Imidazole derivatives

FIELD: organic chemistry, medicine, hormones.

SUBSTANCE: invention describes imidazole derivatives of the formula (I) , racemic-diastereomeric mixtures and optical isomers, pharmaceutical salts wherein ---- represents an optional bond; R1 represents hydrogen atom (H), -(CH2)m-C(O)-(CH2)m-Z1, -(CH2)m-Z1; R2 represents hydrogen atom (H), or R1 and R2 are joined with nitrogen atoms to which they are bound forming compounds represented by formulae (Ia), (Ib) or (Ic) wherein R3 represents -(CH2)m-E-(CH2)m-Z2; R4 represents hydrogen atom (H) or -(CH2)m-A1; R5 represents (C1-C12)-alkyl, (C0-C6)-alkyl-C(O)-NH-(CH2)m-Z3 and optionally substituted phenyl; R6 represents hydrogen atom (H); R7 represents (C1-C12)-alkyl or -(CH2)m-Z4; m = 0 or a whole number from 1 to 6; n is a whole number from 1 to 5. Proposed compounds bind with subtypes of somatostatin receptors selectively.

EFFECT: valuable properties of compounds.

20 cl, 13776 ex

 

Description of the invention presented in the graphical part.

1. Derived imidazole of the formula (I)

racemizes-diastereomeric mixtures and optical isomers of the compounds of formula (I), pharmaceutically acceptable salt,

where -----is an optional bond;

R1represents H, -(CH2)m-C(O)-(CH2)m-Z1or -(CH2)m-Z1;

Z1represents an optionally substituted radical selected from the group comprising (C1-C12)alkyl, benzo[b]thienyl, phenyl, naphthyl, benzo[b]furanyl, thienyl, isoxazolyl, indolyl,

R2represents N;

or R1and R2combined together with the nitrogen atoms to which they are attached, to form compounds of formula (Ia), (Ib) or (Ic),

R3represents -(CH2)m-O-(CH2)m-Z2;

E represents Oh, -NH-C(O)-O or a bond;

Z2represents H, (C1-C12)alkyl, amino, or optionally substituted radical selected from the group comprising phenyl, indolyl and imidazolyl;

R4represents H or -(CH2)m-And1;

And1represents-C(=Y)N(X1X2), -C(=Y)-X2C(=NH)-X2or X2;

Y represents O or S;

X1represents H, (C1-C12)alkyl, -(CH2)m-N-di(C1-C6)alkyl or -(CH2)mis phenyl;

X2represents -(CH2)m-Yl-X3or optionally substituted C1-C12)alkyl;

Y1represents O, S, NH, C=O, -NH-CO-, SO2or communication;

X3represents H, optionally substituted radical selected from the group comprising (C1-C12)alkyl, (C3-C8)cycloalkyl, (C1-C12)alkoxy, (C1-C12)alkylamino, N,N-di(C1-C12)alkylamino, -CH di(C1-C12)alkoxy, pyrrolidinyl, pyridinyl, thienyl, imidazolyl, piperidinyl, piperazinil, benzothiazolyl, furanyl, indolyl, morpholino, benzo[b]furanyl, chinoline, ethenolysis, -(CH2)mis phenyl, naphthyl, pyrimidinyl,

or X1and X2combined together with the nitrogen atom to which they are attached, education optionally substituted radical selected from the group including

Y2represents-CH-X4or(X4X4), -N-X4Il is O;

X4in each case independently represents -(CH2)m-Y3-X5;

Y3represents-C(O)-, -C(O)Oli communication;

X5represents hydroxy, amino or optionally substituted radical selected from the group comprising phenyl, phenyl(C1-C4)alkyl, furanyl, pyridinyl, -CH(phenyl)2,

R5is a (C1-C12)alkyl, (C0-C6)alkyl-C(O)-NH-(CH2)m-Z3or optionally substituted phenyl;

Z3in each case independently represents an amino, (C1-C12)alkylamino, -NH-C(O)-O-(CH2)m-phenyl, -NH-C(O)-O-(CH2)m-(C1-C6)alkyl or optionally substituted radical selected from the group comprising imidazolyl, pyridinyl, morpholino, piperidinyl, piperazinil, pyrazolidine and furanyl;

R6represents N;

R7is a (C1-C12)alkyl or -(CH2)m-Z4;

Z4represents an optionally substituted radical selected from the group comprising phenyl, naphthyl, indolyl, thienyl, benzo[b]furanyl, benzo[b]thienyl, isoxazolyl,

where the optionally substituted radical is obazatelno substituted by one or more substituents, each of which is independently selected from the group comprising Cl, F, Br, CF3CN, N3, NO2HE SO2NH2, -OCF3, (C1-C12)alkoxy, -(CH2)m-phenyl-(X6)n, -S-phenyl-(X6)n, -S-(C1-C12)alkyl, -O-(CH2)m-phenyl-(X6)n, -(CH2)m-C(O)-O-(C1-C6)alkyl, -O-(CH2)mN-di-((C1-C6)alkyl) and (C0-C12)alkyl-(X6)n;

X6in each case, independently selected from the group comprising H, CH2OH, (C1-C12)alkoxy, -(CH2)m-NH2and -(CH2)mN-di-((C1-C6)alkyl);

m in each case independently 0 or an integer from 1 to 6;

n in each case independently an integer from 1 to 5;

provided that

when R5is a (C1-C12)alkyl or optionally substituted phenyl; R7is a (C1-C12)alkyl, and R3represents-O-(CH2)-Z2then Z2is optionally substituted radical selected from the group comprising phenyl, indolyl and imidazolyl.

2. The compound according to claim 1, wherein R1represents H; R2represents H; R3represents-CH2-indol-3-yl; R4is own the th -(CH 2)m-And1where m, with respect to R4is 0; R5represents phenyl or tert-butyl; R6represents N;

where a1represents-C(=Y)N(X1X2);

Y represents O or S; X1represents N;

X2represents -(CH2)m-Y1-X3;

m with respect to X2is 0, 1 or 2;

Y1represents a bond; and X3represents phenyl, o-Cl-phenyl, m-Cl-phenyl, p-phenoxyphenyl, 2,6-diisopropylphenyl, m-CF3-phenyl, p-ethoxycarbonylphenyl, 2,4-differenl, m-NO3-phenyl, p-benzyloxyphenyl, o-ISO-propylphenyl, n-hexyl, 4-morpholino, naphthyl or.

