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US 2017/0280720 A1Published application
Arginine methyltransferase inhibitors and uses thereof
AssigneeEpizyme, Inc.
InventorsRichard CHESWORTH, Lorna Helen MITCHELL, Gideon SHAPIRO, Oscar Miguel MORADEI, Kevin Wayne KUNTZ, Kenneth W. DUNCAN, Lei JIN
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.
Claims393
A compound of Formula (I):
- or a pharmaceutically acceptable salt thereof,
- wherein:
- Ring A is optionally substituted aryl, optionally substituted pyridinyl, optionally substituted bicyclic heteroaryl with one, three, or four nitrogen ring atoms, optionally substituted indazolyl, optionally substituted azaindolyl, or optionally substituted benzoimidazolyl;
- m is 0, 1, 2, 3, or 4;
- Rx is optionally substituted C1-4 alkyl or optionally substituted C3-4 cycloalkyl;
- and
- each of R3a and R3b is independently hydrogen, optionally substituted C1-4 alkyl, or optionally substituted C3-4 cycloalkyl;
- each instance of R1 is independently hydrogen, halogen, —CN, —NO2, —N3, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaryl, —ORA, —N(RB)2, —C(═O)RA, —C(═O)ORA, —OC(═O)RA, —C(═O)N(RB)2, —NRBC(═O)RA, —OC(═O)N(RB)2, —NRBC(═O)ORA, —NRBC(═O)N(RB)2, —S(═O)RA, —OS(═O)2RA, —SO2RA, —NRBSO2RA, or —SO2N(RB)2;
- each instance of RA is independently 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;
- and
- each instance of RB is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;
- or two RB taken together with the intervening nitrogen form optionally substituted heterocyclyl;
- or RA and RB taken together with the intervening atoms form optionally substituted heterocyclyl;
- and
- provided that the optional substituent on Ring A is not an optionally substituted pyridone.
12 more elements
The compound of claim 82, wherein R5 is methyl.
The compound of claim 297, wherein RB is cyclopropyl.
Dependencies are inferred from the claim text.