IP Library › Granted Patent US 9,662,311

Granted Patent B2

US 9,662,311 · App. 14/900,139 · Granted May 30, 2017

Substituted bicyclic compounds as bromodomain inhibitors

Inventors: Shuang Liu (Schenectady, NY); John Frederick Quinn (Albany, NY); Bryan Cordell Duffy (Glenmont, NY); Ruifang Wang (Schenectady, NY); May Xiaowu Jiang (Guilderland, NY); Gregory Scott Martin (Colonie, NY); He Zhao (Madison, CT); Michael Ellis (Clifton Park, NY); Gregory Steven Wagner (Foster City, CA); Peter Ronald Young (San Francisco, CA)

Assignee: Zenith Epigenetics Ltd.

A61K31/4184 A61K31/422 A61K31/423 A61K31/426 A61K31/427 A61K31/428 A61K31/437 A61K31/4439 A61K31/4709 A61K31/4725 A61K31/496 A61K31/497 A61K31/4985 A61K31/501 A61K31/506 A61K31/517 A61K31/538 A61K31/5377 A61K45/06 C07D403/14 C07D405/04 C07D405/14 C07D409/14 C07D413/04 C07D413/14 C07D417/14 C07D471/04 C07D487/04

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Quick Facts

Patent No.: US 9,662,311
App. No.: 14/900,139
Granted: May 30, 2017
Kind: B2

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Abstract

The invention relates to substituted bicyclic compounds, which are useful for inhibition of BET protein function by binding to bromodomains, pharmaceutical compositions comprising these compounds, and use of the compounds and compositions in therapy.

Claims (259)

1. A compound of formula:

or stereoisomer, tautomer, pharmaceutically acceptable salt, or hydrate thereof, wherein:

the A-B bicyclic ring is optionally substituted with one or more groups independently selected from deuterium, —NH 2 , —OH, alkyl(C 1 -C 6 ), thioalkyl(C 1 -C 6 ), and alkoxy(C 1 -C 6 );

R f is selected from hydrogen, deuterium, —NH 2 , amino, heterocycle(C 4 -C 7 ), carbocycle(C 4 -C 7 ), halogen, —CN, —OH, —CF 3 , sulfone, sulfoxide, sulfonamide, alkyl(C 1 -C 6 ), thioalkyl(C 1 -C 6 ), alkenyl(C 1 -C 6 ), alkoxy(C 1 -C 6 ), ketone(C 1 -C 6 ), ester, urea, carboxylic acid, carbamate, and amide(C 1 -C 6 );

D 1 is selected from isoxazole and pyrazole optionally substituted with one or more groups independently selected from deuterium, alkyl(C 1 -C 4 ), —OH, alkoxy(C 1 -C 4 ), amino, halogen, amide, —CF 3 , CN, —OCF 3 , —N 3 , ketone (C 1 -C 4 ), —S(O)Alkyl(C 1 -C 4 ), —SO 2 alkyl(C 1 -C 4 ), -thioalkyl(C 1 -C 4 ), carboxyl, and/or ester,

wherein said alkyl(C 1 -C 4 ), alkoxy(C 1 -C 4 ), amino, amide, ketone (C 1 -C 4 ), —S(O)Alkyl(C 1 -C 4 ), —SO 2 alkyl(C 1 -C 4 ), -thioalkyl(C 1 -C 4 ), and ester may be optionally substituted with F, Cl, Br, —OH, —NH 2 , —NHMe, —NMe 2 , —OMe, —SMe, oxo, and/or thio-oxo;

X is optionally present, and if present, is selected from —(NH)—, —O—, —NHCR x R y —, —NHSO 2 —, —CR x R y NH—, or —NH 2 and R 3 is absent; and

R 3 is selected from isoxazolyl, oxazolyl, pyrazolyl, pyridyl, pyridonyl, thiazolyl, isothiazolyl, pyrimidinyl, thiozolyl, pyrazinyl, pyridazinyl, azetidinyl, pyrrolidyl, piperidinyl, morpholinyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl, optionally substituted with one or more groups independently selected from deuterium, alkyl(C 1 -C 4 ), —OH, alkoxy(C 1 -C 4 ), amino, halogen, amide, —CF 3 , CN, —OCF 3 , —N 3 , ketone (C 1 -C 4 ), —S(O)Alkyl(C 1 -C 4 ), —SO 2 alkyl(C 1 -C 4 ), -thioalkyl(C 1 -C 4 ), carboxyl, and/or ester,

2. The compound of claim 1 , wherein D 1 is

and

X is absent.

