20-hydroxy-pregnen-3-aryl ester base pregnene compound, synthetic method thereof and application thereof in preparation of anti-tumor drugs

A synthesis method and compound technology, which can be used in antitumor drugs, steroids, drug combinations, etc., and can solve problems such as applications that have not been reported.

A synthesis method and compound technology, which can be used in antitumor drugs, steroids, drug combinations, etc., and can solve problems such as applications that have not been reported.

CN107236014AInactive Publication Date: 2017-10-10GUANGXI TEACHERS EDUCATION UNIV
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  • 20-hydroxy-pregnen-3-aryl ester base pregnene compound, synthetic method thereof and application thereof in preparation of anti-tumor drugs
  • 20-hydroxy-pregnen-3-aryl ester base pregnene compound, synthetic method thereof and application thereof in preparation of anti-tumor drugs
  • 20-hydroxy-pregnen-3-aryl ester base pregnene compound, synthetic method thereof and application thereof in preparation of anti-tumor drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Preparation of 20-hydroxyl-pregnene-3-p-fluorobenzoate (4)

[0028] Step 1: the preparation of pregnene-3-p-fluorobenzoate (1)

[0029] Weigh 0.360g (about 1 mmol) of pregnenolone, put it in a 100mL eggplant-shaped flask, pipette 10mL of pyridine into the flask, stir the pregnenolone until it is completely dissolved, and then add 400uL of p-fluorobenzoyl chloride. React in an oil bath at 40°C, track the reaction with TLC, stop the reaction when no raw material is reached, and react for 24 hours. When processing the reaction product, first add 15mL of ice water, extract the aqueous phase with ethyl acetate (15mL×3), combine the organic phases, wash with 1mol / L dilute hydrochloric acid, and then extract with saturated NaCl solution (15mL×3). Wash the organic phase, followed by anhydrous Na 2 SO 4 dry. Finally, the organic solvent is distilled off under reduced pressure, and column chromatography separates (eluent: V 乙酸乙酯 :V 石油醚 =1:5), 0.614g of white solid was obta...

Embodiment 2

[0032] Preparation of 20-hydroxyl-pregnene-3-m-methylbenzoate (5)

[0033] Step 1: the preparation of pregnene-3-m-methylbenzoate (2)

[0034] Weigh 0.339g (about 1 mmol) of pregnenolone, place it in a 100mL eggplant-shaped flask, pipette 10mL of pyridine into the flask, stir the pregnenolone until it is completely dissolved, and then transfer 400uL m-toluoyl chloride. React in an oil bath at 40°C, track the reaction with TLC, stop the reaction when no raw material is reached, and react for 24 hours. When processing the reaction product, first add 15mL of ice water, extract the aqueous phase with ethyl acetate (15mL×3), combine the organic phases, wash with 1mol / L dilute hydrochloric acid, and then extract with saturated NaCl solution (15mL×3). Wash the organic phase, followed by anhydrous Na 2 SO 4 dry. Finally, the organic solvent is distilled off under reduced pressure, and column chromatography separates (eluent: V 乙酸乙酯 :V 石油醚 =1:5), 0.519g of white solid was obtain...

Embodiment 3

[0037] 20-hydroxyl-pregnene-3-p-methylbenzoate (6)

[0038] Step 1: the preparation of pregnene-3-p-methylbenzoate (3)

[0039] Weigh 1.558g (about 5mmol) of pregnenolone, put it in a 100mL eggplant-shaped flask, pipette 15mL of pyridine into the flask, stir the pregnenolone until it is completely dissolved, and then add 400uL of p-toluoyl chloride. React in an oil bath at 40°C, track the reaction with TLC, stop the reaction when no raw material is reached, and react for 24 hours. When processing the reaction product, first add 15mL of ice water, extract the aqueous phase with ethyl acetate (15mL×3), combine the organic phases, wash with 1mol / L dilute hydrochloric acid, and then extract with saturated NaCl solution (15mL×3). Wash the organic phase, followed by anhydrous Na 2 SO 4 dry. Finally, the organic solvent is distilled off under reduced pressure, and column chromatography separates (eluent: V 乙酸乙酯 :V 石油醚 =1:5), 1.962g of white solid was obtained, the yield was: 9...

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Abstract

The invention discloses a 20-hydroxy-pregnen-3-aryl ester base pregnene compound. A steroid nucleus structural formula of the compound is as follows: formula (shown in the description), wherein an R- group can be the formula as follows. The invention further discloses a synthetic method of the 20-hydroxy-pregnen-3-aryl ester base pregnene compound. The synthetic method comprises the following steps: with a steroidal compound pregnenolone as a raw material, firstly esterifying 3-site hydroxide radical of pregnenolone by virtue of aroyl chloride, reacting so as to obtain an intermediate, and reducing 17-site carbonyl of the intermediate, so as to obtain the 20-hydroxy-pregnen-3-aryl ester base pregnene compound. The 20-hydroxy-pregnen-3-aryl ester base pregnene compound has an inhibiting effect to the growth and proliferation of certain cancer cells and can be used as a drug intermediate or a drug to be applied to the preparation of different anti-tumor drugs.

Description

technical field [0001] The invention relates to the technical field of compound synthesis, more specifically, the invention relates to a 20-hydroxyl-pregnene-3-aryl ester group pregnant compound, a synthesis method thereof and an application in the preparation of antitumor drugs. Background technique [0002] Pregnenolone itself has weak anti-inflammatory activity. It has been reported in the literature that the C3-hydroxyl esterification of pregnenolone, salicylate and formate have anti-inflammatory effects equivalent to those of clinically used cortisone, while Trichloroacetate, chloroacetate, furan-2'-ester, p-toluenesulfonate, and phthalate have slightly stronger anti-inflammatory effects than anti-inflammatory pine (Li Zhensu, Wang Haiqing, etc. 5- Synthesis of Pregnene-3β,17α-Diol-20-keto-3-Acetate-17α-Fatty Acid Esters and Their Structure-Activity Relationship[J].Acta Pharmaceutica Sinica,1983,18(2):119-124 .). [0003] The research group has carried out related res...

Claims

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Application Information

Patent Timeline
10 Oct 2017
Publication
CN107236014A
IPC
C07J7/00; A61K31/57; A61P35/00
CPC
C07J7/002
Inventors
黄燕敏; 温海燕