) N, N'-bis-[3-carbonyl-1-(2-cyclopropylamino-2-oxoethyl)pyridine] hereinbefore or other pharmaceutically acceptable salts;
(ac) 1-(2-phenylamino-2-oxoethyl)-4-(vinylsulfonylacetamido)pyridinethione or other pharmaceutically acceptable salts;
ad) 1-(2-(2',4'-dichlorophenyl)-2-oxoethyl)-3-(2(methoxy)ethoxycarbonyl)pyridineboronic or other pharmaceutically acceptable salts;
(ae) 1-(2-phenylamino-2-oxoethyl)-3-((benzoyloxy)ethylaminomethyl)pyridinethione or other pharmaceutically acceptable salts;
(af) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(phenylaminopyrimidine)pyridineboronic or other pharmaceutically acceptable salts;
(ag) 1-(2-phenyl-2-oxoethyl)-3-(2-(acetoxy)ethylaminomethyl)pyridineboronic or other pharmaceutically acceptable salts;
(ah) 1-(2-phenylamino-2-oxoethyl)-3-(vinylsulfonylacetamido)pyridinethione or other pharmaceutically acceptable salts;
(ai) 1-(2-phenylamino-2-oxoethyl)-3-((4-(were)sulfonylhydrazide)pyridinethione or other pharmaceutically acceptable salts;
(aj) 1-(2-phenyl-2-ox is(ak) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(phenylcarbonylamino)pyridineboronic or other pharmaceutically acceptable salts;
(al) 1-(2-ethoxy-2-oxoethyl)-3-((phenylmethyl)sulfonylhydrazide)pyridineboronic or other pharmaceutically acceptable salts;
(am) 1-(2-phenyl-2-oxoethyl)-3-((phenylmethyl)sulfonylhydrazide)pyridineboronic or other pharmaceutically acceptable salts;
(an) N,N'-bis[3-carbonyl-1-(2-furan-2'-yl-2-oxoethyl)pyridine]gidrazzingidrate or other pharmaceutically acceptable salts;
(JSC) 1-(2', 4'-dichlorophenyl-2-oxoethyl)-3-(2-methoxyethylamine)-pyridineboronic or other pharmaceutically acceptable salts;
(ar) 1-(2-Tien-2'-yl-2-oxoethyl)-3-((2-methoxyethyl)aminocarbonyl)-5-bromopyrimidine or other pharmaceutically acceptable salts;
(aq) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridinethione or other pharmaceutically acceptable salts;
(Ah) 1-(2-Tien-2 Il-2-oxoethyl)-3-(2-(2-chloro-3-pyridyl)hydrazinophenyl)-pyridinethione or other pharmaceutically acceptable salts;
(as) 1-(2-cyclopropylamino-2-oxoethyl)-3-(2-methoxyethylamine)-pyridinethione or other pharmaceutically acceptable salts;
(at) 1-(2-isopropylamino-2-oxoethyl)-3-(2-methylsulfonylbenzoyl)-pyridinethione or other pharmaceutically acceptable salts;
(AI) rmaceuticals acceptable salts;
(av) 1-(2-Tien-2'-yl-2-oxoethyl)-3-[2-(benzoyloxy)ethylaminomethyl]-pyridineboronic or other pharmaceutically acceptable salts;
(aw) 1-(4-ethoxy-2,4-DIOXOLANYL)-3-(2-(benzoyloxy)ethylaminomethyl)-pyridinethione or other pharmaceutically acceptable salts;
(Ah) 1-(2-Tien-2'-yl-2-oxoethyl)-3-[1-oxo-1-(2-methoxycarbonyl)pyridyl] hydrazinopyridazine or other pharmaceutically acceptable salts;
(AU) 1-[1-(2-Tien-2'-yl-2-oxoethyl)-5-aminocarbonyl-3-carbonitriding] -2-[1-(2-Tien-2'-yl-2-oxoethyl)-3-carbonitriding]hereinbefore or other pharmaceutically acceptable salts;
(az) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(triftormetilfullerenov)-pyridineboronic or other pharmaceutically acceptable salts;
(ba) 1-[1-(2-Tien-2'-yl-2-oxoethyl)-6-methyl-3-carbonitriding]-2-[1-(2-Tien-2'-yl-2-oxoethyl)-3-carbonitriding] hereinbefore or other pharmaceutically acceptable salts;
(bb) N, N'-bis[3-carbonyl-1-(2-(5-methyltin-2-yl)-2-oxoethyl)pyridine] hereinbefore or other pharmaceutically acceptable salts;