3. A compound of formula:

or a stereoisomer, tautomer, pharmaceutically acceptable salt, or hydrate thereof, wherein:

the A-B bicyclic ring is optionally substituted with one or more groups independently selected from deuterium, —NH 2 , —OH, alkyl(C 1 -C 6 ), thioalkyl(C 1 -C 6 ), and alkoxy(C 1 -C 6 );

X is optionally present, and if present, is selected from —(NH)—, —O—, —NHCR x R y —, —NHSO 2 —, —CR x R y NH—, or —NH 2 and R 3 is absent; and

4. The compound of claim 3 , wherein D 1 is

and

X is absent.

5. A compound selected from:

4,4′-(1H-benzo[d]imidazole-4,6-diyl)bis(3,5-dimethylisoxazole);

3-(6-(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-4-yl)benzonitrile;

4,4′-(quinazoline-2,4-diyl)bis(3,5-dimethylisoxazole);

N-benzyl-6-(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-4-amine;

N-benzyl-2-(3,5-dimethylisoxazol-4-yl)quinazolin-4-amine;

4,4′-(2-methyl-1H-benzo[d]imidazole-4,6-diyl)bis(3,5-dimethylisoxazole);

6-(3,5-dimethylisoxazol-4-yl)-N-phenyl-1H-benzo[d]imidazol-4-amine;

4,4′-(imidazo[1,2-a]pyridine-6,8-diyl)bis(3,5-dimethylisoxazole);

3,5-dimethyl-4-(4-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

4,4′-(imidazo[1,2-a]pyrazine-6,8-diyl)bis(3,5-dimethylisoxazole);

6,8-bis(3,5-dimethylisoxazol-4-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one;

2-(3,5-dimethylisoxazol-4-yl)-6,7-dimethoxy-N-phenylquinazolin-4-amine;

6,8-bis(3,5-dimethylisoxazol-4-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine;

3,5-dimethyl-4-(6-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-4-yl)isoxazole;

6-(3,5-dimethylisoxazol-4-yl)-N-phenyl-[1,2,4]triazolo[4,3-a]pyridin-8-amine;

3,5-dimethyl-4-(4-(1-methyl-1H-pyrazol-5-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

4,4′-([1,2,4]triazolo[1,5-a]pyridine-6,8-diyl)bis(3,5-dimethylisoxazole);

4-(4-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

3,5-dimethyl-4-(4-(2-(trifluoromethyl)phenyl)-1H-benzo[d]imidazol-6-yl)isoxazole;

3,5-dimethyl-4-(4-(4-methylpyridin-3-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

4,4′-(1H-indazole-5,7-diyl)bis(3,5-dimethylisoxazole);

3,5-dimethyl-4-(4-(pyrimidin-5-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

3,5-dimethyl-4-(4-(1-methyl-1H-indazol-4-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

N-benzyl-6-(3,5-dimethylisoxazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-8-amine;

6-(3,5-dimethylisoxazol-4-yl)-N-(4-methoxyphenyl)-1H-benzo[d]imidazol-4-amine;

3,5-dimethyl-4-(4-(4-methylthiazol-5-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

3,5-dimethyl-4-(4-(2-methylpyridin-3-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

1-(2-(6-(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-4-yl)phenyl)-N,N-dimethylmethanamine;

3,5-dimethyl-4-(4-(1-methyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

4,6-bis(3,5-dimethylisoxazol-4-yl)-N-methyl-1H-benzo[d]imidazol-2-amine;

N-benzyl-4,6-bis(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-2-amine;

6-(3,5-dimethylisoxazol-4-yl)-N-(3-fluorophenyl)-1H-benzo[d]imidazol-4-amine;

6-(3,5-dimethylisoxazol-4-yl)-N-(3-methoxyphenyl)-1H-benzo[d]imidazol-4-amine;

4,4′-(2-(trifluoromethyl)-1H-benzo[d]imidazole-4,6-diyl)bis(3,5-dimethylisoxazole);

6-(3,5-dimethylisoxazol-4-yl)-N-(pyridin-3-ylmethyl)-1H-benzo[d]imidazol-4-amine;

3-(6-(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-4-yl)benzamide;

6-(3,5-dimethylisoxazol-4-yl)-N-((1,3,5-trimethyl-1H-pyrazol-4-yl)methyl)-1H-benzo[d]imidazol-4-amine;

6-(3,5-dimethylisoxazol-4-yl)-N-(4-fluorobenzyl)-1H-benzo[d]imidazol-4-amine;

6-(3,5-dimethylisoxazol-4-yl)-N-((3,5-dimethylisoxazol-4-yl)methyl)-1H-benzo[d]imidazol-4-amine;

N-(4-chlorophenyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-4-amine;

3,5-dimethyl-4-(2-methyl-4-(2-methylpyridin-3-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

N-(6-(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-4-yl)-3,5-dimethylisoxazol-4-amine;

6-(3,5-dimethylisoxazol-4-yl)-N-(pyrimidin-2-yl)-1H-benzo[d]imidazol-4-amine;

N-(6-(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-4-yl)-4-methylisoxazol-3-amine;

4,4′-(2-isopropyl-1H-benzo[d]imidazole-4,6-diyl)bis(3,5-dimethylisoxazole);

4,4′-(2-ethoxy-1H-benzo[d]imidazole-4,6-diyl)bis(3,5-dimethylisoxazole);

6-(3,5-dimethylisoxazol-4-yl)-N-(pyridin-2-ylmethyl)-1H-benzo[d]imidazol-4-amine;

4-(4-(2-methoxypyridin-3-yl)-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

3,5-dimethyl-4-(2-methyl-4-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

3,5-dimethyl-4-(2-methyl-4-(4-(trifluoromethyl)pyridin-3-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

4-(4-(2-methoxy-5-methylphenyl)-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

3,5-dimethyl-4-(2-methyl-7-(3-methylisothiazol-4-yl)-1H-benzo[d]imidazol-5-yl)isoxazole;

3,5-dimethyl-4-(2-methyl-4-(4-methylpyridin-3-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

4,4′-(1-methyl-1H-indazole-5,7-diyl)bis(3,5-dimethylisoxazole);

4,4′-(2-methyl-2H-indazole-5,7-diyl)bis(3,5-dimethylisoxazole);

3-(6-(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-4-yl)pyridin-2(1H)-one;

3-(6-(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-4-yl)-2-methylbenzonitrile;

3-(6-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)-4-methylbenzonitrile;

3,5-dimethyl-4-(2-methyl-4-(2-(trifluoromethyl)pyridin-3-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

4-(4-(1,3-dimethyl-1H-pyrazol-4-yl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

3-(6-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)isonicotinonitrile;

6-(3,5-dimethylisoxazol-4-yl)-N-(pyrazin-2-yl)-1H-benzo[d]imidazol-4-amine;

6-(3,5-dimethylisoxazol-4-yl)-2-methyl-N-(3-methylpyridin-2-yl)-1H-benzo[d]imidazol-4-amine;

N-(2-(6-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)phenyl)acetamide;

4,6-bis(3,5-dimethylisoxazol-4-yl)-N-(pyridin-3-ylmethyl)-1H-benzo[d]imidazol-2-amine;

4-(4-(1,5-dimethyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

4-(5-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-7-yl)-N,3-dimethylisoxazole-5-carboxamide;

5-(6-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)-6-methylpyridin-2-amine;

3,5-dimethyl-4-(2-methyl-4-(2-(methylsulfonyl)phenyl)-1H-benzo[d]imidazol-6-yl)isoxazole;

3,5-dimethyl-4-(7-(2-methylpyridin-3-yl)-1H-indazol-5-yl)isoxazole;

2-(6-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)benzonitrile;

4-(4-(4-methoxypyridin-3-yl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

3-(6-(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-4-yl)-2-methylbenzamide;

3-(6-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)-4-methylbenzamide;

3-(6-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)-4-methylbenzoic acid;

4,4′-(2-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazole-5,7-diyl)bis(3,5-dimethylisoxazole);

3,5-dimethyl-4-(2-methyl-4-(2-(trifluoromethoxy)phenyl)-1H-benzo[d]imidazol-6-yl)isoxazole;

3,5-dimethyl-4-(2-methyl-4-(2-(trifluoromethyl)phenyl)-1H-benzo[d]imidazol-6-yl)isoxazole;

