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US 7,915,293 B2Granted
Ubiquitin ligase inhibitors
AssigneeRigel Pharmaceuticals, Inc.
InventorsUsha V. Ramesh, Gary Charles Look, Rajinder Singh, Sarkiz D. Issakani
Life of this patent
Estimating the term…
Abstract
This invention describes compounds useful as ubiquitin ligase inhibitors. The compounds of the invention are useful as inhibitors of the biochemical pathways of organisms in which ubiquitination is involved. The invention also provides for pharmaceutical compositions comprising the compounds described in the invention for the treatment of conditions that require inhibition of ubiquitin ligases. Furthermore, the invention provides for methods of inhibiting ubiquitination in a cell comprising contacting a cell in which inhibition of ubiquitination is desired with a compound according to the invention.
Claims14
A compound having the structure:
- or a pharmaceutically acceptable salt thereof, wherein
- R1 is selected from CF3-phenyl, 1-chloro-4-fluorophenyl, 2,4-difluorophenyl, 3,5-dichlorophenyl;
- R2 is H, C1-C6-hydrocarbyl, or aryl;
- R3 is —H, —Cl, or —NO2;
- R4 is —H, —Cl, or —NO2;
- R5 is —H or —NO2;
- R6 is —H or —Cl;
- R7 is —H or —Cl;
- R8 is —H or —Cl;
- R9 is —H or —F;
- R18 is —H, C1-C6-hydrocarbyl, —C(O)R19, —SO2R19, C(O)NHR19, CSNHR19, CNNHR19, or CO2R19;
- R19 is —H, —OH, or C1-C3-hydrocarbyl;
- and
- Y is —O—, —S—, —S(O)—, or —SO2—;
- wherein each of the aryl, and hydrocarbyl group of R2 is optionally substituted by one or more groups selected from halo, —OH, —NH2, C1-C6-hydrocarbyl-C(O)—, oxo, C1-C6-hydrocarbyl-(O)—, mono- to per-halogenated C1-C6-hydrocarbyl-O—, C1-C6-hydrocarbyl, mono- to per-halogenated C1-C6-hydrocarbyl, —CN, —NO2, —NO, —NH2, —NH—C(O)R18, or —SO2;
- and
- provided that the compound is not the following combination:
- R1
- R2
- R3
- R4
- R5
- R6
- R7
- R8
- R9
- 3,5-dichlorophenyl
- H
- Cl
- Cl
- NO2
- H
- Cl
- H
- H.
32 more elements
A compound having the structure:
- or a pharmaceutically acceptable salt thereof, wherein
- R1 and R2 together with the nitrogen atom to which they are both attached form a piperidinyl which is optionally substituted by one or more groups selected from halo, —OH, —NH2, C1-C4-hydrocarbyl-C(O)—, oxo, C1-C3-hydrocarbyl-(O)—, mono- to per-halogenated C1-C3-hydrocarbyl-O—, C1-C3-hydrocarbyl, mono- to per-halogenated C1-C3-hydrocarbyl, aryl-O—, —CN, —NO2, or —SO2;
- R3 is —H, —Cl, or —NO2;
- R4 is —H, —Cl, or —NO2;
- R5 is —H or —NO2;
- R6 is —H or —Cl;
- R7 is —H or —Cl;
- R8 is —H or —Cl;
- R9 is —H or —F;
- and
- Y is —O—, —S—, —S(O)—, or —SO2—.
8 more elements
A compound having the structure:
- or a pharmaceutically acceptable salt thereof, wherein
- R1 is C1-C3-hydrocarbyl-C(═NH)- which is optionally substituted by one or more groups selected from halo, —OH, —NH2, C1-C4-hydrocarbyl-C(O)—, oxo, C1-C3-hydrocarbyl-(O)—, mono- to per-halogenated C1-C3-hydrocarbyl-O—, C1-C3-hydrocarbyl, mono- to per-halogenated C1-C3-hydrocarbyl, aryl-O—, —CN, —NO2, or —SO2;
- R2 is H, C1-C6-hydrocarbyl, or aryl;
- R3 is —H, —Cl, or —NO2;
- R4 is —H, —Cl, or —NO2;
- R5 is —H or —NO2;
- R6 is —H or —Cl;
- R7 is —H or —Cl;
- R8 is —H or —Cl;
- R9 is —H or —F;
- R18 is —H, C1-C6-hydrocarbyl, —C(O)R19, —SO2R19, C(O)NHR19, CSNHR19, CNNHR19, or CO2R19;
- R19 is —H, —OH, or C1-C3-hydrocarbyl;
- and
- Y is —O—, —S—, —S(O)—, or —SO2—;
- wherein each of the aryl, and hydrocarbyl group of R2 is optionally substituted by one or more groups selected from halo, —OH, —NH2, C1-C6-hydrocarbyl-C(O)—, oxo, C1-C6-hydrocarbyl-(O)—, mono- to per-halogenated C1-C6-hydrocarbyl-O—, C1-C6-hydrocarbyl, mono- to per-halogenated C1-C6-hydrocarbyl, —CN, —NO2, —NO, —NH2, —NH—C(O)R18, or —SO2;
- provided that the compound is not one of the following combinations:
- R1
- R2
- R3
- R4
- R5
- R6
- R7
- R8
- R9
- H
- Cl
- Cl
- NO2
- H
- Cl
- H
- H.
