IP Library › Patent Application 11727163

Patent Application

App. No. 11/727,163

Inhibitors of soluble adenylate cyclase

Loading inventors, assignments & file history…

Monitor This Case

Get email alerts when status or documents change.

Order Certified Copies

Most orders are placed with the USPTO same day — all within 24 business hours.

Order via The Patent Place →

Pre-filled with this patent's details

Quick Facts

Patent No.: US None
App. No.: 11/727,163

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

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

Claims (99)

1 . Compounds of general formula (I),

whereby

R 1 means hydrogen, halogen, CF 3 , C 3 -C 6 -cycloalkyl, which optionally is polysaturated and optionally is polysubstituted, or the group 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 , in which 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 optionally can be interrupted in one or more places, in the same way or differently, by oxygen, sulfur or nitrogen, or the group sulfonyl-C 1 -C 6 -alkyl, sulfonamide, or cyano,

R 2 means halogen, CF 3 , C 3 -C 6 -cycloalkyl, which optionally is polysaturated and optionally is polysubstituted, or the group 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 , in which 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 optionally can be interrupted in one or more places, in the same way or differently, by oxygen, sulfur or nitrogen, or the group sulfonyl-C 1 -C 6 -alkyl, sulfonamide, or cyano,

R 3 means C 6 -C 12 -aryl, which optionally can be substituted in

one or more places, in the same way or differently, with halogen, C 1 -C 6 -alkyl or C 1 -C 6 -acyl, which optionally can be substituted in one or more places, or can be substituted with 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 with CF 3 ;

C 5 -C 12 -heteroaryl, which optionally can be substituted in one or more places, in the same way or differently, with 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 with CF 3 ; or

C 3 -C 6 -cycloalkyl, which optionally can be substituted in one or more places, in the same way or differently, with 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 means hydrogen, C 3 -C 6 -cycloalkyl, which optionally is substituted in

one or more places, in the same way or differently, with 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, with 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 5 -C 12 -heteroaryl, which optionally is substituted in one or more places, in the same way or differently, with 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 means 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, with 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, with 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, and

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

as well as the isomers, diastereomers, enantiomers and salts thereof.

2 . Compounds according to claim 1 , whereby

R 1 means hydrogen, halogen, CF 3 , C 3 -C 6 -cycloalkyl, or the group 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 , in which 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 optionally can be interrupted in one or more places, in the same way or differently, by oxygen, sulfur or nitrogen, or the group sulfonyl-C 1 -C 6 -alkyl, sulfonamide, or cyano,

R 2 means halogen, CF 3 , or C 3 -C 6 -cycloalkyl, or the group 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 , in which 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 optionally can be interrupted in one or more places, in the same way or differently, by oxygen, sulfur or nitrogen, or the group sulfonyl-C 1 -C 6 -alkyl, sulfonamide, or cyano,

R 3 means C 6 -C 12 -aryl, which optionally can be substituted in

one or more places, in the same way or differently, with halogen, with 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, with chlorine and/or fluorine, with 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 with CF 3 ;

C 3 -C 6 -cycloalkyl, which optionally can be substituted in one or more places, in the same way or differently, with chlorine and/or 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 means hydrogen, C 3 -C 6 -cycloalkyl, which optionally is substituted in

one or more places, in the same way or differently, with 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, 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 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,

C 3 -C 6 -cycloalkyl, which optionally is substituted in one or more places, in the same way or differently, with 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,

as well as the isomers, diastereomers, enantiomers and salts thereof.

3 . Compounds according to claim 1 , whereby

R 1 means hydrogen,

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

R 3 means C 6 -C 12 -aryl, which optionally can be substituted in one or more places, in the same way or differently, with 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 means hydrogen,

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

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

as well as the isomers, diastereomers, enantiomers and salts thereof.

