US 9,850,235 B2Granted

PDE4 inhibitor

AssigneeMeiji Seika Pharma Co., Ltd.

InventorsChika Kikuchi, Yuji Tabata, Takeru Yamakawa, Takashi Matsuhira, Naoko Watanabe, Natsuki Kubota, Kaori Kaneda

Life of this patent

Estimating the term…

Abstract

Provided is a compound represented by formula (1a) or a pharmacologically acceptable salt thereof, which can be used as a phosphodiesterase (PDE) inhibitor. R1 to R6 in the formula each independently represent an alkyl group or the like.

Claims13

Dependent claims

A compound represented by formula (1a):

wherein
R1 is selected from the group consisting of a hydrogen atom, a halogen atom, a hydroxy group, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-7 cycloalkyl group, an optionally substituted C6-10 monocyclic or polycyclic aryl group, an optionally substituted C7-11 monocyclic or polycyclic aralkyl group, an optionally substituted 4- to 10-membered monocyclic or bicyclic heterocyclic group containing 1 to 4 heteroatoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, a di-C1-6 alkylamino group, an optionally substituted C3-7 cycloalkylamino group, an optionally substituted C1-6 alkyloxy group, an optionally substituted C3-7 cycloalkyloxy group, an optionally substituted C6-10 monocyclic or polycyclic aryloxy group, an optionally substituted C7-11 monocyclic or polycyclic aralkyloxy group, an optionally substituted 4- to 10-membered monocyclic or bicyclic heterocyclyloxy group containing 1 to 4 heteroatoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, an optionally substituted C1-6 alkylthio group, an optionally substituted C1-6 alkylsulfonyl group, an optionally substituted C1-6 alkylcarbonyl group, a mono-C1-6 alkylaminocarbonyl group, a di-C1-6 alkylaminocarbonyl group, and an optionally substituted hydroxyaminocarbonyl group,
R2, R3 and R4 are each independently selected from the group consisting of a hydrogen atom, a halogen atom, a hydroxy group, a carboxy group, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-7 cycloalkyl group, an optionally substituted C6-10 monocyclic or polycyclic aryl group, an optionally substituted C7-11 monocyclic or polycyclic aralkyl group, an optionally substituted 4- to 10-membered monocyclic or bicyclic heterocyclic group containing 1 to 4 heteroatoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, a di-C1-6 alkylamino group, an optionally substituted C3-7 cycloalkylamino group, an optionally substituted C1-6 alkyloxy group, an optionally substituted C3-7 cycloalkyloxy group, an optionally substituted C6-10 monocyclic or polycyclic aryloxy group, an optionally substituted C7-11 monocyclic or polycyclic aralkyloxy group, an optionally substituted 4- to 10-membered monocyclic or bicyclic heterocyclyloxy group containing 1 to 4 heteroatoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, an optionally substituted C1-6 alkylthio group, an optionally substituted C1-6 alkylsulfonyl group, an optionally substituted C1-6 alkylcarbonyl group, a mono-C1-6 alkylaminocarbonyl group, a di-C1-6 alkylaminocarbonyl group, an optionally substituted C1-6 alkyloxycarbonyl group and an optionally substituted hydroxyaminocarbonyl group,
said optionally substituted groups are optionally substituted with at least one substituent selected from the group consisting of a halogen atom, a cyano group, a hydroxy group, a C1-6 alkyl group, a C3-6 cycloalkyl group, a hydroxy-C1-6 alkyl group, a C1-6 alkyloxy group, an aminocarbonyl group, an oxo group, a nitro group, a C1-6 alkylthio group, a C1-6 alkylsulfonyl group and a C6-10 aryl group, and
R5 and R6 are each independently a hydrogen atom or a C1-6 alkyl group, and
wherein
R4 is not a hydrogen atom or methyl, and
R5 and R6 are not both hydrogen atoms;
or a pharmacologically acceptable salt thereof.

