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Diphenyl ether compounds used in the treatment of liver disease, lung disease, diabetic complications and cardiovascular disease

A compound and liver disease technology, applied in the direction of cardiovascular system diseases, urinary system diseases, diseases, etc., can solve the problems of fat production rate increase, rate decrease, fatty acid β-oxidation rate decrease, etc.

Inactive Publication Date: 2015-08-12
ORCHID CHEM & PHARM LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

(2) Increased rate of fat production due to de novo synthesis of fatty acids and triglycerides in the liver
(3) The rate of fatty acid β-oxidation in the liver decreases
(4) Decreased rate of excretion of cholesteryl esters and triglycerides from the liver as very low density lipoproteins (VLDL)
[0020] Studies of diabetic complications have shown that multiple mechanisms are involved in the pathogenesis of the disease, so targeting a single mechanism may be ineffective in the long-term treatment of diabetic complications

Method used

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  • Diphenyl ether compounds used in the treatment of liver disease, lung disease, diabetic complications and cardiovascular disease
  • Diphenyl ether compounds used in the treatment of liver disease, lung disease, diabetic complications and cardiovascular disease
  • Diphenyl ether compounds used in the treatment of liver disease, lung disease, diabetic complications and cardiovascular disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment -1

[0160] Embodiment-1: the effect of the compound of formula (A) on the body weight of DIO / NAFLD mice

[0161] Rodent obesity and NAFLD models were established by feeding a supranutritional diet capable of stimulating multiple features of human obesity and NAFLD. These features are processed as follows. Thirty C57BL / 6 male mice, 6-8 weeks old, weighing 16-22 g, were used for this study. Animals were divided into 2 groups. The first group (n=8, where n refers to the number of animals) was fed with chow feed (Nutri Rodent, Tetragon Chemie Pvt.Ltd., Bangalore) were fed as a normal control, and the second group (n=20) was fed with a 60Kcal% high-fat diet (HFD) (diet used for research, New Brunswick, NJ, Cat#D12492 with blue dye) for 90 days. Animals were selected based on their body weight. Animals fed with normal diet (n=8) served as normal control (Group I), and animals fed with HFD were divided into two groups: DIO / NAFLD control (Group II) (n=10) and those treated with 100 ...

Embodiment -2

[0162] Example-2: Effect of Compound of Formula (A) on NAFLD / NASH Mice

[0163] A rodent model of NAFLD / NASH was established by feeding a supranutrient diet capable of stimulating multiple features of NAFLD / NASH. These features are processed as follows. Fifty C57BL / 6 male mice, 6-8 weeks old, weighing 16-36 g, were used for this study. Animals were divided into 2 groups. The first group (n=10) was fed with feed (Nutri Rodent, Tetragon Chemie Pvt.Ltd., Bangalore) were fed as a normal control, and the second group (n=40) was fed with 60Kcal% HFD (diet used for research, New Brunswick, NJ, Cat#D12492 with blue dye) and 40 % high fructose liquid (HFL) feeding for 60 days. After 45 days, two animals from the disease induction and normal control groups were sacrificed for liver histopathological examination to confirm the induction of NAFLD / NASH. Animals fed with normal diet served as normal control (group I), animals fed with HFD and HFL were divided into 3 groups (n=6-8): NA...

Embodiment -3

[0164] Example-3: Effect of Compound of Formula (A) on NAFLD / NASH Mice

[0165] According to the scheme in Example-2. The compound of formula (A) was compared with other antidiabetic compounds (Figure-8-13).

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PUM

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Abstract

Described herein are compounds of formula (I), their derivatives, analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts and compositions, metabolites and prodrugs thereof, for use in treating liver diseases such as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), and other fibrotic diseases of the liver; diabetic complications such as macro (ischemic heart disease, cerebrovascular disease and peripheral vascular disease) and micro (cataract, retinopathy nephropathy neuropathy, maculopathy and glaucoma) vascular complication; and cardiovascular diseases such as atherosclerosis, restenosis, hypertension, vasospasm, and cardiac hypertrophy; and lung disorders and lung fibrosis.

Description

technical field [0001] The present invention relates to compounds of formula (I) for use in the prevention and treatment of liver diseases such as nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH); Diabetic complications such as macrovascular complications (ischemic heart disease, cerebrovascular disease, and peripheral vascular disease) and microvascular complications (cataracts, retinopathy, nephropathy, neuropathy, maculopathy, and glaucoma); and cardiovascular diseases such as arterial Atherosclerosis, restenosis, vasospasm, and cardiac hypertrophy. [0002] The present invention discloses the use of compounds of formula (I), derivatives, analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts, compositions, Methods of metabolites and their prodrugs for the treatment of NAFLD / NASH. [0003] Background technique [0004] Hepatic steatosis in people who do ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/426A61P1/16A61P3/10
CPCA61K31/426A61P1/16A61P3/06A61P3/10A61P9/00A61P9/10A61P9/12A61P11/00A61P13/12A61P15/08A61P17/00A61P17/06A61P25/00A61P27/12A61P35/04
Inventor S·纳拉亚南J·穆坎J·库拉辛格尔G·辛格G·巴拉苏布拉玛尼安
Owner ORCHID CHEM & PHARM LTD
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