Gossypol isatin schiff base compounds with antitumor activities and a method of preparing the same

Patent metadata

Field	Value
Publication number	US-10729675-B2
Application number	US-201916270567-A
Country	US
Kind code	B2
Filing date	Feb 7, 2019
Priority date	Nov 13, 2018
Publication date	Aug 4, 2020
Grant date	Aug 4, 2020

Abstract

A gossypol isatin Schiff base compound with antitumor activities represented by formula I:

R 1 and R 2 are independently hydrogen, alkyl, cycloalkyl, alkoxy, nitro, halogen, unsubstituted or substituted phenyl, or unsubstituted or substituted benzyl. A method of preparing the compound of formula I is also disclosed.

First claim

What is claimed is:

1. A compound of formula I:

wherein R 1 and R 2 are independently hydrogen, alkyl, cycloalkyl, alkoxy, nitro, halogen, unsubstituted or substituted phenyl, or unsubstituted or substituted benzyl.

2. The compound of claim 1 , wherein R 1 is independently hydrogen, alkyl, or benzyl.

3. The compound of claim 1 , wherein R 2 is independently hydrogen, alkyl, or halogen.

4. The compound of claim 1 , wherein the compound is selected from the group consisting of:

5. A method of preparing the compound of claim 1 , comprising:

(1) reacting a compound of formula II and hydrazine hydrate (N 2 H 4 .H 2 O) in an organic solvent to obtain a compound of formula III; and
(2) reacting the compound of formula III with gossypol in the presence of a catalyst in the organic solvent to obtain the compound of formula I,
wherein R 1 and R 2 are independently hydrogen, alkyl, cycloalkyl, alkoxy, nitro, halogen, unsubstituted or substituted phenyl, or unsubstituted or substituted benzyl.

6. The method of claim 5 , wherein the organic solvent is methanol, ethanol, or isopropanol.

7. The method of claim 6 , wherein the organic solvent is ethanol.

8. The method of claim 5 , wherein the compound of formula II and hydrazine hydrate (N 2 H 4 .H 2 O) are heated in the organic solvent to 60-100° C. for 4 to 10 hours.

9. The method of claim 5 , wherein the compound of formula III and gossypol are heated in the organic solvent to 60-100° C. for 8 to 14 hours.

10. The method of claim 5 , further comprising:
recrystallizing the compound of formula I in the organic solvent.

11. The method of claim 5 , wherein a molar ratio of the compound of formula II to hydrazine hydrate (N 2 H 4 .H 2 O) is 1:1 to 1:2.5.

12. The method of claim 9 , wherein the molar ratio of the compound of formula II to hydrazine hydrate (N 2 H 4 H 2 O) is 1:1.5.

13. The method of claim 5 , wherein a molar ratio of the compound of formula III to gossypol is 2:1 to 3:1.

14. The method of claim 13 , wherein the molar ratio of the compound of formula III to gossypol is 2.5:1.

15. The method of claim 5 , wherein the catalyst is piperidine or triethylamine.

Assignees

• Liang Chengyuan
• Ju Xingke
• Ding Shunjun
• Tian Lei
• Liu Yuzhi
• Xie Xiaolin
• Zhang Dezhu
• Yao Wenbo
• Yang Dan
• Univ Shaanxi Science & Tech

Inventors

• Liang Chengyuan
• Ju Xingke
• Ding Shunjun
• Tian Lei
• Liu Yuzhi
• Xie Xiaolin
• Zhang Dezhu
• Yao Wenbo
• Yang Dan

Classifications

• C07D209/40 Primary

  Nitrogen atoms, not forming part of a nitro radical, e.g. isatin semicarbazone · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/404 Primary

  Indoles, e.g. pindolol · CPC title

• G01N33/5011

  for testing antineoplastic activity · CPC title