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US 10,632,103 B2Granted
Arginine methyltransferase inhibitors and uses thereof
AssigneeEpizyme, Inc.
InventorsRichard Chesworth, Lorna Helen Mitchell, Gideon Shapiro
Life of this patent
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Abstract
Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds described herein are useful for inhibiting arginine methyltransferase activity. Methods of using the compounds for treating arginine methyltransferase-mediated disorders are also described.
Claims20
A compound of Formula (I):
- or a pharmaceutically acceptable salt thereof,
- wherein
- X is N, Z is NR4, and Y is CR5;
- or
- X is NR4, Z is N, and Y is CR5;
- or
- X is CR5, Z is NR4, and Y is N;
- or
- X is CR5, Z is N, and Y is NR4;
- L1 is a bond, —O—, —N(RB)—, —S—, —C(O)—, —C(O)O—, —C(O)S—, —C(O)N(RB)—, —C(O)N(RB)N(RB)—, —OC(O)—, —OC(O)N(RB)—, —NRBC(O)—, —NRBC(O)N(RB)—, —NRBC(O)N(RB)N(RB)—, —NRBC(O)O—, —SC(O)—, —C(═NRB)—, —C(═NNRB)—, —C(═NORA)—, —C(═NRB)N(RB)—, —NRBC(═NRB)—, —C(S)—, —C(S)N(RB)—, —NRBC(S)—, —S(O)—, —OS(O)2—, —S(O)2—, —SO2—, —N(RB)SO2—, —SO2N(RB)—, or an optionally substituted C1-6 saturated or unsaturated hydrocarbon chain, wherein one or more methylene units of the hydrocarbon chain is optionally and independently replaced with —O—, —N(RB)—, —S—, —C(O)—, —C(O)O—, —C(O)S—, —C(O)N(RB)—, —C(O)N(RB)N(RB)—, —OC(O)—, —OC(O)N(RB)—, —NRBC(O)—, —NRBC(O)N(RB)—, —NRBC(O)N(RB)N(RB)—, —NRBC(O)O—, —SC(O)—, —C(═NRB)—, —C(═NNRB)—, —C(═NORA)—, —C(═NRB)N(RB)—, —NRBC(═NRB)—, —C(S)—, —C(S)N(RB)—, —NRBC(S)—, —S(O)—, —OS(O)2—, —S(O)2—, —SO2—, —N(RB)SO2—, or —SO2N(RB)—;
- each RA is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, and a sulfur protecting group when attached to a sulfur atom;
- each RB is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, and a nitrogen protecting group, or an RB and RW on the same nitrogen atom may be taken together with the intervening nitrogen to form an optionally substituted heterocyclic ring;
- Rx is optionally substituted C1-4 alkyl or optionally substituted C3-4 cycloalkyl;
- RW is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, or optionally substituted alkynyl;
- provided that when L1 is a bond, RW is not hydrogen;
- R3 is hydrogen, C1-4 alkyl, or C3-4 cycloalkyl;
- R4 is hydrogen, substituted C1 alkyl, optionally substituted C2-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted C3-7 cycloalkyl, optionally substituted 4- to 7-membered heterocyclyl;
- or optionally substituted C1-4 alkyl-Cy;
- Cy is optionally substituted C3-7 cycloalkyl, optionally substituted 4- to 7-membered heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
- and
- R5 is hydrogen, halo, —CN, optionally substituted C1-4 alkyl, or optionally substituted C3-4 cycloalkyl.
18 more elements
Dependencies are inferred from the claim text.