Method for treating sepsis

A septicemia and multipurpose technology, applied in the direction of blood diseases, cardiovascular system diseases, metabolic diseases, etc., can solve the problem of lack of apoptosis inhibitors and other problems

Active Publication Date: 2012-07-11
北京安塞迩生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] So far, there is still a lack of effective inhibitors of apoptosis clinically, and the development of novel anti-apoptotic compounds is used for example in the treatment and / or prevention of sepsis and its complications, as well as stroke sepsis and its complications. Complications are compelling research targets

Method used

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  • Method for treating sepsis
  • Method for treating sepsis
  • Method for treating sepsis

Examples

Experimental program
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Embodiment

[0146] A, compound preparation example part

[0147] The following preparation examples exemplarily prepare part of the compounds of formula I of the present invention, each compound is represented by Co.1 to Co.32, and Co.33 represents terazosin. In the reaction schemes of the following preparation examples, "reflux" means reflux, and "1-pentanol" means 1-pentanol.

preparation example 1

[0148] Preparation Example 1: Preparation of Co.1

[0149]

[0150] Step 1: Bubble ammonia gas into a 200 mL tetrahydrofuran solution dissolved in compound 1a (50 mmol), and carry out the reaction at 25° C. for 36 hours. A large amount of white solids were precipitated in the system, and the resulting white solids were filtered and washed with tetrahydrofuran to obtain the final product 1f. Yield: 63%.

[0151]

[0152] Step 2: 15 mL of acetic anhydride was added to compound 1f (10 mmol), and the reaction was refluxed for 2 hours. After cooling to room temperature, a large amount of white solids were precipitated in the system. The resulting white solids were filtered and washed with tetrahydrofuran to obtain 1 g of the final product. Yield: 63%.

[0153]

[0154] Step 3: To a solution of 1 g (2 mmol) of 1-pentanol was added under argon atmosphere for 1 h (2 mmol). After the reaction system was refluxed for 4.5 hours, it was placed in an environment of 0-5° C. f...

preparation example 2

[0156] Preparation Example 2: Preparation of Co.2

[0157]

[0158] Step 1: Compound 1b (20 mmol) was added to compound 1a (20 mmol) in 100 mL of methanol solution, and the reaction was carried out at 25° C. for 4 hours. Thin plate chromatography indicated that 1a was completely converted, and 100 mL of diethyl ether was added to the system, mixed evenly, and placed in a -20°C environment for static crystallization. The resulting white solid was recrystallized from petroleum ether / ethyl acetate to obtain the final product 1c. Yield: 41%.

[0159]

[0160] Step 2: To a solution of 1c (2 mmol) in 1-pentanol was added 1d (2 mmol) under argon atmosphere. After the reaction system was refluxed for 4.5 hours, it was placed in an environment of 0-5° C. for static crystallization. The obtained white crystals were washed twice with 10 mL of acetone, and then recrystallized with ether / methanol to obtain the final product 1e, which was compound Co.2. Yield: 62%.

[0161] 1H ...

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Abstract

The invention relates to a method for treating sepsis, in particular to application of compounds in a formula I and pharmaceutically acceptable salts, solvates, esters and prodrugs of the compounds in preparation of medicines for treating and / or preventing sepsis and complications thereof. In the formula, substituent groups are described in the specifications.

Description

technical field [0001] The present invention relates to a method for treating sepsis, in particular to the use of quinazoline derivatives and quinazoline derivatives such as terazosin in the preparation of medicines for treating and / or preventing sepsis and its complications. Background technique [0002] Sepsis is the leading cause of death in intensive care units worldwide. Sepsis is thought to be a dysregulation of a complex inflammation (Bone et al., 1996). However, many clinical trials of cytokine or anti-inflammatory specific agents have failed to significantly improve the survival of patients with sepsis, and reconsideration of sepsis treatment strategies is warranted. Antibiotic therapy is an important approach in the treatment of sepsis, although its effectiveness is limited. Basic research shows that inhibition of apoptosis is effective in blocking experimental sepsis. In septic patients, apoptosis of immune cells can further weaken the immune response. In addi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/517A61K45/00A61P1/00A61P1/16A61P3/10A61P7/00A61P7/02A61P9/00A61P11/00A61P13/12A61P31/00A61P31/04
Inventor 刘磊许晓椿李笑宇
Owner 北京安塞迩生物科技有限公司
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