70890-53-8Relevant academic research and scientific papers
1,4-Benzodiazepines as inhibitors of respiratory syncytial virus
Carter, Malcolm C.,Alber, Dagmar G.,Baxter, Robert C.,Bithell, Sian K.,Budworth, Jo,Chubb, Ann,Cockerill, G. Stuart,Dowdell, Verity C. L.,Henderson, Elisa A.,Keegan, Sally J.,Kelsey, Richard D.,Lockyer, Michael J.,Stables, Jeremy N.,Wilson, Lara J.,Powell, Kenneth L.
, p. 2311 - 2319 (2007/10/03)
Respiratory syncytial virus (RSV) is the cause of one-fifth of all lower respiratory tract infections worldwide and is increasingly being recognized as a serious threat to patient groups with poorly functioning immune systems. Our approach to finding a novel inhibitor of this virus was to screen a 20 000-member diverse library in a whole cell XTT assay. Parallel assays were carried out in the absence of virus in order to quantify any associated cell toxicity. This identified 100 compounds with IC50's less than 50 μM. A-33903 (18), a 1,4-benzodiazepine analogue, was chosen as the starting point for lead optimization. This molecule was moderately active and demonstrated good pharmacokinetic properties. The most potent compounds identified from this work were A-58568 (47), A-58569 (44), and A-62066 (46), where modifications to the aromatic substitution enhanced potency, and A-58175 (42), where the amide linker was modified.
BENZODIAZEPINE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
-
Page 60, (2008/06/13)
Benzodiazepine derivative of formula (I), and pharmaceutically acceptable salts thereof, are found to be active against RSV. Formula (I) Wherein: - R1 represents C1-6 alkyl, aryl or heteroaryl; - R2 represents hydrogen or C1-6 alkyl; - each R3 is the same or different and represents halogen, hydroxy, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio C1-6 haloalkyl, C1-6 haloalkoxy, amino, mono(C1-6 alkyl)amino, di(C1-6 alkyl)amino, nitro, cyano, -CO2RI, -CONRIRII, -NH-CO-RI, -S(O)RI, -S(O)2RI, -NH-S(O)2RI, -S(O)NRIRII or -S(O)2NRIRII wherein each RI and RII is the same or different and represents hydrogen or C1-6 alkyl; - n is from 0 to 3; R4 represents hydrogen or C1-6 alkyl; - R6 represents C1-6 alkyl, aryl, heteroaryl, carbocyclyl, heterocyclyl, aryl-(C1-6 alkyl)-, heteroaryl-(C1-6 alkyl)-, carbocyclyl-(C1-6 alkyl)-, heterocyclyl-(C1-6 alkyl)-, aryl-C(O)-C(O)-, heteroaryl-C(O)-C(O)-, carbocyclyl-C(O)-C(O)-, heterocyclyl-C(O)-C(O)- or, -XR6; - X represents -CO-, -S(O)- or -S(0)2-; and - R6 represents C1-6 alkyl, hydroxy, C1-6 alkoxy, C1-6 alkylthio, aryl, heteroaryl, carbocyclyl, heterocyclyl, aryl-(C1-6 alkyl)-, heteroaryl-(C1-6 alkyl)-, carbocyclyl-(C1-6 alkyl)-, heterocyclyl-(C1-6 alkyl)-, aryl-(C 1-6hydroxyalkyl)-, heteroaryl-(C1-6 hydroxyalkyl)-, carbocyclyl-(C1-6 hydroxyalkyl)-, heterocyclyl-(C 1-6 hydroxyalkyl)-, aryl-(C 1-6alkyl)-O-, heteroaryl-(C 1-6alkyl)-O-, carbocyclyl-(C1-6 alkyl)-O-, heterocyclyl-(C1-6 alkyl)-O- or -NRIRII wherein each RI and RII is the same or different and represents hydrogen, C1-6 alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, aryl- (C1-6 alkyl)-, heteroaryl-(C1-6 alkyl)-, carbocyclyl-(C1-6 alkyl)- or heterocyclyl-(C1-6 alkyl)-.
