Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Phenylalanine derivative containing benzothiadiazine-3-ketone 1,1-dioxide and preparation method and application thereof

A technology of benzothiadiazine and dioxide, which is applied in the field of organic compound synthesis and pharmaceutical application, can solve the problems of low curative effect, poor drug-like properties, easy induction of drug resistance, etc., and achieve high application value

Active Publication Date: 2019-06-04
SHANDONG UNIV
View PDF5 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although PF-74 has a novel structure, unique mechanism, and clear targets, compared with currently marketed anti-HIV-1 drugs, PF-74 has lower efficacy, poor drug-like properties, and is very easy to induce drug resistance

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Phenylalanine derivative containing benzothiadiazine-3-ketone 1,1-dioxide and preparation method and application thereof
  • Phenylalanine derivative containing benzothiadiazine-3-ketone 1,1-dioxide and preparation method and application thereof
  • Phenylalanine derivative containing benzothiadiazine-3-ketone 1,1-dioxide and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Embodiment 1: (S)-(1-((4-methoxyphenyl)(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate tert-butyl ester (2 ) preparation

[0044] Starting materials Boc-L-phenylalanine (1) (2.90g, 10.93mmol, 1.5eq.), 1H-benzotriazol-1-yloxytripyrrolidinyl hexafluorophosphate (5.69g, 10.93mmol, 1.5eq.) was added to 20mL of dichloromethane, stirred for 30min under ice-bath conditions; then N,N-diisopropylethylamine (3.61mL, 21.87mmol, 3eq.) and N-methyl -4-Aminoanisole (1.0g 7.29mmol, 1eq.), remove the ice bath and transfer to room temperature to stir, TLC monitoring; after 6h, the reaction is complete, the solvent is evaporated under reduced pressure, and then saturated bicarbonate is added to the residue in the bottle Sodium solution 40mL, dichloromethane 40mL extraction, take the organic phase, add 1N HCl solution 40mL to wash, take the organic phase, add saturated sodium chloride solution 40mL to wash, the organic phase is dried with anhydrous sodium sulfate, filter, and the filt...

Embodiment 2

[0049] Example 2: Preparation of (S)-2-amino-N-(4-methoxyphenyl)-N-methyl-3-phenylpropanamide (3)

[0050] Intermediate 2 (4.0g, 10.40mmol, 1.0eq.) was added to 30mL of dichloromethane, then trifluoroacetic acid (3.86mL, 52.02mmol, 5.0eq.) was slowly added to this solution, stirred at room temperature, monitored by TLC After 1h, the reaction was completed, then the pH of the reaction solution was adjusted to 7 with saturated sodium bicarbonate solution, 40 mL of dichloromethane was added for extraction, the organic phase was separated, washed with saturated sodium chloride solution (20 mL × 3 times), and dried over anhydrous sodium sulfate , filtered, and concentrated under reduced pressure to obtain 2.36 g of crude product of intermediate (S)-2-amino-N-(4-methoxyphenyl)-N-methyl-3-phenylpropanamide (3), yellow oil material with a yield of 80%.

[0051] Spectral data:

[0052] 1 H NMR (400MHz, DMSO-d 6 )δ7.29–7.13(m,3H,Ph-H),7.03–6.75(m,6H,Ph-H),3.77(s,3H,OCH 3 ),3.44–3.3...

Embodiment 3

[0055] Example 3: Preparation of intermediate (S)-2-(2-bromoacetyl)-N-(4-methoxyphenyl)-N-methyl-3-phenylpropanamide (4)

[0056] Bromoacetic acid (117mg, 0.84mmol, 1.2eq.), O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate ( 401mg, 1.06mmol, 1.5eq.) was added to 15mL of dichloromethane, stirred in ice bath for 1h; then intermediate 3 (200mg, 0.70mmol, 1eq.) and N,N-diisopropyl Ethylamine (232μL, 1.41mmol, 2eq.), after removing the ice bath, stirred at room temperature, monitored by TLC; after 6h, the reaction was completed, the solvent was evaporated under reduced pressure, and the silica gel column chromatography (eluent EA:PE=1:4 + 2.5% triethylamine) to the intermediate (S)-2-(2-bromoacetyl)-N-(4-methoxyphenyl)-N-methyl-3-phenylpropanamide (4) 190 mg, white oil, yield 68%.

[0057] Spectral data: ESI-MS: m / z 405.4(M+1).C 19 h 21 BrN 2 o 3 [404.1].

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides a phenylalanine derivative containing benzothiadiazine-3-ketone 1,1-dioxide and a preparation method and an application thereof. The derivative has a structure as shown in the following general formula I. The invention also relates to a preparation method of the derivative and the application of the derivative as an HIV-1 inhibitor in preparation of anti-AIDS drugs.

Description

technical field [0001] The invention belongs to the technical field of organic compound synthesis and medical application, and specifically relates to a phenylalanine derivative containing benzothiadiazin-3-one 1,1-dioxide and a preparation method and application thereof. Background technique [0002] AIDS (Acquired Immune Deficiency Syndrome, AIDS) is a major infectious disease mainly caused by Human Immunodeficiency Virus Type 1 (Human Immunodeficiency Virus Type 1, HIV-1), which endangers human life and health. At present, clinically used drugs for the treatment of AIDS are mainly divided into four categories: reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, and invasion inhibitors according to different targets. "Highly Active Antiretroviral Therapy" (Highly Active Antiretroviral Therapy, HAART) prolongs the survival time of patients to a large extent and improves the quality of life of patients, but drug resistance, drug side effects, latent ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07K5/078C07K5/02A61K38/05A61P31/18
CPCY02P20/55
Inventor 刘新泳孙林展鹏黄天广巩志伟李国雄陈阳中慧
Owner SHANDONG UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com