US 12,391,660 B2
Heteroaromatic acetamide derivative, and preparation and use thereof
Yunfeng Cheng, Zhejiang (CN); and Yongzhou Hu, Zhejiang (CN)
Assigned to HANGZHOU WESTAN PHARMACEUTICAL TECHNOLOGY CO., LTD, Zhejiang (CN)
Appl. No. 17/615,659
Filed by Hangzhou Westan Pharmaceutical Technology Co., Ltd, Zhejiang (CN)
PCT Filed May 29, 2020, PCT No. PCT/CN2020/093277
§ 371(c)(1), (2) Date Dec. 1, 2021,
PCT Pub. No. WO2020/244460, PCT Pub. Date Dec. 10, 2020.
Claims priority of application No. 201910477117.1 (CN), filed on Jun. 3, 2019.
Prior Publication US 2022/0315549 A1, Oct. 6, 2022
Int. Cl. C07D 295/185 (2006.01); A61P 11/06 (2006.01); C07D 211/16 (2006.01); C07D 221/20 (2006.01); C07D 401/04 (2006.01); C07D 401/12 (2006.01); C07D 401/14 (2006.01); C07D 403/04 (2006.01); C07D 403/06 (2006.01); C07D 405/06 (2006.01); C07D 405/14 (2006.01); C07D 409/04 (2006.01); C07D 413/12 (2006.01); C07D 413/14 (2006.01); C07D 417/04 (2006.01); C07D 417/12 (2006.01); C07D 417/14 (2006.01); C07D 471/08 (2006.01)
CPC C07D 295/185 (2013.01) [A61P 11/06 (2018.01); C07D 211/16 (2013.01); C07D 221/20 (2013.01); C07D 401/04 (2013.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 403/04 (2013.01); C07D 403/06 (2013.01); C07D 405/06 (2013.01); C07D 405/14 (2013.01); C07D 409/04 (2013.01); C07D 413/12 (2013.01); C07D 413/14 (2013.01); C07D 417/04 (2013.01); C07D 417/12 (2013.01); C07D 417/14 (2013.01); C07D 471/08 (2013.01)] 6 Claims
 
1. A heteroaromatic acetamide derivative, characterized in that the derivative is a compound selected from the following compounds:
4-((1-(4-(4-(trifluoromethyl)phenyl)piperazine-1-carbonyl)cyclopentyl)amino)benzonitrile;
4-((1-(4-(3-(trifluoromethyl)phenyl)piperazine-1-carbonyl)cyclopentyl)amino)benzonitrile;
4-((1-(4-(2-(trifluoromethyl)phenyl)piperazine-1-carbonyl)cyclopentyl)amino)benzonitrile;
4-((1-(4-(2-(trifluoromethoxy)phenyl)piperazine-1-carbonyl)cyclopentyl)amino)benzonitrile;
4-((1-(4-(4-(trifluoromethoxy)phenyl)piperazine-1-carbonyl)cyclopentyl)amino)benzonitrile;
4-((1-(4-(4-chloro-2-methoxyphenyl)piperazine-1-carbonyl)cyclopentyl)amino)benzonitrile;
4-((1-(4-(3-methyl)phenyl)piperazine-1-carbonyl)cyclopentyl)amino)benzonitrile;
4-((1-(4-(5-(trifluoromethyl)pyridin-2-yl)piperazine-1-carbonyl)cyclopentyl)amino)benzonitrile;
4-((1-(4-(6-(trifluoromethyl)pyridin-2-yl)piperazine-1-carbonyl)cyclopentyl)amino)benzonitrile;
4-((1-(4-(6-(trifluoromethyl)pyridin-2-yl)piperazine-1-carbonyl)cyclopropyl)amino)benzonitrile;
