Benzoheterocyclic alkylamine compounds and use thereof

Patent metadata

Field	Value
Publication number	US-10829464-B2
Application number	US-201716461234-A
Country	US
Kind code	B2
Filing date	Nov 17, 2017
Priority date	Nov 23, 2016
Publication date	Nov 10, 2020
Grant date	Nov 10, 2020

Abstract

Disclosed are benzoheterocyclic alkylamine compounds, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, and a preparation method thereof, and use of the same in the manufacture of an antibacterial drug as an inhibitor of staphyloxanthin synthesis in Staphylococcus aureus .

First claim

The invention claimed is:

1. A compound of Formula I, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof:

in the Formula I:
X is S or O;
R 1 is H, or a substituted or unsubstituted C 1 -C 4 linear or branched alkyl;
R 2 is a substituted or unsubstituted C 1 -C 3 linear alkyl, a substituted or unsubstituted C 3 -C 8 cycloalkyl, a substituted or unsubstituted C 2 -C 6 linear or branched alkenyl, -(CH═CH)-p, or a substituted or unsubstituted C 2 -C 6 linear or branched alkynyl, wherein p is a positive integer from 2 to 5;
R 3 is a substituted or unsubstituted C 1 -C 3 linear or branched alkyl, a substituted or unsubstituted C 3 -C 8 cycloalkyl, a substituted or unsubstituted C 3 -C 7 heteroaromatic ring group, or a substituted or unsubstituted C 6 -C 10 aromatic ring group;
n is an integer from 1 to 3:
wherein, the group

is located at position 2 or 3;
wherein, in R 1 , R 2 , and R 3 , the substitution means having 1, 2, 3 or 4 substituents selected from the group consisting of a C 1 -C 6 linear or branched alkyl, a C 1 -C 6 haloalkyl, halogen, nitro, cyano, a C 1 -C 4 linear or branched alkoxy, a -(C═O)-O-C 1 -C 4 alkyl, a C 6 -C 10 aromatic ring group, and a C 3 -C 8 cycloalkyl.

2. The compound of Formula I, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof according to claim 1 , characterized in that the R 1 is H, methyl, ethyl or isopropyl.

3. The compound of Formula I, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof according to claim 1 , characterized in that the R 2 is vinyl, cyclopropyl, ethynyl or (CH═CH)-p, where p is a positive integer from 2 to 3.

4. The compound of Formula I, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof according to claim 1 , characterized in that the R 3 is a substituted C 4 -C 7 cycloalkyl, a substituted C 5 -C 6 heteroaromatic ring group, or a substituted C 6 -C 10 aromatic ring group, wherein the substitution means having 1, 2, 3 or 4 substituents selected from the group consisting of a C 1 -C 6 alkyl, -CF 3 , halogen, nitro, or a C 1 -C 4 linear or branched alkoxy, and the number of substituents is an integer from 1 to 4.

5. The compound of Formula I, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof according to claim 1 , characterized in that the substitution means having 1, 2, 3 or 4 substituents selected from the group consisting of a C 1 -C 3 linear or branched alkyl, a C 1 -C 3 perfluoroalkyl group, a C 1 -C 3 linear or branched alkoxy, halogen or nitro, and the number of substituent is an integer from 1 to 4.

6. The compound of Formula I, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof according to claim 1 , characterized in that the compound of Formula I is selected from the group consisting of:

wherein X, R 1 and R 3 are as defined in claim 1 , and R 4 is H, or a substituted or unsubstituted C 1 -C 3 linear alkyl.

7. The compound of Formula I, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof according to claim 1 , characterized in that the compound of Formula I is selected from the group consisting of:
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-phenylprop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(4-trifluoromethylphenyl)prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(4-chlorophenyl)prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(4-fluorophenyl)prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(4-bromophenyl)prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(4-difluoromethylphenyl)prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(4-cyclopentyl)prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(2-chlorophenyl)prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(3-fluoro-4-trifluoromethylphenyl)prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(naphthalen-1-yl)prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(2,4-dichlorophenyl)prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(3-chlorophenyl)prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(4-methylcarboxylate phenyl)prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(furan-2-yl)-prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(4-methoxyphenyl)-prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(4-nitrophenyl)-prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(4-ethoxyphenyl)-prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(3-trifluoromethylphenyl)-prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(3-fluorophenyl)-prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(3-methoxyphenyl)-prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(4-methylphenyl)-prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(2-nitrophenyl)-prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-but-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(4-cyanophenyl)-prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(4-phenylphenyl)-prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(2-naphthyl)-prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(4-tert-butylphenyl)-prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(2-fluorophenyl)-prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(3-nitrophenyl)-prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(2-trifluoromethylphenyl)-prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(2-fluoro-4-trifluoromethylphenyl)-prop-2-ene-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-cyclopentylprop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-thiophen-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(2-methoxyphenyl)-prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(2-fluoro-4-methoxyphenyl)-prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(2-methylphenyl)-prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(3-methylphenyl)-prop-2-en-1-amine;
(E)-N-methyl-N-[(benzofuran-3-yl)methylene]-3-(3-fluoro-4-methoxyphenyl)-prop-2-en-1-amine;
(E)-N-methyl-N-[(benzothiophen-3-yl)methylene]-3-(3-fluoro-4-methoxyphenyl)-prop-2-en-1-amine;
(E)-N-[(benzofuran-3-yl)methylene]-3-(4-trifluoromethylphenyl)-prop-2-en-1-amine;
(E)-N-ethyl-N-[(benzofuran-3-yl)methylene]-3-(4-trifluoromethylphenyl)-prop-2-en-1-amine;
(E)-N-isopropyl-N-[(benzofuran-3-yl)methylene]-3-(4-trifluoromethylphenyl)-prop-2-en-1-amine;
N-methyl-N-[(benzofuran-7-yl)methylene]-1-[(1S,2S)-2-phenylcyclopropyl]-methylamine;
N-methyl-N-[(6,7,8,9-tetrahydro-5H-benzo[3]annulen-2-yl)methyl]-3-(4-phenylphenyl)-prop-2-yn-1-amine;
N-methyl-N-[(6,7,8,9-tetrahydro-5H-benzo[3]annulen-2-yl)methylene]-3-phenyl-prop-1-amine;
(E)-N-methyl-N-[(benzofuran-2-yl)methylene]-3-(4-phenylphenyl)-prop-2-en-1-amine; or
(E)-N-methyl-N-[(benzothiophen-2-yl)methylene]-3-(4-phenylphenyl)-prop-2-en-1-amine.

8. A pharmaceutical composition comprising:
(1) the compound, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof according to claim 1 as an active ingred

Assignees

• Univ East China Science & Tech
• Shanghai Inst Materia Medica Cas

Inventors

• Li Jian
• Lan Lefu
• Li Baoli
• Chen Feifei
• Ni Shuaishuai
• Liu Yifu
• Wei Hanwen
• Mao Fei
• Zhu Jin

Classifications

• A61P31/04 Primary

  Antibacterial agents · CPC title

• C07D333/58

  Radicals substituted by nitrogen atoms · CPC title

• A61K31/343

  condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone · CPC title

• C07D409/12

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

• C07D307/81 Primary

  Radicals substituted by nitrogen atoms not forming part of a nitro radical · CPC title