81475-44-7Relevant articles and documents
Synthesis and in vitro evaluation of antiviral and cytostatic properties of novel 8-triazolyl acyclovir derivatives
Safti?, Dijana,?ini?, Biserka,Glava?-Obrovac, Ljubica,Studzińska, Miros?awa,Paradowska, Edyta,Le?nikowski, Zbigniew J.
, p. 397 - 414 (2018/12/04)
As a part of the research aimed on identification of new nucleobase derivatives with improved biological properties, a series of novel 8-substituted acyclovir derivatives were synthesized. The 8-azidoguanosine 4 and novel 8-azidoacyclovir 9 were synthesized from commercially available guanosine 1 and acyclovir 6 which were transformed into 8-bromopurine derivatives 2 and 7 and hydrazine derivatives 3 and 8, respectively. 8-Triazolylguanosine 5 and 8-triazolylacyclovir analogs 10–12 were successfully synthesized via the Cu(I) catalyzed 1,3-dipolar cycloaddition reaction of azides 4 and 9 with propargyl alcohol, 4-pentyn-1-ol and 5-hexyn-1-ol. The novel 1,4-disubstituted 1,2,3-triazolyl compounds 5, 10–12 were evaluated for antiviral activity against selected DNA and RNA viruses and cytostatic activity against normal Madine Darby canine kidney (MDCK I) cells, and seven tumor cell lines (HeLa, CaCo-2, NCI-H358, Jurkat, K562, Raji and HuT78). While tested compounds exerted no antiviral activity at nontoxic concentrations, the 8-triazolyl acyclovir derivative 10, with the shortest alkyl substituent at the C-4 of triazole ring, was found to be the most active against the CaCo-2 cell line.
A practical synthesis of 8-hydroxyacyclovir and 9-(carboxymethoxymethyl) guanine, metabolites of acyclovir
Kutsuma, Teruo,Sakai, Yasuo,Ouchi, Hiroyuki,Shiina, Noriaki,Yamagishi, Takehiro,Shibuya, Shiroshi,Yokomatsu, Tsutomu
, p. 1967 - 1973 (2007/10/03)
Improved methods for the synthesis of 8-hydroxyacyclovir and 9-(carboxymethoxymethyl)guanine, metabolites of acyclovir, were examined. The methods were found to be useful for practical preparation of 8-hydoxyacyclovir and 9-(caboxymethoxymethyl)guanine of high purity. Careful spectroscopic analysis of 8-hydroxyacyclovir in DMSO-d6 suggested that it may be exist in an 8-oxo tautomer rather than an 8-hydroxy tautomer under the solution conditions.
Small-molecule immunostimulants. Synthesis and activity of 7,8- disubstituted guanosines and structurally related compounds
Reitz,Goodman,Pope,Argentieri,Bell,Burr,Chourmouzis,Come,Goodman,Klaubert,Maryanoff,McDonnell,Rampulla,Schott,Chen
, p. 3561 - 3578 (2007/10/02)
A series of 7,8-disubstituted guanosine derivatives was designed and prepared as potential B-cell-selective activators of the humoral immune response. These compounds were evaluated for their ability to act as B-cell mitogens and to augment the antibody response of B cells to sheep red blood cell (SRBC) challenge (adjuvanticity). In addition, they were tested for their ability to stimulate the natural killer (NK) cell response in murine in vitro cell assays. Certain of the compounds demonstrated in vivo activity when administered either intravenously, subcutaneously, or orally. Analogues with a medium-length alkyl chain (2-4 carbons, 5-7) on the 7-position of 7- alkyl-8-oxoguanosines were found to be particularly potent. Compounds bearing hydroxyalkyl, aminoalkyl, or substituted aminoalkyl substituents on this 7- position were weakly active. However, benzyl groups, including those substituted with heteroatoms (e.g., p-nitrobenzyl, 14), were active. Oxo, thioxo, and seleno groups on C-8 of the guanosine ring all imparted strong activity, whereas other larger substituents did not (e.g., N=CN). Stereochemical inversion of the 2'-hydroxyl on the ribose ring in this series, giving arabinose analogue 70, lessened activity. However, removal of the 2'-hydroxyl, either with (64) or without (73) removal of the 3'-hydroxyl, resulted in excellent activity and improved solubility; 64 also displayed good oral in vivo activity as well. A series of ketals involving the 2',3'- hydroxyls were prepared; certain of the nonpolar ketals (e.g., 48) were remarkably active, pointing to an ancillary hydrophobic binding region that can augment activity. 5'-Phosphate derivative 57 was fairly active, and acyclovir analogue 90 displayed good NK-selective activity; other N-9 sugar mimetics were also active (97-104), although this activity did not carry over into the human B-cell assay. A total of 80 compounds were prepared and evaluated for their immunostimulating activity. Within this group, compounds could be divided into those that were active in all three assays, those that displayed some measure of selectivity for the adjuvanticity assay, and those that preferentially activated NK responses. Because of its overall biological profile and ease of synthesis, 7-allyl-8-oxoguanosine (6; loxoribine, RWJ- 21757) was chosen for further development. It is among the most potent compounds evaluated in the three biological assays.
Nucleic Acid Related Compounds. 47. Synthesis and Biological Activities of Pyrimidine and Purine "Acyclic" Nucleoside Analogues
Robins, Morris J.,Hatfield, Peter W.,Balzarini, Jan,Clercq, Eric De
, p. 1486 - 1492 (2007/10/02)
Various acyclic, i.e., (2-hydroxyethoxy)methyl and (2-acetoxyethoxy)methyl, analogues of pyrimidine and purine nucleosides have been prepared evaluated for their antiviral, antimetabolic, and cytotoxic properties.All of the pyrimidine analogues, including (E)-5-(2-bromovinyl)-1-uracil (12) and its O-acetyl derivative (13), were virtually devoid of antiviral, cytotoxic, and antimetabolic activities.However, several of the 8-substituted derivatives of 9-guanine (acyclovir) had higher antiviral specificity in vitro than the parent drug.The 8-methyl-, 8-amino-, 8-bromo-, and 8-iodoacyclovir derivatives have activities worthy of further investigation.
