Inhibitors of KRAS G12C and methods of using the same
AssigneeAmgen Inc.
InventorsBrian Alan Lanman, Shon Booker, Clifford Goodman, Anthony B. Reed, Jonathan D. Low, Hui-Ling Wang, Ning Chen, Ana Elena Minatti, Ryan Wurz, Victor J. Cee
Life of this patent
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Abstract
Provided herein are methods of using KRAS G12C inhibitors. These methods of using the inhibitors are useful for treating a number of disorders, including pancreatic, colorectal, and lung cancers.
Claims55
A method of treating cancer having a KRAS G12C mutation in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound having a structure of formula (I)
- wherein
- A is independently N or CH;
- W is independently N or CH;
- wherein one or both of A and W is N;
- R1 and R2 are independently a branched or a linear C1-6alkyl;
- R3 is phenyl substituted by 1 or 2 R5 substituents;
- R5 is independently selected from one or more halo, —OH, or NH2;
- R4 is halo;
- or
- a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof, wherein the cancer having a KRAS G12C mutation is non-small cell lung cancer, pancreatic cancer, colorectal cancer, appendix cancer, endometrial cancer, esophageal cancer, gastric cancer, small intestine cancer, nasal cavity cancer, paranasal sinus cancer, bile duct cancer, skin cancer, or intraocular melanoma.
A method of treating cancer having a KRAS G12C mutation in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound having a structure of formula (II)
- wherein
- A is independently N or CH;
- W is independently N or CH;
- wherein one or both A and W is N;
- R1 and R2 are independently a branched or a linear C1-6alkyl;
- R3 is phenyl substituted by one or two R5 substituents;
- R5 is independently selected from one or more halo, —OH, or NH2;
- and
- R4 is halo;
- or
- a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof, wherein the cancer having a KRAS G12C mutation is non-small cell lung cancer, pancreatic cancer, colorectal cancer, appendix cancer, endometrial cancer, esophageal cancer, gastric cancer, small intestine cancer, nasal cavity cancer, paranasal sinus cancer, bile duct cancer, skin cancer, or intraocular melanoma.
A method of treating cancer having a KRAS G12C mutation in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound having a structure selected from:
- or a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof, wherein the cancer having a KRAS G12C mutation is non-small cell lung cancer, pancreatic cancer, colorectal cancer, appendix cancer, endometrial cancer, esophageal cancer, gastric cancer, small intestine cancer, nasal cavity cancer, paranasal sinus cancer, bile duct cancer, skin cancer, or intraocular melanoma.
A method of treating cancer having a KRAS G12C mutation in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound having a structure selected from:
- or a pharmaceutically acceptable salt thereof, wherein the cancer having a KRAS G12C mutation is non-small cell lung cancer, pancreatic cancer, colorectal cancer, appendix cancer, endometrial cancer, esophageal cancer, gastric cancer, small intestine cancer, nasal cavity cancer, paranasal sinus cancer, bile duct cancer, skin cancer, or intraocular melanoma.
Dependencies are inferred from the claim text.