Unlock instant, AI-driven research and patent intelligence for your innovation.

7-bit substituted comptothecine kind compound and pharmaceutical use thereof

A technology of homocamptothecin and compounds, which is applied in the field of medicine and can solve the problems of high water solubility and high toxicity of drugs

Inactive Publication Date: 2006-06-28
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
View PDF3 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the water solubility and high toxicity of drugs are still problems that need to be solved continuously.

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
  • 7-bit substituted comptothecine kind compound and pharmaceutical use thereof
  • 7-bit substituted comptothecine kind compound and pharmaceutical use thereof
  • 7-bit substituted comptothecine kind compound and pharmaceutical use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] The synthesis of embodiment 1 homocamptothecin

[0039] 1.00g of 9-ethyl-9-hydroxy-2,3,8,9-tetrahydro-5H-6-oxa-3a-aza-cycloheptane-1,4,7-trione and 0.80g Anthranilic aldehyde ethylene glycol acetal in 800mL toluene, reflux to separate water, after 30 minutes, add 0.10g p-toluenesulfonic acid, continue to reflux for 1h, filter after cooling, wash with acetone and methanol to obtain 0.98g yellow solid gaocampus Alkali (70.4%).

[0040] 1 HNMR (DMSO), δ: 0.87(t, 3H), 1.86(q, 2H), 3.06(d, 1H), 3.49(d, 1H), 5.28(s, 2H), 5.39(d, 1H), 5.53 (d, 1H), 6.03(s, 1H), 7.42(s, 1H), 7.72(t, 1H), 7.87(t, 1H), 8.15(q, 2H), 8.69(s, 1H).

Embodiment 2

[0041] The synthesis of embodiment 2 7-hydroxymethyl homocamptothecin

[0042] Add 25 mL of 75% sulfuric acid dropwise to 0.98 g of homocamptothecin suspended in 30 mL of methanol and 25 mL of water, and then add 0.80 g of FeSO 4 .7H 2 O. Cool to 0°C with ice water, add dropwise 5mL 30% H 2 o 2 , Continue stirring to room temperature for 14h. After diluting with 200mL of water, a solid precipitated, filtered, washed with hot DMF, the filtrate was evaporated to remove the solvent, and purified on a silica gel chromatography column (eluent: CH 2 Cl 2 / CH 3 OH 100:4), to obtain 0.61 g of yellow solid 7-hydroxymethyl homocamptothecin (64.7%).

[0043] 1 HNMR (DMSO), δ: 0.88(t, 3H), 1.87(q, 2H), 3.06(d, 1H), 3.47(d, 1H), 5.27(d, 2H), 5.41(s, 2H), 5.40 (d, 1H), 5.53(d, 1H), 5.80(t, 1H), 6.03(s, 1H), 7.40(s, 1H), 7.71(t, 1H), 7.86(t, 1H), 8.16( d, 1H), 8.20(d, 1H).

Embodiment 3

[0044] The synthesis of embodiment 3 7-formyl homocamptothecin

[0045] Heat 0.61g 7-hydroxymethyl homocamptothecin in 200mL acetic acid to reflux for 6h, evaporate the solvent, and purify on a silica gel column (eluent: CH 2 Cl 2 / CH 3 OH 100:4), to obtain 0.32 g of yellow solid 7-formyl homocamptothecin (52.7%).

[0046] 1 HNMR (DMSO), δ: 0.87(t, 3H), 1.88(q, 2H), 3.07(d, 1H), 3.49(d, 1H), 5.42(d, 1H), 5.52(s, 2H), 5.55 (d, 1H), 6.06(s, 1H), 7.46(s, 1H), 7.92(t, 1H), 7.98(t, 1H), 8.31(d, 1H), 9.04(d, 1H), 11.10( s, 1H).

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 relates to 7-place substituting high camptothecin class compound and the application that belongs to chemical technology field. It includes racemic mixture and enantiomer. It has the function of restraining topoismerase and has anti-tumor activity, antifungal activity, and antivirus activity.

Description

technical field [0001] The invention relates to the technical field of medicine, and relates to a novel homocamptothecin compound with antitumor activity and its use as a medicine. Background technique [0002] Camptothecin (camptothecin, CPT) is a natural alkaloid extracted from camptotheca, with a fused five-ring rigid structure, as shown below: [0003] [0004] Camptothecin is the most important inhibitor of topoisomerase I and exhibits antitumor activity against a variety of human tumor cell lines. Years of structure-activity studies have yielded a large number of derivatives with development value, among which irinotecan (CPT-11) and topotecan (Topotecan, TPT) have been approved by the FDA for marketing. [0005] The E ring of the six-membered lactone ring of camptothecin is easily hydrolyzed in vivo to form an inactive carboxylate, which significantly reduces its in vivo activity and leads to its obvious toxicity. In order to improve the stability of camptothecin...

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
IPC IPC(8): C07D491/22A61K31/475A61P31/10A61P31/12A61P35/00
Inventor 张万年缪震元姚建忠盛春泉宋云龙张珉张晶朱杰徐辉
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY