IP Library › Granted Patent US 7,851,626

Granted Patent B2

US 7,851,626 · App. 11/604,558 · Granted Dec 14, 2010

4,4,5,5, tetrasubstituted imidazolines

Assignee: Hoffmann-La Roche Inc.

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Patent No.: US 7,851,626
App. No.: 11/604,558
Granted: Dec 14, 2010
Kind: B2

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Abstract

There is provided a compound of formula I and the pharmaceutically acceptable salts and esters thereof wherein X 1 , X 2 , R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are herein described. The compounds exhibit activity as anticancer agents.

Claims (323)

1. A compound of the formula

wherein X 1 and X 2 are halogen, acetylene, cyano, trifluoromethyl or nitro;

R 1 and R 2 are selected from the group consisting of H, CH 3 , CH 2 CH 3 , CH 2 OH and CH 2 OCH 3 with the proviso that R 1 and R 2 are not both hydrogen;

R 3 is H or —C(═O)—R 7 ;

and where R 6 is hydrogen then

R 4 is —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 F, —OCH 2 CH 2 OCH 3 , or —OCH(CH 3 ) 2 ;

R 5 is

—H

-halogen,

—CH 3 ,

—CF 3 ,

—OCH 3 ,

—C(CH 3 ) 2 ,

-cyclopropyl,

-cyano,

—C(CH 3 ) 3 ,

—C(CH 3 ) 2 OR (where R is H, CH 3 or CH 2 CH 3 ),

—C(CH 3 ) 2 CH—OR (where R is H, CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 OH or CH 2 CH 2 OCH 3 ),

—C(CH 3 ) 2 CN,

—C(CH 3 ) 2 COR (where R is CH 3 ),

—C(CH 3 ) 2 COOR (where R is H, CH 3 , CH 2 CH 3 or CH(CH 3 ) 2 ),

—C(CH 3 ) 2 CONR a R b (where R a is H or CH 3 and R b ═H or CH 3 ),

—SR (where R is CH 3 or CH 2 CH 3 ), or

—SO 2 R (where R is CH 3 , CH 2 CH 3 , 1-pyrrolidine, NH-tert-butyl or N(CH 3 ) 2 );

and where R 6 is not hydrogen then

R 4 is —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 F, —OCH 2 CH 2 OCH 3 , or —OCH(CH 3 ) 2 ;

R 5 is hydrogen, —Cl, —OCH 3 , tert-butyl or —N(CH 3 ) 2 ;

R 6 is —Cl, cyclopropyl, —SO 2 R (where R is CH 3 , CH 2 CH 3 , 1-pyrrolidine, NH-tert-butyl, NH 2 , or N(CH 3 ) 2 );

and R 7 is selected from the group consisting of

i) —CH 3 , —CH(CH 3 ) 2 , —CH 2 CH(CH 3 ) 2 , cyclopropyl, cyclobutyl, —CH 2 CH 2 Ph, 2-furanyl, phenyl, or phenyl substituted by chloro, OCH 3 or cyano,

ii) 4-morpholinyl, 1-piperidinyl, 4-thiomorpholinyl, or 4-thiomorpholinyl-1,1-dioxide,

iii) —NR c 2 (wherein R c is hydrogen, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 OH, —CH 2 CH 2 OCH 3 , or —CH 2 CH(OH)CH 2 OH),

iv) a substituted piperazine of the formula

wherein R is selected from the group consisting of

a) hydrogen,

b) lower alkyl,

c) CH(CH 3 ) 2 ,

d) CH(CH 2 CH 3 ) 2 ,

e) cyclopentyl,

f) —CH 2 CH(OH)CH 3 ,

g) —CH 2 CF 3 ,

h) —CH 2 CH(OH)CF 3 ,

i) —CH 2 C(CH 3 ) 2 OH,

j) —CH 2 -[4-N-methylpiperidinyl],

k) —CH 2 CH 2 R d (wherein R d is —OH, —OCH 3 , —OCH 2 CH 2 OH, —OCH 2 CH 2 OCH 3 , —CN, —CF 3 , —SO 2 CH 3 , —SO 2 NH 2 , —SO 2 N(CH 3 ) 2 , —CONH 2 , —CON(CH 3 ) 2 , —NH 2 , —NHCOCH 3 , —NHSO 2 CH 3 , —N(CH 3 ) 2 , —N(CH 2 CH 3 ) 2 , —N(CH 2 CH 2 CH 3 ) 2 , 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl, 2-isothiazolidinyl-1,1-dioxide, or 2-tetrahydrofuranyl),

l) —CH 2 CH 2 CH 2 R e (wherein R e is —OH, —OCH 3 , —SO 2 CH 3 , —SO 2 CH 2 CH 3 , —SO 2 N(CH 3 ) 2 , —CN, —N(CH 3 ) 2 , —N(CH 2 CH 2 CH 3 ) 2 , 1-imidazoyl, 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl, —COOCH 3 , —COOCH 2 CH 3 , —COOC(CH 3 ) 3 , —CON(CH 3 ) 2 , —CO—R f (wherein R f is CH 3 , CH 2 CH 3 , cyclopropyl, phenyl, 2-thienyl, 3-thienyl, 2-furanyl, 3-furanyl), —COCH 2 —R g (wherein R g is H, —NHCH 2 CH 2 OH, —NHCH 2 CH 2 OCH 3 , —NHCH 2 CH 2 N(CH 3 ) 2 , 1-piperidinyl, 1-(piperidinyl-4-methanol), 4-morpholinyl, or —N(CH 3 )-(3-(1-methylpyrrolidinyl)),