6 more elements

A compound selected from the group consisting of:

(S)-5-chloro-7-isopropyl-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-methoxy-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-acetyl-2-(2-methylpiperazin-1-yl)benzoxazole,
meso-5-chloro-2-(2,6-cis-dimethylpiperazin-1-yl)-7-methylbenzoxazole,
(S)-5-fluoro-7-methyl-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-bromo-7-methyl-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-isopropoxy-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-ethyl-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-ethoxycarbonyl-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-cyano-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-ethyl-2-(2-isopropylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-ethyl-2-(2-isobutylpiperazin-1-yl)benzoxazole,
(S)-2-(2-n-butyl piperazin-1-yl)-5-chloro-7-ethylbenzoxazole,
(S)-5-chloro-7-ethyl-2-(2-ethyl piperazin-1-yl)benzoxazole,
(S)-5-chloro-7-hydroxymethyl-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(thiophen-3-yl)benzoxazole,
(S)-5-chloro-7-(furan-3-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(thiophen-2-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-phenylbenzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(pyrrolidin-1-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(morpholin-1-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(piperidin-1-yl)benzoxazole,
(S)-5-chloro-7-(furan-2-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-(cyclopentylamino)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-diethylamino-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-dimethylamino-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-cyclopropyl-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-(cyclopentyloxy)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-ethoxy-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-n-propoxybenzoxazole,
(S)-5-chloro-7-cyclopentyl-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-7-n-butyl-5-chloro-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(1H-pyrazol-1-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(oxazol-2-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)benzoxazole,
(S)-5-chloro-7-(1H-imidazol-1-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(thiazol-4-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(thiazol-5-yl)benzoxazole,
(S)-5-chloro-7-(5-methylfuran-2-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-(4-methyl-1H-pyrazol-1-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(pyridin-3-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(pyridin-4-yl)benzoxazole,
(S)-5-chloro-7-cyclohexyl-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(2H-1,2,3-triazol-2-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(1H-1,2,4-triazol-1-yl)benzoxazole,
(S)-5-chloro-7-isobutyl-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(2-hydroxymethyl phenyl)benzoxazole,
(S)-5-chloro-7-(1-methyl-1H-imidazol-2-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-(1H-imidazol-2-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-(cyclohexylmethyl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-(cyclohexyloxy)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-(cyclopropylmethoxy)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-(isothiazol-3-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-(5-hydroxymethylthiazol-2-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(pyrimidin-2-yl)benzoxazole,
(S)-5-chloro-7-(5-chlorothiophen-2-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-(5-chloropyridin-2-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-(4-chloropyridin-2-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-(6-fluoropyridin-2-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-(3-fluoropyridin-2-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-(5-cyanothiazol-2-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(5-methylthiazol-2-yl)benzoxazole,
(S)-5-chloro-7-(2-chlorothiophen-3-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-(5-carbamoylthiazol-2-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-(3-cyanopyridin-2-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-(5-fluorothiophen-2-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(3-methyl pyridin-2-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(2-methylthiazol-4-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-phenoxybenzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(2-oxopyrrolidin-1-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(2-oxooxazolidin-3-yl)benzoxazol e,
(S)-5-chloro-7-(5-fluoropyridin-2-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-(5-chlorothiazol-2-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-7-benzyl-5-chloro-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-(5-(hydroxymethyl)thiazol-4-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yloxy)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(5-nitrothiazol-2-yl)benzoxazole,
(S)-5-chloro-7-(3-methoxypyridin-2-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
5-chloro-2-((S)-2-methylpiperazin-1-yl)-7-(tetrahydrofuran-2-yl)benzoxazole,
(S)-5-chloro-7-(4-fluorophenyl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)-4-(trifluoromethyl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(1H-pyrazol-1-yl)-4-(trifluoromethyl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)-4-(trifluoromethyl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)-6-(trifluoromethyl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)-4-(trifluoromethoxy)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)-4-(trifluoromethoxy)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(1H-pyrazol-1-yl)-4-(trifluoromethoxy)benzoxazole,
(S)-4,5-difluoro-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)benzoxazole,
(S)-4,5-difluoro-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)benzoxazole,
(S)-4,5-difluoro-2-(2-methylpiperazin-1-yl)-7-(1H-pyrazol-1-yl)benzoxazole,
(S)-5-chloro-6-fluoro-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)benzoxazole,
(S)-5-chloro-6-fluoro-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)benzoxazole,
(S)-5-chloro-6-fluoro-2-(2-methylpiperazin-1-yl)-7-(1H-pyrazol-1-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-n-propylbenzoxazole,
