Polysubstituted benzene, preparation method thereof, and method of using the same

Patent metadata

Field	Value
Publication number	US-11376228-B2
Application number	US-202016986303-A
Country	US
Kind code	B2
Filing date	Aug 6, 2020
Priority date	Feb 12, 2018
Publication date	Jul 5, 2022
Grant date	Jul 5, 2022

Abstract

A polysubstituted benzene compound, preparation method thereof, and method of using the same. The compound has a formula I or I′, where X represents carbon, sulfur, or oxygen; R1 represents a C1-16 alkyl, C2-16 alkenyl, or C2-10 alkynyl; R2 represents hydrogen, halogen, C1-16 alkyl, C2-16 alkenyl, or C2-10 alkynyl; or an aryl group or a substituted aryl group by 1-5 groups selected from halogen, C1-26 alkyl, C1-3 halogenated alkyl, O—C1-3 alkyl, hydroxyl, amino, nitro, cyano group, aldehyde group and ester group; or a heteroaryl group or a substituted heteroaryl group by 1-5 groups selected from halogen, C1-26 alkyl, C1-3 halogenated alkyl, O—C1-3 alkyl, hydroxyl, amino, nitro, cyano group, aldehyde group and ester group; the heteroaryl group is a 3-10-membered heteroaryl group including N, S, O, or a combination thereof.

First claim

What is claimed is:

1. A compound, having a formula I or I′:

wherein:
X represents carbon, sulfur, or oxygen;
R 1 represents a C 1-16 alkyl, C 2-16 alkenyl, or C 2-10 alkynyl;
R 2 represents hydrogen, halogen, C 1-16 alkyl, C 2-16 alkenyl, or C 2-10 alkynyl; or an aryl group or a substituted aryl group by 1-5 groups selected from halogen, C 1-26 alkyl, C 1-3 halogenated alkyl, O—C 1-3 alkyl, hydroxyl, amino, nitro, cyano group, aldehyde group and ester group; or a heteroaryl group or a substituted heteroaryl group by 1-5 groups selected from halogen, C 1-26 alkyl, C 1-3 halogenated alkyl, O—C 1-3 alkyl, hydroxyl, amino, nitro, cyano group, aldehyde group and ester group;
the heteroaryl group is a 3-10-membered heteroaryl group comprising N, S, O, or a combination thereof;
R 3 represents C 1-6 aldehyde group, C 2-6 acyl group, —COOH, hydroxyl-substituted C 1-6 alkyl, —CH 2 O—C 1-6 alkyl or —CO 2 —C 1-6 alkyl;
R 4 and R 7 , at each occurrence, represent hydrogen, a C 1-20 alkyl, C 2-36 alkenyl, or C 2-10 alkynyl; or an aryl group or a substituted aryl group by 1-5 groups selected from halogen, C 1-3 halogenated alkyl, O—C 1-3 alkyl, C 1-25 alkyl, hydroxyl, amino, nitro, cyano group, aldehyde group and ester group;
R 5 and R 6 , at each occurrence, represent hydrogen, C 1-6 alkyl or C 1-6 silicon;
wherein the dotted line in formula I optionally comprises a carbon chain connecting R 4 to X; and
wherein the dotted line in formula I′ optionally comprises a carbon chain connecting R 4 to X.

2. The compound of claim 1 , wherein:
X represents carbon, sulfur, or oxygen;
R 1 represents a C 1-4 alkyl, C 2-4 alkenyl, or C 3-7 alkynyl;
R 2 represents hydrogen, halogen, C 1-4 alkyl, C 2-4 alkenyl, or C 3-7 alkynyl; or an aryl group or a substituted aryl group by 1-5 groups selected from halogen, C 1-26 alkyl, C 1-3 halogenated alkyl, O—C 1-3 alkyl, hydroxyl, amino, nitro, cyano group, aldehyde group and ester group; or a heteroaryl group or a substituted heteroaryl group by 1-5 groups selected from halogen, C 1-6 alkyl, C 1-3 halogenated alkyl, O—C 1-3 alkyl, hydroxyl, amino, nitro, cyano group, aldehyde group and ester group;
R 3 represents C 1-6 aldehyde group, C 2-6 acyl group, —COOH, hydroxyl-substituted C 1-4 alkyl, —CH 2 O—C 1-4 alkyl or —CO 2 —C 1-6 alkyl;
R 4 and R 7 , at each occurrence, represent hydrogen, C 1-20 alkyl, C 2-36 alkenyl, or C 2-10 alkynyl; or an aryl group or a substituted aryl group by 1-5 groups selected from halogen, C 1-3 halogenated alkyl, O—C 1-3 alkyl, C 1-25 alkyl, hydroxyl, amino, nitro, cyano group, aldehyde group and ester group; and
R 5 and R 6 , at each occurrence, represent hydrogen or C 1-4 alkyl.

