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

Argatroban analogue and preparation method and medical application thereof

A technology of argatroban and analogs, applied in the field of medicinal chemistry, can solve the problems of local pain, patient's physical and mental pain, and intravenous drip taking a long time, and achieve the effect of good dissolution rate

Active Publication Date: 2014-10-15
安庆生命科技园发展有限公司
View PDF4 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

As an injection, it can only be injected intravenously or intravenously or intramuscularly, but its biggest disadvantage is the local pain during administration, which causes great physical and mental pain to the patient. Intravenous infusion takes a long time and cannot meet the needs of different groups of people

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
  • Argatroban analogue and preparation method and medical application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Example 1: (2R,4R)-4-methyl-1-[N2-(R,S)-3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl-L-arginine Preparation of 1-Acetoxyethyl Cytosine]-2-Piperidinecarboxylate

[0043]

[0044]1. Preparation of sodium salt of ethyl hydroxyacrylate

[0045] Ethyl acetate (600ml, 6mol) was added to a 2000ml reaction flask, cooled to 0°C-5°C, sodium methoxide (220g, 4mol) was added, ethyl formate (380ml, 4.8mol) was slowly added dropwise, the dropwise addition was completed, and the temperature was raised Stir and reflux for 3 h, evaporate the solvent under reduced pressure to obtain 413 g of yellow powder, which is directly used in the next step.

[0046] 2. (2R, 4R)-4-methyl-1-[N2-(R, S)-3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl-L-arginine Preparation of Aminoisocytosine]-2-Piperidinecarboxylic Acid

[0047] Suspend 27.6g (0.2mol) of the above yellow powder in 500ml of toluene, stir, add 110g (0.195mol) of argatroban, stir and reflux for 8h, cool to room temperature, add...

Embodiment 2

[0054] Example 2: (2R,4R)-4-methyl-1-[N2-(R,S)-3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl-L-arginine Preparation of Cytosinyl]-2-piperidinecarboxylic acid-1-(isopropoxycarbonyloxy)-ethyl ester

[0055]

[0056] The title compound was synthesized in the same manner as in 3 in Example 1, using 1-iodoisopropoxycarbonylethane instead of 1-acetoxy-1-bromoethane. Yield 72.6%, HPLC content 98.2%.

[0057]

[0058] 1 H—NMR (500MHz, CDCl 3 / TMS, ppm): a total of 46 hydrogen signals

[0059] δ: 8.0 (s, 1H, NH); 5.29 (s, 1H, NH); 7.73; (s, 1H, NH); 2.1 (s, 1H, NH); 4.17 (t, 1H, JJ=7.5); 3.29~3.39 (m, 2H); 2.91~3.16 (m, 2H); 6.98~7.46 (m, 3H); 2.28 (m, 1H); 1,68 (m, 1H); 1.69~1.94 (m, 2H) ); 1.34~1.59 (m, 2H); 2.39~2.63 (m, 2H); 5.09 (m, H); 3.57 (m, H); 2.65 (t, 2H, JJ=7.1); 0.96 (d, 6H , JJ=6.8); 1.80 (t, 2H, JJ=7.1); 1.55~1.59 (m, 2H); 1.32 (d, 6H, JJ=6.8); 4.36 (t, 2H, JJ=7.0); 4.39 ( t, 2H, JJ=7.0); 6.48 (d, 2H, JJ=10.9); 7.95 (d, 2H, JJ=10.9)

[0060] MS: m / z (M...

Embodiment 3

[0061] Example 3: (2R,4R)-4-methyl-1-[N2-(R,S)-3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl-L-arginine Preparation of Ethyl Cytosine]-2-Piperidinecarboxylate

[0062]

[0063] The title compound was synthesized in the same manner as in 3 in Example 1, using 2-bromopropane instead of 1-acetoxy-1-bromoethane. Yield 84.1%, HPLC content 99.1%.

[0064]

[0065] 1 H—NMR (500MHz, CDCl 3 / TMS, ppm): a total of 42 hydrogen signals

[0066] 1 H—NMR (500MHz, CDCl 3 / TMS, ppm): a total of 42 hydrogen signals

[0067] δ: 8.0 (s, 1H, NH); 5.29 (s, 1H, NH); 7.73; (s, 1H, NH); 2.1 (s, 1H, NH); 4.17 (t, 1H, JJ=7.5); 3.29~3.39 (m, 2H); 2.91~3.16 (m, 2H); 6.98~7.46 (m, 3H); 2.28 (m, 1H); 1,68 (m, 1H); 1.69~1.94 (m, 2H) ); 1.34~1.59(m, 2H); 2.39~2.63(m, 2H); 4.55~4.85(d, 2H, JJ=7.0); 3.57(m, H); 2.65(t, 2H, JJ=7.1) ;0.96 (d, 6H, JJ=6.8); 1.80 (t, 2H, JJ=7.1); 1.55~1.59 (m, 2H); 7.25 (t, 1H, JJ=6.8) 6.48 (d, 2H, JJ= 10.9); 7.95 (d, 2H, JJ=10.9)

[0068] MS: m / z (M + ) 586 (...

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 relates to an argatroban analogue expressed in the general formula (I), a preparation method, a pharmaceutical composition containing the argatroban analogue and medical application that the argatroban analogue is adopted as a therapeutic agent, especially as a thrombin inhibitor, wherein the definitions of all substituent groups in the general formula (I) (refer to the Specification) are the same as the definitions in the specification and the argatroban analogue provided by the invention is for oral administration.

Description

technical field [0001] The present invention relates to the field of medicinal chemistry, in particular to an analog of argatroban represented by general formula (I), its preparation method, a pharmaceutical composition containing the analog, and its use as a therapeutic agent, especially as a thrombin Use of Inhibitors. Background technique [0002] Arteriosclerotic occlusive disease is systemic atherosclerosis manifested locally in the limbs. The systemic arterial intima and its middle layer present degenerative and proliferative changes, which make the vessel wall harden, shrink, and lose elasticity, resulting in secondary thrombosis leading to distant Progressive reduction or interruption of terminal blood flow. It can occur in all major arteries of the body, and is more common in the lower end of the abdominal aorta and the large and medium arteries of the lower extremities. The abdominal aorta and two common iliac arteries below the renal arteries are called Leriche ...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07K5/068A61K38/05A61P7/02
Inventor 徐奎刘经星
Owner 安庆生命科技园发展有限公司
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