Stilbene derivative and preparation method thereof

Patent metadata

Field	Value
Publication number	US-10829466-B2
Application number	US-201616067816-A
Country	US
Kind code	B2
Filing date	Oct 26, 2016
Priority date	Dec 31, 2015
Publication date	Nov 10, 2020
Grant date	Nov 10, 2020

Abstract

A stilbene derivative, which is a compound of the following general formula I or general formula II, or an acceptable salt formed by the compound of the general formula I or the general formula II and an inorganic or organic acid;

wherein, in the general formula I or the general formula II, the atom represented by X is a hydrogen atom or a halogen atom;
the substituent represented by R is C1-C6 alkyl, 1-6-membered heteroalkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, substituted C3-C6 cycloalkyl, 3-6-membered heterocycloalkyl, substituted 3-6-membered heterocycloalkyl, 5-18-membered aryl, substituted 5-18-membered aryl, 5-18-membered heteroaryl, or substituted 5-18-membered heteroaryl.

First claim

What is claimed is:

1. A stilbene derivative, wherein the stilbene derivative is a compound of the following formula I or formula II, or an acceptable salt formed by the compound of the formula I or the formula II and an inorganic or organic acid;

wherein, in the formula I or the formula II, wherein X is a hydrogen atom or a halogen atom;
R is C1-C6 alkyl, 1-6-membered heteroalkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, substituted C3-C6 cycloalkyl, 3-6-membered heterocycloalkyl, substituted 3-6-membered heterocycloalkyl, 5-18-membered aryl, substituted 5-18-membered aryl, 5-18-membered heteroaryl, or substituted 5-18-membered heteroaryl;
wherein in the substituted C3-C6 cycloalkyl, the substituted 3-6-membered heterocycloalkyl, the substituted 5-18-membered aryl, and the substituted 5-18-membered heteroaryl, the substitution refers to the C3-C6 cycloalkyl, the 3-6-membered heterocycloalkyl, the 5-18-membered aryl, and the 5-18-membered heteroaryl are substituted with at least one of the following substituents: aryl, heteroaryl, C3-C6 cycloalkyl, 3-6-membered heterocycloalkyl, C1-C6 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, 1-6-membered heteroalkyl, nitro, cyano, hydroxy, halogen, amino.

2. The stilbene derivative according to claim 1 , wherein X is a hydrogen atom or a fluorine atom;
the R is C1-C4 alkyl, 3-5-membered heteroalkyl, C3-C6 cycloalkyl, substituted C3-C6 cycloalkyl, 3-6-membered heterocycloalkyl, and substituted 3-6-membered heterocycloalkyl, 6-10-membered aryl, substituted 6-10-membered aryl, 5-10-membered heteroaryl, or substituted 5-10-membered heteroaryl;
wherein in the substituted C3-C6 cycloalkyl, the substituted 3-6-membered heterocycloalkyl, the substituted 6-10-membered aryl, and the substituted 5-10-membered heteroaryl, the substitution refers to the C3-C6 cycloalkyl, the 3-6-membered heterocycloalkyl, the 6-10-membered aryl, and the 5-10-membered heteroaryl are substituted with at least one of the following substituents: aryl, heteroaryl, C3-C6 cycloalkyl, 3-6-membered heterocycloalkyl, C1-C6 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, 1-6-membered heteroalkyl, nitro, cyano, hydroxy, halogen, amino.

3. The stilbene derivative according to claim 2 , wherein
the C1-C4 alkyl is methyl, ethyl, n-propyl, isopropyl or tert-butyl;
the 3-5-membered heteroalkyl is N,N-dimethylamino, N-methyl-N-ethylamino, N,N-dimethylaminomethyl, N,N-diethylamino, methoxy, ethoxy, isopropoxy or tert-butoxy;
the C3-C6 cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;
the substituted C3-C6 cycloalkyl is methylcyclopropyl, fluorocyclopropyl, cyanocyclopropyl, cyclopropylmethyl or (cyclohexyl)ethyl;
the 3-6-membered heterocycloalkyl is tetrahydrofuranyl, pyrrolidinyl, morpholinyl, piperidinyl, or piperazinyl;
the substituted 3-6-membered heterocycloalkyl is N-methylpiperidinyl, N-ethylpiperidinyl, N-acetylpiperidinyl, or (N-methylpiperidinyl) piperidinyl;
the 6-10 membered aryl is phenyl or naphthyl;
the substituted 6-10-membered aryl is substituted phenyl or substituted naphthyl;
the 5-10-membered heteroaryl is furyl, pyrrolyl, thienyl, pyridyl, quinolinyl or isoquinolinyl;
the substituted 5-10-membered heteroaryl is substituted furyl, substituted pyrrolyl, substituted thienyl, substituted pyridyl, substituted quinolinyl, or substituted isoquinolinyl;
the substituted phenyl is methylphenyl, dimethylphenyl, fluorophenyl, chlorophenyl, bromophenyl, isopropylphenyl, tertiary aminophenyl, methoxyphenyl, dimethoxyphenyl, acetylphenyl, cyanophenyl, (R)-1-phenyl- 1-1-methoxymethyl, (S)-1-phenyl-1-methoxymethyl, benzyl, methoxybenzyl, methylbenzyl, tertiary aminobenzyl, fluorobenzyl, chlorobenzyl, or cyanobenzyl;
the substituted naphthyl is methoxynaphthyl, methylnaphthyl, tertiary aminonaphthyl, fluoronaphthyl, chloronaphthyl, or cyanonaphthyl;
the substituted furyl is methoxyfuryl, methylfuryl, fluorofuryl, chlorofuryl or cyanofuryl;
the substituted thienyl is methoxythienyl, methylthienyl, fluorothienyl, chlorothienyl or cyanothienyl;
the substituted pyridyl is methylpyridyl, methoxypyridyl, fluoropyridyl, chloropyridyl, cyanopyridyl, pyridylmethyl, (pyridyl)ethyl or (pyridylsulfydryl)methyl;
the substituted quinolinyl is methoxyquinolinyl, methylquinolinyl, fluoroquinolinyl, chloroquinolinyl, or cyanoquinolinyl;
the substituted isoquinolinyl is methoxyisoquinolinyl, methylisoquinolinyl, fluoroisoquinolinyl, chloroisoquinolinyl or cyanoisoquinolinyl.