3,5-dimethyl-4-(2-methyl-4-(pyridin-3-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

4-(4-(5-fluoro-2-(trifluoromethyl)phenyl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

4-(2-ethoxy-4-(2-methylpyridin-3-yl)-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

3-(6-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)pyridin-2-amine;

2-(6-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)-6-fluorobenzonitrile;

3,5-dimethyl-4-(2-methyl-4-(3-methylpyridin-2-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

3,5-dimethyl-4-(2-methyl-4-(pyrazin-2-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

3,5-dimethyl-4-(2-methy-4-(6-methylpyridazin-3-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

4,4′-(1H-indazole-4,6-diyl)bis(3,5-dimethylisoxazole);

3,5-dimethyl-4-(2-methyl-4-phenyl-1H-benzo[d]imidazol-6-yl)isoxazole;

3,5-dimethyl-4-(2-methyl-4-(o-tolyl)-1H-benzo[d]imidazol-6-yl)isoxazole;

4-(4-(4-chloro-2-methylphenyl)-2-methy-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

4-(4-(2-fluorophenyl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

4-(4-(5-fluoro-2-methylphenyl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

4,4′-(1-methyl-1H-benzo[d]imidazole-5,7-diyl)bis(3,5-dimethylisoxazole);

2-(6-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)-4-fluorobenzonitrile;

4,4′-(1H-benzo[d][1,2,3]triazole-4,6-diyl)bis(3,5-dimethylisoxazole);

3,5-dimethyl-4-(2-methyl-4-(3-(trifluoromethoxy)phenyl)-1H-benzo[d]imidazol-6-yl)isoxazole;

4-(4-(3,5-dimethylpyridin-4-yl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

4-(4-(4,6-dimethylpyrimidin-5-yl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

5-(6-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)-4,6-dimethylpyrimidin-2-amine;

6-(3,5-dimethylisoxazol-4-yl)-N-ethyl-4-(2-methylpyridin-3-yl)-1H-benzo[d]imidazol-2-amine;

5,7-bis(3,5-dimethylisoxazol-4-yl)-2-methylbenzo[d]oxazole;

N-(6-(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-4-yl)-2-methoxybenzenesulfonamide;

4-(4-(benzo[d][1,3]dioxol-5-yl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

3,5-dimethyl-4-(2-methyl-4-(4-methylthiazol-5-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

4-(4-(5-chloro-2-methylphenyl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

4-(4-(2-fluoro-3-methylphenyl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

4-(4-(5-chloro-2-methoxyphenyl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

4-(4-(2-fluoro-5-methoxyphenyl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

4-(4-(2-ethoxypyridin-3-yl)-2-methyl-1H-benzo[d]imidazol-6-yl-3,5-dimethylisoxazole;

4-(4-(isoquinolin-8-yl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

3,5-dimethyl-4-(2-methyl-4-(quinolin-8-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

4-(4-(5-fluoro-2-methoxyphenyl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

3,5-dimethyl-4-(2-methyl-4-(5-methylthiazol-4-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

4-(4-(2-methoxy-4-methylpyridin-3-yl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

3,5-dimethyl-4-(2-methyl-4-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

4,6-bis(3,5-dimethylisoxazol-4-yl)-N,N-dimethyl-1H-benzo[d]imidazol-2-amine;

4-(4-(2-(methoxymethyl)phenyl)-2-methy-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

4-(4-(2-methoxypyridin-3-yl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

3,5-dimethyl-4-(7-(4-methylpyridin-3-yl)-1H-indazol-5-yl)isoxazole;

4-(7-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-indazol-5-yl)-3,5-dimethylisoxazole;

1-(6-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)-5-methylpyrrolidin-2-one;

1-(6-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)piperidin-2-one;

3-(6-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)-2-methylbenzonitrile;

4-(4-(benzo[d]thiazol-5-yl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

4-(4-(5-fluoro-4-methylpyridin-3-yl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

3-(6-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)-2-methylbenzamide;

3,5-dimethyl-4-(7-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-indazol-5-yl)isoxazole;

3,5-dimethyl-4-(7-(2-(trifluoromethyl)pyridin-3-yl)-1H-indazol-5-yl)isoxazole;

3,5-dimethyl-4-(7-(4-(trifluoromethyl)pyridin-3-yl)-1H-indazol-5-yl)isoxazole;

