Arylpiperazine derivatives, methods for their preparation, pharmaceutical composition and methods of treatment

 

The invention relates to new arylpiperazine derivative of General formula Iand their pharmaceutically acceptable salts, esters, where Y is O; Q is CH; X, Z and Z' each independently represent CH or N; m=0-1; n=0-4; R1and R2independently selected from H, F, Cl, Br, OCH3OC2H5, OCH2CF3CH3With2H5, CF3isopropylate; R3represents H; R4and R5represent H or phenyl, except that R1represents H, R2represents H, Cl or CF3, R3, R4and R5=N, Y=0, and Q=CH, if m=0 and n=1; and also except that R1represents H, R2is OCH3, R3, R4and R5=H, Y=0, Q=CH, if m=0 and n=2. The invention also relates to methods of producing these compounds, pharmaceutical compositions based on them having uroselective antagonistically activity in relation to1-adrenergic receptors, and methods for treating benign prostate hypertrophy, vascular disease, congestive heart failure and hypertension. The technical result - obtaining new soedineniya faxing (see graphic material)

Claims

1. Arylpiperazine derivative, having a structure of General formula I

and their pharmaceutically acceptable salts, esters,

where Y is O;

Q represents CH;

X, Z and Z' each independently represent CH or N;

m=0-1;

n=0-4;

R1and R2independently selected from H, F, Cl, Br, och3OC2H5The co2CF3CH3With2H5, CF3isopropylate;

R3is N;

R4and R5represent H or phenyl,

except that R1represents H; R2represents H, CL or CF3;

R3, R4and R5Is n; Y Is O and Q is CH, if m=0 and n=1, and also except that R1represents H; R2is the co3; R3, R4and R5- H, Y Is O; Q is CH, if m=0 and n=2.

2. Arylpiperazine derivatives under item 1, having the structure of formula II

where n, X, Z, Z', R1, R2and R3are as defined for formula I;

m'=1 or 2, except that R1represents H; R2represents H, Cl or CF3and F3H3and R3is N, if m'=1 and n=2.

3. Connection on p. 1, chosen from:

1-[4-(4-forfinal)piperazine-1-yl]-3-(2,5-dioxopiperidin-1-yl)propane or cleaners containing hydrochloride salt;

1-[4-(2-methoxyphenyl)piperazine-1-yl]-3-(2,5-dioxopiperidin-1-yl)propane or cleaners containing hydrochloride salt;

1-[4-(2-pyridyl)piperazine-1-yl]-3-(2,5-dioxopiperidin-1-yl)propane or cleaners containing hydrochloride salt;

1-[4-(2-pyrimidyl)piperazine-1-yl]-3-(2,5-dioxopiperidin-1-yl)propane or cleaners containing hydrochloride salt;

1-[4-(3,4-dimetilfenil)piperazine-1-yl]-3-(2,5-dioxopiperidin-1-yl)propane or cleaners containing hydrochloride salt;

1-[4-(2-methoxyphenyl)piperazine-1-yl]-2-(2,5-dioxopiperidin-1-yl)ethane or cleaners containing hydrochloride salt;

1-[4-(3-methoxyphenyl)piperazine-1-yl]-3-(2,5-dioxopiperidin-1-yl)propane or cleaners containing hydrochloride salt;

1-[4-(4-methoxyphenyl)piperazine-1-yl]-3-(2,5-dioxopiperidin-1-yl)propane or cleaners containing hydrochloride salt;

1-[4-(2-methoxyphenyl) piperazine-1-yl]-3-(2,6-dioxopiperidin-1-yl)propane or cleaners containing hydrochloride salt;

1-[4-(4-forfinal) piperazine-1-yl]-3-(2,6-dioxopiperidin-1-yl)propane or cleaners containing hydrochloride salt;

1-[4-(4-chlorophenyl) piperazin-1-yl]-3-(2,6-dioxopiperidin-1-yl)propane or cleaners containing hydrochloride salt;

1-[4-(3-triptoreline)piperazine-1-yl]-3 is ridin-1-yl)propane or cleaners containing hydrochloride salt;

1-[4-(2-were) piperazine-1-yl]-3-(2,6-dioxopiperidin-1-yl)propane or cleaners containing hydrochloride salt;

1-[4-(2-pyridyl)piperazine-1-yl]-3-(2,6-dioxopiperidin-1-yl)propane or cleaners containing hydrochloride salt;

1-[4-(3-chlorophenyl)piperazine-1-yl]-3-(2,6-dioxopiperidin-1-yl)propane or cleaners containing hydrochloride salt;

