N4-Hydroxycytidine and Derivatives and Anti-Viral Uses Related Thereto

Abstract

This disclosure related to N4-hydroxycytidine derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to the treatment and prophylaxis of viral infections.

Description

Claims

1-22. (canceled)

23. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound having Formula I, or pharmaceutically acceptable salts thereof, whereinQ is O, —O(C═O)—, or —O(C═O)V—;V is O, NH, or NR7;W is O;X is CH2 or CD2;Y is CR″;Z is CH;each R″ is independently selected from is H, D, F, CH3, CD3, or CF3;R1 is amino, mercapto, formyl, carboxy, carbamoyl, carbanoyl, esteryl, alkoxy, alkylamino, or (alkyl)2amino, or R1O- is selected from amide, lactam, peptide, carboxylic acid ester, or epoxide, wherein R1 is optionally substituted with one or more, the same or different, R20;Y1 is O;Y2 is OH, OR12, or OAlkyl;Y3 is OH;R2 is hydrogen;R3 is hydroxy;R4 is hydroxy, alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, or halogen;R5 is hydrogen, hydroxy, alkoxy, alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, or halogen;R6 is hydrogen;each R7 is independently selected from absent, hydrogen, —(C═O)Oalkyl, —(C═O)alkyl, —(C═O)NHalkyl, —(C═O)N-dialkyl, alkylamino, or (alkyl)2amino;R8 is hydrogen, deuterium, alkyl, alkenyl, alkynyl, halogen, cyano, hydroxy, benzyloxy, formyl, carboxy, carbamoyl, alkoxy, alkylamino, (alkyl)2amino, (C3-C6)carbocyclyl, or aryl, wherein R8 is optionally substituted with one or more, the same or different, R20;R9 is hydrogen, methyl, ethyl, tert-butyl, alkyl, higher alkyl, (C6-C16)alkyl, (C6-C22)alkyl, halogen, cyano, hydroxy, amino, formyl, carboxy, carbamoyl, alkoxy, alkylamino, (alkyl)2amino, (C3-C6)carbocyclyl, or aryl, wherein R9 is optionally substituted with one or more, the same or different, R20;R10 is hydrogen, alkyl, branched alkyl, cycloalkyl, lipid methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl, butyl, pentyl, hexyl, neopentyl, benzyl, halogen, cyano, hydroxy, amino, formyl, carboxy, carbamoyl, alkoxy, alkylamino, (alkyl)2amino, (C3-C6)carbocyclyl, or aryl, wherein R10 is optionally substituted with one or more, the same or different, R20;R11 is hydrogen, deuterium, alkyl, methyl, halogen, cyano, hydroxy, amino, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, (C3-C6)carbocyclyl, or aryl wherein R11 is optionally substituted with one or more, the same or different, R20;R12 is hydrogen, alkyl, aryl, phenyl, 1-naphthyl, 2-naphthyl, aromatic, heteroaromatic, 4-substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, or naphthyl, wherein R12 is optionally substituted with one or more, the same or different, R20;R13 is hydrogen, deuterium, alkyl, alkenyl, alkynyl, halogen, cyano, hydroxy, amino, amido, formyl, carboxy, carbamoyl, lipid, alkoxy, alkylamino, (alkyl)2amino, (C3-C6)carbocyclyl, or aryl, wherein R13 is optionally substituted with one or more, the same or different, R20;R14 is hydrogen, deuterium, alkyl, alkenyl, alkynyl, halogen, cyano, hydroxy, amino, amido, formyl, carboxy, carbamoyl, lipid, alkoxy, alkylamino, (alkyl)2amino, (C3-C6)carbocyclyl, or aryl, wherein R14 is optionally substituted with one or more, the same or different, R20;R20 is deuterium, alkyl, alkenyl, alkynyl, halogen, cyano, hydroxy, amino, amido, formyl, carboxy, carbamoyl, alkoxy, alkylamino, (alkyl)2amino, (C3-C6)carbocyclyl, or aryl, wherein R20 is optionally substituted with one or more, the same or different, R21; andR21 is halogen, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methoxycarbonyl, ethoxycarbonyl, (C3-C6)carbocyclyl, or aryl;wherein the lipid comprises a C6-22 alkyl, alkoxy, polyethylene glycol, or aryl substituted with an alkyl group.