Inhibitors of influenza viruses replication

摘要

Methods of inhibiting the replication of influenza viruses in a biological sample or patient, of reducing the amount of influenza viruses in a biological sample or patient, and of treating influenza in a patient, comprises administering to said biological sample or patient an effective amount of a compound represented by Structural Formula (I):;
or a pharmaceutically acceptable salt thereof, wherein the values of Structural Formula (I) are as described herein. A compound is represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof, wherein the values of Structural Formula (I) are as described herein. A pharmaceutical composition comprises an effective amount of such a compound or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle.

主权项

1. A compound represented by Structural Formula (I): or a pharmaceutically acceptable salt thereof, wherein:
X is —H, —Cl, —Br, —F, —CN, or C1-C6 aliphatic optionally substituted with one or more instances of J1;Ring T is a C3-C10 non-aromatic carbocycle or 4-10 membered, non-aromatic, heterocycle optionally further substituted with one or more instances of JT;Q1 is —C(O)—, —CO2—, —OC(O)—, —O(CRtRs)k—C(O)O—, —C(O)NR′—, —C(O)N(R′)—O—, —C(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR′—, —NRCO2—, —OC(O)NR′—, —OSO2NR′—, —S(O)—, —SO2—, —SO2NR′—, —NRSO2—, —NRSO2NR′—, —P(O)(OR)O—, —OP(O)(ORa)O—, —P(O)2O—, —CO2SO2—, —B(O)2—, or —(CRtRs)—Y1—;Y1 is —C(O)—, —CO2—, —OC(O)—, —O(CRtRs)k—C(O)O—, —C(O)NR′—, —C(O)N(R′)—O—, —C(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR′—, —NRCO2—, —OC(O)NR′—, —OSO2NR′—, —S(O)—, —SO2—, —SO2NR′—, —NRSO2—, —NRSO2NR′—, —P(O)(OR)O—, —OP(O)(ORa)O—, —P(O)2O—, —B(O)2—, or —CO2SO2—;R1 is: i) —H; ii) a C1-C6 aliphatic group optionally substituted with one or more instances of JA; iii) a C3-C10 non-aromatic carbocyclic group or 4-10 membered, non-aromatic, heterocyclic group, each optionally and independently substituted with one or more instances of JB; or iv) a 6-10 membered aryl group or 5-10 membered heteroaryl group, each optionally and independently substituted with one or more instances of JC;optionally R1, together with R′ and the nitrogen to which they are attached, forms a 4-8 membered, non-aromatic, heterocyclic group optionally substituted with one or more instances of J2; oroptionally -Q1-R1 forms, together with Ring T, a 4-10 membered, non-aromatic, spiro ring optionally substituted with one or more instances of J4; andR2 is —H, —OR, —CO2R, —NRR′, —CONRR′, or C1-C6 aliphatic optionally substituted with one or more instances of J1;R3 is —H, —F, —Cl, —CN, —NO2, —OR, —CO2R, —CONRR′, or C1-C6 aliphatic optionally substituted with one or more instances of J1;JA, JB, and JT are each and independently oxo or JC;JC are each and independently selected from the group consisting of halogen, cyano, M, Ra, or Ra-M;M is independently selected from the group consisting of —ORb, —SRb, —S(O)Ra, —SO2Ra, —NRbRc, —C(O)Ra, —C(═NR)Rc, —C(═NR)NRbRc, —NRC(═NR)NRbRc, —C(O)ORb, —OC(O)Rb, —NRC(O)Rb, —C(O)NRbRc, —NRC(O)NRbRc, —NRC(O)ORb, —OCONRbRc, —C(O)NRCO2Rb, —NRC(O)NRC(O)ORb, —C(O)NR(ORb), —OSO2NRbRc, —SO2NRcRb, —NRSO2Rb, —NRSO2NRcRb, —P(O)(ORb)2, —OP(O)(ORb)2, —P(O)2ORb and —CO2SO2Rb; oroptionally, two JT, two JA, two JB, and two JC, respectively, together with the atom(s) to which they are attached, independently form a 4-10-membered ring that is optionally substituted with one or more instances of J4; andRa is independently: i) a C1-C6 aliphatic group optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, —OCO(C1-C4 alkyl), —CO(C1-C4 alkyl), —CO2H, —CO2(C1-C4 alkyl), —O(C1-C4 alkyl), C3-C8 non-aromatic carbocyclic group optionally substituted with one or more instances of J2, 4-8 membered, non-aromatic, heterocyclic group optionally substituted with one or more instances of J2, 5-10 membered heteroaryl group optionally substituted with one or more instances of J3, and 6-10 membered aryl group optionally substituted with one or more instances of J3; ii) a C3-C8 non-aromatic carbocyclic group, or 4-8 membered, non-aromatic, heterocyclic group, each of which is optionally and independently substituted with one or more instances of J2; or iii) a 5-10 membered heteroaryl group, or 6-10 membered aryl group, each of which is optionally and independently substituted with one or more instances of J3; and
Rb and Rc are each independently Ra or —H; or optionally, Rb and Rc, together with the nitrogen atom(s) to which they are attached, each independently form a 4-8 membered, non-aromatic, heterocyclic group optionally substituted with one or more instances of J2;Rt and Rs are each independently —H, halogen, or C1-C6 alkyl optionally substituted with one or more instances of J1, or optionally, Rt and Rs, together with the carbon atom to which they are attached, form a cyclopropane ring optionally substituted with one or more instances of methyl;R and R′ are each independently —H or C1-C6 alkyl optionally and independently substituted with one or more instances of J1, or optionally R and R′, together with the nitrogen to which they are attached, form a 4-8 membered, non-aromatic, heterocyclic group optionally substituted with one or more instances of J2;each J1 is independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, —OCO(C1-C4 alkyl), —CO(C1-C4 alkyl), —COZH, —CO2(C1-C4 alkyl), —O(C1-C4 alkyl), and phenyl;each J2 is independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, —OCO(C1-C4 alkyl), —CO(C1-C4 alkyl), —COZH, —CO2(C1-C4 alkyl), C1-C4 alkyl, C1-C4 haloalkyl, and —O(C1-C4 alkyl);each of J3 and J4 is independently selected from the group consisting of halogen, cyano, hydroxy, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, —OCO(C1-C4 alkyl), —CO(C1-C4 alkyl), —COZH, —CO2(C1-C4 alkyl), C1-C4 alkyl, C1-C4 haloalkyl, and —O(C1-C4 alkyl);p is 1, 2, 3 or 4; andk is 1, 2, 3 or 4.