Heterocyclic compounds for the treatment of disease

A compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof:

• wherein:
• X1, X2, X3, and X4 are each CR1;
• or
• X1 is N;
• X2, X3, and X4 are each CR1;
• or
• X2 is N;
• X1, X3, and X4 are each CR1;
• or
• X3 is N;
• X1, X2, and X4 are each CR1;
• or
• X4 is N;
• X1, X2, and X3 are each CR1;
• is selected from
• Z is —O—, —S—, —N(R4)—, —CH2—, —OCH2—, or —CH2O—;
• each R1 is independently selected from the group consisting of hydrogen, halogen, optionally substituted C1-C6alkyl, optionally substituted C2-C6alkenyl, optionally substituted C2-C6alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C3-C8cycloalkyl, optionally substituted —(C1-C2alkylene)-(C3-C8cycloalkyl), optionally substituted C2-C9heterocycloalkyl, optionally substituted —(C1-C2alkylene)-(C2-C9heterocycloalkyl), optionally substituted —(C1-C2alkylene)-(aryl), optionally substituted —(C1-C2alkylene)-(heteroaryl), —CF3, —OR10, —SR10, —N(R11)R12, —N(R11)S(O)2R15;
• —N(R13)N(R11)R12, —N(R13)N(R11)S(O)2R15, —C(O)R14, —C(O)OR10, —C(S)OR10, —C(O)SR10, —C(O)N(R11)R12, —C(S)N(R11)R12, —C(O)N(R11)S(O)2R15, —C(S)N(R11)S(O)2R15, —C(O)N(R13)N(R11)R12, —C(S)N(R13)N(R11)R12, and —C(O)N(R13)N(R11)S(O)2R15;
• each R2 is independently selected from the group consisting of halogen, optionally substituted C1-C6alkyl, —OR20, —SR20, —N(R21)R22, —C(O)R20, —C(O)N(R21)R22, and —N(R23)C(O)R20;
• R3 is selected from the group consisting of hydrogen, optionally substituted C1-C6alkyl, optionally substituted C2-C6alkenyl, optionally substituted C2-C6alkynyl, optionally substituted C3-C8 cycloalkyl, optionally substituted aryl, optionally substituted —(C1-C2alkylene)-(aryl), optionally substituted heteroaryl, and optionally substituted —(C1-C2alkylene)-(heteroaryl);
• R4 is hydrogen or optionally substituted C1-C6alkyl,
• R10, R13 and R14 are each independently selected from the group consisting of hydrogen, optionally substituted C1-C6alkyl, optionally substituted C2-C6alkenyl, optionally substituted C2-C6alkynyl, optionally substituted C3-C8cycloalkyl, optionally substituted aryl, optionally substituted —(C1-C2alkylene)-(aryl), optionally substituted C2-C9heterocycloalkyl, optionally substituted heteroaryl, and optionally substituted —(C1-C2alkylene)-(heteroaryl);
• R11 and R12 are each independently selected from the group consisting of hydrogen, optionally substituted C1-C6alkyl, optionally substituted C2-C6alkenyl, optionally substituted C2-C6alkynyl, optionally substituted C3-C8cycloalkyl, optionally substituted aryl, optionally substituted —(C1-C2alkylene)-(aryl), optionally substituted C2-C9heterocycloalkyl, optionally substituted heteroaryl, and optionally substituted —(C1-C2alkylene)-(heteroaryl);
• or optionally R11 and R12 together with the nitrogen atom to which they are attached, form an optionally substituted C2-C9heterocycloalkyl ring;
• R15 is selected from the group consisting of optionally substituted C1-C6alkyl, optionally substituted C2-C6alkenyl, optionally substituted C2-C6alkynyl, optionally substituted C3-C8 cycloalkyl, optionally substituted aryl optionally substituted —(C1-C2alkylene)-(aryl), optionally substituted C2-C9heterocycloalkyl, optionally substituted heteroaryl, and optionally substituted —(C1-C2alkylene)-(heteroaryl);
• R20 and R23 are each independently selected from the group consisting of hydrogen, optionally substituted C1-C6alkyl, optionally substituted C2-C6alkenyl, optionally substituted C2-C6alkynyl, optionally substituted C3-C8cycloalkyl, optionally substituted aryl, optionally substituted —(C1-C2alkylene)-(aryl), optionally substituted C2-C9heterocycloalkyl, optionally substituted heteroaryl, and optionally substituted —(C1-C2alkylene)-(heteroaryl);
• R21 and R22 are each independently selected from the group consisting of hydrogen, optionally substituted C1-C6alkyl, optionally substituted C2-C6alkenyl, optionally substituted C2-C6alkynyl, optionally substituted C3-C8cycloalkyl, optionally substituted aryl, optionally substituted —(C1-C2alkylene)-(aryl), optionally substituted C2-C9heterocycloalkyl, optionally substituted heteroaryl, and optionally substituted —(C1-C2alkylene)-(heteroaryl);
• or optionally R21 and R22 together with the nitrogen atom to which they are attached, form an optionally substituted C2-C9heterocycloalkyl ring;
• n is 0-4;
• and
• p is 0 or 1.