1268383-41-0Relevant articles and documents
Imidazopyridazine hepatitis C virus polymerase inhibitors. Structure-activity relationship studies and the discovery of a novel, traceless prodrug mechanism
Leivers, Martin,Miller, John F.,Chan, Stephanie A.,Lauchli, Ryan,Liehr, Sebastian,Mo, Wenyan,Ton, Tony,Turner, Elizabeth M.,Youngman, Michael,Falls, J. Greg,Long, Susan,Mathis, Amanda,Walker, Jill
, p. 1964 - 1975 (2014/04/03)
By reducing the basicity of the core heterocycle in a series of HCV NS5B inhibitors, the hERG liability was reduced. The SAR was then systematically explored in order to increase solubility and enable dose escalation while retaining potency. During this e
Synthesis of HCV replicase inhibitors: Base-catalyzed synthesis of protected α-hydrazino esters and selective aerobic oxidation with catalytic Pt/Bi/C for synthesis of imidazole-4,5-dicarbaldehyde
Bowman, Roy K.,Brown, Andrew D.,Cobb, Jannine H.,Eaddy, John F.,Hatcher, Mark A.,Leivers, Martin R.,Miller, John F.,Mitchell, Mark B.,Patterson, Daniel E.,Toczko, Matthew A.,Xie, Shiping
, p. 11680 - 11690 (2014/01/06)
A robust convergent synthesis of the prodrugs of HCV replicase inhibitors 1-5 is described. The central 5H-imidazo[4,5-d]pyridazine core was formed from acid-catalyzed cyclocondensation of an imidazole-4,5-dicarbaldehyde (20) and a α-hydrazino ester, generated in situ from the bis-BOC-protected precursors 25 and 33. The acidic conditions not only released the otherwise unstable α-hydrazino esters but also were the key to avoid facile decarboxylation to the parent drugs from the carboxylic ester prodrugs 1-5. The bis-BOC α-hydrazino esters 25 and 33 were prepared by addition of ester enolates (from 23 and 32) to di-tert-butyl azodicarboxylate via catalysis with mild inorganic bases, such as Li2CO3. A selective aerobic oxidation with catalytic 5% Pt-Bi/C in aqueous KOH was developed to provide the dicarbaldehyde 20 from the diol 27.
Imidazopyridazine Compounds for Treating Viral Infections
-
, (2011/04/14)
Disclosed are compounds and compositions of Formula (I), pharmaceutically acceptable salts and solvates thereof, and their preparation and uses for treating viral infections mediated at least in part by a virus in the Flaviviridae family of viruses:
