N4-hydroxycytidine and derivatives and anti-viral uses related thereto

Inventors

Painter, George R. • Guthrie, David • BLUEMLING, Gregory R. • Natchus, Michael G.

Assignees

Emory University

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.

Core Innovation

The disclosure is directed to N4-hydroxycytidine-derived nucleoside analogs defined by a broad Formula I and variant sub-structures including Formula IA and Formula IB, together with salts thereof. The core scaffold is expressed with specific ring-position mappings including Q is O, W is O, X is CH2, and Y and Z are both CR3, where each R3 is H. The definition provides extensive optional substituent variation at multiple positions, including R1, R2-R21.

R1 is carboxy, carbonyl, esteryl, or formyl, or R1O— is carboxylic acid ester, with R1 optionally substituted with one or more R20. R2 is hydrogen; R3 and R4 are alkoxy, optionally substituted with one or more R20; R5 and R6 are hydrogen; R7 is hydrogen or (C1–C22)alkyl, optionally substituted with one or more R20; R8 is hydrogen; R9 is (C1–C22)alkyl; Y1 is O; and Y2 is OR12, where R12 is (C1–C22)alkyl optionally substituted with one or more R20.

R20 is alkyl, alkoxy, cyano, carboxy, carbocyclyl, (C1–C22)alkylamino, aryl, or heterocyclyl, with optional substitution by R21. R21 is defined as halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, and other listed functional groups and ring-containing groups. The compounds are also provided in pharmaceutical compositions and as antiviral agents for treatment and prophylaxis of viral infections.

Claims Coverage

The provided material describes one independent compound claim and dependent claims. The inventive coverage is concentrated in the Formula I nucleoside analog scaffold with fixed core variable assignments and broad, position-specific substituent classes for R1, R3/R4, R7/R9/R12, and R20/R21.

Across the provided material, the independent claim defines a Formula I class, including salts, with fixed scaffold elements and multiple substituent positions constrained through detailed R1, R3/R4, R7/R9/R12, and R20/R21 relationships.

Stated Advantages

Documented Applications