| 摘要 |
6-O-substituted erythromycins of e.g. formula (II) and (IX) and their salts and prodrugs are new: Q = X; Q1 = OH; and Q2 = Ra; or Q = O; and Q1 + Q2 = OCH2O; or Q = O; and Q1 + Q2 = OC(O)O; or Q = O; and Q1 + Q2 = N(WRg)CH(O)O; Q3 = a group of formula (i); Q4 = a group of formula (ii); X = O, NOH, NOR1, NOC(R5)(R6)OR1; R1 = 1-12C alkyl (optionally substituted), 3-12C cycloalkyl, SiR2R3R4 or Si(aryl)3; R2-R4 = 1-12C alkyl; R5, R6 = H or 1-12C alkyl (optionally substituted) or R5 + R6 = 3-12C cycloalkyl; Ra, Rb = H or OH; one of Rc and Rd = H the other = optionally protected OH, halo, NR7R8, OCONHaryl, OCONHheteroaryl, OCONR7R8, OSO2-1-6C Alk or OSO2CH2CH2NR7R8; Alk = optionally substituted alkyl; or Rc + Rd = O, NOH or NOR1; R7, R8 = H, 1-12C alkyl (optionally substituted); optionally substituted 1-8C cycloalkyl (sic) or substituted 1-12C alkyl (sic); or NR7R8 = 3-10 membered heterocycloalkyl; Re = OMe, F or OH; Rf = H or hydroxy protecting group; W = absent or O, NHCO, N=CH or NH; Rg = H, 1-6C alkyl (optionally substituted), 3-7C cycloalkyl, Ar or Het; Ar = optionally substituted aryl; Het = optionally substituted heteroaryl; at least 2 of A, B, D and E = H and the others = (i) H, 3-7C cycloalkyl, Ar, Het, heterocycloalkyl or (ii) 1-6C alkyl (optionally substituted), all (ii) further optionally substituted by MR11; or 2 of A, B, D and E complete a 3-7 membered ring optionally containing O, NH, N(1-6C alkyl), N(Ar-1-6C alkyl), N(Het-1-6C alkyl), S, S(O)n', CONH, CONR12, NHCO, NR12CO or C(=NH)NH; M = CONH, NHCO, NH, N=, NMe, NHCOO, NHCONH, OCONH, OCOO, CO, S(O)n', COO, OCO or CO; n' = 0-2; R11 = 1-6C alkyl (optionally substituted); R = Me (substituted by CN, F, CO2R12, S(O)n'R12, NHCOR12, NHCONR13R14, Ar or Het), 2-10C alkyl (optionally substituted), 3C alkenyl (substituted by halo, CHO, COR12, COR11, CONR13R14, CN, Ar, Het, 3-12C cycloalkyl or 1-12C alkyl-heteroaryl), 4-10C alkenyl (optionally substituted) or 3-10C alkynyl (optionally substituted); R12 = 1-3C alkyl (optionally substituted by aryl or heteroaryl); R13, R14 = H or 1-3C alkyl. |
