Hybrid peptide using 3S-tetrahydro-beta-carboline-3-carboxylic acid as connecting arm, and preparation method and application thereof

A carboline, general formula technology, applied in the field of hybrid peptides, can solve problems such as difficulty in detection, and achieve the effect of excellent thrombolytic activity

Inactive Publication Date: 2011-07-13
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] P6A and its analogs as the lead structure of thrombolytic oligopeptides and the metabolites of P6A as the lead structure of thrombolytic oligopeptides have inherent room for improvement, that is, the difficulties in their detection caused by proteins and peptides existing in the body, and LC / MS detection The resulting technical and economic difficulties are subject to improvement

Method used

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  • Hybrid peptide using 3S-tetrahydro-beta-carboline-3-carboxylic acid as connecting arm, and preparation method and application thereof
  • Hybrid peptide using 3S-tetrahydro-beta-carboline-3-carboxylic acid as connecting arm, and preparation method and application thereof
  • Hybrid peptide using 3S-tetrahydro-beta-carboline-3-carboxylic acid as connecting arm, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Embodiment 1 Preparation of Boc-Pro-Ala-Lys(Z)-OBz

[0024] 1) Preparation of Boc-Ala-Lys(Z)-OBzl

[0025] Dissolve 473mg (2.5mmol) Boc-Ala in 10ml anhydrous anhydrous tetrahydrofuran (THF), add 10ml containing 338mg (2.5mmol) N-hydroxybenzotriazole (HOBt) and 619mg (3mmol) bicyclic Hexylcarbodiimide (DCC) in anhydrous THF. The reaction mixture was stirred in an ice bath for 20 minutes to obtain the corresponding active ester solution for use.

[0026] 936mg (2.3mmol) HCl·Lys(Z)-OBzl and 232mg (2.3mmol) N-methylmorpholine were first miscible with 6ml of anhydrous THF, and then with the active ester solution to be used above. The resulting reaction mixture was reacted at room temperature for 24 hours. TLC (developer CHCl3:MeOH=20:1) showed that HCl·Lys(Z)-OBzl disappeared. The reaction mixture was concentrated to dryness under reduced pressure, the residue was dissolved in ethyl acetate, and the insoluble matter was filtered off. The filtrate was washed successively...

Embodiment 2

[0032] Example 2 Boc-Arg (NO 2 Preparation of )-Pro-Ala-Lys(Z)-OBzl

[0033] 1) Preparation of HCl Pro-Ala-Lys(Z)-OBzl

[0034] A mixture of 1.596g (2.5mmol) Boc-Pro-Ala-Lys(Z)-OBzl in 15ml of ethyl acetate (4N) containing hydrogen chloride was stirred under ice bath for 1 hour, TLC (developing agent CHCl 3 :MeOH=20:1) showed that Boc-Pro-Ala-Lys(Z)-OBzl disappeared. Drain the reaction solution with a water pump, add anhydrous ether, and drain the reaction solution with a water pump again, repeating 5 times. The residue was triturated with anhydrous ether 5 times. The obtained title compound was directly used in the next reaction.

[0035] 2) Preparation of Boc-Arg(NO 2 )-Pro-Ala-Lys(Z)-OBzl

[0036] 798mg (2.5mmol) Boc-Arg (NO 2 ) was dissolved in 10ml of anhydrous THF, and 10ml of anhydrous THF solution containing 338mg (2.5mmol) of HOBt and 619mg (3mmol) of DCC was added under ice cooling. The reaction mixture was stirred in ice bath for 20 minutes to obtain the cor...

Embodiment 3

[0038] Example 3 Boc-Ala-Arg (NO 2 Preparation of )-Pro-Ala-Lys(Z)-OBzl

[0039] 1) Preparation of HCl Arg (NO 2 )-Pro-Ala-Lys(Z)-OBzl

[0040] 2.099g (2.5mmol) Boc-Arg (NO 2 )-Pro-Ala-Lys(Z)-OBzl and 15ml of hydrogen chloride-containing ethyl acetate (4N) mixture was stirred under ice bath for 1 hour, TLC (developing agent CHCl 3 : MeOH=10:1) shows that Boc-Arg (NO 2 )-Pro-Ala-Lys(Z)-OBzl disappeared. Drain the reaction solution with a water pump, add anhydrous ether, and drain the reaction solution with a water pump again, repeating 5 times. The residue was soaked and washed with anhydrous ether, rubbed with a plastic shovel, and poured out of anhydrous ether, repeated 5 times. The obtained title compound was directly used in the next reaction.

[0041] 2) Boc-Ala-Arg (NO 2 Preparation of )-Pro-Ala-Lys(Z)-OBzl

[0042] Dissolve 473mg (2.5mmol) of Boc-Ala in 10ml of anhydrous THF, add 10ml of anhydrous THF solution containing 338mg (2.5mmol) of HOBt and 619mg (3mmol)...

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Abstract

The invention discloses a compound with a general formula II and thrombolytic activity and a preparation method thereof, and application of the compound serving as a thrombolytic. The thrombolytic activity of the compound with the general formula II is evaluated by using a rat cervical artery and vein bypass cannula thrombosis model. The result of an animal test shows that the compound with the general formula II has excellent thrombolytic activity and can clinically serve as the thrombolytic.

Description

[0001] This application is the application number "200710100028.2", the application date is June 4, 2007, and the invention name is "Hybrid peptide with 3S-tetrahydro-β-carboline-3-carboxylic acid as the connecting arm, its preparation method and Application" of the divisional application of the invention patent application. technical field [0002] The present invention relates to a hybrid peptide, in particular to a hybrid peptide with 3S-tetrahydro-β-carboline-3-carboxylic acid as a linking arm and a preparation method thereof. The present invention also relates to the application of the hybrid peptide as a thrombolytic agent , belonging to the field of medicine. Background technique [0003] Streptokinase, urokinase, recombinant tissue plasminogen activator and other drugs currently used clinically for the treatment of acute thromboembolic diseases generally have systemic hemorrhage tendency and immunogenic reactions. Finding safe and effective thrombolytic drugs is the ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06C07K1/06A61K38/08A61P7/02
CPCY02P20/55
Inventor 彭师奇赵明崔国辉温敏
Owner PEKING UNIV
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