30 more elements
A compound having the structure:
- or a pharmaceutically acceptable salt thereof, wherein
- R1 is C4-C10-hydrocarbyl-NH—CO—C6H4- which is optionally substituted by one or more groups selected from halo, —OH, —NH2, C1-C4-hydrocarbyl-C(O)—, oxo, C1-C3-hydrocarbyl-(O)—, mono- to per-halogenated C1-3-hydrocarbyl-O—, C1-C3-hydrocarbyl, mono- to per-halogenated C1-C3-hydrocarbyl, aryl-O—, —CN, —NO2, or —SO2;
- R2 is H, C1-C6-hydrocarbyl, or aryl;
- R3 is —H, —Cl, or —NO2;
- R4 is —H, —Cl, or —NO2;
- R5 is —H or —NO2;
- R6 is —H or —Cl;
- R7 is —H or —Cl;
- R8 is —H or —Cl;
- R9 is —H or —F;
- R18 is —H, C1-C6-hydrocarbyl, —C(O)R19, —SO2R19, C(O)NHR19, CSNHR19, CNNHR19, or CO2R19;
- R19 is —H, —OH, or C1-C3-hydrocarbyl;
- and
- Y is —O—, —S—, —S(O)—, or —SO2—;
- wherein each of the aryl, and hydrocarbyl group of R2 is optionally substituted by one or more groups selected from halo, —OH, —NH2, C1-C6-hydrocarbyl-C(O)—, oxo, C1-C6-hydrocarbyl-(O)—, mono- to per-halogenated C1-C6-hydrocarbyl-O—, C1-C6-hydrocarbyl, mono- to per-halogenated C1-C6-hydrocarbyl, —CN, —NO2, —NO, —NH2, —NH—C(O)R18, or —SO2.
12 more elements
A compound having the structure:
- or a pharmaceutically acceptable salt thereof, wherein R1 is selected from:
- —CH3
- CH3CH2—
- HC≡C—C(CH3)2—
- CN—(CH2)2—
- R2 is H, C1-C6-hydrocarbyl, or aryl;
- R3 is —H, —Cl, or —NO2;
- R4 is —H, —Cl, or —NO2;
- R5 is —H or —NO2;
- R6 is —H or —Cl;
- R7 is —H or —Cl;
- R8 is —H or —Cl;
- R9 is —H or —F;
- R18 is —H, C1-C6-hydrocarbyl, —C(O)R19, —SO2R19, C(O)NHR19, CSNHR19, CNNHR19, or CO2R19;
- R19 is —H, —OH, or C1-C3-hydrocarbyl;
- and
- Y is —O—, —S—, —S(O)—, or —SO2—;
- wherein each of the aryl, and hydrocarbyl group of R2 is optionally substituted by one or more groups selected from halo, —OH, —NH2, C1-C6-hydrocarbyl-C(O)—, oxo, C1-C6-hydrocarbyl-(O)—, mono- to per-halogenated C1-C6-hydrocarbyl-O—, C1-C6-hydrocarbyl, mono- to per-halogenated C1-C6-hydrocarbyl, —CN, —NO2, —NO, —NH2, —NH—C(O)R18, or —SO2;
- and
- provided that the compound is not one of the following combinations:
- R1
- R2
- R3
- R4
- R5
- R6
- R7
- R8
- R9
- H
- Cl
- Cl
- NO2
- H
- Cl
- H
- H
- H
- Cl
- Cl
- NO2
- H
- Cl
- H
- H
- H
- Cl
- H
- NO2
- H
- Cl
- H
- H
- 3,5-dichlorophenyl
- H
- Cl
- Cl
- NO2
- H
- Cl
- H
- H
- 3-chloro,4-fluorophenyl
- H
- Cl
- Cl
- NO2
- H
- Cl
- H
- H
- cyclohexyl
- H
- H
- H
- NO2
- H
- H
- H
- H
- CH3
- H
- H
- H
- NO2
- H
- H
- H
- H.
