Anti-viral compounds
Inventors
Bardiot, Dorothée Alice Marie-Eve • Vandyck, Koen • Boland, Sandro • Stoycheva, Antitsa Dimitrova • Marchand, Arnaud Didier Marie • Raboisson, Pierre Jean-Marie Bernard • Beigelman, Leonid
Assignees
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Publication Number
US-12065428-B2
Publication Date
2024-08-20
Expiration Date
Abstract
Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts thereof, pharmaceutical compositions that include a compound described herein (including pharmaceutically acceptable salts of a compound described herein) and methods of synthesizing the same. Also provided herein are methods of treating diseases and/or conditions with a compound of Formula (I), or a pharmaceutically acceptable salt thereof.
Core Innovation
The invention relates to compounds of Formula (I), or pharmaceutically acceptable salts thereof, defined by a specific structural framework including Ring A1 and Ring A2 as unsubstituted or substituted monocyclic C3-6 cycloalkyl. The scaffold further includes substituent positions R1, R2, R3, R4, R8a, and R8b, together with defined substitution-count constraints and permitted substituent classes for the selected groups.
R1 is selected from cyano, an unsubstituted or substituted C2-5 alkynyl, an unsubstituted or substituted ketoamide, and phosphorus/oxygen-containing group options including CH(OH)(S(=O)O)2O, CH(OH)((P(=O)(OR6)2), and C(=O)CH2O((P(=O)(OR7)2). R2 and R4 are hydrogen, deuterium or halogen, while R3 is selected from unsubstituted or substituted C-amido(C1-4 alkyl), monocyclic or bicyclic nitrogen-containing heteroaryl(C1-4 alkyl), and monocyclic or bicyclic nitrogen-containing heterocyclyl(C1-4 alkyl) options.
R8a and R8b are each selected from defined alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, and heterocyclyl groups with substitution-count limits and permitted substituent types. Each R6 and each R7 are independently hydrogen, an unsubstituted C1-6 alkyl, an unsubstituted C2-6 alkenyl, an unsubstituted C1-6 haloalkyl, or an unsubstituted or substituted aryl or aryl(C1-4 alkyl). The content also describes examples of Formula (I) compounds, illustrative ring variants, and explicit exclusions of certain substituent combinations from WO 2021/252491.
Claims Coverage
The consolidated claim coverage includes three independent claim themes: a compound of Formula (I), a method of treating a coronavirus infection, and a method of inhibiting a coronavirus protease compared to Cathepsin L. The compound claim contains multiple inventive feature categories centered on Ring A1/Ring A2 and defined substituent sets for R1, R2, R3, R4, R8a, R8b, R6, and R7.
Formula (I) compound with Ring A1 and Ring A2
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, in which Ring A1 and Ring A2 are an unsubstituted or substituted monocyclic C3-6 cycloalkyl.
Defined R1 substituent classes
R1 is selected from cyano, an unsubstituted or substituted C2-5 alkynyl, an unsubstituted or substituted ketoamide, and the specified phosphorus/oxygen-containing group options.
R2 and R4 limited to hydrogen, deuterium, or halogen
R2 and R4 are each independently hydrogen, deuterium or halogen.
Defined R3 amido/heteroaryl/heterocyclyl options
R3 is selected from unsubstituted or substituted C-amido(C1-4 alkyl), monocyclic nitrogen-containing heteroaryl(C1-4 alkyl), monocyclic nitrogen-containing heterocyclyl(C1-4 alkyl), bicyclic nitrogen-containing heteroaryl(C1-4 alkyl), or bicyclic nitrogen-containing heterocyclyl(C1-4 alkyl).
R8a substitution-count limited alkyl/alkenyl/alkynyl/cycloalkyl/heterocyclyl
R8a is selected from unsubstituted or substituted C2-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, monocyclic C3-6 cycloalkyl, bicyclic C5-8 cycloalkyl, and monocyclic 4- to 6-membered heterocyclyl, with defined substitution-count limits and permitted substituent types.
R8b substitution-count limited alkyl/haloalkyl/cycloalkyl/heteroaryl/heterocyclyl
R8b is selected from unsubstituted or substituted C1-6 alkyl, C1-6 haloalkyl, monocyclic C3-6 cycloalkyl, bicyclic C5-6 cycloalkyl, monocyclic heteroaryl, and monocyclic heterocyclyl, with additional substitution constraints.
Independent R6 and R7 definitions
Each R6 and each R7 are independently hydrogen, an unsubstituted C1-6 alkyl, an unsubstituted C2-6 alkenyl, an unsubstituted C1-6 haloalkyl, an unsubstituted or substituted aryl, or an unsubstituted or substituted aryl(C1-4 alkyl).
Coronavirus treatment method
A method of treating a coronavirus infection by administering an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, to a subject in need.
Selective coronavirus protease inhibition
A method inhibiting a coronavirus protease by contacting coronavirus-infected cells with an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein the compound selectively inhibits the coronavirus protease compared to Cathepsin L.
The claim coverage is centered on a Formula (I) compound with a monocyclic C3-6 cycloalkyl Ring A1/Ring A2 framework, defined R1/R2/R3/R4 substituent selections, and substitution-count controlled R8a/R8b groups, together with independently defined R6 and R7. The coverage also includes coronavirus treatment and selective coronavirus protease inhibition relative to Cathepsin L.
Stated Advantages
Selectively inhibits the coronavirus protease compared to Cathepsin L.
Documented Applications
Treating a coronavirus infection by administering an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, to a subject in need.
Inhibiting a coronavirus protease in coronavirus-infected cells with selective inhibition compared to Cathepsin L.
Coronavirus replication inhibition, including use spanning -coronavirus, -coronavirus, and multiple named coronavirus variants.
Antiviral scope including picornavirus, with rhinovirus A/B/C mentioned.
Antiviral scope including norovirus.
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