(bc) N,N'-bis[3-carbonyl-1-(2-(5-chlortan-2-yl)-2-oxoethyl)pyridine]hereinbefore or other pharmaceutically acceptable salts;
(bd) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(methanesulfonyl the Nile-1-(2-(4-nitration-2-yl)-2-oxoethyl)pyridine] hereinbefore or other pharmaceutically acceptable salts;
(bf) 1-(2-phenylamino-2-oxoethyl)-3-(phenylhydrazone)pyridinethione or other pharmaceutically acceptable salts;
(bg) 1-(2-(4-nitration-2-yl)-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridineboronic or other pharmaceutically acceptable salts;
(bh) 1-(2-(5-nitration-2-yl)-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridinethione or other pharmaceutically acceptable salts;
(bi) 1-(2-(5-chlortan-2-yl)-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridineboronic or other pharmaceutically acceptable salts;
(bk) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(isopropylaminocarbonyl)pyridineboronic or other pharmaceutically acceptable salts;
(b1) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(methanesulfonylaminoethyl)-5-bromopyrimidine or other pharmaceutically acceptable salts;
(bm) 1-(2-(2-ethoxycarbonylpyrimidine-1-yl)-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridinethione or other pharmaceutically acceptable salts;
(bn) 1-(2-(5-methyltin-2-yl)-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridinethione or other pharmaceutically acceptable salts;
(bo) 1-(2-(4-carbethoxytetramic-3-yl)-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridinethione hydrazinecarboxamide)pyridinethione or other pharmaceutically acceptable salts;
(bq) N, N'-bis[3-carbonyl-1-(2-(2-ethoxycarbonylpyrimidine-1-yl)-2-oxoethyl)pyridine] hereinbefore or other pharmaceutically acceptable salts;
(br) 1-(2-phenylamino-2-oxoethyl)-4-[2-(benzoyloxy)ethylaminomethyl] pyridinethione or other pharmaceutically acceptable salts;
(bs) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(phenylhydrazone)pyridineboronic or other pharmaceutically acceptable salts;
(bt) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(p-methoxyphenylhydrazine)pyridineboronic or other pharmaceutically acceptable salts;
(bu) 1-(2-ethoxy-2-oxoethyl)-3-(phenylaminopyrimidine)pyridineboronic or other pharmaceutically acceptable salts;
(bv) 1-(2-ethoxy-2-oxoethyl)-3-(p-colorselectionmodel)pyridineboronic or other pharmaceutically acceptable salts;
(bw) 1-(2-phenyl-2-oxoethyl)-3-(phenylaminopyrimidine)pyridineboronic or other pharmaceutically acceptable salts;
(b) 1-(2-phenylamino-2-oxoethyl)-3-(benzyltriethylammonium)pyridinethione or other pharmaceutically acceptable salts;
(by) 1-(2-phenyl-2-oxoethyl)-4-(methanesulfonylaminoethyl)pyridineboronic or other pharmaceutically acceptable salts;
salt;
(ca) 1-(2-ethoxy-2-oxoethyl)-4-[2-(benzoyloxy)ethylaminomethyl]pyridineboronic or other pharmaceutically acceptable salts;
(cb) 1-(2-ethoxy-2-oxoethyl)-3-(phenylhydrazone)pyridineboronic or other pharmaceutically acceptable salts;
(cc) 1-(2-phenyl-2-oxoethyl)-3-(p-methoxyphenylhydrazine)pyridineboronic or other pharmaceutically acceptable salts;
(cd) 1-(2-phenyl-2-oxoethyl)-4-[2-(benzoyloxy)ethylaminomethyl]pyridineboronic or other pharmaceutically acceptable salt; and
(ce) 1-(2-ethoxy-2-oxoethyl)-4-(p-methanesulfonylaminoethyl)pyridineboronic or other pharmaceutically acceptable salt.

7. 1-(2-Tien-2'-yl-2-oxoethyl)-3-(ethoxycarbonylmethylene)pyridineboronic or its pharmaceutically acceptable salt.

8. The method of obtaining derivatives of pyridinium salts under item 1, characterized in that the derivatives of pyridine of General formula (II)


subjected to interaction with the compound of the formula (III)
where R1, R2, R3, X and m have the meanings given in paragraph 1,
boiling in alcohol solvents and/or high-boiling solvents for onset 6 to 48 hours

9. Connection total lekarstvennogo tools for the treatment of diabetic complications and diseases associated with age, including renal disease, disorders of the nervous system, retinopathy, atherosclerosis, microangiopathy, endothelial dysfunction, dermatological disorders, darkening of the teeth and dysfunction of other organs.

11. The compound according to any one of paragraphs.9 and 10, representing
(a) N, N'-bis[3-carbonyl-1-(2-Tien-2'-yl-2-oxoethyl)-3-pyridine]gidrazzingidrate or other pharmaceutically acceptable salts;
(b) 1-(2-ethoxy-2-oxoethyl)-3-(2-(2-pyridyl)hydrazinophenyl)pyridineboronic or other pharmaceutically acceptable salts;
(c) 1-(2-ethoxy-2-oxoethyl)-3-(2-(benzoyloxy)ethylaminomethyl)pyridineboronic or other pharmaceutically acceptable salts;
(d) N,N'-bis[3-carbonyl-1-(2-phenyl-2-oxoethyl)pyridine]gidrazzingidrate or other pharmaceutically acceptable salts;
(e) 1-(2-phenyl-2-oxoethyl)-3-(hydrazinophenyl)pyridineboronic or other pharmaceutically acceptable salts;
(f) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridineboronic or other pharmaceutically acceptable salts;
(g) N,N'-bis[3-carbonyl-1-(2-(2,4-dichlorophenyl)-2-oxoethyl)pyridine]gidrazzingidrate or other pharmaceutically acceptable salts;
(h) 1-(2-phenyl-2-oxoethyl)-3-(methanesulfonylaminoethyl sulfonylhydrazide)pyridineboronic or other pharmaceutically acceptable salts;
(j) 1-(2-phenyl-2-oxoethyl)-3-(vinylsulfonylacetamido)pyridineboronic or other pharmaceutically acceptable salts;
(k) 1-(2-phenyl-2-oxoethyl)-2-chloro-3-(vinylsulfonylacetamido)pyridineboronic or other pharmaceutically acceptable salts;
(l) 1-(2-Tien-2'-yl-2-oxoethyl)-4-(2-(benzoyloxy)ethylaminomethyl)pyridineboronic or other pharmaceutically acceptable salts;
(m) 1-(2-(2,4-dichlorophenyl)-2-oxoethyl)-3-(2-(benzoyloxy)ethylaminomethyl)pyridineboronic or other pharmaceutically acceptable salts;
(n) 1-(2-phenyl-2-oxoethyl)-3-((2-(methoxy)carbonyl)ethoxycarbonyl)pyridineboronic or other pharmaceutically acceptable salts;
(o) 1-(2-ethoxy-2-oxoethyl)-3-(2-(benzoyloxy)ethoxycarbonyl)pyridineboronic or other pharmaceutically acceptable salts;
(aa) N,N'-bis[3-carbonyl-1-(2-Tien-2'-yl-2-oxoethyl)pyridine]hereinbefore or other pharmaceutically acceptable salts;
(ab) N, N'-bis-[3-carbonyl-1-(2-cyclopropylamino-2-oxoethyl)pyridine] hereinbefore or other pharmaceutically acceptable salts;
(ac) 1-(2-phenylamino-2-oxoethyl)-4-(vinylsulfonylacetamido)pyridinethione or other pharmaceutically acceptable salts;
ad) 1-(2-(2',4'-dichlorophenyl)-2-oxoproline-2-oxoethyl)-3-((benzoyloxy)ethylaminomethyl)pyridinethione or other pharmaceutically acceptable salts;
(af) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(phenylaminopyrimidine)pyridineboronic or other pharmaceutically acceptable salts;
(ag) 1-(2-phenyl-2-oxoethyl)-3-(2-(acetoxy)ethylaminomethyl)pyridineboronic or other pharmaceutically acceptable salts;
(ah) 1-(2-phenylamino-2-oxoethyl)-3-(vinylsulfonylacetamido)pyridinethione or other pharmaceutically acceptable salts;
(ai) 1-(2-phenylamino-2-oxoethyl)-3-((4-(were)sulfonylhydrazide)pyridinethione or other pharmaceutically acceptable salts;
(aj) 1-(2-phenyl-2-oxoethyl)-3-(2-(benzoyloxy)ethoxycarbonyl)pyridineboronic or other pharmaceutically acceptable salts;
(ak) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(phenylcarbonylamino)pyridineboronic or other pharmaceutically acceptable salts;
(A1) 1-(2-ethoxy-2-oxoethyl)-3-((phenylmethyl)sulfonylhydrazide)pyridineboronic or other pharmaceutically acceptable salts;
(am) 1-(2-phenyl-2-oxoethyl)-3-((phenylmethyl)sulfonylhydrazide)pyridineboronic or other pharmaceutically acceptable salts;
(an) N,N'-bis[3-carbonyl-1-(2-furan-2'-yl-2-oxoethyl)pyridine]gidrazzingidrate or other pharmaceutically acceptable salts;
(JSC) 1-(2', 4'-dichloride;
(ar) 1-(2-Tien-2'-yl-2-oxoethyl)-3-((2-methoxyethyl)aminocarbonyl)-5-bromopyrimidine or other pharmaceutically acceptable salts;
(aq) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridinethione or other pharmaceutically acceptable salts;
(Ah) 1-(2-Tien-2 Il-2-oxoethyl)-3-(2-(2-chloro-3-pyridyl)hydrazinophenyl)-pyridinethione or other pharmaceutically acceptable salts;