3. The compound of claim 1 , wherein:
X represents carbon, sulfur, or oxygen;
R 1 represents a C 1-3 alkyl, allyl, or C 3-4 alkynyl;
R 2 represents hydrogen, halogen, C 1-4 alkyl, allyl, or C 3-7 alkynyl; or an aryl group or a substituted aryl group by 1-5 groups selected from halogen, methyl, methoxyl, C 2-26 alkyl, hydroxyl, nitro, cyano group, aldehyde group and ester group; or a heteroaryl group or a substituted heteroaryl group by 1-5 groups selected from halogen, C 1-6 alkyl, C 1-3 halogenated alkyl, O—C 1-3 alkyl, hydroxyl, nitro, cyano group, aldehyde group and ester group;
the heteroaryl group is a 5-6-membered heteroaryl group comprising N, S, O, or a combination thereof;
R 3 represents C 1-3 aldehyde group, C 2-4 acyl group, —COOH, hydroxyl-substituted C 1-4 alkyl, —CH 2 O—C 1-4 alkyl or —CO 2 —C 1-4 alkyl;
R 4 and R 7 , at each occurrence, represent hydrogen, a C 1-17 alkyl, C 2-36 alkenyl, or C 2-10 alkynyl; or an aryl group or a substituted aryl group by 1-5 groups selected from halogen, methoxyl, C 1-25 alkyl, hydroxyl, nitro, cyano group, aldehyde group and ester group; and
R 5 and R 6 , at each occurrence, represent hydrogen or methyl.

4. The compound of claim 1 , wherein:
X represents carbon, sulfur, or oxygen;
R 1 represents a C 1-3 alkyl, allyl, or C 3-4 alkynyl;
R 2 represents hydrogen, halogen, C 1-4 alkyl, allyl, or C 3-7 alkynyl; or an aryl group or a substituted aryl group by 1-5 groups selected from halogen, methyl, methoxyl, C 2-26 alkyl, hydroxyl, nitro, cyano group, aldehyde group and ester group;
R 3 represents C 1-3 aldehyde group, acetyl group, —COOH, hydroxyl-substituted C 1-4 alkyl, —CH 2 O—C 1-4 alkyl or —CO 2 —C 1-4 alkyl;
R 4 and R 7 , at each occurrence, represent hydrogen, C 1-17 alkyl, C 2-36 alkenyl, or C 2-10 alkynyl; or an aryl group or a substituted aryl group by 1-5 groups selected from halogen, methoxyl, C 1-25 alkyl, hydroxyl, nitro, cyano group, aldehyde group and ester group; and
R 5 and R 6 , at each occurrence, represent hydrogen or methyl.

5. The compound of claim 1 , wherein
X represents carbon, sulfur, or oxygen;
R 1 represents a C 1-3 alkyl, allyl, or C 3-4 alkynyl;
R 2 represents hydrogen, halogen, C 1-4 alkyl, allyl, or C 3-7 alkynyl; or an aryl group or a substituted aryl group by 1-5 groups selected from halogen, methyl, methoxyl, C 2-26 alkyl, hydroxyl, nitro, cyano group, aldehyde group and ester group; or a heteroaryl group or a substituted heteroaryl group by 1-5 groups selected from halogen, C 1-6 alkyl, C 1-3 halogenated alkyl, O—C 1-3 alkyl, hydroxyl, nitro, cyano group, aldehyde group and ester group;
the heteroaryl group is a 5-6-membered heteroaryl group comprising N, S, O, or a combination thereof;
R 3 represents formyl, acetyl, —COOH, hydroxyl-substituted C 1-2 alkyl, —CH 2 O—C 1-2 alkyl or —CO 2 —C 1-4 alkyl;
R 4 and R 7 , at each occurrence, represent hydrogen, C 1-17 alkyl, C 2-36 alkenyl, or C 2-10 alkynyl; or an aryl group or a substituted aryl group by 1-5 groups selected from halogen, methoxyl, C 1-25 alkyl, hydroxyl, nitro, cyano group, aldehyde group and an ester group; and
R 5 and R 6 , at each occurrence, represent hydrogen or methyl.

6. The compound of claim 1 , wherein the compound has one of the following formulas:

7. A pharmaceutical composition, comprising the compound of claim 1 and a pharmaceutically acceptable excipient.

Assignees

• Genifarm Laboratories Inc
• Univ South China Tech

Inventors

• Zhu Shifa
• Cao Tongxiang
• Wang Yongdong
• Huang Zhipeng

Classifications

• A61K31/09 Primary

  having two or more such linkages · CPC title

• C07D309/26 Primary

  Carboxaldehyde radicals · CPC title

• C07D307/42

  Singly bound oxygen atoms · CPC title

• C07D307/46

  Doubly bound oxygen atoms, or two oxygen atoms singly bound to the same carbon atom · CPC title

• C07C45/60

  in six-membered rings · CPC title