Patent classifications
C07D243/14
Inhibitors of KRAS G12C mutant proteins
Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, tautomer, stereoisomer or prodrug thereof, wherein A, B R.sup.1, R.sup.2a, R.sup.2b, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b, G.sup.1, G.sup.2, m.sup.1, m.sup.2, L.sup.1, L.sup.2 and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided. ##STR00001##
Inhibitors of KRAS G12C mutant proteins
Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, tautomer, stereoisomer or prodrug thereof, wherein A, B R.sup.1, R.sup.2a, R.sup.2b, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b, G.sup.1, G.sup.2, m.sup.1, m.sup.2, L.sup.1, L.sup.2 and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided. ##STR00001##
COMBINATION COMPOSITIONS COMPRISING BISFLUOROALKYL-1,4- BENZODIAZEPINONE COMPOUNDS AND METHODS OF USE THEREOF
The present invention provides compositions comprising bisfluoroalkyl-1,4-benzodiazepinone compounds, including compounds of Formula (I) or prodrugs thereof;
##STR00001##
in combination with an additional cancer therapeutic agent, and methods of use thereof for treating diseases and disorders such as cancer.
COMBINATION COMPOSITIONS COMPRISING BISFLUOROALKYL-1,4- BENZODIAZEPINONE COMPOUNDS AND METHODS OF USE THEREOF
The present invention provides compositions comprising bisfluoroalkyl-1,4-benzodiazepinone compounds, including compounds of Formula (I) or prodrugs thereof;
##STR00001##
in combination with an additional cancer therapeutic agent, and methods of use thereof for treating diseases and disorders such as cancer.
3-ARYL-4-AMIDO-BICYCLIC [4,5,0] HYDROXAMIC ACIDS AS HDAC INHIBITORS
The present disclosure relates to inhibitors of zinc-dependent histone deacetylases (HDACs) useful in the treatment of diseases or disorders associated with an HDAC, e.g., HDAC6, having a Formula I:
##STR00001##
where R, L, X.sup.1, X.sup.2, X.sup.3, X.sup.4, Y.sup.1, Y.sup.2, Y.sup.3, and Y.sup.4 are described herein.
3-ARYL-4-AMIDO-BICYCLIC [4,5,0] HYDROXAMIC ACIDS AS HDAC INHIBITORS
The present disclosure relates to inhibitors of zinc-dependent histone deacetylases (HDACs) useful in the treatment of diseases or disorders associated with an HDAC, e.g., HDAC6, having a Formula I:
##STR00001##
where R, L, X.sup.1, X.sup.2, X.sup.3, X.sup.4, Y.sup.1, Y.sup.2, Y.sup.3, and Y.sup.4 are described herein.
3-ALKYL BICYCLIC [4,5,0] HYDROXAMIC ACIDS AS HDAC INHIBITORS
The present disclosure relates to inhibitors of zinc-dependent histone deacetylases (HDACs) useful in the treatment of diseases or disorders associated with an HDAC, e.g., HDAC6, having a Formula I:
##STR00001##
where R, L, X.sup.1, X.sup.2, X.sup.3, X.sup.4, Y.sup.1, Y.sup.2, Y.sup.3, and Y.sup.4 are described herein.
3-ALKYL BICYCLIC [4,5,0] HYDROXAMIC ACIDS AS HDAC INHIBITORS
The present disclosure relates to inhibitors of zinc-dependent histone deacetylases (HDACs) useful in the treatment of diseases or disorders associated with an HDAC, e.g., HDAC6, having a Formula I:
##STR00001##
where R, L, X.sup.1, X.sup.2, X.sup.3, X.sup.4, Y.sup.1, Y.sup.2, Y.sup.3, and Y.sup.4 are described herein.
3-ARYL-BICYCLIC [4,5,0] HYDROXAMIC ACIDS AS HDAC INHIBITORS
The present invention relates to inhibitors of zinc-dependent histone deacetylases (HDACs) useful in the treatment of diseases or disorders associated with HDAC6, having a Formula I:
##STR00001##
where R, L, X.sup.1, X.sup.2, X.sup.3, X.sup.4, Y.sup.1, Y.sup.2, Y.sup.3, and Y.sup.4 are described herein.
3-ARYL-BICYCLIC [4,5,0] HYDROXAMIC ACIDS AS HDAC INHIBITORS
The present invention relates to inhibitors of zinc-dependent histone deacetylases (HDACs) useful in the treatment of diseases or disorders associated with HDAC6, having a Formula I:
##STR00001##
where R, L, X.sup.1, X.sup.2, X.sup.3, X.sup.4, Y.sup.1, Y.sup.2, Y.sup.3, and Y.sup.4 are described herein.