Compounds for use in the treatment of parasitic diseases

摘要

The present invention relates to compounds useful for treating parasitic diseases, which are infectious diseases caused or transmitted by a parasite. Compounds of the invention are particularly active against the causative pathogens in malaria. Such compounds are selective inhibitors of parasitic histone deacetylase (PfHDAC) and suppress the growth of parasites, such as Plasmodium falciparum, at a lower concentration than the concentration required for the inhibition of the growth of mammalian cells.

主权项

1. A compound selected from the group consisting of:
(S)-N-(1-(5-(6-methoxynaphthalen-2-yl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)quinuclidine-4-carboxamide; (S)-N-(1-(5-(6-fluoronaphthalen-2-yl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)quinuclidine-4-carboxamide; (S)-N-(1-(5-(3-(aminomethyl)phenyl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)thiazole-5-carboxamide; (S)-N-(1-(5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)quinuclidine-4-carboxamide; (S)-N-(1-(5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)thiazole-5-carboxamide; (S)-7-(5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl)-N-methyl-7-(4-cyanophenylsulfonamido)heptanamide; (S)-N-(1-(5-(4-(1H-pyrazol-5-yl)phenyl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)thiazole-5-carboxamide; (S)-N-(7-(methylamino)-7-oxo-1-(5-(quinolin-6-yl)-1H-imidazol-2-yl)heptyl)thiazole-5-carboxamide; (S)-N-(1-(5-(1H-indol-5-yl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)thiazole-5-carboxamide; (S)-N-(7-(methylamino)-7-oxo-1-(5-(2-oxo-1,2-dihydroquinolin-3-yl)-1H-imidazol-2-yl)heptyl)thiazole-5-carboxamide; (S)-N-(7-(methylamino)-7-oxo-1-(5-(quinolin-3-yl)-1H-imidazol-2-yl)heptyl)thiazole-5-carboxamide; (S)-N-(1-(5-(4-(1H-pyrazol-1-yl)phenyl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)thiazole-5-carboxamide; (S)-N-(1-(5-(1H-indazol-5-yl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)thiazole-5-carboxamide; (S)-N-(1-(5-(isoquinolin-7-yl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)thiazole-5-carboxamide; (S)-N-(1-(5-(4-(1-methyl-1H-pyrazol-3-yl)phenyl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)thiazole-5-carboxamide; (S)-N-(1-(5-(isoquinolin-7-yl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)isothiazole-4-carboxamide; (S)-N-(7-(methylamino)-7-oxo-1-(5-(3-(trifluoromethyl)isoquinolin-7-yl)-1H-imidazol-2-yl)heptyl)thiazole-5-carboxamide; (S)-N-(1-(5-(3-methoxyisoquinolin-7-yl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)thiazole-5-carboxamide; (S)-N-(1-(5-(isoquinolin-7-yl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)isothiazole-5-carboxamide; (S)-1-isopropyl-N-(1-(5-(isoquinolin-7-yl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)-1H-pyrazole-4-carboxamide; (S)-N-(1-(5-(isoquinolin-7-yl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)-2-methylthiazole-5-carboxamide; (S)-N-(1-(5-(4-(1-methyl-1H-pyrazol-3-yl)phenyl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)isothiazole-5-carboxamide; (S)-1-isopropyl-N-(1-(5-(4-(1-methyl-1H-pyrazol-3-yl)phenyl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)-1H-pyrazole-4-carboxamide; (S)-2-methyl-N-(1-(5-(4-(1-methyl-1H-pyrazol-3-yl)phenyl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)thiazole-5-carboxamide; (S)-N-(1-(5-(4-(1-methyl-1H-pyrazol-3-yl)phenyl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)isothiazole-4-carboxamide; (S)-N-(1-(5-(4-(1-methyl-1H-pyrazol-3-yl)phenyl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)-2-(pyrrolidin-1-ylmethyl)thiazole-5-carboxamide; (S)-1-methyl-N-(1-(5-(4-(1-methyl-1H-pyrazol-3-yl)phenyl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)-1H-pyrazole-4-carboxamide; (S)-1-isopropyl-N-(1-(5-(3-methoxyisoquinolin-7-yl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)-1H-pyrazole-4-carboxamide; (S)-N-(7-(methylamino)-7-oxo-1-(5-(4-(thiazol-2-yl)phenyl)-1H-imidazol-2-yl)heptyl)thiazole-5-carboxamide; (S)-N-(7-(methylamino)-7-oxo-1-(5-(4-(thiazol-4-yl)phenyl)-1H-imidazol-2-yl)heptyl)thiazole-5-carboxamide;and pharmaceutically acceptable salts, tautomers, stereoisomers thereof.