4-(4-(3,5-dichloropyridin-4-yl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

4-(4-(5-fluoro-2-methoxypyridin-3-yl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

4-(4-(3,4-difluoro-2-methylphenyl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

4,6-bis(1,3-dimethyl-1H-pyrazol-4-yl)-2-methyl-1H-benzo[d]imidazole;

2-methyl-4,6-bis(1-methyl-1H-pyrazol-5-yl)-1H-benzo[d]imidazole;

4-(4-(2-methoxy-6-methylpyridin-3-yl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

5-(6-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)benzo[d]oxazole;

4-(4-(benzo[d]isothiazol-5-yl)-2-methy-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

3,5-dimethyl-4-(2-methyl-4-(naphthalen-1-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

4,4′-(2-methyl-1H-benzo[d]imidazole-4,6-diyl)bis(3-methylisothiazole);

4,4′-(3-methyl-1H-indole-4,6-diyl)bis(3,5-dimethylisoxazole);

2-methyl-4,6-bis(4-methylthiophen-3-yl)-1H-benzo[d]imidazole;

6-(3,5-dimethylisoxazol-4-yl)-N-phenethyl-1H-benzo[d]imidazol-4-amine;

6-(3,5-dimethylisoxazol-4-yl)-2-methyl-N-(2-methylpyridin-3-yl)-1H-benzo[d]imidazol-4-amine;

4-(4-(2-chlorophenyl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

4-(4-(benzo[b]thiophen-2-yl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

6-(3,5-dimethylisoxazol-4-yl)-2-methyl-N-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-4-amine;

1-(6-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)azetidin-2-one;

3,5-dimethyl-4-(2-methyl-4-phenoxy-1H-benzo[d]imidazol-6-yl)isoxazole;

6,8-bis(3,5-dimethylisoxazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one;

2-((4,6-bis(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-2-yl)amino)ethanol;

6-(3,5-dimethylisoxazol-4-yl)-N,N-diphenethyl-1H-benzo[d]imidazol-4-amine;

4-(4-(2-fluoro-3-methoxyphenyl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

3,5-dimethyl-4-(2-methyl-4-(quinoxalin-6-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

3,5-dimethyl-4-(2-methyl-4-(3-(methylsulfonyl)phenyl)-1H-benzo[d]imidazol-6-yl)isoxazole;

3,5-dimethyl-4-(2-methyl-4-((2-methylpyridin-3-yl)oxy)-1H-benzo[d]imidazol-6-yl)isoxazole;

4-(4-([1,2,4]triazolo[4,3-a]pyridin-6-yl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

4-(4-(2-fluoro-5-(trifluoromethyl)phenyl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

(E)-3,5-dimethyl-4-(2-methyl-4-styryl-1H-benzo[d]imidazol-6-yl)isoxazole;

4,4′-(quinoxaline-5,7-diyl)bis(3,5-dimethylisoxazole);

4,6-di(furan-3-yl)-2-methyl-1H-benzo[d]imidazole;

3,5-dimethyl-4-(2-methyl-4-phenethyl-1H-benzo[d]imidazol-6-yl)isoxazole;

4-(4-(2-chloro-5-(trifluoromethyl)phenyl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

3,5-dimethyl-4-(2-methyl-4-(quinolin-3-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

2-methyl-4,6-di(1H-pyrrol-3-yl)-1H-benzo[d]imidazole;

N-(6-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)benzamide;

3,5-dimethyl-4-(2-methyl-4-(4-methylthiophen-3-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

4,6-bis(1,4-dimethyl-1H-pyrazol-5-yl)-2-methyl-1H-benzo[d]imidazole;

5,5′-(2-methyl-1H-benzo[d]imidazole-4,6-diyl)bis(2,4-dimethylthiazole);

4-(4-(1,4-dimethyl-1H-pyrazol-5-yl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

4-(4-(2,4-dimethylthiazol-5-yl)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

4-(4-((4-methoxypyridin-3-yl)oxy)-2-methyl-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

3-((6-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)oxy)-4-methylbenzonitrile;

4-(6-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)morpholine;

3-((6-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)oxy)-4-methylbenzamide;

3-((6-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)oxy)-4-methylbenzoic acid;

4,4′-(2-methyl-3H-imidazo[4,5-b]pyridine-5,7-diyl)bis(3,5-dimethylisoxazole);

