Substituted 3-cyanohydrine

 

The invention relates to substituted 3-cyanohydrins formula (1), where R1, R2, R3, R4, Y and X are such as defined in the claims. Also describes how to obtain these compounds, methods of treatment and inhibition using these compounds and pharmaceutical composition thereof. The invention can be used in medicine to treat diseases that are the result of a breach of some regulation of receptor proteincontaining. 14 C. and 33 C.p. f-crystals, 14 PL.

Description text in facsimile form (see drawings) T T T Tr

Claims

1. Substituted 3-cyanohydrine formulas (1)in which X represents cycloalkyl of 3-7 carbon atoms or represents a ring pyridinyl or phenyl, where the ring pyridinyl or phenyl may be optionally mono-, di - or tizamidine Deputy selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, quinil of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halogenmethyl, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, is dialkylamino of 2-12 carbon atoms, alkanolamine of 3-8 carbon atoms; n = 0-1; Y is-NH-, -O - or-NR-; R is alkyl of 1-6 carbon atoms; R1, R2, R3and R4is each, independently, hydrogen, halogen, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, hydroxy, nitro, amino, dialkylamino of 2-12 carbon atoms, N,N-dialkylaminoalkyl of 3-14 carbon atoms, R5-CONH(CH2)p-

or
Z-(C(R6)2)qY
R5is alkyl of 1-6 carbon atoms, alkyl, optionally substituted by one or more halogen atoms;
R6represents hydrogen;
R8represents hydrogen, alkyl of 1-6 carbon atoms, N,N-dialkylaminoalkyl of 3-12 carbon atoms, morpholino-N-alkyl in which the alkyl group contains 1-6 carbon atoms, piperidino-N-alkyl in which the alkyl group contains 1-6 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, alkoxyalkyl of 2-8 carbon atoms, chlorine, fluorine or bromine;
Z is alkoxy of 1-6 carbon atoms, dialkylamino, in which each of the alkyl fragments has 1-6 carbon atoms, morpholino or pyrrolidino;
q = 1-3;
p = 0;
any of Zam the CTE to be the divalent radical-O-(R8)2-O-;
or its pharmaceutically acceptable salt, provided that when Y is-NH-, R1, R2, R3and R4represent hydrogen and n = 0, X is not 2-were; and provided that when Y is-NH-, R1, R2and R4represent hydrogen, R3is chlorine and n = 0, X is not a phenyl or 3-chlorophenyl.

2. Connection on p. 1, in which Y represents-NH - and n = 0, or its pharmaceutically acceptable salt.

3. Connection on p. 2, in which X represents optionally substituted phenyl, or its pharmaceutically acceptable salt.

4. Connection on p. 3 in which R1and R4represent hydrogen, or its pharmaceutically acceptable salt.

5. Connection on p. 1, which is 4-[(3-bromophenyl)amino]-6,7-diethoxy-3-hinolincarbonova, or its pharmaceutically acceptable salt.

6. Connection on p. 1, which is [4-(3-chloro-4-forgenerating)-3-cyano-7-methoxyquinoline-6-yl] amide of 4-dimethylamino-2-ene acid or its pharmaceutically acceptable salt.

7. Connection on p. 1, which is [4-(3-chloro-4-forgenerating)-3-cyano-7-methoxyquinoline-6-yl]amide of 4-diethylamino-2-ene acid or its pharmaceutically acceptable salt.

9. Connection on p. 1, which is [4-(3-brompheniramine)-3-cyano-7-ethoxyquinoline-6-yl] amide of 4-dimethylamino-2-ene acid or its pharmaceutically acceptable salt.

10. Connection on p. 1, which is [4-(3-brompheniramine)-3-cyano-7-ethoxyquinoline-6-yl] amide of 4-diethylamino-2-ene acid or its pharmaceutically acceptable salt.

11. Connection on p. 1, which is [4-(3-chloro-4-forgenerating)-3-cyano-7-methoxyquinoline-6-yl] amide of 4-morpholine-4-albut-2-ene acid or its pharmaceutically acceptable salt.

12. Connection on p. 1, which is [4-(3-brompheniramine)-3-cyano-7-methoxyquinoline-6-yl] amide of 4-dimethylamino-2-ene acid or its pharmaceutically acceptable salt.

13. Connection on p. 1, which is N-[4-[(3-bromophenyl)amino]-3-cyano-6-chinoline] -4-methoxy-2-butanamide or its pharmaceutically acceptable salt.

14. Connection on p. 1, which is N-{4-[(3-chloro-4-forfinal)amino] -3-cyano-6-chinoline}-4-dimethylamino-2-butanamide or its pharmaceutically acceptable salt.