86 more elements
A compound having the structure:
- or a pharmaceutically acceptable salt thereof, wherein
- R1 is C1-6-hydrocarbyl, C5-C12-heterocyclyl-C0-C6-hydrocarbyl, aryl-C1-C6-hydrocarbyl, C5-C12-heteroaryl-C0-C6-hydrocarbyl, —C(═X)-L1-R10, C4-C10-hydrocarbyl-NH—C(O)—C6H4—, aryl-oxy-C1-C6-hydrocarbyl-, aryl-oxy-aryl-SO2—, (CH3)2N—C1-C6-hydrocarbyl, (NH2)(NH)C—NH—(CH2)3—CH(NH2CO)—, or ═C(R13)(R14);
- X is ═O, ═S, or ═NH;
- L1 is a covalent bond, —NH—, —O—, —S—, or C1-C3-hydrocarbyl;
- R10 is —C1-C6-hydrocarbyl, C5-C12-heterocyclyl, aryl, or C5-C12-heteroaryl;
- R2 is selected from H—, —CH3, —Cl, CH3CH2—,
- R3 is —H, —Cl, or —NO2;
- R4 is —H, —Cl, or —NO2;
- R5 is —H or —NO2;
- R6 is —H or —Cl;
- R7 is —H or —Cl;
- R8 is —H or —Cl;
- R9 is —H or —F;
- R18 is —H, C1-C6-hydrocarbyl, —C(O)R19, —SO2R19, C(O)NHR19, CSNHR19, CNNHR19, or CO2R19;
- R19 is —H, —OH, or C1-C3-hydrocarbyl;
- and
- Y is —O—, —S—, —S(O)—, or —SO2—;
- wherein each of the aryl, heterocyclyl, and hydrocarbyl group of R1 is optionally substituted by one or more groups selected from halo, —OH, —NH2, C1-C6-hydrocarbyl-C(O)—, oxo, C1-C6-hydrocarbyl-(O)—, mono- to per-halogenated C1-C6-hydrocarbyl-O—, C1-C6-hydrocarbyl, mono- to per-halogenated C1-C6-hydrocarbyl, —CN, —NO2, —NO, —NH2, —NH—C(O)R18, or —SO2;
- and
- provided that the compound is not one of the following combinations:
- R1
- R2
- R3
- R4
- R5
- R6
- R7
- R8
- R9
- H
- Cl
- Cl
- NO2
- H
- Cl
- H
- H
- H
- Cl
- Cl
- NO2
- H
- Cl
- H
- H
- H
- Cl
- H
- NO2
- H
- Cl
- H
- H
- —CH3
- NO2
- H
- NO2
- H
- H
- H
- H
- —CH3
- —CH3
- Cl
- H
- NO2
- H
- H
- H
- H
- H
- H
- H
- NO2
- H
- H
- H
- H
- 3,5-dichlorophenyl
- H
- Cl
- Cl
- NO2
- H
- Cl
- H
- H
- 3-chloro,4-fluorophenyl
- H
- Cl
- Cl
- NO2
- H
- Cl
- H
- H
- cyclohexyl
- H
- H
- H
- NO2
- H
- H
- H
- H
- CH3
- CH3
- H
- H
- NO2
- H
- H
- H
- H
- CH3
- H
- H
- H
- NO2
- H
- H
- H
- H
- CH3CH2
- CH3
- Cl
- Cl
- NO2
- H
- H
- H
- H
- CH3C═O
- H
- H
- H
- NO2
- H
- H
- H
- H.
138 more elements
A compound having the structure:
- or a pharmaceutically acceptable salt thereof, wherein
- R1 and R2 together with the nitrogen to which they are both covalently bound form a moiety selected from
- R3 is —H, —Cl, or —NO2;
- R4 is —H, —Cl, or —NO2;
- R5 is —H or —NO2;
- R6 is —H or —Cl;
- R7 is —H or —Cl;
- R8 is —H or —Cl;
- R9 is —H or —F;
- and
- Y is —O—, —S—, —S(O)—, or —SO2—.
8 more elements
A compound having the structure:
- or a pharmaceutically acceptable salt thereof, wherein
- R1 and R2 together are
- R3 is —H, —Cl, or —NO2;
- R4 is —H, —Cl, or —NO2;
- R5 is —H or —NO2;
- R6 is —H or —Cl;
- R7 is —H or —Cl;
- R8 is —H or —Cl;
- R9 is —H or —F;
- and
- Y is —O—, —S—, —S(O)—, or —SO2—.
