Shikonin, alkannin; and racemic parent nucleus cabonyl oxime derivatives and applications thereof

Patent metadata

Field	Value
Publication number	US-9630912-B2
Application number	US-201314759024-A
Country	US
Kind code	B2
Filing date	Jun 25, 2013
Priority date	Jan 16, 2013
Publication date	Apr 25, 2017
Grant date	Apr 25, 2017

Abstract

A structural formula of a shikonin naphthazarin parent nucleus hydroxyl methylation carbonyl oxime derivative is shown in Formula (I) or (II); a structural formula of an alkannin naphthazarin parent nucleus hydroxyl methylation carbonyl oxime derivative is shown in Formula (III) or (IV); and a structural formula of a racemic shikonin naphthazarin parent nucleus hydroxyl methylation carbonyl oxime derivative is shown in Formula (V) or (VI), wherein R1 is alkane, olefin, arene, or substituting arene comprising 1 to 6 carbon atoms; and R2 is alkane, olefin, arene, or substituting arene comprising 1 to 6 carbon atoms or is H. The shikonin, alkannin, and racemic oxime derivatives of the present invention have novel structures, and in-vitro experiments show that the present invention has good growth inhibitory activity against tumor cells and can be used in tumor treatment.

First claim

What is claimed is:

1. A series of shikonin naphthazarin parent nucleus hydroxyl methylation carbonyl oxime derivatives, as shown in Formula (I) or (II):

wherein R 1 is alkane, olefin, arene, or substituting arene comprising 1 to 6 carbon atoms; and R 2 is alkane, olefin, arene, or substituting arene comprising 1 to 6 carbon atoms or is H.

2. The shikonin naphthazarin parent nucleus hydroxyl methylation carbonyl oxime derivatives, as described in claim 1 , wherein R 1 is methyl, isopropyl, isobutyl, 2-hydroxyl-2-methylpropyl, phenyl, 2-fluorophenyl, 4-fluorophenyl, 1-methylethylene, 2-clorophenyl, 4-clorophenyl, 4-methoxyphenyl, ethylene, 2-thiophenyl, 4-nitrophenyl or 2-pyridyl; R 2 is hydrogen, methyl, ethyl or isopentyl.

3. A series of alkannin naphthazarin parent nucleus hydroxyl methylation carbonyl oxime derivatives, as shown in Formula (III) or (IV):

wherein R1 is alkane, olefin, arene, or substituting arene comprising 1 to 6 carbon atoms; and R2 is alkane, olefin, arene, or substituting arene comprising 1 to 6 carbon atoms or is H.

4. The alkannin naphthazarin parent nucleus hydroxyl methylation carbonyl oxime derivatives, as described in claim 3 , wherein R 1 is methyl, isopropyl, isobutyl, 2-hydroxyl-2-methylpropyl, phenyl, 2-fluorophenyl, 4-fluorophenyl, 1-methylethylene, 2-clorophenyl, 4-clorophenyl, 4-methoxyphenyl, ethylene, 2-thiophenyl, 4-nitrophenyl or 2-pyridyl; R 2 is hydrogen, methyl, ethyl or isopentyl.

5. A series of racemic naphthazarin parent nucleus hydroxyl methylation carbonyl oxime derivatives, as shown in Formula (V) or (VI):

wherein R1 is alkane, olefin, arene, or substituting arene comprising 1 to 6 carbon atoms; and R2 is alkane, olefin, arene, or substituting arene comprising 1 to 6 carbon atoms or is H.

6. The racemic naphthazarin parent nucleus hydroxyl methylation carbonyl oxime derivatives, as described in claim 5 , wherein R 1 is methyl, isopropyl, isobutyl, 2-hydroxyl-2-methylpropyl, phenyl, 2-fluorophenyl, 4-fluorophenyl, 1-methylethylene, 2-clorophenyl, 4-clorophenyl, 4-methoxyphenyl, ethylene, 2-thiophenyl, 4-nitrophenyl or 2-pyridyl; R 2 is hydrogen, methyl, ethyl or isopentyl.

7. A method for preparing antitumor drugs, comprising applying the shikonin naphthazarin parent nucleus hydroxyl methylation carbonyl oxime derivatives as described in claim 1 .

8. A method for preparing antitumor drugs, comprising applying the alkannin naphthazarin parent nucleus hydroxyl methylation carbonyl oxime derivatives as described in claim 3 .

9. A method for preparing antitumor drugs, comprising applying the racemic naphthazarin parent nucleus hydroxyl methylation carbonyl oxime derivatives as described in claim 5 .

Assignees

• Univ Shanghai Jiaotong

Inventors

• Li Shaoshun
• Wang Rubing
• Zheng Xiaogang
• Zhang Xu

Classifications

• A61K31/222

  with compounds having aromatic groups, e.g. dipivefrine, ibopamine · CPC title

• A61K31/15 Primary

  Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) {; Imines (C—N=C)} · CPC title

• C07D213/79

  Acids; Esters · CPC title

• C07D333/40

  Thiophene-2-carboxylic acid · CPC title

• A61P35/02

  specific for leukemia · CPC title