Synthesis, Characterization, and Biological Activity of Amino Acid Derivatives of the Heteropolytungstophosphoric Acid (original) (raw)
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An efficient and simple approach has been developed for the synthesis of eight dialkyl/aryl[(5-phenyl-1,3,4-oxadiazol-2-ylamino)(aryl)methyl]phosphonates through the Pudovik-type reaction of dialkyl/arylphosphite with imines, obtained from 5-phenyl-1,3,4-oxadiazol-2-amine and aromatic aldehydes, under microwave irradiation. Five of them were hydrolyzed to lead to the corresponding phosphonic acids. Selected synthesized compounds were screened for their in vitro antiviral activity against the avian bronchitis virus (IBV). In the MTT cytotoxicity assay, the dose-response curve showed that all test compounds were safe in the range concentration of 540–1599 µM. The direct contact of novel synthesized compounds with IBV showed that the diethyl[(5-phenyl-1,3,4-oxadiazol-2-ylamino)(4-trifluoromethoxyphenyl)methyl]phosphonate (5f) (at 33 µM) and the [(5-phenyl-1,3,4-oxadiazol-2-ylamino)(4-trifluoromethylphenyl)methyl] phosphonic acid (6a) (at 1.23 µM) strongly inhibited the IBV infectivity,...
Novel α-aminophosphonic acids. Design, characterization, and biological activity
Bioorganic & Medicinal Chemistry, 2006
Novel a-aminophosphonic acids are synthesized reacting 1,3-oxazolidin-2-one derivatives with formaldehyde and phosphorus trichloride. Treatment of N-(phosphonomethyl)oxazolidinones with aqueous NaOH gave the expected a-aminophosphonic acids. The oxidation of (2-hydroxy-1,1-dimethylethylamino)methyl phosphonic acid in the presence of CdO and water resulted in N-phosphonomethyl-2-methyl-1-propanoic acid. Their structures were proved by means of IR, 1 H, 13 C, and 31 P NMR spectroscopy. The genotoxic, clastogenic, and antiproliferative effects of newly synthesized original aminophosphonic acids were investigated for the first time.
Monatshefte für Chemie/Chemical Monthly, 2008
Methyl 2,3-O-isopropylidene--D-ribofuranoside was synthesized and oxidized with HIO 4 to afford the corresponding carboxylic acid. The latter was coupled with the appropriate acylated amino acids in the presence of HOBt and DDC as coupling reagents to give the corresponding amides. The methyl acetate derivative was hydrolyzed with 2 N KOH=MeOH to the corresponding carboxylic acid, which was coupled with L-glycine methyl ester to furnish the amide. Deprotection was carried out with 70% AcOH at reflux temperature. The prepared glycopeptides were tested for antiviral activity against Herpes Simplex virus type-1 (HSV-1) and hepatitis-A virus (HAV). The plaque reduction infectivity assay was used to determine virus count reduction as a result of treatment with tested compounds.
European Journal of Medicinal Chemistry, 2012
Hexadecyloxypropyl esters of acyclic nucleoside phosphonates containing guanine (G) or hypoxanthine (Hx) and a (S)-[3-hydroxy-2-(phosphonomethoxy)propyl] [(S)-HPMP] or 2-(2-phosphonoethoxy)ethyl (PEE) acyclic moiety have been prepared. The activity of the prodrugs was evaluated in vitro against different virus families. Whereas ester derivatives of PEEHx and (S)-HPMPHx were antivirally inactive, monoesters of PEEG, and mono-and diesters of (S)-HPMPG showed pronounced antiviral activity against vaccinia virus and/or herpesviruses. Monoesters of (S)-HPMPG emerged as the most potent and selective derivatives against these DNA viruses. None of the compounds were inhibitory against RNA viruses and retroviruses.
Monatshefte Fur Chemie, 2007
Methyl 2,3-O-isopropylidene-β-d-ribofuranoside was synthesized and oxidized with HIO4 to afford the corresponding carboxylic acid. The latter was coupled with the appropriate acylated amino acids in the presence of HOBt and DDC as coupling reagents to give the corresponding amides. The methyl acetate derivative was hydrolyzed with 2 N KOH/MeOH to the corresponding carboxylic acid, which was coupled with l-glycine methyl ester to furnish the amide. Deprotection was carried out with 70% AcOH at reflux temperature. The prepared glycopeptides were tested for antiviral activity against Herpes Simplex virus type-1 (HSV-1) and hepatitis-A virus (HAV). The plaque reduction infectivity assay was used to determine virus count reduction as a result of treatment with tested compounds.
[The synthesis and antiherpetic activity of acyclovir phosphonate esters]
Bioorganicheskaia khimiia
Alkyl esters of acyclovir phosphite, alkoxycarbonylphosphonate, ethoxycarbonylmethylphosphonate, and aminocarbonylphosphonate were synthesized. Most of them were shown to inhibit the replication of type 1 herpes simplex virus in Vero cell culture. The stability in phosphate buffer and human blood serum was studied for several of the derivatives. A correlation between the stability and antiviral activity of the synthesized compounds is discussed. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 6; see also http://www.maik.ru.
Synthesis and Antiherpetic Activity of Acyclovir Phosphonates
Nucleosides, Nucleotides and Nucleic Acids, 2003
2 Abbreviations: ACV, acyclovir, 9-[(2-hydroxyethoxy)methyl]guanine; Adm, 1-adamantyl; cHx, cyclohexyl; CT 50 , 50% cytotoxic dose for uninfected Vero cells; DCC, 1,3dicyclohexylcarbodiimide; HSV-1/L 2, type 1 herpes simplex virus; HSV-1/L 2 /R, type 1 herpes simplex virus resistant to ACV; ID 50 and ID 95 , doses inhibiting the viral cytopathogenic effect by 50 and 95%, respectively; SI, selectivity index (CT 50 /ID 50 ); and TPS-Cl, 2,4,6-triisopropylbenzenesulfonyl chloride.
Moscow University Chemistry Bulletin, 2008
Two types of novel nucleoside analogs have been synthesized: acyclic (Z)-and (E)-isomers of 9-[3-(phosphonometoxy)prop-1-en-1-yl]adenine and a carbocyclic isosteric analog of guanosine monophosphate. The (Z)-and (E)-isomers inhibit the replication of herpes simplex virus (HSV) and human immunodeficiency virus (HIV) and are nontoxic for cells. The (Z)-isomer activities against both viruses are higher than the (E)-isomer activities. Diphosphates of these compounds display substrate activities towards recombinant HSV DNA polymerase and HIV reverse transcriptase (RT). Diphosphate of the carbocyclic guanosine analog has no substrate activity towards HSV DNA polymerase but is active as a RT substrate.