Amidinov compounds and pharmaceutical composition having factor xa inhibitory activity

 

Describes new compounds of amidine formula (I), where R represents a group of formula a), b) or C), R4is a hydrogen atom or halogen atom, R5is a hydrogen atom, cyano-, carboxy - or lower alkoxycarbonyl group, R6- the hydrogen atom of the hydroxy-, carboxy-, lower alkoxycarbonyl group, phenyl group which is optionally substituted by amidinopropane; pyridyl, optionally substituted by 1-3 substituents selected from lower alkyl groups, benzoylamino, hinely, pyrimidyl, X2is an oxygen atom, a sulfur atom, X3- (CH2)m, where m is 0, an integer from 1 to 3, X4- -C(=NH)-, -SO2NH-, pyridinyl, or a direct link; X5- Allenova group containing 1-6 carbon atoms, alkenylamine group containing 2-6 carbon atoms, or a direct bond; R7is a hydrogen atom or the groupwhere R9- NH, NR11where R11- lower alkyl group, benzyl group, R10lower alkyl group or amino group, R8- cycloalkyl group, optionally substituted by carboxypropyl; phenyl group, benzyl group, Y1is an oxygen atom or-NR12-, R12-Y6-R13, R13is a hydrogen atom, NY, - or -(Y6-CO -, - COCO2- or -(CH2)r), r = 0, 1, Y2is an oxygen atom or a simple bond; Y3- pyridinyl orwhere s and t are the same or different and each is an integer from 1 to 3, Y4- CO-, -CONH-, -CH=CH-, Y5- -CH2)p, -CH AK(CH2)p"orAK - lower alkyl group, p is 0 or an integer from 1 to 3, R"is 0; And - a group of the formulaj is 1, K is 0, m and n are the same and each is an integer 1, R1, R2and R3the same or different and each represents hydrogen or a hydroxy-group, or its salt. Technical result: the compounds possess inhibitory activity against factor in the blood coagulation Ha. Describes a pharmaceutical composition having factor XA inhibitory action on the basis of the claimed compounds. 2 C. and 10 C.p. f-crystals, 15 PL.



or

Description text in facsimile form (see graphic part). T T T T Tr


Formula izaberete the PU formula (a), b) or (C)


or

where R4represents a hydrogen atom or a halogen atom;
R5represents a hydrogen atom, a cyano, carboxypropyl or lower alkoxycarbonyl group;
R6represents a hydrogen atom, a hydroxy-group, carboxypropyl, lower alkoxycarbonyl group, phenyl group, optionally substituted by amidinopropane, heteroaryl group (where specified heteroaryl group selected from the group pyridyl, chinoline and pyrimidyl, and where specified Peregrina group optionally substituted by 1-3 substituents selected from lower alkyl groups and benzoylamino);
X2represents an oxygen atom, a sulfur atom;
X3represents -(CH2)m-, where m = 0 or an integer from 1 to 3;
X4represents-C(=NH)-, -SO2NH-group of formula (d)

or a direct link;
X5is a group of alkylene containing 1-6 carbon atoms, a group of Alcanena containing 2-6 carbon atoms, or a direct link;
R7represents a hydrogen atom or a group formset a lower alkyl group, or benzyl group;
R10represents a lower alkyl group, or amino group;
R8represents cycloalkyl group optionally substituted by carboxypropyl, phenyl group or benzyl group;
Y1represents an oxygen atom or-NR12- where R12represents-Y6-R13where R13represents a hydrogen atom, a lower alkyl group or a phenyl group(substituted carboxypropyl or lower alkoxycarbonyl group);
Y6represents-CO-, -COCO2- or -(CH2)rwhere r = 0 or 1;
Y2represents an oxygen atom or a simple bond;
Y3represents a group of formula (d) or f)

or

where s and t are the same or different and each is an integer from 1 to 3;
Y4represents-CO-, -CONH -, or-CH=CH-;
Y5represents -(CH2)p-Afternoon snack-(CH2)por a group of formula (h)

where AK represents a lower alkyl group;
p = 0 or an integer from 1 to 3;
R= 0;
ring And represents a group of formula (i) or (j)R1, R2and R3the same or different and each represents a hydrogen atom or a hydroxy-group,
or its salt.