8 more elements
A compound selected from:
- 4-(2-chloro-6-nitrophenoxy)-N-(4-fluorophenyl)benzenesulfonamide;
- 4-{[4-(2-chloro-6-nitrophenoxy)phenyl]sulfonyl}morpholine;
- {3-chloro-2-[4-(morpholin-4-ylsulfonyl)phenoxy]phenyl}amine;
- 4-(2-amino-6-chlorophenoxy)-N-(4-fluorophenyl)benzenesulfonamide;
- N-{3-chloro-2-[4-(morpholin-4-ylsulfonyl)phenoxy]phenyl}-2,2,2-trifluoroacetamide;
- 4-(2-chloro-6-nitrophenoxy)-N-(1-phenylethyl)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide;
- 4-(2-chloro-6-nitrophenoxy)-N-(1,1-dimethylpropyl)benzenesulfonamide;
- N-(3-aminopropyl)-4-(2-chloro-6-nitrophenoxy)-N-methylbenzenesulfonamide;
- 4-{[3,5-dichloro-4-(4-nitrophenoxy)phenyl]sulfonyl}morpholine;
- 1-{[3,5-dichloro-4-(4-nitrophenoxy)phenyl]sulfonyl}piperidine;
- 1-{[3,5-dichloro-4-(4-nitrophenoxy)phenyl]sulfonyl}pyrrolidine;
- 4-{[3,5-dichloro-4-(4-nitrophenoxy)phenyl]sulfonyl}-2,6-dimethylmorpholine;
- 3,5-dichloro-N-(3-chloro-4-fluorophenyl)-4-(2-chloro-4-nitrophenoxy)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(2,4-difluorophenyl)benzenesulfonamide;
- 1-{[3,5-dichloro-4-(2-chloro-4-nitrophenoxy)phenyl]sulfonyl}-3,5-dimethylpiperidine;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(4-fluorophenyl)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(3,5-dichlorophenyl)benzenesulfonamide;
- 4-chloro-N-{[3,5-dichloro-4-(2-chloro-4-nitrophenoxy)phenyl]sulfonyl}benzene-carboximidamide;
- 2-chloro-N-{[3,5-dichloro-4-(2-chloro-4-nitrophenoxy)phenyl]sulfonyl}ethanimidamide;
- N-{[3,5-dichloro-4-(4-nitrophenoxy)phenyl]sulfonyl}pyridine-3-carboximidamide;
- N-{[3,5-dichloro-4-(4-nitrophenoxy)phenyl]sulfonyl}pyridine-4-carboximidamide;
- N-{[3,5-dichloro-4-(4-nitrophenoxy)phenyl]sulfonyl}ethanimidamide;
- 4-(2-chloro-6-nitrophenoxy)benzenesulfonamide;
- 4-(2-chloro-6-nitrophenoxy)-N-[(1E)-(dimethylamino)methylene]benzenesulfonamide;
- 4-(2-chloro-6-nitrophenoxy)-N-(1,1-dimethylpropyl)benzenesulfonamide;
- N-(3-aminopropyl)-4-(2-chloro-6-nitrophenoxy)-N-methylbenzenesulfonamide;
- 4-{[3,5-dichloro-4-(4-nitrophenoxy)phenyl]sulfonyl}morpholine;
- 1-{[3,5-dichloro-4-(4-nitrophenoxy)phenyl]sulfonyl}piperidine;
- 1-{[3,5-dichloro-4-(4-nitrophenoxy)phenyl]sulfonyl}pyrrolidine;
- 4-{[3,5-dichloro-4-(4-nitrophenoxy)phenyl]sulfonyl}-2,6-dimethylmorpholine;
- 4-{[3,5-dichloro-4-(2-chloro-4-nitrophenoxy)phenyl]sulfonyl}morpholine;
- 3,5-dichloro-N-(3-chloro-4-fluorophenyl)-4-(2-chloro-4-nitrophenoxy)benzene-sulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(2,4-difluorophenyl)benzenesulfonamide;
- 4-{[3,5-dichloro-4-(2-chloro-4-nitrophenoxy)phenyl]sulfonyl}-2,6-dimethylmorpholine;
- 1-{[3,5-dichloro-4-(2-chloro-4-nitrophenoxy)phenyl]sulfonyl}-4-methylpiperidine;
- 1-{[3,5-dichloro-4-(2-chloro-4-nitrophenoxy)phenyl]sulfonyl}-3,5-dimethylpiperidine;
- 1-{[3,5-dichloro-4-(2-chloro-4-nitrophenoxy)phenyl]sulfonyl}piperidine;
- 1-{[3,5-dichloro-4-(2-chloro-4-nitrophenoxy)phenyl]sulfonyl}pyrrolidine;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(4-fluorophenyl)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(3,5-dichlorophenyl)benzenesulfonamide;
- 3,5-dichloro-N-(3-chloro-2-methylphenyl)-4-(2-chloro-4-nitrophenoxy)benzene-sulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-{[(3,4-dichlorophenyl)amino]carbonothioyl}benzene sulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-[(1Z)-[(4-chlorophenyl)amino](hydroxy-amino)methylene]benzenesulfonamide;
- N-{[3,5-dichloro-4-(2-chloro-4-nitrophenoxy)phenyl]sulfonyl}pyridine-4-carboximidamide;
- 2-chloro-N-{[3,5-dichloro-4-(4-nitrophenoxy)phenyl]sulfonyl}ethanimidamide;
- 4-chloro-N-{[3,5-dichloro-4-(4-nitrophenoxy)phenyl]sulfonyl}benzenecarboximidamide;
