Synthesis of syn and anti isomers of 6-[[(hydroxyimino)phenyl]methyl]-1-[(1-methylethyl)sulfonyl]-1H-benzimidazol-2-amine. Inhibitors of rhinovirus multiplication

Abstract

The synthesis and antirhinovirus activity of syn and anti isomers of 6-[[(hydroxyimino)phenyl]methyl]-1-[(1-methylethyl)sulfonyl]-1H-benzimidazol-2-amine (4 and 5) are reported. The structural assignments of 4 and 5 are based upon 13C NMR spectra of both isomers and also X-ray analysis of 5. The anti-isomer 5 was more potent than the syn-isomer 4 when compared as an inhibitor of rhinovirus multiplication in vitro. Both isomers inhibited multiplication of 15 different serotypes of rhinovirus.

Coxsackievirus mutants that can bypass host factor PI4KIIIβ and the need for high levels of PI4P lipids for replication

“…Enviroxime was synthesized as described previously [9]. Guanidine hydrochloride and GW5074 were purchased from Sigma Aldrich.…”

“…The search for inhibitors of virus replication has resulted in the identification of various compounds that affect the specific stages of the viral life cycle. One of these is enviroxime, a compound already discovered in the late 1970s that inhibits initiation of positive-strand RNA synthesis of PV, HRV, and coxsackievirus B3 (CVB3) [7][8][9]. Enviroxime-resistant enteroviruses were subsequently isolated in an attempt to identify the target of the compound.…”

Poliovirus Studies during the Endgame of the Polio Eradication Program

“…In the post-vaccine era, PV serves as one of the most well-established models for positive-stranded RNA viruses, and infections with this virus have been extensively studied with modern molecular biological techniques. Enumerating all of the milestones reached in PV studies is far beyond the scope of this review, however, this list would include sequencing of the PV genome (9,10), the development of reverse genetics for the virus (11), elucidation of the crystal structure of the virion (12), identification of the internal ribosomal entry site (IRES) (13), identification of the PV receptor (PVR, CD155) (14,15), development of a transgenic mouse model of poliomyelitis (16,17), identification of attenuation determinants in oral polio vaccine (OPV) strains (18,19), identification of drug candidates (20,21), development of a cell-free replication system (22), identification of cis-acting replication elements (23,24), identification of circulating vaccine-derived PVs (cVDPVs) (25), and identification of host targets for drug candidates (26)(27)(28)(29)(30). PV studies in the post-vaccine era have produced valuable tools and information essential to the eradication program, including nucleotide sequences of PV and other enteroviruses (9,10,31), which have been used to design primers for current reverse transcription (RT)-PCR systems for PV detection (32,33); neurovirulence determinants of PV that are used for quality control of vaccines and evaluations of environmental isolates (18,34,35); PV-sensitive murine cell line (L20B) (14), which is a cell line that expresses the PVR and is currently used for PV surveillance because of its high specificity for PV infection, a PVR-transgenic mouse (TgPVR21) model as an alternative to monkeys used in neurovirulence tests for PV vaccines (36), and candidate compounds for ...…”

Antipicornavirus Drugs: Current Status

“…7) Washington DC, 1978: Abstract P234;Wikel et al, 1980). The compound was found to cause serious side-effects when administered orally in humans and did not demonstrate statistically significant clinical efficacy (Hayden & Gwaltney, 1982;Miller et al, 1985;Phillpotts et al, 1983).…”