2. Amidinov compound of the formula [I] by p. 1, where R represents a group of formula a) or b)

or

where R4, R5, R6X2X3X4X5, j and k have the meanings specified above,
or its salt.

3. Amidinov compound of the formula [I] according to p. 2, where R represents a group of formula (a)

where R4, R5, R6X2X3X4X5, j and k have the meanings specified above,
or its salt.

4. Amidinov compound of the formula [I] according to p. 2, where R represents a group of the formula

where R4, R5, R6X2X3X4X5, j and k have the meanings specified above,
or its salt.

5. Amidinov compound of the formula [I] according to p. 4, where X3represents -(CH2)m-, where m is defined above, X4represents a group of formula (d)

j = 1,
or its salt.

6. Amidinov compound of the formula [I] on p. 5, where R6p is astou communication, or its salt.

7. Amidinov compound of the formula [I] by p. 1, where R represents a group of formula (C)

where R7, R8, Y1, Y2, Y3, Y4, Y5, ring A, m and n have the meanings mentioned above,
or its salt.

8. Amidinov compound of the formula [I] according to p. 7, where the ring And represents a group of formula (i)

or its salt.

9. Amidinov connection on p. 1, which is selected from a group including:
1) 7-[1-(pyridine-4-yl)piperidine-4-ylethoxy] -1,2,3,4-tetrahydroisoquinoline-2-carboxamidine,
2) 7-[1-(quinoline-4-yl)piperidine-4-ylethoxy] -1,2,3,4-tetrahydroisoquinoline-2-carboxamidine,
3) the reaction of 7-[1-(pyridine-4-yl)piperidine-4-ylethoxy] -1,2,3,4-tetrahydroisoquinoline-2-carboxamide,
4) ethyl ester of 4-(2-amidino-1,2,3,4-tetrahydro-isoquinoline-7-intoximeter)-1-(pyridine-4-yl)piperidine-4-carboxylic acid,
5) 4-(2-amidino-1,2,3,4-tetrahydroisoquinoline-7-intoximeter)-1-(pyridine-4-yl)piperidine-4-carboxylic acid,
6) ethyl ester of 4-(2-amidino-1,2,3,4-tetrahydro-isoquinoline-7-intoximeter)-1-(2,6-dimethylpyridin-4-yl) piperidine-4-carboxylic acid,
7) 4-(2-amidino-1,2,3,4-tetrahydroisoquinoline-7-intoximeter)-1-(2,6-dimethylpyridin-4-yl)piperidine-4-carboxylic acid,
9) 4-(2-amidino-1,2,3,4-tetrahydroisoquinoline-7-intoximeter)-1-(pyrimidine-4-yl)piperidine-4-carboxylic acid,
10) ethyl ester 4-[2-(2-amidino-1,2,3,4-tetrahydro-isoquinoline-7-yloxy)ethyl]-1-(pyridine-4-yl)piperidine-4-carboxylic acid,
11) 4-[2-(2-amidino-1,2,3,4-tetrahydroisoquinoline-7-yloxy)ethyl] -1-(pyridine-4-yl)piperidine-4-carboxylic acid,
12) 4-[N-[5-amidino-1-(1-phenylethylamine)benzimidazole-2-ylmethyl] -N-[4-(1-acetamidopiperidine-4-yloxy) phenyl]benzoic acid
13) 4-[N-[5-amidino-1-(4-benzyloxycarbonylamino) benzimidazole-2-ylmethyl] -N-[4-(1-acetamidopiperidine-4-yloxy) phenyl]carbarnoyl]benzoic acid