(S)-5-chloro-7-dimethyl aminocarbonyl-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-diethylaminocarbonyl-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-hydroxyaminocarbonyl-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-carboxy-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-methyl aminocarbonyl-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-ethylaminocarbonyl-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-fluoro-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)benzoxazole,
(S)-5-fluoro-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)benzoxazole,
(S)-5-fluoro-2-(2-methylpiperazin-1-yl)-7-(oxazol-2-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(1,2,4-oxadiazol-3-yl)benzoxazole,
(S)-5-chloro-7-(4,5-dihydrooxazol-2-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-(methoxymethyl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-(isoxazol-3-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-7-(isoxazol-5-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-7-bromo-5-chloro-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-cyano-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)benzoxazole,
(S)-5-cyano-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)benzoxazole,
(S)-5-cyano-2-(2-methylpiperazin-1-yl)-7-(oxazol-2-yl)benzoxazole,
(S)-5-methyl-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)benzoxazole,
(S)-5-methyl-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)benzoxazole,
(S)-5-methyl-2-(2-methylpiperazin-1-yl)-7-(oxazol-2-yl)benzoxazole,
(S)-5-fluoro-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)-4-(trifluoromethyl)benzoxazole,
(S)-5-fluoro-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)-4-(trifluoromethyl)benzoxazole,
(S)-5-fluoro-2-(2-methylpiperazin-1-yl)-7-(1H-pyrazol-1-yl)-4-(trifluoromethyl)benzoxazole,
(S)-5-chloro-4,6-difluoro-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)benzoxazole,
(S)-5-chloro-4,6-difluoro-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)benzoxazole,
(S)-4,5,6-trifluoro-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)benzoxazole,
(S)-4,5,6-trifluoro-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)benzoxazole,
(S)-4,5,6-trifluoro-2-(2-methylpiperazin-1-yl)-7-(1H-pyrazol-1-yl)benzoxazole,
(S)-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)-5-(trifluoromethyl)benzoxazole,
(S)-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)-5-(trifluoromethyl)benzoxazole,
(S)-2-(2-methylpiperazin-1-yl)-7-(oxazol-2-yl)-5-(trifluoromethyl)benzoxazole,
(S)-5-chloro-4-fluoro-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)benzoxazole,
(S)-5-chloro-4-fluoro-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)benzoxazole,
(S)-5-chloro-4-fluoro-2-(2-methylpiperazin-1-yl)-7-(1H-pyrazol-1-yl)benzoxazole,
(S)-5-chloro-4-methyl-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)benzoxazole,
(S)-5-chloro-4-methyl-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)benzoxazole,
(S)-5-chloro-4-methyl-2-(2-methylpiperazin-1-yl)-7-(1H-pyrazol-1-yl)benzoxazole,
(S)-5-fluoro-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)-4-(trifluoromethoxy)benzoxazole,
(S)-5-fluoro-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)-4-(trifluoromethoxy)benzoxazole,
(S)-5-fluoro-2-(2-methylpiperazin-1-yl)-7-(1H-pyrazol-1-yl)-4-(trifluoromethoxy)benzoxazole,
(S)-5-chloro-6-methyl-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)benzoxazole,
(S)-5-chloro-6-methyl-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)benzoxazole,
(S)-5-chloro-6-methyl-2-(2-methylpiperazin-1-yl)-7-(1H-pyrazol-1-yl)benzoxazole,
(S)-5-chloro-6-methoxy-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)benzoxazole,
(S)-5-chloro-6-methoxy-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)benzoxazole,
(S)-5-chloro-6-cyano-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)benzoxazole,
(S)-5-chloro-4-cyano-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)benzoxazole,
(S)-5-fluoro-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)-6-(trifluoromethyl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(methyl sulfonyl)benzoxazole,
(S)-5-chloro-4-iodo-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)benzoxazole,
(S)-5-chloro-6-iodo-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-4-phenyl-7-(pyridin-2-yl)benzoxazole,
(S)-5-chloro-4-cyclopropyl-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-4-(methylthio)-7-(pyridin-2-yl)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-4-(methylsulfonyl)-7-(pyridin-2-yl)benzoxazole,
(S)-6-bromo-5-chloro-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)benzoxazole,
(S)-5-chloro-4-methoxy-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)benzoxazole,
(S)-5-chloro-4-methoxy-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)benzoxazole,
(S)-5-chloro-4-methoxy-2-(2-methylpiperazin-1-yl)-7-(1H-pyrazol-1-yl)benzoxazole,
(R)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)-4-(trifluoromethoxy)benzoxazole,
(R)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)-4-(trifluoromethoxy)benzoxazole,
(R)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(1H-pyrazol-1-yl)-4-(trifluoromethoxy)benzoxazole,
(S)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)-6-(trifluoromethoxy)benzoxazole,
(S)-5-chloro-6-methoxy-7-methyl-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-6-hydroxy-7-methyl-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-4-bromo-6-chloro-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-6-chloro-4-(furan-2-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(R)-6-chloro-4-(furan-2-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-6-chloro-2-(2-methylpiperazin-1-yl)-4-(1H-pyrazol-1-yl)benzoxazole,
(S)-5-bromo-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-cyano-7-methoxy-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-6,7-dimethoxy-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-6-methyl-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-5-chloro-6-methoxy-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-7-methyl-5-(pyrrolidin-1-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(S)-7-methyl-5-(thiophen-3-yl)-2-(2-methylpiperazin-1-yl)benzoxazole,
(R)-5-chloro-7-ethyl-2-(2-methylpiperazin-1-yl)benzoxazole,
5-chloro-2-(piperazin-1-yl)-7-(thiazol-2-yl)-4-(trifluoromethoxy)benzoxazole,
(R)-5-chloro-2-(3-methylpiperazin-1-yl)-7-(thiazol-2-yl)-4-(trifluoromethoxy)benzoxazole,
(S)-5-chloro-2-(3-methylpiperazin-1-yl)-7-(thiazol-2-yl)-4-(trifluoromethoxy)benzoxazole,
(R)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(pyridin-2-yl)-4-(trifluoromethyl)benzoxazole,
(R)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(thiazol-2-yl)-4-(trifluoromethyl)benzoxazole, and
(R)-5-chloro-2-(2-methylpiperazin-1-yl)-7-(1H-pyrazol-1-yl)-4-(trifluoromethyl)benzoxazole,
or a pharmacologically acceptable salt thereof.