15. Connection on p. 1, which is a
a) 4-[(3-bromophenyl)amino]-7-methoxy-3-hinolincarbonova;
b) 4-[(3-bromophenyl)amino]-7-methoxy-6-nitro-3-hinolincarbonova;
c) 6-amino-4-[INAME;
e) N-[4-[(3-bromophenyl)amino] -3-cyano-7-methoxy-6-chinoline]-2-propenamide;
f) 4-[(3-bromophenyl)amino]-6-nitro-3-hinolincarbonova;
g) 6-amino-4-[(3-bromophenyl)amino]-3-hinolincarbonova;
h) N-[4-[(3-bromophenyl)amino]-3-cyano-6-chinoline]-2-butanamide;
i) N-[4-[(3-bromophenyl)amino]-3-cyano-6-chinoline]ndimethylacetamide;
j) N-[4-[(3-bromophenyl)amino]-3-cyano-6-chinoline]butanamide;
k) N-[4-[(3-bromophenyl)amino]-3-cyano-6-chinoline]-2-propenamide;
1) N-[4-[(3-bromophenyl)amino]-3-cyano-6-chinoline]-2-chloracetamide;
m) N-[(3,4-dibromophenyl)amino]-6-nitro-3-hinolincarbonova;
n) 6-amino-4-[(3,4-dibromophenyl)amino]-3-hinolincarbonova;
o) N-[4-(3,4-dibromophenyl)amino]-3-cyano-6-chinoline]-2-butanamide;
p) 6-nitro-4-[(3-triptoreline)amino]-3-hinolincarbonova;
q) 6-amino-4-[(3-triptoreline)amino]-3-hinolincarbonova;
r) N-[4-[(3-triptoreline)amino]-3-cyano-6-chinoline]-2-butanamide;
s) 4-[(3-bromophenyl)amino]-6,7-dimethoxy-3-hinolincarbonova;
t) 4-[(3-forfinal)amino]-6,7-dimethoxy-3-hinolincarbonova;
u) 4-(cyclohexylamino)-6,7-dimethoxy-3-hinolincarbonova;
v) 4-[(3-bromophenyl)amino]-6,7-dihydroxy-3-hinolincarbonova;
w) 8-[(3-bromophenyl)amino]-[1,3]-dioxolo[4,5-g]quinoline-7-carbonitrile;
x) 4-[(3-chlorophenyl)amino]-6,7-dimethoxy-3-hinolincarbonova the methoxy-3-hinolincarbonova;
AA) 4-[(were)amino]-6,7-dimethoxy-3-hinolincarbonova;
bb) 4-[(3-cyanophenyl)amino]-6,7-dimethoxy-3-hinolincarbonova;
cc) 4-[(4-forfinal)amino]-6,7-dimethoxy-3-hinolincarbonova;
dd) 4-[(3-hydroxymethyl)phenyl)amino]-6,7-dimethoxy-3-hinolincarbonova;
ee) 4-(3-bromophenoxy)-6,7-dimethoxy-3-hinolincarbonova;
ff) 4-[(4-bromophenyl)sulfanyl]-6,7-dimethoxy-3-hinolincarbonova;
(gg) N-[4-[(3-bromophenyl)amino] -3-cyano-6-chinoline] -3(S)-chloro-2-propenamide;
hh) N-[4-[(3-bromophenyl)amino] -3-cyano-6-chinoline] -3(Z)-chloro-2-propenamide;
ii) N-[4-[(3-bromophenyl)amino]-3-cyano-6-chinoline]-2-methyl-2-propenamide;
jj) N-[4-[(3,4-dibromophenyl)amino]-3-cyano-6-chinoline]-2-propenamide;
kk) N-[4-[(5-bromo-3-pyridinyl)amino]-6,7-dimethoxy-3-hinolincarbonova;
11) 4-[(3-bromophenyl)amino] -6,7-bis(2-methoxyethoxy)-3-hinolincarbonova;
mm) N-[4-[(3-bromophenyl)amino] -3-cyano-6-chinoline] -4-hydroxy-2-butanamide;
nn) N-[4-[(3-bromophenyl)amino] -3-cyano-6-chinoline]-4-morpholino-2-butanamide;
OO) N-[4-[(3-bromophenyl)amino] -3-cyano-6-chinoline] -4-dimethylamino-2-butanamide;
RR) N-[4-[(3-bromophenyl)amino] -3-cyano-6-chinoline]-4-methoxy-2-butanamide;
qq) 4-(3-brompheniramine)-6,7-diethoxy-3-hinolincarbonova;
rr) 4-(3-phenylethylamine)-6,7-diethoxy-3-hinolincarbonova;
ss) 4-(3,unlinkability;
uu) [4-(3-brompheniramine)-3-cyanohydrin-6-yl]amide of 4-methoxybutyl-2-ene acid;
vv) 4-(4-chloro-2-forgenerating)-7-(3-chloropropoxy)-6-methoxyquinoline-3-carbonitrile;
ww) 4-(4-chloro-2-forgenerating)-6-methoxy-7-(3-morpholine-4-ylpropionic)quinoline-3-carbonitrile;
XX) 7-(2-dimethylaminoethoxy)-4-(3-hydroxy-4-methylphenylimino)-6-methoxyquinoline-3-carbonitrile;
yy) 4-(3-hydroxy-4-methylphenylimino)-6-methoxy-7-(2-morpholine-4-yl-ethoxy)quinoline-3-carbonitrile or
zz) 4-(4-chloro-2-fluoro-5-hydroxyphenylazo)-7-(3-dimethylaminopropoxy)-6-methoxyquinoline-3-carbonitrile;
or its pharmaceutically acceptable salt.

16. Connection on p. 1, which is
a) 4-(4-chloro-2-fluoro-5-hydroxyphenylazo)-6-methoxy-7-(3-morpholine-4-ylpropionic)quinoline-3-carbonitrile;
b) 4-(4-chloro-2-fluoro-5-hydroxyphenylazo)-7-(2-dimethylaminoethoxy)-6-methoxyquinoline-3-carbonitrile;
c) 4-(4-chloro-2-fluoro-5-hydroxyphenylazo)-6-methoxy-7-(2-morpholine-4-ylethoxy)quinoline-3-carbonitrile;
d) N-[3-cyano-4-(3-forgenerating)quinoline-6-yl]acrylamide;
e) 6,7-dimethoxy-4-(3-nitrophenylamino)quinoline-3-carbonitrile;
f) 4-(3-brompheniramine)-6-ethoxy-7-methoxyquinoline-3-carbonitrile
g) 6-ethoxy-4-(3-hydroxy-4-methylphenylimino)-7-methoxyquinoline-3-carbonitrile;
h) [4-(3-brompheniramine)-3-cyanohydrin the-2-ene acid;
(j) [4-(3-brompheniramine)-3-cyanohydrin-6-yl] amide of 4-methylamino-2-ene acid;
k) 4-[(3-bromophenyl)amino]-8-methyl-6-nitro-3-hinolincarbonova;
1) 4-[(3-bromophenyl)amino]-8-dimethylaminomethyl-6-nitro-3-hinolincarbonova;
m) 6-amino-4-[(3-bromophenyl)amino] -8-dimethylaminomethyl-3-hinolincarbonova;
n) N-{4-[(3-bromophenyl)amino]-3-cyano-8-dimethylaminomethyl-6-chinoline}-2-butanamide;
o) N-{4-[(3-bromophenyl)amino]-3-cyano-8-dimethylaminomethyl-6-chinoline}-2-propenamide;
p) N-{ 4-[(3-bromophenyl)amino] -3-cyano-8-dimethylaminomethyl-6-chinoline} ndimethylacetamide;
q) 4-[(3-chloro-4-forfinal)amino] -7-methoxy-6-(3-morpholino-4-ylpropionic)-3-hinolincarbonova
r) 4-[(3-bromophenyl)amino]-7-methoxy-6-(morpholinoethoxy)-3-hinolincarbonova;
s) 4-[(4-chloro-2-forfinal)amino] -7-methoxy-6-(morpholinoethoxy)-3-hinolincarbonova;
t) 4-[(3-hydroxy-4-were)amino]-7-methoxy-6-(morpholinoethoxy)-3-hinolincarbonova;
u) N-{3-cyano-4-[(3-itfinal)amino]-6-chinoline}-2-propenamide;
v) 6-amino-4-[(3-itfinal)amino]-3-hinolincarbonova;
w) 4-[(3-itfinal)amino]-6-nitro-3-hinolincarbonova;
x) N-{3-cyano-4-[(3-were)amino]-6-chinoline}-2-butanamide;
y) 6-amino-4-[(3-were)amino]-3-hinolincarbonova;
z) 6-nitro-4-[(3-were)amino]-3-hinolincarbonova carbonitrile;
cc) 4-[(3-chlorophenyl)amino]-6-nitro-3-hinolincarbonova;
dd) N-{3-cyano-4-[(3-methoxyphenyl)amino]-6-chinoline}-2-propenamide;
it) N-{3-cyano-4-[(3-methoxyphenyl)amino]-6-chinoline}-2-butanamide;
ff) N-{ 3-cyano-4-[(3-methoxyphenyl)amino]-6-chinoline}-4-piperidino-2-butanamide;
(gg) 6-amino-4-[(3-methoxyphenyl)amino]-3-hinolincarbonova;
hh) 4-[(3-methoxyphenyl)amino]-6-nitro-3-hinolincarbonova;
ii) N-{4-[(3-chloro-4-forfinal)amino]-3-cyano-6-chinoline}-2-butanamide;
jj) N-{4-[(3-chloro-4-forfinal)amino]-3-cyano-6-chinoline}-2-propenamide;
kk) N-{ 4-[(3-chloro-4-forfinal)amino]-3-cyano-6-chinoline}-4-diethylamino-2-butanamide;
11) N-{4-[(3-chloro-4-forfinal)amino]-3-cyano-6-chinoline}-4-morpholino-2-butanamide;
mm) N-{ 4-[(3-chloro-4-forfinal)amino]-3-cyano-6-chinoline}-2-morpholine-4-ylmethyl-2-propenamide;
nn) 6-amino-4-[(3-chloro-4-forfinal)amino]-3-hinolincarbonova;
OO) 4-[(3-chloro-4-forfinal)amino]-6-nitro-3-hinolincarbonova;
RR) N-{4-[(4-bromophenyl)amino]-3-cyano-6-chinoline}-2-propenamide;
qq) 6-amino-4-[(4-bromophenyl)amino]-3-hinolincarbonova;
rr) [(4-bromophenyl)amino]-6-nitro-3-hinolincarbonova;
ss) N-{3-cyano-4-[(3,4-differenl)amino]-6-chinoline]-2-propenamide;
tt) 6-amino-4-[(3,4-differenl)amino]-3-hinolincarbonova;
uu) 4-[(3,4-differenl)amino]-6-nitro-3-Hino is-4-thiopheneacetyl)amino]-3-hinolincarbonova;
yy) 4-[(3-chloro-4-thiopheneacetyl)amino]-6-nitro-3-hinolincarbonova or
zz) N-{3-cyano-4-[(3-cyanophenyl)amino]-6-chinoline}-2-propenamide
or its pharmaceutically acceptable salt.