14) 7-[1-(2-hydroxyethyl)piperidine-4-ylethoxy] -1,2,3,4-tetrahydroisoquinoline-2-carboxamidine,
15) 7-[1-(pyridine-4-ylmethyl)piperidine-4-ylethoxy] -1,2,3,4-tetrahydroisoquinoline-2-carboxamidine,
16) 7-(1-acetamidopiperidine-4-ylethoxy)-1,2,3,4-tetrahydroisoquinoline-2-carboxamidine,
17) 7-(1-phenylacetonitrile-4-ylethoxy)-1,2,3,4-tetrahydroisoquinoline-2-carboxamidine,
18) N-[2-[4-(2-amidino-1,2,3,4-tetrahydroisoquinoline-7-intoximeter)piperidine-1-yl]pyridin-5-yl]acetamide", she
19) N-[2-[4-(2-amidino-1,2,3,4-tetrahydroisoquinoline-7-intoximeter)piperidine-1-yl]pyridin-5-yl]benzamide,
20) ethyl ester 3-[4-[4-(2-amidino-1,2,3,4-amidino-1,2,3,4-tetrahydro-isoquinoline-7-intoximeter)piperidine-1-yl]pyridine-3-carboxylic acid,
22) 7-[2-[4-cyano-1-(pyridine-4-yl)piperidine-4-yl] ethoxy]-1,2,3,4-tetrahydroisoquinoline-2-carboxamidine,
23) 4-(2-amidino-1,2,3,4-tetrahydroisoquinoline-7-ylthio-methyl)-1-(pyridine-4-yl)piperidine-4-carboxylic acid,
24) 4-[2-(2-amidino-1,2,3,4-tetrahydroisoquinoline-7-ylthio) ethyl] -1-(pyridine-4-yl)piperidine-4-carboxylic acid,
25) trance-4-[2-[4-(1-acetamidopiperidine-4-yloxy) phenoxymethyl]-5-amidinotransferase-1-recetelenmesi]cyclohexanecarbonyl acid,
26) 2-[4-(1-acetamidopiperidine-4-yloxy)phenoxymethyl] -1-phenacylbromides-5-carboxamidine,
27) 1-(cyclohexylcarbonyl)-2-[N-[1-(pyridine-4-yl) piperidine-4-yl] -N-amoxillisinopril]benzimidazole-5-carboxamidine,
28) N-[5-amidino-1-(cyclohexylcarbonyl)benzimidazole-2-ylmethyl]-N-[1-(pyridine-4-yl)piperidine-4-yl] aminosilane acid,
29) 2-[N-[4-(1-acetamidopiperidine-4-yloxy)phenyl] -N-ethoxycarbonylmethylene]-1-(cyclohexylcarbonyl) benzimidazole-5-carboxamidine,
30) N-[5-amidino-1-cyclohexylcarbonyl)benzimidazole-2-ylmethyl] -N-[4-(1-acetamidopiperidine-4-yloxy)phenyl]carbamoylating acid,
31) 2-[N-[4-(1-amidinopropane-4-yloxy)phenyl] -N-(4-methoxycarbonylbenzyl)aminomethyl] -1-cyclohexylcarbonyl) benzimidazole-5-carboxamide] carbamoylating acid,
33) N-benzyl-4-(2-amidino-1,2,3,4-tetrahydroisoquinoline-7-intoximeter)piperidine-1-sulfonamide,
34) ethyl ester 3-[4-[4-(2-amidino-1,2,3,4-tetrahydroisoquinoline-7-intoximeter)piperidine-1-yl]pyridine-3-yl] propionic acid,
35) 3-[4-[4-(2-amidino-1,2,3,4-tetrahydroisoquinoline-7-intoximeter)piperidine-1-yl]pyridine-3-yl]propionic acid,
36) ethyl ester of 4-(2-amidino-1,2,3,4-tetrahydro-isoquinoline-7-intoximeter)-1-(2,6-dimethylpyridin-4-yl) piperidine-4-carboxylic acid,
37) ethyl ester of 4-(2-amidino-1,2,3,4-tetrahydro-isoquinoline-7-intoximeter)-1-(2-methylpyridin-4-yl)piperidine-4-carboxylic acid,
or their salt.

