102728-64-3Relevant articles and documents
Theoretical design of prodrug-enhancer combination based on a skin diffusion model: Prediction of permeation of acyclovir prodrugs treated with 1-geranylazacycloheptan-2-one
Bando, Hiroto,Takagi, Toshihide,Yamashita, Fumiyoshi,Takakura, Yoshinobu,Hashida, Mitsuru
, p. 427 - 432 (1996)
Purpose. A theoretical design of percutaneous penetration enhancement in which prodrug derivation and enhancer application are combined is proposed based on the skin diffusion model and it is experimentally verified. Methods. Employing acyclovir as a model drug, the hypothesis was tested by synthesis of its prodrugs and evaluation of their in vitro permeation in the rat skin, with or without a penetration enhancer, 1-geranylazacycloheptan-2-one (GACH). Results. Among five acyclovir prodrugs, those with higher lipophilicities (propionate, butyrate, valerate, and hexanoate prodrugs) showed greater skin penetration than those of hydrophilic prodrugs (acetate), when administered in combination with GACH. Furthermore, the observed enhancement ratios were in good agreement with those predicted by theoretical consideration. Conclusions. Thus, skin permeation of prodrugs applied with an enhancer can be predicted and optimized by model analysis.
Some aspects on acyclonucleoside synthesis
Ubasawa, Masaru,Takashima, Hideaki,Sekiya, Kouichi
, p. 2241 - 2247 (1998)
An acyclonucleoside synthesis was investigated on the regioselective introduction of an acyclochain. We found that iodotrimethylsilane catalyzed the reaction of acyclochain introduction as well as its migration from S2 to N1 of 2-thiothymine and from N7 to N9 position of guanine. By taking the findings into account, several acyclonucleosides were synthesized in a simple one-pot procedure.
Transport of acyclovir ester prodrugs through rabbit cornea and SIRC-rabbit corneal epithelial cell line
Tak, Rahul V.,Pal, Dhananjay,Gao, Hongwu,Dey, Surajit,Mitra, Ashim K.
, p. 1505 - 1515 (2001)
The purpose of this study is to assess the permeability of acyclovir (ACV) prodrugs through the rabbit corneal cell line (SIRC) as well as the cornea, and characterize the SIRC cell line for transport and metabolism studies of ester prodrugs. Prodrug derivatization of an acycloguanosine antiviral agent, acyclovir, was employed to improve its permeability across the cornea. New Zealand albino rabbits were used as an animal model for corneal studies. The SIRC cell line grown on polyester membranes was used for transport of these prodrugs. SIRC cells grown on the membrane support for 10 days developed four to six layers of epithelial cells, and this is comparable to the normal rabbit corneal epithelial layer. Transport experiments were conducted across the rabbit cornea and confluent SIRC cells using side-by-side diffusion-cell apparatus. Enzymatic hydrolysis of these compounds was evaluated in SIRC cell lysates. Appropriate reversed phase HPLC method(s) were employed for quantitation of both the prodrug and ACV simultaneously. Corneal permeabilities of some of these prodrugs (Malonyl ACV and Acetyl ACV) were higher relative to ACV. The SIRC cell line permeability values of all the prodrugs were higher compared to that of the intact cornea. The total amount of ACV-prodrugs transported, i.e., unhydrolyzed prodrugs and regenerated ACV, across the SIRC cell line was more relative to ACV. Hydrolytic studies in the SIRC cell line homogenate demonstrated the bioreversion potential of the prodrugs and the presence of enzymes, particularly the cholinesterase in the SIRC cell line. It may be concluded that the SIRC cell line is leakier compared to the cornea. Keeping in mind the limitations, the SIRC cell line after further characterization may be used for transport and metabolism studies of ester prodrugs.
Chemoselective N-Deacetylation of Protected Nucleosides and Nucleotides Promoted by Schwartz's Reagent
Ferrari, Valentina,Serpi, Michaela,McGuigan, Christopher,Pertusati, Fabrizio
, p. 799 - 814 (2015)
Protection and deprotection strategies involving the N-acetyl group are widely utilized in nucleoside and nucleotide chemistry. Herein, we present a mild and selective N-deacetylation methodology, applicable to purine and pyrimidine nucleosides, by means of Schwartz's reagent, compatible with most of the common protecting groups used in nucleoside chemistry.
Novel water-soluble prodrugs of acyclovir cleavable by the dipeptidyl-peptidase IV (DPP IV/CD26) enzyme
Diez-Torrubia, Alberto,Cabrera, Silvia,De Castro, Sonia,García-Aparicio, Carlos,Mulder, Gwenn,De Meester, Ingrid,Camarasa, María-José,Balzarini, Jan,Velázquez, Sonsoles
, p. 456 - 468 (2013/11/19)
We herein report for the first time the successful use of the dipeptidyl peptidase IV (DPPIV/CD26) prodrug approach to guanine derivatives such as the antiviral acyclovir (ACV). The solution- and solid-phase synthesis of the tetrapeptide amide prodrug 3 and the tripeptide ester conjugate 4 of acyclovir are reported. The synthesis of the demanding tetrapeptide amide prodrug of ACV 3 was first established in solution and successfully transferred onto solid support by using Ellman's dihydropyran (DHP) resin. In contrast with the valyl ester prodrug (valacyclovir, VACV), the tetrapeptide amide prodrug 3 and the tripeptide ester conjugate 4 of ACV proved fully stable in PBS. Both prodrugs converted to VACV (for 4) or ACV (for 3) upon exposure to purified DPPIV/CD26 or human or bovine serum. Vildagliptin, a potent inhibitor of DPPIV/CD26 efficiently inhibited the DPPIV/CD26-catalysed hydrolysis reaction. Both amide and ester prodrugs of ACV showed pronounced anti-herpetic activity in cell culture and significantly improved the water solubility in comparison with the parent drug.