3. The compound according to claim 1, wherein R1represents H; R2represents H; R3represents-CH2-indol-3-yl; R4represents -(CH2)m-And1where m, with respect to R4is 0; R5represents phenyl; R6represents N;

where a1represents-C(=Y)-X2;

Y represents O; X2represents -(CH2)m-Y1-X3;

where m, applied to X21;

Y1represents O or a bond; and X3is Soboh is phenyl, p-AMINOPHENYL or p-NO2is phenyl.

4. The compound according to claim 1, wherein R1represents H; R2represents H; R3represents-CH2-indol-3-yl; R4represents -(CH2)m-And1where m, with respect to R4is 0; R5represents phenyl or tert-butyl; R6represents N;

where a1represents-C(=Y)N(X1X2);

Y represents O; X1represents hydrogen,

X2represents -(CH2)m-Y1-X3;

where m, applied to X2is 0, 1, 2 or 3;

Y1represents O or a bond; and X3is cyclopentyl, 4-HE-butyl, N,N-diethylamino, N-methylpyrrolidine-2-yl, -CH(ethoxy)2, phenyl, p-SO2NH2-phenyl, p-OH-phenyl, o-CF3-phenyl, p-Cl-phenyl, -CH(phenyl)2or

5. The compound according to claim 1, wherein R1represents H; R2represents H; R3represents-CH2-indol-3-yl; R4represents -(CH2)m-And1where m with respect to R40; R5represents phenyl or tert-butyl; R6represents H; And where the1represents-C(=Y)-X2; Y represen who allows themselves; X2represents -(CH2)m-Y1-X3; where m with respect to X2is 0 or 1; Y1is a bond and X3represents tert-butyl, phenyl, n-Cl-phenyl, m-CF3-phenyl, p-methoxyphenyl, indol-3-yl or p-AMINOPHENYL.

6. The compound according to claim 1, wherein R1represents H; R2represents H; R3represents-CH2-indol-3-yl, -(CH2)4-NH-CO-O-tert-Bu or -(CH2)4-NH2; R4represents -(CH2)m-And1where m with respect to R40; R5represents phenyl, o-methoxyphenyl, p-Br-phenyl, p-nitrophenyl or p-N,N-diethylaminophenyl; R6represents H; And where the1represents-C(=Y)N(X1X2); Y is O; X1represents H; X2represents -(CH2)m-Y1-X3; where m with respect to X20;

Y1is a bond and X3is an o-Br-phenyl, m-Br-phenyl, p-Br-phenyl, o-Cl-phenyl, m-Cl-phenyl, n-Cl-phenyl, o-nitrophenyl, m-nitrophenyl, p-nitrophenyl, o-CF3-phenyl, m-CF3-phenyl, p-CF3-phenyl, p-F-phenyl, 2,4-di-F-phenyl, 2,5-di-F-phenyl, 2,5-acid, m-OMe-phenyl, p-OMe-phenyl, 2-CF3-4-Cl-phenyl, or 3-nitro-4-F-phenyl.

7. The compound according to claim 1, wherein R12represents H; R3represents -(CH2)-indol-3-yl, -(CH2)4-NH-CO-O-tert-Bu or -(CH2)4-NH2; R4represents -(CH2)m-And1where m with respect to R40; R5represents phenyl, o-methoxyphenyl, p-methoxyphenyl, p-Br-phenyl, p-nitrophenyl or p-N,N-diethylaminophenyl; R6represents H; And where the1represents-C(=Y)-X2; Y is O; X2represents -(CH2)m-Y1-X3; where m with respect to X2is 1; Y1is a bond and X3represents phenyl, o-Br-phenyl, m-Br-phenyl, p-Br-phenyl, o-Cl-phenyl, m-Cl-phenyl, n-Cl-phenyl, o-nitrophenyl, m-nitrophenyl, p-nitrophenyl, o-CF3-phenyl, m-CF3-phenyl, p-CF3-phenyl, o-F-phenyl, M-F-phenyl, n-F-phenyl, p-N,N-dimethylaminophenyl, o-OMe-phenyl, m-OMe-phenyl, p-OMe-phenyl, 3,4-di-Cl-phenyl, 3,4,5-tri-OMe-phenyl, p-Me-phenyl, p-OH-phenyl, or 2,4-di-F-phenyl.

8. The compound according to claim 1, wherein R1represents H; R2represents H; R3represents -(CH2)4-NH-CO-O-tert-Bu or -(CH2)4-NH2; R4represents -(CH2)m-And1where m with respect to R40; R5represents phenyl; R6represents H; And where the1p is ecstasy a-C(=Y)-X 2; Y is O; X2represents -(CH2)m-Y1-X3; where m with respect to X2is 0, 1 or 2; Y1represents S, SO2or link and X3represents phenyl, 3,4-di-Cl-phenyl, 3,4,5-tri-OMe-phenyl, p-Me-phenyl, p-OH-phenyl, 2,4-di-F-phenyl, 2-furanyl, 2-pyridinyl, 3-pyridinyl, naphthyl, 2-chinoline, 3-chinoline, 4-chinoline, 8-chinoline, 1-ethenolysis, 2-thienyl or 2-pyrimidinyl.

9. The compound according to claim 1, wherein R1represents H; R2represents H; R3represents -(CH2)4-NH-CO-O-tert-Bu or -(CH2)4-NH2; R4represents -(CH2)m-And1where m with respect to R40; R5represents phenyl; R6represents H; And where the1represents-C(=Y)-X2; Y is O; X2represents -(CH2)m-Y1-X3; where m with respect to X2is 0, 1, 2 or 3; Y1is a bond and X3represents a 5-indolyl, 3-indolyl, 4-indolyl, 2-indolyl, 5-OMe-indol-3-yl, 5-OMe-indol-2-yl, 5-Oh-indole-2-yl, 5-Oh-indole-3-yl, 5-Br-indol-3-yl, 2-Me-indol-3-yl, 2-benzothiazyl, 3-benzothiazol or 2-benzofuranyl.

10. The compound according to claim 1, wherein R1represents H; R2represents H; R3p is ecstasy a -(CH 2)m-indol-3-yl, -(CH2)4-NH-CO-O-tert-Bu or -(CH2)4-NH2; R4represents -(CH2)m-And1where m with respect to R40; R5represents phenyl, o-OMe-phenyl or p-OMe-phenyl; R6represents H; And where the1is a X2; X2represents -(CH2)m-Y1-X3; where m with respect to X2represents 1 or 2; Y1represents O or a bond, and X3represents phenyl, o-HE-phenyl, p-OH-phenyl, o-F-phenyl, m-F-phenyl, n-F-phenyl, o-CF3-phenyl, o-OMe-phenyl, m-OMe-phenyl, o-nitrophenyl, p-nitrophenyl, 3,4-di-Cl-phenyl, 2-nitro-3-OMe-phenyl, o-Br-phenyl, m-Br-phenyl, p-Br-phenyl, 2-thienyl, 3,4,5-tri-OMe-phenyl, p-N,N-dimethylaminophenyl, p-OCF3-phenyl, n-(3-(N,N-dimethylamino)propoxy)phenyl, 3-F-4-OMe-phenyl, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 2-Cl-quinoline-3-yl, 2-chinoline, methyl, n-butyl, n-pentyl, n-hexyl, 3,3-dimethylbutyl, benzyl, cyclohexyl or n-tert-Bu-phenyl.

11. The compound according to claim 1, wherein R1represents H; R2represents H; R3represents -(CH2)4-NH-CO-O-tert-Bu or -(CH2)4-NH2; R4represents -(CH2)m-A1where m with respect to R4represents 0; R5represents phenyl; R6is the fight N; where a1is a X2; X2represents - CH2)m-Y1-X3; where m with respect to X2is 1 or 2; Y1represents O or a bond, and X3represents phenyl, o-HE-phenyl, p-OH-phenyl, o-F-phenyl, m-F-phenyl, n-F-phenyl, o-CF3-phenyl, o-OMe-phenyl, m-OMe-phenyl, p-OMe-phenyl, o-nitrophenyl, p-nitrophenyl, 3,4-di-Cl-phenyl, 2-nitro-3-OMe-phenyl, o-Br-phenyl, m-Br-phenyl, p-Br-phenyl, p-phenylphenyl, 2-thienyl, 3,4,5-tri-OMe-phenyl, n-N,N-dimethylaminophenyl, p-benzyloxyphenyl, p-OCF3-phenyl, p-(3-(N,N-dimethylamino)propoxy)phenyl, 3-F-4-OMe-phenyl, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 2-Cl-quinoline-3-yl, 2-chinoline, 3-indolyl, 6-methoxycarbonylmethyl-3-yl, 1-methylindol-3-yl, methyl, n-butyl, n-pentyl, n-hexyl, 3,3-dimethylbutyl, benzyl, p-tert-Bu is phenyl or cyclohexyl.

12. The compound according to claim 1, wherein R1represents -(CH2)-CO-Z1; R2represents H; R3represents -(CH2)4-NH-CO-O-tert-Bu, -(CH2)4-NH-CO-O-benzyl, -(CH2)-phenyl or -(CH2)-indol-3-yl; R4represents -(CH2)m-A1where m with respect to R40; R5represents phenyl; R6represents H; where Z1represents ethyl, phenyl, p-OMe-phenyl, p-phenylphenol, n-Cl-phenyl, p-Br-phenyl, p-N3-phenyl, n-F-phenyl, m-nor is Ravenel, p-nitrophenyl, n-CN-phenyl, 2,5-di-OMe-phenyl, 3,4-di-Cl-phenyl, n-N,N-dimethylaminophenyl, 3-methyl-4-Cl-phenyl, or naphthyl; And1represents-C(=Y)-X2Y represents O; X2represents -(CH2)m-Y1-X3; where m with respect to X20; Y1represents O and X3represents tert-butyl.

13. The compound according to claim 1, wherein R' represents a-CH2-CO-(CH2)m-Z1where m with respect to R1represents 0 or 1; R2represents H; R3represents-CH2-indol-3-yl or -(CH2)4-NH-CO-O-tert-Bu; R4represents H or -(CH2)m-And1where m with respect to R4represents 0; R5represents phenyl, o-OMe-phenyl, p-nitrophenyl, p-Br-phenyl or tert-butyl; R6represents H; where Z1represents ethyl, propyl, phenyl, p-OMe-phenyl, p-Cl-phenyl, p-Br-phenyl, n-F-phenyl, p-nitrophenyl, m-nitrophenyl, p-CN-phenyl, p-N3-phenyl, p-phenylphenyl, 3-Me-4-Cl-phenyl, p-N,N-diethylaminophenyl, 2,5-di-OMe-phenyl, 3,4-di-Cl-phenyl, 3,4-di-F-phenyl, p-OCF3-phenyl, p-benzyloxyphenyl, p-pentylphenol, 3,4,5-tri-OMe-phenyl, 3-nitro-4-Cl-phenyl, 3-Cl-4-nitrophenyl, 3-methyl-5-chlorobenzoate-2-yl, 2-benzofuranyl, 3-benzothiazol, 3-phenylisoxazol-5-yl, 3-(2,4-di-Cl-phenyl)isoxazol-5-yl, 3-indolyl, 5-Br-Tien-2-the l naphthyl,

And1represents-C(=Y)-X2; Y is Oh; X represents -(CH2)m-Y1-X3; where m with respect to X2represents 0; Y1represents O; and X3represents tert-butyl.

