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US 2012/0058986 A1Published application
Di-azetidinyl diamide as monoacylglycerol lipase inhibitors
OwnerPeter J. Connolly, Mark J. Macielag +1inventors
InventorsPeter J. Connolly, Mark J. Macielag, Bin Zhu
Life of this patent
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Abstract
Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula (I) as follows: wherein Q and Z are defined herein.
Claims15
A compound of Formula (I)
- wherein
- Q is selected from
- wherein
- Y is C6-10aryl or a heteroaryl that is thiazolyl, pyrrolyl, or oxazolyl;
- R1 is hydrogen or C1-4 alkyl;
- and
- m is an integer from 1 to 3;
- Z is C6-10aryl or a heteroaryl selected from the group consisting of quinolinyl, benzothiophenyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, indolyl, and indazolyl;
- wherein Z is
- (i) optionally independently substituted with one to three substituents selected from the group consisting of C1-4 alkyl, fluoro, chloro, bromo, trifluoromethyl, and piperidin-1-yl;
- provided that no more than one substituent on Z is piperidin-1-yl or
- (ii)
- (a) substituted with
- and
- (b) optionally further substituted with one additional methyl, chloro, fluoro, or phenyl substituent;
- wherein
- ring A is phenyl, thienyl, or benzothiophenyl;
- provided that
- when ring A is thienyl or benzothiophenyl, G is a bond or —CH2— or
- when A is phenyl, G is selected from the group consisting of a bond, O, —CH2—, SO2, and C(O);
- and
- R2 is trifluoromethyl, fluoro, chloro, or methanesulfonyl;
- r is an integer from 0 to 3;
- and enantiomers, diastereomers, and pharmaceutically acceptable salts thereof.
21 more elements
A compound of Formula (I)
- wherein:
- Q is selected from
- wherein
- Y is phenyl or thiazolyl;
- R1 is hydrogen or methyl;
- and
- m is 1;
- Z is C6-10aryl or a heteroaryl selected from the group consisting of benzothiophenyl, benzoxazolyl, benzothiazolyl, indolyl, and indazolyl;
- wherein Z is
- (i) independently substituted with one to two substituents selected from the group consisting of C1-4 alkyl, fluoro, chloro, bromo, trifluoromethyl, and piperidin-1-yl;
- provided that no more than one substituent on Z is piperidin-1-yl or
- (ii)
- (a) substituted with
- and
- (b) optionally further substituted with one additional methyl, chloro, fluoro, or phenyl substituent;
- wherein
- ring A is phenyl, thienyl, or benzothiophenyl;
- provided that
- when ring A is thienyl or benzothiophenyl, G is a bond or —CH2— or
- when ring A is phenyl, G is a bond, O, —CH2—, SO2, or C(O);
- and
- R2 is trifluoromethyl, fluoro, chloro, or methanesulfonyl;
- and
- r is an integer from 0 to 3;
- and enantiomers, diastereomers, and pharmaceutically acceptable salts thereof.
22 more elements
A compound of Formula (I)
- wherein:
- Q is selected from
- wherein
- Y is phenyl or thiazolyl;
- R1 is hydrogen;
- and
- m is 1;
- Z is C6-10aryl or a heteroaryl selected from the group consisting of benzothiophenyl, benzoxazolyl, benzothiazolyl, indolyl, and indazolyl;
- wherein Z is
- (i) independently substituted with one to two substituents selected from the group consisting of C1-4 alkyl, fluoro, chloro, bromo, and trifluoromethyl or
- (ii)
- (a) substituted with
- and
- (b) optionally further substituted with one additional methyl, chloro, fluoro, or phenyl substituent;
- wherein
- ring A is phenyl or thienyl;
- provided that
- when ring A is thienyl, G is a bond or —CH2— or
- when ring A is phenyl G is a bond, —CH2—, or SO2;
- R2 is trifluoromethyl, fluoro, chloro, or methanesulfonyl;
- and
- r is an integer from 0 to 2;
- and enantiomers, diastereomers, and pharmaceutically acceptable salts thereof.
