NOVEL FUNCTIONALIZED 4-(PHENOXYMETHYL(-1,3-DIOXOLANE ANALOGS EXHIBITING CYTOCHROME P450 INHIBITION AND THEIR METHOD OF USE
Embodiments of the present invention relate to 4-(phenoxymethyl)-1,3-dioxolane analogs and pharmaceutical compositions thereof having a disease-modifying action in the treatment of diseases associated with the overproduction of cortisol that include metabolic syndrome, and any involving the overproduction of cortisol.
1 . A compound having formula (I):
wherein:
R 1a , R 1b , R 1c , R 1d , and R 1e are each independently selected from the group consisting of hydrogen, halogen, OH, optionally substituted C 1-6 linear alkyl, optionally substituted C 1-6 branched alkyl, optionally substituted C 3-7 cycloalkyl, optionally substituted C 1-6 haloalkyl, C 1-6 , optionally substituted alkoxy, —NR 4a R 4b , —NR 5 COR 6 , —CO 2 R 6 , —CO 2 NR 4a R 4b , NHSO 2 R 7 , —SH, —SR 7 , SO 2 R 7 and —SO 2 NHR 6 ;
R 2a , R 2b , R 2c , R 2d , R 2e , R 2f and R 2g are each independently selected from the group consisting of hydrogen, halogen, OH, optionally substituted C 1-6 linear alkyl, optionally substituted C 1-6 branched alkyl, optionally substituted C 3-7 cycloalkyl, optionally substituted C 1-6 haloalkyl, C 1-6 optionally substituted alkoxy, —NR 4a R 4b , —NR 5 COR 6 , —CO 2 R 6 , —CO 2 NR 4a R 4b , —NHSO 2 R 7 , —SH, —SR 7 , SO 2 R 7 and —SO 2 NHR 6 ;
R 3 is selected from a group consisting of —SO 2 R 8 , —C(O)NR 9 R 10 , —C(O)OR 7 , —C(O)OR 7 ,
and
R 4a and R 4b are each independently selected from the group consisting of hydrogen, optionally substituted C 1-6 linear alkyl, optionally substituted C 1-6 branched alkyl, and optionally substituted C 3-7 cycloalkyl;
R 5 is selected from the group consisting of hydrogen, optionally substituted C 1-6 linear alkyl, optionally substituted C 1-6 branched alkyl, and optionally substituted C 3-7 cycloalkyl;
R 6 is selected from the group consisting of hydrogen, optionally substituted C 1-6 linear alkyl, optionally substituted C 1-6 branched alkyl, and optionally substituted C 3-7 cycloalkyl;
R 7 is selected from the group consisting of optionally substituted C 1-6 linear alkyl, optionally substituted C 1-6 branched alkyl, and optionally substituted C 3-7 cycloalkyl;
R 8 is selected from the group consisting of optionally substituted C 1-6 linear alkyl, optionally substituted C 1-6 branched alkyl, optionally substituted C 3-7 cycloalkyl, optionally substituted C 1-6 haloalkyl, optionally substituted aryl, optionally substituted heteroaryl, and optionally substituted C 3-7 heterocyclyl;
R 9 is selected from the group consisting of hydrogen, optionally substituted C 1-6 linear alkyl, optionally substituted C 1-6 branched alkyl, optionally substituted C 3-7 cycloalkyl, optionally substituted C 1-6 haloalkyl
and
R 10 is selected from the group consisting of hydrogen, optionally substituted C 1-6 linear alkyl, and optionally substituted C 1-6 branched alkyl;
R 11a and R 11b are each independently selected from the group consisting of hydrogen, optionally substituted C 1-6 linear alkyl, optionally substituted C 1-6 branched alkyl, optionally substituted aryl, optionally substituted benzyl, —CH 2 OR 6 , and CH 2 Heteroaryl
and hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, prodrugs and complexes thereof.
2 . The compound of claim 1 , having the formula (IIa):
and hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, prodrugs and complexes thereof.
3 . The compound of claim 1 , having the formula (IIb):
including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, prodrugs and complexes thereof.
4 . The compound of claim 1 , having the formula (IIIa):
including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, prodrugs and complexes thereof.
5 . The compound of claim 1 , having the formula (IIIb):
including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, prodrugs and complexes thereof.
6 . The compound of claim 1 , having the formula (IVa):
including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, prodrugs and complexes thereof.
7 . The compound of claim 1 , having the formula (IVb):
including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, prodrugs and complexes thereof.
8 . The compound of claim 1 , having the formula (Va):
including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, prodrugs and complexes thereof.