14. The compound according to claim 1, wherein R1and R2combined with the formation of the compounds of formula (Ib) or (1C); R3represents-CH2-phenyl, -CH2-indol-3-yl or -(CH2)4-NH-CO-O-benzyl; R5represents phenyl, o-OMe-phenyl, p-OMe-phenyl, p-Br-phenyl, p-nitrophenyl, tert-butyl or-CH(CH3)2-CO-NH-(CH2)2-NH2; R6represents H; R7represents ethyl, propyl, phenyl, p-OMe-phenyl, n-Cl-phenyl, p-Br-phenyl, n-F-phenyl, p-nitrophenyl, m-nitrophenyl, n-CN-phenyl, n-N3-phenyl, p-phenylphenyl, 3-Me-4-Cl-phenyl, p-N,N-diethylaminophenyl, 2,5-di-OMe-phenyl, 3,4-di-Cl-phenyl, 3,4-di-F-phenyl, p-OCF3-phenyl, p-benzyloxyphenyl, p-pentylphenol, 3,4,5-tri-OMe-phenyl, 3-nitro-4-Cl-phenyl, 3-Cl-4-nitrophenyl, 3-methyl-5-chlorobenzoate-2-yl, 2-benzo-furanyl, 3-benzothiazol, 3-phenylisoxazol-5-yl, 3-(2,4-di-Cl-phenyl)isoxazol-5-yl, 3-indolyl, 5-Br-Tien-2-yl, naphthyl,

15. Derived imidazole represented by the formula (II)

racemizes-diastereomeric mixtures and optical isomers of the compounds represented by formula (II), pharmaceutically acceptable salt,

where --- represents an optional bond;

R1represents H, -(CH2)m-C(O)-(CH2)m-Z1or -(CH2)m-Z1;

Z1represents an optionally substituted radical selected from the group comprising (C1-C12)alkyl, benzo[b]thienyl, phenyl, naphthyl, benzo[b]furanyl, thienyl, isoxazolyl, indolyl,

R2represents N;

or R1and R2taken together with the nitrogen atoms to which they are attached, form a compound represented by the formula (IIa), (IIb) or (IIc):

R3represents -(CH2)m-E-(CH2)m-Z2;

E is O, -NH-C(O)-O-or a bond;

Z2represents H, (C1-C12)alkyl, amino or optionally substituted radical selected from the group comprising phenyl, indolyl and imidazolyl;

R4represents H or -(CH2)m-And1;

And1represents-C(=Y)N(X1X2), -C(=Y)-X2, -C(NH)-X2or X2;

Y presented yet an O or S;

X1represents H, (C1-C12)alkyl, -(CH2)mN-di-(C1-C6)alkyl or -(CH2)mis phenyl;

X2represents -(CH2)m-Y1-X3or optionally substituted (C1-C12)alkyl;

Y1represents O, S, NH, C=O, (C2-C12)alkenyl, -NH-CO-, SO2or communication;

X3represents H, optionally substituted radical selected from the group comprising (C1-C12)alkyl, (C3-C8)cycloalkyl, (C1-C12)alkoxy, phenyloxy, (C1-C12)alkylamino, N,N-di-(C1-C12)alkylamino, -CH di(C1-C12)alkoxy, pyrrolidinyl, pyridinyl, thienyl, imidazolyl, piperidinyl, piperazinil, benzothiazolyl, furanyl, indolyl, morpholino, benzo[b]furanyl, chinoline, ethenolysis, -(CH2)mis phenyl, naphthyl, pyrimidinyl,

or X1and X2taken together with the nitrogen atom to which they are attached, form an optionally substituted radical selected from the group comprising thiazolyl,

Y2represents-CH-X4, -N-X4or-C(X4X4or About;

X4in each case independently represents H or -(CH2 )m-Y3-X5;

Y3represents-C(O)-, -C(O)O-or a bond;

X5represents hydroxy, (C1-C12)alkyl, amino, (C1-C12)alkylamino, N,N-di-(C1-C12)alkylamino, or optionally substituted radical selected from the group comprising phenyl, phenyl(C1-C4)alkyl, furanyl, pyridinyl, piperidinyl, -CH(phenyl)2,

R5is a (C1-C12)alkyl, (C0-C6)alkyl-C(O)-NH-(CH2)m-Z3or optionally substituted phenyl;

Z3in each case independently represents an amino, (C1-C12)alkylamino, amino(C1-C12)alkyl, (C5-C7)cyclooctylamino, amino(C5-C7)cycloalkyl, N-(C1-C12)alkylamino, N,N-di-(C1-C12)alkylamino, -NH-C(O)-O-(CH2)m-phenyl, -NH-C(O)-O-(CH2)m-(C1-C6)alkyl, -CH(phenyl)2, (C5-C7)cycloalkyl,

H2N(C1-C6)alkyl-C(O)-O-(C1-C6)alkyl, optionally substituted phenyl-(CH2)m-O-C(O)-NH-(C1-C6)alkyl→

|

C(O)-O-(C1-C6)alkyl,

or optionally substituted radical selected from the group vklyuchayuschimisya, pyridinyl, morpholino, piperidinyl, piperazinil, pyrazolidine and furanyl, provided that when m is 0 in the formula, R5then Z3is not-NH-C(O)-O-(CH2)m-(C1-C6)alkyl;

R6represents N;

R7is a (C1-C12)alkyl or -(CH2)m-Z4;

Z4represents an optionally substituted radical selected from the group comprising phenyl, naphthyl, indolyl, thienyl, benzo[b]furanyl, benzo[b]thienyl, isoxazolyl,

where the optionally substituted moiety is optionally substituted by one or more substituents, each of which is independently selected from the group comprising Cl, F, Br, CF3CN, N3, NO2HE SO2NH2, -OCF3, (C1-C12)alkoxy, -(CH2)m-phenyl-(X6)n, -S-phenyl-(X6)n, -S-(C1-C12)alkyl, -O-(CH2)m-phenyl-(X6)n, -(CH2)m-C(O)-O-(C1-C6)alkyl, -O-(CH2)mN-di-((C1-C6)alkyl) and -(C0-C12)alkyl-(X6)n;

X6in each case, independently selected from the group comprising hydrogen, HE, NO2, Cl, F, -CF3, (C1-C12)alkyl, (C1-C12)alkoxy, -(CH2)m-H 2and -(CH2)mN-di-((C1-C6)alkyl);

m in each case independently represents 0 or an integer from 1 to 6, and

n in each case independently represents an integer from 1 to 5;

provided that:

when R5is a (C1-C12)alkyl; R7is a (C1-C12)alkyl; and R3represents-O-Z2then Z2is not optionally substituted phenyl.

