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Camptothecin E ring analogues and applications thereof as drugs

A technology of camptothecin and analogs, applied in the field of camptothecin E-ring analogs and their use as medicines

Inactive Publication Date: 2012-07-25
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The new structure compound we studied has not been reported at home and abroad, and it is a new structure compound invented

Method used

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  • Camptothecin E ring analogues and applications thereof as drugs
  • Camptothecin E ring analogues and applications thereof as drugs
  • Camptothecin E ring analogues and applications thereof as drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1、21

[0074] Embodiment 1, 21-hydroxycamptothecin

[0075] Suspend 1.00g of camptothecin in 50mL of methanol, stir at room temperature for 5 minutes, add 0.30g of potassium borohydride, and continue to react for 1h at room temperature. Make it dissolve, and then adjust the pH to be acidic with acetic acid in an ice-water bath. At this time, a large amount of solid precipitates, which is filtered, washed with water, and vacuum-dried to obtain 0.99 g of light yellow solid 21-hydroxycamptothecin (98.4%).

[0076] 1 H-NMR (DMSO):

[0077] 0.91(t, 3H), 1.72(q, 2H), 4.49-4.63(q, 2H), 4.94(s, 1H), 5.00(d, 1H), 5.25(s, 2H), 6.73(d, 1H) , 7.38(s, 1H), 7.69(t, 1H), 7.85(t, 1H), 8.11(d, 1H), 8.16(d, 1H), 8.66(s, 1H).

Embodiment 2、10

[0078] The synthesis of embodiment 2,10-methoxy-21-hydroxycamptothecin

[0079] Suspend 1.00 g of 10-methoxycamptothecin in 50 mL of methanol, stir at room temperature for 5 minutes, add 0.30 g of potassium borohydride, and continue to react for 1 h at room temperature. At this time, the reaction solution is clear, and the solvent is evaporated to obtain light green Solid, add 50mL of water to dissolve it, then adjust the pH to acidic with acetic acid in an ice-water bath, at this time a large amount of solid precipitates, filter and wash with water, and dry in vacuo to obtain 0.96g of light yellow solid 10-methoxy-21-hydroxycamptotheca Alkali (95.4%).

[0080] 1 H-NMR (DMSO):

[0081] 0.90(t, 3H), 1.70(q, 2H), 3.93(s, 3H), 4.46-4.64(q, 2H), 4.91(s, 1H), 4.97(d, 1H), 5.21(s, 2H) , 6.74(d, 1H), 7.30(s, 1H), 7.47(d, 1H), 7.50(s, 1H), 8.05(d, 1H), 8.51(s, 1H).

Embodiment 3

[0082] The synthesis of embodiment 3,9-nitro-21-hydroxycamptothecin

[0083] Suspend 1.00 g of 9-nitrocamptothecin in 50 mL of methanol, stir at room temperature for 5 minutes, add 0.30 g of potassium borohydride, and continue to react for 1 h at room temperature. At this time, the reaction solution is clear, and the solvent is evaporated to obtain a light green solid , add 50mL of water to make it dissolve, then adjust PH to be acidic with acetic acid under ice-water bath, at this moment, separate out a large amount of solids, wash with suction filtration, dry in vacuo to obtain 0.95g light yellow solid 21-hydroxycamptothecin (94.5%).

[0084] 1 HNMR (DMSO):

[0085] 0.91(t, 3H), 1.72(q, 2H), 4.70-4.81(q, 2H), 4.94(s, 1H), 5.14(d, 1H), 5.27(s, 2H), 6.77(d, 1H) , 7.44(s, 1H), 8.03(t, 1H), 8.52(t, 1H), 8.57(d, 1H), 9.15(s, 1H).

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Abstract

The present invention relates to the technical field of medicine, particularly relates to camptothecin E ring analogues and applications of the camptothecin E ring analogues as drugs. The structures of the compounds provided by the invention are shown as general formula I, including forms of racemates, diastereoisomers and optional mixtures or pharmaceutically-acceptable salts of these forms. The compounds provided by the invention have function of inhibiting activity of topoisomerase I, and can be used for preparing antitumor drugs and antiviral or antifungal infection drugs.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a camptothecin E-ring analog and its use as medicine. Background technique [0002] Camptothecin (Camptothecin) is an alkaloid extracted from the Chinese Davidiaceae plant Camptotheca acuminata by American chemist Wall et al. Camptothecin is a five-ring rigid structure composed of indolizine[1,2-b]quinoline fragments fused with six-membered-hydroxylactone. The 20th carbon with-hydroxyl is asymmetrical, which endows the molecule with Optical properties. Its structure is as follows: [0003] [0004] Camptothecin is the earliest discovered, most studied, and most widely used specific topoisomerase I inhibitor (Topo I), and is also the most classic Topo I specific inhibitor. exhibited good antitumor activity. After years of research on the structure-activity relationship, a large number of camptothecin derivatives with application value have been developed, among which Irino...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D491/22A61K31/4745A61P35/00A61P35/02
Inventor 张万年祝令建缪震元盛春泉姚建忠庄春林张永强郭子照
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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