9 . The compound of claim 1 , having the formula (Vb):
including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, prodrugs and complexes thereof.
10 . The compound of claim 1 , having the formula (VIa):
including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, prodrugs and complexes thereof.
11 . The compound of claim 1 , having the formula (VIb):
including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, prodrugs and complexes thereof.
12 . The compound of claim 1 , having the formula (VIIa):
including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, prodrugs and complexes thereof.
13 . The compound of claim 1 , having the formula (VIIb):
including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, prodrugs and complexes thereof.
14 . The compound of claim 1 , having the formula (VIIIa):
including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, prodrugs and complexes thereof.
15 . The compound of claim 1 , having the formula (VIIIb):
including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, prodrugs and complexes thereof.
16 . The compound of claim 1 , having the formula (IXa):
including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, prodrugs and complexes thereof.
17 . The compound of claim 1 , having the formula (IXb):
including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, prodrugs and complexes thereof.
18 . A compound selected from the group consisting of:
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-methanesulfonylpiperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(propane-2-sulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(propane-2-sulfonyl)piperazine;
1-(cyclopropanesulfonyl)-4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine;
1-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-methanesulfonylpiperazine;
1-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(ethanesulfonyl)piperazine;
1-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(propane-2-sulfonyl)piperazine;
1-(cyclopropanesulfonyl)-4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(2,2,2-trifluoroethanesulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-trifluoromethanesulfonylpiperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(propane-1-sulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(2-methylpropanesulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(thiophene-2-sulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(1-methylimidazol-2-ylsulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-methanesulfonylmethanesulfonylpiperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(3,3,3-trifluoropropanesulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-difluoromethanesulfonylpiperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(2,2-difluoroethanesulfonyl)piperazine;
2-[4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-ylsulfonyl]acetonitrile;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(2-methoxyethanesulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(oxane-4-sulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(4,5-dihydro-1,3-oxazol-2-yl)piperazine;
4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-N-ethylpiperazine-1-carboxamide;
ethyl 2-{[4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]carbonylamino}acetate;
4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-N-ethylpiperazine-1-carboxamide;
ethyl 2-{[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]carbonylamino}acetate;
methyl (2S)-2-{[4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]carbonylamino}-3-methylbutanoate;
methyl (2S)-2-{[4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]carbonylamino}-3-phenylpropanoate;
methyl (2S)-2-{[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]carbonylamino}-3-methylbutanoate;
methyl (2S)-2-{[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]carbonylamino}-3-phenylpropanoate;
4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine-1-carboximidamide;
(rac)-methyl 4-(4-(((2S,4R)-2-((1H-imidazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazine-1-carboxylate;
(rac)-2-methoxyethyl 4-(4-(((2S,4R)-2-((1H-imidazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazine-1-carboxylate;
(rac)-4-(4-(((2S,4R)-2-((1H-imidazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)-N,N-dimethylpiperazine-1-carboxamide;
or a pharmaceutically acceptable form thereof.
19 . A composition comprising an effective amount of at least one compound according to claim 1 and at least one pharmaceutically acceptable excipient.
20 . A composition according to claim 19 , wherein the at least on compound is at least one member selected from the group consisting of:
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-methanesulfonylpiperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(propane-2-sulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(propane-2-sulfonyl)piperazine;
1-(cyclopropanesulfonyl)-4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine;
1-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-methanesulfonylpiperazine;
1-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(ethanesulfonyl)piperazine;
1-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(propane-2-sulfonyl)piperazine;
1-(cyclopropanesulfonyl)-4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(2,2,2-trifluoroethanesulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-trifluoromethanesulfonylpiperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(propane-1-sulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(2-methylpropanesulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(thiophene-2-sulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(1-methylimidazol-2-ylsulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-methanesulfonylmethanesulfonylpiperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(3,3,3-trifluoropropanesulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-difluoromethanesulfonylpiperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(2,2-difluoroethanesulfonyl)piperazine;
2-[4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-ylsulfonyl]acetonitrile;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(2-methoxyethanesulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(oxane-4-sulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(4,5-dihydro-1,3-oxazol-2-yl)piperazine;
4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-N-ethylpiperazine-1-carboxamide;
ethyl 2-{[4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]carbonylamino}acetate;
4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-N-ethylpiperazine-1-carboxamide;
ethyl 2-{[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]carbonylamino}acetate;
methyl (2S)-2-{[4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]carbonylamino}-3-methylbutanoate;
methyl (2S)-2-{[4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]carbonylamino}-3-phenylpropanoate;
methyl (2S)-2-{[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]carbonylamino}-3-methylbutanoate;
methyl (2S)-2-{[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]carbonylamino}-3-phenylpropanoate;
4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine-1-carboximidamide;
(rac)-methyl 4-(4-(((2S,4R)-2-((1H-imidazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazine-1-carboxylate;
(rac)-2-methoxyethyl 4-(4-(((2S,4R)-2-((1H-imidazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazine-1-carboxylate;
(rac)-4-(4-(((2S,4R)-2-((1H-imidazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)-N,N-dimethylpiperazine-1-carboxamide;
or a pharmaceutically acceptable form thereof.