m) —CH 2 —CO—R h (wherein R h is —OCH 3 , OCH 2 CH 3 , —NH 2 , —NHCH 2 CH(CH 3 ) 2 , —NHCH 2 CF 3 , —NH-cyclopropyl, —NH-tert-butyl, —NHCH 2 CH 2 CH 2 OH, —N(CH 3 ) 2 , —N(CH 2 CH 3 ) 2 , —N(CH 2 CH 2 OH) 2 , —N(CH 2 CH 2 OCH 3 ) 2 , —N(CH 3 )CH 2 CH 2 OH, —N(CH 3 )CH 2 CH 2 OCH 3 , —NHCH 2 CH 2 OCH 3 , 1-pyrrolidinyl, 1-piperidinyl, 1-(piperidinyl-4-methanol), 1-(piperidinyl-3-carboxamide), 4-morpholinyl, 4-thiomorpholinyl, 4-thiomorpholinyl-1,1-dioxide, 1-piperazinyl, 1-(4-acetylpiperazinyl), 1-(3-oxopiperazinyl),

n) —SO 2 R i (wherein R i is —CH 3 , —CH 2 CH 3 , —CH(CH 3 ) 2 , phenyl, 4-methylphenyl, 4-propylphenyl, CF 3 , 2-thienyl, 3-thienyl, NH 2 , NHCH 3 , N(CH 3 ) 2 , NHCH 2 CH 2 OCH 3 , N(CH 2 CH 2 OCH 3 ) 2 , 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl, 1-piperazyl-4-ethanol, 1-(4-acetylpiperazinyl), 1-(3-oxopiperazinyl)),

o) —COR j (wherein R j is —CH 3 , —CH 2 CH 3 , —CH(CH 3 ) 2 , 2-tetrahydrofuranyl, 2-thienyl, 3-thienyl, NH 2 , NHCH 3 , N(CH 3 ) 2 , 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl, 1-piperazinyl-4-ethanol, 1-(4-acetylpiperazinyl), or 1-(3-oxopiperazinyl)),

p) 4-tetrahydro-2H-thiopyranyl-1,1-dioxide,

q) 4-piperidinyl-1-acetyl,

r) 4-piperidinyl-1-dimethylcarboxamide, and

s) 3-tetrahydro-thiophenyl-1,1-dioxide;

v) a substituted oxopiperazine of the formula

wherein R is H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 OH, or —CH 2 CH 2 OCH 3

and

vi) a substituted piperidine of the formula

wherein R is H, COOCH 3 , COOCH 2 CH 3 , CONH 2 , —OH, CH 2 OH, CH 2 CH 2 OH, CH 2 —N(CH 2 CH 3 ) 2 , —CH 2 -(1-piperazinyl), CH 2 -(1-(3-oxopiperazinyl)), NH 2 , NHCOCH 3 , NHCOCH 2 NH 2 , NHCOCH 2 NHCH 3 , NHCOCH 2 N(CH 3 ) 2 , NHCOCH 2 N(CH 2 CH 2 OH) 2 , NHCOCH 2 N(CH 2 CH 2 OCH 3 ) 2 , NHCOCH 2 NHCH 2 CH 2 OH, NHCOCH 2 -(1-(4-acetylpiperazinyl)), NHCOCH 2 -(1-(3-oxopiperazinyl)), NHCOCH 2 -(1-piperidinecarboxamide), NHCOCH 2 —(N,N-diethyl-1-piperidinylcarboxamide), NHCOCH 2 -(1-(3-hydroxypiperidinyl)), NHCOCH 2 -(1-(piperidinyl-4-methanol)), NHCON(CH 3 ) 2 , NHCSNHCH 3 , NHCSNHPh, NHCH 2 CONH 2 , 1-pyrrolidinyl, 1-piperidinyl, 1-(4-methylpiperazinyl), or 4-morpholinyl;

and the pharmaceutically acceptable salts and esters thereof.

2. Compound of claim 1 wherein X 1 and X 2 are —Cl.

3. Compound of claim 2 wherein R 3 is —C(═O)—R 7 .

4. Compound of claim 3 where R 6 is hydrogen; R 4 is —OCH 3 , —OCH 2 CH 3 , or —OCH(CH 3 ) 2 ; and R 5 is —C(CH 3 ) 3 , —C(CH 3 ) 2 OR (where R is H or CH 3 ), —C(CH 3 ) 2 CH—OR (where R is H or CH 3 ), —C(CH 3 ) 2 CN, —C(CH 3 ) 2 COR (where R is CH 3 ), —SO 2 R (where R is CH 3 , 1-pyrrolidine, NH-tert-butyl or N(CH 3 ) 2 ).

5. The compound of claim 3 where R 4 is —OCH 3 , —OCH 2 CH 3 , or —OCH(CH 3 ) 2 ; R 5 is —Cl; and R 6 is —SO 2 R (where R is CH 3 , 1-pyrrolidine, NH-tert-butyl, NH 2 , or N(CH 3 ) 2 ).

6. The compound of claim 3 wherein R 7 is

and wherein R is —CHCOR h .

7. The compound of claim 6 wherein R h is 4-morpholinyl, 1-pyrrolidinyl, 1-piperidinyl, NH 2 , or N(CH 3 ) 2 .

8. The compound of claim 3 wherein R 7 is

and wherein R is —CH 2 CH 2 CH 2 R e .

9. The compound of claim 8 wherein R e is —SO 2 CH 3 or —SO 2 CH 2 CH 3 .

10. The compound of claim 3 wherein R 7 is

and wherein R is —CH 2 CH 2 R d .

11. The compound of claim 10 wherein R d is —SO 2 CH 3 , —NHSO 2 CH 3 , —NHCOCH 3 , or CF 3 .

12. The compound of claim 3 wherein R 7 is

and R is 4-tetrahydro-2H-thiopyranyl-1,1-dioxide.

13. A compound of claim 1 selected from the group consisting of:

rac-(4S*,5R*)-4,5-Bis(4-chlorophenyl)-2-(4-(tert-butyl)-2-ethoxy-phenyl)-4,5-dimethyl-4,5-dihydro-1H-imidazole,

(4S,5R)-4-[[4-[[4,5-Bis(4-chlorophenyl)-2-[4-(tert-butyl)-2-ethoxy-phenyl]-4,5-dimethyl-4,5-dihydro-1H-imidazol-1-yl]carbonyl]-1-piperazinyl]acetyl]-morpholine,

(4S,5R)-4-[[4-[[4,5-bis(4-chlorophenyl)-2-[4-(tert-butyl)-2-ethoxy-phenyl]-4,5-dimethyl-4,5-dihydro-1H-imidazol-1-yl]carbonyl]-1-piperidine,

((4S,5R)-1-[[4-[[4,5-bis(4-chlorophenyl)-2-[4-(tert-butyl)-2-ethoxy-phenyl]-4,5-dimethyl-4,5-dihydro-1H-imidazol-1-yl]]-carbonyl]-4-[3,3,3-trifluoropropyl]-piperazine,

2-{4-[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-acetamide,

2-{4-[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-1-pyrrolidin-1-yl-ethanone and

N-(2-{4-[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-ethyl)-acetamide.

14. A compound of claim 1 selected from the group consisting of

N-(2-{4-[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-ethyl)-methanesulfonamide,

[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-methanone,

(S)-4-[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-1-methyl-piperazine-2-carboxylic acid methyl ester,

5-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-1-[4-(3-methanesulfonyl-propyl)-piperazine-1-carbonyl]-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl}-2-tert-butyl-4-ethoxy-N,N-dimethyl-benzenesulfonamide,

rac-2-{4-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl]-3-ethoxy-phenyl}-2-methyl-propionitrile,

2-(4-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-1-[4-(3-methanesulfonyl-propyl)-piperazine-1-carbonyl]-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl}-3-ethoxy-phenyl)-2-methyl-propionitrile,

N-[2-(4-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-[4-(cyano-dimethyl-methyl)-2-ethoxy-phenyl]-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl}-piperazin-1-yl)-ethyl]-methanesulfonamide,

N-[2-(4-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-[4-(cyano-dimethyl-methyl)-2-ethoxy-phenyl]-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl}-piperazin-1-yl)-ethyl]-acetamide and

2-(4-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-1-[4-(2-hydroxy-ethyl)-piperazine-1-carbonyl]-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl}-3-ethoxy-phenyl)-2-methyl-propionitrile.

15. A compound of claim 1 selected from the group consisting of

2-(4-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-1-[4-(1,1-dioxo-tetrahydro-2H-thiopyran-4-yl)-piperazine-1-carbonyl]-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl}-3-ethoxy-phenyl)-2-methyl-propionitrile,

2-(4-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-[4-(cyano-dimethyl-methyl)-2-ethoxy-phenyl]-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl}-piperazin-1-yl)-acetamide,

2-[4-((4S,5R)-4,5-Bis-(4-chloro-phenyl)-1-{4-[2-(1,1-dioxo-isothiazolidine-2-yl)-ethyl]-piperazine-1-carbonyl}-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl)-3-ethoxy-phenyl]-2-methyl-propionitrile,

2-(4-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-4,5-dimethyl-1-[4-(2-oxo-2-pyrrolidin-1-yl-ethyl)-piperazine-1-carbonyl]-4,5-dihydro-1H-imidazol-2-yl}-3-ethoxy-phenyl)-2-methyl-propionitrile,

2-{4-[(4S,5R)-1-[4-(1-Acetyl-piperidin-4-yl)-piperazine-1-carbonyl]-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl]-3-ethoxy-phenyl}-2-methyl-propionitrile,

4-(4-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-[4-(cyano-dimethyl-methyl)-2-ethoxy-phenyl]-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl}-piperazin-1-yl)-piperidine-1-carboxylic acid isopropylamide,

rac-(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(pyrrolidine-1-sulfonyl)-phenyl]-4,5-dimethyl-4,5-dihydro-1H-imidazole and

rac-(4S*,5R*)-4-[(4,5-Bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl]-N-tert-butyl-3-ethoxy-benzenesulfonamide.

