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Drug for preventing or treating lactic acidosis

A technology of lactic acidosis and medicine, which is applied in the direction of pharmaceutical formulations, medical preparations containing active ingredients, drug delivery, etc., and can solve unknown problems

Inactive Publication Date: 2018-11-23
KEIO UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it is not known that 5-hydroxypyrimidine-4-carboxamide derivatives have the effect of preventing or treating lactic acidosis

Method used

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  • Drug for preventing or treating lactic acidosis
  • Drug for preventing or treating lactic acidosis
  • Drug for preventing or treating lactic acidosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0129] ({[5-Hydroxy-2-({1-[4'-(hydroxymethyl)biphenyl-4-yl]piperidin-4-yl}methyl)-6-methylpyrimidin-4-yl] Carbonyl} amino) acetic acid (compound A) preparation

[0130] Compound A was prepared according to the method of Example 1 of WO2011 / 049126 (Patent Document 1). Compounds prepared by 1 Compound A was identified by H-NMR (proton nuclear magnetic resonance spectrum) and mass analysis.

Embodiment 2

[0132] [({5-Hydroxy-2-[(1-{4'-[(2S)-2-hydroxypropyl]biphenyl-4-yl}piperidin-4-yl)methyl]-6-methyl Preparation of pyrimidin-4-yl}carbonyl)amino]acetic acid (compound B)

[0133] Compound B was prepared according to the method of Example 45 of WO2011 / 049126 (Patent Document 1). Compounds prepared by 1 Compound B was identified by H-NMR and mass analysis.

preparation example 1

[0154] Preparation example 1 (tablet)

[0155] 100 mg of the powdered Example compound, 124 mg of lactose, 25 mg of cellulose, and 1 mg of magnesium stearate were mixed and compressed with a tablet machine to prepare one 200 mg tablet. The tablets are optionally coated with sugar.

[0156] As shown above, the compound represented by the general formula (I) of the present invention significantly improved the survival rate of lethal metformin-induced lactic acidosis and chronic kidney disease lactic acidosis by oral single-dose administration.

[0157] From the above results, it was found that the preventive or therapeutic medicament for lactic acidosis of the present invention can be used for new prevention or treatment of lactic acidosis.

[0158] (industrial availability)

[0159] The medicine for the prevention or treatment of lactic acidosis of the present invention can be used for drug-induced lactic acidosis, renal failure-induced lactic acidosis, shock-induced lactic a...

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PUM

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Abstract

The purpose of the present invention is to provide a drug containing a compound having excellent preventive or therapeutic effect for lactic acidosis. The present invention provides a drug for preventing or treating lactic acidosis, the drug containing a compound represented by general formula (I), or a pharmacologically acceptable salt thereof as an active constituent. In the general formula (I),R1 represents a hydroxy C1-C6 alkyl group, a C2-C7 alkanoyl group, a C2-C7 alkanoyl, a C1-C6 alkyl group, a (C1-C6 alkoxy)carbonyl group, a (C1-C6 alkoxy)carbonyl, a C1-C6 alkyl group, a carboxy group, or a carboxy C1-C6 alkyl group.

Description

technical field [0001] The present invention relates to a medicine for preventing or treating lactic acidosis containing 5-hydroxypyrimidine-4-carboxamide derivative as an active ingredient. [0002] This application claims the priority of Japanese Application No. Japanese Patent Application No. 2016-078492, which is incorporated herein by reference. Background technique [0003] Lactic acidosis is a serious disease with a high mortality rate and has been reported in severe infectious diseases including ischemic diseases or sepsis, diabetic patients prescribed metformin, a biguanide drug that lowers blood sugar levels by inhibiting hepatic gluconeogenesis, Especially in patients with chronic kidney disease (there is a condition called "CKD" hereinafter). [0004] In addition to lowering blood sugar levels, metformin can also inhibit the proliferation of cancer cells and reduce the incidence of cancer, which is also related to longevity. Therefore, it is considered that the...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/506A61P3/12
CPCA61K31/506A61P3/00A61K9/0053
Inventor 南岛洋司寅丸智子寿原朋宏山口京二
Owner KEIO UNIV
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