17. Connection on p. 1, which is
a) N-{ 3-cyano-4-[(3-cyanophenyl)amino] -6-chinoline}-4-piperidino-2-butanamide;
b) 6-amino-4-[(3-cyanophenyl)amino]-3-hinolincarbonova;
c) 4-[(3-cyanophenyl)amino]-6-nitro-3-hinolincarbonova;
d) N-{3-cyano-4-[(3-ethynylphenyl)amino]-6-chinoline}-2-butanamide
e) N-{3-cyano-4-[(3-ethynylphenyl)amino]-6-chinoline}-2-propenamide;
f) N-{ 3-cyano-4-[(3-ethynylphenyl)amino]-6-chinoline}-4-piperidino-2-butanamide;
g) 6-amino-4-[(3-ethynylphenyl)amino]-3-hinolincarbonova;
h) 4-[(3-ethynylphenyl)amino]-6-nitro-3-hinolincarbonova;
i) N-{ 4-[(3-bromophenyl)amino]-3-cyano-6-chinoline}-4-piperidino-2-butanamide;
j) N-[4-[(3-bromophenyl)amino] -3-cyano-6-chinoline] -4-dipropylamino-2-butanamide;
k) N-{ 4-[(3-bromophenyl)amino] -3-cyano-6-chinoline} -2-morpholine-4-ylmethyl-2-propenamide;
1) N-{ 4-[(3-bromo-4-forfinal)amino]-3-cyano-6-chinoline}-4-dimethylamino-2-butanamide;
m) N-{ 4-[(3-bromo-4-forfinal)amino] -3-cyano-6-chinoline}-4-diethylamino-2-butanamide;
n) N-{ 4-[(3-bromo-4-forfinal)amino]-3-cyano-6-chinoline}-4-morpholino-2-butanamide;
o) N-{ 4-[(3-bromo-4-ftorhinolonami;
q) 7-ethoxy-4-[(3-hydroxy-4-were)amino] -6-methoxy-3-hinolincarbonova;
r) N-{4-[(3-chloro-4-forfinal)amino]-3-cyano-6-chinoline}-4-dimethylamino-(Z)-2-butanamide;
s) N-{ 4-[(3-chloro-4-forfinal)amino] -3-cyano-6-chinoline} -4-methoxy-(Z)-2-butanamide;
t) 4-[[4-[(3-bromophenyl)amino]-3-cyano-6-chinoline]amino]-2-methylene-4-oxobutanoic acid;
u) N-[4-[(3-bromophenyl)amino] -3-cyano-6-chinoline] -4-diethylamino-2-butanamide;
v) N-[4-[(3-bromophenyl)amino] -3-cyano-6-chinoline] -4-(n-ethylpiperazine)-2-butanamide;
w) N-[4-[(3-chloro-4-forfinal)amino] -3-cyano-6-chinoline] -4-diethylamino-2-butanamide;
x) N-[4-[(3-bromophenyl)amino] -3-cyano-6-chinoline] -4-(n-methylpiperazine)-2-butanamide;
u) N-[4-[(3-bromophenyl)amino] -3-cyano-6-chinoline]-4-(n-isopropyl-n-methylamino)-2-butanamide;
z) N-[4-[(3-bromophenyl)amino] -3-cyano-6-chinoline]-4-diisopropylamino-2-butanamide;
AA) N-[4-[(3-chloro-4-forfinal)amino]-3-cyano-6-chinoline]-4-dimethylamino-2-butanamide;
bb) N-[4-[(3-chloro-4-forfinal)amino]-3-cyano-6-chinoline]-4-methoxy-2-butanamide;
cc) 4-[(3-bromo-4-forfinal)amino]-6-nitro-3-hinolincarbonova;
dd) 6-amino-4-[(3-bromo-4-forfinal)amino]-3-hinolincarbonova;
it) N-[4-[(3-bromo-4-forfinal)amino] -3-cyano-6-chinoline] -4-dimethylamino-2-butanamide;
ff) [4-(3-brompheniramine)-3-cyano-7-methoxyquinazoline-4-albut-2-ene acid;
hh) 4-(3-chloro-4-forgenerating)-7-methoxy-6-nitroquinoline-3-carbonitrile;
ii) 6-amino-4-(3-chloro-4-forgenerating)-7-methoxyquinoline-3-carbonitrile;
jj) 4-(3-bromo-4-forgenerating)-7-methoxy-6-nitroquinoline-3-carbonitrile;
kk) 6-amino-4-(3-bromo-4-forgenerating)-7-methoxyquinoline-3-carbonitrile;
11) [4-(3-bromo-4-forgenerating)-3-cyano-7-methoxyquinoline-6-yl]amide of 4-diethylamino-2-ene acid;
mm) of 4-(3-brompheniramine)-7-ethoxy-6-nitroquinoline-3-carbonitrile;
nn) 6-amino-4-(3-brompheniramine)-7-ethoxyquinoline-3-carbonitrile;
OO) [4-(3-brompheniramine)-3-cyano-7-ethoxyquinoline-6-yl]amide of 4-brombach-2-ene acid;
PP) [4-(3-brompheniramine)-3-cyano-7-ethoxyquinoline-6-yl] amide of 4-morpholine-4-albut-2-ene acid;
qq) 6-amino-4-(3-brompheniramine)-8-methoxyquinoline-3-carbonitrile;
ss) [4-(3-brompheniramine)-3-cyano-8-methoxyquinoline-6-yl] amide of 4-brombach-2-ene acid;
tt) [4-(3-brompheniramine)-3-cyano-8-methoxyquinoline-6-yl] amide of 4-dimethylamino-2-ene acid;
uu) [4-(3-brompheniramine)-3-cyano-8-methoxyquinoline-6-yl] amide of 4-diethylamino-2-ene acid;
vv) [4-(3-brompheniramine)-3-cyano-8-methoxyquinoline-6-yl] amide of 4-morpholine-4-albut-2-ene acid;
ww) [4-(3-brompheniramine)-3-cyano-7-methoxyquinoline-6-yl] amide of 4-dimethylamino-2-ene acid;
chinolin-3-carbonitrile or
zz) 4-(3-dimethylaminopropylamine)-6,7,8-trimethoxyaniline-3-carbonitrile;
or its pharmaceutically acceptable salt.

