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Fatty acylaminoacylcytarabine conjugate, preparation method and application thereof

A technology of fatty amidoacyl cytarabine and fatty amido arabinocytidine, which is applied in sugar derivatives, drug combinations, pharmaceutical formulations, etc., and can solve problems such as low bioavailability, weak transmembrane ability, and short half-life. problem to achieve good antitumor activity

Inactive Publication Date: 2008-08-13
CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The first technical problem to be solved by the present invention is to overcome the short half-life of the antineoplastic drug cytarabine due to its short half-life, weak transmembrane ability and low bioavailability due to the easy metabolic inactivation of the 4-amino group of cytarabine, and to provide a A fatty amidoacyl cytarabine conjugate, which has the advantages of strong transmembrane ability, high bioavailability, long half-life, and amphiphilicity

Method used

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  • Fatty acylaminoacylcytarabine conjugate, preparation method and application thereof
  • Fatty acylaminoacylcytarabine conjugate, preparation method and application thereof
  • Fatty acylaminoacylcytarabine conjugate, preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0024] Embodiment 1 prepares caproyl valine methyl ester (3a)

[0025] Dissolve 0.69g (4mmol) capric acid, 0.91g (4.4mmol) DCC and 0.54g (4mmol) HOBt in cold anhydrous THF, stir in ice bath for 20min, then add 0.67g (4mmol) HCl·H-Val-OMe Adjust the pH value to 8-9 with 0.5ml NMM, stir at room temperature for 1 day, TLC (chloroform / methanol, 20:1) showed that HCl·H-Val-OMe disappeared. Dicyclohexyl urea (DCU) was filtered off, the filtrate was concentrated to dryness under reduced pressure, and the residue was dissolved in 20 ml of ethyl acetate. The resulting solution was sequentially washed with 5% NaHCO 3 Washing with aqueous solution, washing with saturated NaCl aqueous solution, 5% KHSO 4 Wash with aqueous solution and saturated NaCl aqueous solution until neutral. Ethyl acetate layer with anhydrous Na 2 SO 4 Dry, filter, and concentrate the filtrate under reduced pressure to afford 1.01 g (89%) of the title compound as a colorless solid. Mp.60-62℃; [α] D 25 20 =-...

Embodiment 2

[0026] Embodiment 2 prepares caproyl methionine methyl ester (3b)

[0027] According to the operation of Example 1, 1.17g was prepared from 0.69g (4mmol) capric acid, 0.91g (4.4mmol) DCC, 0.54g (4mmol) HOBt, 0.8g (4mmol) HCl H-Met-OMe and 0.5mlNMM (92%) The title compound as a colorless solid. Mp.50-52℃; [α] D 25 20 =-19.5 (c=1.0, methanol); ESI-MS (m / e) 318.0 [M+H] + , 635.1[2M+H] + , 657.1[2M+Na] + .

Embodiment 3

[0028] Embodiment 3 prepares caproyl tyrosine methyl ester (3c)

[0029] According to the operation of Example 1, 1.09g was prepared from 0.69g (4mmol) capric acid, 0.91g (4.4mmol) DCC, 0.54g (4mmol) HOBt, 0.93g (4mmol) HCl H-Tyr-OMe and 0.5mlNMM (80%) The title compound as a colorless solid. Mp.27-29℃; [α] D 25 20 =-17.7 (c=1.0, methanol); ESI-MS (m / e) 350.0 [M+H] + , 699.2[2M+H] + .

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Abstract

The invention discloses a conjugate of fatty aminoacyl alexan, preparation and application in anti-tumor thereof. The invention also discloses a pharmacosome of the conjugate of fatty aminoacyl alexan, preparation thereof, and its applicant in anti-tumor and preparation of target medicine material of microemulsion, lipid medicine carrier. In comparison with alexan, the inventive conjugate of fatty aminoacyl alexan has a strong transmembrane ability, high bioavailability, long halflife, and amphipathic nature. It is demonstrated that the inventive compound and pharmacosome have great anti-tumor activity.

Description

technical field [0001] The present invention relates to derivatives of cytarabine, in particular to fatty amidoacyl cytarabine conjugates; the present invention also relates to a preparation method of fatty amidoacyl cytarabine conjugates, and preparation of the conjugates into medicines The plastid method and the application of fatty amidoacyl cytarabine conjugates in anti-tumor and targeted preparation materials for preparation of microemulsions and liposome drug carriers belong to the field of biomedicine. Background technique [0002] Many drugs need to cross the biomembrane multiple times in the body to reach the target site (organ, tissue, cell and organelle). Among the many factors affecting drug transmembrane, hydrophilic-lipophilic balance or oil-water partition coefficient are obvious physical and chemical factors. Strongly water-soluble drugs are compatible with body fluids and cannot easily pass through biological membranes composed of lipid bilayers. Although ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H19/067A61K31/7068A61K47/16A61K47/48A61K9/127A61K9/107A61P35/00A61K47/54
Inventor 崔国辉彭师奇赵明刘伯阳
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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