Epidithiodioxopiperazine compound or derivative thereof, or pharmaceutical composition for preventing or treating pulmonary hypertension, containing pharmaceutically acceptable salts thereof

A technique for dithiodioxopiperazine and pulmonary arterial hypertension, which is applied in the field of pharmaceutical compositions for the prevention or treatment of pulmonary arterial hypertension, and can solve problems such as side effects, difficulty in application, and no significant effect of pulmonary arterial hypertension

Active Publication Date: 2020-03-24
瓦西特拉有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Currently, there are methods of using general vasodilators as drugs for the treatment of pulmonary hypertension, but most of the vasodilators are calcium channel blockers, which are difficult to apply since they generally have no significant effect on pulmonary hypertension and have side effects associated with administration

Method used

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  • Epidithiodioxopiperazine compound or derivative thereof, or pharmaceutical composition for preventing or treating pulmonary hypertension, containing pharmaceutically acceptable salts thereof
  • Epidithiodioxopiperazine compound or derivative thereof, or pharmaceutical composition for preventing or treating pulmonary hypertension, containing pharmaceutically acceptable salts thereof
  • Epidithiodioxopiperazine compound or derivative thereof, or pharmaceutical composition for preventing or treating pulmonary hypertension, containing pharmaceutically acceptable salts thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation Embodiment 1

[0056] Preparation Example 1: Preparation of Monocrotaline-Induced Pulmonary Hypertension Experimental Animals

[0057] Male SD rats weighing about 210 g were used as animal models. To induce pulmonary hypertension, a single intraperitoneal injection of monocrotaline (MCT) was administered at a dose of 60 mg / kg. Accordingly, the rat model in which pulmonary hypertension was induced was maintained for 3 weeks with or without administration of the test drug, and then the rat model was sacrificed. Thereafter, hearts were excised and analyzed.

Embodiment 1

[0058] Example 1: Therapeutic Effects of Table Dithiodioxopiperazine Compounds on Pulmonary Hypertension 1

[0059] 5,7-dimethyl-2,3-dithia-5,7-diazabicyclo[2.2.2]octane-6,8-dione (compound of formula 3; hereinafter referred to as "A-2 ”) is an epidithiodioxopiperazine compound, each of which was administered to the animal model of pulmonary hypertension prepared according to Preparation Example 1 above at doses of 3 μg and 6 μg every 3 days. As in Preparation Example 1, normal rats not administered with MCT were used as the control group, and rats administered with MCT alone to induce pulmonary hypertension were used as the MCT group. The control group and each experimental group consisted of 3 to 4 rats.

[0060] Similar to Preparation Example 1, the rats were maintained for 2 weeks, and then the hearts were excised. Measure the total mass of the excised heart. Afterwards, the right ventricle was isolated, and the masses of the right ventricle, left ventricle, and cardiac...

Embodiment 2

[0066] Example 2: Therapeutic effect of epidithiodioxopiperazine compounds on pulmonary arterial hypertension 2

[0067] Through Example 1, the efficacy of an epidithiodioxopiperazine derivative compound, namely A-2, for the treatment of pulmonary arterial hypertension was confirmed, thus confirming whether another epidithiodioxopiperazine derivative compound has the same effect.

[0068] Specifically, in addition to using 2,3-dithia-5,7-diazabicyclo[2.2.2]octane-6,8-dione (compound of formula 2; hereinafter referred to as "A-1") In the case of 4,5,7-trimethyl-2,3-dithia-5,7-diazabicyclo[2.2.2]octane-6,8-dione ( Formula 4 compound; hereinafter referred to as "A-3"), 5,7-diallyl-2,3-dithia-5,7-diazabicyclo[2.2.2]octane-6,8 - diketone (compound of formula 5; hereinafter referred to as "A-5") and 7-(4-methoxybenzyl)-2,3-dithia-5,7-diazabicyclo[2.2.2 ] Octane-6,8-dione (compound of formula 6; hereinafter referred to as "A-6") instead of A-2, carried out the same method as in Ex...

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Abstract

The present invention relates to: an epidithiodioxopiperazine (ETP) compound or a derivative thereof; or a pharmaceutical composition for preventing or treating pulmonary hypertension, containing pharmaceutically acceptable salts thereof.

Description

technical field [0001] The present invention relates to a pharmaceutical composition for preventing or treating pulmonary hypertension, which comprises an epidithiodioxopiperazine (ETP) compound or a derivative thereof or a pharmaceutically acceptable salt thereof. Background technique [0002] The pulmonary artery is the artery that carries blood from the right ventricle to the lungs for oxygen supply, and pulmonary hypertension is defined as a mean pulmonary arterial pressure greater than or equal to 25 mmHg at rest or 30 mmHg during exercise. Pulmonary hypertension is divided into "primary pulmonary hypertension", which is a condition for which no specific cause has been found, and specific disease "associated pulmonary hypertension", which occurs secondary to a specific predisposing disease. Examples of the latter condition include genetically linked familial pulmonary hypertension and disease-specific pulmonary hypertension that may be caused by collagen vascular diseas...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/549A61K31/548
CPCA61K31/548A61K31/549A61P9/12
Inventor 姜相元权起焕
Owner 瓦西特拉有限公司
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