Modulators of resistant androgen receptor
AssigneeMemorial Sloan Kettering Cancer Center
InventorsMinna D. Balbas, Michael J. Evans, Charles L. Sawyers, Yang Shen, David Hosfield, Geoffrey L. Greene
Life of this patent
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Abstract
The present invention provides compounds useful as modulators, agonists or antagonists of androgen receptor (AR), compositions thereof, and methods of making and using the same.
Claims21
A compound of formula I:
- or a pharmaceutically acceptable salt thereof, wherein:
- X is N;
- and
- Z is —CH2— or Ring B;
- and
- Ring B is an 5-14 membered saturated or partially unsaturated carbocyclic monocyclic or bicyclic ring substituted with n instances of Rb, wherein said ring is spiro-fused at point Z;
- n is 0 to 4;
- each Rb is independently substituted or unsubstituted C1-6 aliphatic, and
- wherein ring B is not cyclohexyl.
(canceled)
A method of preparing a compound of formula I:
- or a pharmaceutically acceptable salt thereof, wherein:
- X is CH or N;
- and
- Z is —CH2— or Ring B;
- and
- Ring B is an 5-14 membered saturated or partially unsaturated carbocyclic monocyclic or bicyclic ring substituted with n instances of Rb, wherein said ring is spiro-fused at point Z;
- n is 0 to 4;
- and
- each Rb is independently substituted or unsubstituted C1-6 aliphatic;
- the method comprising a step of reacting one of a 5-amino-2-cyano-3-trifluoromethylpyridine or a 4-amino-2-(trifluoromethyl)benzonitrile with a N-methyl-4-(1-cyanocycloalkylamino)-2-fluorobenzamide.
A method of manufacturing a pharmaceutical composition comprising formulating a compound of formula I with a pharmaceutically acceptable carrier, adjuvant, or vehicle, wherein the compound of formula I is represented by the following structural formula:
- or a pharmaceutically acceptable salt thereof, wherein:
- X is CH or N;
- and
- Z is —CH2— or Ring B;
- and
- Ring B is an 5-14 membered saturated or partially unsaturated carbocyclic monocyclic or bicyclic ring substituted with n instances of Rb, wherein said ring is spiro-fused at point Z;
- n is 0 to 4;
- and
- each Rb is independently substituted or unsubstituted C1-6 aliphatic.
A composition comprising a therapeutic entity, the therapeutic entity comprising a compound of formula I in association with a payload, wherein the compound of formula I is represented by the following structural formula:
- or a pharmaceutically acceptable salt thereof, wherein:
- X is CH or N;
- and
- Z is —CH2— or Ring B;
- and
- Ring B is an 5-14 membered saturated or partially unsaturated carbocyclic monocyclic or bicyclic ring substituted with n instances of Rb, wherein said ring is spiro-fused at point Z;
- n is 0 to 4;
- and
- each Rb is independently substituted or unsubstituted C1-6 aliphatic.
Dependencies are inferred from the claim text.