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US 2019/0241542 A1Published application
Substituted hydantoin and thiohydantoin derivatives as androgen receptor antagonists
AssigneeJanssen Pharmaceutica NV
InventorGilles Bignan
Life of this patent
Estimating the term…
Abstract
Disclosed are compounds, compositions and methods for treating of disorders that are affected by the antagonism of one or more androgen receptor types. Such compounds are represented by Formula (I) as follows: wherein R1, R2a, R2b, Z, X, Y, and G are defined herein.
Claims26
A compound of Formula (I)
- wherein
- Z is S;
- R1 is selected from the group consisting of chloro, methyl, methoxy, difluoromethyl, and trifluoromethyl;
- R2a and R2b are independently C1-6alkyl;
- or, R2a and R2b are taken together with the carbon atom to which they are attached to form an unsubstituted or substituted C3-C10cycloalkyl or an unsubstituted or substituted C3-C10heterocyclyl selected from the group consisting of pyrrolidinyl and piperidinyl;
- wherein said substituted C10cycloalkyl or substituted C3-C10heterocyclyl are optionally independently substituted with a C1-3alkyl or cyclopropyl substituent;
- X is C
- Y is C;
- G is selected from the group consisting of g1 and g2
- wherein R3 is selected from the group consisting of hydrogen;
- C1-6alkyl optionally independently substituted with a substituent selected from hydroxy, methoxy, cyano, or fluoro;
- C3-6cycloalkyl optionally independently substituted with a substituent selected from hydroxy or fluoro;
- and —C(O)OR4, wherein R4 is C1-6alkyl or —CH2(C6-10aryl) wherein C6-10aryl is optionally substituted with a methoxy substituent;
- such that a substituent on C1-6alkyl or C3-6cycloalkyl is attached at a carbon atom other than the carbon atom directly attached to the G-nitrogen atom;
- wherein any nitrogen-containing heterocyclic substituent of G is optionally substituted with an oxido substituent to form an N-oxide;
- or an enantiomer, diastereomer, or pharmaceutically acceptable salt form thereof.
13 more elements
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(canceled)
A compound of Formula (I)
- wherein
- Z is S;
- R1 is selected from the group consisting of chloro, methyl, methoxy, and trifluoromethyl;
- R2a and R2b are independently methyl;
- or, R2a and R2b are taken together with the carbon atom to which they are attached to form an unsubstituted cyclobutyl ring;
- X is C;
- Y is C;
- G is selected from the group consisting of g1
- wherein R3 is selected from the group consisting of hydrogen;
- C1-4alkyl optionally independently substituted with a substituent selected from hydroxy, methoxy, or fluoro;
- C3-6cycloalkyl optionally independently substituted with a substituent selected from hydroxy or fluoro;
- and —C(O)OR4, wherein R4 is C1-6alkyl or —CH2(phenyl), and wherein the phenyl is optionally substituted with a methoxy substituent;
- such that a substituent on C1-4alkyl or C3-6cycloalkyl is attached at a carbon atom other than the carbon atom directly attached to the G-nitrogen atom ;
- wherein any nitrogen-containing heterocyclic substituent of G is optionally substituted with an oxido substituent to form an N-oxide;
- or an enantiomer, diastereomer, or pharmaceutically acceptable salt form thereof.
12 more elements
A compound of Formula (I)
- wherein
- Z is S;
- R1 is chloro, methyl, or trifluoromethyl;
- R2a and R2b are independently methyl;
- or, R2a and R2b are taken together with the carbon atom to which they are attached to form an unsubstituted cyclobutyl ring;
- X is C;
- Y is C;
- G is selected from the group consisting of g1
- wherein R3 is selected from the group consisting of hydrogen;
- C1-3alkyl optionally independently substituted with a substituent selected from methoxy or fluoro;
- and —C(O)OR4, wherein R4 is C1-6alkyl or —CH2(phenyl) and wherein the phenyl is optionally substituted with a methoxy substituent;
- such that a substituent on C1-3alkyl is attached at a carbon atom other than the carbon atom directly attached to the G-nitrogen atom;
- wherein any nitrogen-containing heterocyclic substituent of G is optionally substituted with an oxido substituent to form an N-oxide;
- or an enantiomer, diastereomer, or pharmaceutically acceptable salt form thereof.
11 more elements
A compound of Formula (I)
- wherein
- Z is S;
- R1 is chloro or trifluoromethyl;
- R2a and R2b are independently methyl;
- or, R2a and R2b are taken together with the carbon atom to which they are attached to form an unsubstituted cyclobutyl ring;
- X is C;
- Y is C;
- G is selected from the group consisting of g1
- wherein R3 is selected from the group consisting of hydrogen;
- methyl, and —C(O)OR4, wherein R4 is C1-4alkyl or —CH2(phenyl);
- wherein any nitrogen-containing heterocyclic substituent of G is optionally substituted with an oxido substituent to form an N-oxide;
- or an enantiomer, diastereomer, or pharmaceutically acceptable salt form thereof.
9 more elements
(canceled)
(canceled)
(canceled)
selected from the group consisting of
- 2-Chloro-4-(4,4-dimethyl-5-oxo-3-(4-(piperidin-4-yloxy)phenyl)-2-thioxoimidazolidin-1-yl)benzonitrile;
- 2-Chloro-4-(4,4-dimethyl-3-(4-((1-methylpiperidin-4-yl)oxy)phenyl)-5-oxo-2-thioxoimidazolidin-1-yl)benzonitrile;
- 4-(8-Oxo-5-(4-(piperidin-4-yloxy)phenyl)-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-2-(trifluoromethyl)benzonitrile;
- 4-(5-(4-((1-Methylpiperidin-4-yl)oxy)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-2-(trifluoromethyl)benzonitrile;
- 2-Methyl-4-(5-(4-((1-methylpiperidin-4-yl)oxy)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)benzonitrile;
- 2-Methoxy-4-(5-(4-((1-methylpiperidin-4-yl)oxy)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)benzonitrile;
- 2-Methoxy-4-(5-(6-((1-methylpiperidin-4-yl)oxy)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)benzonitrile;
- 2-Chloro-4-(8-oxo-5-(4-(piperidin-4-yloxy)phenyl)-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)benzonitrile;
- 2-Chloro-4-(5-(4-((1-methylpiperidin-4-yl)oxy)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)benzonitrile;
- and
- 2-Chloro-4-(8-oxo-5-(6-(piperidin-4-yloxy)pyridin-3-yl)-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)benzonitrile;
- or a pharmaceutically acceptable salt form thereof.
9 more elements
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-35. (canceled)
Dependencies are inferred from the claim text.