- Synthesis and anti-HBV evaluation of mono l-amino acid ester, mono non-steroid anti-inflammation drug carboxylic ester derivatives of acyclonucleoside phosphonates
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A series of mono l-amino acid ester, mono non-steroid anti-inflammation drug (NSAID), carboxylic ester derivatives of acyclonucleoside phosphonates were prepared by using a one pot synthesis method and their in vitro anti-HBV activity were evaluated in HepG 2.2.15 cells. Compound 9a exhibited more potent anti-HBV activity and lower cytotoxicity than those of adefovir dipivoxil with IC50 and selective index (SI) values of 0.48 μmol/L and 763.72, respectively.
- Fu, Xiao-Zhong,Jiang, Feng-Jie,Ou, Yu,Fu, Sheng,Cha, Yu-Feng,Zhang, Shun,Liu, Zong-Yuan,Zhou, Wen,Wang, Ai-Min,Wang, Yong-Lin
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- An improved synthesis of adefovir and related analogues
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An improved synthesis of the antiviral drug adefovir is presented. Problems associated with current routes to adefovir include capricious yields and a reliance on problematic reagents and solvents, such as magnesium tert-butoxide and DMF, to achieve high conversions to the target. A systematic study within our laboratory led to the identification of an iodide reagent which affords higher yields than previous approaches and allows for reactions to be conducted up to 10 g in scale under milder conditions. The use of a novel tetrabutylammonium salt of adenine facilitates alkylations in solvents other than DMF. Additionally, we have investigated how regioselectivity is affected by the substitution pattern of the nucleobase. Finally, this chemistry was successfully applied to the synthesis of several new adefovir analogues, highlighting the versatility of our approach.
- Jones, David J.,O’Leary, Eileen M.,O’Sullivan, Timothy P.
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supporting information
p. 801 - 810
(2019/04/17)
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- PMEA LIPID CONJUGATES
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The present invention relates to PMEA lipid conjugates and to methods of using the conjugates to treat diseases caused by viruses such as herpes, cytomegalovirus, varicella, paramyxovirus, polyoma virus, and human papillomavirus. Methods for making the PMEA lipid conjugates are also provided.
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Page/Page column 30-31
(2009/01/24)
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- Synthesis of acyclic nucleoside phosphonates as antiviral compounds
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Reaction of 6-chloropyrimidines with diethyl [(2-aminoethoxy)methyl]phosphonate allows for a ready access to acyclic nucleoside phosphonates. A series of 5-substituted pyrimidines bearing a phosphonate side chain at position 6 were synthesized and tested against herpes simplex viruses (HSV-1 and HSV-2) and human immunodeficiency virus (HIV-1). Some compounds showed weak antiviral activity against HSV-1.
- Wormstadt,Brinckmann,Gutschow,Eger
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p. 1187 - 1191
(2007/10/03)
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- SYNTHESIS OF N-(2-PHOSPHONYLMETHOXYETHYL) DERIVATIVES OF HETEROCYCLIC BASES
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The preparation of N-(2-phosphonylmethoxyethyl) derivatives of purine and pyrimidine bases, IV, as analogs of the antiviral 9-(2-phosphonylmethoxyethyl)adenine (PMEA,I), is described.The synthesis consists in alkylation of alkali metal salts of heterocyclic bases or their N- or O-substituted derivatives with diethyl 2-p-toluenesulfonyloxyethoxymethylphosphonate (IIa), 2-chloroethoxymethylphosphonate (IIb) or 2-bromoethoxymethylphosphonate (IIc).The obtained N-(2-diethoxyphosphonylmethoxyethyl) derivatives of heterocyclic bases (III) were treated with bromotrimethylsilane to give phosphonic acids IV.Compounds IV were prepared from pyrimidines (uracil, cytosine and their 5-methyl derivatives), purines (adenine and its N6- and C(2)-substituted derivatives, hypoxanthine, guanine, 6-hydrazinopurine and 6-methylthiopurine etc.) and their analogs (3-deazaadenine etc.).
- Holy, Antonin,Rosenberg, Ivan,Dvorakova, Hana
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p. 2190 - 2210
(2007/10/02)
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- SYNTHESIS OF 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE AND RELATED COMPOUNDS
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Diethyl 2-hydroxyethoxymethanephosphonate (VIII) was converted into diethyl 2-halogenoethoxymethanephosphonates IXa and IXb by reaction with triphenylphosphine and tetrachloromethane or tetrabromomethane; analogous reaction of VIII with p-toluenesulfonyl chloride afforded diethyl 2-(p-toluenesulfonyloxy)ethoxymethanephosphonate (IXc).Reaction of sodium salt of adenine with compounds IX led to 9-(2-diethoxyphosphonylmethoxyethyl)adenine (X).Compound X was converted into 9-(2-phosphonylmethoxyethyl)adenine (II) by treatment with bromotrimethylsilane whereas alkaline hydrolysis of X gave ethyl ester Vb.Reaction of 9-(2-hydroxyethyl)adenine (IIIa) or its N6-benzoyl derivative IIIb with dimethyl p-toluenesulfonyloxymethanephosphonate (IV) in the presence of sodium hydride, followed by alkaline hydrolysis yielded methyl ester Va.Morpholide XI reacted with an inorganic phosphate and diphosphate to give 9-(2-phosphorylphosphonylmethoxyethyl)adenine (XII) and 2-(diphosphorylphosphonylmethoxyethyl)adenine (XIII), respectively.
- Holy, Antonin,Rosenberg, Ivan
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p. 2801 - 2809
(2007/10/02)
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