IP Library › Granted Patent US 7,449,459

Granted Patent B2

US 7,449,459 · App. 11/727,167 · Granted Nov 11, 2008

Inhibitors of soluble adenylate cyclase

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Quick Facts

Patent No.: US 7,449,459
App. No.: 11/727,167
Granted: Nov 11, 2008
Kind: B2

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Abstract

The invention relates to compounds of general formula I as well as the production and use thereof as a medication.

Claims (166)

1. A compound of formula (I),

wherein

R 1 is hydrogen, halogen, CF 3 , C 3 -C 6 -cycloalkyl, which optionally is polysaturated and optionally is polysubstituted, C 1 -C 6 -alkyl, C 1 -C 6 -aryl, C 1 -C 6 -acyl, halo-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-C 1 -C 6 -acyl, C 1 -C 6 -acyl-C 1 -C 6 -acyl, C 1 -C 6 -alkyl-C 1 -C 6 -aryl, or C 1 -C 6 -aryl-C 1 -C 6 -alkyl, wherein C 1 -C 6 -alkyl, C 1 -C 6 -aryl, C 1 -C 6 -acyl, halo-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-C 1 -C 6 -acyl, C 1 -C 6 -acyl-C 1 -C 6 -acyl, C 1 -C 6 -alkyl-C 1 -C 6 -aryl or C 1 -C 6 -aryl-C 1 -C 6 -alkyl groups are optionally interrupted in one or more places, in the same way or differently, by oxygen, sulfur, nitrogen, sulfonyl-C 1 -C 6 -alkyl, sulfonamide, or cyano,

R 2 is halogen, CF 3 , C 3 -C 6 -cycloalkyl which optionally is polysaturated and optionally is polysubstituted, C 1 -C 6 -alkyl, C 1 -C 6 -aryl, C 1 -C 6 -acyl, halo-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-C 1 -acyl, C 1 -C 6 -acyl-C 1 C 6 -acyl, C 1 -C 6 -alkyl-C 1 -C 6 -aryl, or C 1 -C 6 -aryl-C 1 -C 6 -alkyl, wherein C 1 -C 6 -alkyl, C 1 -C 6 -aryl, C 1 -C 6 -acyl, halo-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-C 1 -C 6 -acyl, C 1 -C 6 -acyl-C 1 -C 6 -acyl, C 1 -C 6 -alkyl-C 1 -C 6 -aryl, or C 1 -C 6 -aryl-C 1 -C 6 -alkyl groups are optionally interrupted in one or more places, in the same way or differently, by oxygen, sulfur, nitrogen, sulfonyl-C 1 -C 6 -alkyl, sulfonamide, or cyano,

R 3 is C 6 -C 12 -aryl, which is optionally substituted in one or more places, in the same way or differently, by halogen, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, hydroxy, cyano, CO 2 —(C 1 -C 6 -alkyl), N—(C 1 -C 6 -alkyl) 2 , CO—NR 4 R 5 , CF 3 or C 1 -C 6 -acyl;

C 5 -C 12 -heteroaryl, which optionally is substituted in one or more places, in the same way or differently, by halogen, C 1 -C 6 -alkyl, C 1 -C 6 -acyl, C 1 -C 6 -alkoxy, hydroxy, cyano, CO 2 —(C 1 -C 6 -alkyl), N—(C 1 -C 6 -alkyl) 2 , CO—NR 4 R 5 or CF 3 ; or

C 3 -C 6 -cycloalkyl, which optionally is substituted in one or more places, in the Same way or differently, by halogen, CF 3 , hydroxy, cyano, CO 2 —(C 1 -C 6 -alkyl), C 1 -C 6 -alkyl, C 1 -C 6 -acyl, N—(C 1 -C 6 -alkyl) 2 , CO—NR 4 R 5 or C 1 -C 6 -alkoxy,

R 4 is hydrogen, or C 3 -C 6 -cycloalkyl, which optionally is substituted in one or more places, in the same way or differently, by C 1 -C 6 -alkyl, C 1 -C 6 -acyl, C 1 -C 6 -alkoxy or CF 3 ;

