1401791-45-4Relevant articles and documents
Asymmetric synthesis of host-directed inhibitors of myxoviruses
Moore, Terry W.,Sana, Kasinath,Yan, Dan,Thepchatri, Pahk,Ndungu, John M.,Saindane, Manohar T.,Lockwood, Mark A.,Natchus, Michael G.,Liotta, Dennis C.,Plemper, Richard K.,Snyder, James P.,Sun, Aiming
, p. 197 - 203 (2013/03/29)
High-throughput screening (HTS) previously identified benzimidazole 1 (JMN3-003) as a compound with broad antiviral activity against different influenza viruses and paramyxovirus strains. In pursuit of a lead compound from this series for development, we sought to increase both the potency and the aqueous solubility of 1. Lead optimization has achieved compounds with potent antiviral activity against a panel of myxovirus family members (EC50 values in the low nanomolar range) and much improved aqueous solubilities relative to that of 1. Additionally, we have devised a robust synthetic strategy for preparing 1 and congeners in an enantio-enriched fashion, which has allowed us to demonstrate that the (S)-enantiomers are generally 7- to 110-fold more potent than the corresponding (R)-isomers.