18. Connection on p. 1, which is
a) 4-(3-hydroxy-4-methylphenylimino)-6,7,8-trimethoxyaniline-3-carbonitrile;
b) 4-(4-chloro-2-forgenerating)-6,7,8-trimethoxyaniline-3-carbonitrile;
c) 4-(4-chloro-2-forgenerating)-5,8-dimethoxyindole-3-carbonitrile;
d) 4-(3-hydroxy-4-methylphenylimino)-5,8-dimethoxyindole-3-carbonitrile;
e) 4-(3-brompheniramine)-5,8-dimethoxyindole-3-carbonitrile;
f) 4-(3-brompheniramine)-6,7,8-trimethoxyaniline-3-carbonitrile;
g) 4-(3-dimethylaminopropylamine)-5,8-dimethoxyindole-3-carbonitrile;
h) 4-(4-chloro-2-fluoro-5-hydroxyphenylazo)-5,8-dimethoxyindole-3-carbonitrile;
i) 4-(4-chloro-2-fluoro-5-hydroxyphenylazo)-6,7,8-trimethoxyaniline-3-carbonitrile;
j) 4-(3-hydroxy-2-methylphenylimino)-6,7-dimethoxyindole-3-carbonitrile;
k) 4-(2-hydroxy-6-methylphenylimino)-6,7-dimethoxyindole-3-carbonitrile;
1) 4-(3-bromo-4-methylphenylimino)-6,7-dimethoxyindole-3-carbonitrile;
m) 4-(3-chloro-4-hydroxyphenylazo)-6,7-dimethoxyindole-3-carbonitrile;
n) of 6,7-dimethoxy-4-(2-methylsulfonylamino)quinoline-3-carbonitrile;
R) 4-[3-chloro-4-(phenylthio)phenylamino]-6,7-diethoxy-3-hinolincarbonova;
q) 4-[3-CHL is carbonitrile;
s) 4-(3-acetylamino)-6,7-diethoxy-3-hinolincarbonova;
t) 4-(n-methylpentylamino)-6,7-diethoxy-3-hinolincarbonova;
u) 4-(phenylamino)-6,7-diethoxy-3-hinolincarbonova;
v) 4-(4-forgenerating)-6,7-diethoxy-3-hinolincarbonova;
w) 4-(4-fluoro-2-methylphenylimino)-6,7-diethoxy-3-hinolincarbonova;
x) 4-(3-chlorpheniramine)-6,7-diethoxy-3-hinolincarbonova;
u) 4-(3-forgenerating)-6,7-diethoxy-3-hinolincarbonova;
z) 4-(3-aminophenylamino)-6,7-dimethoxy-3-hinolincarbonova;
AA) 4-(3-acetamidophenyl)-6,7-dimethoxy-3-hinolincarbonova
bb) 4-[3-(2-butanamine)phenylamino)] -6,7-dimethoxy-3-hinolincarbonova;
cc) 4-[3-(hydroxymethyl)phenylamino]-6,7-dimethoxy-3-hinolincarbonova;
dd) 4-[3-(chloromethyl)phenylamino]-6,7-dimethoxy-3-hinolincarbonova;
her 4-[3-(acetyltributyl)phenylamino]-6,7-dimethoxy-3-hinolincarbonova;
ff) 4-[3-(thiomethyl)phenylamino]-6,7-dimethoxy-3-hinolincarbonova;
(gg) 4-[(3-bromophenyl)amino]-8-methoxy-3-hinolincarbonova;
hh) 4-(4-chloro-2-forgenerating)-8-methoxyquinoline-3-carbonitrile;
ii) 4-(3-hydroxy-4-methylphenylimino)-8-methoxyquinoline-3-carbonitrile;
jj) 4-(3-dimethylaminopropylamine)-8-methoxyquinoline-3-carbonitrile;
kk) 4-(4-bromo-3-hydroxytyramine)-8-methoxyquinoline-3-carbonitrile;
nn) 4-(3-hydroxy-4-methylphenylimino)-7-methoxyquinoline-3-carbonitrile;
OO) 4-(4-chloro-2-fluoro-5-hydroxyphenylazo)-7-methoxyquinoline-3-carbonitrile;
RR) 4-(4-chloro-2-forgenerating)-6-methoxyquinoline-3-carbonitrile;
qq) 4-(3-hydroxy-4-methylphenylimino)-6-methoxyquinoline-3-carbonitrile;
rr) 4-(4-chloro-2-fluoro-5-hydroxyphenylazo)-6-methoxyquinoline-3-carbonitrile;
ss) 4-(3,5-dichloro-4-hydroxyphenylazo)-6,7-dimethoxyindole-3-carbonitrile;
tt) 4-(2-hydroxy-4-methylphenylimino)-6,7-dimethoxyindole-3-carbonitrile;
uu) 4-(4-hydroxy-3,5-dimethylphenylimino)-6,7-dimethoxyindole-3-carbonitrile;
vv) 4-(5-chloro-2-hydroxyphenylazo)-6,7-dimethoxyindole-3-carbonitrile;
ww) 4-(3,5-dibromo-4-hydroxyphenylazo)-6,7-dimethoxyindole-3-carbonitrile;
XX) 4-(4-hydroxy-2-methylphenylimino)-6,7-dimethoxyindole-3-carbonitrile;
yy) of 6,7-dimethoxy-4-(pyridine-3-ylamino)quinoline-3-carbonitrile or
zz) of 6,7-dimethoxy-4-(3-methylsulfonylamino)quinoline-3-carbonitrile;
or its pharmaceutically acceptable salt.

