1,2-diphenylethene derivatives for treatment of immune diseases
View Patent ↗The invention provides novel 1,2-diphenylethene derivatives and pharmaceutically acceptable salts thereof, the process for production of these compounds and their pharmaceutical composition and the use of these compounds as modulators of T-cells, neutrophils, macrophages and their associated cytokines as agents for treating immune, inflammatory and auto-immune diseases.
1. A pharmaceutical composition comprising a compound of formula Ib:
wherein R 1 is isopropyl;
R 2 is selected from a group consisting of
a) H,
b) alkyl, alkenyl, alkynyl, aryl, aralkyl, 4-methylbenzyl, 3-fluorobenzyl, or 3,5-difluorobenzyl,
c) COOR 6 ,
d) NR 7 R 8 ,
e) S(O) 2 NR 7 R 8 ,
f) COR 9 ,
g) OR 10 , and
h) S(O) n R 11 , n=0−2,
R 3 is selected from a group consisting of
a) H,
b) alkyl, alkenyl, alkynyl, aryl, aralkyl, 4-methylbenzyl, 3-fluorobenzyl, or 3,5-difluorobenzyl,
c) halo,
e) NR 7 R 8 ,
f) S(O) 2 NR 7 R 8 ,
g) COR 9 ,
h) OR 10 , and
i) S(O) n R 11 , n=0−2,
R 4 and R 5 are independently each selected from the group consisting of
a) H,
b) alkyl, cycloalkyl, aryl or aralkyl, or
c) acyl;
R 6 is selected from
a) alkyl, cycloalkyl, aryl or aralkyl
R 7 and R 8 are independently selected from a group consisting of
a) H, or
b) alkyl, cycloalkyl, aryl or aralkyl;
R 9 is selected from
a) H, or
b) alkyl, cycloalkyl, aryl, or aralkyl,
R 10 is selected from
a) H,
b) alkyl, cycloalkyl, aryl, or aralkyl, or
c) acyl;
R 11 is selected from
a) H, or
b) alkyl, cycloalkyl, aryl or aralkyl;
Ar is an unsubstituted phenyl, or a phenyl monosubstituted or multisubstituted independently with unsubstituted or substituted alkyl, alkenyl, alkynyl, aryl or aralkyl, halogen, CN, COOR 6 , NR 7 R 8 , S(O) 2 NR 7 R 8 , COR 9 , OR 10 , or S(O) n R 11 wherein n=0−2;
provided that R 2 and R 3 cannot be H simultaneously,
the configuration of the double bond is Z or E, or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier or excipient.
2. The composition according to claim 1 wherein R 4 and R 5 are each independently selected from hydrogen, alkyl or acyl.
3. The composition according to claim 2 wherein R 4 and R 5 are each independently selected hydrogen, methyl or acyl.
4. The composition according to claim 3 wherein R 4 and R 5 are both hydrogen.
5. The composition according to claim 3 wherein R 4 and R 5 are both methyl.
6. The composition according to claim 3 wherein R 4 and R 5 are both acyl.
7. The composition according to claim 1 wherein Ar is an unsubstituted phenyl.
8. The composition according to claim 2 wherein Ar is an unsubstituted phenyl.
9. The composition according to claim 1 wherein Ar is a phenyl mono or multi-substituted with alkyl or halogen.
10. The composition according to claim 9 wherein the alkyl is methyl and the halogen is fluoro.
11. The composition according to claim 10 wherein the Ar is 4-methylphenyl, 3-F-phenyl, or 3,5-difluorophenyl.
12. The composition according to claim 2 wherein Ar is a phenyl mono or multi-substituted with alkyl or halogen.
13. The composition according to claim 12 wherein the Ar is 4-methylphenyl, 3-F-phenyl, or 3,5-difluorophenyl.
14. The composition according to claim 1 wherein R 2 and R 3 are independently selected from hydrogen, alkyl, COR 9 , phenyl, benzyl, 4-methylbenzyl, 3-fluorobenzyl, or 3,5-difluorobenzyl.
15. The composition according to claim 2 wherein R 2 and R 3 are independently selected from hydrogen, methyl, C(O)CH 3 , phenyl, benzyl, 4-methylbenzyl, 3-fluorobenzyl, or 3,5-difluorobenzyl.
16. The composition according to claim 8 wherein R 2 and R 3 are independently selected from hydrogen, methyl, C(O)CH 3 , phenyl, benzyl, 4-methylbenzyl, 3-fluorobenzyl, or 3,5-difluorobenzyl.
17. The composition according to claim 9 wherein R 2 and R 3 are independently selected from hydrogen, methyl, C(O)CH 3 , phenyl, benzyl, 4-methylbenzyl, 3-fluorobenzyl, or 3,5-difluorobenzyl.
18. The composition according to claim 1 wherein R 2 and R 3 are independently selected from hydrogen, alkyl, COR 9 , phenyl, benzyl, 4-methylbenzyl, 3-fluorobenzyl, or 3,5-difluorobenzyl, R 4 and R 5 are each independently selected from hydrogen, alkyl or acyl, Ar is an unsubstituted phenyl or Ar is a phenyl mono or multi-substituted with alkyl or halogen.
19. The composition according to claim 1 wherein the compound of Formula Ib is:
5-(1-Benzyl-2-phenylethenyl)-2-i-propyl-1,3-benzenediol;
5-[1-(4-Methylbenzyl)-2-(4-methylphenyl)ethenyl]-2-i-propyl-1,3-benzenediol;
5-[1-(3-Fluorobenzyl)-2-(3-fluorophenyl)ethenyl]-2-i-propyl-1,3-benzenediol;
5-[1-(3,5-Difluorobenzyl)-2-(3,5-difluorophenyl)ethenyl]-2-i-propyl-1,3-benzenediol;
5-(1-Methyl-2-phenylethenyl)-2-i-propyl-1,3-benzenediol;
5-(2,2-Diphenylethenyl)-2-i-propyl-1,3-benzenediol (8);
1-(3,5-Dimethoxy-4-i-propylphenyl)-2-phenylpropene;
5-(2-Methyl-2-phenylethenyl)-2-isopropyl-1,3-benzenediol;
1-(3,5-Dimethoxyphenyl)-2-phenylpropene;
5-(2-Methyl-2-phenylethenyl)-1,3-benzenediol;
5-(2-Methyl-2-phenylethenyl)-2-i-propyl-1,3-benzenediol diacetate;
2-(3,5-Dihydroxy-4-i-propylphenyl)-3-phenylpropenoic acid; or
3-(3,5-Dihydroxy-4-i-propylphenyl)-2-phenylpropenoic acid.
20. The composition according to claim 1 adapted for systemic, oral or topical administration.
21. The composition according to claim 20 adapted for topical administration.