Treatment of diseases by epigenetic regulation
AssigneeRVX Therapeutics Inc.
InventorsKevin G. McLure, Peter R. Young
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Abstract
The present disclosure provides non-naturally occurring polyphenol compounds that inhibit the bromodomain and extra terminal domain (BET) proteins. The disclosed compositions and methods can be used for treatment and prevention of diseases or disorders that are susceptible to administration of a BET inhibitor.
Claims32
A method of inhibiting BET (bromodomain and extra terminal domain protein) proteins comprising administering to the subject in need thereof, a therapeutically effective amount of at least one compound of Formula I:
- or a stereoisomer, tautomer, pharmaceutically acceptable salt, or hydrate thereof, wherein:
- Q is selected from N and CRa3;
- V is selected from N and CRa4;
- W is selected from N and CH;
- X is selected from OH, SH, NH2, S(O)H, S(O)2H, S(O)2NH2, S(O)NH2, NHAc, and NHSO2Me;
- Ra1, Ra3, and Ra4 are independently selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, and halogen;
- Ra2 is selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, amino, amide, and halogen;
- Rb3 and Rb5 are independently selected from hydrogen, halogen, C1-C6 alkyl, C3-C6 cycloalkyl, and C1-C6 alkoxy;
- provided that at least one of Ra1, Ra2, Ra3, and Ra4 is not hydrogen.
A method of inhibiting BET (bromodomain and extra terminal domain protein) proteins comprising administering a therapeutically effective amount of at least one compound of Formula II:
- or a stereoisomer, tautomer, pharmaceutically acceptable salt, or hydrate thereof, wherein:
- P is selected from N and CRa1;
- V is selected from N and CH;
- W is selected from N and CH;
- X is selected from O, S, CH2, and NH;
- Ra1 and Ra3 are independently selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, and halogen;
- Rb3 and Rb5 are independently selected from hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 alkoxy, halogen, and amino;
- Rd is selected from C1-C6 alkyl, C1-C6 alkoxy, and C3-C6 cycloalkyl, wherein Rd may be connected to Rb3 or Rb5 to form a heterocycle,
- provided that
- at least one of Ra1 and Ra3 is not hydrogen;
- and
- if —XRd is —OCH2CH2OH, then Rb3 is not pyrrolidine.
Dependencies are inferred from the claim text.