Antiviral compounds with a heterotricycle moiety

摘要

Disclosed are compounds of formula (I) for use as antiviral agents, particularly as anti-hepatitis virus C agents, wherein A, B, U, R1-R7, m, n, and q are as described herein. Also disclosed are pharmaceutical compositions and methods of treating or preventing viral infection in a host by the use of these compounds, either alone or in combination with other pharmaceutically active agents. Further disclosed are methods of preparing such compounds.;

主权项

1. A compound of formula (I), its tautomeric form, its stereoisomer, or its pharmaceutically acceptable salt, wherein, A is selected from —CR7═, —C(H)(R7)— and —O—; B is selected from —C(R7)═ and —S—; U is selected from —N═ and —S—; with a proviso that B and U both cannot be S at the same time; “” represents a single or double bond; R1 and R4 are divalent groups, each of which along with the respective carbon atoms to which they are attached form a 3 to 7 membered carbocyclic ring or a 5 to 7 membered heterocyclic ring containing nitrogen, and optionally oxygen; R2 and R3 are each independently selected from hydrogen, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-aryl, substituted- or unsubstituted-heteroaryl, substituted- or unsubstituted-heterocyclyl, R8aC(═O)—, R8aS(═O)2—, R8aOC(═O)—, (R9)R8NC(═O)—, R8aOC(═O)N(R9)CRb(Ra)C(═O)—, R8aOC(═O)N(R9)CRb(Ra)C(Rd)(Rc)C(═O)—, R8aC(═O)N(R9)C(Rb)(Ra)C(═O)—, R8aC(═O)N(R9)CRb(Ra)C(Rd)(Rc)C(═O)—, (R9)R8NC(═O)N(R10)C(Rb)(Ra)C(═O)—, and R9(R8)NC(═O)N(R10)CRb(Ra)C(Rd)(Rc)C(═O)—; R5 and R6 are each independently selected from hydrogen, halogen, substituted- or unsubstituted-alkyl, and substituted- or unsubstituted-cycloalkyl; R7 is selected from hydrogen, halogen, and substituted- or unsubstituted C1-3 alkyl; R8 is selected from hydrogen, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-aryl, substituted- or unsubstituted-heteroaryl, and substituted- or unsubstituted-heterocyclyl; R9 and R10 are each independently selected from hydrogen and substituted- or unsubstituted-alkyl; R8a is independently selected from the group consisting of substituted- or unsubstituted-alkyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-aryl, substituted- or unsubstituted-heteroaryl, and substituted- or unsubstituted-heterocyclyl; Ra, Rb, Rc and Rd, are independently selected from hydrogen, substituted- or unsubstituted-C1-6 alkyl, substituted- or unsubstituted-aryl, substituted- or unsubstituted-heteroaryl, substituted- or unsubstituted-cycloalkyl, and substituted- or unsubstituted-heterocyclyl, or Ra, Rb, Rc and Rd together with the carbon atom(s) to which they are attached forming substituted- or unsubstituted-carbocycle, or substituted- or unsubstituted-heterocycle; m and n are integers independently selected from 0 and 1; q is an integer selected from 1, 2, and 3; when the alkyl group is a substituted alkyl group, the alkyl group is substituted with 1 to 4 substituents selected independently from oxo, halogen, cyano, perhaloalkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, R11aO—, (alkyl)S(═O)2—, (alkyl)C(═O)—, (alkyl)OC(═O)—, (alkyl)C(═O)O—, R11N(H)C(═O)—, R11(alkyl)NC(═O)—, (alkyl)C(═O)N(H)—, R11N(H)—, R11(alkyl)N—, R11(H)NC(═O)N(H)—, and R11(alkyl)NC(═O)N(H)—; when the ‘cycloalkyl’ and the carbocyclic groups are substituted, each of them is substituted with 1 to 3 substituents selected independently from oxo, halogen, cyano, C1-6 alkyl, perhaloalkyl, R11aO—, (alkyl)S(═O)2—, (alkyl)C(═O)—, (alkyl)OC(═O)—, (alkyl)C(═O)O—, R11(H)NC(═O)—, R11(alkyl)NC(═O)—, (alkyl)C(═O)N(H)—, R11(H)N—, R11(alkyl)N—, R11(H)NC(═O)N(H)—, and R11(alkyl)NC(═O)N(H)—; when the aryl group is substituted, it is substituted with 1 to 3 substituents selected independently from halogen, cyano, hydroxy, C1-6 alkyl, perhaloalkyl, alkyl-O—, perhaloalkyl-O—, alkyl(alkyl)N—, alkyl(H)N—, H2N—, alkyl-S(═O)2—, alkyl-C(═O)(alkyl)N—, alkyl-C(═O)N(H)—, alkyl(alkyl)NC(═O)—, alkyl(H)NC(═O)—, H2NC(═O)—, alkyl(alkyl)NS(═O)2—, alkyl(H)NS(═O)2—, and H2NS(═O)2—; when the heteroaryl group is substituted, it is substituted with 1 to 3 substituents selected independently from halogen, cyano, hydroxy, C1-6 alkyl, perhaloalkyl, alkyl-O—, perhaloalkyl-O—, alkyl(alkyl)N—, alkyl(H)N—, H2N—, alkyl-S(═O)2—, alkyl-C(═O)(alkyl)N—, alkyl-C(═O)N(H)—, alkyl(alkyl)NC(═O)—, alkyl(H)NC(═O)—, H2NC(═O)—, alkyl(alkyl)NS(═O)2—, alkyl(H)NS(═O)2—, and H2NS(═O)2—; when the heterocyclic group is substituted, it can be substituted either on a ring carbon atom or on a ring hetero atom, and when it is substituted on a ring carbon atom, it is substituted with 1-3 substituents selected independently from halogen, cyano, oxo, C1-6 alkyl, perhaloalkyl, R11a(alkyl)OC(═O)—, (alkyl)C(═O)O—, R11(H)NC(═O)—, R11(alkyl)NC(═O)—, (alkyl)C(═O)N(H)—, R11(H)N—, R11(alkyl)N—, R11(H)NC(═O)N(H)—, and R11(alkyl)NC(═O)N(H)—; and when the ‘heterocyclic’ group is substituted on a ring nitrogen, it is substituted with a substituent selected from C1-6 alkyl, (alkyl)SO2—, (alkyl)C(═O)—, (alkyl)OC(═O)—, R11(H)NC(═O)—, and R11(alkyl)NC(═O)—; R11 is selected from hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl; R11a is selected from hydrogen, alkyl, perhaloalkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl.