Patent EP-2610263-A1 (EP)
Inventor: BROSSMER REINHARD PROF DR
IPC: A61K31/7028
Filed: 2011-12-30
Abstract: Sialic acid derivatives (I) are new. Sialic acid derivatives of formula (I) or their salts, metabolites or prodrugs are new. A1, A2 : D1-[Y3-D2] m-; D1, D2 : mono- or polycyclic and aromatic, partially unsaturated or saturated 3-14C hydrocarbyl or aromatic, partially unsaturated or saturated 3-8-membered heterocyclyl (both optionally mono- or polysubstituted by X1); X1 : halo, CN, NO 2, OH, mercapto, NH 2, carboxy, hydroxylamino, azido, B(OH) 2, SO, SO 3M, OSO 3M, SO 2NH 2, SO 2CF 3, PO 3M, OPO 3M, cyanomethyl, 1-8C (halo)alkyl, 2-8C alkenyl, 2-8C alkynyl, (halo)alkyloxy, 2-8C alkenyloxy, 2-8C alkynyloxy, alkylthio, alkylamino, dialkylamino, trialkyl-amino, formyl, alkylcarbonyl, alkylsulfonyl, alkyl-sulfoxy, alkylamino-sulfoxy, dialkylamino-sulfoxy, alkyloxycarbonyl, alkylcarbonyloxy, aminocarbonyl, aminothiocarbonyl, alkylaminocarbonyl, alkylcarbonylamino, dialkylaminocarbonyl, alkylamino-thiocarbonyl, =O, =S, 1-8C alkyl-imino or 1-8C alkyl-oximino; either Y1, Y2 : 1-4C (halo)alkyl, 1-4C alkyl-CO, -C(O)-, -CH 2-C(O)-, -CH=CH-C(O)-, -CC-C(O)-, -S(O) 2-, -CH 2-S(O) 2-, -NR11-C(O)-, -CH(CF 3)-, -NR11-3-cyclobutene-1,2-dione-4-yl, -CH 2-NR11-3-cyclobutene-1,2-dione-4-yl, -NR11-3,2,5-thiadiazole-1-oxide-4-yl or -NR11-3,2,5-thiadiazole-1,1-dioxide-4-yl; or Y1+N to which it is bonded+R8, Y2+N to which it is bonded+R8 : 1H-(1,2,3)triazol-1-yl (which is bonded to A in 4th position), 1H-(1,2,3)triazol-1-yl- (which is bonded to A in 5th position), -CH 2-1H-(1,2,3)triazol-1-yl (which is bonded to CH 2 in 4th position) or -CH 2-5-1H-(1,2,3)triazol-1-yl (which is bonded to CH 2 in 5th position); Y3 : bond, O, S, S(O), S(O) 2, CH 2, C(O), C(R11) 2 or NR11; m : 0-2; Z1 : O, S, CH 2 or NR11; D11 : Z2-T1-Y4-A3-Y5-T2-Z2; Z2 : -O-, -S-, -NR11-, -NH-C(O)-, -CH 2-, -CF 2-, -CH(OH)-, -N(R11)-O-, -O-NR11-, -O-N=CH-, 1H-(1,2,3)triazol-1-yl (which is bonded to T1 or T2 in 4th position) or 1H-(1,2,3)triazol-1-yl (5) (which is bonded to T1 or T2 in 5th position); T1, T2 : 1-30C alkanediyl (in which at least one non-terminal -CH 2- is optionally replaced by -O-, -S-, -S(O)-, -S(O) 2-, -S +>(CH 3)-, -P(O 2)- or -NR11-, at least one H is optionally replaced by F, Cl, OR11, OSO 3M, =O, =S, carboxy, NH 2, NHR12 or NHR13, at least one non-terminal -CH 2-CH2- is optionally replaced by 1H-(1,2,3)triazol-1-yl (which is bonded with remaining part of molecule in 5th position) or -CR11=CR11- or -CC-, -CH 2CH 2CH 2 is optionally replaced by 1H-(1,2,3)triazol-1-yl (yl (which is bonded with remaining part of molecule in 4th position) or -O-N=CH, and -CH 2CH 2CH 2CH 2- is optionally replaced by phenyl-1,4-diyl); Y4, Y5 : bond, O, S, NR11, S(O), S(O) 2, -C(O)-, -C(O)-NR11-, -NR11-C(O)-, -C(O)-O-, -O-C(O)-, -NR11-CO-NR11-, -NR11-S(O) 2-, -S(O) 2-NR11-, -CH 2-NR11-C(O)-, -CH 2-C(O)-NR11, -CH 2-NR11-, -CH(CF 3)-NR11, -CH=N-O- or -O-N=CH-; A3 : 1-8C alkanediyl, 2-8C alkenediyl, 2-8C alkynediyl or 4-8C alkadiene-diyl (in all groups several -CH 2- are replaced by O, S, S(O), S(O) 2, NR11 or C(O), and at least one H is optionally replaced by X2), A4-[Z3-A5] n, 1,1'-ferrocene-diyl, 1,1'-cobaltocendiyl, 1,1'-ruthenocene or diamino-dichloroplatinum-diyl; A4, A5 : saturated, partially unsaturated or aromatic 3-14C mono- or polycyclic hydrocarbyl or aromatic, partially unsaturated or saturated and mono-or polycyclic 3-8-membered heterocyclyl (both optionally substituted by X2); Z3 : bond, O, S, S(O), S(O) 2, NR11, C(O) or C(R11) 2; X2 : 1-4C (halo)alkyl or (halo)alkyloxy (both containing F or Cl), F, Cl, Br, NO 2, hydroxylamino, B(OH) 2, SO 3M, OSO 3M, SO 2NH 2, PO 3M, OPO 3M, alkylthio, alkylamino, dialkylamino, trialkyl-amino, alkylcarbonyl, alkylsulfonyl, alkyl-sulfoxy, alkylamino-sulfoxy, dialkylamino-sulfoxy, alkoxycarbonyl, alkylcarbonyloxy, aminocarbonyl, alkylaminocarbonyl, alkylcarbonylamino, dialkylaminocarbonyl, alkylamino-thiocarbonyl, 1-4C alkyl-imino or 1-4C alkyl-oxyimino; n : 0 or 1; R1 : C(O)OM, O-PO 3(M) 2, O-SO 3M, SO 3M, C(O)-NH-S(O) 2-R11, PO 3(M) 2 or C(O)NOM; R2, R3 : H or F; R4, R7 : H, OH, OR13, OC(O)NHR12 or NR11; R6 : H or R13; R5 : H, R11, (R11) 2, C(O)H, C(O)CH 2OH or C(O)-haloalkyl; R8 : R11; M : H, 1-6C alkyl or cation; R11 : H, R12 or R13; R12 : 1-6C alkyl, phenyl or benzyl; and R13 : -C(O)-1-6C alkyl, -C(O)-phenyl or -C(O)-1-4C alkylphenyl. [Image] ACTIVITY : Antibacterial; Virucide; Antiparasitic; Immunomodulator. MECHANISM OF ACTION : None given.