20 more elements
A compound of Formula (Ia)
- selected from the group consisting of
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 1-(4-trifluoromethylphenyl)-1H-indol-5-yl;
- a compound wherein Y is thiazol-4-yl, R1 is H, and Z is 4-(3-trifluoromethylphenyl)phenyl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 1-(phenylsulfonyl)-1H-indol-5-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 2-phenyl-benzothiazol-6-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 4-(3-trifluoromethylphenyl)phenyl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 6-phenyl-benzothiophen-2-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 6-trifluoromethyl-benzothiophen-2-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 4-trifluoromethyl-benzothiophen-2-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 4-(5-trifluoromethyl-thien-2-yl)-phenyl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 4-(phenylmethyl)-phenyl;
- a compound wherein Y is thiazol-4-yl, R1 is H, and Z is 1-(4-fluorophenyl)-1H-indol-5-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 4-(4-trifluoromethylphenyl)-phenyl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 1-phenyl-1H-indol-5-yl;
- a compound wherein Y is thiazol-4-yl, R1 is H, and Z is 4-(4-trifluoromethylphenyl)-phenyl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 3-methyl-5-chloro-benzothiophen-2-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 4-(4-trifluoromethylphenylmethyl)-phenyl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 2-phenyl-benzoxazol-6-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 4-(3-methanesulfonylphenyl)phenyl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 5-bromo-naphth-2-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 4-(3-trifluoromethylphenylmethyl)-phenyl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 6-phenyl-naphth-2-yl;
- a compound wherein Y is thiazol-4-yl, R1 is H, and Z is 2-phenyl-benzothiazol-6-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 6-bromo-benzothiophen-2-yl;
- a compound wherein Y is phenyl, R1 is H, and Z is 5-bromo-naphth-2-yl;
- a compound wherein Y is phenyl, R1 is H, and Z is 5-phenyl-naphth-2-yl;
- a compound wherein Y is phenyl, R1 is H, and Z is 4-(4-trifluoromethyl phenylmethyl)-phenyl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 1-phenyl-1H-indol-6-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 2-(3-trifluoromethylphenyl)-benzoxazol-6-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 4-phenyl-phenyl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 2-(4-trifluoromethylphenyl)-benzoxazol-6-yl;
- a compound wherein Y is phenyl, R1 is H, and Z is 4-(phenylmethyl)-phenyl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 4-phenoxy-phenyl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 2-(4-chlorophenyl)-benzoxazol-6-yl;
- a compound wherein Y is phenyl, R1 is H, and Z is 6-phenyl-naphth-2-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 2-phenyl-benzoxazol-5-yl;
- a compound wherein Y is phenyl, R1 is H, and Z is 3-methyl-5-chloro-benzothiophen-2-yl;
- a compound wherein Y is thiazol-2-yl, R1 is methyl, and Z is 6-trifluoromethyl-benzothiophen-2-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 4-(phenylcarbonyl)-phenyl;
- a compound wherein Y is phenyl, R1 is H, and Z is 4-phenyl-phenyl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 6-bromo-naphth-2-yl;
- a compound wherein Y is phenyl, R1 is H, and Z is 2-phenyl-benzoxazol-6-yl;
- a compound wherein Y is phenyl, R1 is H, and Z is 6-bromo-naphth-2-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 4-bromophenyl;
- a compound wherein Y is phenyl, R1 is H, and Z is 5-trifluoromethyl-benzothiophen-2-yl;
- a compound wherein Y is phenyl, R1 is H, and Z is 4-phenoxy-phenyl;
- a compound wherein Y is thiazol-4-yl, R1 is H, and Z is 2-bromo-benzothiazol-6-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 5-trifluoromethyl-benzothiazol-2-yl;
- a compound wherein Y is thiazol-4-yl, R1 is methyl, and Z is 6-trifluoromethyl-benzothiophen-2-yl;
- a compound wherein Y is thiazol-4-yl, R1 is H, and Z is 6-trifluoromethyl-benzothiophen-2-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 3-chloro-6-trifluoromethyl-benzothiophen-2-yl;
- a compound wherein Y is thiazol-4-yl, R1 is H, and Z is 3-chloro-6-trifluoromethyl-benzothiophen-2-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 1-phenyl-1H-indazol-5-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 5-phenyl-naphth-2-yl;
- a compound wherein Y is thiazol-4-yl, R1 is H, and Z is 1-(3,4-difluorophenyl)-1H-indol-5-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 1-(2,4-difluorophenyl)-1H-indol-5-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 3-methyl-6-trifluoromethyl-benzothiophen-2-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 1-(3,4-difluorophenyl)-1H-indol-5-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 2-methyl-4-(3-trifluoromethylphenyl)-phenyl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 2-fluoro-4-(4-trifluoromethylphenyl)-phenyl;
- a compound wherein Y is thiazol-4-yl, R1 is H, and Z is 1-(2,4-difluorophenyl)-1H-indol-5-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 1-(4-fluorophenyl)-1H-indol-5-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 1-(4-fluorophenyl)-3-methyl-1H-indol-5-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 2-methyl-4-(4-trifluoromethylphenyl)phenyl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 2-fluoro-4-(3-trifluoromethylphenyl)-phenyl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 3-methyl-6-bromo-benzothiophen-2-yl;
- a compound wherein Y is thiazol-2-yl, R1 is H, and Z is 3-methyl-6-phenyl-benzothiophen-2-yl;
- and
- a compound wherein Y is thiazol-4-yl, R1 is H, and Z is 3-methyl-6-trifluoromethyl-benzothiophen-2-yl;
- and pharmaceutically acceptable salt forms thereof.