4-((1-(4-(6-(trifluoromethyl)pyridin-2-yl)piperazine-1-carbonyl)cyclobutyl)amino)benzonitrile;
4-((3,3-dimethyl-1-oxo-1-(4-(6-trifluoromethyl)pyridin-2-yl)piperazine-1-yl)butan-2-yl)amino)benzonitrile;
4-((1-(4-(6-methylpyridin-2-yl)piperazine-1-carbonyl)cyclopentyl)amino)benzonitrile;
6-(4-(1-((4-cyanophenyl)amino)cyclopentane-1-carbonyl)piperazine-1-yl)N,N-dimethylnicotinamide;
4-((1-(4-(5-(trifluoromethyl)pyrimidin-2-yl)piperazine-1-carbonyl)cyclopentyl)amino)benzonitrile;
4-((1-(4-(4-(trifluoromethyl)pyrimidin-2-yl)piperazine-1-carbonyl)cyclopentyl)amino)benzonitrile;
4-((1-(4-(6-(trifluoromethyl)pyridazin-3-yl)piperazine-1-carbonyl)cyclopentyl)amino)benzonitrile;
4-((1-(4-(6-(trifluoromethyl)pyridazin-3-yl)piperazine-1-carbonyl)cyclopentyl)amino)chlorobenzene;
4-((1-(4-(6-(trifluoromethyl)pyridazin-3-yl)piperazine-1-carbonyl)cyclopentyl)amino)nitrobenzene;
2-chloro-4-((1-(4-(6-(trifluoromethyl)pyridazin-3-yl)piperazine-1-carbonyl)cyclopentyl)amino)benzonitrile;
2-chloro-4-((1-(4-(6-(trifluoromethyl)pyridazin-3-yl)piperazine-1-carbonyl)phenyl)amino)benzonitrile;
4-((1-(4-(5-(trifluoromethyl)thien-2-yl)piperazine-1-carbonyl)cyclopentyl)amino)benzonitrile;
4-((1-(4-(5-(trifluoromethyl)thiazol-2-yl)piperazine-1-carbonyl)cyclopentyl)amino)benzonitrile;
4-((1-(4-(1-methyl-1H-pyrazol-3-yl)piperazine-1-carbonyl)cyclopentyl)amino)benzonitrile;
4-((1-(4-(6-(trifluoromethyl)pyridin-2-yl)piperazine-1-carbonyl)cyclopentyl)amino)phenylacetylene;
4-((1-(4-(cyclopentanemethyl)piperazine-1-carbonyl)cyclopentyl)amino)benzonitrile;
4-((1-(4-(tert-butyl)piperidine-1-carbonyl)cyclopentyl)amino)benzonitrile;
4-((1-(4-(isobutyl)piperidine-1-carbonyl)cyclopentyl)amino)benzonitrile;
4-((1-(4-(cyclopentyl)piperidine-1-carbonyl)cyclopentyl)amino)benzonitrile;
4-((1-(8-aza-spiro [4.5]decane-8-carbonyl)cyclopentyl)amino)benzonitrile;
4-((1-(4-(cyclohexyl)piperidine-1-carbonyl)cyclopentyl)amino)benzonitrile;
4-((1-(4-(tert-butyl)piperidine-1-carbonyl)cyclopentyl)amino)phenylacetylene;
4-((1-(4-(tert-butyl)piperidine-1-carbonyl)cyclobutyl)amino)benzonitrile;
4-((1-(4-(tert-butyl)piperidine-1-carbonyl)cyclopropyl)amino)benzonitrile;
2-((1-(4-(tert-butyl)piperidine-1-carbonyl)cyclopentyl)amino) thiazole-4-carbonitrile;
2-((1-(4-(tert-butyl)piperidine-1-carbonyl)cyclopentyl)amino) thiazole-5-carbonitrile;
2-((1-(4-(tert-butyl)piperidine-1-carbonyl)cyclopentyl)amino) oxazole-4-carbonitrile;
4-((1-(4-(tert-butyl)piperidine-1-carbonyl)cyclopentyl)amino)-1-methyl-1H-imidazole-2-carbonitrile;
4-((1-(4-(tert-butyl)piperidine-1-carbonyl)tert-butyl)amino)benzonitrile;