1-[4-(3,4-dimetilfenil)piperazine-1-yl]-3-(2,6-dioxopiperidin-1-yl)propane or cleaners containing hydrochloride salt;

1-[4-(2-pyrimidyl)piperazine-1-yl]-3-(2,6-dioxopiperidin-1-yl)propane or cleaners containing hydrochloride salt;

1-[4-(3-methoxyphenyl)piperazine-1-yl]-3-(2,6-dioxopiperidin-1-yl)propane or cleaners containing hydrochloride salt;

1-[4-(4-methoxyphenyl)piperazine-1-yl]-3-(2,6-dioxopiperidin-1-yl)propane or cleaners containing hydrochloride salt;

1-[4-(2-methoxyphenyl)piperazine-1-yl]-4-(2,6-dioxopiperidin-1-yl)butane or cleaners containing hydrochloride salt;

1-[4-(2-methoxyphenyl)piperazine-1-yl]-3-[2,5-dioxo-3-phenylpyrrolidine-1-yl]propane or cleaners containing hydrochloride salt;

1-[4-(phenyl)piperidine-1-yl]-3-[2,5-dioxopiperidin-1-yl]propane or cleaners containing hydrochloride salt.

4. Pharmaceutical composition having prolonged uroselective antagonistically activity in relation to1-adrenergic receptors, including a connection on p. 1 and its pharmaceutically who rychecky receptor in a mammal, includes introduction to the specified mammal, the compound having the structure of formula I

and its pharmaceutically acceptable salts, esters,

where Y is O;

Q represents CH;

X, Z and Z' each independently represent CH or N;

m=0-1;

n=0-4;

R1and R2independently selected from H, F, CL, Br, och3OC2H5The co2CF3CH3With2H5, CF3isopropylate;

R3is N;

R4and R5represent H or phenyl, except that R1represents H; R2represents H, CL or CF3; R3, R4and R5- N.; Y = O and Q - CH, if m=0 and n=1, and also except that R1represents H; R2is the co3; R3, R4and R5Is H; Y Is O; Q is CH, if m=0 and n=2.

6. The method according to p. 5, where the specified connection has the structure of formula II

where n, X, Z, Z', R1, R2and R3are as defined for formula I;

m'=1 or 2, except that R1represents H; R2represents H, Cl or CF3and F3is N, if m'=1 and n=1, and also except that RPO p. 6, where the specified compound is 1-[4-(2-methoxyphenyl)piperazine-1-yl]-3-(2,5-dioxopiperidin-1-yl) propane or cleaners containing hydrochloride salt.

8. The method according to p. 6, where the specified compound is 1-[4-(2-methoxyphenyl)piperazine-1-yl]-3-(2,6-dioxopiperidin-1-yl) propane or cleaners containing hydrochloride salt.

9. A method for the treatment of benign hypertrophy of prostate cancer in a mammal, comprising an introduction to the specified mammal, the compound having the structure of formula I

and its pharmaceutically acceptable salts, esters,

where Y is O;

Q represents CH;

X, Z and Z' each independently represent CH or N;

m=0-1;

n=0-4;

R1and R2independently selected from H, F, CL, Br, och3OC2H5The co2CF3CH3With2H5, CF3isopropylate;

R3is N;

R4and R5represent H or phenyl, except that R1is N;

R2represents H, CL or CF3; R3, R4and R5- N, Y Is O and Q is CH, if m=0 and n=1, and also except that R1represents H; R2is the co3; R3, R4and R5- H, Y Is O, Q=CH, if m=0 and n=

where n, X, Z, Z', R1, R2and R3are as defined for formula I;

m'=1 or 2, except that R1represents H; R2represents H, Cl or CF3and F3is N, if m'=1 and n=1, and also except that R1represents H, R2is the co3and R3is N, if m'=1, and n=2.

11. The method according to p. 10, where the specified compound is 1-[4-(2-methoxyphenyl)piperazine-1-yl]-3-(2,5-dioxopiperidin-1-yl) propane or cleaners containing hydrochloride salt.

12. The method according to p. 10, where the specified compound is 1-[4-(2-methoxyphenyl)piperazine-1-yl]-3-(2,6-dioxopiperidin-1-yl) propane or cleaners containing hydrochloride salt.