177 more elements

A pharmaceutical composition comprising

(i) a phosphodiesterase 4 (PDE4) inhibitor compound represented by formula (1a) or a pharmacologically acceptable salt thereof as an active ingredient:
wherein
R1, R2, R3 and R4 are each independently selected from the group consisting of a hydrogen atom, a halogen atom, a hydroxy group, a carboxy group, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-7 cycloalkyl group, an optionally substituted C6-10 monocyclic or polycyclic aryl group, an optionally substituted C7-11 monocyclic or polycyclic aralkyl group, an optionally substituted 4- to 10-membered monocyclic or bicyclic heterocyclic group containing 1 to 4 heteroatoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, a di-C1-6 alkylamino group, an optionally substituted C3-7 cycloalkylamino group, an optionally substituted C1-6 alkyloxy group, an optionally substituted C3-7 cycloalkyloxy group, an optionally substituted C6-10 monocyclic or polycyclic aryloxy group, an optionally substituted C7-11 monocyclic or polycyclic aralkyloxy group, an optionally substituted 4- to 10-membered monocyclic or bicyclic heterocyclyloxy group containing 1 to 4 heteroatoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, an optionally substituted C1-6 alkylthio group, an optionally substituted C1-6 alkylsulfonyl group, an optionally substituted C1-6 alkylcarbonyl group, a mono-C1-6 alkylaminocarbonyl group, a di-C1-6 alkylaminocarbonyl group, an optionally substituted C1-6 alkyloxycarbonyl group and an optionally substituted hydroxyaminocarbonyl group,
said optionally substituted groups are optionally substituted with at least one substituent selected from the group consisting of a halogen atom, a cyano group, a hydroxy group, a C1-6 alkyl group, a C3-6cycloalkyl group, a hydroxy-C1-6 alkyl group, a C1-6alkyloxy group, an aminocarbonyl group, an oxo group, a nitro group, a C1-6 alkylthio group, a C1-6 alkylsulfonyl group and a C6-10aryl group,
R5 and R6 are each independently a hydrogen atom or a C1-6 alkyl group, and
wherein
R4 is not a hydrogen atom or methyl, and
R5 and R6 are not both hydrogen atoms, and
(ii) an excipient, a disintegrant, a binder, a lubricant or a colorant.

