| 摘要 |
A compound or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof has the formula (I) and is useful for inhibiting picornaviral protease activity, wherein: M is O or S and R1 is H, F, alkyl, OH, SH or O-alkyl; G is -X-Y1-A1(D1)-B1 and G' is -X-Y2-A2(D2)-B2; R2 and R5 are independently H, alkyl, G or G' provided that the alkyl is different from G or G' and that at least one of R2 or R5 must be is G or G' and when R2 or R5 is G then X is =CH or =CF and Y1 is =CH or =CF or X and Y1 together with Q' form a three-membered ring in which Q' is -C(R10)(R11)- or -O-, X is -CH- or -CF-, and Y1 is -CH-, -CF- or -C(alkyl)- or X is -CH2-, -CF2-, -CHF-, or -S-, and Y1 is -O-, -S-, -NR12-, -C(R13)(R14)-, -C(O)-, -C(S)- or -C(CR13R14)-; A1 is C, CH, CF, S, P, Se, N, NR15, S(O), Se(O), P-OR15, or P-NR15R16; D1 is a moiety with a lone pair of electrons capable of forming a hydrogen bond and B1 is H, F, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, -OR17, -SR17, -NR17R18, -NR19NR17R18, or -NR17OR18 or when R2 or R5 is G' X is =CH or =CF and Y2 is =C, =CH or =CF, or X and Y2 together with Q' form a three-membered ring in which Q' defined above, X is -CH- or -CF-, and Y2 is -CH-, -CF-, or -C(alkyl)- or X is -CH2-, -CF2-, -CHF- or -S-, and Y1 is -O-, -S-, -NR'12 -, -C(R'13)(R'14)-, -C(O)-, -C(S)--, or -C(CR'13R'14)-; A2 is the same as A1 as defined above; D2 is the same as D1 as defined above and B2 is the same as B1 as defined above or further wherein any combination of Y2, A2, B2, and D2 forms a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group; R3 and R6 are independently H, F, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, -C(O)R17, -OR17, -SR17, -NR17R18, -NR19NR17R18, or -NR17OR18 or, together with the carbon atom to which they are attached, form a cycloalkyl group or a heterocycloalkyl group; R4 is any suitable organic moiety, or R4 and R3 or R6, together with the atoms to which they are attached, form a heterocycloalkyl group; R7 is H, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, -OR17, -SR17, -NR17R18, -NR19NR17R18 or -NR17OR18 or R7, together with R3 or R6 and the atoms to which they are attached, forms a heterocycloalkyl group; R8 is H, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, -NR29R30, -OR29, or -C(O)R29 or R8, together with R4 and the nitrogen atom to which they are attached, forms a heterocycloalkyl group or a heteroaryl group, or R8 and R3 or R6, together with the atoms to which they are attached, forms a heterocycloalkyl group; limited by the provisos listed in the specification including the proviso that when R7 is H, R8 is a moiety other than H and R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R'12, R'13, R'14, R29, R30, Z and Z1 are as defined in the specification.
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