19. Connection on p. 1, which is
a) 4-(2-hydroxy-5-methylphenylimino)-6,7-dimethoxyindole-3-carbonitrile;
b) 4-(2-chloro-4-hydroxyphenylazo)-6,7-dimethoxyindole-3-carbonitrile;
c) 6,7-dimethoxy-4-(4-methylsulfonylamino)quinoline-3-CT is about)-6,7-dimethoxyindole-3-carbonitrile;
f) 4-[2-(2-hydroxyethyl)phenylamino]-6,7-dimethoxyindole-3-carbonitrile;
g) 4-(3-brompheniramine)-6,7-dihydroxy-3-hinolincarbonova;
h) 4-(3-brompheniramine)-6,7-di-n-propoxy-3-hinolincarbonova;
i) 4-[(3-bromophenyl)-n-acetylamino]-6,7-dihydroxy-3-hinolincarbonova;
j) 4-(3-brompheniramine)-6,7-di-n-butoxy-3-hinolincarbonova;
k) 4-(4-chloro-2-forgenerating)-7-methoxy-3-hinolincarbonova;
1) 4-(4-chloro-2-forgenerating)-7-hydroxy-3-hinolincarbonova;
m) 4-[(4-chloro-2-forgenerating)-n-acetylamino] -7-hydroxy-3-hinolincarbonova;
n) 4-(4-chloro-2-forgenerating)-7-ethoxy-3-hinolincarbonova;
o) 4-[(3-bromophenyl)amino]-6,7-bis(2-methoxyethoxy)-3-hinolincarbonova;
R) 4-(2-aminophenylamino)-6,7-diethoxy-3-hinolincarbonova
q) 4-(3,4-dipohenhydramine)-6,7-diethoxy-3-hinolincarbonova;
r) [4-(3-brompheniramine)hinzelin-6-yl] amide of 4-methoxybutyl-2-ene acid;
s) 7-benzyloxy-4-(4-chloro-2-forgenerating)-6-methoxyquinoline-3-carbonitrile;
t) 4-(4-chloro-2-fluoro-5-hydroxyphenylazo)-7-methoxy-6-(3-morpholine-4-yl)propoxyphenol-3-carbonitrile;
u) N-[4-[(3-brompheniramine)-3-cyanohydrin-6-yl]-3-chloro-(Z)-acrylamide;
v) N-[4-[(3-brompheniramine)-3-cyanohydrin-6-yl]-3-chloro-(Z)-acrylamide;
w) N-[4-[(3-bromophenyl)amino] -3-cyano-6-Hino is) N-[4-[(3-bromophenyl)amino] -3-cyano-6-chinoline]-4-tert-butyldimethylsiloxy-2-butanamide
z) N-[4-[(3-bromophenyl)amino] -3-cyano-6-chinoline]-4-hydroxy-2-butanamide;
AA) 4-(3-hydroxymethyl-2-methylphenylimino)-6,7-dimethoxyindole-3-carbonitrile;
bb) 4-(2-amino-4,5-dimethylphenylimino)-6,7-dimethoxyindole-3-carbonitrile;
cc) 4-(4-ethylvanillin)-6,7-dimethoxyindole-3-carbonitrile;
dd) 4-(4-chloro-2-methylphenylimino)-6,7-dimethoxyindole-3-carbonitrile;
her 6,7-dimethoxy-4-(3-phenoxypropylamine)quinoline-3-carbonitrile;
ff) 4-(4-chloro-3-triptoreline)-6,7-dimethoxyindole-3-carbonitrile;
(gg) 4-(3-hydroxytyramine)-6,7-dimethoxyindole-3-carbonitrile;
hh) 4-(4-methylphenylimino)-6,7-dimethoxyindole-3-carbonitrile;
ii) 4-(3-hydroxy-4-methylphenylimino)-8-methoxy-6-nitroquinoline-3-carbonitrile;
jj) 4-(4-chloro-2-forgenerating)-8-methoxy-6-nitroquinoline-3-carbonitrile;
kk) 4-(3-hydroxy-4-methoxybenzylamine)-8-methoxy-6-nitroquinoline-3-carbonitrile;
11) 6-amino-4-(3-hydroxy-4-methylphenylimino)-8-methoxyquinoline-3-carbonitrile;
mm) 6-amino-4-(3-hydroxy-4-methoxybenzylamine)-8-methoxyquinoline-3-carbonitrile;
nn) N-{4-[(3-bromo-4-forfinal)amino]-3-cyano-7-methoxy-6-chinoline}-4-bromo-2-butanamide;
oo) N-{4-[(3-bromophenyl)amino]-3-cyano-7-methoxy-6-chinoline}-4-chloro-2-butanamide;
RR) N-{3-cyano-4-[(3-itfinal)amino]-6-chinoline}-2-butanamide;
qq) N-{3-qi is /> ss) N-{ 4-[(3-chloro-4-thiopheneacetyl)amino]-3-cyano-6-chinoline}-2-propenamide;
tt) N-{3-cyano-4-[(3,4-differenl)amino]-6-chinoline}-2-butanamide;
uu) N-{4-[(3-chlorophenyl)amino]-3-cyano-6-chinoline}-2-butanamide;
vv) N-{3-cyano-4-[(3-isopropylphenyl)amino]-6-chinoline}-2-butanamide;
ww) N-{3-cyano-4-[(3-isopropylphenyl)amino]-6-chinoline}-2-propenamide;
XX) 6-amino-4-[(3-isopropylphenyl)amino]-3-hinolincarbonova;
yy) 4-[(3-isopropylphenyl)amino]-6-nitro-3-hinolincarbonova or
zz) 4-(3-brompheniramine)-6-(3-pyrrolidin-1-yl-propylamino)quinoline-3-carbonitrile
or its pharmaceutically acceptable salt.

20. Connection on p. 1, which is
a) 4-(3-azidoaniline)-6,7-dimethoxyindole-3-carbonitrile;
b) 6-amino-4-[(4-chloro-2-forfinal)amino]-7-methoxy-3-hinolincarbonova;
c) 4-[(4-chloro-2-forfinal)amino]-7-methoxy-6-nitro-3-hinolincarbonova;
d) 4-[(3,4-dichlorophenyl)amino]-6-nitro-3-hinolincarbonova;
e) 6-amino-4-[(3-methylsulfinylphenyl)amino]-3-hinolincarbonova;
f) 4-[(3-methylsulfinylphenyl)amino]-6-nitro-3-hinolincarbonova;
g) 4-[(3-trifloromethyl)amino]-6-nitro-3-hinolincarbonova;
h) 4-(3-dimethylaminopropylamine)-6,7-dimethoxyindole-3-carbonitrile;
i) of 6,7-dimethoxy-4-(4-methoxy-2-methylphenylimino)quinoline-3-Carbo is about)-6,7-dimethoxyindole-3-carbonitrile;
1) 6,7-dimethoxy-4-(4-phenoxybenzamine)quinoline-3-carbonitrile;
m) 4-(5-chloro-2-methoxybenzylamine)-6,7-dimethoxyindole-3-carbonitrile;
n) 3-(3-cyano-6,7-dimethoxyquinazolin-4-ylamino)-2-methylbenzoic acid;
o) 4-(4-chloro-2-forgenerating)-6,7-dihydroxyquinoline-3-carbonitrile;
R) 4-(3-hydroxy-2-methylphenylimino)-6,7-dimethoxyindole-3-carbonitrile;
q) 4-(3-chloro-4-methoxybenzylamine)-6,7-dimethoxyindole-3-carbonitrile;
r) of 6,7-dimethoxy-4-(4-triptoreline)quinoline-3-carbonitrile;
s) 4-(3,4-dibromoethene)-6-nitroquinoline-3-carbonitrile;
t) 6-amino-4-(3-triptoreline)quinoline-3-carbonitrile;
u) 6-amino-4-(3,4-dibromoethene)quinoline-3-carbonitrile;
v) N-[3-cyano-4-(3,4-dibromoethene)quinoline-6-yl]acrylamide;
w) N-[4-(3-brompheniramine)-3-cyanohydrin-6-yl]propionamide;
x) [4-(3-brompheniramine)-C-cyanohydrin-6-yl] amide (E)-but-2-ene acid;
u) N-[4-[(3-brompheniramine)-3-cyanohydrin-6-yl]-2-methyl-acrylamide;
z) 4-(3-forgenerating)-6-nitroquinoline-3-carbonitrile;
AA) 6-amino-4-(3-forgenerating)quinoline-3-carbonitrile;
bb) 4-(3-dimethylaminopropylamine)-6-nitroquinoline-3-carbonitrile;
cc) 4-(4-dimethylaminobenzylidene)-6-nitroquinoline-3-carbonitrile;
dd) 6-amino-4-(3-dimethylaminopropylamine)quinoline-3-carbonitrile;
buta-2-invoi acid;
(gg) N-[3-cyano-4-(3-dimethylaminopropylamine)quinoline-6-yl]acrylamide;
hh) N-[3-cyano-4-(4-dimethylaminobenzylidene)quinoline-6-yl]acrylamide;
ii) [3-cyano-4-(3-dimethylaminopropylamine)quinoline-6-yl]amide booth-2-invoi acid;
jj) [3-cyano-4-(4-dimethylaminobenzylidene)quinoline-6-yl]amide booth-2-invoi acid;
kk) of the Hydrochloride of 4-(3-brompheniramine)-6-dimethylaminophenyl-3-carbonitrile;
ll) of the Hydrochloride of 6-dimethylamino-4-(3-methoxybenzylamine)quinoline-3-carbonitrile
mm) of 2-bromo-n-[4-(3-brompheniramine)-3-cyanohydrin-6-yl]ndimethylacetamide;
nn) 6-iodine-4-(3-methoxybenzylamine)quinoline-3-carbonitrile;
OO) 4-(4-hydroxy-2-methylphenylimino)-6-methoxy-7-(3-morpholine-4-ylpropionic)quinoline-3-carbonitrile;
RR) 4-(3-brompheniramine)-6-methoxy-7-(3-morpholine-4-ylpropionic)quinoline-3-carbonitrile;
qq) 6-methoxy-4-(2-methylsulfanyl-phenylamino)-7-(3-morpholine-4-ylpropionic)quinoline-3-carbonitrile or
rr) 4-(4-hydroxy-3,5-dimethylphenylimino)-6-methoxy-7-(3-morpholino-4-ylpropionic)quinoline-3-carbonitrile
or its pharmaceutically acceptable salt.

