1. Additive composition for controlling and inhibition of polymerization of aromatic vinyl monomers including styrene consisting of:
(a) one or more of quinone methide derivatives; and
CHARACTERIZED IN THAT the composition further comprises:
(b) one or more of tertiary amines,
wherein said tertiary amine is selected from a group consisting of:
(i) tri isopropanol amine (TIPA),
(ii) N,N,N\u2032,N\u2032-Tetrakis(2-hydroxyethyl)ethylene-diamine) (THEED), and
(iii) mixture thereof.
2. The additive composition as claimed in claim 1, wherein the composition consists of:
(a) one or more of quinone methide derivatives; and
CHARACTERIZED IN THAT the composition further comprises:
(b) one or more of tertiary amines,
wherein said tertiary amine is tri isopropanol amine (TIPA).
3. The additive composition as claimed in claim 1, wherein the composition consists of:
(a) one or more of quinone methide derivatives; and
CHARACTERIZED IN THAT the composition further comprises:
(b) one or more of tertiary amines,
wherein said tertiary amine is N,N,N\u2032,N\u2032-Tetrakis(2-hydroxyethyl)ethylene-diamine) (THEED).
4. The additive composition as claimed in claim 1, wherein the composition consists of:
(a) one or more of quinone methide derivatives; and
CHARACTERIZED IN THAT the composition further comprises:
(b) one or more of tertiary amines,
wherein said tertiary amine is combination of:
(i) tri isopropanol amine (TIPA), and
(ii) N,N,N\u2032,N\u2032-Tetrakis(2-hydroxyethyl)ethylene-diamine) (THEED).
5. The additive composition as claimed in any one of the preceding claims 1 to 4, wherein the quinone methide derivative is selected from a group comprising:
i) alkyl-(3,5-di-tert-butyl-4-oxocyclohexane-2,5-dienylidene)-cyano derivative of quinone methide;
ii) alkyl-(3,5-di-tert-butyl-4-oxocyclohexane-2,5-dienylidene)-acid derivative of quinone methide;
iii) alkyl-(3,5-di-tert-butyl-4-oxocyclohexane-2,5-dienylidene)-ester derivative of quinone methide; and
iv) combination thereof.
6. The additive composition as claimed in any one of the preceding claims 1 to 5, wherein the quinone methide derivative is alkyl-(3,5-di-tert-butyl-4-oxocyclohexane-2,5-dienylidene)-ester derivative of quinone methide.
7. The additive composition as claimed in claim 5 or claim 6, wherein the alkyl group is selected from a group comprising methyl-group, ethyl-group and propyl-group.
8. The additive composition as claimed in any one of the preceding claims 1 to 7, wherein the quinone methide derivative does not include 7-aryl quinone methide derivatives.
9. The additive composition as claimed in any one of the preceding claims 1 to 8, wherein the composition does not comprise one or more of following amines:
i) N,N,N\u2032,N\u2032-Tetrakis(2-hydroxypropyl)ethylene-diamine) Quadrol\xae;
ii) tetraethylenepentamine (TEPA);
iii) triethanolamine (TEA);
iv) Tris(N-butylamine) (TBA); and
v) ethylene diamine (EDA).
10. The additive composition as claimed in any one of the preceding claims 1 to 9, wherein the composition does not comprise nitroxide (i.e. nitroxyl) compound including 1-oxyl-2,2,6,6, tetramethylpiperidin-4-ol (or 4 Hydroxy Tempo or 4-HT).
11. The additive composition as claimed in any one of the preceding claims 1 to 10, wherein the quinone methide derivative and the tertiary amine are present in a weight percent ratio, wherein the weight percent ratio is selected from the group comprising the weight percent ratio of quinone methide derivative:tertiary amine varying from:
i. about 99.99:0.01 to about 40:60,
ii. about 99.9:0.1 to about 50:50,
iii. about 99:1 to about 60:40,
iv. about 95:5 to about 70:30, and
v. about 90:10 to about 85:15.