(as) 1-(2-cyclopropylamino-2-oxoethyl)-3-(2-methoxyethylamine)-pyridinethione or other pharmaceutically acceptable salts;
(at) 1-(2-isopropylamino-2-oxoethyl)-3-(2-methylsulfonylbenzoyl)-pyridinethione or other pharmaceutically acceptable salts;
(AI) 1-(2-phenylamino-2-oxoethyl)-3-({ 2-(1-oxo-3-cyclohexyl)propyl}-hydrazinophenyl)pyridineboronic or other pharmaceutically acceptable salts;
(av) 1-(2-Tien-2'-yl-2-oxoethyl)-3-[2-(benzoyloxy)ethylaminomethyl]-pyridineboronic or other pharmaceutically acceptable salts;
(aw) 1-(4-ethoxy-2,4-DIOXOLANYL)-3-(2-(benzoyloxy)ethylaminomethyl)-pyridinethione or other pharmaceutically acceptable salts;
(Ah) 1-(2-Tien-2'-yl-2-oxoethyl)-3-[1-oxo-1-(2-methoxycarbonyl)pyridyl] hydrazinopyridazine or other pharmaceuticles)-3-carbonitriding]hereinbefore or other pharmaceutically acceptable salts;
(az) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(triftormetilfullerenov)-pyridineboronic or other pharmaceutically acceptable salts;
(ba) 1-[1-(2-Tien-2'-yl-2-oxoethyl)-6-methyl-3-carbonitriding]-2-[1-(2-Tien-2'-yl-2-oxoethyl)-3-carbonitriding] hereinbefore or other pharmaceutically acceptable salts;
(bb) N, N'-bis[3-carbonyl-1-(2-(5-methyltin-2-yl)-2-oxoethyl)pyridine] hereinbefore or other pharmaceutically acceptable salts;
(bc) N,N'-bis[3-carbonyl-1-(2-(5-chlortan-2-yl)-2-oxoethyl)pyridine]hereinbefore or other pharmaceutically acceptable salts;
(bd) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(methanesulfonylaminoethyl)-6-methylpyridinium or other pharmaceutically acceptable salts;
(be) N, N'-bis[3-carbonyl-1-(2-(4-nitration-2-yl)-2-oxoethyl)pyridine] hereinbefore or other pharmaceutically acceptable salts;
(bf) 1-(2-phenylamino-2-oxoethyl)-3-(phenylhydrazone)pyridinethione or other pharmaceutically acceptable salts;
(bg) 1-(2-(4-nitration-2-yl)-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridineboronic or other pharmaceutically acceptable salts;
(bh) 1-(2-(5-nitration-2-yl)-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridinethione or druryidligibe or other pharmaceutically acceptable salts;
(bk) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(isopropylaminocarbonyl)pyridineboronic or other pharmaceutically acceptable salts;
(b1) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(methanesulfonylaminoethyl)-5-bromopyrimidine or other pharmaceutically acceptable salts;
(bm) 1-(2-(2-ethoxycarbonylpyrimidine-1-yl)-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridinethione or other pharmaceutically acceptable salts;
(bn) 1-(2-(5-methyltin-2-yl)-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridinethione or other pharmaceutically acceptable salts;
(bo) 1-(2-(4-carbethoxytetramic-3-yl)-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridinethione or other pharmaceutically acceptable salts;
(b) 1-(2-(4-benzylpiperidine-1-yl)-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridinethione or other pharmaceutically acceptable salts;
(bq) N, N'-bis[3-carbonyl-1-(2-(2-ethoxycarbonylpyrimidine-1-yl)-2-oxoethyl)pyridine] hereinbefore or other pharmaceutically acceptable salts;
(br) 1-(2-phenylamino-2-oxoethyl)-4-[2-(benzoyloxy)ethylaminomethyl] pyridinethione or other pharmaceutically acceptable salts;
(bs) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(phenylhydrazone)pyridinedicarboxylic)pyridineboronic or other pharmaceutically acceptable salts;
(bu) 1-(2-ethoxy-2-oxoethyl)-3-(phenylaminopyrimidine)pyridineboronic or other pharmaceutically acceptable salts;
(bv) 1-(2-ethoxy-2-oxoethyl)-3-(p-colorselectionmodel)pyridineboronic or other pharmaceutically acceptable salts;
(bw) 1-(2-phenyl-2-oxoethyl)-3-(phenylaminopyrimidine)pyridineboronic or other pharmaceutically acceptable salts;
(b) 1-(2-phenylamino-2-oxoethyl)-3-(benzyltriethylammonium)pyridinethione or other pharmaceutically acceptable salts;
(by) 1-(2-phenyl-2-oxoethyl)-4-(methanesulfonylaminoethyl)pyridineboronic or other pharmaceutically acceptable salts;
(bz) 1-(2-phenyl-2-oxoethyl)-3-(phenylhydrazone)pyridineboronic or other pharmaceutically acceptable salts;
(ca) 1-(2-ethoxy-2-oxoethyl)-4-[2-(benzoyloxy)ethylaminomethyl]pyridineboronic or other pharmaceutically acceptable salts;
(cb) 1-(2-ethoxy-2-oxoethyl)-3-(phenylhydrazone)pyridineboronic or other pharmaceutically acceptable salts;
(cc) 1-(2-phenyl-2-oxoethyl)-3-(p-methoxyphenylhydrazine)pyridineboronic or other pharmaceutically acceptable salts;
(cd) 1-(2-phenyl-2-oxoethyl)-4-[2-(benzoyloxy)ESA)-4-(p-methanesulfonylaminoethyl)pyridineboronic or other pharmaceutically acceptable salt.