- N-(3-bromophenyl)-3,5-dichloro-4-(2-chloro-4-nitrophenoxy)benzenesulfonamide;
- 4-[2-(aminomethyl)-3-chlorophenoxy]-N-phenylbenzenesulfonamide;
- {2-chloro-6-[4-(morpholin-4-ylsulfonyl)phenoxy]benzyl}amine;
- 4-[2-(aminomethyl)-3-chlorophenoxy]-N-(4-chlorobenzyl)benzenesulfonamide;
- 4-[2-(aminomethyl)-3-chlorophenoxy]-N-benzyl-N-methylbenzenesulfonamide;
- {2-[4-(morpholin-4-ylsulfonyl)phenoxy]-1,3-phenylene}dimethanamine;
- 4-[2,6-bis(aminomethyl)phenoxy]-N-phenylbenzenesulfonamide;
- 4-(2-chloro-6-nitrophenoxy)-N-(4-fluorophenyl)benzenesulfonamide;
- p4-{[4-(2-chloro-6-nitrophenoxy)phenyl]sulfonyl}morpholine;
- 3-chloro-2-[4-(morpholin-4-ylsulfonyl)phenoxy]aniline;
- 4-(2-amino-6-chlorophenoxy)-N-(4-fluorophenyl)benzenesulfonamide;
- N-{3-chloro-2-[4-(morpholin-4-ylsulfonyl)phenoxy]phenyl}-2,2,2-trifluoroacetamide;
- 4-(2-chloro-6-nitrophenoxy)-N-(1-phenylethyl)benzenesulfonamide;
- 4-[2-(aminomethyl)-3-chlorophenoxy]-N-(2,4-dichlorophenyl)benzenesulfonamide;
- 3,5-dichloro-N-[(1E)-(dimethylamino)methylene]-4-(4-nitrophenoxy)benzene-sulfonamide;
- 4-[2-(aminomethyl)-3-chlorophenoxy]-N-(1,2,2-trimethylpropyl)benzenesulfonamide;
- 4-[2-(aminomethyl)-3-chlorophenoxy]-N-phenylbenzenesulfonamide;
- 1-{2-chloro-6-[4-(morpholin-4-ylsulfonyl)phenoxy]phenyl}methanamine;
- 4-[2-(aminomethyl)-3-chlorophenoxy]-N-(4-chlorobenzyl)benzenesulfonamide;
- 4-[2-(aminomethyl)-3-chlorophenoxy]-N-benzyl-N-methylbenzenesulfonamide;
- {2-[4-(morpholin-4-ylsulfonyl)phenoxy]-1,3-phenylene}dimethanamine;
- 4-[2,6-bis(aminomethyl)phenoxy]-N-phenylbenzenesulfonamide;
- 3,5-dichloro-N-[(1E)-(dimethylamino)methylene]-4-(4-nitrophenoxy)benzene-sulfonamide;
- 4-[2-(aminomethyl)-3-chlorophenoxy]-N-(1,2,2-trimethylpropyl)benzenesulfonamide;
- N-(3-fluorophenyl)-4-(4-nitrophenoxy)benzenesulfonamide;
- 4,4′-oxybis(N,N-diethylbenzenesulfonamide);
- 1-{[4-(4-nitrophenoxy)phenyl]sulfonyl}piperidine;
- 1-methyl-4-{[4-(4-nitrophenoxy)phenyl]sulfonyl}piperazine;
- 4-chloro-N-{4-[4-(morpholin-4-ylsulfonyl)phenoxy]phenyl}benzenesulfonamide;
- N-cyclohexyl-4-(4-nitrophenoxy)benzenesulfonamide;
- 4-(4-nitrophenoxy)-N-phenylbenzenesulfonamide;
- 4,4′-oxybis[N-(3-nitrophenyl)benzenesulfonamide];
- N-(3-nitrophenyl)-4-phenoxybenzenesulfonamide;
- N-(3-acetylphenyl)-4-(4-nitrophenoxy)benzenesulfonamide;
- N-(2-methoxyphenyl)-4-(4-nitrophenoxy)benzenesulfonamide;
- 1-{[4-(4-nitrophenoxy)phenyl]sulfonyl}indoline;
- 1,1′-[oxybis(4,1-phenylenesulfonyl)]dipiperidine;
- 4-{[4-(4-nitrophenoxy)phenyl]sulfonyl}morpholine;
- N,N-diethyl-4-(4-nitrophenoxy)benzenesulfonamide;
- 4,4′-oxybis(N,N-diethylbenzenesulfonamide);
- 1,1′-[oxybis(4,1-phenylenesulfonyl)]dipiperidine;
- N-{4-[4-(morpholin-4-ylsulfonyl)phenoxy]phenyl}-4-phenoxybenzamide;
- N-{4-[4-(morpholin-4-ylsulfonyl)phenoxy]phenyl}-4-nitrobenzamide;
- 4,4′-oxybis[N-(4-methylphenyl)benzenesulfonamide];
- 4-{[4-(4-nitrophenoxy)phenyl]sulfonyl}morpholine;
- N-(3-nitrophenyl)-4-phenoxybenzenesulfonamide;
- N-(3-acetylphenyl)-4-(4-nitrophenoxy)benzenesulfonamide;
- 4-({4-[2,6-dinitro-4-(trifluoromethyl)phenoxy]phenyl}sulfonyl)morpholine;
- 1-({4-[2,6-dinitro-4-(trifluoromethyl)phenoxy]phenyl}sulfonyl)-4-methylpiperazine;
- 4-[2,6-dinitro-4-(trifluoromethyl)phenoxy]-N-(pyridin-2-ylmethyl)benzenesulfonamide;
- N-(5-chloropyridin-2-yl)-4-phenoxybenzenesulfonamide;
- 1-{[4-(2,4-dichlorophenoxy)-2-fluorophenyl]sulfonyl}piperidine;