C 6 -C 12 -aryl, which optionally is substituted in one or more places, in the same way or differently, by halogen, C 1 -C 6 -alkyl, C 1 -C 6 -acyl, C 1 -C 6 -alkoxy, N—C 1 -C 6 -alkyl-C 1 -C 6 -alkyl, CF 3 or cyano;

C 5 -C 12 -heteroaryl, which optionally is substituted in one or more places, in the same way or differently, by halogen, C 1 -C 6 -alkyl, C 1 -C 6 -acyl, C 1 -C 6 -alkoxy, N—C 1 -C 6 -alkyl-C 1 -C 6 -alkyl, CF 3 or cyano; or

C 1 -C 6 -alkyl, which can be substituted in any way desired,

R 5 is hydrogen, or C 1 -C 6 alkyl-C 3 -C 6 -cycloalkyl, which optionally is substituted in one or more places, in the same way or differently, by C 1 -C 6 -alkyl, C 1 -C 6 -acyl, C 1 -C 6 -alkoxy or CF 3 ;

C 3 -C 6 -cycloalkyl, which optionally is substituted in one or more places, in the same way or differently, by C 1 -C 6 -alkyl, C 1 -C 6 -acyl, C 1 -C 6 -alkoxy or CF 3 ;

C 1 -C 6 -alkyl, which can be substituted in any way desired,

R 4 and R 5 together can also form a 5- to 8-membered ring, which can contain additional heteroatoms, and

X is sulfonyl, (CH 2 ) n or carbonyl,

Y is —(CH 2 ) n — or —CH═CH—, and

n is 1-4, or

or a diastereomer, or an enantiomer, or a physiologically compatible salt thereof.

2. A compound according to claim 1 , wherein

R 1 is hydrogen, halogen, CF 3 , C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkyl, C 1 -C 6 -aryl, C 1 -C 6 -acyl, halo-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-C 1 -C 6 -acyl, C 1 -C 6 -acyl-C 1 -C 6 -acyl, C 1 -C 6 -alkyl-C 1 -C 6 -aryl, C 1 -C 6 -aryl-C 1 -C 6 -alkyl or CF 3 , wherein C 1 -C 6 -alkyl, C 1 -C 6 -aryl, C 1 -C 6 -acyl, halo-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-C 1 -C 6 -acyl, C 1 -C 6 -acyl-C 1 -C 6 -acyl, C 1 -C 6 -alkyl-C 1 -C 6 -aryl or C 1 -C 6 -aryl-C 1 -C 6 -alkyl groups are optionally interrupted in one or more places, in the same way or differently, by oxygen, sulfur, nitrogen, or sulfonyl-C 1 -C 6 -alkyl, sulfonamide, or cyano,

R 2 is halogen, CF 3 , C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkyl, C 1 -C 6 -aryl, C 1 -C 6 -acyl, halo-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-C 1 -C 6 -acyl, C 1 -C 6 -acyl-C 1 -C 6 -acyl, C 1 -C 6 -alkyl-C 1 -C 6 -aryl, C 1 -C 6 -aryl-C 1 -C 6 -alkyl or CF 3 , wherein C 1 -C 6 -alkyl, C 1 -C 6 -aryl, C 1 -C 6 -acyl, halo-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-C 1 -C 6 -acyl, C 1 -C 6 -acyl-C 1 -C 6 -acyl, C 1 -C 6 -alkyl-C 1 -C 6 -aryl or C 1 -C 6 -aryl-C 1 -C 6 -alkyl groups are optionally interrupted in one or more places, in the same way or differently, by oxygen, sulfur, nitrogen, or sulfonyl-C 1 -C 6 -alkyl, sulfonamide, or cyano,

R 3 is C 6 -C 12 -aryl, which optionally can be substituted in one or more places, in the way or differently, by halogen, C 1 -C 6 -alkyl, C 1 -C 3 -acyl, C 1 -C 3 -alkoxy, cyano, hydroxy, N—(CH 3 ) 2 , CO 2 —(C 1 -C 3 -alkyl), CO—NR 4 R 5 or CF 3 ;

