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US 10,059,687 B2Granted
Histone demethylase inhibitors
AssigneeCelgene Quanticel Research, Inc.
InventorsYoung K. Chen, Michael Brennan Wallace
Life of this patent
Estimating the term…
Abstract
The present disclosure relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted pyridine derivative compounds, and compositions (including pharmaceutical compositions) that include these compounds. The subject compounds and compositions are useful for inhibition of at least one histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer or neoplastic disease, such as prostate cancer, breast cancer, bladder cancer, lung cancer, melanoma, retinoblastoma, or multiple endocrine neoplasia type 1.
Claims17
A compound having the structure of Formula 1:
- wherein a compound of Formula 1 includes isomers and pharmaceutically acceptable salts thereof, and wherein:
- n is 0 or 1;
- R4 is hydrogen or optionally substituted C1-C6 alkyl;
- R6 is hydrogen or X—Y, wherein
- X is a bond, O, S, N(R), C(O), N(R)C(O), C(O)N(R), or optionally substituted C1-C3 alkyl, wherein
- R is hydrogen or optionally substituted C1-C6 alkyl, and
- Y is optionally substituted alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
- and
- R5, R7, and R8 are each independently selected from hydrogen, halogen, hydroxyl, cyanyl, N(R1)(R2), or optionally substituted C1-C6 alkyl, C1-C6 alkynyl, C1-C6 alkenyl, C1-C6 alkoxy, C3-C7 carbocyclyl, C3-C7 carbocyclyloxy, C4-C12 carbocyclylalkyl, C4-C12 carbocyclylalkoxy, C6-C10 aryl, C6-C10 aryloxy, C6-C10 aryl-S, C6-C10 aryl-SO2, C7-C14 aralkoxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclyloxy, heterocyclylalkyl, heterocyclylalkoxy or heteroaryl-S, wherein
- R1 is hydrogen or optionally substituted C1-C6 alkyl, and
- R2 is optionally substituted alkyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkylalkyl, aryl-CO, heteroaryl-CO, cycloalkyl-CO, or alkyl-CO.
8 more elements
A compound of Formula 2:
- wherein a compound of Formula 2 includes isomers and pharmaceutically acceptable salts thereof, and wherein:
- n is 0 or 1;
- R4 is hydrogen or optionally substituted C1-C6 alkyl;
- and
- R3 is N(R)(R9), N(R)C(O), C(O)N(R), or optionally substituted C3-C7 carbocyclyl, C3-C7 carbocyclyloxy, C4-C12 carbocyclylalkyl, C4-C12 carbocyclylalkoxy, C6-C10 aryl, C6-C10 aryloxy, C6-C10 aryl-S, C6-C10 aryl-SO2, C7-C14 aralkoxy, C1-C6 alkoxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclyloxy, heterocyclylalkyl, heterocyclylalkoxy or heteroaryl-S, wherein
- R is hydrogen or optionally substituted C1-C6 alkyl, and
- R9 is optionally substituted C3-C7 carbocyclyl, C3-C7 carbocyclyloxy, C1-C6 alkoxy, C4-C12 carbocyclylalkyl, C4-C12 carbocyclylalkoxy, C6-C10 aryl, C6-C10 aryloxy, C6-C10 aryl-S, C6-C10 aryl-SO2, C7-C14 aralkoxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclyloxy, heterocyclylalkyl, heterocyclylalkoxy or heteroaryl-S.
4 more elements
A compound having the structure of Formula 3:
- wherein the compound of Formula 3 includes isomers and pharmaceutically acceptable salts thereof, and wherein:
- n is 0 or 1;
- R6 is X—Y, wherein
- X is a bond, O, S, N(R), C(O), N(R)C(O), C(O)N(R), or optionally substituted C1-C3 alkyl, wherein
- R is hydrogen or optionally substituted C1-C6 alkyl, and
- Y is optionally substituted C1-C6 alkyl, cycloalkyl, C3-C7 carbocyclyl, C1-C6 alkoxy, C3-C7 carbocyclyloxy, C4-C12 carbocyclylalkyl, C4-C12 carbocyclylalkoxy, C6-C10 aryl, C6-C10 aryloxy, C6-C10 aryl-S, C6-C10 aryl-SO2, C7-C14 aralkoxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclyloxy, heterocyclylalkyl, heterocyclylalkoxy or heteroaryl-S;
- and
- R5, R7, and R8 are each independently selected from hydrogen, halogen, hydroxyl, cyanyl, or N(R1)(R2), or optionally substituted C1-C6 alkyl, C1-C6 alkynyl, C1-C6 alkenyl, C1-C6 alkoxy, C3-C7 carbocyclyl, C3-C7 carbocyclyloxy, C4-C12 carbocyclylalkyl, C4-C12 carbocyclylalkoxy, C6-C10 aryl, C6-C10 aryloxy, C6-C10 aryl-S, C6-C10 aryl-SO2, C7-C14 aralkoxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclyloxy, heterocyclylalkyl, heterocyclylalkoxy, or heteroaryl-S, in which
- R1 is hydrogen or optionally substituted C1-C6 alkyl, and
- R2 is optionally substituted alkyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkylalkyl, aryl-CO, heteroaryl-CO, cycloalkyl-CO, or alkyl-CO.
7 more elements
A compound of Formula 4:
- wherein a compound of Formula 4 includes isomers and pharmaceutically acceptable salts thereof, and wherein:
- n is 0 or 1;
- and
- R3 is N(R)(R9), N(R)C(O), C(O)N(R), or optionally substituted C3-C7 carbocyclyl, C3-C7 carbocyclyloxy, C4-C12 carbocyclylalkyl, C4-C12 carbocyclylalkoxy, C6-C10 aryl, C6-C10 aryloxy, C6-C10 aryl-S, C6-C10 aryl-SO2, C7-C14 aralkoxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclyloxy, heterocyclylalkyl, heterocyclylalkoxy, or heteroaryl-S, wherein
- R is hydrogen or optionally substituted C1-C6 alkyl, and
- R9 is optionally substituted C3-C7 carbocyclyl, C3-C7 carbocyclyloxy, C4-C12 carbocyclylalkyl, C4-C12 carbocyclylalkoxy, C6-C10 aryl, C6-C10 aryloxy, C6-C10 aryl-S, C7-C14 aralkoxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclyloxy, heterocyclylalkyl, heterocyclylalkoxy, C6-C10 aryl-SO2, or heteroaryl-S.
3 more elements
Dependencies are inferred from the claim text.