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|Title:||Nucleoside phosphoramidate prodrugs|
|Abstract:||Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: ##STR00001## Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula I.|
|Inventor(s):||Du; Jinfa (Redwood City, CA), Nagarathnam; Dhanapalan (Bethany, CT), Sofia; Michael Joseph (Doylestown, PA), Wang; Peiyuan (Foster City, CA)|
|Assignee:||Gilead Pharmasset LLC (Foster City, CA)|
|Filing Date:||Apr 17, 2014|
|Claims:||1. Biomimetic reactions are in harmony with loss of 2'-substituents as free radicals (not anions) during mechanism-based inactivation of ribonucleotide reductases. differential interactions of azide, halogen, and alkylthio groups with tributylstannane and triphenylsilane," Journal of the American Chemical Society, vol. 118, No. 46, pp. 11341-11348, (1996). cited by applicant .|
Saneyoshi, "Facile synthesis of 2'-O-cyanoethyluridine by ring-opening reaction of 2,2'-anhydrouridine with cyanoethyl trimethylsilyl ether in the presence of BF.sub.3 Et.sub.2O," Tetrahedron Letters, vol. 48, pp. 8554-8557, (2007). cited by applicant .
Van Rompaey, et al., "Mycobacterium tuberculosis thymidine monophosphate kinase inhibitors; biological evaluation and conformational analysis of 2'-and 3'-modified thymidine analogues," Eur. J. Org. Chem., pp. 2911-2918, (2003). cited by applicant .
Vanheusden, et al., "Synthesis and evaluation of thymidine-5'-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase," Bioorganic & Medicinal Chemistry Letters, vol. 12, pp. 2695-2698, (2002). cited by applicant .
Vanheusden, et al., "Discovery of bicyclic thymidine analogues as selective and high-affinity inhibitors of mycobacterium tuberculosis thymidine monophosphate kinase," J. Med. Chem., vol. 47, pp. 6187-6194, (2004). cited by applicant.
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