Naphthyridinone derivatives and their use in the treatment of arrhythmia

A method of treating a disease or disorder selected from cardiac arrhythmia, atrial fibrillation, primary hyperaldosteronism, hypertension, and sick sinus syndrome comprising administering to a subject in need thereof a therapeutically effective amount of a compound according to Formula I:

• wherein:
• X2 is CR2 or N;
• X3 is CH or N;
• R1 is C1-4alkyl, —CH2CN, —CN, C1-4alkoxyC1-4alkyl, halo-C1-4alkyl, —CH═N—OH, —CH═N—O—C1-4alkyl, —CH═N—O-(hydroxyC1-4alkyl), hydroxy-C1-4alkyl, —CH2OP(O)(OH)2, or C3-5cycloalkyl;
• R3 is —ORa;
• —NHRb;
• —C(O)NH2;
• —C(O)[hydroxyC1-4alkyl];
• 4- to 7-membered heterocyclyl containing at least one heteroatom selected from O, N, and S and optionally substituted with one or more substituents independently selected from OH and hydroxyC1-4alkyl;
• and 5- or 6-membered heteroaryl containing 1 to 4 heteroatoms independently selected from O, N, and S and optionally substituted with one or more C1-4alkyl;
• or
• R3 is C1-4alkyl substituted with one or more substituents independently selected from —C(O)[hydroxyC1-4alkyl] and —ORc;
• Ra is —C1-6alkyl substituted with one or more substituents independently selected from —ORc, —SO2C1-4alkyl, —NHS(O)2C1-4alkyl, and 4- to 7-membered heterocyclyl containing at least one heteroatom selected from O, N, and S, which is further optionally substituted with one or more substituents independently selected from C1-4alkyl and hydroxyC1-4alkyl;
• or
• Ra is H, —[CH2—CH2—O]m—CH3, or 5- or 6-membered heteroaryl containing 1 to 4 heteroatoms independently selected from O, N, and S and optionally substituted with one or more C1-4alkyl;
• wherein n is 2-6 and m is 1-6;
• Rb is —C1-6alkyl substituted with one or more substituents independently selected from —ORc, —C(O)NH—C1-4alkyl, —C(O)NH-(hydroxyC1-4alkyl), hydroxyC1-4alkyl, 5- or 6-membered heteroaryl containing 1 to 4 heteroatoms independently selected from O, N and S, 4- to 7-membered heterocyclyl containing at least one heteroatom selected from O, N, and S, —SO2C1-4alkyl, and —NHS(O)2C1-4alkyl;
• or
• Rb is —S(O)2-(5- or 6-membered heteroaryl containing 1 to 4 heteroatoms independently selected from O, N, and S);
• or
• Rb is 4- to 7-membered heterocyclyl containing at least one heteroatom selected from O, N, and S and optionally substituted with one or more hydroxy groups;
• or
• Rb is H, —ORc;
• —[CH2—CH2—O]m—CH3, or 5- or 6-membered heteroaryl containing 1 to 4 heteroatoms independently selected from O, N, and S and optionally substituted with one or more C1-4alkyl;
• wherein n is 2-6 and m is 1-6;
• Rc is H or hydroxyC1-4alkyl;
• R2 is H, C1-4alkoxy, halo-C1-4alkoxy, halo, C1-4alkyl, —S—C1-4alkyl, or —NH—C1-4alkyl;
• R4 is H, halo, halo-C1-4alkyl, C1-4alkyl, or C3-5cycloalkyl;
• R5 is H, halo, CN, C1-4alkoxy, hydroxy-C1-4alkoxy, C1-4alkoxy-C1-4alkoxy, —CH═NH—O—C1-4alkyl, or —CH═NH—O(hydroxyC1-4alkyl);
• or
• R5 is C2-6alkynyl optionally substituted with OH or NRgRh, wherein Rg and Rh are independently H or C1-4alkyl;
• or Rg and Rh form together with the nitrogen to which they are attached a 4- to 7-membered heterocyclyl optionally containing an additional heteroatom selected from O, N, and S, wherein the heteroatom can be in its oxidized form;
• and wherein said heterocyclyl is optionally substituted with C1-4alkyl;
• and
• R6 is halo, C1-4 alkyl, or CN;
• or a pharmaceutically acceptable salt thereof.