C21 steroid sapogenin derivative of dihydro parazole piperazidine, and preparation method and application thereof

A technology of saponin and derivatives, applied in steroids, drug combinations, antitumor drugs, etc., can solve the problems of insufficient research and achieve the effect of mild experimental environment, high selectivity and low toxicity

Inactive Publication Date: 2015-09-02
JIANGSU NAIQUE BIOLOGICAL ENG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Currently for such C 21 The research on steroidal saponins is still not in-depth, mainly based on their physical and chemical properties, separation, purification, analysis and detection research, structural modification research on its mother nucleus, and pharmacological activity research on its structural characteristics

Method used

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  • C21 steroid sapogenin derivative of dihydro parazole piperazidine, and preparation method and application thereof
  • C21 steroid sapogenin derivative of dihydro parazole piperazidine, and preparation method and application thereof
  • C21 steroid sapogenin derivative of dihydro parazole piperazidine, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066] N-methyl-4-(3-((3aR,4aS,8S,10aS,11S,12S,12aS)-(8,11,12-trihydroxyl)-(10a,12a-dimethyl)-(1 ,2-cyclopentyl)-1,10a-b-epoxy tetradecyl)-(4,5-dihydropyrazole)) preparation of benzoylpiperazine (compound 18)

[0067]

[0068] Under stirring at -20°C, add the corresponding intermediate 18 (10.0mmol) and dichloromethane (25mL) obtained in step 7 to a 50mL round bottom flask in turn, and gradually add boron tribromide (5.0mmol) dropwise and continue stirring After reacting for 1 h, the reaction flask was transferred to room temperature, and the reaction was continued for 12 h. TLC tracking reaction (developing agent V AcOEt :V 正己烷 =1:2), after the reaction was completed, filtered, the solid was washed with distilled water, and finally dried in vacuum, the obtained solid was dissolved in absolute ethanol, purified by recrystallization, and the target compound 22 was obtained as crystals.

[0069] White crystals were obtained with a yield of 81.6%. m.p.198~199℃; 1 H NMR (D...

Embodiment 2

[0071] N-methyl-4-(5-methyl-3-((3aR,4aS,8S,10aS,11S,12S,12aS)-(8,11,12-trihydroxy)-(10a,12a-dimethyl Base)-(1,2-cyclopentyl)-1,10a-b-epoxytetradecyl)-(4,5-dihydropyrazole))benzoylpiperazine (compound 23) preparation of

[0072]

[0073] The preparation method refers to Example 1.

[0074] White crystals were obtained with a yield of 77.6%. m.p.203~205℃; 1 H NMR (DMSO-d 6 ,300MHz)δ:8.00(d,J=8.1Hz,2H,ArH),7.69(d,J=7.7Hz,2H,ArH),5.37(s,2H,OH),4.49(s,1H,OH) ,3.58~3.33(m,7H,CH and CH 2 ),2.70~2.66(m,1H,CH),2.38~2.31(m,6H,CH 2 ),2.18(s,3H,CH 3 ), 2.01(t, J=7.3Hz, 1H, CH), 1.79~1.21(m, 18H, CH, CH 2 and CH 3 ),1.14(dd,J 1 =7.1Hz,J 2 =7.8Hz,1H,CH),0.88(s,3H,CH 3 ),0.81(s,3H,CH 3 ).ESI-MS:593.8[M+H] + .Anal.Calcd for C 35 h 50 N 4 o 5 .

Embodiment 3

[0076] N-methyl-4-(5-ethyl-3-((3aR,4aS,8S,10aS,11S,12S,12aS)-(8,11,12-trihydroxy)-(10a,12a-dimethyl Base)-(1,2-cyclopentyl)-1,10a-b-epoxytetradecyl)-(4,5-dihydropyrazole))benzoylpiperazine (compound 24) preparation.

[0077]

[0078] The preparation method refers to Example 1.

[0079]White crystals were obtained with a yield of 83.9%. m.p.211~212℃; 1 H NMR (DMSO-d 6 ,300MHz)δ:7.97(d,J=8.1Hz,2H,ArH),7.68(d,J=7.7Hz,2H,ArH),5.37(s,2H,OH),4.49(s,1H,OH) ,3.56~3.34(m,7H,CH and CH 2 ),2.71~2.68(m,1H,CH),2.38~2.31(m,6H,CH 2 ),2.18(s,3H,CH 3 ), 2.01(t, J=7.3Hz, 1H, CH), 1.79~1.21(m, 17H, CH and CH 2 ),1.14(dd,J 1 =7.1Hz,J 2 =7.8Hz,1H,CH),0.89(s,3H,CH 3 ),0.87(s,3H,CH 3 ),0.83(s,3H,CH 3 ).ESI-MS:621.8[M+H] + .Anal.Calcd for C 36 h 52 N 4 o 5 .

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Abstract

The invention discloses a C21 steroid sapogenin derivative, and a preparation method and application thereof in preparation of an anti-tumour drug; and the structure of the C21 steroid sapogenin derivative is represented by the following formula shown in the description, wherein R1 is H, CH3 or CH2CH3. The C21 steroid sapogenin derivative disclosed by the invention has the advantages of being better in biological activity, higher in selectivity and lower in toxicity and has the obvious effect of inhibiting human breast cancer cells, cervical cancer cells, lung cancer cells and liver cancer cells.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, in particular to a dihydropyrazole piperazine C 21 Steroidal saponin aglycon derivatives, and preparation methods and applications thereof. Background technique [0002] Steroidal saponins can be obtained through extraction, separation and purification from the traditional Chinese medicine Tongguanteng. The aglycone is a unique steroidal saponin structure composed of 21 C atoms, so it is called C 21 steroidal saponins. Existing studies have shown that with C 21 Steroidal saponin core compounds have pharmacological activities such as immunoregulation and anti-asthma, and have been widely used clinically as the index active ingredients of drugs. [0003] The inventor finds through research: have C 21 The compound of steroidal saponin core has good antitumor activity, and has good inhibitory effect on various tumors, such as liver cancer, lung cancer, esophageal cancer, etc., has good inhibito...

Claims

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Application Information

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IPC IPC(8): C07J71/00A61P35/00
CPCC07J71/001
Inventor 杨永安魏元刚金显友钟慧朱海亮
Owner JIANGSU NAIQUE BIOLOGICAL ENG
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