4 . Compounds according to claim 1 , whereby

R 1 means hydrogen,

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

R 3 means C 6 -C 12 -aryl, which optionally can be substituted in one or two places, in the same way or differently, with 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 can be substituted in one or two places, in the same way or differently, with chlorine and/or fluorine, with 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 means hydrogen,

R 5 means 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, with 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, with 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,

as well as the isomers, diastereomers, enantiomers and salts thereof.

5 . Compounds according to claim 1 , whereby

R 1 means hydrogen,

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

R 3 means the group

R 4 means hydrogen,

R 5 means hydrogen or the group —(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, or —CHCH 3 —CH 2 —OH, whereby m=1-3,

as well as the isomers, diastereomers, enantiomers and salts thereof.

6 . Compounds according to claim 1 , whereby

R 1 means hydrogen,

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

R 3 means the group

R 4 means hydrogen,

R 5 means hydrogen or the group —(CH 2 )—CHCH 3 —OH, —(CH 2 ) 2 —O—CH 3 , or —CHCH 3 —CH 2 —OH,

as well as the isomers, diastereomers, enantiomers and salts thereof.

7 . Compounds according to claim 1 , selected from a group that contains the following compounds:

1. 5-(4-tert-Butyl-phenylsulfamoyl)-3-phenyl-1H-indole-2-carboxylic acid(tetrahydro-pyran-4-yl)-amide

2. 5-(4-tert-Butyl-phenylsulfamoyl)-3-phenyl-1H-indole-2-carboxylic acid(2-morpholin-4-yl-ethyl)-amide

3. (±)-5-(4-tert-Butyl-phenylsulfamoyl)-3-phenyl-1H-indole-2-carboxylic acid-(2-hydroxy-1-methyl-ethyl)-amide

4. (±)-5-(4-tert-Butyl-phenylsulfamoyl)-3-phenyl-1H-indole-2-carboxylic acid-(2-hydroxy-propyl)-amide

5. 5-(4-tert-Butyl-phenylsulfamoyl)-3-(3-fluoro-phenyl)-1H-indole-2-carboxylic acid(tetrahydro-pyran-4-yl)-amide

6. 5-(4-tert-Butyl-phenylsulfamoyl)-3-(3-fluoro-phenyl)-1H-indole-2-carboxylic acid(2-morpholin-4-yl-ethyl)-amide

7. 5-(4-tert-Butyl-phenylsulfamoyl)-3-(3-methoxy-phenyl)-1H-indole-2-carboxylic acid (tetrahydro-pyran-4-yl)-amide

8. 5-(4-tert-Butyl-phenylsulfamoyl)-3-(3-methoxy-phenyl)-1H-indole-2-carboxylic acid(2-morpholin-4-yl-ethyl)-amide

9. 5-(4-tert-Butyl-phenylsulfamoyl)-3-phenyl-1H-indole-2-carboxylic acid(pyridin-4-yl)-amide

8 . Pharmaceutical agents that contain at least one of the compounds according to claim 1 .

9 . Pharmaceutical agents according to claim 8 in which the compound of general formula I is contained in an effective dose.

10 . Compounds of general formula (I) according to claim 1 for the production of pharmaceutical agents.

11 . Pharmaceutical agents according to claim 10 for the treatment of diseases.

12 . Pharmaceutical agents according to claim 11 , whereby the diseases are caused by disorders in cAMP metabolism.

13 . Pharmaceutical agents according to claim 10 for contraception.

14 . Pharmaceutical agents according to claim 10 for inhibition of soluble adenylate cyclase.

15 . Pharmaceutical agents according to claim 10 with suitable formulation substances and vehicles.

16 . Use of the compounds of general formula (I) according to claim 1 in the form of a pharmaceutical preparation for enteral, parenteral, vaginal and oral administration.

17 . Process for the production of the compounds of general formula (I), whereby the process contains the reaction of the compounds of general formula (II) to form the compounds of general formula (I).

18 . Intermediate products of general formulas (II), (V), and (VII).

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

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 Jul 23, 2007

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

To: BAYER SCHERING PHARMA AG

Reel/Frame 019634/0128 →