142356-40-9Relevant articles and documents
Design, Synthesis, and Antiviral Activity of Certain 2,5,6-Trihalo-1-(β-D-ribofuranosyl)benzimidazoles
Townsend, Leroy B.,Devivar, Rodrigo V.,Turk, Steven R.,Nassiri, M. Reza,Drach, John C.
, p. 4098 - 4105 (1995)
A new series of 2-substituted 5,6-dichlorobenzimidazole ribonucleosides has been synthesized and tested for activity against two human herpes viruses and for cytotoxicity. 2,5,6-Trichloro-1-(β-D-ribofuranosyl)benzimidazole (TCRB) was prepared by ribosylation of the heterocycle 2,5,6-trichlorobenzimidazole followed by a removal of the protecting groups.The 2-bromo derivative (BDCRB) was made in a similar fashion from 2-bromo-5,6-dichlorobenzimidazole.In contrast, the 2-iodo derivative presented a more difficult problem since the appropriate heterocycle was unavailable.This prompted us to prepare the 2-amino derivative followed by nonaqueous diazotization and removal of the blocking groups.Biological evaluation revealed marked differences in the activities of these compounds and the closely related known compound 5,6-dichloro-1-(β-D-ribofuranosyl)benzimidazole (DRB).DRB was weakly active against both human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1), (IC50's = 42 and 30 μM, respectively) but was cytotoxic to uninfected human foreskin fibroblasts and KB cells in the same dose range.Similar results were obtained with the heterocycle 2,5,6-trichlorobenzimidazole.In marked contrast, the ribonucleoside of 2,5,6-trichlorobenzimidazole (TCRB) was active against HCMV (IC50 = 2.9 μM, plaque assay; IC90 = 1.4 μM, yield assay) but only weakly active against HSV-1 (IC50 = 102 μM, plaque assay).Little to no cytotoxicity was observed in HFF and KB cells at concentrations up to 100 μM.By changing the substituent at the 2-position from chlorine to bromine (BDCRB), a 4-fold increase in activity against HCMV was observed without any significant increase in cytotoxicity.In contrast, the 2-I and 2-NH2 derivatives were only weakly active against HCMV and HSV-1 with activity not well-separated from cytotoxicity.These data establish that for maximum activity against HCMV with separation from cytotoxicity, ribose is preferred at the 1-position and that Cl or Br is apparently preferred at the 2-position.The activity and selectivity of both TCRB and BDCRB were better than that observed with either ganciclovir or foscarnet.
Synthesis and in vitro antimicrobial activity of some novel substituted benzimidazole derivatives having potent activity against MRSA
Tuncbilek, Meral,Kiper, Tulug,Altanlar, Nurten
scheme or table, p. 1024 - 1033 (2009/09/06)
The novel benzimidazole derivatives (3, 5, 8, 9, 12-14, 18-41) were prepared in this paper and the antimicrobial activities of these compounds against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA, standard and clinical isolates), Bacillus subtilis, Escherichia coli and Candida albicans were evaluated. Compounds 24-26 which have no substitution of N-1 position displayed better antibacterial activities than those of standards (ciprofloxacin, ampicillin and sultamicillin) against both the drug-resistant bacteria (MRSA, standard and clinical isolates). These derivatives (24-26), 2,5,6-trihalogenobenzimidazole analogues (8, 12), 5,6-dichloro-2-amino derivative (13), and 5-chloro-2-(4-benzyloxyphenyl)benzimidazole (35) exhibited the most potent antibacterial activity with MIC 3.12 μg/ml against S. aureus.
Design, synthesis, and antiviral evaluations of 1-(substituted benzyl)- 2-substituted-5,6-dichlorobenzimidazoles as nonnucleoside analogues of 2,5,6- trichloro-1-(β-D-ribofuranosyl)benzimidazole
Porcari, Anthony R.,Devivar, Rodrigo V.,Kucera, Louis S.,Drach, John C.,Townsend, Leroy B.
, p. 1252 - 1262 (2007/10/03)
We have recently reported that certain ribosylated polyhalogenated benzimidazoles are potent and selective inhibitors of HCMV replication at noncytotoxic concentrations. To extend the structure-activity relationship beyond these first-generation compounds, we alkylated 5,6dichloro-2- substituted-benzimidazoles with either a series of substituted benzyl halides or (2bromoethyl)benzene to obtain five series of nonnucleoside analogues. Evaluation of these compounds for activity against herpes viruses revealed that the new compounds were less active than the benzimidazole ribonucleosides against human cytomegalovirus (HCMV) and inactive against herpes simplex virus type 1 (HSV-1). However, as part of our broader antiviral testing, we found that some of these compounds were active against HIV. Comparisons of the biological data revealed that a chloro or bromo group was required at the 2-position for the best separation of activity against HIV and cytotoxicity. Evaluation of the most active compounds against drug- resistant HIV suggested that they act by a mechanism other than inhibition of reverse transcriptase.
