Amino acid modified spinacin derivative and preparation method and application thereof

An amino acid, glycine acyl technology, applied in drug combinations, dipeptide components, blood diseases, etc., can solve problems such as bioavailability limitation and poor solubility

Inactive Publication Date: 2012-12-05
CAPITAL UNIVERSITY OF MEDICAL SCIENCES
View PDF2 Cites 32 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] S-carboline carboxylic acid is an alkaloid isolated from edible plants. It has certain antithrombotic activity, but its bioavailability is severely limited due to poor solubility, and its antiplatelet function cannot be well exerted.

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
  • Amino acid modified spinacin derivative and preparation method and application thereof
  • Amino acid modified spinacin derivative and preparation method and application thereof
  • Amino acid modified spinacin derivative and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Embodiment 1 (6S)-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-6-carboxylic acid synthesis

[0021] Put 10g of L-His in a 250ml eggplant-shaped bottle, dissolve it with a mixed solution of 80ml of distilled water and 20ml of formaldehyde, add 1ml of concentrated H 2 SO 4 , react in an oil bath at 60-70°C for 12h, cool to room temperature, add concentrated ammonia water dropwise under an ice bath to adjust the pH to 7-8, a large amount of colorless precipitate precipitated, and filtered to obtain 10.5g (97%) of the title compound as a colorless solid. ESI-MS(m / z): 167[M+H] +

Embodiment 2

[0022] Example 2 (6S)-3,5-two (tert-butoxycarbonyl)-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-6-carboxylic acid synthesis

[0023] Dissolve 1.67g (10mmol) (6S)-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-6-carboxylic acid in 2N aqueous sodium hydroxide solution under ice-bath conditions , take 5.23g (24mmol) (Boc) 2 O, dissolved with dioxane, added to the reaction solution. Stir at room temperature, TLC monitors the disappearance of the reaction raw material point, after the completion of the reaction, use saturated KHSO 4 The pH of the aqueous solution was adjusted to neutral, and concentrated under reduced pressure to remove dioxane. The aqueous layer was saturated with KHSO 4 The aqueous solution was acidified to pH=2, extracted with ethyl acetate and concentrated under reduced pressure to remove dioxane, the aqueous layer was extracted and washed with ethyl acetate (30ml×3), and the combined ethyl acetate layers were washed repeatedly with saturated NaCl until neutr...

Embodiment 3

[0024] Example 3 (6S)-3,5-bis(tert-butoxycarbonyl)-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-6-formyl-amino acid benzyl General method for the preparation of esters (3a-q)

[0025] Weigh 1.101g (3mmol) (6S)-3,5-bis(tert-butoxycarbonyl)-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-6-carboxyl Dissolve the acid in a 100ml eggplant-shaped bottle with a small amount of anhydrous tetrahydrofuran (THF), and then add 486mg (3.6mmol) of 1-hydroxybenzotriazole (HOBt) and 768mg (3.6mmol) of di Cyclohexylcarbodiimide (DCC), after activating for 30min, weigh AA-OBzl (3.6mmol) in a 25ml small Erlenmeyer flask, suspend it with anhydrous tetrahydrofuran (THF), and use N-methylmorpholine (NMM) Adjust the pH to neutral, then drop the suspension into the reaction solution, finally adjust the pH value of the reaction solution to about 8 with NMM, react overnight at room temperature, monitor by TLC until the raw material spots disappear, filter to remove dicyclohexyl urea ( DCU), the filtrate...

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 discloses a compound (6S)-4,5,6,7- tetrahydro-3H-imidazole[4,5-c]-pyridine-6-formyl-L-amino acid, and relates to seventeen compounds 5a-q shown as the general formula I, a preparation method and application in preparation of anti-thrombosis medicines. The blood clot dissolving effect of the compounds is evaluated on a rat cervical arteriovenous shunt thrombosis cannula model. The preparation method is simple, raw materials are easy to obtain, safe and low in cost, and the compounds shown as the general formula I have anti-platelet aggregation activity and anti-thrombosis activity and can be applied to preparation of anti-thrombosis medicines.

Description

technical field [0001] The present invention relates to an artificially synthesized compound and its preparation method and application, in particular to a (6S)-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-6 - formyl-L-amino acid, the present invention also relates to its preparation method and its application in the preparation of antithrombotic drugs. Background technique [0002] S-carboline carboxylic acid is an alkaloid isolated from edible plants. It has certain antithrombotic activity, but its bioavailability is severely limited due to poor solubility, and its antiplatelet function cannot be well exerted. According to literature reports (Ming Zhao, Lanrong Bi, Wei Bi, ChaoWang, Zhe Yang, Jingfang Ju, Shiqi Peng. Synthesis of new class dipeptide analogues with improved permeability and antithrombotic activity. Bioorganic & Medicinal Chemistry, Volume 14, Issue 14, 15 July 2006, Pages 4761-4774.), introducing endogenous amino acids into the 3-carboxyl group of carbolin...

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): C07K5/078A61K38/05A61P7/02
Inventor 彭师奇赵明史薇薇
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap