Methods for treating cytokine release syndrome

A method of treating a subject with aberrant cytokine release from a disease or condition or at risk of developing aberrant cytokine release from a disease or condition, comprising administering to the subject an effective amount of a compound represented by the following structural formula:

• or a pharmaceutically acceptable salt thereof, wherein:
• one of X1, X2, and X3 is S, the other two are each independently CR;
• R is H, —F, —Cl, —Br, —OH, —(C1-C4)alkyl, —(C1-C4)haloalkyl, —(C1-C4)alkoxy, —(C1-C4)alkylene-OH or 4-7 membered monocyclic heterocyclyl optionally substituted with 1-3 groups selected from —F, —Cl, —Br, —OH, —(C1-C4)alkyl, —(C1-C4)haloalkyl, —(C1-C4)alkoxy, or —CO2—(C1-C4)alkyl;
• R1 is —NRaRb or —ORa1;
• Ra for each occurrence is independently —H, —(C1-C6)alkyl, —(CH2)n—(C3-C7)cycloalkyl, —(CH2)n-3-7 membered monocyclic heterocyclyl, —(CH2)n-bridged (C6-C12)cycloalkyl, optionally substituted —(CH2)n-5-10 membered heteroaryl;
• or —(CH2)n-6-12 membered bridged heterocyclyl, wherein —(C1-C6)alkyl, —(CH2)n—(C3-C7)cycloalkyl, —(CH2)n-3-7 membered monocyclic heterocyclyl, —(CH2)n-bridged (C6-C12)cycloalkyl, —(CH2)n-5-10 membered heteroaryl, or —(CH2)n-6-12 membered bridged heterocyclyl, is optionally substituted with 1-3 groups selected from —F, —Cl, —Br, —CN, —NH2, —OH, oxo, —(C1-C4)alkyl, —(C1-C4)haloalkyl, —(C1-C4)alkoxy, —(C1-C4)haloalkoxy, —(C1-C4)alkylene-OH, or —(C1-C4)alkylene-NH2;
• Rb for each occurrence is independently —H or —(C1-C6)alkyl;
• or,
• Ra and Rb, together with the nitrogen to which they are attached, form —(C3-C10)heterocyclyl;
• Ra1 for each occurrence is independently —H, (C1-C6)alkyl, (C3-C10)cycloalkyl, 3-10 membered heterocyclyl, (C6-C10)aryl, or 3-10 membered heteroaryl;
• R2 and R3 are independently H or —(C1-C4)alkyl;
• R4 and R5, together with the nitrogen to which they are attached, form 4-7 membered monocyclic heterocyclyl or 6-12 membered bridged heterocyclyl, wherein the 4-7 membered monocyclic heterocyclyl or 6-12 membered bridged heterocyclyl is optionally substituted with 1-3 groups selected from —F, —Cl, —Br, —CN, —NH2, —OH, oxo, —(C1-C4)alkyl, —(C1-C4)haloalkyl, —(C1-C4)alkoxy, —(C1-C4)haloalkoxy, —(C1-C4)alkylene-OH, or —(C1-C4)alkylene-NH2;
• R6 for each occurrence is independently —F, —Cl, —Br, —CN, —NH2, —OH, —(C1-C6)alkyl;
• —(C1-C6)haloalkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, (C3-C6)cycloalkyl, —(C1-C6)alkoxy, —(C1-C6)haloalkoxy, —(C1-C6)alkylene-OH, or —(C1-C6)alkylene-NH2;
• m is 0, 1, 2, or 3;
• and
• n is 0, 1, or 2.