1186482-11-0Relevant articles and documents
Piperazine oxadiazole inhibitors of acetyl-CoA carboxylase
Bourbeau, Matthew P.,Siegmund, Aaron,Allen, John G.,Shu, Hong,Fotsch, Christopher,Bartberger, Michael D.,Kim, Ki-Won,Komorowski, Renee,Graham, Melissa,Busby, James,Wang, Minghan,Meyer, James,Xu, Yang,Salyers, Kevin,Fielden, Mark,Véniant, Murielle M.,Gu, Wei
supporting information, p. 10132 - 10141 (2014/01/17)
Acetyl-CoA carboxylase (ACC) is a target of interest for the treatment of metabolic syndrome. Starting from a biphenyloxadiazole screening hit, a series of piperazine oxadiazole ACC inhibitors was developed. Initial pharmacokinetic liabilities of the piperazine oxadiazoles were overcome by blocking predicted sites of metabolism, resulting in compounds with suitable properties for further in vivo studies. Compound 26 was shown to inhibit malonyl-CoA production in an in vivo pharmacodynamic assay and was advanced to a long-term efficacy study. Prolonged dosing with compound 26 resulted in impaired glucose tolerance in diet-induced obese (DIO) C57BL6 mice, an unexpected finding.
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.
ANTI-VIRAL COMPOUNDS, COMPOSITIONS, AND METHODS OF USE
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Page/Page column 22, (2010/08/04)
Disclosed are compounds of Formula (I), pharmaceutically acceptable salts thereof, compositions thereof, and methods for their preparation and uses for treating viral infections mediated at least in part by a virus in the Flaviviridae family of viruses.
ANTI-VIRAL COMPOUNDS, COMPOSITIONS, AND METHODS OF USE
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, (2009/09/25)
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.