21. A method of inhibiting the biological action of a protein kinase with impaired regulation in mammals, which includes an introduction to the specified mammal an effective amount of a compound having the formula


or
Z-(C(R6)2)qY
R5is alkyl of 1-6 carbon atoms, alkyl, optionally substituted by one or more halogen atoms;
R6represents hydrogen;
R8is hydrogen, ALK is the PAP contains 1-6 carbon atoms, piperidino-N-alkyl in which the alkyl group contains 1-6 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, alkoxyalkyl of 2-8 carbon atoms, chlorine, fluorine or bromine;
Z is alkoxy of 1-6 carbon atoms, dialkylamino, in which each of the alkyl fragments has 1-6 carbon atoms, morpholino or pyrrolidino;
q = 1-3;
p = 0;
any of the substituents R1, R2, R3or R4that are located on adjacent carbon atoms may together be the divalent radical-O-(R8)2-O-;
or its pharmaceutically acceptable salt, provided that when Y is-NH-, R1, R2, R3and R4represent hydrogen and n = 0, X is not 2-were.

22. A method of treating, inhibiting the growth or eradicate tumors in a mammal, in need, which includes an introduction to the specified mammal an effective amount of a compound having the formula

in which X represents cycloalkyl of 3-7 carbon atoms or represents a ring pyridinyl or phenyl, where the ring pyridinyl or phenyl may be optionally mono-, di - or tizamidine Deputy selected from the group consisting of a Gal is, is halogenmethyl, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifloromethyl, cyano, nitro, carboxy, carballa of 2-7 carbon atoms, phenoxy, thiophenoxy, amino, dialkylamino of 2-12 carbon atoms, alkylamino of 3-8 carbon atoms;
n = 0-1;
Y represents-NH-, -O - or-NR-;
R is alkyl of 1-6 carbon atoms;
R1, R2, R3and R4is each, independently, hydrogen, halogen, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, hydroxy, nitro, amino, dialkylamino of 2-12 carbon atoms, N,N-dialkylaminoalkyl of 3-14 carbon atoms,
R5-CONH(CH2)p-,


or
Z-(C(R6)2)qY
R5is alkyl of 1-6 carbon atoms, alkyl, optionally substituted by one or more halogen atoms;
R6represents hydrogen;
R8represents hydrogen, alkyl of 1-6 carbon atoms, N,N-dialkylaminoalkyl of 3-12 carbon atoms, morpholino-N-alkyl in which the alkyl group contains 1-6 carbon atoms, piperidino-N-alkyl in which the alkyl group contains 1-6 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, Ilumina, in which each of the alkyl fragments has 1-6 carbon atoms, morpholino or pyrrolidino;
q = 1-3;
p = 0;
any of the substituents R1, R2, R3and R4that are located on adjacent carbon atoms may together be the divalent radical-O-(R8)2-O-;
or its pharmaceutically acceptable salt, provided that when Y is-NH-, R1, R2, R3and R4represent hydrogen and n = 0, X is not 2-were.

23. The method according to p. 22, in which the tumor expresses EGFR.

24. The method according to p. 22, in which the tumor expresses MARK.

25. The method according to p. 22, in which the tumor expresses the ESQ.

26. The method according to p. 22, in which the tumor expresses KDR.

27. The method according to p. 22, in which the tumor is selected from the group consisting of tumors of the breast, kidney, bladder, mouth, pharynx, esophagus, stomach, colon, ovary and lung.

28. A method of treating, inhibiting the progression of, or eradicating polycystic kidney disease in a mammal, which includes an introduction to the specified mammal an effective amount of a compound having the formula

in which X represents cycloalkyl from 3-7 and is optionally mono-, di - or tizamidine Deputy selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, quinil of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halogenmethyl, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifloromethyl, cyano, nitro, carboxy, carballa of 2-7 carbon atoms, phenoxy, thiophenoxy, amino, dialkylamino of 2-12 carbon atoms, alkylamino of 3-8 carbon atoms;
n = 0-1;
Y represents-NH-, -O - or-NR-;
R is alkyl of 1-6 carbon atoms;
R1, R2, R3and R4is each, independently, hydrogen, halogen, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, hydroxy, nitro, amino, dialkylamino of 2-12 carbon atoms, N,N-dialkylaminoalkyl of 3-14 carbon atoms,
R5-CONH(CH2)p-


or
Z-(C(R6)2)qY
R5is alkyl of 1-6 carbon atoms, alkyl, optionally substituted by one or more halogen atoms;
R6represents hydrogen;
R8represents hydrogen, alkyl of 1-6 carbon atoms, N,N-dialkylaminoalkyl of 3-12 carbon atoms, may group contains 1-6 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, alkoxyalkyl of 2-8 carbon atoms, chlorine, fluorine or bromine;
Z is alkoxy of 1-6 carbon atoms, dialkylamino, in which each of the alkyl fragments has 1-6 carbon atoms, morpholino or pyrrolidino;
q = 1-3;
p = 0;
any of the substituents R1, R2, R3and R4that are located on adjacent carbon atoms may together be the divalent radical-O-(R8)2-O-;
or its pharmaceutically acceptable salt, provided that when Y is-NH-, R1, R2, R3and R4represent hydrogen and n = 0, X is not 2-were.

29. Pharmaceutical composition for inhibiting the biological action of a protein kinase, which comprises a compound having the formula

in which X represents cycloalkyl of 3-7 carbon atoms; or represents a ring pyridinyl or phenyl, where the ring pyridinyl or phenyl may be optionally mono-, di - or tizamidine Deputy selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, quinil of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halogenmethyl, alkoxy of 1-6 atoms peoplered, phenoxy, thiophenoxy, amino, dialkylamino of 2-12 carbon atoms, alkylamino of 3-8 carbon atoms;
n = 0-1;
Y represents-NH-, -O - or-NR-;
R is alkyl of 1-6 carbon atoms;
R1, R2, R3and R4is each, independently, hydrogen, halogen, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, hydroxy, nitro, amino, dialkylamino of 2-12 carbon atoms, N,N-dialkylaminoalkyl of 3-14 carbon atoms,
R5-CONH(CH2)p-


or
Z-(C(R6)2)qY
R5is alkyl of 1-6 carbon atoms, alkyl, optionally substituted by one or more halogen atoms;
R6represents hydrogen;
R8represents hydrogen, alkyl of 1-6 carbon atoms, N,N-dialkylaminoalkyl of 3-12 carbon atoms, morpholino-N-alkyl in which the alkyl group contains 1-6 carbon atoms, piperidino-N-alkyl in which the alkyl group contains 1-6 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, alkoxyalkyl of 2-8 carbon atoms, chlorine, fluorine or bromine;
Z is alkoxy of 1-6 carbon atoms, dialkylamino, in which each of the alkyl fragmentu, R3and R4that are located on adjacent carbon atoms may together be the divalent radical-O-(R8)2-O-;
or its pharmaceutically acceptable salt, provided that when Y is-NH-, R1, R2, R3and R4represent hydrogen and n = 0, X is not 2-a were and a pharmaceutically acceptable carrier.

