دورية
Prodrugs of 2’,3’-Didehydro-3’-deoxythymidine (D4T): Synthesis, Antiviral Activity, and Rapid Pharmacokinetic Evaluation
| العنوان: | Prodrugs of 2’,3’-Didehydro-3’-deoxythymidine (D4T): Synthesis, Antiviral Activity, and Rapid Pharmacokinetic Evaluation |
|---|---|
| المؤلفون: | Tortolani, David R., Russell, John W., Whiterock, Valerie J., Mansuri, Muzammil M., Starrett, John E., Hitchcock, Michael J.M., Martin, John C. |
| المصدر: | Journal of Pharmaceutical Sciences; March 1994, Vol. 83 Issue: 3 p339-343, 5p |
| مستخلص: | A series of 5’-derivatives and modified pyrimidine analogues of 2’,3’-didehydro-3’-deoxythymidine (d4T, stavudine, 1) were synthesized to determine their potential as oral prodrugs of d4T. Utilizing a screen developed for the rapid evaluation of a variety of prodrugs in mice, it was determined that 5’-acetate 2 provided comparable plasma levels of d4T after oral administration of the prodrug to that when d4T was administered alone. The relative oral bioavailabillty of methoxy acetate 3 and cyclohexyl carbonate 5 was 79 and 41%, respectively. Dihydropyridine ester 6 did not provide detectable levels of d4T up to 1h after oral administration of 6. Thiopyrimidines 8 and 9, as well as aminopyrimidine 10 also failed to provide measurable levels of d4T after oral administration. 5’-Derivatives 3, 5, and 6 showed similar activity to that of d4T against HIV and MuLV, as did 5’-benzoyl-4-thio derivative 8. However, the corresponding 4-thio 5’- alcohol 9 was inactive. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 00223549 15206017 |
|---|---|
| DOI: | 10.1002/jps.2600830315 |