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A kind of aminopyridine antifungal compound and its preparation and application

A technology of aminopyridine and antifungal drug, applied in the field of medicine, can solve the problems such as low practicability of echinocandins

Active Publication Date: 2016-08-24
YANTAI DONGCHENG PHARMA GRP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Considering the high drug resistance of fungi, the toxic and side effects of amphotericin B, and the lack of practicability of echinocandins, it is increasingly urgent to develop antifungal drugs with the latest mechanism of action for safer, more efficient, and less toxic antifungal drugs

Method used

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  • A kind of aminopyridine antifungal compound and its preparation and application
  • A kind of aminopyridine antifungal compound and its preparation and application
  • A kind of aminopyridine antifungal compound and its preparation and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] Example 1: Preparation of 6a2-amino-N-((5-((2-methylaniline)methyl)thiophen-2-yl)methyl)nicotinamide Step 1: 5-((2-methylaniline ) Preparation of methyl) thiophene-2-formonitrile

[0063] Dissolve 5-formylthiophene-2-carbonitrile (1 mmol) and 2-methylaniline (1 mmol) in methanol (10 mL), add sodium cyanoborohydride (188 mg), a drop of concentrated hydrochloric acid, and react overnight at room temperature. The crude solution was spin-dried and used directly in the next step.

[0064] Step 2: Preparation of N-((5-(aminomethyl)thiophen-2-yl)methyl-2-methylaniline

[0065] Dissolve 5-((2-methylaniline)methyl)thiophene-2-carbonitrile (1 mmol of crude product) in anhydrous tetrahydrofuran (25 mL), add lithium aluminum hydride (4 eq), react at 50 °C for 1 h, monitor by TLC, After the reaction was complete, water was added to quench, the solid was filtered, the filtrate was spin-dried, and the crude product was directly used in the next step.

[0066] Step 3: Preparation of...

Embodiment 2

[0070] Example 2: Preparation step 1 of 6b2-amino-N-((5-((3-methylaniline)methyl)thiophen-2-yl)methyl)nicotinamide: 5-((3-methylaniline ) Preparation of methyl) thiophene-2-formonitrile

[0071] Dissolve 5-formylthiophene-2-carbonitrile (1 mmol) and 3-methylaniline (1 mmol) in methanol (10 mL), add sodium cyanoborohydride (188 mg), a drop of concentrated hydrochloric acid, and react overnight at room temperature. The crude solution was spin-dried and used directly in the next step.

[0072] Step 2: Preparation of N-((5-(aminomethyl)thiophen-2-yl)methyl-3-methylaniline

[0073] Dissolve 5-((3-methylaniline)methyl)thiophene-2-carbonitrile (crude product 1 mmol) in anhydrous tetrahydrofuran (25 mL), add lithium aluminum hydride (4 eq), react at 50°C for 1 h, monitor by TLC, After the reaction was complete, water was added to quench, the solid was filtered, the filtrate was spin-dried, and the crude product was directly used in the next step.

[0074] Step 3: Preparation of 2-a...

Embodiment 3

[0078] Example 3: Preparation step 1 of 6c2-amino-N-((5-((4-methylaniline)methyl)thiophen-2-yl)methyl)nicotinamide: 5-((4-methylaniline ) Preparation of methyl) thiophene-2-formonitrile

[0079] Dissolve 5-formylthiophene-2-carbonitrile (1 mmol) and 4-methylaniline (1 mmol) in methanol (10 mL), add sodium cyanoborohydride (188 mg), a drop of concentrated hydrochloric acid, and react overnight at room temperature. The crude solution was spin-dried and used directly in the next step.

[0080] Step 2: Preparation of N-((5-(aminomethyl)thiophen-2-yl)methyl-4-methylaniline

[0081] Dissolve 5-((4-methylaniline)methyl)thiophene-2-carbonitrile (crude product 1 mmol) in anhydrous THF (25 mL), add lithium aluminum hydride (4 eq), react at 50 ° C for 1 h, monitor by TLC, After the reaction was complete, water was added to quench, the solid was filtered, the filtrate was spin-dried, and the crude product was directly used in the next step.

[0082] Step 3: Preparation of 2-amino-N-((5...

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Abstract

The invention relates to the medicine technical field. The invention provides an aminopyridines antifungal compound 2-amino-((5-N-substituted amine methylthiophene-2-group)methyl)nicotinamides compound and its salt, a chemical structure of the compound is shown as a formula I, wherein R represents phenyl or substituted phenyl. The invention also provides a preparation method and an application of the above compound. The compound has strong antifungal activity, and has advantages of low toxicity and wide antimicrobial spectrum, and the compound can be used for preparing the antifungal medicines.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to an aminopyridine antifungal compound and its preparation and application. Background technique [0002] Antifungal drugs are a general term for a class of drugs that kill or inhibit the growth and reproduction of fungi. Since the discovery of the first antifungal drug griseofulvin in 1939, humans have been fighting fungal infections for more than 70 years. antifungal drugs. There are three main mechanisms of action of antifungal drugs that are widely used clinically, triazoles (such as fluconazole) that target the cytochrome P450 enzyme system 14α demethylase, [0003] Polyenes (such as amphotericin B) that target ergosterol on the cell membrane and echinocandins that target β-(1,3)-D-glucan synthase on the cell wall (such as caspofungin). [0004] Considering the high drug resistance of fungi, the toxic and side effects of amphotericin B, and the lack of practicability of e...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D409/12A61K31/4436A61P31/10
CPCC07D409/12
Inventor 张大志姜远英仰振球倪廷峻弘安毛毛蔡瞻李晏田淑娟臧成旭谭善伦接浩华黄鑫陈思敏阎澜
Owner YANTAI DONGCHENG PHARMA GRP