4-((1-(4-(tert-butyl)piperidine-1-carbonyl)cyclopentyl)methylamino)benzonitrile;
4-((1-(4-(tert-butyl)piperidine-1-carbonyl)cyclopentyl)methylamino)trifluoromethylbenzene;
4-((1-(4-(tert-butyl)piperidine-1-carbonyl)cyclopentyl)amino)chlorobenzene;
4-((1-(4-(6-(trifluoromethyl)pyridin-2-yl)piperazine-1-carbonyl)cyclopentyl)oxy)benzonitrile;
4-((1-(4-(m-methylphenyl)piperazine-1-carbonyl)cyclopentyl)oxy)benzonitrile;
4-((1-(4-(trifluoromethyl)phenyl)piperazine-1-carbonyl)cyclopentyl)oxy)benzonitrile;
4-((1-(4-(4-(trifluoromethyl)pyrimidin-2-yl)piperazine-1-carbonyl)cyclopentyl)oxy)benzonitrile;
4-((1-(4-(4-(trifluoromethyl)pyrimidin-2-yl)piperazine-1-carbonyl)tert-butyl)oxy)benzonitrile;
4-((1-(4-(6-(trifluoromethyl)pyridazin-3-yl)piperazine-1-carbonyl)cyclopentyl)oxy)benzonitrile;
4-((1-(4-(6-(trifluoromethyl)pyridazin-3-yl)piperazine-1-carbonyl)cyclopentyl)oxy)nitrobenzene;
4-((1-(4-(tert-butyl)piperidine-1-carbonyl)cyclopentyl)oxy)benzonitrile;
4-((1-(4-(tert-butyl)piperazine-1-carbonyl)cyclopentyl)oxy)benzonitrile;
4-((1-(4-(6-(trifluoromethyl)pyridin-2-yl)piperazine-1-carbonyl)cyclobutyl)oxy)benzonitrile;
4-((1-(4-(4-(trifluoromethyl)pyrimidin-2-yl)piperazine-1-carbonyl)cyclopentyl)oxy)oxazole-4-carbonitrile;
2-chloro-4-((1-(4-(6-(trifluoromethyl)pyridazin-3-yl)piperazine-1-carbonyl)cyclopentyl)oxy)benzonitrile;
1-methyl-4-((1-(4-(5-(trifluoromethyl)pyridin-2-yl)piperazine-1-carbonyl)cyclopentyl)oxy)-1H-imidazole-2-carbonitrile;
2-((1-(4-(5-(trifluoromethyl)pyridin-2-yl)piperazine-1-carbonyl)cyclopentyl)oxy)thiazole-5-carbonitrile;
4-(1-phenyl-2-(4-6-(trifluoromethyl)pyridazin-3-yl)piperazine-1-yl)ethoxy)benzonitrile;
4-((1-(4-(tert-butyl)piperazine-1-carbonyl)cyclopentyl)oxy)trifluoromethylbenzene;
5-((1-(4-(tert-butyl)piperidine-1-carbonyl)cyclopentyl)oxy)-1-methyl-1H-pyrrole-3-carbonitrile;
4-((1-(4-(tert-butyl)piperazine-1-carbonyl)cyclopentyl)sulfanyl)benzonitrile;
5-((1-(4-(tert-butyl)piperidine-1-carbonyl)cyclopentyl)sulfanyl)-1-methyl-1H-indole;
4-((1-(8-(6-(trifluoromethyl)pyridin-2-yl)-3,8-diazabicyclo [3.2.1] octane-3-carbonyl)cyclopentyl)amino)benzonitrile;
4-((1-(5-(6-(trifluoromethyl)pyridin-2-yl)-2,5-diazabicyclo [2.2.2] octane-2-carbonyl)cyclopentyl)amino)benzonitrile;
4-((1-(8-(6-(trifluoromethyl)pyridin-2-yl)-3,8-diazabicyclo [3.2.1] octane-3-carbonyl)cyclopentyl)amino)benzonitrile; and
4-((1-(5-(6-(trifluoromethyl)pyridin-2-yl)-2,5-diazabicyclo [2.2.2] octane-2-carbonyl)cyclopentyl)oxy)benzonitrile or a pharmaceutically acceptable salt thereof.