16. The connection 15, represented by the following formula

where X2represents a p-chlorophenyl, p-methoxyphenyl, 2,4-differenl or thienyl.

17. The connection 15, represented by the following formula

where X2represents a p-chlorophenyl, p-methoxyphenyl, phenyl or thienyl.

18. The connection 15, represented by the following formula

19. The connection 15, represented by the following formula

20. The connection 15, represented by the following formula

where R5represents

and R7represents

or R5represents

and R7represents 3,4-dichlorophenyl.



 

Same patents:

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention describes 2-phenyl-substituted imidazotriazinones of the general formula (I): wherein R1 and R2 mean independently linear (C1-C4)-alkyl; R3 and R4 are similar or distinct and represent hydrogen atom or linear or branched (C1-C4)-alkenyl or (C1-C4)-alkoxy-group, linear or branched (C1-C6)-alkyl chain that can be broken by oxygen atom, and/or it can comprise from to some similar or different the following substitutes: methoxy-, hydroxy-, carboxyl, linear or branched (C1-C4)-alkoxycarbonyl, and/or residues of formulae -SO3H, -(A)a-NR7R8, -O-CO-NR7'R8', and/or wherein A means a number 0 or 1; A means residue -CO or -SO2; R7 and R8 mean hydrogen atom (H), cyclopentyl, cyclohexyl, cycloheptyl, phenyl, piperidinyl or pyridyl that can be substituted with different substitutes, methoxy-, (C1-C6)-alkyl and others; R7' and R8' mean (C1-C6)-alkyl. Also, other values of radicals R3 and R4 are given, a method for their preparing and a pharmaceutical composition. Described compounds are inhibitors of phosphodiesterases and can be used in manufacturing agents showing an anti-thrombosis, anti-proliferative, anti-vasospastic and vasodilating effect.

EFFECT: improved preparing method, valuable biochemical and medicinal properties.

10 cl, 6 tbl, 337 ex

FIELD: pharmaceutical chemistry, medicine.

SUBSTANCE: invention relates to substituted pyridines and pyridazines with angiogenesis inhibition activity of general formula I

(I)1, wherein ring containing A, B, D, E, and L represents phenyl or nitrogen-containing heterocycle; X and Y are various linkage groups; R1 and R2 are identical or different and represent specific substituents or together form linkage ring; ring J represents aryl, pyridyl or cycloalkyl; and G's represent various specific substituents. Also disclosed are pharmaceutical composition containing claimed compounds, as well as method for treating of mammalian with abnormal angiogenesis or treating of increased penetrability using the same.

EFFECT: new pyridine and pyridazine derivatives with angiogenesis inhibition activity.

26 cl, 6 tbl, 114 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new compounds of the general formula (1)

wherein A represents bicyclic or tricyclic azepine derivative; V1 and V2 both represent hydrogen atom (H) or one among V1 and V2 represents hydrogen atom (H), OMe, OBn, OPh, O-acyl, Br, Cl, F, N3, NH2, NHBn and another represents hydrogen atom (H); or V1 and V2 represent in common =O or -O(CH2)pO-; W1 represents oxygen (O) or sulfur (S) atom; X1 and X2 both represent hydrogen atom (H) or in common represent =O or =S; Y represents OR5 or NR6R7; R1 means hydrogen atom (H), lower alkyl, F, Cl and Br; R2 means lower alkoxy-group or values given for R1; R3 and R5 are taken independently among hydrogen atom (H) and lower alkyl; R4 means hydrogen atom (H); R6 and R7 are taken independently among hydrogen atom (H) and lower alkyl, or they in common mean -(CH2)n-; n = 3, 4, 5 or 6; p = 2 or 3. These compounds are agonists of vasopressin V2 receptors and useful as antidiuretic and procoagulants, and also to pharmaceutical compositions comprising these vasopressin agonists. These compositions are useful especially in treatment of diabetes insipidus of the central origin and night enuresis.

EFFECT: valuable medicinal properties of compounds, improved method for treatment.

26 cl, 1 tbl, 119 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new azaheterocycles comprising fragment of piperidin-2-yl- of the general formula (1):

as separate enantiomers or mixture of enantiomers, or their pharmaceutically acceptable salts, oxides or hydrates. In compounds of the formula (1) R1 represents hydrogen atom, inert substitute or NH-protecting substitute; W represents optionally substituted azaheterocycle, such as: pyridin-3-yl, pyrazolo[1,5-a]pyridin-6-yl, 3,4-dihydro-2H-pyrido[1,2-a]pyrimidin-7-yl, 3,4-dihydro-2H-pyrido[1,2-a]pyrimidin-9-yl, imidazo[1,2-a]pyrimidin-6-yl, imidazo[1,2-a]pyrimidin-8-yl or [1,8]naphthyridin-3-yl. Compounds elicit activity with respect to nicotine receptors and can be used in pharmaceutical industry. Also, invention relates to the focused library for search of physiologically active compound-leaders, and to pharmaceutical compositions based on new compounds of the formula (1).

EFFECT: valuable medicinal and pharmacological properties of compounds.

9 cl, 1 tbl, 15 sch, 22 ex

FIELD: organic chemistry of heterocyclic compounds, medicine, pharmacy.