12. The additive composition as claimed in any one of the preceding claims 1 to 11, wherein the composition is used in an amount which is selected from the group comprising the amount varying from:
a. about 0.01 to about 2000 ppm,
b. about 1 to about 1200 ppm,
c. about 5 to about 1000 ppm,
d. about 50 to about 500 ppm, and
e. about 100 to about 300 ppm, and
is added to the aromatic vinyl monomers stream based on weight of the monomer.
13. A method of preparation of the additive composition for control and inhibition of polymerization of aromatic vinyl monomers including styrene as claimed in any one of the preceding claims 1 to 10, wherein the method comprises mixing one or more of the quinone methide derivatives and one or more of the tertiary amines.
14. The method as claimed in claim 13, wherein the quinone methide derivatives and the tertiary amines are mixed in a weight percent ratio selected from the group comprising the weight percent ratio of
quinone methide derivative:tertiary amine varying from
i. about 99.99:0.01 to about 40:60,
ii. about 99.9:0.1 to about 50:50,
iii. about 99:1 to about 60:40,
iv. about 95:5 to about 70:30, and
v. about 90:10 to about 85:15.
15. A method of using the additive composition of any one of the preceding claims 1 to 10 for control and inhibition of polymerization of aromatic vinyl monomers including styrene, wherein the method comprises adding the additive composition to a processing or manufacturing unit for styrene polymerization, wherein the additive composition consists of mixture of one or more of the quinone methide derivatives and one or more of the tertiary amines.
16. A method of using the additive composition of any one of the preceding claims 1 to 10 for control and inhibition of polymerization of aromatic vinyl monomers including styrene, wherein the method comprises separately adding components of the additive composition to a processing or manufacturing unit for styrene polymerization, wherein the additive composition consists of component a) one or more of the quinone methide derivatives and component b) one or more of the said tertiary amines.
17. The method as claimed in claim 15 or claim 16, wherein the quinone methide derivatives and the tertiary amines are added to the processing or manufacturing unit for styrene polymerization in a weight percent ratio selected from the group comprising the weight percent ratio of
quinone methide derivative:tertiary amine varying from
i. about 99.99:0.01 to about 40:60,
ii. about 99.9:0.1 to about 50:50,
iii. about 99:1 to about 60:40,
iv. about 95:5 to about 70:30, and
v. about 90:10 to about 85:15.
18. The method as claimed in any one of the preceding claims 15 to 17, wherein the compositions is added in an amount selected from the group comprising:
a. varying from about 0.01 to about 2000 ppm,
b. varying from about 1 to about 1200 ppm,
c. varying from about 5 to about 1000 ppm,
d. varying from about 50 to about 500 ppm, and
e. varying from about 100 to about 300 ppm,
to the aromatic vinyl monomers stream in the processing or manufacturing unit for styrene polymerization based on weight of the monomers.
19. The method as claimed in any one of the preceding claims 15 to 18, wherein the quinone methide derivatives and the tertiary amines are added either separately or after mixing with each other.
20. The method as claimed in any one of the preceding claims 15 to 18, wherein the quinone methide derivatives and the tertiary amines are added after mixing with a solvent which dissolves the derivatives and the amines.
21. A method for controlling and inhibition of polymerization of aromatic vinyl monomers including styrene, wherein the method comprises adding the additive composition any one of the preceding claims 1 to 10 to a processing or manufacturing unit for styrene polymerization, wherein the additive composition consists of one or more of the quinone methide derivatives and one or more of the tertiary amines.
22. The method as claimed in claim 21, wherein the quinone methide derivatives and the tertiary amines are added in a weight percent ratio selected from the group comprising the weight percent ratio of
quinone methide derivative:tertiary amine varying from
i. about 99.99:0.01 to about 40:60,
ii. about 99.9:0.1 to about 50:50,
iii. about 99:1 to about 60:40,
iv. about 95:5 to about 70:30, and
v. about 90:10 to about 85:15.
23. The method as claimed in claim 21 or claim 22, wherein the is added in an amount selected from the group comprising:
a. varying from about 0.01 to about 2000 ppm,
b. varying from about 1 to about 1200 ppm,
c. varying from about 5 to about 1000 ppm,
d. varying from about 50 to about 500 ppm, and
e. varying from about 100 to about 300 ppm.