13. A method of treating vascular disease, congestive heart failure or hypertension in a mammal, comprising an introduction to the specified mammal, the compound having the structure of formula I

and its pharmaceutically acceptable salts, esters,

where Y is O;

Q represents CH;

X, Z and Z' each independently represent CH or N;

m=0-1;

n=0-4;

R1and R2independently selected from H, F, CL, Br, och3OC2H5The co2CF3CH3the t H or phenyl, except that R1represents H; R2represents H, CL or CF3; R3, R4and R5- N, Y Is O and Q is CH, if m=0 and n=1, and also except that R1represents H; R2is the co3; R3, R4and R5- H, Y Is O; Q is CH, if m=0 and n=2.

14 the Method according to p. 13 where the specified connection has the structure of formula II

where n, X, Z, Z', R1, R2and R3are as defined for formula I;

m'=1 or 2, except that R1represents H; R2represents H, Cl or CF3and F3is N, if m'=1 and n=1, and also except that R1represents H; R2is the co3and R3is N, if m'=1, and n=2.

15. The method according to p. 14, where the specified compound is 1-[4-(2-methoxyphenyl)piperazine-1-yl]-3-(2,5-dioxopiperidin-1-yl) propane or cleaners containing hydrochloride salt.

16. The method according to p. 14, where the specified compound is 1-[4-(2-methoxyphenyl)piperazine-1-yl]-3-(2,6-dioxopiperidin-1-yl) propane or cleaners containing hydrochloride salt.

17. The method of obtaining compounds having the structure formula

and its pharmaceutically acceptable solen or N;

m=0-1;

n=0-4;

R1and R2independently selected from H, F, CL, Br, och3OC2H5The co2CF3CH3With2H5, CF3isopropylate;

R3is N;

R4and R5represent H or phenyl, except that R1represents H; R2represents H, CL or CF3; R3, R4and R5- N, Y Is O and Q is CH, if m=0 and n=1, and also except that R1represents H; R2is the co3; R3, R4and R5- H, Y Is O; Q is CH, if m=0 and n=2,

which includes the interaction of compounds having the structure of formula III'

with a compound having the structure of formula IV

obtaining the compounds of formula I.

18. The method according to p. 17 to obtain compounds having the structure of formula II

where n, X, Z, Z', R1, R2and R3are as defined for formula I;

m'=1 or 2, except that R1represents H; R2represents H, Cl or CF3and F3is N, if m'=1 and n=1, and also except that R1represents H; R2not only is th the structure of formula III

with the specified compound of formula IV.

19. The method of obtaining compounds having the structure formula

its pharmaceutically acceptable salts, esters,

where Y is O;

Q represents CH;

X, Z and Z' each independently represent CH or N;

m=0-1;

n=0-4;

R1and R2independently selected from H, F, CL, Br, och3OC2H5The co2CF3CH3With2H5, CF3isopropylate;

R3is N;

R4and R5represent H or phenyl, except that R1represents H; R2represents H, CL or CF3; R3, R4and R5- N, Y Is O and Q is CH, if m=0 and n=1, and also except that R1represents H; R2is the co3; R3, R4and R5- H, Y Is O, Q is CH, if m=0 and n=2,

which includes the interaction of compounds having the structure of formula VI'

with a compound having the structure of formula V

obtaining the compounds of formula I.

20. The method according to p. 19 to obtain compounds having the structure of formula II

m'=1 or 2, except that R1represents H; R2represents H, Cl or CF3and F3is N, if m'=1 and n=1, and also except that R1represents H; R2is the co3and R3is N, if m'=1, and n=2,

which includes the interaction of compounds having the structure of formula VI

with the specified connection formula V.

21. The method of obtaining compounds having the structure formula

its pharmaceutically acceptable salts, esters,

where Y is O;

Q represents CH;

X, Z and Z' each independently represent CH or N;

m=0-1;

n=0-4;

R1and R2independently selected from H, F, CL, Br, och3OC2H5The co2CF3CH3With2H5, CF3isopropylate;

R3is N;

R4and R5represent H or phenyl, except that R1represents H; R2represents H, CL or CF3; R3, R4and R5- N, Y Is O and Q is CH, if m=0 and n=1, and also except that R1represents H; R2is the co3; R3, R4and R5- H, Y - p://img.russianpatents.com/img_data/71/717839.gif">

with a compound having the structure of formula VIII

obtaining the compounds of formula I.

22. The method according to p. 21 to obtain compounds having the structure of formula II

where n, X, Z, Z', R1, R2and R3are as defined for formula I;

m'=1 or 2, except that R1represents H; R2represents H, Cl or CF3and F3is N, if m'=1 and n=1, and also except that R1represents H; R2is the co3and R3is N, if m'=1, and n=2,

where this method involves reacting a compound having the structure of formula VII

with the specified compound of formula VIII.

 

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