| 主权项 |
1. A method of inhibiting the replication of influenza viruses in a biological sample or patient, comprising the step of administering to said biological sample or patient an effective amount of a compound represented by the following structural formula (I):or a pharmaceutically acceptable salt thereof, wherein:
Z1 is —R*, —F, —Cl, —CN, —OR*, —CO2R*, —NO2, or —CON(R*)2; Z2 is —R*, —OR*, —CO2R*, —NR*2, or —CON(R*)2; Z3 is —H, —OH, halogen, —NH2; —NH(C1-C4 alkyl); —N(C1-C4 alkyl)2, —O(C1-C4 alkyl), or C1-C6 alkyl that is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, and —O(C1-C4 alkyl); R1 is —H or C1-C6 alkyl; R2 is —H; —F; —NH2; —NH(C1-C4 alkyl); —N(C1-C4 alkyl)2; —C═N—OH; cyclopropyl that is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, —OCH3, and —CH3; or C1-C4 alkyl that is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, and —O(C1-C4 alkyl); and R3 is —H, —Cl, —F, —OH, —O(C1-C4 alkyl), —NH2, —NH(C1-C4 alkyl), —N(C1-C4alkyl)2, —Br, —CN, or C1-C4 aliphatic that is optionally substituted with one or more substituents 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), —CO2H, —CO2(C1-C4 alkyl), and C1-C4 alkoxy; R4 is:wherein ring T is a C3-C10 non-aromatic carbocycle optionally substituted with one or more instances of JA, or a 3-10 membered non-aromatic heterocycle optionally substituted with one or more instances of JB, or ring T and R9 optionally form a non-aromatic C5-C10 membered carbocycle optionally substituted with one or more instances of JA or 5-10 membered non-aromatic heterocycle optionally substituted with one or more instances of JB;wherein ring J is a 3-10 membered non-aromatic heterocycle optionally substituted with one or more instances of JB; orwherein ring D is a 4-10 membered non-aromatic heterocycle optionally substituted with one or more instances of JD1; and
each of JA and JB is independently selected from the group consisting of halogen, cyano, oxo, —NCO, and Q1-R5; or optionally two JA and two JB, respectively, together with the atom(s) to which they are attached, independently form a 4-8 membered ring that is optionally substituted with one or more instances of JE1; Q1 is independently a bond, —O—, —S—, —NR′—, —C(O)—, —C(═NR)—, —C(═NR)NR—, —NRC(═NR)NR—, —CO2—, —OC(O)—, —C(O)NR′, —C(O)NRC(O)O—, —NRC(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR′, —NRCO2—, —OC(O)NR′, —S(O)—, —SO2—, —SO2NR′, —NRSO2, or —NRSO2NR′—, —P(O)(OR)O—, —OP(O)(ORa)O—, —P(O)2O—, —CO2SO2—, or —(CR6R7)p—Y1—; Y1 is independently a bond, —O—, —S—, —NR′—, —C(O)—, —C(═NR)—, —C(═NR)NR—, —NRC(═NR)NR—, —CO2, —OC(O)—, —C(O)NR′, —C(O)NRC(O)O—, —NRC(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR′, —NRCO2—, —OC(O)NR′, —S(O)—, —SO2—, —SO2NR′, —NRSO2, —NRSO2NR′—, —P(O)(OR)O—, —OP(O)(ORa)O—, —P(O)2O—, or —CO2SO2—; R5 is: i) —H; ii) a C1-C6 aliphatic group optionally substituted with one or more instances of JC1; iii) a C3-C10 non-aromatic carbocycle, or a 6-10 membered carbocyclic aryl group, each optionally and independently substituted with one or more instances of fi; or iv) a 4-10 membered non-aromatic heterocycle, or a 5-10 membered heteroaryl group, each optionally and independently substituted with one or more instances of JD1; or R5, together with Q1, optionally forms a 4-8 membered, non-aromatic ring optionally substituted with one or more instances of JE1; and R6 and R7 are each independently —H or C1-C6 alkyl optionally substituted with one or more substitutents selected from the group consisting of halogen, cyano, hydroxy, oxo, amino, carboxy, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 aminoalkoxy, C1-C6cyanoalkoxy, C1-C6hydroxyalkoxy and C2-C6 alkoxyalkoxy, or optionally R6 and R7, together with the carbon atom to which they are attached, form a cyclopropane ring optionally substituted with one or more instances of methyl; R9 is independently —H, halogen, cyano, hydroxy, amino, carboxy, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cyanoalkyl, C2-C6 alkoxyalkyl, C1-C6 