16. A compound of claim 1 selected from the group consisting of

{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(pyrrolidine-1-sulfonyl)-phenyl]-4,5-dimethyl-4,5-dihydro-imidazol-1-yl}-[4-(3-methanesulfonyl-propyl)-piperazin-1-yl]-methanone,

2-(4-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(pyrrolidine-1-sulfonyl)-phenyl]-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl}-piperazin-1-yl)-acetamide,

2-(4-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(pyrrolidine-1-sulfonyl)-phenyl]-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl}-piperazin-1-yl)-1-pyrrolidin-1-yl-ethanone,

N-[2-(4-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(pyrrolidine-1-sulfonyl)-phenyl]-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl}-piperazin-1-yl)-ethyl]-methanesulfonamide,

N-[2-(4-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(pyrrolidine-1-sulfonyl)-phenyl]-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl}-piperazin-1-yl)-ethyl]-acetamide,

{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(pyrrolidine-1-sulfonyl)-phenyl]-4,5-dimethyl-4,5-dihydro-imidazol-1-yl}-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-methanone,

4-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-1-[4-(3-methanesulfonyl-propyl)-piperazine-1-carbonyl]-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl}-N-tert-butyl-3-ethoxy-benzenesulfonamide,

2-{4-[(4S,5R)-2-(4-tert-Butylsulfamoyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-acetamide,

rac-(4S*,5R*)-5-[4,5-Bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl]-N-tert-butyl-2-chloro-4-ethoxybenzenesulfonamide and

5-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-1-[4-(3-methanesulfonyl-propyl)-piperazine-1-carbonyl]-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl}-N-tert-butyl-2-chloro-4-ethoxy-benzenesulfonamide.

17. A compound of claim 1 selected from the group consisting of

5-{(4S,5R)-4,5-Bis-(4-chlorophenyl)-1-[4-(2-methanesulfonylaminoethyl)piperazine-1-carbonyl]-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl}-N-tert-butyl-2-chloro-4-ethoxybenzenesulfonamide,

N-{(4S,5R)-(2-{4-[2-(5-tert-Butylsulfamoyl-4-chloro-2-ethoxyphenyl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazin-1-yl}ethyl)acetamide,

5-{(4S,5R)-4,5-Bis-(4-chlorophenyl)-1-[4-(2-hydroxyethyl)piperazine-1-carbonyl]-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl}-N-tert-butyl-2-chloro-4-ethoxybenzenesulfonamide,

5-{(4S,5R)-4,5-Bis-(4-chlorophenyl)-4,5-dimethyl-1-[4-(2-oxo-2-pyrrolidin-1-yl-ethyl)-piperazine-1-carbonyl]-4,5-dihydro-1H-imidazol-2-yl}-N-tert-butyl-2-chloro-4-ethoxybenzenesulfonamide,

2-{4-[(4S,5R)-2-(5-tert-Butylsulfamoyl-4-chloro-2-ethoxyphenyl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazin-1-yl}-acetamide,

(S)-4-[(4S,5R)-2-(5-tert-Butylsulfamoyl-4-chloro-2-ethoxyphenyl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-1-methylpiperazine-2-carboxylic acid methyl ester,

rac-(4S*,5R*)-2-[4-Chloro-2-ethoxy-5-(pyrrolidine-1-sulfonyl)phenyl]-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydro-1H-imidazole,

5-{(4S,5R)-2-[4-Chloro-2-ethoxy-5-(pyrrolidine-1-sulfonyl)phenyl]-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydroimidazol-1-yl]-[4-(3-methanesulfonylpropyl)-piperazin-1-yl]methanone and

rac-(4S*,5R*)-4,5-Bis-(4-chlorophenyl)-2-[2-ethoxy-4-methoxy-5-(pyrrolidine-1-sulfonyl)phenyl]-4,5-dimethyl-4,5-dihydro-1H-imidazole.

18. A compound of claim 1 selected from the group consisting of

{(4S,5R)-4,5-Bis-(4-chlorophenyl)-2-[2-ethoxy-4-methoxy-5-(pyrrolidine-1-sulfonyl)-phenyl]-4,5-dimethyl-4,5-dihydroimidazol-1-yl}-[4-(3-methanesulfonylpropyl)-piperazin-1-yl]methanone,

rac-(4S*,5R*)-2-(4-Chloro-2-ethoxy-5-methanesulfonylphenyl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydro-1H-imidazole,

[(4S,5R)-2-(4-Chloro-2-ethoxy-5-methanesulfonyl-phenyl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazol-1-yl]-[4-(3-methanesulfonylpropyl)-piperazin-1-yl]methanone,

rac-(4S*,5R*)-4,5-Bis-(4-chlorophenyl)-2-[2-ethoxy-5-(pyrrolidine-1-sulfonyl)phenyl]-4,5-dimethyl-4,5-dihydro-1H-imidazole,

{(4S,5R)-4,5-Bis-(4-chlorophenyl)-2-[2-ethoxy-5-(pyrrolidine-1-sulfonyl)phenyl]-4,5-dimethyl-4,5-dihydroimidazol-1-yl}-[4-(3-methanesulfonylpropyl)-piperazin-1-yl]methanone,

rac-4-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl]-3-ethoxy-benzonitrile and

4-{(4S,5R)-4,5-Bis-(4-chlorophenyl)-1-[4-(3-methanesulfonylpropyl)-piperazine-1-carbonyl]-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl}-3-ethoxybenzonitrile.

