2,3-fluorinated glycosides as neuraminidase inhibitors and their use as anti-virals

摘要

Compounds of structural formula (I) useful for the treatment or prophylaxis of viral infection, particularly viral influenza are provided Pharmaceutical preparations thereof and methods for their preparation are also described. The therapeutic effect is achieved via inhibition of viral neuraminidases, also known as viral sialidases. These neuraminidases are classified under the GH34 family of viral enzymes.;

主权项

1. A compound of formula I: wherein T is COOH or COOR1, wherein R1 is a C1-20 linear, branched or cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of the group consisting of: oxo, OH, F, Cl, Br, I, NH2, CN, SH, SO3H and NO2, and wherein zero to ten backbone carbons of the optionally substituted alkyl group are optionally and independently substituted with O, N or S; Z is F, Cl, Br, or OSO2R2, wherein R2 is a C1-20 linear, branched or cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of the group consisting of: oxo, OH, F, Cl, Br, I, NH2, CN, SH, SO3H and NO2, and wherein zero to ten backbone carbons of the optionally substituted alkyl group are optionally and independently substituted with O, N or S; A is selected from the group consisting of: H, F, Cl, Br, OH, CN, OR3, NO2, SO2R3, SR3 and COR3, wherein R3 is a C1-20 linear, branched or cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of the group consisting of: oxo, OH, F, Cl, Br, I, NH2, CN, SH, SO3H and NO2, and wherein zero to ten backbone carbons of the optionally substituted alkyl group are optionally and independently substituted with O, N or S; D is selected from the group consisting of: H, F, Cl, Br, OH, CN, OR4, NO2, SO2R4, SR4 and COR4, provided A and D are not both H, and wherein R4 is a C1-20 linear, branched or cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of the group consisting of: oxo, OH, F, Cl, Br, I, NH2, CN, SH, SO3H and NO2, and wherein zero to ten backbone carbons of the optionally substituted alkyl group are optionally and independently substituted with O, N or S; collectively, A and D, optionally form an oxo group; X is selected from the group consisting of: NH2, NHR5, NHC(NH)NH2, NHC(NH)NHR5, NR5R6, NHC(NR6)NR5, and NHC(NH)N(R5)R6, wherein R5 and R6 are independently C6H5, CH2C6H5 or a C1-8 alkyl group; E is selected from the group consisting of: NH2, NHC(O)CH3, OR7, NHR7 and N(R7)(R8), wherein R7 and R8 are independently a C1-20 linear, branched or cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of the group consisting of: oxo, OH, F, Cl, Br, I, NH2, CN, SH, SO3H and NO2, and wherein zero to ten backbone carbons of the optionally substituted alkyl group are optionally and independently substituted with O, N or S; Q is wherein each of J and G is independently selected from the group: H, OH, OAc, OC(O)CH3, F, Cl, Br, NO2, CN, OR12, SO2R12, COR12 and SR12, wherein R12 is CH3, CH2CH3 or CH2CH2CH3, and M is H, OH, OAc, OC(O)CH3, NH2, F or Cl, and L is H, OH, OAc, OC(O)R13 or NH2, wherein R13 is a C1-20 linear, branched or cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of the group: oxo, OH, F, Cl, Br, I, NH2, CN, SH, SO3H and NO2, and wherein zero to ten backbone carbons of the optionally substituted alkyl group are optionally and independently substituted with O, N or S.