Covalent Inhibitors As 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;
• B 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 3- to 8-membered heterocyclic ring;
• R4, R5, and R7 are each independently selected from the group consisting of hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C3-C8 cycloalkyl, optionally substituted 3- to 8-membered heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
• L1 and L2 are each independently selected from the group consisting of —(CR21R23)q—, —CR21═CR22, —C≡C—, —(CR21R23)q—O—, —(CR21R23)q—S—, —(CR21R23)q—NR12—,
• —(CR21R23)q—NR12C(O)—, —(CR21R23)q—NR12C(O)O—, —(CR21R23)q—NR12C(O)NR13—, —(CR21R23)q—C(O)N(R12)—, —(CR21R23)q— N(R12)C(O)—, —(CR21R23)q—C(O)—, —(CR21R23)q—OC(O)—, —(CR21R23)q—S(O)2—, —(CR21R23)q—S(O)—, —(CR21R23)q—S(O)(NR12)—, —(CR21R23)q—(NR12)S(O)—, —(CR21R23)q—S(O)2NR12—, —(CR21R23)q— NR12S(O)2—, optionally substituted C3-C12 cycloalkyl, optionally substituted C3-C12 cycloalkenyl, optionally substituted 3- to 12-membered heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl;
• L1 connects to B through a carbon, nitrogen, sulfur, or oxygen atom;
• q is 0, 1, 2, 3 or 4;
• each R11 is 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;
• 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;
• 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;
• in certain embodiments, R21 and R22 are both hydrogen;
• R23 at each occurrence is 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;
• alternatively, R4 and a substituent of L2 are taken together with the intervening atoms to form 3- to 8-membered heterocyclic ring;
• X is selected from the group consisting of hydrogen, halogen, —CN, —C(O)R25, —CH(OH)SO3R26, —C(O)NR27R28, —C(O)OR27, —C(O)C(O)OR27, —C(O)C(O)NR27R28, —C(O)(CR21R23)C(O)OR27, —C(O)(CR21R23)C(O)NR27R28, —C(O)S(O)2NR27R28, —C(O)S(O)NR27R28,
• R25 is hydrogen, halogen, hydroxy, or optionally substituted C1-C8 alkyl;
• R26 is hydrogen or Na+;
• R27 and R28 at each occurrence are each 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, R27 and R28 are taken together with the nitrogen atom to which they are attached to form an optionally substituted 3- to 8-membered heterocyclic ring;
• R31, R32 and R33 are each 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 heteroaryl, —CN, —NO2, —NO, —C(O)R21, —CH(OH)SO3R26;
• —C(O)NR27R28, —C(O)OR27, —C(O)SR27, —S(O)2R27, —S(O)2OR27, —S(O)R27, —S(O)OR27, —S(O)2NR27R28, —S(O)NR27R21, —P(O)R27R28, —P(O)OR27R28, —P(O)OR27OR28, —P(O)NR12R27R28, —P(O)NR12R13NR27R28, —P(O)NR12R13OR28, —C(O)C(O)NR27R28, —C(O)C(O)OR27, —C(O)S(O)2NR27R28, and —C(O)S(O)NR27R28;
• alternatively, R31 and R33 are taken together with the carbon atoms to which they are attached to form an optionally substituted C4-C8 cycloalkyl, C4-C8 cycloalkenyl or optionally substituted C4-C8 cycloalkenyl or 4- to 8-membered heterocyclic ring;
• alternatively, R32 and R33 are taken together with the carbon atom to which they are attached to form an optionally substituted C3-C8 cycloalkyl or optionally substituted 3- to 8-membered heterocyclic ring;
• alternatively, R31 and L2 are taken together with the nitrogen, carbon, sulfur, or oxygen atom to which they are attached to form an optionally substituted 3- to 8-membered heterocyclic ring;
• and
• alternatively, R32 and a substituent of L2 are taken together with the intervening atoms to form an optionally substituted 4- to 8-membered heterocyclic ring.