| 摘要 |
Disclosed are 4-amino-2-oxo-1-benzyl-2,3-dihydro-1H-imidazo[4,5-c]pyridine derivatives of the general formula (C) which are substituted with alkylphosphonic acid groups as TLR7 agonists for attachment to insoluble metal salts and for raising an immune response in the treatment of a viral disease, a bacterial disease, a fungal disease, and/or a parasitic disease; wherein: Xc is CH; P3 is selected from H, alkyl, trifluoromethyl, and H-((CH2)pO)q(CH2)pOs- and -Y-L-X-P(O)(ORx)(ORy); P4 is selected from H, alkyl, alkylaryl and -Y-L-X-P(O)(ORx)(ORy); Rx and Ry are independently selected from H and alkyl; Rc is selected from H and alkyl; X is selected from a covalent bond, O and NH; Y is selected from a covalent bond, O, C(=O), S and NH; L is selected from, a covalent bond, alkylene, alkenylene, arylene, heteroarylene, alkyleneoxy and -((CH2)pO)q(CH2)p- each optionally substituted with 1 to 4 substituents independently selected from halo, OH, alkyl, -OP(O)(OH)2 and P(O)(OH)2; p is 1-6; q is 1-4; and s is selected from 0 and 1; with the proviso that at least one of P3 and P4 is -Y-L-X-P(O)(ORx)(ORy). Representative compounds are selected from (4-(4-((4-amino-6-(2-methoxyethoxy)-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-1-yl)methyl)phenoxy)butyl)phosphonic acid, (4-(4-((4-amino-2-oxo-6-(trifluoromethyl)-2,3-dihydro-1H-imidazo[4,5-c]pyridin-1-yl)methyl)phenoxy)butyl)phosphonic acid, (3-((4-amino-1-(4-(butyloxyphosphonate)benzyl)-2-oxo-2,3-dihydro-1Himidazo[4,5-c]pyridin-6-yl)amino)propyl)phosphonic acid, (3-((4-amino-1-benzyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-6-yl)thio)propyl) phosphonic acid and (4-((4-amino-6-(2-methoxyethoxy)-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-1-yl)methyl)benzyl)phosphonic acid. Also disclosed is a composition comprising: (i) a TLR7 agonist as defined above and; (ii) an insoluble metal salt, for treating or preventing a viral disease, a bacterial disease, a fungal disease, and/or a parasitic disease. |
