Pyridazinone compounds and methods for the treatment of cystic fibrosis

A compound of Formula II:

• or a pharmaceutically acceptable salt thereof;
• Wherein represents a single or double bond;
• m is 0, 1, 2, 3 or 4;
• d is 0, 1 or 2;
• X10 is CH, CH2, S or O;
• Cy1 is absent, an aryl, substituted aryl, carbocycle, substituted carbocycle, heterocyclyl, substituted heterocyclyl, heteroaryl, or substituted heteroaryl group having one, two or three rings;
• Cy2 is an aryl, substituted aryl, carbocycle, substituted carbocycle, heterocyclyl, substituted heterocyclyl, heteroaryl, or substituted heteroaryl group having one, two or three rings;
• A1 is absent, —[C(R100)(R101)]n—, —C(O)—, —C(S), —S(O)—, —C(O)N(R100)—, —S(O)2N(R100)—, —S(O)2—, —[C(R25)(R26)]n-, —[C(R25)(R26)]n-C═C—[C(R27)(R28)]p, or —[C(R25)(R26)]n-C≡C—[C(R27)(R28)]p, carbocycle, substituted carbocycle, heterocycle, substituted heterocycle, aromatic, substituted aromatic, heteroaromatic or substituted heteroaromatic;
• wherein n is 0, 1, 2, 3, 4, 5, 6 or 7;
• wherein each R100 and R101 is hydrogen, deuterium, halogen, alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aliphatic, substituted aliphatic, aryl and substituted aryl, —OR200, —SR200, —C(O)R200, —C(O)N(R200)2, —NC(O)R200, —S(O)2R200 wherein R200 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl;
• alternatively two of R100 and R101 groups together with the atoms to which they are attached and any intervening atoms may form an additional optionally substituted, 3, 4, 5, 6 or 7 membered ring;
• A2 is absent or —[C(R100)(R101)]n-, —C(O)—, —C(S)—, —S(O)—, —C(O)N(R100)—, —C(O)N(R100)(R101), N(R100)(R101), —S(O)2—, —S(O)2R100, —S(O)2N(R100)(R101),—[C(R25)(R26)]n-, —[C(R25)(R26)]n-C═C—[C(R27)(R28)]p, or —[C(R25)(R26)]n-C≡C—[C(R27)(R28)]p;
• A3 is absent or —[C(R100)(R101)]n-, —C(O)—, —C(S)—, —S(O)—, —C(O)N(R100)—, —C(O)N(R100)(R101), N(R100)(R101), —S(O)2—, S(O)2R100, S(O)R100, S(O)2N(R100)(R101), —[C(R25)(R26)]n-, —[C(R25)(R26)]n-C═C—[C(R27)(R28)]p, or —[C(R25)(R26)]n-C≡C—[C(R27)(R28)]p;
• A4 is absent or —[C(R25)(R26)]n-, —[C(R25)(R26)]n-C═C—[C(R27)(R28)]p, or —[C(R25)(R26)]n-C≡C—[C(R27)(R28)]p;
• wherein each R25, R26, R27 and R28 is independently selected hydrogen, deuterium, halogen, alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aliphatic, substituted aliphatic, aryl, substituted aryl, —OR100, —SR100, —NR100R101, —C(O)R100, —C(O)OR100, —C(O)NR100R101, —N(R100)C(O)R101, —S(O)2R100, —S(O)R100, —SR100, —S(O)2N(R100)R101, —CF3, —CN, —NO2, and —N3;
• alternatively two of R25, R26, R27 and R28 groups together with the atoms to which they are attached and any intervening atoms may form an additional optionally substituted, 3, 4, 5, 6 or 7 membered ring;
• p is 0, 1, 2, 3, 4, 5, 6, or 7;
• R2 is independently selected from hydrogen, deuterium, halogen, alkyl, substituted alkyl, cycloalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aliphatic, substituted aliphatic, aryl, substituted aryl, heterocyclyl, substituted heterocyclyl, heteroaryl, or substituted heteroaryl —OR100, —SR100, —NR100R101, —C(O)R100, —C(O)OR100, —C(O)NR100R101, —N(R100)C(O)R101, —S(O)2R100, —S(O)R100, —SR100, —S(O)2N(R100)R101, —CF3, —CN, —NO2, —N3;
• alternatively two R2 together with the atoms to which they are attached may form an optionally substituted 3, 4, 5, 6 or 7 membered ring;
• and,
• each R3 and R4 is independently selected from hydrogen, deuterium, halogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aliphatic, substituted aliphatic, aryl, substituted aryl, heterocyclyl, substituted heterocyclyl, heteroaryl, substituted heteroaryl, or —OR100, —SR100, —NR100R101, —C(O)R100, —C(O)OR100, —C(O)NR100R101, —N(R100)C(O)R101, —S(O)2R100, —S(O)R100, —SR100, —S(O)2N(R100)R101, —CF3, —CN, —NO2, —N3.