6 more elements

A pharmaceutical composition comprising

(i) a phosphodiesterase 4 (PDE4) inhibitor compound represented by formula (1) or a pharmacologically acceptable salt thereof as an active ingredient:
wherein
R1 is selected from the group consisting of a hydrogen atom, a halogen atom, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-7 cycloalkyl group, an optionally substituted C6-10 monocyclic or polycyclic aryl group, an optionally substituted 5- to 7-membered monocyclic heterocyclic group containing 1 to 4 heteroatoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, an optionally substituted C1-6 alkyloxy group, an optionally substituted C1-6 alkylthio group and an optionally substituted C1-6 alkylsulfonyl group,
R2 is selected from the group consisting of a hydrogen atom, a halogen atom, a cyano group, an optionally substituted C1-6 alkyl group and an optionally substituted 5- to 7-membered monocyclic heterocyclic group containing 1 to 4 heteroatoms selected from an oxygen atom, a nitrogen atom and a sulfur atom,
R3 is selected from the group consisting of a hydrogen atom, a halogen atom, a hydroxy group, a cyano group, an optionally substituted C1-6 alkyl group and an optionally substituted C1-6 alkyloxy group, and
R4 is selected from the group consisting of a halogen atom, a carboxy group, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-7 cycloalkyl group, an optionally substituted C6-10 monocyclic or polycyclic aryl group, an optionally substituted C7-11 monocyclic or polycyclic aralkyl group, an optionally substituted 5- to 7-membered monocyclic heterocyclic group containing 1 to 4 heteroatoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, a di-C1-6 alkylamino group, an optionally substituted C3-7 cycloalkylamino group, an optionally substituted C1-6 alkyloxy group, an optionally substituted C3-7 cycloalkyloxy group, an optionally substituted C6-10 monocyclic or polycyclic aryloxy group, an optionally substituted 5- to 7-membered monocyclic heterocyclyloxy group containing 1 to 4 heteroatoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, an optionally substituted C1-6 alkylsulfonyl group, an optionally substituted C1-6 alkylcarbonyl group, a mono-C1-6 alkylaminocarbonyl group, a di-C1-6 alkylaminocarbonyl group, an optionally substituted C1-6 alkyloxycarbonyl group and an optionally substituted hydroxyaminocarbonyl group,
said optionally substituted groups are optionally substituted with at least one substituent selected from the group consisting of a halogen atom, a cyano group, a hydroxy group, a C1-6 alkyl group, a C3-6cycloalkyl group, a hydroxy-C1-6 alkyl group, a C1-6alkyloxy group, an aminocarbonyl group, an oxo group, a nitro group, a C1-6 alkylthio group, a C1-6 alkylsulfonyl group and a C6-10aryl group, and
R5 to R8 are each independently a hydrogen atom or a C1-6alkyl group, and
wherein
R4 is not methyl, and
R5 and R6 are not both hydrogen atoms, and
(ii) an excipient, a disintegrant, a binder, a lubricant or a colorant.

9 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/903,707Filed 10 Jul 2014
Priority: WO PCT/JP2013/06890210 Jul 2013
Published: US 2016/0159783 A19 Jun 2016
Granted: 26 Dec 2017
Term ends: Not estimatedThe source records don’t support an estimate.

