title: Asymmetric synthesis of host-directed inhibitors of myxoviruses.
abstract: 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 (EC(50) 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.
authors: Emory Institute for Drug Development, Emory University, 1515 Dickey Drive, Atlanta, GA 30322, USA.
authors: Terry W
authors: TW
authors: Moore
authors: Kasinath
authors: K
authors: Sana
authors: Dan
authors: D
authors: Yan
authors: Pahk
authors: P
authors: Thepchatri
authors: John M
authors: JM
authors: Ndungu
authors: Manohar T
authors: MT
authors: Saindane
authors: Mark A
authors: MA
authors: Lockwood
authors: Michael G
authors: MG
authors: Natchus
authors: Dennis C
authors: DC
authors: Liotta
authors: Richard K
authors: RK
authors: Plemper
authors: James P
authors: JP
authors: Snyder
authors: Aiming
authors: A
authors: Sun
keywords: asymmetric synthesis; benzimidazole; host-directed; myxovirus; small molecule inhibitor
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