Bis(sulfonamide) derivatives and their use as mpges inhibitors

一种苯磺酰胺、乙基亚磺酰氨基的技术,应用在酰胺有效成分、抗炎剂、药物组合等方向,达到改善效力和选择性、降低副作用、降低胃肠毒性和肾脏毒性的效果

Inactive Publication Date: 2017-08-01
EKDURUM REAL ESTATE LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] NSAIDs reduce PGE2 by inhibiting cyclooxygenase, but at the same time reduce other prostaglandins, which brings side effects such as peptic ulcer

Method used

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  • Bis(sulfonamide) derivatives and their use as mpges inhibitors
  • Bis(sulfonamide) derivatives and their use as mpges inhibitors
  • Bis(sulfonamide) derivatives and their use as mpges inhibitors

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0129] Compound preparation

[0130] The compounds of the present invention can be prepared as free bases or pharmaceutically acceptable salts thereof by the following methods. In the following description of such methods, it is understood that suitable protecting groups, where appropriate, will be added and subsequently removed from various reactants and intermediates in a manner readily understood by those skilled in the art of organic synthesis. Conventional methods of using such protecting groups as well as examples of suitable protecting groups are eg described in Protective Groups in Organic Synthesis by T.W. Greene, P.G.M Wutz, 3rd Edition, Wiley-Interscience, New York, 1999.

[0131] general method

[0132] All solvents used were of analytical grade, and commercially available anhydrous solvents were routinely used for reactions. Starting materials used were obtained from commercial sources or were prepared according to literature procedures. Room temperature means...

Embodiment 1

[0288] 2-(2-(4-Chloro-2-phenylethoxyphenyl)ethylsulfonamido)benzenesulfonamide

[0289]

[0290] Dissolve N-tert-butyl-2-(2-(4-chloro-2-phenethoxyphenyl)ethylsulfonylamino)benzenesulfonamide (0.058g, 0.11mmol) in 2,2,2 - in trifluoroacetic acid (1.5ml, 19.47mmol) and stirred for 5h. The reaction mixture was co-evaporated with toluene and purified by preparative HPLC to afford the title compound (0.033 g, 64%). 1 H NMR (500MHz, DMSO-d 6 )δppm2.84-2.98(m,4H)3.37-3.46(m,2H)4.13(t,2H)6.88(dd,1H)7.00(d,1H)7.13(d,1H)7.17-7.24(m,1H )7.24-7.36(m,5H)7.55-7.69(m,2H)7.81-7.95(m,3H)8.95(s,1H); MS(ES - )m / z493,495,497[M-H] - .

Embodiment 2

[0292] 2-(2-(4-Chloro-2-(2-methoxyphenethoxy)phenyl)ethylsulfonamido)benzenesulfonamide

[0293]

[0294] To N-tert-butyl-2-(2-(4-chloro-2-(2-methoxyphenethoxy)phenyl)ethylsulfonamido)benzenesulfonamide (77mg, 0.13mmol) Trifluoroacetic acid (1 mL, 13.06 mmol) was added, and the mixture was stirred at room temperature for 2 hours. The solvent was evaporated, followed by co-evaporation with toluene (1 mL). Purification by preparative HPLC afforded the title compound (39.0 mg, 56.1%). 1 HNMR (500MHz, DMSO-d 6 )δppm 2.84-2.94(m,4H)3.43(m,2H)3.81(s,3H)4.05(t,2H)6.83-6.90(m,2H)6.96(d,1H)7.03(d,1H)7.13( d,1H)7.21(m,2H)7.31(t,1H)7.57-7.66(m,2H)7.84(s,2H)7.88(d,1H)8.95(s,1H); MS(ES - )m / z 523,525[M-H] - .

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Abstract

The present invention relates to bis(sulfonamide) compounds and pharmaceutically acceptable salts thereof. The present invention also relates to pharmaceutical compositions comprising these compounds and to their use as a medicament for the treatment and / or prevention of a disease, disorder or condition in which modulation of microsomal prostaglandin E synthase-1 activity is beneficial, such as pain, inflammation and cancer.

Description

technical field [0001] The present invention relates to bis(sulfonamide) compounds and pharmaceutically acceptable salts thereof. The present invention also relates to pharmaceutical compositions comprising these compounds, and their use in the treatment and / or prevention of diseases, disorders or conditions in which modulation of microsomal prostaglandin E synthase-1 activity is beneficial, such as pain, inflammation and cancer, etc. use of the drug. Background technique [0002] Regulation of prostaglandin metabolism is central to current anti-inflammatory treatments. NSAIDs and COX-2 inhibitors block the activity of cyclooxygenase and its ability to convert arachidonic acid to prostaglandin H2 (PGH2). PGH2 can then be metabolized to the corresponding biologically active PGs, namely PGI2, thromboxane (Tx)A2, PGD2, PGF2α and PGE2, via terminal prostaglandin synthase. A combination of pharmacological, genetic, and neutralizing antibody approaches suggests the importance o...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C311/21A61K31/18A61K31/404A61P29/00C07D209/08C07D209/34
CPCA61K45/06C07C311/39C07D209/08C07D209/34A61P29/00A61P35/00A61K31/18A61K31/277A61K31/404C07C311/44
Inventor P·索德曼M·斯文松A·柯尔斯L·欧博格K·奥格丁A·黑特曼J·哈尔贝格M·埃克J·拜兰J·努德
Owner EKDURUM REAL ESTATE LTD
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