- Design, synthesis and antiviral activity of α-L-arabinofuranosyl derivatives of 2-substituted-5,6-dichlorobenzimidazoles
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A number of 2.-s. have been prepared by condensation of 2-bromo-5,6- dichlorobenzimidazole or 2,5,6-trichlorobenzimidazole with tetra-O-acetyl-L- arabinofuranose. 2-Alkylamino derivatives were prepared by a substitution of the 2-chloro group with the appropriate amines. All target compounds were evaluated for activity against HCMV and HSV-1. The 2-chloro and 2-bromo derivatives showed moderate activity against HCMV at non-cytotoxic concentrations.
- Girardet, Jean-Luc,Drach, John C.,Chamberlain, Stanley D.,Koszalka, George W.,Townsend, Leroy B.
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- Crystalline forms of an antiviral benzimidazole compound
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The invention relates to crystalline forms of 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole, pharmaceutical compositions comprising the same, processes for preparing the same, and their use in medical therapy.
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Page/Page column 14-15
(2015/11/10)
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- Lyxofuranosyl benzimidazoles as antiviral agents
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The present invention pertains to D- and L-lyxofuranosyl benzimidazole compounds. In one embodiment, the present invention pertains to D- and L-lyxofuranosyl benzimidazole compounds selected from the group consisting of compounds having a formula selected from the following: wherein R2, R4, R5, R6, and R7are independently the same or different and independently selected from the group consisting of: —H, —F, —Cl, —Br, —I, —NO2, —N(R8)2, —OR8, —SR12, and —CF3, wherein R8is independently —H or an alkyl group having 1-6 carbon atoms and wherein R12is independently —H or a hydrocarbyl group having 1-10 carbon atoms; and, R9, R10and R11are independently the same or different and are H or a hydroxyl protecting group; anomeric and optical isomers thereof; and, pharmaceutically acceptable salts and prodrug derivatives thereof. The present invention also pertains to antiviral compositions using these compounds, methods of treating a viral infection using these compounds, and the use of these compounds in the preparation of a medicament for use in the treatment of a viral infection.
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- Form vi 5,6-dichloro-2-(isopropylamino)-1-(β-l-ribofuranosyl)-1h-bezimimidazole
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The invention relates to Form VI 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole, pharmaceutical compositions comprising the same, and their use in medical therapy.
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- Crystalline forms of an antiviral benzimidazole compound
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The invention relates to Form physical forms of 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole, pharmaceutical compositions comprising the same, and their use in medical therapy.
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- L-benzimidazole nucleosides
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The present invention relates to benzimidazole derivatives and their use in medical therapy particularly for the treatment or prophylaxis of virus infections such as those caused by herpes viruses. The invention also relates to the preparation of the benzimidazole derivatives and pharmaceutical formulations containing them.
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- Antiviral benzimidazole nucleoside analogues and method for their preparation
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The present invention relates to benzimidazole derivatives and their use in medical therapy particularly for the treatment or prophylaxis of virus infections such as those caused by herpes viruses. The invention also relates to the preparation of the benzimidazole derivatives and pharmaceutical formulations containing them.
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- Design, synthesis, and antiviral activity of α-nucleosides: D- and L- isomers of lyxofuranosyl- and (5-deoxylyxofuranosyl)benzimidazoles
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Several 2-substituted α-D- and α-L-lyxofuranosyl and 5- deoxylyxofuranosyl derivatives of 5,6-dichloro-2-(isopropylamino)-1-(β-L- ribofuranosyl)benzimidazole (1263W94) and 2,5,6-trichloro1-(β-D- ribofuranosyl)benzimidazole (TCRB) were synthesized and evaluated for activity against two herpesviruses (HSV-1 and HCMV) and for their cytotoxicity against HFF and KB cells. Condensation of 1,2,3,5-tetra-O- acetyl-L-lyxofuranose (2a) with 2,5,6-trichlorobenzimidazole (1) yielded the α-nucleoside 3a. The 2-bromo derivative and 2-methylamino derivative were prepared by treatment of 3a with HBr followed by deprotection or from methylamine, respectively. Compound 3a was deprotected and the resultant nucleoside used to prepare the 2-cyclopropylamino and 2-isopropylamino derivatives. The 2-alkylthio nucleosides were prepared by condensing 2a with 5,6-dichlorobenzimidazole-2-thione followed by deprotection. Alkylation of this adduct gave the 2-methylthio and 2-benzylthio derivatives. Condensation of 5-deoxy-1,2,3-tri-O-acetyl-L-lyxofuranosyl, prepared from L-lyxose, with 1 or 2-bromo-5,6-dichlorobenzimidazole (15), followed by deprotection, gave the 2-chloro or 2-bromo-5'-deoxylyxofuranosyl derivative, respectively. The cyclopropylamino derivative was prepared from the 2-chloro derivative. All D- isomers were prepared in an analogous fashion from D-lyxose. Either compounds were inactive against HSV-1 or weak activity was poorly separated from cytotoxicity. In contrast, the 2-halogen derivatives in both the α-lyxose and 5-deoxy-α-lyxose series were active against the Towne strain of HCMV. The 5-deoxy α-L analogues were the most active, IC50'S = 0.2-0.4 μM, plaque assay; IC90's = 0.2-2 μM, yield reduction assay. All of the 2- isopropylamino or 2-cyclopropylamino derivatives were less active (IC50's = 60-100 μM, plaque assay; IC90's = 17-100 μM, yield reduction assay) and were not cytotoxic. The methylamino, thio, and methylthio derivatives were neither active nor cytotoxic. The benzylthio derivatives were weakly active, but this activity was poorly separated from cytotoxicity. The α-lyxose L- isomers were more active in a plaque assay against the AD169 strain of HCMV compared to the Towne strain, thereby providing additional evidence of antiviral specificity.
- Migawa, Michael T.,Girardet, Jean-Luc,Walker II, John A.,Koszalka, George W.,Chamberlain, Stanley D.,Drach, John C.,Townsend, Leroy B.
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p. 1242 - 1251
(2007/10/03)
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