10. Amidinov connection on p. 3, which is selected from the group including
1) 7-[1-(pyridine-4-yl)piperidine-4-ylethoxy] -1,2,3,4-tetrahydroisoquinoline-2-carboxamidine,
2) 7-[1-(quinoline-4-yl)piperidine-4-ylethoxy] -1,2,3,4-tetrahydroisoquinoline-2-carboxamidine,
3) the reaction of 7-[1-(pyridine-4-yl)piperidine-4-ylethoxy]-1,2,3,4-tetrahydroisoquinoline-2-carboxamide,
4) ethyl ester of 4-(2-amidino-1,2,3,4-tetrahydro-isoquinoline-7-intoximeter)-1-(pyridine-4-yl)piperidine-4-carboxylic acid,
5) 4-(2-amidino-1,2,3,4-tetrahydroisoquinoline-7-yloxy-methyl)-1-(pyridine-4-yl)piperidine-4-carboxylic acid,
6) ethyl ester of 4-(2-amidino-1,2,3,4-tetrahydro-Ishino inolin-7-intoximeter)-1-(2,6-dimethylpyridin-4-yl)piperidine-4-carboxylic acid,
8) 4-(2-amidino-1,2,3,4-tetrahydroisoquinoline-7-intoximeter)-1-(2-methylpyridin-4-yl)piperidine-4-carboxylic acid,
9) 4-(2-amidino-1,2,3,4-tetrahydroisoquinoline-7-intoximeter)-1-(pyrimidine-4-yl)piperidine-4-carboxylic acid,
10) ethyl ester 4-[2-(2-amidino-1,2,3,4-tetrahydro-isoquinoline-7-yloxy)ethyl]-1-(pyridine-4-yl)piperidine-4-carboxylic acid,
11) 4-[2-(2-amidino-1,2,3,4-tetrahydroisoquinoline-7-yloxy)ethyl] -1-(pyridine-4-yl)piperidine-4-carboxylic acid,
12) 7-[1-(2-hydroxyethyl)piperidine-4-ylethoxy] -1,2,3,4-tetrahydroisoquinoline-2-carboxamidine,
13) 7-[1-(pyridine-4-ylmethyl)piperidine-4-ylethoxy] -1,2,3,4-tetrahydroisoquinoline-2-carboxamidine,
14) 7-(1-acetamidopiperidine-4-ylethoxy)-1,2,3,4-tetrahydroisoquinoline-2-carboxamidine,
15) 7-(1-phenylacetonitrile-4-ylethoxy)-1,2,3,4-tetrahydroisoquinoline-2-carboxamidine,
16) N-[2-[4-(2-amidino-1,2,3,4-tetrahydroisoquinoline-7-intoximeter)piperidine-1-yl]pyridin-5-yl]benzamide,
17) ethyl ester 3-[4-[4-(2-amidino-1,2,3,4-tetrahydro-isoquinoline-7-intoximeter)piperidine-1-yl]pyridine-3-yl]-2-propanolol acid,
18) methyl ester of 4-[4-(2-amidino-1,2,3,4-tetrahydroisoquinoline-7-intoximeter)piperidine-1-yl]pyridine-3-carboxylic acid,
19) 7-[2-[4-cyano-1-(pyridine-4-yl)piperidine-4-yl] ethoxy] -1,2,3,4-tetrahydro the-4-carboxylic acid,
21) 4-[2-(2-amidino-1,2,3,4-tetrahydroisoquinoline-7-ylthio) ethyl] -1-(pyridine-4-yl)piperidine-4-carboxylic acid,
22) N-benzyl-4-(2-amidino-1,2,3,4-tetrahydroisoquinoline-7-intoximeter)piperidine-1-sulfonamide,
23) ethyl ester 3-[4-[4-(2-amidino-1,2,3,4-tetrahydro-isoquinoline-7-intoximeter)piperidine-1-yl]pyridine-3-yl] propionic acid,
24) 3-[4-[4-(2-amidino-1,2,3,4-tetrahydroisoquinoline-7-intoximeter)piperidine-1-yl]pyridine-3-yl]propionic acid,
25) ethyl ester of 4-(2-amidino-1,2,3,4-tetrahydro-isoquinoline-7-intoximeter)-1-(2,6-dimethylpyridin-4-yl) piperidine-4-carboxylic acid,
26) ethyl ester of 4-(2-amidino-1,2,3,4-tetrahydro-isoquinoline-7-intoximeter)-1-(2-methylpyridin-4-yl)piperidine-4-carboxylic acid,
or their salts.