4. The stilbene derivative according to claim 2 , wherein
the substituted C3-C6 cycloalkyl is a substituted C3 cycloalkyl;
the 3-6-membered heterocycloalkyl is 5-6-membered heterocycloalkyl;
the 6-10 membered aryl is 6-membered aryl;
the substituted 6-10-membered aryl is substituted 6-membered aryl;
the 5-10-membered heteroaryl is a 5-6-membered heteroaryl;
the substituted 5-10-membered heteroaryl is substituted 6-membered heteroaryl;
wherein in the substituted C3-C6 cycloalkyl, the substituted 6-10-membered aryl, and the substituted 5-10-membered heteroaryl, the substitution refers to the C3-C6 cycloalkyl, the 6-10-membered aryl, and the 5-10-membered heteroaryl are substituted with at least one of the following substituents: aryl, heteroaryl, C3-C6 cycloalkyl, 3-6-membered heterocycloalkyl, C1-C6 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, 1-6-membered heteroalkyl, nitro, cyano, hydroxy, halogen, amino.

5. The stilbene derivative according to claim 4 , wherein
the C1-C4 alkyl is methyl, ethyl, n-propyl or isopropyl;
the 3-5-membered heteroalkyl is N,N-dimethylamino;
the C3-C6 cycloalkyl is cyclopropyl or cyclobutyl;
the 6-membered aryl is phenyl.

6. The stilbene derivative according to claim 4 , wherein
the C1-C4 alkyl is tert-butyl;
the C3-C6 cycloalkyl is cyclopentyl or cyclohexyl;
the substituted C3 cycloalkyl is cyanocyclopropyl;
the 5-6-membered heterocycloalkyl is pyrrolidinyl;
the 3-5 membered heteroalkyl is N-methyl-N-ethylamino, N,N-dimethylaminomethyl, N,N-diethylamino, methoxy, ethoxy, isopropoxy or tert-butoxy;
the 5-6-membered heteroaryl is thienyl or pyridyl;
the substituted 6-membered aryl is benzyl, methylphenyl, fluorophenyl, chlorophenyl, or cyanophenyl;
the substituted 6-membered heteroaryl is pyridinylmethyl;
the C2-C4 alkenyl is vinyl or propenyl;
the C2-C4 alkynyl is ethynyl or propynyl.

7. The stilbene derivative according to claim 2 , wherein
the substituted C3-C6 cycloalkyl is methylcyclopropyl, fluorocyclopropyl, cyclopropylmethyl or (cyclohexyl)ethyl;
the 3-6-membered heterocycloalkyl is tetrahydrofuranyl, pyrrolidinyl, morpholinyl, piperidinyl, or piperazinyl;
the substituted 3-6-membered heterocycloalkyl is N-methylpiperidinyl, N-ethylpiperidinyl, N-acetylpiperidinyl, or (N-methylpiperidinyl) piperidinyl;
the 6-10-membered aryl is naphthyl;
the substituted 6-10-membered aryl is substituted phenyl or substituted naphthyl;
the 5-10-membered heteroaryl is furyl, pyrrolyl, quinolinyl or isoquinolinyl;
the substituted 5-10-membered heteroaryl is substituted furyl, substituted pyrrolyl, substituted thienyl, substituted pyridyl, substituted quinolinyl, or substituted isoquinolinyl;
the substituted phenyl is dimethylphenyl, bromophenyl, isopropylphenyl, tertiary aminophenyl, methoxyphenyl, dimethoxyphenyl, acetylphenyl, (R)- 1-phenyl-1-methoxymethyl, (S)-1-phenyl-1-methoxymethyl, benzyl, methoxybenzyl, methylbenzyl, tertiary aminobenzyl, fluorobenzyl, chlorobenzyl, or cyanobenzyl;
the substituted naphthyl is methoxynaphthyl, methylnaphthyl, tertiary aminonaphthyl, fluoronaphthyl, chloronaphthyl, or cyanonaphthyl;
the substituted furyl is methoxyfuryl, methylfuryl, fluorofuryl, chlorofuryl or cyanofuryl;
the sub

Assignees

• Beijing Institute Tech

Inventors

• Liang Jianhua
• Qing Hong
• Wu Si
• Liu Sisi
• Li Nuomin
• Yang Liang

Classifications

• C07D317/58

  Radicals substituted by nitrogen atoms (nitro radicals C07D317/52) · CPC title

• C07D405/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D317/50 Primary

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring · CPC title

• C07D407/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D409/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title