12. 1-(2-Tien-2'-yl-2-oxoethyl)-3-(ethoxycarbonylmethylene)pyridineboronic or its pharmaceutically acceptable salt according to p. 7 for obtaining a medicinal product for the treatment of diabetic complications and diseases associated with age, including renal disease, disorders of the nervous system, retinopathy, atherosclerosis, microangiopathy, endothelial dysfunction, dermatological disorders, darkening of the teeth and dysfunction of other organs.

13. Pharmaceutical composition having AGE-destructive activity, comprising a pharmaceutically effective amount of one or more compounds of General formula (I), as defined in paragraph 1, or its pharmaceutically acceptable salts (salts) in a mixture with a pharmaceutically acceptable carrier, diluent, solvent or excipient.

14. The pharmaceutical composition according to p. 13 for the treatment of diabetic complications and age-related diseases, which comprises a pharmaceutically effective amount of one or more compounds of General formula (I), as defined in paragraph 1, or its pharmaceutically acceptable salts (salts) in a mixture with a pharmaceutically acceptable carrier, diluent, solvent or excipient.

15. The pharmaceutical composition is an objective number 1-(2-Tien-2'-yl-2-oxoethyl)-3-(ethoxycarbonylmethylene)pyridinylamino or its pharmaceutically acceptable salts (salts) in a mixture with a pharmaceutically acceptable carrier, diluent, solvent or excipient.

16. The pharmaceutical composition according to any one of paragraphs.13-15 in the form intended for oral administration.

17. The pharmaceutical composition according to any one of paragraphs.13-15, where the specified pharmaceutically acceptable carrier is chosen from one or more of the compounds: starch, lactose, polyvinylpyrrolidone (K-30), talc and magnesium stearate.

18. The pharmaceutical composition according to any one of paragraphs.13-15 in the form of compositions for parenteral administration.

19. The pharmaceutical composition according to any one of paragraphs.13-15 in the form of lotions, gargle for mouth and tooth paste.

20. The pharmaceutical composition according to any one of paragraphs.13, 14, 16 - 19, where the aforementioned compound or compounds selected from the group including
(a) N, N'-bis[3-carbonyl-1-(2-Tien-2'-yl-2-oxoethyl)-3-pyridine]gidrazzingidrate or other pharmaceutically acceptable salts;
(b) 1-(2-ethoxy-2-oxoethyl)-3-(2-(2-pyridyl)hydrazinophenyl)pyridineboronic or other pharmaceutically acceptable salts;
(c) 1-(2-ethoxy-2-oxoethyl)-3-(2-(benzoyloxy)ethylaminomethyl)pyridineboronic or other pharmaceutically acceptable salts;
(d) N,N'-bis[3-carbonyl-1-(2-phenyl-2-oxoethyl)pyridine]gidrazzingidrate or other pharmaceutically pickup is ielemia salt;
(f) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridineboronic or other pharmaceutically acceptable salts;
(g) N,N'-bis[3-carbonyl-1-(2-(2,4-dichlorophenyl)-2-oxoethyl)pyridine]gidrazzingidrate or other pharmaceutically acceptable salts;
(h) 1-(2-phenyl-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridineboronic or other pharmaceutically acceptable salts;
(i) 1-(2-ethoxy-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridineboronic or other pharmaceutically acceptable salts;
(j) 1-(2-phenyl-2-oxoethyl)-3-(vinylsulfonylacetamido)pyridineboronic or other pharmaceutically acceptable salts;
(k) 1-(2-phenyl-2-oxoethyl)-2-chloro-3-(vinylsulfonylacetamido)pyridineboronic or other pharmaceutically acceptable salts;
(l) 1-(2-Tien-2'-yl-2-oxoethyl)-4-(2-(benzoyloxy)ethylaminomethyl)pyridineboronic or other pharmaceutically acceptable salts;
(m) 1-(2-(2,4-dichlorophenyl)-2-oxoethyl)-3-(2-(benzoyloxy)ethylaminomethyl)pyridineboronic or other pharmaceutically acceptable salts;
(n) 1-(2-phenyl-2-oxoethyl)-3-(2-(methoxy)carbonyl)ethoxycarbonylpyrimidine or other pharmaceutically acceptable salts;
(o) 1-(2-ethoxy-2-oxoethyl)-3-(2-(barebones-1-(2-Tien-2'-yl-2-oxoethyl)pyridine]hereinbefore or other pharmaceutically acceptable salts;
(ab) N, N'-bis-[3-carbonyl-1-(2-cyclopropylamino-2-oxoethyl)pyridine] hereinbefore or other pharmaceutically acceptable salts;
(ac) 1-(2-phenylamino-2-oxoethyl)-4-(vinylsulfonylacetamido)pyridinethione or other pharmaceutically acceptable salts;
ad) 1-(2-(2',4'-dichlorophenyl)-2-oxoethyl)-3-(2(methoxy)ethoxycarbonyl)pyridineboronic or other pharmaceutically acceptable salts;
(ae) 1-(2-phenylamino-2-oxoethyl)-3-((benzoyloxy)ethylaminomethyl)pyridinethione or other pharmaceutically acceptable salts;
(af) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(phenylaminopyrimidine)pyridineboronic or other pharmaceutically acceptable salts;
(ag) 1-(2-phenyl-2-oxoethyl)-3-(2-(acetoxy)ethylaminomethyl)pyridineboronic or other pharmaceutically acceptable salts;
(ah) 1-(2-phenylamino-2-oxoethyl)-3-(vinylsulfonylacetamido)pyridinethione or other pharmaceutically acceptable salts;
(ai) 1-(2-phenylamino-2-oxoethyl)-3-((4-(were)sulfonylhydrazide)pyridinethione or other pharmaceutically acceptable salts;
(aj) 1-(2-phenyl-2-oxoethyl)-3-(2-(benzoyloxy)ethoxycarbonyl)pyridineboronic or other pharmaceutically acceptable salts;
(ak) 1-(2-Tien-2'-and what if;
(A1) 1-(2-ethoxy-2-oxoethyl)-3-((phenylmethyl)sulfonylhydrazide)pyridineboronic or other pharmaceutically acceptable salts;
(am) 1-(2-phenyl-2-oxoethyl)-3-((phenylmethyl)sulfonylhydrazide)pyridineboronic or other pharmaceutically acceptable salts;
(an) N,N'-bis[3-carbonyl-1-(2-furan-2'-yl-2-oxoethyl)pyridine]gidrazzingidrate or other pharmaceutically acceptable salts;
(JSC) 1-(2', 4'-dichlorophenyl-2-oxoethyl)-3-(2-methoxyethylamine)-pyridineboronic or other pharmaceutically acceptable salts;
(ar) 1-(2-Tien-2'-yl-2-oxoethyl)-3-((2-methoxyethyl)aminocarbonyl)-5-bromopyrimidine or other pharmaceutically acceptable salts;
(aq) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridinethione or other pharmaceutically acceptable salts;
(Ah) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(2-(2-chloro-3-pyridyl)hydrazinophenyl)-pyridinethione or other pharmaceutically acceptable salts;
(as) 1-(2-cyclopropylamino-2-oxoethyl)-3-(2-methoxyethylamine)-pyridinethione or other pharmaceutically acceptable salts;
(at) 1-(2-isopropylamino-2-oxoethyl)-3-(2-methylsulfonylbenzoyl)-pyridinethione or other pharmaceutically acceptable salts;
(AI)farmacevtichesky acceptable salts;