30. Substituted 3-cyanohydrine formula

in which X represents a phenyl ring which may be optionally mono-, di - or tizamidine Deputy selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, quinil of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, trifloromethyl, cyano, thiophenoxy, dialkylamino of 2-12 carbon atoms;
n = 0;
Y represents-NH-;
R1and R4represent hydrogen;
R2is


R3represents hydrogen, alkoxy of 1-6 carbon atoms,
R8represents hydrogen, alkyl of 1-6 carbon atoms, N,N-dialkylaminoalkyl from 3-12 carbon atoms or morpholino-N-alkyl in which the alkyl group contains 1-6 carbon atoms;
p = 0-3;
or farmacevticheskogo agent.

32. The compound of formula 1 according to any one of paragraphs.1-20 and 30 for use in the inhibition of the biological actions of the protein kinase with impaired regulation of a mammal, in need thereof.

33. The compound of formula 1 according to any one of paragraphs.1-20 and 30 for use in treating, inhibiting the growth of, or eradicating a tumor in a mammal, in need thereof.

34. The compound of formula 1 on p. 31, in which the tumor expresses EGFR.

35. The compound of formula 1 on p. 31, in which the tumor expresses MARK.

36. The compound of formula 1 on p. 31, in which the tumor expresses the ESQ.

37. The compound of formula 1 on p. 31, in which the tumor expresses KDR.

38. The compound of formula 1 on p. 31, in which the tumor is selected from the group consisting of tumors of the breast, kidney, bladder, mouth, pharynx, esophagus, stomach, colon, ovary and lung.

39. The compound of formula 1 according to any one of paragraphs.1-20 and 30 for use in treating, inhibiting the progression of, or eradicating polycystic kidney disease in a mammal.

40. Method of producing compounds of the formula

in which Y and n are described in paragraph 1 values;
X' represents cycloalkyl or phenyl, optionally of Namestnikov carbon the quinil of 2-6 carbon atoms, halogenmethyl, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, trifloromethyl, cyano, nitro, carballa of 2-7 carbon atoms, phenoxy, thiophenoxy, dialkylamino of 2-12 carbon atoms;
R1', R2', R3' and R4' are each, independently, hydrogen, halogen, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, nitro, dialkylamino of 2-12 carbon atoms, N,N-dialkylaminoalkyl of 3-14 carbon atoms, N-allylcarbamate of 1-6 carbon atoms, N,N-dialkylamino of 2-12 carbon atoms; or any of the substituents R1', R2', R3' and R4'that are located on adjacent carbon atoms may be together a bivalent radical-O-(R8)2-O-;
including the hydrolysis of ester of the acid of formula 2

in which R' represents alkyl fragment containing 1-6 carbon atoms,
base with formation of the compound of formula 3:

then the transformation of the carboxylic acid group of the formula 3 in allmydata by heating it with carbonyldiimidazole in an inert solvent followed by the addition of ammonia to obtain the amide of formula 4

41. The method of obtaining compounds of formula 11

where Y, R and n are defined in paragraph 1 values;
X is selected from the group consisting of cycloalkyl or phenyl, optionally substituted by one or more substituents selected from the group consisting of hydrogen, halogen, alkyl of 1-6 carbon atoms, quinil of 2-6 carbon atoms, halogenmethyl, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, trifloromethyl, cyano, nitro, carboxy, carballa of 2-7 carbon atoms, phenoxy, thiophenoxy, dialkylamino of 2-12 carbon atoms, alkanolamine from 3-8 carbon atoms and fragments (R10)ksubmit 1-3 substituent on the aromatic ring, which may be the same or different and independently selected from the group consisting of hydrogen, halogen, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, nitro, dialkylamino of 2-12 carbon atoms, N,N-dialkylaminoalkyl of 3-14 carbon atoms, N-allylcarbamate of 1-6 carbon atoms, N,N-dialkylamino of 2-12 carbon atoms;
R11represents a radical selected from the group
>and R8are defined in paragraph 1 values;
which involves the acylation of compounds of formula 6

or acid chloride of the acid of formula 8, or a mixed anhydride of formula 9, in which R"' represents alkyl of 1-6 carbon atoms,


in the presence of organic base to obtain the compounds of formula 11; and optional education then its pharmaceutically acceptable salt.

42. The method of obtaining the compounds of formula 18

in which X, Y, and n are defined in paragraph 1 values;
R1', R2', R3' and R4' are defined in paragraph 40, which comprises heating a substituted aniline of formula 12

with a reagent of formula 13

obtaining the compounds of formula 14

which is then subjected to thermolysis in a high-boiling solvent to obtain compounds of formula 15

then heating the compounds of formula 15 with gloriouse agent with obtaining the compounds of formula 16
the uly 18, and optional education then its pharmaceutically acceptable salt.

43. The method of obtaining the compounds of formula 15

in which R1', R2', R3' and R4' are defined in 40 p. value
includes heating the compounds of formula 19

with dimethylacetal of dimethylformamide to obtain the compound of formula 20

which is then subjected to interaction with acetonitrile in the presence of a base to obtain the compounds of formula 15.

44. The method of obtaining compounds of formula 22 in which R1, R2, R3, R4and n are defined in paragraph 1 values and X' is defined in paragraph 40

which, when one or more of R1, R2, R3or R4are nitrogroup, includes the conversion to the corresponding amino group using a reducing agent.

45. The method of obtaining compounds of formula 22 in which R1, R2, R3, R4and n are defined in paragraph 1 values and X' is defined in paragraph 40

which, when one or more of R

46. The method of obtaining compounds of formula 22 in which R1, R2, R3, R4and n are defined in paragraph 1 values and X' is defined in paragraph 40

which, when one or more of R1, R2, R3or R4are adjacent methoxypropane, includes the transformation in connection with neighboring hydroxyl groups by heating with pyridinium chloride.

47. The method of obtaining compounds of formula 22 in which R1, R2, R3, R4and n are defined in paragraph 1 values and X' is defined in paragraph 40

which, when one or more of R1, R2, R3or R4are adjacent hydroxy groups, includes the transformation of the connection, which together two adjacent groups R1, R2, R3or R4are the divalent radical-O-(R8)2-O-, in which R8is described in paragraph (1 values, through reaction with a reagent J-C(R8)2-J, in which J represents chlorine, bromine or iodine, and each J may be the same or different, with the use of reason.