21 . A method of treating a disease associated with overproduction of cortisol, said method comprising administering to a subject an effective amount of at least one compound according to the claim 1 to treat the disease.
22 . The method of claim 22 , wherein the at least one compound is administered in a composition further comprising at least one excipient.
23 . The method of claim 23 , wherein the at least one compound is at least one member selected from the group consisting of
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-methanesulfonylpiperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(propane-2-sulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(propane-2-sulfonyl)piperazine;
1-(cyclopropanesulfonyl)-4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine;
1-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-methanesulfonylpiperazine;
1-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(ethanesulfonyl)piperazine;
1-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(propane-2-sulfonyl)piperazine;
1-(cyclopropanesulfonyl)-4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(2,2,2-trifluoroethanesulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-trifluoromethanesulfonylpiperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(propane-1-sulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(2-methylpropanesulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(thiophene-2-sulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(1-methylimidazol-2-ylsulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-methanesulfonylmethanesulfonylpiperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(3,3,3-trifluoropropanesulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-difluoromethanesulfonylpiperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(2,2-difluoroethanesulfonyl)piperazine;
2-[4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-ylsulfonyl]acetonitrile;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(2-methoxyethanesulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(oxane-4-sulfonyl)piperazine;
1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(4,5-dihydro-1,3-oxazol-2-yl)piperazine;
4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-N-ethylpiperazine-1-carboxamide;
ethyl 2-{[4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]carbonylamino}acetate;
4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-N-ethylpiperazine-1-carboxamide;
ethyl 2-{[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]carbonylamino}acetate;
methyl (2S)-2-{[4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]carbonylamino}-3-methylbutanoate;
methyl (2S)-2-{[4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]carbonylamino}-3-phenylpropanoate;
methyl (2S)-2-{[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]carbonylamino}-3-methylbutanoate;
methyl (2S)-2-{[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]carbonylamino}-3-phenylpropanoate;
4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine-1-carboximidamide;
(rac)-methyl 4-(4-(((2S,4R)-2-((1H-imidazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazine-1-carboxylate;
(rac)-2-methoxyethyl 4-(4-(((2S,4R)-2-((1H-imidazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazine-1-carboxylate;
(rac)-4-(4-(((2S,4R)-2-((1H-imidazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)-N,N-dimethylpiperazine-1-carboxamide;
or a pharmaceutically acceptable form thereof.
24 . The method of claim 22 , wherein the disease associated with overproduction of cortisol is metabolic syndrome, obesity, headache, depression, hypertension, diabetes mellitus type II, Cushing's Syndrome, pseudo-Cushing syndrome, cognitive impairment, dementia, heart failure, renal failure, psoriasis, glaucoma, cardiovascular disease, stroke or incidentalomas.
25 . The method of claim 23 , wherein the disease associated with overproduction of cortisol is metabolic syndrome, obesity, headache, depression, hypertension, diabetes mellitus type II, Cushing's Syndrome, pseudo-Cushing syndrome, cognitive impairment, dementia, heart failure, renal failure, psoriasis, glaucoma, cardiovascular disease, stroke or incidentalomas.
26 . A method of treating a disease associated with excess Cyp17 activity, said method comprising administering to a subject an effective amount of at least one compound according to the claim 1 to treat the disease.
27 . The method of claim 27 , wherein the at least one compound is administered in a composition further comprising at least one excipient.
28 . A method of treating a disease associated with excess Cyp11B1 activity, said method comprising administering to a subject an effective amount of at least one compound according to the claim 1 to treat the disease.
29 . The method of claim 29 , wherein the at least one compound is administered in a composition further comprising at least one excipient.
30 . A method of treating a disease associated with excess Cyp21 activity, said method comprising administering to a subject an effective amount of at least one compound according to the claim 1 to treat the disease.
31 . The method of claim 31 , wherein the at least one compound is administered in a composition further comprising at least one excipient.