C 5 -C 12 -heteroaryl, which optionally can be substituted in one or more places, in the same way or differently, by chlorine, fluorine, C 1 -C 6 -alkyl, C 1 -C 3 -acyl, C 1 -C 3 -alkoxy, cyano, hydroxy, N—(CH 3 ) 2 , CO 2 —(C 1 -C 3 -alkyl), CO—NR 4 R 5 or CF 3 ; or

C 3 -C 6 -cycloalkyl, which optionally can be substituted in one or more places, in the same way or differently, by chlorine, fluorine, CF 3 , cyano, C 1 -C 3 -alkyl, C 1 -C 3 -acyl, hydroxy, N—(CH 3 ) 2 , CO 2 —(C 1 -C 3 -alkyl), CO—NR 4 R 5 or C 1 -C 3 -alkoxy,

R 4 is hydrogen, C 3 -C 6 -cycloalkyl, which optionally is substituted in one or more places, in the same way or differently, by C 1 -C 3 -alkyl, C 1 -C 3 -acyl, C 1 -C 3 -alkoxy or CF 3 ;

C 6 -C 12 -aryl, which optionally is substituted in one or more places, in the same way or differently, by halogen, C 1 -C 3 -alkyl, C 1 -C 3 -acyl, C 1 -C 3 -alkoxy, N—C 1 -C 3 -alkyl-C 1 -C 3 -alkyl, CF 3 or cyano;

C 5 -C 12 -heteroaryl, which optionally is substituted in one or more places, in the same way or differently, by halogen, C 1 -C 3 -alkyl, C 1 -C 3 -acyl, C 1 -C 3 -alkoxy, N—C 1 -C 3 -alkyl-C 1 -C 3 -alkyl, CF 3 or cyano; or

C 1 -C 6 -alkyl, which can be substituted in any way desired,

R 5 is hydrogen, or C 1 -C 6 -alkyl-C 3 -C 6 -cycloalkyl, which optionally is substituted in one or more places, in the same way or differently, by C 1 -C 3 -alkyl, C 1 -C 6 -acyl, C 1 -C 6 -alkoxy or CF 3 ;

C 3 -C 6 -cycloalkyl, which optionally is substituted in one or more places, in the same way or differently, by C 1 -C 3 -alkyl, C 1 -C 3 -acyl, C 1 -C 3 -alkoxy or CF 3 ;

C 5 -C 12 -heteroaryl, which optionally is substituted in one or more places, in the same way or differently, with halogen, C 1 -C 3 -alkyl, C 1 -C 3 -acyl, C 1 -C 3 -alkoxy, N—C 1 -C 3 -alkyl-C 1 -C 3 -alkyl, CF 3 or cyano; or

C 1 -C 6 -alkyl, which can be substituted in any way desired,

R 4 and R 5 together can also form a 5- to 8-membered ring, which can contain additional heteroatoms, and

X is the groups sulfonyl, (CH 2 ) n or carbonyl,

Y is —(CH 2 ) n — or —CH═CH—, and

n is 1-2.

3. A compound according to claim 1 , wherein

R 1 is hydrogen,

R 2 is C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkyl, CF 3 , cyano, bromine, —OCF 3 , or —SO 2 —CH 3 ,

R 3 is C 6 -C 12 -aryl, which is optionally substituted in one or more places, in the same way or differently, by halogen, C 1 -C 6 -alkyl, C 1 -C 3 -acyl, C 1 -C 3 -alkoxy, cyano, hydroxy, N—(CH 3 ) 2 , CO 2 —(C 1 -C 3 -alkyl), CO—NR 4 R 5 or CF 3 ;

R 4 is hydrogen,

R 5 is hydrogen, C 1 -C 6 -alkyl-C 3 -C 6 -cycloalkyl, which optionally is substituted in one or more places, in the same way or differently, by C 1 -C 6 -alkyl, C 1 -C 6 -acyl, C 1 -C 6 -alkoxy or CF 3 ;

C 3 -C 6 -cycloalkyl, which optionally is substituted in one or more places, in the same way or differently, by C 1 -C 3 -alkyl, C 1 -C 3 -acyl, C 1 -C 3 -alkoxy or CF 3 ;

C 1 -C 6 -alkyl, which can be substituted in any way desired,

X is sulfonyl,

Y is —(CH 2 ) n — or —CH═CH—, and

n is 1-2.

4. A compound according to claim 1 , wherein

R 1 is hydrogen,

R 2 is C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkyl, CF 3 , sec-butyl, cyano, bromine, or the group —OCF 3 , or —SO 2 —CH 3 , and is in para-position,

R 3 is C 6 -C 12 -aryl, which optionally is substituted in one or two places, in the same way or differently, by halogen, C 1 -C 3 -alkyl, acetyl, methoxy, ethoxy, cyano, hydroxy, N—(CH 3 ) 2 , CO 2 —(C 1 -C 3 -alkyl), CO—NHR 5 or CF 3 ;

C 5 -C 12 -heteroaryl, which optionally is substituted in one or two places, in the same way or differently, by chlorine, fluorine, C 1 -C 3 -alkyl, acetyl, methoxy, ethoxy, cyano, hydroxy, N—(CH 3 ) 2 , CO 2 —(C 1 -C 3 -alkyl), CO—NHR 5 or with CF 3 ; or

C 3 -C 6 -cycloalkyl,

R 4 is hydrogen,

R 5 is hydrogen, or C 1 -C 6 -alkyl-C 3 -C 6 -cycloalkyl, which optionally is substituted in one or more places, in the same way or differently, by C 1 -C 6 -alkyl, C 1 -C 6 -acyl, C 1 -C 6 -alkoxy or CF 3 ;

C 3 -C 6 -cycloalkyl, which optionally is substituted in one or more places, in the same way or differently, by C 1 -C 3 -alkyl, C 1 -C 3 -acyl, C 1 -C 3 -alkoxy or CF 3 ;

C 1 -C 6 -alkyl, which can be substituted in any way desired,

X is sulfonyl,

Y is —(CH 2 ) n — or —CH═CH—, and

n is 1-2.

5. A compound according to claim 1 , wherein

R 1 is hydrogen,

R 2 is tert-butyl, iso-propyl, iso-butyl, sec-butyl, cyano, bromine, —O—CF 3 , or —SO 2 —CH 3 , and is in para-position,

R 3 is

R 4 is hydrogen,

R 5 is hydrogen, —(CH 2 ) n —N—(CH 3 ) 2 , —(CH 2 ) 2 —CH 3 , —(CH 2 ) 2 —NH—COCH 3 , —(CH 2 )—CHCH 3 —OH, —(CH 2 ) 2 —O—CH 3 , —(CH 2 ) 2 —OH, —CHCH 3 —CH 2 —OH,

X is sulfonyl,

Y is —(CH 2 ) n — or —CH═CH—, and

n is 1-2.

6. A compound according to claim 1 , wherein

R 1 is hydrogen,

R 2 is tert-butyl, iso-propyl, iso-butyl, sec-butyl, cyano, bromine, —O—CF 3 , or —SO 2 —CH 3 , and is in para-position,

R 3 is

R 4 is hydrogen,

R 5 is hydrogen, —(CH 2 )—CHCH 3 —OH, —(CH 2 ) 2 —O—CH 3 , —CHCH 3 —CH 2 —OH,

X is sulfonyl,

Y is —(CH 2 ) n — or —CH═CH—, and

n is 1-2.

7. A compound according to claim 1 , wherein said compound is:

1. (E)-3-[5-(4-tert-Butyl-phenylsulfonylamino)-3-phenyl-1H-indol-2-yl]-N-(tetrahydro-pyran-4-yl)-acrylic acid amide,

2. (E)-3-[5-(4-tert-Butyl-phenylsulfonylamino)-3-phenyl-1H-indol-2-yl]-N-(2-morpholin-4-yl-ethyl)-acrylic acid amide,

3. (±)-(E)-3-[5-(4-tert-Butyl-phenylsulfonylamino)-3-phenyl-1H-indol-2-yl]-N-(2-hydroxy-1-methyl-ethyl)-acrylic acid amide,

4. (±)-(E)-3-[5-(4-tert-Butyl-phenylsulfonylamino)-3-phenyl-1H-indol-2-yl]-N-(2-hydroxy-propyl)-acrylic acid amide,

5. 3-[5-(4-tert-Butyl-phenylsulfonylamino)-3-phenyl-1H-indol-2-yl]-N-(2-morpholin-4-yl-ethyl)-propionic acid amide,

6. (E)-3-[5-(4-tert-Butyl-phenylsulfonylamino)-3-(3-fluorophenyl)-1H-indol-2-yl]-N-(tetrahydro-pyran-4-yl)-acrylic acid amide,

7. (E)-3-[5-(4-tert-Butyl-phenylsulfonylamino)-3-(3-fluorophenyl)-1H-indol-2-yl]-N-(2-morpholin-4-yl-ethyl)-acrylic acid amide,

8. (E)-3-[5-(4-tert-Butyl-phenylsulfonylamino)-3-(3-methoxy-phenyl)-1H-indol-2-yl]-N-(tetrahydro-pyran-4-yl)-acrylic acid amide,

9. (E)-3-[5-(4-tert-Butyl-phenylsulfonylamino)-3-(3-methoxy-phenyl)-1H-indol-2-yl]-N-(2-morpholin-4-yl-ethyl)-acrylic acid amide,

10. (E)-3-[5-(4-tert-Butyl-phenylsulfonylamino)-3-(3-fluorophenyl)-1H-indol-2-yl]-N-(pyridin-4-yl)-acrylic acid amide, or

11. (E)-3-[5-(4-tert-Butyl-phenylsulfonylamino)-3-(3-methoxy-phenyl)-1H-indol-2-yl]-N-(pyridin-4-yl)-acrylic acid amide,

or a physiologically compatible salt thereof.

8. A pharmaceutical composition comprising at least one compound according to claim 1 and a carrier.

9. A pharmaceutical composition according to claim 8 , wherein said compound is contained in an amount of 0.5-1000 mg.

10. A method of achieving contraception in a patient, comprising administering to said patient a compound according to claim 1 .

11. A method of inhibiting soluble adenylate cyclase in a patient, comprising administering to said patient a compound according to claim 1 .

12. A pharmaceutical composition according to claim 8 , wherein said composition is in a form suitable for enteral, parenteral, vaginal or oral administration.

13. A process for preparing a compound according to claim 1 , said process comprising:

reacting a compound of formula (II)

in which R 1 , R 2 , R 3 , X and Y have the meanings in formula I and R 6 is hydrogen or C 1 -C 6 -alkyl, with an amine of formula III

in which R 4 and R 5 have the meanings in formula I, and

optionally cleaving protective groups and/or hydrogenating double bonds, to form a compound of formula (I).

14. A method of inhibiting soluble adenylate cyclase comprising administering a compound of claim 1 .

15. A compound according to claim 1 , wherein acyl is formyl, acetyl, propionyl, butyroyl, iso-butyroyl, or valeroyl.

16. A compound according to claim 1 , wherein cycloalkyl in each case is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

17. A compound according to claim 1 , wherein heteroaryl in each case is thienyl, furanyl, pyrrolyl, oxazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, enzofuranyl, benzothienyl, benzooxazolyl, benzimidazolyl, indazolyl, indolyl, isoindolyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, quinolyl, isoquinolyl, azoinyl, indolizinyl, purinyl, quinolinyl, isoquinolinyl, cinnnnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, xanthenyl, oxepinyl, thiophenyl, or pyridinyl.

18. A compound according to claim 1 , wherein

C 3 -C 6 -cycloalkyl, which optionally is substituted in one or more places, in the same way or differently, by halogen, CF 3 , hydroxy, cyano, CO 2 —(C 1 -C 6 -alkyl), C 1 -C 6 -alkyl, C 1 -C 6 -acyl, N—(C 1 -C 6 -alkyl) 2 , CO—NR 4 R 5 or C 1 -C 6 -alkoxy,

R 4 is hydrogen, or C 3 -C 6 -cycloalkyl, which optionally is substituted in one or more places, in the same way or differently, by C 1 -C 6 -alkyl, C 1 -C 6 -acyl, C 1 -C 6 -alkoxy or CF 3 ;

