Pyrazolopyridines alkynylbenzene compound and medicinal composition and application

A technology of pyrazolopyridines and compounds, which is applied in drug combination, organic chemistry, antineoplastic drugs, etc., can solve the problem of huge quantity, and achieve the effects of high drugability, good pharmacokinetics and low toxicity

Active Publication Date: 2013-07-24
ASCENTAGE PHARMA SUZHOU CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] The applicant disclosed a heterocyclic alkyne benzene compound in the patent application 201010216603.7, which can effectively inhibit the growth of various tumor cells. However, due to the huge number of such compounds, it can efficiently inhibit the growth of various tumor cells and Compounds with low toxicity remain to be further studied by those skilled in the art

Method used

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  • Pyrazolopyridines alkynylbenzene compound and medicinal composition and application
  • Pyrazolopyridines alkynylbenzene compound and medicinal composition and application
  • Pyrazolopyridines alkynylbenzene compound and medicinal composition and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] 4-methyl-3-((3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl)-N-(4-((4-methylpiperazine- 1-yl)methyl)-3-trifluoromethylphenyl)benzamide

[0064] 4-methyl-3-((3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl)-N-(4-((4-methylpiperazin-1-yl)methyl)- 3-(trifluoromethyl)phenyl)benzamide

[0065]

[0066] step 1.

[0067] 5-Bromo-2-chloro-N-methoxy-N-methylnicotinamide

[0068] 5-bromo-2-chloro-N-methoxy-N-methylnicotinamide

[0069]

[0070] Dissolve 96g (294.07mmol) of 5-bromo-2-chloronicotinic acid in 1L of dichloromethane, and add 31.45g (323.48mmol) of N, O-dimethylhydroxylamine hydrochloride and 62g (323.48mmol) of EDC hydrochloride under stirring. mmol), finally dropwise added triethylamine 39.2g (388.17mmol), stirred overnight, the reaction solution was washed with water, washed with saturated brine, the organic phase was dried with anhydrous sodium sulfate, the solvent was spin-dried under reduced pressure, and column chromatography obtained 65g of a white s...

Embodiment 2

[0128] N-(3-(1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)-4-methyl-3-((3-methyl-1H-pyrazolo[3,4 -b]pyridin-5-yl)ethynyl)benzamide

[0129] N-(3-(1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)-4-methyl-3-((3-methyl-1H-pyrazolo[3,4-b]pyri din-5- yl)ethynyl)benzamide

[0130]

[0131] The synthetic method is as embodiment 1

[0132] 1 HNMR (400MHz, d-DMSO), δppm 13.49(s, 1H), 10.75(s, 1H), 8.69(d, J=2.0Hz, 1H), 8.52(d, J=2.0Hz, 1H), 8.34( s, 2H), 8.22(s, 2H), 7.95(d, J=8.0Hz, 1H), 7.79(s, 2H), 7.56(d, J=8.0Hz, 1H), 7.17(s, 1H), 2.60(s, 3H), 2.53(s, 3H).

[0133] MS (ESI), m / z: 501 (M + +H + ).

Embodiment 3

[0135] 4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((3-methyl-1H-pyrazole And[3,4-b]pyridin-5-yl)ethynyl)benzamide

[0136] 4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((3-methyl-1H-pyrazolo[3,4-b]pyridin -5-yl)ethynyl)benzamide

[0137]

[0138] The synthetic method is as embodiment 1

[0139] 1 HNMR (400MHz, d-DMSO), δppm 13.49(s, 1H), 10.72(s, 1H), 8.70(d, J=1.6Hz, 1H), 8.52(d, J=1.6Hz, 1H), 8.30( s, 1H), 8.21(s, 2H), 8.17(s, 2H), 7.95(m, 2H), 7.74(s, 2H), 7.56(d, J=8.0Hz, 1H), 7.49(s, 2H ), 2.60(s, 3H), 2.54(s, 3H), 2.19(s, 3H).

[0140] MS (ESI), m / z: 515 (M + +H + ).

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Abstract

The invention discloses a pyrazolopyridines alkynylbenzene compound having a structural characteristic shown in a formula (I) or its pharmaceutically acceptable salt or a stereisomer or prodrug molecules, and an application of the compound and its pharmaceutically acceptable salt or the stereisomer in preparation of medicines for treating or preventing tumor. Compared with a clinical used antitumor drug (imatinib), the compound has obvious advantage for resisting the activity of a plurality of tumor-derived type and drug resistance type cells, and the compound has the characteristics of good pharmacokinetics and low toxicity. The definitions of groups in the formula are disclosed in the specification.

Description

technical field [0001] The present invention belongs to the field of chemical medicine, in particular to a pyrazolopyridyne benzene compound having the structural characteristics of formula (I) or a pharmaceutically acceptable salt or stereoisomer thereof and a prodrug molecule thereof. Pharmaceutical compositions and applications of these compounds or compositions in the preparation of medicaments. Background technique [0002] Tumor is currently the number one killer of human health and life, and its incidence rate is second only to cardiovascular diseases. And with the impact of environmental pollution or other factors, the incidence of malignant tumors is rapidly increasing. According to the data released by the World Health Organization in 2003, there were 10 million malignant tumor patients in the world in 2000, and 6.2 million deaths due to malignant tumors, accounting for 12% to 25% of the total deaths. It is expected that by 2020, there will be 15 million new case...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D471/04A61K31/496A61K31/437A61K31/5377A61K31/4545A61P35/00A61P35/02
Inventor 丁克冯玉冰陆小云潘小芬张章龙活尤任小梅李伟华
Owner ASCENTAGE PHARMA SUZHOU CO LTD
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