Inhibitors of glycogen synthase 1 (GYS1) and methods of use thereof

A method of treating a disease, disorder, or condition selected from the group consisting of Pompe disease, Cori disease (GSD III), adult polyglucosan body disease (APBD), and Lafora disease, or condition in an individual in need thereof, comprising administering to the individual an effective amount of a compound of formula (I-A):

• or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:
• Y1 is CH or N;
• Rx and Rz are independently H, halo, C1-6alkyl, or —NH2, wherein, when Y1 is CH, the C1-6alkyl of Rx or Rz may be optionally substituted with one or more halo;
• Ry is (i) C1-6alkyl, or (ii) C3-10cycloalkyl, wherein the C3-10cycloalkyl is optionally substituted with one or more halo or C1-6alkyl;
• Rk is H, halo, —OH, —NH2, or —NH—C(O)C1-6alkyl;
• R2 is C1-6alkyl, wherein the C1-6alkyl of R2 is substituted with one or more Ra, wherein Ra is —OH or 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl of Ra is optionally substituted with one or more Rb;
• and
• Rb is halo, C1-6alkyl, C1-6alkoxy, —NH2, —NH(C1-6alkyl), —N(C1-6alkyl)2, C3-10cycloalkyl, 3-15 membered heterocyclyl, or —C(O)—C1-6alkoxy, wherein the C1-6alkyl of Rb is optionally substituted with one or more halo, —NH2, —NH(C1-6alkyl), —N(C1-6alkyl)2, —NH—C(O)C1-6alkyl, or —NH—C(O)—C1-6alkoxy, and the 3-15-membered heterocyclyl of Rb is optionally substituted with one or more halo or —C(O)—C1-6alkoxy.