24. The method as claimed in any one of the preceding claims 21 to 23, wherein the quinone methide derivatives and the tertiary amines are added either separately or after mixing with each other.
25. The method as claimed in any one of the preceding claims 21 to 23, wherein the quinone methide derivatives and the tertiary amines are added after mixing with a solvent which dissolves the derivatives and the amines.
26. The method as claimed in any of the preceding claims 13 to 25, wherein said composition is used at a temperature range which is selected from the group comprising the temperature varying from about 60\xb0 C. to about 180\xb0 C., and from about 90\xb0 C. to about 140\xb0 C.
27. The method as claimed in any of the preceding claims 13 to 26, wherein said monomers are in a processing stage.
28. The method as claimed in any of the preceding claims 13 to 27, wherein said monomers are at a temperature varying from about 60\xb0 C. to about 180\xb0 C.
29. The method as claimed in any of the preceding claims 13 to 28, wherein said monomers are in a manufacturing stage.
30. Additive composition for controlling and inhibition of polymerization of aromatic vinyl monomers including styrene substantially as herein described and illustrated with the help of foregoing examples.
31. A method of preparation of the additive composition for control and inhibition of polymerization of aromatic vinyl monomers including styrene substantially as herein described and illustrated with the help of foregoing examples.
32. A method of using the additive composition for control and inhibition of polymerization of aromatic vinyl monomers including styrene substantially as herein described and illustrated with the help of foregoing examples.
33. A method for controlling and inhibition of polymerization of aromatic vinyl monomers including styrene substantially as herein described and illustrated with the help of foregoing examples.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A compound of formula I,
wherein
n1 is 0;
X is, independently for each occurrence, (CHR11)n3(CH2)n4Z(CH2)n5,
Z is 0, N(R12), S, or a bond;
n3 is, independently for each occurrence, 0 or 1;
n4 and n5 each is, independently for each occurrence, 0, 1, 2, or 3;
Y is, independently for each occurrence, CO, CH2, CS, or a bond;
R1 is
R2, R11 and R12 each is, independently for each occurrence, H or an optionally substituted moiety selected from the group consisting of (C1-6)alkyl and aryl, wherein said optionally substituted moiety is optionally substituted with one or more of R8 or R30;
R3 is, independently for each occurrence, H or an optionally substituted moiety selected from the group consisting of (C1-6)alkyl, (C2-6)alkenyl, (C2-6)alkynyl, (C3-6)cycloalkyl, (C3-6)cycloalkyl(C1-6)alkyl, (C5-7)cycloalkenyl, (C5-7)cycloalkenyl(C1-6)alkyl, aryl, aryl(C1-6)alkyl, heterocyclyl, and heterocyclyl(C1-6)alkyl, wherein said optionally substituted moiety is optionally substituted with one or more R30;
R4 and R5 each is, independently for each occurrence, H or an optionally substituted moiety selected from the group consisting of (C1-6)alkyl, (C3-6)cycloalkyl, aryl, and heterocyclyl, wherein said optionally substituted moiety is optionally substituted with one or more R30, wherein each said substituent is independently selected;