- N-(cyclopropylmethyl)-2-({[3,5-dichloro-4-(2-chloro-4-nitrophenoxy)phenyl]sulfonyl}amino)benzamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-[3-(3,5-dichlorophenoxy)propyl]benzene-sulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-[2-(2,4-dichlorophenyl)ethyl]benzene-sulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(pyridin-4-ylmethyl)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(4-isopropoxyphenyl)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-methylbenzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(4-cyanophenyl)-N-(1,3-dichloro-2-(2-chloro-4-nitrophenoxy)-5-sulfonylbenzene)-benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(4-methylphenyl)-N-(1,3-dichloro-2-(2-chloro-4-nitrophenoxy)-5-sulfonylbenzene)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(1,3-dichloro-2-(2-chloro-4-nitrophenoxy)-5-sulfonylbenzene)-N-(4-nitrophenyl)benzenesulfonamide;
- 1-{[3,5-dichloro-4-(2-chloro-4-nitrophenoxy)phenyl]sulfonyl}-2,6-dimethylpiperidine
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-mesityl-N-(1,3-dichloro-2-(2-chloro-4-nitrophenoxy)-5-sulfonylbenzene)benzenesulfonamide;
- 3,5-dichloro-N-(3-chloro-2-methylphenyl)-4-(2-chloro-4-nitrophenoxy)-N-(1,3-dichloro-2-(2-chloro-4-nitrophenoxy)-5-sulfonylbenzene)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-mesitylbenzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(2,6-dimethylphenyl)-N-(1,3-dichloro-2-(2-chloro-4-nitrophenoxy)-5-sulfonylbenzene)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(2,6-dimethylphenyl)benzenesulfonamide;
- 3,5-dichloro-N-(3-chloro-2-methylphenyl)-4-(2-chloro-4-nitrophenoxy)benzene-sulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-{[(3,4-dichlorophenyl)amino]carbonothioyl}benzene sulfonamide;
- methylN-(4-chlorophenyl)-N′-{[3,5-dichloro-4-(2-chloro-4-nitrophenoxy)phenyl]sulfonyl}imidothio carbamate;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-[(1Z)-[(4-chlorophenyl)amino](hydroxyamino)methylene]benzenesulfonamide;
- N-(cyclopropylmethyl)-3-({[3,5-dichloro-4-(2-chloro-4-nitrophenoxy)phenyl]sulfonyl}amino)benzamide;
- N-(cyclopropylmethyl)-4-({[3,5-dichloro-4-(2-chloro-4-nitrophenoxy)phenyl]sulfonyl}amino)benzamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(3-chlorophenyl)benzenesulfonamide;
- 3,5-dichloro-N-(3-chloro-4-methoxyphenyl)-4-(2-chloro-4-nitrophenoxy)-N-(1,3-dichloro-2-(2-chloro-4-nitrophenoxy)-5-sulfonylbenzene)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(2-chlorophenyl)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(2,3,4-trimethoxyphenyl)benzene-sulfonamide;
- N-(3-bromophenyl)-3,5-dichloro-4-(2-chloro-4-nitrophenoxy)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(2-isopropyl-6-methylphenyl)benzene-sulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(3-methylphenyl)benzenesulfonamide;
- N-1,3-benzodioxol-5-yl-3,5-dichloro-4-(2-chloro-4-nitrophenoxy)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(3-methoxyphenyl)benzenesulfonamide;
- 3,5-dichloro-N-(5-chloro-2-methoxyphenyl)-4-(2-chloro-4-nitrophenoxy)benzene-sulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-3-thienylbenzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(2-fluoro-3-methoxyphenyl)benzene-sulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(3,4-dichlorophenyl)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-1H-indol-7-ylbenzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(3-cyanophenyl)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(3,4-dimethoxyphenyl)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-1H-indol-6-ylbenzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-1H-indol-5-ylbenzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-dibenzo[b,d]furan-4-ylbenzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(3,5-difluorophenyl)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(2,3-dichlorophenyl)benzenesulfonamide;
