Claims for Patent: 8,735,372

Summary for Patent: 8,735,372

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 (Totowa, NJ)
Assignee:	Gilead Pharmasset LLC (Foster City, CA)
Application Number:	14/057,675
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,735,372
Patent Claims:	1. A method of treating a human infected by hepatitis C virus, comprising administering to the subject an effective amount of an NS5a inhibitor and an effective amount of a compound represented by the following formula: ##STR00091## wherein R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, or a substituted or unsubstituted phenyl, where the substitutent of the substituted phenyl is at least one of a CH.sub.3, OCH.sub.3, F, Cl, Br, I, nitro, cyano, and a CH.sub.3-qX.sub.q, where X is F, Cl, Br, or I, and q is 1-3; R.sup.2 is hydrogen or CH.sub.3; R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, --CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, --CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4'-OH)-Ph), CH.sub.2SH, or lower cycloalkyl, or R.sup.3a is CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, --CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, --CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4'-OH)-Ph), CH.sub.2SH, or lower cycloalkyl and R.sup.3b is H; R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl; and R.sup.7 and R.sup.8 are independently H, F, Cl, Br, I, OH, OCH.sub.3, SH, SCH.sub.3, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, CH.sub.3, CH.sub.3-qX.sub.q, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO.sub.2H, CO.sub.2CH.sub.3, CONH.sub.2, CONHCH.sub.3, or CON(CH.sub.3).sub.2, wherein R' is a C.sub.1-20 alkyl; a C.sub.1-20 cycloalkyl; a C.sub.2-C.sub.6 alkenyl, a C.sub.2-C.sub.6 alkynyl. 2. The method of claim 1, wherein the compound is ##STR00092##