Indolin phenylsulfonamide derivatives

An alkyl and methyl technology, applied in the field of indoline phenylsulfonamide derivatives, can solve problems such as weak interactions, large side effects, and high daily doses

Inactive Publication Date: 2005-10-05
BAYER HEALTHCARE AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

A disadvantage of the fibrates that have been approved so far is that they only interact weakly with this receptor and thus require high daily doses, thus causing considerable side effects

Method used

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  • Indolin phenylsulfonamide derivatives
  • Indolin phenylsulfonamide derivatives
  • Indolin phenylsulfonamide derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0262] [4-({3-isopropyl-7-methyl-5-[4-(trifluoromethyl)phenyl]-2,3-dihydro-1H-indol-1-yl}-sulfonyl )-2-Methylphenoxy]acetic acid

[0263]

[0264] Step a):

[0265] 1-(4-Bromo-2-methylphenyl)hydrazine

[0266]

[0267] 50 g (267.7 mmol) of 4-bromo-2-methylaniline were heated in 190 ml of concentrated hydrochloric acid at 80° C. for 30 min. After cooling to 5° C., 18.5 g (267.7 mmol) of sodium nitrite in 95 ml of water were added dropwise thereto within 30 minutes. After it was stirred at 5° C. for 30 minutes, the reaction mixture was added dropwise to a solution of 384 g (2 mol) of stannous chloride in 190 ml of concentrated hydrochloric acid within 45 min. After it was stirred at RT for a further 45 min, the mixture was made basic with 50% concentrated aqueous sodium hydroxide. The precipitate was filtered off and extracted repeatedly with dichloromethane and ethyl acetate. The combined organic phases were dried over magnesium sulfate and concentrated. This gave 4...

Embodiment 2

[0313] [2-Methyl-4-({2,3,7-trimethyl-5-[4-(trifluoromethyl)phenyl]-2,3-dihydro-1H-indol-1-yl }sulfonyl)phenoxy]acetic acid

[0314]

[0315] Step a):

[0316] 5-Bromo-2,3,7-trimethyl-1H-indole

[0317]

[0318] 8 g (39.8 mmol) of 1-(4-bromo-2-methylphenyl)hydrazine (example 1 / step a) were suspended in 14 ml of ethanol, and 3.7 g (52 mmol) of methyl ethyl ketone were added thereto. After it was stirred at RT for 30 minutes, the solvent was removed under reduced pressure and the intermediate was melted without further purification at 170° C. together with 5.9 g (43 mmol) of anhydrous zinc chloride. After 30-45 min, the melt was cooled to RT, taken up with dichloromethane and extracted with dilute hydrochloric acid and water. The organic phase was dried over magnesium sulfate and the solvent was removed under reduced pressure. The crude product was dissolved in ethyl acetate and purified on silica gel (mobile phase: cyclohexane-ethyl acetate 9:1). This gives 3.8 g of pro...

Embodiment 3

[0344] [4-({3,7-Dimethyl-5-[4-(trifluoromethyl)phenyl]-2,3-dihydro-1H-indol-1-yl}sulfonyl)-2- Methylphenoxy]acetic acid

[0345]

[0346] Step a):

[0347] 5-bromo-3,7-dimethyl-1H-indole

[0348]

[0349] 5 g (24.8 mmol) of 1-(4-bromo-2-methylphenyl)hydrazine (example 1 / step a) were suspended in 14 ml of ethanol, and 1.8 g (32 mmol) of propionaldehyde were added thereto. The mixture was stirred at RT for 30 min, then the solvent was removed under reduced pressure and the intermediate was melted at 170° C. without further purification together with 3.7 g (27 mmol) of anhydrous zinc chloride. After 30-45 min, the melt was cooled to RT, taken up with dichloromethane and extracted with dilute hydrochloric acid and water. The organic phase was dried over magnesium sulfate and the solvent was removed under reduced pressure. The crude product was dissolved in ethyl acetate and purified on silica gel (mobile phase: cyclohexane-ethyl acetate 9:1). This gives 1.5 g of product (2...

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PUM

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Abstract

The invention relates to novel substituted indolin phenylsulfonamide derivatives, to a method for the production thereof and to the use thereof in medicaments, especially as potent PPAR-delta activating compounds for the prophylaxis and / or treatment of cardiovascular diseases, especially dyslipidaemia and coronary heart diseases.

Description

technical field [0001] The present invention relates to novel substituted indoline phenyl sulfonamide derivatives, their preparation methods and their use in medicine, especially as drugs for the prevention and / or treatment of cardiovascular disorders, especially dyslipidemia (Dyslipid mien), arteriosclerosis and coronary heart disease for the application of effective PPAR-δ activating compounds. Background technique [0002] Despite many successful therapies, coronary heart disease (CHD) remains a serious public health problem. Treatment with statins, which inhibit HMG-CoA-reductase, successfully lowered plasma concentrations of LDL cholesterol, thereby significantly reducing mortality in patients at risk of the disease; There are still no convincing therapeutic strategies for the treatment of patients with an unfavorable HDL / LDL cholesterol ratio and / or hypertriglyceridemia. [0003] Currently, fibrates are the only treatment option for patients at these risks. It is a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/404A61K31/437A61P3/06A61P9/00A61P9/10C07D405/04C07D209/08C07D209/96C07D471/04
CPCC07D471/04C07D209/96C07D209/08A61P3/00A61P3/06A61P9/00A61P9/10
Inventor H·比肖夫E·迪特里希-温根罗特M·乌特克H·赫克罗特W·蒂勒曼M·沃尔特林M·奥特内德
Owner BAYER HEALTHCARE AG
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