 

Same patents:

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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 compounds of the formula I

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in which R1denotes-C(=NH)-NH2which may be substituted once by a group-COA, -CO-[C(R6)2]n-Ar, -COOA, -HE or normal aminosidine group

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R2denotes H, A, OR6N(R6)2, NO2CN, Hal, NHCOA, NHCOAr, NHSO2A, NHSО2Ar, COOR6, SOPS(R6)2, CONHAr, COR6, COAr, S(O)nA or S(O)nAr,

R3means And, cycloalkyl, - [C(R6)2]nAr, - [C(R6)2]n-O-Ar, -[C(R6)2]nHet or-C(R6)2=C(R6)2-Ar,

R6denotes H, a or benzyl,

X is absent or represents-CO-, -C(R6)2-, -C(R6)2-C(R6)2-, -C(R6)2-CO-, -C(R6)2-C(R6)2-CO-, -C(R6)= C(R6)-CO-, NR6CO-, -N{[CR6)2]n-COOR6} -CO - or-C(COOR6R6-C(R6)2-CO-,

Y represents-C(R6)2-, -SO2-, -CO-, -COO - or-CONR6-,

And denotes alkyl with 1-20 C-atoms, where one or two CH2-groups can be replaced by O - or S-atom or single, two - or three-fold substituted by the group And, Ah', OR6N(R6)2, NO2CN, Hal, NHCOA, NHCOAr', NHSO2A, NHSО2Ar', COOR6, CON(R6)2, CONHAr', COR6, COAr', S(O)nA or S(O)nAr is phenyl or naphthyl,

AG' refers to unsubstituted or one-, two - or three-fold substituted by a group A, OR6N(R6)2, NO2CN, Hal, NHCOA, COOR6, SOPS(R6)2, COR6or S(0)nA phenyl or naphthyl,

Het denotes a single or dual core unsubstituted or one - or multi-substituted by a group of Hal, A, Ar', COOR6, CN, N(R6)2, NO2, Ar-CONH-CH2and/or carbonyl oxygen saturated or unsaturated heterocyclic ring system containing one, two, three or four identical or different heteroatoms, such as nitrogen, oxygen or sulphur,

Hal denotes F, C1, Br or J,

n denotes 0, 1 or 2,

and their salts

The invention relates to a vitreous form 8-[3-[N-[(E)-3-(6-acetamidophenyl-3-yl)agrilogic] -N-methylamino] -2,6-dichloraniline] -2-methylinosine, how you can get it by heating the crystalline modification a or a mixture of crystalline modification a and crystalline modification of hydrate 8-[3-[N-[(E)-3-(6-acetamidophenyl-3-yl)agrilogic]-N-methylamino] -2,6-dichloraniline] -2-methylinosine at a temperature below its melting point and then cooled

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The invention relates to novel ortho-sulfonamidophenylhydrazine heteroaryl hydroxamic acids of the formula

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where W and X are both carbon, T is nitrogen, U represents CR1where R1represents hydrogen, or alkyl containing 1-8 carbon atoms, R represents-N(CH2R5)-SO2Z, Q represents -(C=O)-NHOH, with

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is a benzene ring, or is a heteroaryl ring of 5 to 6 atoms in the cycle, which may contain 0-2 heteroatoms selected from nitrogen, oxygen and sulfur, in addition to the heteroatom of nitrogen, denoted as W, where benzene or heteroaryl ring may optionally contain one or two substituent R1where permissible; Z is phenyl, which is optionally substituted by phenyl, alkyl with 1-8 carbon atoms, or a group OR2; R1represents halogen, alkyl with 1-8 carbon atoms, alkenyl with 2-6 carbon atoms, perfluoroalkyl from 1 to 4 carbon atoms, phenyl, optionally substituted by 1-2 groups OR2group-NO2group -(CH2)nZ, where Z is a phenyl which allows an alkyl with 1-8 carbon atoms, phenyl, optionally substituted with halogen, or heteroaryl radical containing 5 to 6 atoms in the cycle, including 1-2 heteroatoms selected from nitrogen, oxygen and sulfur; R5represents hydrogen, alkyl with 1-8 carbon atoms, phenyl, or heteroaryl containing 5 to 6 atoms in the cycle, including 1-2 heteroatoms selected from nitrogen, oxygen and sulfur; or their pharmaceutically acceptable salts

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 a new method of obtaining derivatives of 3-pyrrolin-2-carboxylic acid of the formula I, where1- C1-C6-allyloxycarbonyl; R2is hydroxyl, WITH1-C4-alkoxy or their ammonium salts, the removal of base sulfoxylate residue from the compounds of formula II, where R1and R2as above; R3- C1-C6-alkyl, benzyl, trifluoromethyl, naphthyl, phenyl which may be substituted by a residue comprising SN3, NO2, halogen

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 propanolamine formula (I) and their pharmaceutically acceptable salts, where R1and R2means phenyl, naphthyl, pyridyl, thienyl, pyrimidyl, thiazolyl, hinely, piperazinil, oxazolyl, which may be substituted with halogen, HE, NO2, NH2, COOH, etc., R3-R8mean hydrogen, hydroxyl, (C1-C8-alkoxy, NH2-THE OTHER9, -N(R9R10, R9-R10mean hydrogen or (C1-C8)alkyl, X is CH or N, Y represents CH or N, provided that the residues R1, R2X and Y are not simultaneously mean R1- phenyl, R2is phenyl, X is CH, Y is CH

The invention relates to new derivatives of azetidine and pyrrolidine General formula

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where a represents an optionally unsaturated 5 - or 6-membered ring which may contain heteroatom selected from N and S, and which may be substituted by oxo or (1-6C) alkyl; R1, R2and R3independently of one another represent H, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkoxy-(1-6C)alkyl, and halogen atom; X is an atom of O or S and n = 1 or 2, or its pharmaceutically acceptable salt, except 3-(naphthas-1-yl-oxy)-pyrrolidine and 3-(5,6,7,8-tetrahydro-naphthas-1-yl-oxy)-pyrrolidin

The invention relates to the field of organic chemistry, and in particular to an improved process for the preparation of omeprazole, which is the first drug from the group of drugs to regulate the secretion of gastric acid

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The invention relates to novel ortho-sulfonamidophenylhydrazine heteroaryl hydroxamic acids of the formula

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where W and X are both carbon, T is nitrogen, U represents CR1where R1represents hydrogen, or alkyl containing 1-8 carbon atoms, R represents-N(CH2R5)-SO2Z, Q represents -(C=O)-NHOH, with

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is a benzene ring, or is a heteroaryl ring of 5 to 6 atoms in the cycle, which may contain 0-2 heteroatoms selected from nitrogen, oxygen and sulfur, in addition to the heteroatom of nitrogen, denoted as W, where benzene or heteroaryl ring may optionally contain one or two substituent R1where permissible; Z is phenyl, which is optionally substituted by phenyl, alkyl with 1-8 carbon atoms, or a group OR2; R1represents halogen, alkyl with 1-8 carbon atoms, alkenyl with 2-6 carbon atoms, perfluoroalkyl from 1 to 4 carbon atoms, phenyl, optionally substituted by 1-2 groups OR2group-NO2group -(CH2)nZ, where Z is a phenyl which allows an alkyl with 1-8 carbon atoms, phenyl, optionally substituted with halogen, or heteroaryl radical containing 5 to 6 atoms in the cycle, including 1-2 heteroatoms selected from nitrogen, oxygen and sulfur; R5represents hydrogen, alkyl with 1-8 carbon atoms, phenyl, or heteroaryl containing 5 to 6 atoms in the cycle, including 1-2 heteroatoms selected from nitrogen, oxygen and sulfur; or their pharmaceutically acceptable salts
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