Bilobalide A derivatives and pharmaceutical application thereof

A kind of technology of ginkgolide and derivatives, applied in the field of medicine

Inactive Publication Date: 2006-09-27
南通集智知识产权服务有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these compounds have certain deficiencies in aspects such as action on the central nervous system, pharmacodynamics, oral availability, water solubility, efficacy for intravenous administration, and shelf life.

Method used

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  • Bilobalide A derivatives and pharmaceutical application thereof
  • Bilobalide A derivatives and pharmaceutical application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0164] Example 1. Preparation and structure confirmation of 10-(2'-dimethylaminoethoxy)-ginkgolide A

[0165] Dissolve 600mg of ginkgolide A in 40mL of acetonitrile, add 300mg of N,N-dimethylchloroethylamine, 2.5g of potassium carbonate, and 300mg of potassium iodide in sequence, pass inert gas, heat and reflux for 2h, concentrate under reduced pressure, dissolve in chloroform, filter, The filtrate was concentrated. The obtained product was separated by column chromatography (eluent: ethyl acetate / petroleum ether=1 / 1) to obtain 670 mg of the expected product (yield 95.2%).

[0166] 1 H-NMR (DMSO-d 6 )δ6.31(s, 1H), 6.05(s, 1H), 5.31(d, 1H), 5.11(s, 1H), 4.55(d, 1H), 4.30(t, 1H), 3.50(t, 1H ), 2.81(q, 1H), 2.60(d, 2H), 2.30(d, 2H), 2.15(s, 6H), 2.13(dd, 1H), 1.86(ddd, 1H), 1.60(dd, 1H) , 1.10(d, 3H), 1.05(s, 9H).

Embodiment 2

[0167] Example 2. Preparation and structure confirmation of 10-(2'-diethylaminoethoxy)-ginkgolide A

[0168] Dissolve 600mg of ginkgolide A in 40mL of acetonitrile, add N,N-diethylchloroethylamine 350mg, potassium carbonate 2.5g, potassium iodide 300mg, pass inert gas, and heat to reflux for 2h. Concentrate under reduced pressure, dissolve in chloroform, filter, and concentrate the filtrate. The obtained product was separated by column chromatography (eluent: ethyl acetate / petroleum ether=1 / 1) to obtain 705 mg of the expected product (yield 94.2%).

[0169] 1 H-NMR (DMSO-d 6 )δ6.20(s, 1H), 6.07(s, 1H), 5.26(d, 1H), 5.14(s, 1H), 4.65(d, 1H), 4.30(t, 1H), 1.95(d, 1H ), 3.52(t, 1H), 2.84(q, 1H), 2.60(d, 2H), 2.5(s, 4H), 2.30(d, 2H), 2.15(s, 6H), 1.88(ddd, 1H) , 1.76 (dd, 1H), 1.21 (d, 3H), 1.10 (s, 9H).

Embodiment 3

[0170] Example 3. Preparation and Structure Confirmation of 10-Benzyloxy-Ginkgolide A

[0171] Dissolve 600mg of ginkgolide A in 40mL of acetonitrile, add 500mg of benzyl bromide, 2.5g of potassium carbonate in sequence, pass inert gas, and heat to reflux for 2h. Concentrate under reduced pressure, dissolve in chloroform, filter, and concentrate the filtrate. The obtained product was separated by column chromatography (eluent: ethyl acetate / petroleum ether=1 / 1) to obtain 705 mg of the expected product (yield 96.1%).

[0172] 1 H-NMR (CDCl 3 )δ7.28~7.11(m, 5H), 6.34(s, 1H), 6.05(s, 1H), 5.18(brs, 1H), 5.25(s, 1H), 5.02(ABq, 2H), 4.60(d , 1H), 4.17(dd, 1H), 2.87(q, 1H), 2.71(d, 1H), 2.24(dd, 1H), 2.03(dd, 1H), 1.86(td, 1H), 1.73(dd, 1H), 1.15(d, 1H), 1.01(s, 9H)

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Abstract

The invention provides a bilobalide A derivative and the use in pharmacy, wherein the bilobalide A derivative has a structural formula disclosed in the specification, R1 represents -X-Ar, -X-Z-Ar, -X-COOH, -CO-Ar, -SO2-Ar, -X-Het, X1-CO-X2-NR4R5 or -X-NR4R5, wherein X, X1, X2 represent C1-C8 alkylidene, Z represents C, O, S or N, Ar represents phenyl, pyridinyl, naphthyl, pyrimidinyl, or quinoline.

Description

technical field [0001] The present invention relates to a compound derivative and its preparation method, and its application in pharmacy, especially relates to ginkgolide A derivative, its preparation method, and its application in pharmacy, and belongs to the field of medical technology. Background technique [0002] In 1972, Benveniste et al discovered a factor that could strongly cause platelet aggregation from rabbit basophils. This factor is named platelet activating factor (hereinafter abbreviated as PAF). Hanahan et al. proved this factor in 1980 as an alkyl ether type phosphoglyceride with an acetyl group at the 2-position, namely 1-O-hexadecyl or octadecyl-2-acetyl-srl - Glycero-3-phosphocholine. [0003] The physiological role of PAF has been extensively examined, and it is known that PAF is an important factor in a variety of physiological responses, including platelet aggregation, blood pressure reduction, immediate immune response, smooth muscle contraction, ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D493/22A61K31/365A61K9/08A61K9/14A61K9/20A61K9/48A61P31/00A61P11/06A61P9/10
Inventor 秦引林
Owner 南通集智知识产权服务有限公司
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