19. A compound of claim 1 selected from the group consisting of

[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-piperazin-1-yl-methanone,

1-{4-[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-ethanone,

N-tert-Butyl-2-{4-[(4S,5R)-2-(4-tert-butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-acetamide,

rac-(4S*,5R*)-2-(4-Bromo-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-1H-imidazole,

rac-(4S*,5R*)-2-(4-Bromo-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(3-methanesulfonyl-propyl)-piperazin-1-yl]-methanone,

rac-2-{4-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl]-3-ethoxy-phenyl}-propan-2-ol and

[(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(3-methanesulfonyl-propyl)-piperazin-1-yl]-methanone.

20. A compound of claim 1 selected from the group consisting of

2-{4-[(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-acetamide,

{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(1-hydroxy-1-methyl-ethyl)-phenyl]-4,5-dimethyl-4,5-dihydro-imidazol-1-yl}-[4-(3-methanesulfonyl-propyl)-piperazin-1-yl]-methanone,

2-(4-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(1-hydroxy-1-methyl-ethyl)-phenyl]-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl}-piperazin-1-yl)-acetamide,

{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(1-hydroxy-1-methyl-ethyl)-phenyl]-4,5-dimethyl-4,5-dihydro-imidazol-1-yl}-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-methanone,

2-(4-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(1-hydroxy-1-methyl-ethyl)-phenyl]-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl}-piperazin-1-yl)-1-pyrrolidin-1-yl-ethanone,

N-[2-(4-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(1-hydroxy-1-methyl-ethyl)-phenyl]-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl}-piperazin-1-yl)-ethyl]-acetamide,

N-[2-(4-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(1-hydroxy-1-methyl-ethyl)-phenyl]-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl}-piperazin-1-yl)-ethyl]-methanesulfonamide,

{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(1-hydroxy-1-methyl-ethyl)-phenyl]-4,5-dimethyl-4,5-dihydro-imidazol-1-yl}-[4-(1,1-dioxo-tetrahydro-2H-thiopyran-4-yl)-piperazin-1-yl]-methanone,

rac-(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4,5-dimethyl-4,5-dihydro-1H-imidazole.

21. A compound of claim 1 selected from the group consisting of

rac-(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(3-methanesulfonyl-propyl)-piperazin-1-yl]-methanone,

rac-2-{4-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-acetamide,

rac-2-{4-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-1-morpholin-4-yl-ethanone,

rac-4-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-2-one,

rac-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(2-methanesulfonyl-ethyl)-piperazin-1-yl]-methanone,

rac-(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(1-methoxy-1-methyl-ethyl)-phenyl]-4,5-dimethyl-4,5-dihydro-1H-imidazole,

2-(4-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(1-methoxy-1-methyl-ethyl)-phenyl]-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl}-piperazin-1-yl)-acetamide,

{rac-(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(1-methoxy-1-methyl-ethyl)-phenyl]-4,5-dimethyl-4,5-dihydro-imidazol-1-yl}-[4-(3-methanesulfonyl-propyl)-piperazin-1-yl]-methanone and

{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(1-methoxy-1-methyl-ethyl)-phenyl]-4,5-dimethyl-4,5-dihydro-imidazol-1-yl}-[4-(1,1-dioxo-tetrahydro-2H-thiopyran-4-yl)-piperazin-1-yl]-methanone.

22. A compound of claim 1 selected from the group consisting of

rac-1-[(4S*,5R*)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-ethanone,

1-[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-2-methyl-propan-1-one,

[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-cyclopropyl-methanone,

[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-cyclobutyl-methanone,

1-[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-3-methyl-butan-1-one,

1-[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-3-phenyl-propan-1-one,

4-[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-benzonitrile,

[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-furan-2-yl-methanone,

[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-phenyl-methanone and

rac-[(4S*,5R*)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-(4-methoxy-phenyl)-methanone.

23. A compound of claim 1 selected from the group consisting of

rac-[(4S*,5R*)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-(4-chloro-phenyl)-methanone,

rac-(4S*,5R*)-2-(4-tert-Butyl-5-chloro-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-1H-imidazole,

[(4S,5R)-2-(4-tert-Butyl-5-chloro-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(3-methanesulfonyl-propyl)-piperazin-1-yl]-methanone,

2-{4-[(4S,5R)-2-(4-tert-Butyl-5-chloro-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-acetamide,

rac-(2-{4-[4S*,5R*)-2-(4-tert-Butyl-5-chloro-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-1-morpholin-4-yl-ethanone,

rac-[(4S*,5R*)-2-(4-tert-Butyl-5-chloro-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-(4-dimethylamino-piperidin-1-yl)-methanone,

rac-[(4S*,5R*)-2-(4-tert-Butyl-5-chloro-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone,

rac-[1,4′]Bipiperidinyl-1′-yl-[(4S*,5R*)-2-(4-tert-butyl-5-chloro-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-methanone and

rac-{1-[(4S*,5R*)-2-(4-tert-Butyl-5-chloro-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperidin-4-yl}-carbamic acid tert-butyl ester.

24. A compound of claim 1 selected from the group consisting of

rac-(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dimethyl-4,5-dihydro-1H-imidazole,

rac-4-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-2-one,

rac-1-{4-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-ethanone,

[(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(3-methanesulfonyl-propyl)-piperazin-1-yl]-methanone,

rac-2-{4-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-1-morpholin-4-yl-ethanone,

rac-(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-(4-ethanesulfonyl-piperazin-1-yl)-methanone,

rac-(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carboxylic acid (1-methanesulfonyl-piperidin-4-yl)-amide,

rac-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-methanone and

rac-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-(4-morpholin-4-yl-piperidin-1-yl)-methanone.

25. A compound of claim 1 selected from the group consisting of

rac-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-(4-hydroxy-piperidin-1-yl)-methanone,

rac-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-(4-hydroxymethyl-piperidin-1-yl)-methanone,

rac-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(2-hydroxy-ethyl)-piperidin-1-yl]-methanone,

rac-1-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperidine-4-carboxylic acid amide,

rac-(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carboxylic acid bis-(2-hydroxy-ethyl)-amide,

rac-(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carboxylic acid (2,3-dihydroxy-propyl)-amide,

3-{4-[4,5-Bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl]-3-ethoxy-phenyl}-3-methyl-butan-2-one,

3-(4-{4,5-Bis-(4-chloro-phenyl)-1-[4-(3-methanesulfonyl-propyl)-piperazine-1-carbonyl]-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl}-3-ethoxy-phenyl)-3-methyl-butan-2-one and

3-(4-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-1-[4-(1,1-dioxo-tetrahydro-2H-thiopyran-4-yl)-piperazine-1-carbonyl]-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl}-3-ethoxy-phenyl)-3-methyl-butan-2-one.

26. A compound of claim 1 selected from the group consisting of

2-(4-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-[4-(1,1-dimethyl-2-oxo-propyl)-2-ethoxy-phenyl]-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl}-piperazin-1-yl)-acetamide,

rac-(4S*,5R*)-2-(4-tert-Butyl-2-isopropoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-1H-imidazole,

rac-1-{4-[(4S*,5R*)-2-(4-tert-Butyl-2-isopropoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-ethanone,

rac-[(4S*,5R*)-2-(4-tert-Butyl-2-isopropoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-(4-isopropyl-piperazin-1-yl)-methanone,

rac-4-{4-[(4S*,5R*)-2-(4-tert-Butyl-2-isopropoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-butyronitrile,

rac-[(4S*,5R*)-2-(4-tert-Butyl-2-isopropoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(3-methoxy-propyl)-piperazin-1-yl]-methanone,

rac-[(4S*,5R*)-2-(4-tert-Butyl-2-isopropoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(2-morpholin-4-yl-ethyl)-piperazin-1-yl]-methanone,

rac-[(4S*,5R*)-2-(4-tert-Butyl-2-isopropoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(tetrahydro-furan-2-ylmethyl)-piperazin-1-yl]-methanone and

rac-[(4S*,5R*)-2-(4-tert-Butyl-2-isopropoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-(hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-methanone.

27. A compound of claim 1 selected from the group consisting of

rac-[(4S*,5R*)-2-(4-tert-Butyl-2-isopropoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-(octahydro-pyrido[1,2-a]pyrazin-2-yl)-methanone,

rac-(4S*,5R*)-2-(4-tert-Butyl-2-isopropoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carboxylic acid bis-(2-methoxy-ethyl)-amide,

rac-[(4S*,5R*)-2-(4-tert-Butyl-2-isopropoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(2-methoxy-ethyl)-piperazin-1-yl]-methanone,

[(4S,5R)-2-(4-tert-Butyl-2-isopropoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(3-methanesulfonyl-propyl)-piperazin-1-yl]-methanone,

[(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-isopropyl-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(3-methanesulfonyl-propyl)-piperazin-1-yl]-methanone,

[(4S,5R)-2-(5-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(3-methanesulfonyl-propyl)-piperazin-1-yl]-methanone,

[(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-5-methanesulfonyl-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(3-methanesulfonyl-propyl)-piperazin-1-yl]-methanone,

[(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-methanesulfonyl-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(3-methanesulfonyl-propyl)-piperazin-1-yl]-methanone,

[(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-(4-cyclopropyl-2-ethoxy-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(3-methanesulfonyl-propyl)-piperazin-1-yl]-methanone and

[(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-(5-cyclopropyl-2-ethoxy-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(3-methanesulfonyl-propyl)-piperazin-1-yl]-methanone.

28. A compound of claim 1 selected from the group consisting of

[(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-(4-ethanesulfonyl-2-ethoxy-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(3-methanesulfonyl-propyl)-piperazin-1-yl]-methanone,

[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-diethyl-4,5-dihydro-imidazol-1-yl]-[4-(3-methanesulfonyl-propyl)-piperazin-1-yl]-methanone,

[(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-ethylsulfanyl-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(3-methanesulfonyl-propyl)-piperazin-1-yl]-methanone,

[(4S,5R)-2-(4-tert-Butyl-2-methoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(3-methanesulfonyl-propyl)-piperazin-1-yl]-methanone,

[(4S,5R)-2-(4-Chloro-2-ethoxy-5-methanesulfonyl-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(1,1-dioxo-tetrahydro-2H-thiopyran-4-yl)-piperazin-1-yl]-methanone,

[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(1,1-dioxo-tetrahydro-thiophen-3-yl)-piperazin-1-yl]-methanone,

[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-(3-ethanesulfonyl-propyl)-piperazin-1-yl]-methanone,

2-(4-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-1-[4-(3-ethanesulfonyl-propyl)-piperazine-1-carbonyl]-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl}-3-ethoxy-phenyl)-2-methyl-propionitrile,

(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4-methyl-4,5-dihydro-1H-imidazole.

29. A compound of claim 1 selected from the group consisting of

[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4-methyl-4,5-dihydro-imidazol-1-yl]-piperazin-1-yl-methanone,

1-[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4-methyl-4,5-dihydro-imidazole-1-carbonyl]-piperidine-4-carboxylic acid amide,

1-{4-[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4-methyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-ethanone,

rac-(4S*,5R*)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4-methyl-4,5-dihydro-imidazole-1-carboxylic acid (2-dimethylamino-ethyl)-amide,

rac-4-[(4S*,5R*)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4-methyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-2-one,

rac-2-{4-[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4-methyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-1-morpholin-4-yl-ethanone,

rac-[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4-methyl-4,5-dihydro-imidazol-1-yl]-(4-methanesulfonyl-piperazin-1-yl)-methanone,

rac-2-{4-[(4S*,5R*)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4-methyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-1-pyrrolidin-1-yl-ethanone and

rac-[(4S*,5R*)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4-methyl-4,5-dihydro-imidazol-1-yl]-[4-(tetrahydro-furan-2-carbonyl)-piperazin-1-yl]-methanone.

30. A compound of claim 1 selected from the group consisting of

rac-4-[(4S*,5R*)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4-methyl-4,5-dihydro-imidazole-1-carbonyl]-piperazine-1-carboxylic acid dimethylamide,

rac-2-{4-[(4S*,5R*)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4-methyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-acetamide,

rac-2-{4-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4-methyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-1-pyrrolidin-1-yl-ethanone,

rac-4-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4-methyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-2-one,

rac-2-{4-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4-methyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-1-morpholin-4-yl-ethanone,

rac-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4-methyl-4,5-dihydro-imidazol-1-yl]-(4-methanesulfonyl-piperazin-1-yl)-methanone,

rac-1-{4-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4-methyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-ethanone,

rac-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4-methyl-4,5-dihydro-imidazol-1-yl]-[4-(tetrahydro-furan-2-carbonyl)-piperazin-1-yl]-methanone,

rac-2-{4-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4-methyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-acetamide and

rac-4-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4-methyl-4,5-dihydro-imidazole-1-carbonyl]-piperazine-1-carboxylic acid dimethylamide.

31. A compound of claim 1 selected from the group consisting of

rac-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4-methyl-4,5-dihydro-imidazol-1-yl]-[4-(3-methanesulfonyl-propyl)-piperazin-1-yl]-methanone,

rac-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4-methyl-4,5-dihydro-imidazol-1-yl]-piperazin-1-yl-methanone,

rac-(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4-methyl-4,5-dihydro-imidazole-1-carboxylic acid (2-dimethylamino-ethyl)-amide,

rac-1-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4-methyl-4,5-dihydro-imidazole-1-carbonyl]-piperidine-4-carboxylic acid amide,

rac-4-[(4S*,5R*)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4-ethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-2-one,

rac-1-[(4S*,5R*)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4-ethyl-4,5-dihydro-imidazole-1-carbonyl]-piperidine-4-carboxylic acid amide,

rac-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-4-ethyl-2-(2-isopropoxy-4-methoxy-phenyl)-4,5-dihydro-imidazol-1-yl]-[4-(tetrahydro-furan-2-carbonyl)-piperazin-1-yl]-methanone,

rac-2-{4-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-4-ethyl-2-(2-isopropoxy-4-methoxy-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-1-morpholin-4-yl-ethanone and

rac-4-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-4-ethyl-2-(2-isopropoxy-4-methoxy-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazine-1-carboxylic acid dimethylamide.

32. A compound of the formula:

(4S,5R)-1-[[4-[[4,5-bis(4-chlorophenyl)-2-[4-(tert-butyl)-2-ethoxy-phenyl]-4,5-dimethyl-4,5-dihydro-1H-imidazol-1-yl]]-carbonyl]-4-[3-(methylsulfonyl)propyl]-piperazine and the pharmaceutically acceptable salts thereof.