67 more elements
A compound of Formula (Ib)
- selected from the group consisting of
- a compound wherein m is 1, and Z is 3-chloro-6-phenyl-benzothiophen-2-yl;
- a compound wherein m is 1, and Z is 6-phenyl-naphth-2-yl;
- a compound wherein m is 1, and Z is 1-(4-trifluoromethylphenyl)-1H-indol-5-yl;
- a compound wherein m is 1, and Z is 1-(phenylsulfonyl)-1H-indol-5-yl;
- a compound wherein m is 1, and Z is 6-(3-methanesulfonylphenyl)-benzothiophen-2-yl;
- a compound wherein m is 1, and Z is 3-chloro-6-bromo-benzothiophen-2-yl;
- a compound wherein m is 1, and Z is 3,6-diphenyl-benzothiophen-2-yl;
- a compound wherein m is 1, and Z is 1-(3-trifluoromethylphenyl)-1H-indol-5-yl;
- a compound wherein m is 1, and Z is 4-(5-trifluoromethyl-thien-2-yl)-phenyl;
- a compound wherein m is 1, and Z is 2-phenyl-benzoxazol-5-yl;
- a compound wherein m is 1, and Z is 2-(3-trifluoromethylphenyl)-benzoxazol-6-yl;
- a compound wherein m is 1, and Z is 5-phenyl-benzothiophen-2-yl;
- a compound wherein m is 1, and Z is 4-(3-methanesulfonylphenyl)phenyl;
- a compound wherein m is 1, and Z is 6-trifluoromethyl-benzothiophen-2-yl;
- a compound wherein m is 1, and Z is 5-(3-methanesulfonylphenyl)benzothiophen-2-yl;
- a compound wherein m is 1, and Z is 5-bromo-naphth-2-yl;
- a compound wherein m is 1, and Z is 2-phenyl-benzoxazol-6-yl;
- a compound wherein m is 1, and Z is 1-phenyl-1H-indol-5-yl;
- a compound wherein m is 1, and Z is 4-(3-trifluoromethylphenylmethyl)phenyl;
- a compound wherein m is 1, and Z is 6-bromo-benzothiophen-2-yl;
- a compound wherein m is 1, and Z is 2-(4-chlorophenyl)-benzoxazol-6-yl;
- a compound wherein m is 1, and Z is 1-(2-trifluoromethylphenyl)-1H-indol-5-yl;
- a compound wherein m is 1, and Z is 6-bromo-naphth-2-yl;
- a compound wherein m is 1, and Z is 4-piperadin-1-yl-phenyl;
- a compound wherein m is 1, and Z is 4-phenyl-phenyl;
- a compound wherein m is 1, and Z is 5-bromo-benzothiophen-2-yl;
- a compound wherein m is 1, and Z is 4-(phenylmethyl)phenyl;
- a compound wherein m is 1, and Z is 4-(benzothiophen-2-yl)phenyl a compound wherein m is 1, and Z is 4-bromophenyl;
- a compound wherein m is 1, and Z is 5-phenyl-naphth-2-yl;
- a compound wherein m is 1, and Z is 6-phenyl-benzothiophen-2-yl;
- a compound wherein m is 1, and Z is 3-chloro-6-trifluoromethyl-benzothiophen-2-yl;
- a compound wherein m is 1, and Z is 3-chloro-6-fluoro-benzothiophen-2-yl;
- a compound wherein m is 1, and Z is 3-methyl-6-trifluoromethyl-benzothiophen-2-yl;
- and
- a compound wherein m is 1, and Z is 1-(4-fluorophenyl)-1H-indol-5-yl;
- and pharmaceutically acceptable salt forms thereof.
34 more elements
A compound of Formula (Ic)
- selected from the group consisting of
- a compound wherein Z is 3-methyl-6-trifluoromethyl-benzothiophen-2-yl;
- a compound wherein Z is 2-methyl-4-(3-trifluoromethylphenyl)phenyl;
- a compound wherein Z is 2-methyl-4-(4-trifluoromethylphenyl)phenyl;
- and
- a compound wherein Z is 1-(4-trifluoromethylphenyl)-1H-indol-5-yl;
- and pharmaceutically acceptable salt forms thereof.
4 more elements
Dependencies are inferred from the claim text.