- N-biphenyl-3-yl-3,5-dichloro-4-(2-chloro-4-nitrophenoxy)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(2,2,3,3-tetrafluoro-2,3-dihydro-1,4-benzodioxin-5-yl)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(3,4-difluorophenyl)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(3-fluoro-4-methylphenyl)benzene-sulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(2,4,5-trifluorophenyl)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(4-cyanophenyl)benzenesulfonamide;
- 3,5-dichloro-N-(3-chloro-4-methoxyphenyl)-4-(2-chloro-4-nitrophenoxy)benzene-sulfonamide;
- 3,5-dichloro-N-(4-chloro-2,5-dimethoxyphenyl)-4-(2-chloro-4-nitrophenoxy)benzene-sulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(2,5-dichlorophenyl)benzenesulfonamide;
- N-(4-bromopyridin-2-yl)-3,5-dichloro-4-(2-chloro-4-nitrophenoxy)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(2,6-dimethoxypyridin-3-yl)benzene-sulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(2-chloropyridin-3-yl)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(4-methoxyphenyl)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(2-iodophenyl)benzenesulfonamide;
- N-{[3,5-dichloro-4-(2-chloro-4-nitrophenoxy)phenyl]sulfonyl}-3-nitrobenzene-carboximidamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-[[(4-chlorophenyl)amino](imino)methyl]benzene sulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(2,2-difluoro-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(4-chloro-2-nitrophenyl)benzene-sulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-pyridin-2-ylbenzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(4,6-dibromopyridin-2-yl)benzene-sulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-quinolin-8-ylbenzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(2-fluoro-5-nitrophenyl)benzene-sulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(2,3-dihydro-1H-inden-2-yl)benzene-sulfonamide;
- N-[(1H-benzimidazol-2-ylamino)(imino)methyl]-3,5-dichloro-4-(2-chloro-4-nitrophenoxy)benzene sulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-[2-methyl-3-(trifluoromethyl)phenyl]benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-[2-methyl-5-(trifluoromethyl)phenyl]benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-[2-(trifluoromethyl)phenyl]benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(2,6-di-tert-butylphenyl)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(3-fluorophenyl)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(3-fluoro-2-methylphenyl)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-[5-fluoro-2-(trifluoromethyl)phenyl]benzene sulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(4-fluoro-2-methylphenyl)benzene-sulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(2,6-difluorophenyl)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(5-fluoro-2-methylphenyl)benzene-sulfonamide;
- N-{3-chloro-4-[2,6-dinitro-4-(trifluoromethyl)phenoxy]phenyl}-4-methylbenzenesulfonamide;
- 4-chloro-N-{3-chloro-4-[2,6-dinitro-4-(trifluoromethyl)phenoxy]phenyl}benzene-sulfonamide;
- 3,5-dichloro-N-[5-chloro-2-(trifluoromethyl)phenyl]-4-(2,4-dichlorophenoxy)benzene-sulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-(3-iodo-4-methylphenyl)benzene-sulfonamide;
- 3,5-dichloro-N-(2-chloro-4-methylphenyl)-4-(2-chloro-4-nitrophenoxy)benzene-sulfonamide;
- 3,5-dichloro-N-(5-chloro-2-methylphenyl)-4-(2-chloro-4-nitrophenoxy)benzene-sulfonamide;
- 3-chloro-N-(2-fluoro-5-nitrophenyl)-4-[4-nitro-2-(trifluoromethyl)phenoxy]benzene-sulfonamide;
- 3-chloro-N-(2,5-dichlorophenyl)-4-[4-nitro-2-(trifluoromethyl)phenoxy]benzene-sulfonamide;
- 3-chloro-N-(2,5-difluorophenyl)-4-[4-nitro-2-(trifluoromethyl)phenoxy]benzene-sulfonamide;
- 3-chloro-N-(2,5-dichloropyridin-3-yl)-4-[4-nitro-2-(trifluoromethyl)phenoxy]benzene-sulfonamide;