Classification4 codes

C07D 413/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
C07D 413/14
Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms:…
C07D 417/14
Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms,…
C07D
Heterocyclic compounds

Family

US 2016/0159783 A1Pre-grant publication · published 9 Jun 2016
US 9,890,142 B2Related patent
US 9,850,235 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound represented by formula (1a):

wherein
R1 is selected from the group consisting of a hydrogen atom, a halogen atom, a hydroxy group, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-7 cycloalkyl group, an optionally substituted C6-10 monocyclic or polycyclic aryl group, an optionally substituted C7-11 monocyclic or polycyclic aralkyl group, an optionally substituted 4- to 10-membered monocyclic or bicyclic heterocyclic group containing 1 to 4 heteroatoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, a di-C1-6 alkylamino group, an optionally substituted C3-7 cycloalkylamino group, an optionally substituted C1-6 alkyloxy group, an optionally substituted C3-7 cycloalkyloxy group, an optionally substituted C6-10 monocyclic or polycyclic aryloxy group, an optionally substituted C7-11 monocyclic or polycyclic aralkyloxy group, an optionally substituted 4- to 10-membered monocyclic or bicyclic heterocyclyloxy group containing 1 to 4 heteroatoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, an optionally substituted C1-6 alkylthio group, an optionally substituted C1-6 alkylsulfonyl group, an optionally substituted C1-6 alkylcarbonyl group, a mono-C1-6 alkylaminocarbonyl group, a di-C1-6 alkylaminocarbonyl group, and an optionally substituted hydroxyaminocarbonyl group,
R2, R3 and R4 are each independently selected from the group consisting of a hydrogen atom, a halogen atom, a hydroxy group, a carboxy group, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-7 cycloalkyl group, an optionally substituted C6-10 monocyclic or polycyclic aryl group, an optionally substituted C7-11 monocyclic or polycyclic aralkyl group, an optionally substituted 4- to 10-membered monocyclic or bicyclic heterocyclic group containing 1 to 4 heteroatoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, a di-C1-6 alkylamino group, an optionally substituted C3-7 cycloalkylamino group, an optionally substituted C1-6 alkyloxy group, an optionally substituted C3-7 cycloalkyloxy group, an optionally substituted C6-10 monocyclic or polycyclic aryloxy group, an optionally substituted C7-11 monocyclic or polycyclic aralkyloxy group, an optionally substituted 4- to 10-membered monocyclic or bicyclic heterocyclyloxy group containing 1 to 4 heteroatoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, an optionally substituted C1-6 alkylthio group, an optionally substituted C1-6 alkylsulfonyl group, an optionally substituted C1-6 alkylcarbonyl group, a mono-C1-6 alkylaminocarbonyl group, a di-C1-6 alkylaminocarbonyl group, an optionally substituted C1-6 alkyloxycarbonyl group and an optionally substituted hydroxyaminocarbonyl group,
said optionally substituted groups are optionally substituted with at least one substituent selected from the group consisting of a halogen atom, a cyano group, a hydroxy group, a C1-6 alkyl group, a C3-6 cycloalkyl group, a hydroxy-C1-6 alkyl group, a C1-6 alkyloxy group, an aminocarbonyl group, an oxo group, a nitro group, a C1-6 alkylthio group, a C1-6 alkylsulfonyl group and a C6-10 aryl group, and
R5 and R6 are each independently a hydrogen atom or a C1-6 alkyl group, and
wherein
R4 is not a hydrogen atom or methyl, and
R5 and R6 are not both hydrogen atoms;
or a pharmacologically acceptable salt thereof.

6 more elements

Facts

Application

14/903,707Filed 10 Jul 2014

Priority

WO PCT/JP2013/06890210 Jul 2013

Published

US 2016/0159783 A19 Jun 2016

Granted

26 Dec 2017

Term ends

Not estimatedThe source records don’t support an estimate.

Classification4 codes

C07D 413/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
C07D 413/14
Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms:…
C07D 417/14
Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms,…
C07D
Heterocyclic compounds