| 摘要 |
Effector conjugates of epithilones (I) as a single isomer or mixture of different isomer and/or their salts are new. Effector conjugates of epithilones of formula (I) as a single isomer or mixture of different isomer and/or their salts are new; R1a, R1b = H, 1-10C alkyl, aryl, aralkyl; or R1a+R1b = (CH2)m; either R2a, R2b = H, 1-10C alkyl, aryl, aralkyl; or R2a+R2b = (CH2)n; R3 = H, 1-10C alkyl, aryl or aralkyl; either R4a, R4b = H, 1-10C alkyl, aryl aralkyl; or R4a+R4b = (CH2)p; R5 = 1-10C alkyl, aryl, aralkyl, CO2H, CH2O alkyl, CH2O acyl, CN, CH2NH2, CH2N (alkyl, acyl)1,2 or CH2 Hal; Hal = halo; either R6, R7 = H; or R6+R7 = bond, O, NH, N alkyl or CH2; G = O or CH2; D-E = H2C-CH2, HC=CH, Ctriple bondC, CH(OH)-CH(OH), CH(OH)-CH2, CH2CH(OH), ethylene epoxide, OCH2; when G = CH2, D-E = CH2O; W = C(=X)R8, bicyclic or tricyclic aromatic or heteroaromatic; L3 = H; or when W = OH, L3 = OL4 or when W = amino, L3 = NR25L4; Z = O or H/OR12; A-Y = OC(=O), OCH2, CH2C(=O), NR21C(=O) or NR21SO2; L1, L2, L4 = H, C(=O)Cl, C(=S)Cl, PG-Y or a linker of formula (III) or IV; and m,n,p = 2-5. Provided that at least one of L1, L2 or L4 represents a linker of formula (III) or (IV). Full definitions are given in the DEFINITIONS - Full Definitions field. Independent claims are also included for: (1) Linkers of formula (IIIa) where RG = RG1 (III1), where RG = RG2 (III2), where RG = RG3 (III3), and formula (IVa) where RG = RG1 (IV1), where RG = RG2 (IV2), where RG = RG3 (IV3); and (2) Effector recognition unit conjugate of formula (I'). In formula (I1), FG1 = 1-10C alkyl S3 or Z1 and at least one FG2a or FG2b; FG2a = -S-S, S-substituted Z1; where Z1 = hydantoin, C(=O)CH=CH, C(=O)-C(Br)=C, C(=O)-C(Cl)=S, S(=O)2C=C; FG2b = CONH; RG1 = O=C=N or S=C=N; RG2 = Hal-C(=T)-CHR22, Hal-C(=T)-CHR22-NR23-C(=T), R26 = 1-10C alkyl, aryl or aralkyl; and RG3 = OH, NHR24a or COOH. Provided that in formula (III3), compound 1-(4-amino-phenyl)-pyrrole-2,5-dione is not included. |
