Orally-bioavailable nucleoside analogs
Inventors
Burns, Christopher J. • COBURN, Glen • Chu, Guo-Hua • Condon, Stephen M. • Boyd, Steven A. • Pevear, Daniel C.
Assignees
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Publication Number
US-12102648-B2
Publication Date
2024-10-01
Expiration Date
Abstract
Described herein are orally-bioavailable nucleoside analogs and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for the treatment of coronavirus infections, including SARS-CoV-2 infection.
Core Innovation
The invention relates to compounds of Formula (V), or pharmaceutically acceptable salts, solvates, or stereoisomers thereof. The compounds are defined by a structural framework in which X is hydrogen or —CN, and G is defined through R12 as —C(=O)R22, —C(=O)OR22, or C1-C6 alkyl optionally substituted with one or more R12a, with broad substituent sets for R22 and optional R22a substitution patterns.
The Formula (V) framework further includes R13, R14, R15, R25, R16, and R26, together with optional substituent sets R25a and R26a. R13 is hydrogen or C1-C6 alkyl, R14 is —OH or fluoro, and R15 is hydrogen or carbonyl/ester-linked alternatives involving R25, while R16 is carbonyl/ester-linked or C1-C6 alkyl optionally substituted with R16a.
The document also describes related stereodefined examples built on a pyrrolo[2,1-f][1,2,4]triazin-7-yl core and a tetrahydrofuran scaffold with cyano and hydroxyl features. The examples vary ester, acyl, amide, carbamate, phosphate, and prodrug-like substituent patterns, and the examples are characterized by MS (ESI), 1H NMR, LC-MS, 19F NMR, and yields.
Claims Coverage
The consolidated claim coverage centers on one independent claim to a compound of Formula (V), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, with dependent claims narrowing substituent values and extending to pharmaceutical composition and viral infection treatment claims. The independent claim contains the core inventive chemical framework, and the consolidated set includes five inventive features.
Formula (v) compound framework with variable substituents
A compound of Formula (V), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein X is hydrogen or —CN and G is defined through R12 as —C(=O)R22, —C(=O)OR22, or C1-C6 alkyl optionally substituted with one or more R12a.
Substituent diversity for r22 and optional r22a substitution patterns
R22 is defined as C1-C6 alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or alkylene-linked aryl/heteroaryl/heterocycloalkyl/cycloalkyl groups, with optional and independently defined substitution using R22a.
Definitions for r13, r14, r15 and r25 groups
R13 is hydrogen or C1-C6 alkyl; R14 is —OH or fluoro; R15 is hydrogen, —C(=O)R25, —C(=O)OR25, —CH2—O—C(=O)R25, or —CH2—O—C(=O)OR25; and R25 is defined broadly with optional R25a substituents.
Definitions for r16 and optional r16a substitution patterns
R16 is —C(=O)R26, —C(=O)OR26, —CH2—O—C(=O)R26, —CH2—O—C(=O)OR26, or C1-C6 alkyl optionally substituted with one or more R16a, where R26 is defined broadly and R16a supports optional substitution.
Pharmaceutical composition and viral infection treatment
A pharmaceutical composition comprising the compound of Formula (V), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, together with at least one pharmaceutically acceptable carrier, and a method of treating a viral infection by administering a therapeutically effective amount of the compound to a subject in need.
The claim scope includes Formula (V) compounds through explicit substituent-variable ranges for X, G, R12/R22, R13/R14/R15/R25, and R16/R26, as well as pharmaceutically acceptable salts, solvates, and stereoisomers. The claim set also includes pharmaceutical composition and viral infection treatment coverage.
Stated Advantages
Treating viral infections, preferably coronavirus infections.
Documented Applications
Treating a viral infection by administering a therapeutically effective amount of the compound, or a pharmaceutically acceptable salt, solvate, or stereoisomer, to a subject in need.
Treating viral infections, preferably coronavirus infections.
A pharmaceutical composition comprising the compound, or a pharmaceutically acceptable salt, solvate, or stereoisomer, together with at least one pharmaceutically acceptable carrier.
Administration routes include oral administration.
Combination use with other antivirals including remdesivir, ribavirin, favipiravir, and molnupiravir.
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