- 3-chloro-N-[2-chloro-5-(trifluoromethyl)phenyl]-4-[4-nitro-2-(trifluoromethyl)phenoxy]benzene sulfonamide;
- 3-chloro-N-[2-chloro-4-(trifluoromethyl)phenyl]-4-[4-nitro-2-(trifluoromethyl)phenoxy]benzene sulfonamide;
- 3-chloro-N-[4-fluoro-2-(trifluoromethyl)phenyl]-4-[4-nitro-2-(trifluoromethyl)phenoxy]benzene sulfonamide;
- 3-chloro-N-[5-chloro-2-(trifluoromethyl)phenyl]-4-[4-nitro-2-(trifluoromethyl)phenoxy]benzene sulfonamide;
- 3-chloro-N-(2,6-difluorophenyl)-4-[4-nitro-2-(trifluoromethyl)phenoxy]benzene-sulfonamide;
- N-(3-bromophenyl)-3-chloro-4-[4-nitro-2-(trifluoromethyl)phenoxy]benzene-sulfonamide;
- 2,5-dichloro-N-[4-(4-nitrophenoxy)phenyl]benzenesulfonamide;
- 3-chloro-2-methyl-N-[4-(4-nitrophenoxy)phenyl]benzenesulfonamide;
- 3-chloro-N-[4-(4-nitrophenoxy)phenyl]benzenesulfonamide;
- 2,5-dichloro-N-[4-(4-chlorophenoxy)phenyl]benzenesulfonamide;
- 2,5-dichloro-N-{4-[2-chloro-5-(trifluoromethyl)phenoxy]-2-fluorophenyl}benzene-sulfonamide;
- N-[3-bromo-4-(4-fluorophenoxy)phenyl]-2,5-dichlorobenzenesulfonamide;
- 2,5-dichloro-N-[4-(2,4,6-trichlorophenoxy)phenyl]benzenesulfonamide;
- N-acetyl-N-[3-chloro-4-(2,6-dichloro-4-{[(3-chlorophenyl)amino]sulfonyl}phenoxy)phenyl]acetamide;
- N-[3-bromo-4-(4-fluorophenoxy)phenyl]-3-chloro-2-methylbenzenesulfonamide;
- N-[3-bromo-4-(4-fluorophenoxy)phenyl]-3-chlorobenzenesulfonamide;
- N-[3-bromo-4-(4-fluorophenoxy)phenyl]-4-fluorobenzenesulfonamide;
- N-[3-bromo-4-(4-fluorophenoxy)phenyl]-4-(trifluoromethoxy)benzenesulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-[2-(1H-pyrrol-1-yl)phenyl]benzene-sulfonamide;
- N-{4-[2-chloro-5-(trifluoromethyl)phenoxy]-2-fluorophenyl}-4-fluorobenzene-sulfonamide;
- N-{4-[2-chloro-5-(trifluoromethyl)phenoxy]-2-fluorophenyl}-4-methoxybenzene-sulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-[2-(trifluoromethoxy)phenyl]benzene-sulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-[3-(trifluoromethoxy)phenyl]benzene-sulfonamide;
- 3,5-dichloro-4-(2-chloro-4-nitrophenoxy)-N-{4-[2-chloro-5-(trifluoromethyl)phenoxy]-2-fluorophenyl}benzenesulfonamide;
- N-[3-bromo-4-(4-fluorophenoxy)phenyl]-3,5-dichloro-4-(2-chloro-4-nitrophenoxy) benzenesulfonamide;
- or a pharmaceutically acceptable salt thereof.
209 more elements
A compound having the structure:
- or a pharmaceutically acceptable salt thereof, wherein
- R200 is —S(O)2—N(R1)(R2);
- R1 is phenyl substituted with halogen, trifluoromethoxy or both,
- R2 is hydrogen;
- R3 is halo;
- R400 is halo;
- R5 is NO2;
- R35 is —H;
- R6 is —H;
- R7 is halo;
- R17 is —H or —C1-C6-hydrocarbyl;
- R18 is —H, C1-C6-hydrocarbyl, —C(O)R19, —SO2R19, C(O)NHR19, CSNHR19, CNNHR19, or CO2R19;
- R19 is —H, —OH, or C1-C3-hydrocarbyl;
- wherein each of the aryl, heteroaryl, heterocyclyl, and hydrocarbyl groups above is optionally substituted by one or more groups selected from halo, —OH, —NH2, C1-C6-hydrocarbyl-C(O)—, oxo, C1-C6-hydrocarbyl-(O)—, mono- to per-halogenated C1-C6-hydrocarbyl-O—, C1-C6-hydrocarbyl, mono- to per-halogenated C1-C6-hydrocarbyl, —CN, —NO2, —NO, —NH2, —NH—C(O)R18, or —SO2;
- provided that when R35 is H, the compound is not one of the following combinations:
- R1
- R2
- R3
- R400
- R5
- R6
- R7
- 3,5-dichlorophenyl
- H
- Cl
- Cl
- NO2
- H
- Cl
- 3-chloro-4-fluorophenyl
- H
- Cl
- Cl
- NO2
- H
- Cl.
33 more elements
A compound selected from:
- N-(2-bromo-5-(trifluoromethoxy)phenyl)-3,5-dichloro-4-(2-chloro-4-nitrophenoxy)benzenesulfonamide;
- N-(3-bromo-4-(4-fluorophenoxy)phenyl)-3-chlorobenzamide;
- and
- 1-(3-bromo-4-(4-fluorophenoxy)phenyl)-3-(3-chlorophenyl)urea.
1 more element
Dependencies are inferred from the claim text.