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Bicyclic derivatives serving as CRTH2 receptor antagonist

A compound, cycloalkyl technology, applied in the field of bicyclic derivatives as CRTH2 receptor antagonists, can solve the problems of prolonged thromboplastin time, poor selectivity, weak CRTH2 receptor antagonistic effect, etc.

Inactive Publication Date: 2013-10-30
KBP BIOSCIENCES CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Ramatroban (Ramatroban) is listed as a thromboxane A2 receptor antagonist. It has a strong platelet activation effect, but has a weak antagonism effect on the CRTH2 receptor, and its selectivity is poor. The main adverse reactions are purpura, prothrombin time / activation Prolonged partial thromboplastin time, subcutaneous hemorrhage

Method used

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  • Bicyclic derivatives serving as CRTH2 receptor antagonist
  • Bicyclic derivatives serving as CRTH2 receptor antagonist
  • Bicyclic derivatives serving as CRTH2 receptor antagonist

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0121] Example 1 Preparation of 2-[1-(4-chlorophenylthio)imidazo[1,5-a]pyridin-3-yl]acetic acid (Compound 1)

[0122]

[0123] (1) Ethyl malonate monoyl chloride

[0124] Ethyl malonate (13.2g, 100.0mmol) and N,N-dimethylformamide (0.05mL) were stirred and dissolved in dichloromethane (200mL), cooled to 0°C in an ice-water bath, and oxalyl chloride ( 25.4g, 200mmol), the mixture was stirred at room temperature for 2h, and concentrated to obtain ethyl malonyl chloride (14.5g, 97%) as a white oil.

[0125] (2) Ethyl 3-oxo-3-(pyridin-2-ylmethyleneamino)propionate

[0126]

[0127] Ethyl malonyl chloride (14.5g, 96.7mmol) was dissolved in dichloromethane (150mL), cooled to 0°C in an ice-water bath, and triethylamine (19.5g, 193mmol) dissolved in 50mL of dichloromethane was added dropwise and 2-aminomethylpyridine (13.6g, 125.7mmol), stirred at room temperature for 3 hours. Then the solvent was removed by rotary evaporation, and the residue was separated by silica gel colu...

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Abstract

The invention belongs to the technical field of medicine, and particularly relates to bicyclic derivatives (shown in a general formula (I)) serving as CRTH2 receptor antagonist and pharmaceutically acceptable salt and stereoisomeride thereof, wherein in the general formula (I), X1, X2, X3, X4, X5, X6, X7, X8, Y, Z, R1 and R2 are as defined in the specification. The invention also relates to a preparation method of these compounds, a pharmaceutical preparation and pharmaceutical composition containing these compounds, and application of these compounds in preparation of medicaments for treating and / or preventing diseases related to CRTH2 activity.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to biscyclic derivatives as CRTH2 receptor antagonists, pharmaceutically acceptable salts and stereoisomers thereof, preparation methods of these compounds, pharmaceutical preparations and medicines containing these compounds The composition, and the application of these compounds, their pharmaceutically acceptable salts or their stereoisomers in the preparation of medicines for treating and / or preventing diseases related to CRTH2 activity. Background technique [0002] CRTH2 is a G protein-coupled chemoattractant receptor expressed on Th2 cells, eosinophils. Th2-polarization has been observed in allergic diseases such as asthma, allergic rhinitis, atopic dermatitis and allergic conjunctivitis. Th2 cells regulate allergic diseases by producing Th2 cytokines, such as IL-4, IL-5 and IL-3. In allergic diseases, these Th2 cytokines directly or indirectly induce the migrat...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D471/04C07D487/04A61K31/437A61K31/5025A61K31/53A61K31/519A61K31/4985A61P11/06A61P11/02A61P27/14A61P35/02A61P17/00A61P17/06A61P1/00A61P19/02A61P11/00
Inventor 吴永谦张艳
Owner KBP BIOSCIENCES CO LTD
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