Isoxazole Carboxamides as Irreversible SMYD Inhibitors
AssigneeEpizyme, Inc.
InventorsRichard Chesworth, Megan Alene Cloonan Foley, Kevin Wayne Kuntz, Lorna Helen Mitchell, Jennifer C. Petter, Carl Eric Schwartz
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Abstract
The present disclosure provides provides substituted isoxazole carboxamides having Formula (I), and the pharmaceutically acceptable salts and solvates thereof, wherein R1, R2a, R2b, R3a, R3b, X, n, and m are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I to treat a disorder responsive to the blockade of SMYD proteins such as SMYD3 or SMYD2. Compounds of the present disclosure are especially useful for treating cancer.
Claims22
A compound having Formula I:
- or a pharmaceutically acceptable salt or hydrate thereof,
- wherein:
- R1 is cyclopropyl;
- R2a, R2b, R3a, and R3b are selected from the group consisting of hydrogen and C1-4 alkyl;
- X is selected from the group consisting of —N(—Y—Z)— and —CH[N(H)—Y—Z]—;
- Y is selected from the group consisting of —C(═O)— and —S(═O)2—;
- Z is selected from the group consisting of
- —CH═CH2,
- —CH═C(H)CH2NH2,
- —CH═C(H)CH2N(H)CH3,
- —CH═C(H)CH2N(CH3)2,
- —CH═C(H)CH2CH2NH2,
- —CH═C(H)CH2CH2N(H)CH3,
- —CH═C(H)CH2CH2N(CH3)2,
- —CH2Cl,
- —CH2Br, and
- —CH2I;
- n is 0 or 1;
- and
- m is 0 or 1.
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19-24. (canceled)
Dependencies are inferred from the claim text.