SUBSTANCE: invention describes bicyclical nitrogen-containing heterocycles of the general formula (I): , wherein R1 means hydrogen atom, (C1-C7)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(C1-C4)-alkyl, pyridyl, naphthyl, furyl-(C1-C4)-alkyl, phenyl optionally substituted with di-(C1-C7)-alkylamino-(C1-C7)-group, halogen atom, (C1-C7)-alkoxy-group or hydroxy-(C1-C7)-alkyl, or phenyl-(C1-C7)-alkyl optionally substituted with (C1-C7)-alkoxy-group, amino-(C1-C7)-alkyl, amino-group or di-(C1-C7)-alkylamino-(C1-C7)-alkoxy-group; R2 means (C1-C7)-alkyl, (C3-C7)-cycloalkyl, furyl-(C1-C4)-alkyl, pyridyl or its N-oxide; phenyl optionally substituted with halogen atom, (C1-C7)-alkyl, (C1-C7)-alkoxy-group, hydroxy-group or trifluoromethyl, or phenyl-(C1-C7)-alkyl optionally substituted with (C1-C7)-alkoxy-group; R3 means hydrogen atom, (C1-C7)-alkyl, (C3-C7)-cycloalkyl-(C1-C4)-alkyl, (C3-C7)-cycloalkenyl, pyridyl-(C1-C4)-alkyl, naphthyl, phenyl optionally substituted with phthalimido-(C1-C4)-alkyl, amino-(C1-C7)-alkyl, hydroxy-(C1-C7)-alkyl, (C1-C7)-alkylamino-(C1-C7)-alkyl, di-(C1-C7)-alkylamino-(C1-C7)-alkyl, morpholino-(C1-C4)-alkyl or piperazinyl-(C1-C4)-alkyl, or phenyl-(C1-C7)-alkyl optionally substituted with (C1-C7)-alkoxycarbonyl or carboxy-group. Also, invention relates to pharmaceutically acceptable salts of compounds of the formula (I) as a base with acids or pharmaceutically acceptable salts of compounds of the formula (I) as acid with bases, and pharmaceutical composition based on thereof. Compounds described above show inhibitory activity with respect to tyrosine kinase and can be used in treatment or prophylaxis of inflammatory, immunological, oncological, bronchopulmonary, dermatological and cardiovascular diseases, for treatment of asthma, disorders in the central nervous system or complications associated with diabetes mellitus, or for prophylaxis against transplant rejection after surgery transplantation.

EFFECT: valuable medicinal properties of compounds and composition.

14 cl, 1 tbl, 92 ex

FIELD: organic chemistry, medicine, gastroenterology, pharmacy.

SUBSTANCE: invention relates to a pyrrolopyridazine derivative of the following formula: wherein R1 represents (C3-C7)-cycloalkyl-(C1-C6)-alkyl group that can be substituted optionally with (C1-C6)-alkyl group; R2 represents (C1-C6)-alkyl group; R3 represents hydroxymethyl group, (C2-C6)-aliphatic acyloxymethyl group, (C6-C10)-arylcarbonyloxymethyl group, (C1-C6)-alkoxycarbonyloxymethyl group, formyl group, carboxyl group, (C1-C6)-alkoxycarbonyl group or (C6-C10)-aryloxycarbonyl group; R4 represents (C6-C10)-aryl group that can be substituted optionally with substitutes taken among the group consisting of (C1-C6)-alkyl groups, halogen-(C1-C6)-alkyl groups, (C1-C6)-alkoxy-groups, halogen-(C1-C6)-alkoxy-groups and halogen atoms; A represents imino-group, oxygen or sulfur atom, or its pharmaceutically acceptable salt. Pyrrolopyridazine derivatives elicit inhibitory activity with respect to gastric juice secretion and protective activity with respect to stomach mucosa and can be useful as a curative agent for prophylaxis or treatment of ulcer disease. Except for, invention relates to a pharmaceutical composition based on compounds of the invention and to a method for prophylaxis and treatment of ulcer disease.

EFFECT: valuable medicinal properties of compound.

25 cl, 1 tbl, 11 ex

FIELD: organic chemistry, pharmaceutical composition.

SUBSTANCE: compounds satisfying the formula I 1 are disclosed, wherein each R1 and R2 independently to one another are H, OH, OA or Hal; or R1 and R2 together are -O-CH2-O- or -O-CH2-CH2-O-; R3 and R4 are A-group; X - group monosubstituted with R8, R5 or R7; R5 is linear or branched C1-C10-alkylene, wherein one or two CH2-groups may be substituted with oxygen atom; R7 is phenyl or phenylmethyl; R8 is COOH, COOA, CONH2, CONHA, CON(A)2 or CN; F is C1-C6-alkyl; and Hal is F, Cl, Br, or I, as well as physiologically acceptable salts or solvates thereof. Methods for production of claimed compounds (I) and pharmaceutical composition containing the same also are disclosed. Said compounds and pharmaceutical composition have activity as phosphodiesterase V inhibitors and are useful in treatment of cardiovascular diseases and potency disorders.

EFFECT: pharmaceutically applicable compounds and compositions.

7 cl, 16 ex

FIELD: organic chemistry, pharmaceutical compositions.

SUBSTANCE: invention relates to novel pyrasolbenzodiazepines of formula I 1 (in formula R1 is hydrogen, -NO2, -CN, halogen, -OR5, -COOR7, -CONR8R9, -NR10R11, NHCOR12, NHSO2R13; each R2 and R4 independently of one another are hydrogen, halogen, -NO2, -CF3; R3 is hydpegen, C3-C8-cycloalkyl, aryl, in particular C6-C10-aromatic group having 1 or 2 rings, 5-10-membered heteroaryl, having 1 or 2 rings and1-3 heteroatoms, selected from N, O, and S, -COOR7, CN, C2-C6-alkenyl, -CONR8R9 or C1-C6-alkyl optionally substituted with OR9-group, F or aryl as mentioned above; R5 is C1-C6-alkyl; R7 is hydrogen or C1-C6-alkyl; each independently of one another are hydrogen or C1-C6-alkyl optionally substituted with hydroxyl or NH2, or alternatively R8 and R9 together form morpholino group; each R10,R11 and R12 independently of one another are hydrogen or C1-C6-alkyl; R13 is C1-C6-alkyl optionally substituted with halogen or -NR14R15; each R14 and R15 independently of one another are hydrogen or C1-C6-alkyl optionally substituted with halogen; or alternatively -NR14R15 is morpholino group) or pharmaceutically acceptable salts thereof, as well as to certain pyrasolbenzodiazepine derivatives, thiolactam intermediates for production of compound (I) and pharmaceutical compositions containing the same. Compound and pharmaceutical composition of present invention are cycline-dependent kinase (CDK2) inhibitors and antiproliferation agents used in treatment or controlling disorders associated with cell proliferation, in particular breast, colon, lung and/or prostate tumors.

EFFECT: new antiproliferation agents.

20 cl, 12 tbl, 8 ex

FIELD: organic chemistry.

