Triazole compound, synthesis method and application thereof

A compound, triazole technology, applied in the field of biomedicine, can solve problems such as adverse reactions, long-term use of high-dose selective COX2 inhibitors, and side effects are not recommended

A compound, triazole technology, applied in the field of biomedicine, can solve problems such as adverse reactions, long-term use of high-dose selective COX2 inhibitors, and side effects are not recommended

CN108929281AActive Publication Date: 2018-12-04EAST CHINA NORMAL UNIV +1
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  • Triazole compound, synthesis method and application thereof
  • Triazole compound, synthesis method and application thereof
  • Triazole compound, synthesis method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1-1

[0116] Example 1-1, Compound (S)-4-(1-(1-(4-(trifluoromethyl)benzyl)-4-methyl-1hydrogen-1,2,3-triazole-5 - Preparation of formamido) ethyl) benzoic acid (YJ001)

[0117]

[0118] Take 4-trifluoromethylbenzyl bromide (717mg, 3mmol) in anhydrous dimethyl sulfoxide (4ml), add sodium azide (215mg, 3.3mmol), and stir at room temperature for 24h. After the reaction was completed, it was extracted with ethyl acetate, and the crude product 4-trifluoromethylbenzyl azide (556 mg, 92%) was obtained after conventional treatment.

[0119] Dissolve 4-trifluoromethylbenzyl azide (556mg, 2.77mmol) in anhydrous toluene (5ml), add ethyl 2-butynoate (224mg, 2mmol), react at 120°C for 12h and cool to room temperature. Most of the solvent was removed under reduced pressure, and after conventional treatment, it was passed through a silica gel column to obtain the intermediate 1-(4-(trifluoromethyl)benzyl)-1H-1,2,3-triazole-4-methyl-5- Ethyl formate (210 mg, 35%).

[0120] Dissolve ethyl 1-(4...

Embodiment 1-37

[0128] Example 1-37, Compound (S)-4-(1-(1-(4-(trifluoromethyl)benzyl)-4-(4-fluorophenyl)-1hydrogen-1,2,3 - Preparation of triazole-5-carboxamido) ethyl) benzoic acid (YJ037)

[0129]

[0130]Take 4-trifluoromethylbenzyl bromide (23.9g, 100mmol) in anhydrous dimethyl sulfoxide (30ml), add sodium azide (7.15g, 110mmol), and stir at room temperature for 24h. After the reaction was completed, it was extracted with ethyl acetate, and the crude product 4-trifluoromethylbenzyl azide (18.492 g, 92%) was obtained after conventional treatment.

[0131] Dissolve ethyl propiolate (9.8g, 100mmol) in acetone (30ml), add silver nitrate (1.7g, 10mmol), and react with N-bromosuccinimide (19.58g, 110mmol) at room temperature for 12h , most of the solvent was removed under reduced pressure, and after routine treatment, it was passed through a silica gel column to obtain ethyl bromopropiolate (17.6 g, 99%).

[0132] Dissolve 4-trifluoromethylbenzyl azide (18.492g, 92mmol) in anhydrous toluen...

Embodiment 1-45

[0141] Example 1-45, compound (S)-4-(1-(5-(trifluoromethyl)-1-(4-(trifluoromethyl)benzyl)-1H-1,2,3-tri Preparation of azole-4-carboxamido)ethyl)benzoic acid (YJ045)

[0142]

[0143] Take 4-trifluoromethylbenzyl bromide (717mg, 3mmol) in anhydrous dimethyl sulfoxide (4ml), add sodium azide (215mg, 3.3mmol), and stir at room temperature for 24h. After the reaction was completed, it was extracted with ethyl acetate, and the crude product 4-trifluoromethylbenzyl azide (556 mg, 92%) was obtained after conventional treatment.

[0144] Dissolve 4-trifluoromethylbenzyl azide (556mg, 2.77mmol) in anhydrous toluene (5ml), add 4,4,4-trifluoro-2-butyne ethyl ester (332mg, 2mmol), in After reacting at 120°C for 12h, it was cooled to room temperature. Most of the solvent was removed under reduced pressure, and the silica gel column was passed after conventional treatment to obtain the intermediate ethyl 5-(trifluoromethyl)-1-(4-(trifluoromethyl)benzyl)-1H-1,2,3 - Ethyl triazole-4-car...

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Abstract

The invention discloses a triazole compound as shown in a formula I and a formula II, and a pharmaceutical derivative and a hydrate of the triazole compound, a composition containing the triazole compound and a preparation method thereof. The invention also discloses a use of the triazole compound serving as a prostaglandin EP4 receptor antagonist for preventing and treating prostaglandin PGE2 mediated diseases, including malignant tumors, autoimmune diseases, inflammation, pains or osteoarthritis.

Description

technical field [0001] The invention belongs to the field of biomedicine, and relates to a class of triazole compounds and their synthesis method and application. The triazole compounds of the present invention are used as prostaglandin receptor EP4 antagonists for preventing and treating diseases mediated by prostaglandin PGE2. Including malignancy, autoimmune disease, inflammation, pain, etc. Background technique [0002] Gene mutations, epigenetic changes, chronic inflammation, poor diet and lifestyle are all key factors that induce cancer. Among them, high-fat diet can lead to the occurrence of various malignant tumors such as colorectal cancer, pancreatic cancer, breast cancer and prostate cancer. It is a biologically active lipid formed by the metabolism of arachidonic acid (AA) in animal fat through related metabolic pathways mediated by human cyclooxygenase (Cyclooxygenase, COX) and lipoxygenase (Lipoxygenase, LOX), Eicosanoids such as prostaglandins (PGs) and leuk...

Claims

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Application Information

Patent Timeline
04 Dec 2018
Publication
CN108929281A
IPC
C07D249/04; C07D409/04; C07D405/04; C07D405/06; A61K31/4192; A61P37/04; A61P37/06; A61P37/08; A61P29/00; A61P19/08; A61P35/00; A61P35/02
CPC
C07D249/04; C07D405/04; C07D405/06; C07D409/04
Inventors
章涵堃; 卢伟强