Cyclohexyl tetrahydro imidazo pyrido indole-diketone acetyl amino acids, and synthesis, antithrombotic effect and application thereof

A kind of technology of diketoacetyl and tetrahydroimidazole, applied in the field of biomedicine

Inactive Publication Date: 2013-12-18
CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although inhibiting the expression of insoluble P-selectin and its cleavage to soluble P-selectin is considered an important target for the design of antithrombotic drugs, few antithrombotic compounds are currently associated with this target

Method used

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  • Cyclohexyl tetrahydro imidazo pyrido indole-diketone acetyl amino acids, and synthesis, antithrombotic effect and application thereof
  • Cyclohexyl tetrahydro imidazo pyrido indole-diketone acetyl amino acids, and synthesis, antithrombotic effect and application thereof
  • Cyclohexyl tetrahydro imidazo pyrido indole-diketone acetyl amino acids, and synthesis, antithrombotic effect and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Example 1 Preparation of 3S-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (1)

[0023] While stirring, first add 5g (24.5mmol) L-tryptophan to 25ml sulfuric acid (1N), then add dropwise 75ml deionized water and 4ml (45.6mmol) formaldehyde solution (38%), the reaction solution becomes clear quickly, about 5 A large amount of solid precipitated out within minutes. After reacting for 6 hours, 8 ml of concentrated ammonia water was added dropwise to adjust the pH to 7. The reaction solution was allowed to stand overnight, filtered with suction, and the filter cake was washed with 5 ml of cold water to obtain 4.1 g (77%) of the title compound as an off-white powder. Mp 280~282℃.EI-MS 217[M+H] + . (c=0.5, CH 3 OH:HCl(1N)=1:1, v / v). 1 H-NMR (500M, DMSO-d 6 ): δ / ppm=10.99(s, 1H), 7.44(d, J=7.5Hz, 1H), 7.33(t, J=7.5Hz, 1H), 7.08(t, J=7.5Hz, 1H), 6.98 (t, J=7.5Hz, 1H), 4.30(m, 2H); 3.69(dd, J=10.5Hz, J=5.1Hz, 1H), 3.18(dd, J=10.5Hz, J=2.4Hz, 1H ), 2.83(ddd, J=10.5Hz, ...

Embodiment 2

[0024] Example 2 Preparation of 2-cyclohexyl-5,6,11,11a-tetrahydro-3,5,6,11-tetrahydro-1H-imidazo[1',5':1,6]-pyrido[ 3,4-b]indole-1,3-dione (2)

[0025] Dissolve 0.554g (2.20mmol) of 3S-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (1) in 15ml of anhydrous DMSO and place it in an eggplant-shaped bottle under ice-bath condition , after dissolving 1.057g (5.13mmol) of DCC in 10ml of anhydrous DMSO, drop it into the above system. After the dropwise addition, the reaction solution was transferred into a microwave reaction tank, and reacted in microwave at 70°C for 6h. After the reaction was completed, cool, add water to the reaction solution, extract the aqueous layer with chloroform three times, combine the organic layers, wash with brine, dry over anhydrous sodium sulfate, filter, concentrate, silica gel column chromatography (petroleum ether / ethyl acetate=3: 1), 0.433 g (50%) of the title compound B was obtained as a yellow powder. Mp: 228-230℃; EI-MS: 323.4[M] + , 346.3...

Embodiment 3

[0026] Example 3 Preparation of 2-cyclohexyl-5,6,11,11a-tetrahydro-3,5,6,11-tetrahydro-1H-imidazo[1',5':1,6]-pyrido[ 3,4-b]indole-1,3-dione-6-ethyl acetate (3)

[0027] 1.84 g (5.70 mmol) of 2-cyclohexyl-5,6,11,11a-tetrahydro-3,5,6,11-tetrahydro-1H-imidazo[1',5':1,6]- Pyrido[3,4-b]indole-1,3-dione (2) was dissolved in 20ml of acetone, 2.36g (24mmol) of potassium carbonate and 1.3ml (11.4mmol) of ethyl bromoacetate were added and refluxed overnight. After the reaction was completed, the system was diluted with 200 ml of ethyl acetate, the ester layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain 2.33 g (99%) of the title compound as a pale yellow oil. ESI-MS(m / z)410[M+H] + . 1 HNMR (500M, DMSO-d 6 ): δ / ppm=7.50(d, J=7.5Hz, 1H), 7.24(d, J=3.6Hz, 2H), 7.15(m, 1H), 5.07(d, J=15.0Hz, 1H), 4.74 (s, 2H), 4.34(d, J=12.0Hz, 1H), 4.14(q, J=5.5Hz, 1H), 3.97(m, 1H), 3.38(dd,...

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Abstract

The invention discloses 10 kinds of cyclohexyl tetrahydro imidazo pyrido indole-diketone acetyl amino acids represented by the general formula I (wherein AA represents a valine residue, a leucine residue, an isoleucine residue, a glycine residue, a glutamic acid residue, a tryptophan residue, a methionine residue, an aspartic acid residue, a phenylalanine residue and a tyrosine residue), discloses a synthesis method thereof, discloses in vitro platelet aggregation inhibition experiments thereof, further discloses an antithrombotic activity thereof in a rat arteriovenous bypass cannula thrombosis model, and thus discloses an application thereof in preparation of antithrombotic agents.

Description

technical field [0001] The present invention relates to 10 kinds of cyclohexyltetrahydroimidazopyridoindole-diketone acetyl amino acids represented by general formula I (AA represents valine residue in the formula, leucine residue, isoleucine residue, glycine residues, glutamic acid residues, tryptophan residues, methionine residues, aspartic acid residues, phenylalanine residues and tyrosine residues), their synthetic methods, and Their in vitro anti-platelet aggregation experiments further relate to their antithrombotic activity in rat jugular arteriovenous bypass cannulation thrombosis models, so the present invention relates to their application in the preparation of antithrombotic agents. The invention belongs to the field of biomedicine. [0002] Background technique [0003] Globally, thrombotic disease is the leading cause of morbidity and mortality. There are two types of thrombus in patients with thrombosis, one is a thrombus formed by the cross-linking of pla...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D471/14A61K31/437A61P7/02
Inventor 彭师奇赵明王玉记吴建辉李伯楠
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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