R 5 is hydrogen, or C 1 -C 6 -alkyl-C 3 -C 6 cycloalkyl, which optionally is substituted in one or more places, in the same way or differently, by C 1 -C 6 -alkyl, C 1 -C 6 -acyl, C 1 -C 6 -alkoxy or CF 3 ;

C 3 -C 6 -cycloalkyl, which optionally is substituted in one or more places, in the way or differently, by C 1 -C 6 -alkyl, C 1 -C 6 -acyl, C 1 -C 6 -alkoxy or CF 3 ;

R 4 and R 5 together can also form a 5- to 8-membered ring, which can contain additional heteroatoms, and

X is sulfonyl, (CH 2 ) n or carbonyl,

Y is —(CH 2 ) n — or —CH═CH—, and

n is 1-4.

19. A compound according to claim 1 , wherein

R 4 is hydrogen, or C 3 -C 6 -cycloalkyl, which optionally is substituted in one or more places, in the same way or differently, by C 1 -C 6 -alkyl, C 1 -C 6 -acyl, C 1 -C 6 -alkoxy or CF 3 ;

C 1 -C 6 -alkyl,

C 3 -C 6 -cycloalkyl, which optionally is substituted in one or more places, in the same way or differently, by C 1 -C 6 -alkyl, C 1 -C 6 -acyl, C 1 -C 6 -alkoxy or CF 3 ;

C 6 -C 12 -aryl, which optionally is substituted in one or morn places, in the same way or differently, by halogen, C 1 -C 6 -alkyl, C 1 -C 6 -acyl, C 1 -C 6 -alkoxy, N—C 1 -C 6 -alkyl-C 1 -C 6 -alkyl, CF 3 or cyano;

C 1 -C 6 -alkyl, or

R 4 and R 5 together can also form a 5- to 8-membered ring, which can contain additional heteroatoms.

20. A compound according to claim 2 , wherein

R 4 is hydrogen, C 3 -C 6 -cycloalkyl, which optionally is substituted in one or more places, in the same way or differently, by C 1 -C 3 -alkyl, C 1 -C 3 -acyl, C 1 -C 3 -alkoxy or CF 3 ;

C 6 -C 12 -aryl, which optionally is substituted in one or morn places, in the same way or differently, by halogen, C 1 -C 3 -alkyl, C 1 -C 3 -acyl, C 1 -C 3 -alkoxy, N—C 1 -C 3 -alkyl-C 1 -C 3 -alkyl, CF 3 or cyano;

C 1 -C 6 -alkyl,

C 3 -C 6 -cycloalkyl, which optionally is substituted in one or more places, in the same way or differently, by C 1 -C 3 -alkyl, C 1 -C 3 -acyl, C 1 -C 3 -alkoxy or CF 3 ;

C 1 -C 6 -alkyl, or

R 4 and R 5 together can also form a 5- to 8-membered ring, which can contain additional heteroatoms.

21. A compound according to claim 3 , wherein

C 3 -C 6 -cycloalkyl, which optionally is substituted in one or more places, in the same way or differently, by C 1 -C 3 -alkyl, C 1 -C 3 -acyl, C 1 -C 3 -alkoxy or CF 3 ;

C 1 -C 6 -alkyl.

22. A compound according to claim 4 , wherein

C 3 -C 6 -cycloalkyl, which optionally is substituted in one or more places, in the same way or differently, by C 1 -C 3 -alkyl, C 1 -C 3 -acyl, C 1 -C 3 -alkoxy or CF 3 ;

C 1 -C 6 -alkyl.

Assignments (2)

CHANGE OF NAME Recorded Nov 14, 2007

From: SCHERING AKTIENGESELLSCHAFT

To: BAYER SCHERING PHARMA AKTIENGESELLSCHAFT

Reel/Frame 020110/0334 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 15, 2007

From: BUCHMANN, BERND; KOSEMUND, DIRK; MENZENBACH, BERND; FRITSCH, MARTIN

To: BAYER SCHERING PHARMA AG

Reel/Frame 019435/0391 →