33. A pharmaceutical composition comprising a compound of the formula

wherein X 1 and X 2 are halogen, acetylene, cyano, trifluoromethyl or nitro;

R 1 and R 2 are selected from the group consisting of H, CH 3 , CH 2 CH 3 , CH 2 OH and CH 2 OCH 3 with the proviso that R 1 and R 2 are not both hydrogen;

R 3 is H or —C(═O)—R 7 ;

and where R 6 is hydrogen then

R 4 is —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 F, —OCH 2 CH 2 OCH 3 , or —OCH(CH 3 ) 2 ;

R 5 is

—H

-halogen,

—CH 3 ,

—CF 3 ,

—OCH 3 ,

—C(CH 3 ) 2 ,

-cyclopropyl,

-cyano,

—C(CH 3 ) 3 ,

—C(CH 3 ) 2 OR (where R is H, CH 3 or CH 2 CH 3 ),

—C(CH 3 ) 2 CH—OR (where R is H, CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 OH or CH 2 CH 2 OCH 3 ),

—C(CH 3 ) 2 CN,

—C(CH 3 ) 2 COR (where R is CH 3 ),

—C(CH 3 ) 2 COOR (where R is H, CH 3 , CH 2 CH 3 or CH(CH 3 ) 2 ),

—C(CH 3 ) 2 CONR a R b (where R a is H or CH 3 and R b ═H or CH 3 ),

—SR (where R is CH 3 or CH 2 CH 3 ), or

—SO 2 R (where R is CH 3 , CH 2 CH 3 , 1-pyrrolidine, NH-tert-butyl or N(CH 3 ) 2 );

and where R 6 is not hydrogen then

R 4 is —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 F, —OCH 2 CH 2 OCH 3 , or —OCH(CH 3 ) 2 ;

R 5 is hydrogen, —Cl, —OCH 3 , tert-butyl or —N(CH 3 ) 2 ;

R 6 is —Cl, cyclopropyl, —SO 2 R (where R is CH 3 , CH 2 CH 3 , 1-pyrrolidine, NH-tert-butyl, NH 2 , or N(CH 3 ) 2 );

and R 7 is selected from the group consisting of

i) —CH 3 , —CH(CH 3 ) 2 , —CH 2 CH(CH 3 ) 2 , cyclopropyl, cyclobutyl, —CH 2 CH 2 Ph, 2-furanyl, phenyl, or phenyl substituted by chloro, OCH 3 or cyano,

ii) 4-morpholinyl, 1-piperidinyl, 4-thiomorpholinyl, or 4-thiomorpholinyl-1,1-dioxide,

iii) —NR c 2 (wherein R c is hydrogen, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 OH, —CH 2 CH 2 OCH 3 , or —CH 2 CH(OH)CH 2 OH),

iv) a substituted piperazine of the formula

wherein R is selected from the group consisting of

a) hydrogen,

b) lower alkyl,

c) CH(CH 3 ) 2 ,

d) CH(CH 2 CH 3 ) 2 ,

e) cyclopentyl,

f) —CH 2 CH(OH)CH 3 ,

g) —CH 2 CF 3 ,

h) —CH 2 CH(OH)CF 3 ,

i) —CH 2 C(CH 3 ) 2 OH,

j) —CH 2 -[4-N-methylpiperidinyl],

l) —CH 2 CH 2 CH 2 R e (wherein R e is —OH, —OCH 3 , —SO 2 CH 3 , —SO 2 CH 2 CH 3 , —SO 2 N(CH 3 ) 2 , —CN, —N(CH 3 ) 2 , —N(CH 2 CH 2 CH 3 ) 2 , 1-imidazoyl, 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl, —COOCH 3 , —COOCH 2 CH 3 , —COOC(CH 3 ) 3 , —CON(CH 3 ) 2 , —CO—RF (wherein R f is CH 3 , CH 2 CH 3 , cyclopropyl, phenyl, 2-thienyl, 3-thienyl, 2-furanyl, 3-furanyl), —COCH 2 —R g (wherein R g is H, —NHCH 2 CH 2 OH, —NHCH 2 CH 2 OCH 3 , —NHCH 2 CH 2 N(CH 3 ) 2 , 1-piperidinyl, 1-(piperidinyl-4-methanol), 4-morpholinyl, or —N(CH 3 )-(3-(1-methylpyrrolidinyl)),

p) 4-tetrahydro-2H-thiopyranyl-1,1-dioxide,

q) 4-piperidinyl-1-acetyl,

r) 4-piperidinyl-1-dimethylcarboxamide, and

s) 3-tetrahydro-thiophenyl-1,1-dioxide;

v) a substituted oxopiperazine of the formula

wherein R is H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 OH, or —CH 2 CH 2 OCH 3

and

vi) a substituted piperidine of the formula

and the pharmaceutically acceptable salts and esters thereof together with a pharmaceutically acceptable excipient.

Continuity (3)

Provisional Application 6085274700 · Oct 19, 2006

Provisional Application 6074122300 · Dec 1, 2005

Related Publication 20070129416A1 · Jun 7, 2007