R6 is, independently for each occurrence, H or an optionally substituted moiety selected from the group consisting of (C1-6)alkyl, (C2-6)alkenyl, (C3-6)cycloalkyl, (C3-6)cycloalkyl (C1-6)alkyl, (C5-7)cycloalkenyl, (C5-7)cycloalkenyl(C1-6)alkyl, aryl, aryl(C1-6)alkyl, heterocyclyl, and heterocyclyl (C1-6)alkyl, wherein said optionally substituted moiety is optionally substituted with one or more substituents each independently selected from the group consisting of OH, (C1-6)alkyl, (C1-6)alkoxy, \u2014N(R8R9), \u2014COOH, \u2014CON(R8R9), and halo,
where R8 and R9 each is, independently for each occurrence, H, (C1-6)alkyl, (C2-6)alkenyl, (C2-6)alkynyl, aryl, or aryl(C1-6)alkyl;
R7 is, independently for each occurrence, H, \u2550O, \u2550S, or an optionally substituted moiety selected from the group consisting of (C1-6)alkyl, (C2-6)alkenyl, (C3-6)cycloalkyl, (C3-6)cycloalkyl(C1-6)alkyl, (C5-7)cycloalkenyl, (C5-7)cycloalkenyl(C1-6)alkyl, aryl, aryl(C1-6)alkyl, heterocyclyl, and heterocyclyl(C1-6)alkyl, wherein said optionally substituted moiety is optionally substituted with one or more substituents each independently selected from the group consisting of OH, (C1-6)alkyl, (C1-6)alkoxy, \u2014N(R8R9), \u2014COOH, \u2014CON(R6R9), and halo;
R10 is C;
R21 is, independently for each occurrence, H or an optionally substituted moiety selected from the group consisting of (C1-6)alkyl and aryl(C1-6)alkyl, wherein said optionally substituted moiety is optionally substituted with one or more substituents each independently selected from the group consisting of R8 and R30;
R22 is H, (C1-6)alkylthio, (C3-6)cycloalkylthio, R8\u2014CO\u2014, or a substituent according to the formula
R24 and R25 each is, independently for each occurrence, H, (C1-6)alkyl, or aryl(C1-6)alkyl;
R30 is, independently for each occurrence, (C1-6)alkyl, \u2014O\u2014R8, \u2014S(O)n6R8, \u2014S(O)n7N(R8R9), \u2014N(R8R9), \u2014CN, \u2014NO2, \u2014CO2R8, \u2014CON(R8R9), \u2014NH-CO-R8, or halogen;
n6 and n7 each is, independently for each occurrence, 0, 1, or 2;
wherein said heterocyclyl is azepinyl, benzimidazolyl, benzisoxazolyl, benzofurazanyl, benzopyranyl, benzothiopyranyl, benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, chromanyl, cinnolinyl, dihydrobenzofuryl, dihydrobenzothienyl, dihydrobenzothiopyranyl, dihydrobenzothio-pyranyl sulfone, furyl, imidazolidinyl, imidazolinyl, imidazolyl, indolinyl, indolyl, isochromanyl, isoindolinyl, isoquinolinyl, isothiazolidinyl, isothiazolyl, isothiazolidinyl, morpholinyl, naphthyridinyl, oxadiazolyl, 2-oxoazepinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, piperidyl, piperazinyl, pyridyl, pyridyl N\u2014oxide, quinoxalinyl, tetrahydrofuryl, tetrahydroisoquinolinyl, tetrahydro-quinolinyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiazolyl, thiazolinyl, thienofuryl, thienothienyl, or thienyl; and
wherein said aryl is phenyl or naphthyl; or a pharmaceutically acceptable salt thereof.
2. A compound according to claim 1, wherein:
R1 is and
X is CH(R11)n3(CH2)n4 or Z, wherein Z is O, S or N(R12);
or a pharmaceutically acceptable salt thereof.
3. A compound according to claim 2,
wherein:
R1 is
X is CH(R11)n3(CH2)n4; and
n1 is 0;
or a pharmaceutically acceptable salt thereof.
4. A compound according to claim 2, wherein:
R1 is
n3, n4, and n5 each is 0;
Z is a bond;
Y is, independently for each occurrence, CO or CS; and
n1 is 0;
or a pharmaceutically acceptable salt thereof.