11. Pharmaceutical composition having factor XA inhibitory activity, including amidinov compound according to any one of paragraphs.1-10 or its salt as an active ingredient.

12. Amidinov connection on p. 1, where this salt is a hydrochloride or methanesulfonate.

Priority items:
10.04.1998 - p. 7;
25.08.1998 - PP.10 and 11;
09.04.1999 - PP.1-6, 8, 9, 12.

 

Same patents:

Arylalkylamine // 2201923
The invention relates to arylalkylamines formula I, where B - A, OA, NH2, CF3, aromatic heterocycle selected from pyridine, pyrazine and pyrimidine; Q is absent or denotes alkylene with 1-6 carbon atoms; R1and R2independently from each other represent OR5where R5- Or cycloalkyl with 3-7 carbon atoms; And the alkyl with 1-10 carbon atoms, and their physiologically acceptable salts

The invention relates to the derivatives of hintline formula I, where m is an integer from 1 to 2; R1represents hydrogen, nitro or1-3alkoxy; R2represents hydrogen or nitro; R3represents hydroxy, halogen, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy or cyano; X1represents-O-, -S-, -SO - or-SO2-; R4is one of 13 groups described in paragraph 1 of the claims

The invention relates to the derivatives of hintline formula I in which Z denotes-O-, -NH - or-S-; m = 1-5, integer, provided that when Z represents-NH-, m = 3 - 5; R1is hydrogen, C1-3alkoxy; R2is hydrogen; R3hydroxy, halogen, C1-3alkyl, C1-3-alkoxy, C1-3alkanoyloxy, trifluoromethyl or cyano; X1denotes-O-, -NR7, -NR8CO-, where R7and R8each is hydrogen, C1-3alkyl; R4choose one of the listed in paragraph 1 of the claims of the seven groups, except 4-(3,4,5-trimethoxyphenyl)-6,7-dimethoxyquinazoline, 4-(3-methoxybenzylthio)-6,7-dimethoxyquinazoline, 4-(3-chlorophenylthio)-6,7-dimethoxyquinazoline, 4-(3-chlorophenoxy)-6,7-dimethoxyquinazolin and 4-(3,4,5-trimethoxyaniline)-6,7-dimethoxyquinazolin, or their salts