4-(6-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)-3-methylmorpholine;

4-(6-(1,4-dimethyl-1H-pyrazol-yl)-2-methyl-1H-benzo[d]imidazol-4-yl)-3,5-dimethylisoxazole;

4,4′-(3-methyl-1H-indazole-4,6-diyl)bis(3,5-dimethylisoxazole);

4-(4-(3,5-dimethyl-1H-pyrazol-4-yl)-3-methyl-1H-indazol-6-yl)-3,5-dimethylisoxazole;

3,5-dimethyl-4-(2-(4-methylpiperazin-1-yl)-4-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

3,5-dimethyl-4-(1-methyl-7-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-5-yl)isoxazole;

3,5-dimethyl-4-(2-(4-methylpiperazin-1-yl)-4-(2-methylpyridin-3-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

4-(6-(3,5-dimethylisoxazol-4-yl)-4-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-2-yl)morpholine;

6-(3,5-dimethylisoxazol-4-yl)-N-(1-methylpiperidin-4-yl)-4-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-2-amine;

3-(6-(3,5-dimethylisoxazol-4-yl)-2-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-4-yl)-4-methylbenzonitrile;

3,5-dimethyl-4-(2-(methylthio)-4-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

3,5-dimethyl-4-(1-methyl-2-(methylthio)-4-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

3-(6-(3,5-dimethylisoxazol-4-yl)-2-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-4-yl)-4-methylbenzamide;

6-(3,5-dimethylisoxazol-4-yl)-N-(tetrahydro-2H-pyran-4-yl)-4-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-2-amine;

3,5-dimethyl-4-(1-methyl-2-(methylthio)-7-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-5-yl)isoxazole;

4,4′-(7-bromo-1H-benzo[d]imidazole-4,6-diyl)bis(3,5-dimethylisoxazole);

3-(6-(3,5-dimethylisoxazol-4-yl)-2-morpholino-1H-benzo[d]imidazol-4-yl)-4-methylbenzonitrile;

3,5-dimethyl-4-(2-(methylsulfinyl)-7-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-5-yl)isoxazole;

3,5-dimethyl-4-(2-(methylsulfonyl)-7-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-5-yl)isoxazole;

4-(6-(3,5-dimethylisoxazol-4-yl)-4-(4-methylpyridin-3-yl)-1H-benzo[d]imidazol-2-yl)morpholine;

3-(6-(3,5-dimethylisoxazol-4-yl)-2-morpholino-1H-benzo[d]imidazol-4-yl)-4-methylbenzamide;

3-(6-(3,5-dimethylisoxazol-4-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)-1H-benzo[d]imidazol-4-yl)-4-methylbenzonitrile;

3,5-dimethyl-4-(2-(4-methylpiperazin-1-yl)-4-(4-methylpyridin-3-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

3-(6-(3,5-dimethylisoxazol-4-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)-1H-benzo[d]imidazol-4-yl)-4-methylbenzamide;

6-(3,5-dimethylisoxazol-4-yl)-4-(4-methylpyridin-3-yl)-N-(tetrahydro-2H-pyran-4-yl)-1H-benzo[d]imidazol-2-amine;

3-(6-(3,5-dimethylisoxazol-4-yl)-2-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-4-yl)-2-methylbenzonitrile;

3-(6-(3,5-dimethylisoxazol-4-yl)-2-morpholino-1H-benzo[d]imidazol-4-yl)-2-methylbenzonitrile;

3-(6-(3,5-dimethylisoxazol-4-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)-1H-benzo[d]imidazol-4-yl)-2-methylbenzonitrile;

3-(6-(3,5-dimethylisoxazol-4-yl)-2-((1-methylpiperidin-4-yl)amino)-1H-benzo[d]imidazol-4-yl)-4-methylbenzonitrile;

3-(6-(3,5-dimethylisoxazol-4-yl)-2-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-4-yl)-2-methylbenzamide;

3-(6-(3,5-dimethylisoxazol-4-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)-1H-benzo[d]imidazol-4-yl)-2-methylbenzamide;

3-(6-(3,5-dimethylisoxazol-4-yl)-2-morpholino-1H-benzo[d]imidazol-4-yl)-2-methylbenzamide;

3-(2-(4-aminopiperidin-1-yl)-6-(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-4-yl)-2-methylbenzonitrile;