aminoalkyl, C1-C6 hydroxyalkyl, C1-C6 carboxyalkyl, C1-C6alkoxy, C1-C6haloalkoxy, C1-C6aminoalkoxy, C1-C6cyanoalkoxy, C1-C6hydroxyalkoxy and C2-C6 alkoxyalkoxy; R13 and R14 are each independently —H, halogen, or C1-C6 alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, hydroxy, oxo, amino, carboxy, C1-C6alkoxy, C1-C6haloalkoxy, C1-C6 aminoalkoxy, C1-C6 cyanoalkoxy, C1-C6hydroxyalkoxy, and C2-C6 alkoxyalkoxy; optionally, R13 and R14, 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 substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, amino, carboxy, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 aminoalkoxy, C1-C6 cyanoalkoxy, C1-C6hydroxyalkoxy and C2-C6 alkoxyalkoxy; or optionally R′, together with R5 and the nitrogen atom to which they are attached, forms a 5-7 membered non-aromatic heterocycle optionally substituted with one or more instances of JD1; R* is independently: i) —H; ii) a C1-C6 alkyl group optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, amino, carboxy, C3-C8 non-aromatic carbocycle, 5-6 membered non-aromatic heterocycle, phenyl, 5-6 membered heteroaryl, —O(C1-C6 alkyl), and —C(O)(C1-C6-alkyl); wherein each of said alkyl groups in —O(C1-C6 alkyl), and —C(O)(C1-C6-alkyl) is optionally and independently substituted with one or more substituents 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), —CO2H, —CO2(C1-C4 alkyl), and C1-C4 alkoxy; and wherein each of said carbocycle, heterocycle, phenyl, and heteroaryl is independently and optionally substituted with one or more instances of JE1; or iii) a C3-C8 non-aromatic carbocycle, or a 4-8 membered non-aromatic heterocycle, each of which is independently and optionally substituted with one or more instances of JE1; and each of JC1 and JD1 is independently selected from the group consisting of halogen, cyano, oxo, Ra, —ORb, —SRb, —S(O)Ra, —SO2Ra, —NRbRc, —C(O)Rb, —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), —SO2NRcRb, —NRSO2Rb, —NRSO2NRcRb, —P(O)(ORa), —OP(O)(ORa), —P(O)2ORa and —CO2SO2Rb, or optionally, two JC1 and two JD1, respectively, together with the atom(s) to which they are attached, independently form a 4-8-membered ring that is optionally substituted with one or more instances of JE1; each JE1 is independently selected from the group consisting of halogen, cyano, hydroxy, oxo, amino, carboxy, amido, C1-C6 alkyl, —O(C1-C6 alkyl), and —C(O)(C1-C6-alkyl), wherein each of said alkyl groups is optionally and independently substituted with one or more substituents 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), —CO2H, —CO2(C1-C4 alkyl), and C1-C4 alkoxy; and Ra is independently: i) a C1-C6 aliphatic group optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, amino, carboxy, amido, —O(C1-C6 alkyl), —C(O)(C1-C6-alkyl), C3-C8 non-aromatic carbocycle, 4-8 membered non-aromatic heterocycle, 5-10 membered heteroaryl group, and 6-10 membered carbocyclic aryl group; wherein each of said alkyl groups for the substituents of the C1-C6 aliphatic group represented by Ra is optionally and independently substituted with one or more substituents 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), —CO2H, —CO2(C1-C4 alkyl), and C1-C4 alkoxy; and wherein each of said carbocycle, heterocycle, heteroaryl and carbocyclic aryl groups for the substituents of the C1-C6 aliphatic group represented by Ra is optionally and independently substituted with one or more instances of JE1;ii) a C3-C8 non-aromatic carbocycle, or a 4-8 membered non-aromatic heterocycle, each of which is optionally and independently substituted with one or more instances of JE1; oriii) a 5-10 membered heteroaryl, or 6-10 membered carbocyclic aryl group, each of which is optionally and independently substituted with one or more instances of JE1; 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 5-7 membered non-aromatic heterocycle optionally substituted with one or more instances of JE1; p is independently 1, 2, 3 or 4; t is 0, 1 or 2; j is 1 or 2; and z is 1 or 2. |