The invention relates to substituted 1-phenylpyrazol-3-carboxamide formula (Ia) in which R1xis in position 4 or 5 and denotes the group-T-CONRaRbin which T represents a direct bond or (C1-C7-alkylen; NRaRbdenotes a group selected from (a), (b), (C); R5and R6denote, independently of one another, hydrogen, (C1-C6)-alkyl, (C3-C8)-alkenyl or R5and R6together with the nitrogen atom to which they are linked, represent a heterocycle selected from pyrrolidine, piperidine, research, piperazine, substituted in position 4 by Deputy R9; R7denotes hydrogen, (C1-C4)-alkyl or benzyl; R8denotes hydrogen, (C1-C4)-alkyl, or R7and R8together with the carbon atom to which they are attached, form a (C3-C5-cycloalkyl; R9denotes hydrogen, (C1-C4)-alkyl, benzyl or a group-X-NR'5R'6in which R'5and R'6represent, independently from each other, (C1-C6)-alkyl; R10denotes hydrogen, (C1-C4)-alkyl; s= 0-3; t=0-3, provided that (s+t) in the same group greater than or equal to 1; the divalent radicals a and E together with the atom is which in addition, may be substituted by one or more (C1-C4-alkilani; R2xand R3xdenote, independently of one another, hydrogen, (C1-C6)-alkyl, (C3-C8-cycloalkyl, (C3-C8-cyclooctylmethyl provided that R2xand R3xdo not simultaneously denote hydrogen or R2xand R3xtogether form tetramethylene group; and their pharmaceutically acceptable salts

The invention relates to the derivatives of hintline formula (I), where Y1represents-O-, -S-, -NR5CO-, where R5is hydrogen; R1represents hydrogen or C1-3alkoxy; R2represents hydrogen; m is an integer from 1 to 5; R3represents hydroxy, halogen, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl or cyano; R4is one of five groups, which is optionally substituted by Spiridonova, phenyl or aromatic heterocyclic group with 1-3 heteroatoms selected from O, N and S, or contains such a group; and their salts, to processes for their preparation and to pharmaceutical compositions containing a compound of the formula (I) or its pharmaceutically acceptable salt as an active ingredient

The invention relates to sulphonilecarbomide acids of the formula

< / BR>
and/or their stereoisomeric forms and/or physiologically acceptable salts, where R1means phenyl, phenyl, one or twice substituted by a group WITH1-C6-alkyl-Oh, halogen, trifluoromethyl, a group WITH1-C6-alkyl-O-C(O)-, methylenedioxy-, R4-(R5)N-; triazole, thiophene, pyridine; R2means H, C1-C6alkyl; R4and R5are adnikowymi or different and denote H, C1-C6-alkyl; R3means H, C1-C10-alkyl, where alkyl unsubstituted and/or one hydrogen atom of the alkyl residue substituted by hydroxyl,2-C10alkenyl, R2-S(O)n-C1-C6-alkyl, where n means 0, 1, 2; R2-S(O)(=NH)-(C1-C6)-alkyl and the other, or R2and R3together form a cycle with a carboxyl group as a substituent cycle of partial formula II:

< / BR>
where r is 0, 1, 2, 3 and/or one of the carbon atoms in the cycle replaced by-O-, and/or the carbon atom in the cycle part of the formula II substituted once by phenyl; a represents a covalent bond, -O-;

The invention relates to acylaminocinnamic derivative of the formula (I), where R denotes phenyl which is not substituted or may be substituted with halogen, alkyl, trifluoromethyl, hydroxy and alkoxygroup, R1is hydrogen, alkyl, R2is hydrogen, alkyl or phenyl which is not substituted or may be substituted with halogen, alkyl, trifluoromethyl, hydroxy and alkoxygroup, R3is phenyl which is not substituted or may be substituted with halogen, alkyl, trifluoromethyl, hydroxy and alkoxygroup, or represents naphthyl, lH-indol-3-yl or 1-alcheringa-3-yl, R4' and R4"is hydrogen, alkyl, and one of the radicals R4' and R4"is hydrogen, and R5- cycloalkyl, D-azacycloheptan-2-he-3-yl or L-azacycloheptan-2-he-3-yl, or its salt

The invention relates to an improved process for the preparation of 8-methyl-8-azabicyclo[3,2,1]Oct-3-silt ester of indole-3-carboxylic acid hydrochloride which is a substance tropisetrona and is used as an antiemetic, effective for vomiting caused by anticancer chemotherapy drugs