SUBSTANCE: invention relates to improved synthesis method of pyrlindone hydrochloride having formula (I) 1. Method features intramolecular cyclization of 6-methyl-1-(2-chloroethyl-imino)-1,2,3,4-tetrahydrocarbazole hydrochloride of formula IV 2 at 80°-140°C with alkali agent in presence of phase transfer catalyst to provide 1,2,5,6-tetrahydro-8-methyl-pyrazine[3,2,1-j,k]-4H-carbazole of formula VI 3 followed by reduction at 80°-120°C. Method of present invention makes in possible to produce compound of formula I with yield nearly 70 % and purity more than 99 %.

EFFECT: method of high yield with reduced amount of alkali agent and phase transfer catalyst.

7 cl, 2 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to a new derivative of bicyclic heteroaromatic compound of the general formula (I) or its pharmaceutically acceptable salt eliciting agonistic activity with respect to luteinizing hormone (LH). Compounds can be used for preparing medicinal agents for control ability for conception. In compounds of the general formula (I) R1 represents R7 wherein R7 represents (C6-C10)-aryl optionally substituted with halogen atom at ortho- and/or meta-position; NHR8, OR8 wherein R8 means (C1-C8)-alkyl that can be substituted with halogen atom, (C1-C8)-alkylcarbonyl, (C1-C8)-alkylcarbonyloxy-group, phenyl, (C6-C10)-arylcarbonylamino-group, 5-methyl-2-phenylimidazol-4-yl, (C6)-heterocycloalkyl wherein 1-2 heteroatoms are taken among nitrogen and oxygen atoms, ethyloxycarbonylmethylthio-(C1-C4)-alkoxy-group, amino-group, (C6-C7)-heteroaryl; or (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; R2 represents (C1-C8)-alkyl or (C6-C10)-aryl optionally substituted with one or more substitutes taken among (C1-C8)-alkoxy-group; or (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; R3 represents (C1-C8)-alkyl possibly substituted with (C6-C14)-aryl possibly substituted with halogen atom, (C1-C4)-alkoxy-group, (C1-C4)-alkoxycarbonyl, mono- or tri-(C6-C10)-cycloalkyl, (C6-C10)-aryl, (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; (C5-C7)-heterocycloalkyl comprising 2 heteroatoms taking among nitrogen or oxygen atom; (C3-C8)-cycloalkyl, (C2-C7)-heterocycloalkyl comprising 2 heteroatoms taking among nitrogen or oxygen atom; or (C6-C10)-aryl optionally substituted with one or more substitutes taken among (C1-C8)-alkoxy-group; X represents sulfur atom (S) or N(R4); Y represents nitrogen atom (N); R4 represents (C1-C8)-alkyl, phenyl-(C1-C8)-alkyl; or X represents sulfur atom (S), and Y represents CH; Z represents NH2 or OH; A represents sulfur (S), oxygen atom (O) or a bond. Also, invention relates to a pharmaceutical composition.

EFFECT: valuable properties of compounds and composition.

14 cl, 1 tbl, 119 ex

FIELD: organic chemistry, heterocyclic compounds, medicine.

SUBSTANCE: invention relates to derivatives of piperazine and piperidine of the formula (I): wherein ---Z represents =C or -N; Q means benzyl or 2-, 3- or 4-pyridylmethyl that can be substituted with one or more substitutes taken among group comprising halogen atom, cyano-group, (C1-C3)-alkoxy-group, CF3, OCF3, SCF3, (C1-C4)-alkyl, (C1-C3)-alkylsulfonyl and their salts, and to a method for their preparing also. It has been found that these compounds elicit valuable pharmacological properties owing to combination of (partial) agonism with respect to members of dopamine receptors subtype and affinity with respect to corresponding serotonin and/or noradrenergic receptors and can be useful in preparing compositions used in treatment of fear and/or depression or Parkinson's disease.

EFFECT: valuable medicinal properties of compounds.

7 cl, 1 tbl, 3 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes derivatives of benzodiazepines of the general formula (I):

wherein X means ordinary bond or ethynediyl group wherein if X mean ordinary bond then R1 means halogen atom or phenyl substituted with halogen atom optionally or (C1-C7)-alkyl group; in case when X means ethynediyl group then R1 mean phenyl substituted with halogen atom optionally; R2 means halogen atom, hydroxy-group, lower alkyl, lower alkoxy-group, hydroxymethyl, hydroxyethyl, lower alkoxy-(ethoxy)n wherein n = 1-4, cyanomethoxy-group, morpholine-4-yl, thiomorpholine-4-yl, 1-oxothiomorpholine-4-yl, 1,1-dioxothiomorpholine-4-yl, 4-oxopiperidine-1-yl, 4-(lower)-alkoxypiperidine-1-yl, 4-hydroxypiperidine-1-yl, 4-hydroxyethoxypiperidine-1-yl, 4-(lower)-alkylpiperazine-1-yl, lower alkoxycarbonyl, 2-di-(lower)-alkylaminoethylsulfanyl, N,N-bis-(lower)-alkylamino-(lower)-alkyl, (lower)-alkoxycarbonyl-(lower)-alkyl, (lower)-alkylcarboxy-(lower)-alkyl, lower alkoxycarbonylmethylsulfanyl, carboxymethylsulfanyl, 1,4-dioxa-8-azaspiro[4,5]dec-8-yl, carboxy-(lower)-alkoxy-group, cyano-(lower)-alkyl, 2-oxo[1,3]dioxolane-4-yl-(lower)-alkoxy-group, 2,2-dimethyltetrahydro[1,3]dioxolo[4,5-c]pyrrole-5-yl, (3R)-hydroxypyrrolidine-1-yl, 3,4-dihydroxypyrrolidine-1-yl, 2-oxooxazolidine-3-yl, carbamoylmethyl, carboxy-(lower)-alkyl, carbamoylmethoxy-, hydroxycarbamoyl-(lower)-alkoxy-, lower alkoxycarbamoyl-(lower)-alkoxy-, (lower)-alkylcarbamoylmethoxy-group; R3 means phenyl, thiophenyl, pyridinyl that are substituted with halogen atom, cyano-group, carbamoyl, imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl or isoxazolyl wherein groups of 1,2,3-triazolyl, 1,2,4-triazolyl or isoxazolyl are substituted optionally with (C1-C7)-alkyl or (C1-C7)-alkylsulfanyl, and to their pharmaceutically acceptable salts. Also, invention describes a medicinal agent that is antagonist of mGlu receptors of the group II based on compound of the formula (I). The medicinal agent can be used in treatment and prophylaxis of acute and/or chronic neurological disturbances including psychosis, schizophrenia, Alzheimer's disease, disturbances in cognitive ability and memory damage.

