Aminoisoquinoline Derivatives as Protein Kinase Inhibitors

A compound of formula (I):

• or a tautomer, a prodrug, or a pharmaceutically acceptable salt or solvate thereof, wherein:
• Y is hydrogen or C1-C4 alkyl, and Z is selected from hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, and —NRaRb;
• or alternatively, Y and Z are connected through a double bond (“Z═Y”) and are each independently CRy, CRz, or nitrogen (N), wherein Ry and Rz are each independently selected from hydrogen, halogen, hydroxyl, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy,
• X1, X2, X3, and X4 are each independently selected from hydrogen, halogen, hydroxyl, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;
• R is selected from C1-C6 alkyl, C3-C6 cycloalkyl, C6-C10 aryl, and 5- to 10-membered heteroaryl, 5- to 10-membered heterocyclyl, C3-C6 cycloalkyl-(C1-C4)-alkyl, C6-C10 aryl-(C1-C4)-alkyl, 5- to 10-membered heteroaryl-(C1-C4)-alkyl, and 5- to 10-membered heterocyclyl-(C1-C4)-alkyl, each optionally substituted with one, two, or three substituents independently selected from halogen, hydroxyl, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, —NRcRd, cyano, nitro, oxo, —C(O)R6, —C(O)OR7, and —C(O)NRcRd;
• Rx is hydrogen or C1-C4 alkyl, or alternatively, Rx and R, together with the nitrogen (N) and sulfur (S) atoms to which they are attached, form a five- or six-membered ring;
• R1 is hydrogen, C1-C6 alkyl, C6-C10 aryl, benzyl, —C(O)R6, or —C(O)OR7, each optionally substituted with one, two or three substituents independent selected from halogen, C1-C4 alkyl, haloalkyl, C1-C4 alkoxy, C1-C4 alkoxy, cyano, and NRaRb;
• R2, R3, R4, and R5 are each independently hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;
• Ra and Rb are each independently selected from hydrogen, C1-C6 alkyl, benzyl, and —C(O)OR7, and
• R6 is hydrogen or C1-C4 alkyl;
• R7 is C1-C4 alkyl;
• and
• Rc and Rd are each independently hydrogen or C1-C4 alkyl.