3-(2-(benzylamino)-6-(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-4-yl)-4-methylbenzonitrile;

3-(6-(3,5-dimethylisoxazol-4-yl)-2-((pyridin-3-ylmethyl)amino)-1H-benzo[d]imidazol-4-yl)-4-methylbenzonitrile;

N-benzyl-6-(3,5-dimethylisoxazol-4-yl)-4-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-2-amine;

3,5-dimethyl-4-(2-(pyrrolidin-1-yl)-4-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

6-(3,5-dimethylisoxazol-4-yl)-N-methyl-4-(4-methylpyridin-3-yl)-1H-benzo[d]imidazol-2-amine;

3-(6-(3,5-dimethylisoxazol-4-yl)-2-(pyrrolidin-1-yl)-1H-benzo[d]imidazol-4-yl)-4-methylbenzonitrile;

3-(6-(3,5-dimethylisoxazol-4-yl)-2-((1-methylpiperidin-4-yl)amino)-1H-benzo[d]imidazol-4-yl)-2-methylbenzonitrile;

4-(2-(azetidin-1-yl)-4-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole;

(3-(6-(3,5-dimethylisoxazol-4-yl)-2-(pyrrolidin-1-yl)-1H-benzo[d]imidazol-4-yl)-4-methylphenyl)(pyrrolidin-1-yl)methanone;

3-(6-(3,5-dimethylisoxazol-4-yl)-2-((pyridin-3-ylmethyl)amino)-1H-benzo[d]imidazol-4-yl)-4-methylbenzamide;

3-(2-(benzylamino)-6-(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-4-yl)-4-methylbenzamide;

6-(3,5-dimethylisoxazol-4-yl)-N-(pyridin-3-ylmethyl)-4-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-2-amine;

N-benzyl-6-(3,5-dimethylisoxazol-4-yl)-4-(4-methylpyridin-3-yl)-1H-benzo[d]imidazol-2-amine;

6-(3,5-dimethylisoxazol-4-yl)-4-(4-methylpyridin-3-yl)-N-(pyridin-3-ylmethyl)-1H-benzo[d]imidazol-2-amine;

3,5-dimethyl-4-(4-(4-methylpyridin-3-yl)-2-(pyrrolidin-1-yl)-1H-benzo[d]imidazol-6-yl)isoxazole;

3-amino-5-(6-(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-4-yl)-1-methylpyridin-2(1H)-one;

4-(4,6-bis(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-2-yl)morpholine;

4,4′-(5-methoxy-2-methyl-1H-benzo[d]imidazole-4,6-diyl)bis(3,5-dimethylisoxazole);

4,4′-(2-(tetrahydro-2H-pyran-4-yl)-1H-benzo[d]imidazole-4,6-diyl)bis(3,5-dimethylisoxazole);

4,6-bis(3,5-dimethylisoxazol-4-yl)-N-(tetrahydro-2H-pyran-4-yl)-1H-benzo[d]imidazol-2-amine;

3,5-dimethyl-4-(5-(1-methyl-1H-pyrazol-5-yl)-1H-benzo[d]imidazol-7-yl)isoxazole;

4,4′-(2-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazole-4,6-diyl)bis(3,5-dimethylisoxazole);

4,6-bis(3,5-dimethylisoxazol-4-yl)-N-(1-methylpiperidin-4-yl)-1H-benzo[d]imidazol-2-amine;

4,6-bis(3,5-dimethylisoxazol-4-yl)-N-(piperidin-4-yl)-1H-benzo[d]imidazol-2-amine; and

stereoisomers, tautomers, pharmaceutically acceptable salts, and hydrates thereof.

6. A pharmaceutical composition comprising a compound of claim 5 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or hydrate thereof, and a pharmaceutically acceptable carrier.

Assignments (2)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 23, 2016

From: ZENITH CAPITAL CORP.

To: ZENITH EPIGENETICS LTD.

Reel/Frame 041182/0891 →

CHANGE OF NAME Recorded Dec 21, 2016

From: ZENITH EPIGENETICS CORP.

To: ZENITH CAPITAL CORP.

Reel/Frame 041120/0548 →

Continuity (3)

Provisional Application 61911668 · Dec 4, 2013

Provisional Application 61837830 · Jun 21, 2013

Related Publication 20160184273A1 · Jun 30, 2016