EFFECT: valuable medicinal properties of compounds.

7 cl, 1 tbl, 98 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention describes derivatives of benzodiazepine of the general formula (I)

and their pharmaceutically acceptable acid-additive salts wherein X means a ordinary bond or ethynediyl group; when X means ordinary bond then R1 means halogen atom, (lower)-alkyl, (lower)-alkylcarbonyl, (lower)-cycloalkyl, benzoyl, phenyl substituted optionally with halogen atom, hydroxyl, (lower)-alkyl, (lower)-alkoxy-group, halogen-(lower)-alkoxy-group or cyano-group; styryl, phenylethyl, naphthyl, diphenyl, benzofuranyl, or 5- or 6-membered heterocyclic ring representing thiophenyl, furanyl, pyridinyl, dihydropyridinyl, tetrahydropyridinyl which are optionally substituted; when X means ethynediyl group then R1 means hydrogen atom, (lower)-alkyl substituted optionally with oxo-group; (lower)-cycloalkyl substituted with hydroxyl; (lower)-cycloalkenyl substituted optionally with oxo-group; (lower)-alkenyl, optionally substituted phenyl; 5- or 6-membered heterocyclic ring representing thiophenyl, thiazolyl, pyridinyl, dihydropyridinyl, tetrahydropyridinyl or dihydropyranyl and substituted optionally; R3 means phenyl, pyridyl, thiophenyl or thiazolyl which are substituted optionally. These compounds can be used for treatment or prophylaxis of acute and/or chronic neurological diseases, such as psychosis, schizophrenia, Alzheimer's disease, disorder of cognitive ability and memory disorder. Also, invention describes a medicinal agent based on these compounds and a method for preparing compounds of the formula (I).

EFFECT: improved method for preparing, valuable medicinal properties of compounds.

10 cl, 1 tbl, 173 ex

FIELD: organic chemistry, agriculture.

SUBSTANCE: substituted benzoylisoxazols of general formula I are described, wherein R1 is cycloalkyl; R2 is hydrogen, alkoxycarbonyl; R3 is halogen, substituted alkyl, alkoxyl; R4 is halogen, alkoxil; Z is substituted 5-membered saturated or unsaturated heterocycle having 1-3 nitrogen atoms and additionally including one oxogroup (C=O). Also disclosed is herbicidal agents, containing compounds of formula I.

EFFECT: effective suppression of weeds in such cultures as maize and wheat.

16 cl, 6 tbl, 4 ex

The invention relates to new oxazolidinones derivative of the formula (I), their enantiomers or pharmaceutically acceptable salts, where R is hydrogen or C1-6alkyl, optionally substituted by a group selected from cyano, fluorine, chlorine, hydroxy or carbamoyl; R1and R2independently is fluorine or hydrogen; R3- C1-6alkyl; X Is O, and S

The invention relates to new derivatives (tetrahydro-1-oxido-thiopyran-4-yl)phenyloxazolidine General formula I, in which R1means methyl, ethyl, cyclopropyl, dichloromethyl, R2and R3are identical or different and denote hydrogen or fluorine, or their pharmaceutically acceptable salts, and the new derived (tetrahydro-1,1-oxido-thiopyran-4-yl)phenyloxazolidine General formula II in which R2and R3are identical or different and denote hydrogen or fluorine, R4means ethyl or dichloromethyl, or their pharmaceutically acceptable salts

The invention relates to new triazinyl compounds of formulas Ia and Ib:

< / BR>
or their salts, where in the formula Ia W represents N or C-CO-R, where R denotes HE OC1-C6alkyl or NR3R4where R3and R4- N or C1-C6alkyl, or formula Ib Az denotes imidazopyridine and in both formulas Ia and Ib R1represents C1-C4alkyl, R2denotes phenyl fragment or 2,5-cyclohexadiene-3,4-ridin-1 silt fragment

The invention relates to new derivatives of phenyloxazolidine that have a relationship with a 4-8-membered heterocyclic rings of formula I and their pharmaceutically acceptable salts, where X represents NR1, S(O)gor Oh, R1represents H, C1-6alkyl, optionally zamesheny one or more CN or halogen, -(CH2)h-phenyl, -COR1-1, -СООR1-2, -CO-(CH2)h-COR1-1, -SO2- C1-6alkyl or -(CO)i-Het, R2represents H, -CO-(C1-6)alkyl or fluorine, R3and R4are the same or different and represent H or halogen, R5is1-6alkyl and C3-6cycloalkyl, optionally substituted by one or more halogen, g=0, 1, or 2, h=1 or 2, i=0 or 1, m=0, 1, 2, 3, n= 0, 1, 2, 3, provided that m and n taken together, is equal to 1, 2, 3, 4 or 5

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to new substituted derivatives of pyrrole of the formula (I): wherein R1 and R1' mean independently hydrogen atom (H) or (lower)-alkyl, unsubstituted or substituted (lower)-alkoxy-group; R2 means hydrogen atom (H), nitro-group (-NO2), cyano-group (-CN), halogen atom, unsubstituted (lower)-alkyl or substituted with halogen atom or (lower)-alkoxy-group; R2' means thiazolyl, thiophenyl, isothiazolyl, furanyl and pyrazolyl that is unsubstituted or substituted with (lower)-alkyl, pyrimidinyl, unsubstituted morpholinyl, unsubstituted pyrrolidinyl and imidazolyl that is unsubstituted or substituted with (lower)-alkyl, unsubstituted piperidinyl or piperazinyl that is unsubstituted or substituted with (lower)-alkyl, or ethoxy-group substituted with imidazolyl, or its pharmaceutically acceptable salt. Compounds of the formula (I) inhibit cell proliferation in G2/M phase of mitosis that allows their using in the pharmaceutical composition.

EFFECT: valuable biological properties of compounds.

36 cl, 4 sch, 1 tbl, 21 ex

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