Macrocyclic chalcone-amide derived antiviral agents

A compound represented by Formula (I), or a pharmaceutically acceptable salt thereof,

• wherein:
• A is selected from the group consisting of optionally substituted aryl, optionally substituted heteroaryl, optionally substituted —C3-C8 cycloalkyl, and optionally substituted 3- to 8-membered heterocycloalkyl;
• R1 and R3 are each independently selected from the group consisting of hydrogen, optionally substituted —C1-C4 alkyl, optionally substituted —C2-C4 alkenyl, optionally substituted —C2-C4 alkynyl, and optionally substituted —C3-C6 cycloalkyl;
• alternatively, R1 and R3 are taken together with the carbon atom to which they are attached to form an optionally substituted 3- to 8-membered carbocyclic or a 3- to 8-membered heterocyclic ring;
• each R2 is selected from the group consisting of halogen, —OR11, —OC(O)R11, —C(O)OR11, —OC(O)NR12R13, —NR12R13, —NR12C(O)R11, —NR12C(O)OR13, —NR12C(O)NR12R13, —C(O)NR12R13, —N3, —CN, optionally substituted —C1-C8 alkyl, optionally substituted —C2-C8 alkenyl, optionally substituted —C2-C8 alkynyl, optionally substituted —C3-C8 cycloalkyl, optionally substituted 3- to 8-membered heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl;
• R11 is selected from the group consisting of hydrogen, optionally substituted —C1-C8 alkyl, optionally substituted —C2-C8 alkenyl, optionally substituted —C2-C8 alkynyl, optionally substituted —C3-C8 cycloalkyl, optionally substituted 3- to 8-membered heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl;
• R12 and R13 at each occurrence are independently selected from the group consisting of hydrogen, optionally substituted —C1-C8 alkyl, optionally substituted —C2-C8 alkenyl, optionally substituted —C2-C8 alkynyl, optionally substituted —C3-C8 cycloalkyl, optionally substituted 3- to 8-membered heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl;
• alternatively R12 and R13 are taken together with the nitrogen atom to which they are attached to form an optionally substituted 3- to 8-membered heterocyclic ring;
• n is 0, 1, 2, or 3;
• L1 and L2 are independently selected from the group consisting of —CR21═CR22—, —CR21R23—CR22R24—, —(CR21R23)m—O—, —(CR21R23)m—S—, —(CR21R23)m—NR12—,
• —(CR21R23)m—NR12C(O)—, —(CR21R23)m—NR12C(O)O—, —(CR21R23)m—NR12C(O)NR13—, —(CR21R23)m—C(O)N(R12)—, —(CR21R23)m—C(O)—, —(CR21R23)m—S(O)2—, —(CR21R23)m—S(O)(NH)—, —(CR21R23)m—S(O)2NR12—, optionally substituted —C3-C8 cycloalkyl, optionally substituted 3- to 8-membered heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl;
• m is 0, 1, 2, 3 or 4;
• R21 and R22 at each occurrence are independently selected from the group consisting of hydrogen, halogen, optionally substituted —C1-C8 alkyl, optionally substituted —C2-C8 alkenyl, optionally substituted —C2-C8 alkynyl, optionally substituted —C3-C8 cycloalkyl, optionally substituted 3- to 8-membered heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl;
• R23 and R24 at each occurrence are independently selected from the group consisting of hydrogen, halogen, —OR11, —OC(O)R11, —OC(O)OR11, —OC(O)NR12R13, —NR12R13, —NR12C(O)R11, —NR12C(O)OR13, —NR12C(O)NR12R13, —C(O)NR12R13, —N3, —CN, optionally substituted —C1-C8 alkyl, optionally substituted —C2-C8 alkenyl, optionally substituted —C2-C8 alkynyl, optionally substituted —C3-C8 cycloalkyl, optionally substituted 3- to 8-membered heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl;
• W is selected from the group consisting of optionally substituted —C1-C8 alkyl, optionally substituted —C3-C8 cycloalkyl, optionally substituted 3- to 8-membered heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl;
• —(CR21R23)q1—O—(CR22R24)q2—, —(CR21R23)q1—NR12—(CR22R24)q2—, and —(CR21R23)q1—S—(CR22R24)q2—;
• q1 is 0, 1, 2, 3, 4, 5, 6, 7, or 8;
• q2 is 0, 1, 2, 3, 4, 5, 6, 7, or 8;
• X is selected from the group consisting of halogen, optionally substituted —C1-C6 alkyl, optionally substituted —C2-C6 alkenyl, optionally substituted —C3-C6 cycloalkyl,
• Z1 and Z2 are each independently an amino protecting group, R13,
• R31, R32, R33 and R34 at each occurrence are independently selected from the group consisting of hydrogen, optionally substituted —CH3, and halogen;
• R35 and R36 at each occurrence are each independently selected from the group consisting of hydrogen, optionally substituted —CH3, halogen, and —CN;
• i1, i2, i3, and i4 are each independently 0, 1, 2, 3, 4;
• Q is selected from absent, —O—, and —NR12—;
• E is selected from optionally substituted aryl, optionally substituted heteroaryl;
• and
• Y is selected from the group consisting of hydrogen, halogen, —CF3;
• —CN, —C(O)R11, —C(O)OR12, —C(O)NR12R13, —S(O)2R11, —S(O)2NR12R13, optionally substituted aryl, and optionally substituted heteroaryl.