Substituted sulfonamide compounds

a technology of sulfonamide and derivatives, which is applied in the direction of drug compositions, antibacterial agents, metabolic disorders, etc., can solve the problems of increasing the cost of transgenic animals, increasing the cost of working with transgenic animals, and increasing the cost of working with unchanged animals

Inactive Publication Date: 2008-06-26
GRUNENTHAL GMBH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0008]It is an object of the present invention to provide new pharmaceutically useful compounds.

Problems solved by technology

When developing B1R modulators there is, however, the problem that the human and the rat B1R receptor are so very different from one another that many compounds that are good B1R modulators on the human receptor exhibit only poor affinity or no affinity for the rat receptor.
This makes animal pharmacological studies considerably more difficult, because many studies are normally carried out on the rat.
However, it is more expensive to work with transgenic animals than with the unchanged animals.
Nonetheless, because long-term toxicity studies on the rat form part of the standard studies that are carried out when developing medicaments, but such studies are meaningless where there is an absence of activity on the receptor, there is no important, established instrument for checking safety when developing such compounds.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 8

2-[1-(4-methoxy-2,6-dimethyl-phenylsulfonyl)-piperidin-2-ylmethoxy]-1-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-ethanone

[0761]

[0762]N,N′-Carbonyldiimidazole (114 mg, 0.706 mmol) was added to a solution of 2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetic acid (250 mg, 0.673 mmol) in dichloromethane (15 ml), and the mixture was stirred for 1 h at room temperature. A solution of 1-(1-methylpiperidin-4-yl)piperazine (123 mg, 0.673 mmol) in dichloromethane (5 ml) was then added, and the reaction mixture was stirred for 15 h at room temperature. The reaction mixture was then extracted with water (20 ml) and saturated sodium chloride solution (20 ml), and the organic phase was dried over magnesium sulfate and concentrated in vacuo. The crude product was purified by flash chromatography using dichloromethane / methanol (97:3→90:10).

[0763]Yield: 296 mg (82%), brown resin

[0764]1H-NMR (600 MHz, DMSO-d6): 1.27 (1H); 1.42 (1H); 1.55 (4H); 1.69 (2H); 1.79 (1H); 1.89 (2H)...

example 97

2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)-1-(4-(1-methyl-piperidin-4-yl)piperazin-1-yl)ethanone dihydrochloride

[0765]N,N′-Carbonyldiimidazole (272 mg, 1.696 mmol) was added to a solution of 2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetic acid (600 mg, 1.615 mmol) in dichloromethane (15 ml), and the mixture was stirred for 1 h at room temperature. A solution of 1-(1-methylpiperidin-4-yl)piperazine (293 mg, 1.615 mmol) in dichloromethane (5 ml) was then added, and the reaction mixture was stirred for 15 h at room temperature. Saturated sodium hydrogen carbonate solution (20 ml) was then added to the reaction mixture, and then the aqueous phase was extracted with dichloromethane (2×20 ml). The combined organic phases were extracted with saturated sodium chloride solution (20 ml), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by flash chromatography using dichloromethane / methanol (5:1). 2-((1-(4-me...

example 92

3-((4-(2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)-methoxy)acetyl)piperazin-1-yl)methyl)benzonitrile hydrochloride

[0768]

[0769]N,N′-Carbonyldiimidazole (68 mg, 0.424 mmol) was added to a solution of 2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetic acid (150 mg, 0.404 mmol) in dichloromethane (4 ml), and the mixture was stirred for 1 h at room temperature. A solution of 3-(piperazin-1-ylmethyl)benzonitrile (81 mg, 0.404 mmol) in dichloromethane (1 ml) was then added, and the reaction mixture was stirred for 15 h at room temperature. Saturated sodium hydrogen carbonate solution (5 ml) was then added to the reaction mixture, and then the aqueous phase was extracted with dichloromethane (2×10 ml). The combined organic phases were extracted with saturated sodium chloride solution (10 ml), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by flash chromatography using ethyl acetate / hexane (20:1). 3-((4-(2-((1-(4-met...

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Abstract

Substituted sulfonamide derivatives, a process for their preparation, pharmaceutical compositions containing these compounds, and to the use of substituted sulfonamide derivatives in the treatment or inhibition of pain and/or various disorders or disease states.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority based on co-pending U.S. provisional patent application No. 60 / 849,438, filed Oct. 5, 2006, the entire disclosure of which is corporated herein by reference. Priority is also claimed based on Federal Republic of Germany patent application no. DE 10 2006 046 743.4, filed Sep. 29, 2006.BACKGROUND OF THE INVENTION[0002]The present invention relates to substituted sulfonamide derivatives, to a process for their preparation, to medicaments containing these compounds, and to the use of substituted sulfonamide derivatives in the preparation of pharmaceutical compositions and in treatment and / or inhibition of pain and / or various disease states.[0003]Unlike the constitutive expression of the bradykinin 2 receptor (B2R), the bradykinin 1 receptor (B1R) is not expressed or is expressed only weakly in most tissues. However, the expression of B1R in various cells is inducible. For example, following inflammation reacti...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/4523C07D211/08C07D217/22A61K31/496A61P25/00A61P3/00A61K31/47C07D241/04
CPCC07D471/04C07D403/14C07D401/12C07D401/14C07D409/14A61P1/04A61P11/00A61P17/00A61P25/00A61P25/04A61P25/06A61P29/00A61P3/00A61P3/10A61P31/04A61P35/00A61P3/04A61P43/00C07D403/12
Inventor OBERBOERSCH, STEFANREICH, MELANIESCHUNK, STEFANHEES, SABINEJOSTOCK, RUTHENGELS, MICHAEL FRANZ-MARTINKLESS, ACHIMCHRISTOPH, THOMASSCHIENE, KLAUSGERMANN, TIENOBIJSTERVELD, EDWARD
Owner GRUNENTHAL GMBH
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