5. A compound according to claim 3, wherein said compound is
8-butyl-7-(3-(imidazol-5-yl)-1-oxopropyl)-2-(2-methoxyphenyl)-5,6,7, 8-tetrahydroimidazo1,2apyrazine;
8-butyl-2-(2-hydroxyphenyl)-7-(imidazol-4-yl-propyl)-5,6,7,8-tetrahydroimidazo1,2apyrazine;
8-butyl-7-(4imidazolylpropyl)-2-(2-methoxyphenyl)-5,6,7,8-tetrahydroimidazo 1, 2apyrazine;
7-(2-(imidazol-4-yl)-1-oxo-ethyl)-2-(2-methoxyphenyl)-8-(1-methylpropyl)-5,6,7,8-tetrahydroimidazo 1,2apyrazine;
2-(2-methoxyphenyl)-8-(1-methylpropyl)-7-(1-oxo-2-(1-(phenylmethyl)-imidazol-5-yl)ethyl)-5,6,7,8-tetrahydroimidazo 1,2apyrazine;
2-(2-methoxyphenyl)-8-(1-methylpropyl)-7-((2-(1-phenylmethyl)-imidazol-5-yl) ethyl)-5, 6,7, 8-tetrahydroimidazo 1,2apyrazine;
7-(2-(1-(4-cyanophenylmethyl)-imidazol-5-yl)-1-oxo-ethyl)-2-(2-methoxyphenyl)-8-(1-methylpropyl)-5,6,7,8-tetrahydroimidazo 1,2apyrazine;
7-((1H-imidazol-4-yl)methyl)-2-(2-methoxyphenyl)-8-(1-methylpropyl)-5,6,7,8-tetrahydroimidazo 1,2apyrazine;
7-((4-imidazolyl)carbonyl)-2-(2-methoxyphenyl)-8-(1-methylpropyl)-5,6,7,8-tetrahydroimidazo 1,2apyrazine;
7-(1-(4-cyanophenylmethyl)-imidazol-5-yl)methyl-2-(2-methoxyphenyl)-8-(1-methylpropyl)-5, 6,7,8-tetrahydroimidazo 1,2apyrazine;
7-((2-(4-cyanophenylmethyl)-imidazol-5-yl)-1-oxo-ethyl)-2-(2-methoxyphenyl)-5,6,7,8-tetrahydroimidaz1,2-apyrazine;
5-butyl-7-(2-(4-cyanophenylmethylimidazol-5-yl)-1-oxo-ethyl)-2-phenyl-5,6,7,8-tetrahydroimidazo1,2apyrazine;
6-butyl-7-(2-(4-cyanophenylmethylimidazol-5-yl)-l-oxo-ethyl)-2-(2-methoxyphenyl)-5,6,7,8-tetrahydroimidazo1,2-apyrazine;
6-butyl-7-(2-(4-cyanophenylmethylimidazol-5-yl)-1-oxo-ethyl)-2-phenyl-5,6,7,8-tetrahydroimidazo1,2-apyrazine;
5-butyl-7-(2-(1-(4-cyanopheriylmethyl)-imidazole-5-yl)-1-oxo-ethyl)-2-(2-methoxyphenyl)-5,6,7,8-tetrahydroimidazo 1,2apyrazine;
7-(2-(1-(4-cyanophenylmethyl)-imidazole-5-yl)-1-oxo-ethyl)-8-(cyclohexylmethyl)-2-(2-methoxyphenyl)-5,6,7,8-tetrahydroimidazo1,2apyrazine;
5-butyl-7-(2-(1H-imidazole-5-yl)-1-oxo-ethyl)-2-(2-methoxyphenyl)-5,6,7,8-tetrahydroimidazo 1,2apyrazine;
7-((2-(4-cyanophenylmethyl)-imidazol-5-yl)-1-oxo-ethyl)-2-(2-(phenylmethoxy)-phenyl)-5,6,7,8-tetrahydroimidazo1,2-apyrazine; or
2-(2-butoxyphenyl)-7-((2-(4-cyanophenylmethyl)-imidazol-5-yl)-1-oxo-ethyl)-5,6,7,8-tetrahydroimidazo1,2-apyrazine;
or a pharmaceutically acceptable salt thereof.
6. A compound according to claim 2, wherein said compound is
or a pharmaceutically acceptable salt thereot.
7. A pharmaceutical composition comprising an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
8. A method of treating a disease in a subject in need thereof, said method comprising administering to said subject a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein said disease is selected from the group consisting of fibrosis, benign prostatic hyperplasia, atherosclerosis, restenosis, breast cancer, colon cancer, pancreas cancer, prostate cancer, lung cancer, ovarian cancer, epidermal cancer, hematopoietic cancer, and hepatitis delta virus infection.