The invention relates to new carboxyterminal cyclic carboxamide derivative of formula 1

< / BR>
where G1- CH2; G2- C(O); m = 2 or 3, n is 0 or 1; R1is 1-3 substituent, independently selected from H, G, C1-C6alkoxy; R2is 1-3 substituent, independently selected from H, C1-C6alkoxy; R3means N or

< / BR>
< / BR>
< / BR>
R4- H; Ar1means

< / BR>
< / BR>
R8means 1-3 substituent, independently selected from H, G; R9means N;

And means

< / BR>
< / BR>
< / BR>
where p = 1, 2, 3, or 4; X is-O-, -CH2-; R10-H, C1-C6alkyl or

< / BR>
">< / BR>
< / BR>
< / BR>
where q = 2 or 3; R5- C1-C4alkyl, (CH2)2HE; R6- C1-C4alkyl, -(CH2)2HE, (CH2)2N(CH3)2; R5', R6' - C1-C4alkyl; R7- C1-C6alkyl, and the stereoisomers and pharmaceutically acceptable salts

The invention relates to new derivatives of pyrrolidine or piperidine F.-ly (I), their enantiomers and pharmaceutically acceptable salts

< / BR>
where R10- H or C(O)N(R1)YZ, R1- N, Y - (CH2)p, (CH2)qCH(R3) or CH(R3)(CH2)q, R3- aryl, aralkyl or heteroaryl, q = 1-3, p = 2 or 3, Z - CO2H, CO2-alkyl or 5-tetrazol, X-S(O) M-(CH2)nor piperidine-1-yl, m = 2, n = 2, R5Mr. And selected from piperidine-2-yl, piperidine-3-yl, piperidine-4-yl or N-substituted piperidine

The invention relates to new imidazole derivative of General formula (1), where n1is an integer from 1 to 3, a represents hydrogen, linear or branched C1-C10-alkyl, which may be optionally substituted C3-C7-cycloalkyl or lower alkoxy, or a radical selected from the group shown in the formula of the invention, Y represents a radical selected from the group described in the claims, or to his new pharmaceutically acceptable salts

The invention relates to a new derived pyridonecarboxylic acid of the formula I or salts thereof, which possess high antibacterial activity and can find application in medicine

The invention relates to new derivatives of barbituric acid and a pharmaceutical composition having activity of inhibiting metalloprotease

The invention relates to new derivatives naphthiridine formula I, where R1denotes phenyl, benzyl, 3-nitrophenyl, 3-chlorophenyl, 3-tianfeng, 3-(tetrazolyl)phenyl or benzofuranyl; R2denotes a hydroxy-group, tripterocalyx, allyl, alkyl, alkenyl, quinil, alkoxygroup, phenyl, phenyloxy, carboxyphenyl, carboxymethyl, carbamoylmethyl, phenylamino, diphenylamino-, amino-, elcamino, Alcaidaria, where "ALK" refers to aliphatic fragment having up to 8 carbon atoms and optionally including carboxylate, ether carboxylic acid or a hydroxy-group and/or optionally containing ether and/or ester bond, or its N-oxide in free form or in the form of a pharmaceutically acceptable salt

The invention relates to new sulfonamidnuyu derivatives or their pharmaceutically acceptable salts, which have the properties of inhibitor action of endothelin receptors and can find application in the treatment of diseases associated with disorders in the circulatory system, such as hypertension, ischemia, angina, spasms of the blood vessels as well as to pharmaceutical drugs based on them

Arylalkylamine // 2201923
The invention relates to arylalkylamines formula I, where B - A, OA, NH2, CF3, aromatic heterocycle selected from pyridine, pyrazine and pyrimidine; Q is absent or denotes alkylene with 1-6 carbon atoms; R1and R2independently from each other represent OR5where R5- Or cycloalkyl with 3-7 carbon atoms; And the alkyl with 1-10 carbon atoms, and their physiologically acceptable salts
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