Toshinori Ohmine

Synthesis and anti-HIV activity of arylpiperazinyl fluoroquinolones: a new class of anti-HIV agents.

Synthesis and anti-HIV activity of a series of novel arylpiperazinyl fluoroquinolones are reported. In the SAR study, the aryl substituents on the piperazine nitrogen were found to play an important role for the anti-HIV-1 activity. A few of the compounds exhibited potent anti-HIV activity: IC50=0.06 microM in chronically infected cells.

Anti-HIV-1 Activities and Pharmacokinetics of New Arylpiperazinyl Fluoroquinolones

Anti-HIV-1 activities and pharmacokinetics of a series of novel arylpiperazinyl fluoroquinolones are reported. Modification at the C-8 position with a trifluoromethyl group was superior to that with a difluoromethoxy group to achieve higher anti-HIV-1 activity. Two compounds studied exhibited quite high anti-HIV-1 activities (IC(50)<50 nM) in vitro and high bioavailabilities (BA>90%) in monkeys.

A New Fluoroquinolone Derivative Exhibits Inhibitory Activity against Human Immunodeficiency Virus Type 1 Replication

The inhibitory activity of several fluoroquinolone antibiotics against human immunodeficiency virus type 1 (HIV-1) replication was investigated. R-71762, (±) 9-fluoro-3-fluoromethyl-2,3-dihydro-10-[4-(2-pyridyl)-1-piperazinyl]-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid, protected MT-4 cells from HIV-1-induced cytopathic effects. Furthermore, the compound inhibited virus replication both in acutely and in chronically HIV-1-infected cells. On the other hand, ofloxacin, levofloxacin, ciprofloxacin, norfloxacin and enoxacin, that were previously reported to be protective against HIV-1-induced cytopathic effects, did not show any protective activity in our assay system. These results indicate that R-71762 is a novel inhibitor of HIV-1 replication and is effective even in HIV-1 chronically infected cells.

Biologically Active Oligodeoxyribonucleotides - IV 1 : Anti-HIV-1 Activity of Tgggag Having Hydrophobic Substituent at Its 5′-End via Phosphodiester Linkage §

Abstract Hexadeoxyribonucleotides (6-mers) having a 5′-TGGGAG-3′ sequence bearing hydrophobic substituents at their 5′-ends via phosphodiester linkages were prepared and evaluated for anti-HIV-1 activity in vitro. Some of these modified 6-mers showed weak anti-HIV-1 activities and they were less potent than the 6-mer having a DMTr group directly attached at its 5′-terminus. 1. Part 111: Hotoda, H.; Koizumi, M.; Koga, R.; Momota, K.; Ohmine, T.; Furukawa, H.; Nishigaki, T.; Kinoshita, T.; Kaneko, M.; Kimura, S.; and Shimada, K. (1994) Proceedings of First International Antisense Conjierence of Japan p62 (Pl-24): In print in Antisense Research and Development. §This paper is dedicated to Dr. Yoshihisa Mizuno, Emeritus Professor of Hokkaido University, on the occasion of his 75th birthday.

Biologically Active Oligodeoxyribonucleotides. VII. Anti-HIV-1 Activity of Hexadeoxyribonucleotides Bearing 3′- and 5′-End-Modifications

Abstract It has been determined that hexadeoxyribonucleotides (5′TGGGAG3′), which have modified aromatic groups such as the trityl group at the 5′-end, exhibit anti-HIV-1 activity in vitro. The 6-mer (S-1443) bearing a 3,4-dibenzyloxybenzyl (3,4-DBB) group at the 5′-end and a 2-hydroxyethylphosphate group at the 3′end exhibited the most potent activity and the least cytotoxicity. Moreover, it was found that the S-1443 was the most stable, when the 6-mer analogues were incubated with mouse, rat, or human plasma.