(av) 1-(2-Tien-2'-yl-2-oxoethyl)-3-[2-(benzoyloxy)ethylaminomethyl]-pyridineboronic or other pharmaceutically acceptable salts;
(aw) 1-(4-ethoxy-2,4-DIOXOLANYL)-3-(2-(benzoyloxy)ethylaminomethyl)-pyridinethione or other pharmaceutically acceptable salts;
(Ah) 1-(2-Tien-2'-yl-2-oxoethyl)-3-[1-oxo-1-(2-methoxycarbonyl)pyridyl] hydrazinopyridazine or other pharmaceutically acceptable salts;
(AU) 1-[1-(2-Tien-2'-yl-2-oxoethyl)-5-aminocarbonyl-3-carbonitriding] -2-[1-(2-Tien-2'-yl-2-oxoethyl)-3-carbonitriding]hereinbefore or other pharmaceutically acceptable salts;
(az) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(triftormetilfullerenov)-pyridineboronic or other pharmaceutically acceptable salts;
(ba) 1-[1-(2-Tien-2'-yl-2-oxoethyl)-6-methyl-3-carbonitriding]-2-[1-(2-Tien-2'-yl-2-oxoethyl)-3-carbonitriding] hereinbefore or other pharmaceutically acceptable salts;
(bb) N, N'-bis[3-carbonyl-1-(2-(5-methyltin-2-yl)-2-oxoethyl)pyridine] hereinbefore or other pharmaceutically acceptable salts;
(b) N,N'-bis[3-carbonyl-1-(2-(5-chlortan-2-yl)-2-oxoethyl)pyridine]hereinbefore or other pharmaceutically acceptable salts;
(bd) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(methanesulfonyl is of IMT-1-(2-(4-nitration-2-yl)-2-oxoethyl)pyridine] hereinbefore or other pharmaceutically acceptable salts;
(bf) 1-(2-phenylamino-2-oxoethyl)-3-(phenylhydrazone)pyridinethione or other pharmaceutically acceptable salts;
(bg) 1-(2-(4-nitration-2-yl)-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridineboronic or other pharmaceutically acceptable salts;
(bh) 1-(2-(5-nitration-2-yl)-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridinethione or other pharmaceutically acceptable salts;
(bi) 1-(2-(5-chlortan-2-yl)-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridineboronic or other pharmaceutically acceptable salts;
(bk) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(isopropylaminocarbonyl)pyridineboronic or other pharmaceutically acceptable salts;
(b1) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(methanesulfonylaminoethyl)-5-bromopyrimidine or other pharmaceutically acceptable salts;
(bm) 1-(2-(2-ethoxycarbonylpyrimidine-1-yl)-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridinethione or other pharmaceutically acceptable salts;
(bn) 1-(2-(5-methyltin-2-yl)-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridinethione or other pharmaceutically acceptable salts;
(bo) 1-(2-(4-carbethoxytetramic-3-yl)-2-oxoethyl)-3-(methanesulfonylaminoethyl)pyridinethione hydrazinecarboxamide)pyridinethione or other pharmaceutically acceptable salts;
(bq) N, N'-bis[3-carbonyl-1-(2-(2-ethoxycarbonylpyrimidine-1-yl)-2-oxoethyl)pyridine] hereinbefore or other pharmaceutically acceptable salts;
(br) 1-(2-phenylamino-2-oxoethyl)-4-[2-(benzoyloxy)ethylaminomethyl] pyridinethione or other pharmaceutically acceptable salts;
(bs) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(phenylhydrazone)pyridineboronic or other pharmaceutically acceptable salts;
(bt) 1-(2-Tien-2'-yl-2-oxoethyl)-3-(p-methoxyphenylhydrazine)pyridineboronic or other pharmaceutically acceptable salts;
(bu) 1-(2-ethoxy-2-oxoethyl)-3-(phenylaminopyrimidine)pyridineboronic or other pharmaceutically acceptable salts;
(bv) 1-(2-ethoxy-2-oxoethyl)-3-(p-colorselectionmodel)pyridineboronic or other pharmaceutically acceptable salts;
(bw) 1-(2-phenyl-2-oxoethyl)-3-(phenylaminopyrimidine)pyridineboronic or other pharmaceutically acceptable salts;
(b) 1-(2-phenylamino-2-oxoethyl)-3-(benzyltriethylammonium)pyridinethione or other pharmaceutically acceptable salts;
(by) 1-(2-phenyl-2-oxoethyl)-4-(methanesulfonylaminoethyl)pyridineboronic or other pharmaceutically acceptable salts;
salt;
(ca) 1-(2-ethoxy-2-oxoethyl)-4-[2-(benzoyloxy)ethylaminomethyl]pyridineboronic or other pharmaceutically acceptable salts;
(cb) 1-(2-ethoxy-2-oxoethyl)-3-(phenylhydrazone)pyridineboronic or other pharmaceutically acceptable salts;
(cc) 1-(2-phenyl-2-oxoethyl)-3-(p-methoxyphenylhydrazine)pyridineboronic or other pharmaceutically acceptable salts;
(cd) 1-(2-phenyl-2-oxoethyl)-4-[2-(benzoyloxy)ethylaminomethyl]pyridineboronic or other pharmaceutically acceptable salt; and
(ce) 1-(2-ethoxy-2-oxoethyl)-4-(p-methanesulfonylaminoethyl)pyridineboronic or other pharmaceutically acceptable salt.

21. The production method of the composition for parenteral administration by p. 18, where the method involves the dissolution of the active ingredient of General formula (I), under item 1 in polyethylene glycol 400 and dilution thus obtained solution of saline or water to the desired concentration.

22. A method of treating diabetic patients by destroying pre-formed in the specified patient AGE, which includes the introduction of an effective amount of the compounds on p. 1, either alone or in combination with other medicines for protevtive the data age, which includes the introduction in need of such treatment to the patient an effective amount of the compounds of formula (I), p. 1, either alone or in combination with a pharmaceutically acceptable carrier, diluent or excipient.

24. The method according to p. 22, which is a disease that prevent or treat is nephrological disease, neurological disease, atherosclerosis, impaired retina, dermatological disease, not associated with enzymes polarisavenue mouth, endothelial dysfunction or dysfunction of other organs and impaired growth.

 

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The invention relates to 2-(iminomethyl)aminoaniline derivative of General formula I, And where the aromatic residue of the formula Ia, R1and R2independently H, halogen, HE, linear or branched C1-C6alkyl, linear or branched C1-C6alkoxyl, R3-H, linear or branched C1-C6alkyl, or-COR4where R4-C1-C6alkyl or the residue IC, linear or branched C1-C6the five-membered alkyl or a heterocycle containing 1-4 heteroatoms selected from O, S, N, and in particular: thiophene, furan, pyrrole or thiazole, carbon atoms which is unsubstituted or substituted by one or more groups selected from linear or branched C1-C6of alkyl, C1-C6alkoxyl or halogen; X is-CO-N(R3)-X'-, -NH-CO-X'-, -CH=,-CO -, or a bond, and X' represents -(CH2)n- where n = 0-6; Y means Y'-, -Y'-NH-CO-, -CO-Y', Y'-CO-, -N(R3)-Y'-, -Y,-N(R3)-, Y'-CH2-N(R3)-CO-, -Y'-O-, -Y'-O-Y' - or a bond, and Y' is -(CH2)n- where n = 0-6; Неt-pyrrole, pyrrolidine, furan, thiophene, imidazole, imidazoline, oxazole, isoxazol, oxazoline, isoxazole, thiazole, thiazoline, thiazolidine, thiazolidine, azetidine, piperidine, imidazolidine, they

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The invention relates to 1,4-disubstituted the piperazines of General formula I, the method of production thereof, containing compositions and their use for the clinical treatment of painful conditions, increased pain sensitivity and/or inflammatory conditions in which the pathophysiological role of C-fibers, causing neurogenic pain or inflammation

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The invention relates to new substituted derivatives of piperidine derivatives, to processes for their preparation, to pharmaceutical compositions and to their use in medical therapy, particularly in treatment of psychotic disorders

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< / BR>
and their pharmaceutically acceptable salts, where R1is hydrogen, C1-C6-alkyl, C2-C6alkenyl, C3-C8-cycloalkyl, C6-C10aryl that may be substituted for CH3, halogen, OR5where R5- C1-C6-alkyl, C1-C2-alkyl-heteroaryl containing as heteroatoms of S, N or O; And a is phenyl, substituted carbonyl or amino group; - C6-C10-aryl or C5-C10-heteroaryl containing as heteroatoms of S, N or O

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di-(C1-C6)alkylamino-C1-C6by alkyl, hydroxyl, formyl, carboxyla,1-C6alkoxycarbonyl,1-C6alkanoyloxy, thiol, carboxamido,1-C6alkanolamine,

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< / BR>
in which X denotes O or S;

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Ar denotes one of the following groups or WITH:

< / BR>
T represents hydrogen or (C1-C6)alkyl;

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as well as their additive salts with pharmaceutically acceptable acids or bases, and method of production thereof, pharmaceutical compositions and drug manifesting gipolipedimecescoe and antiatherosclerotic action based on them
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