Anti-viral compounds
Inventors
Vandyck, Koen • Raboisson, Pierre Jean-Marie Bernard • Beigelman, Leonid • Serebryany, Vladimir • Stoycheva, Antitsa Dimitrova • Bardiot, Dorothée Alice Marie-Eve • Boland, Sandro • Marchand, Arnaud Didier Marie
Assignees
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Publication Number
US-11952365-B2
Publication Date
2024-04-09
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, having a defined structural framework in which Z1 is C(=O) or CH(CF3), Z2 is O, S, or NR8 with R8 being H or an unsubstituted C1-4 alkyl, and Z3 is N or C, with the constraint that when Z3 is N, R5 is absent. Ring A1 is selected from an unsubstituted or substituted azetidine, pyrrolidine, or piperidine, optionally substituted with R_x groups, and connected to a cyclic moiety in fused-fashion or spiro-fashion.
The cyclic moiety is selected from monocyclic C3-7 cycloalkyl, bicyclic C5-9 cycloalkyl, monocyclic C3-7 cycloalkenyl, bicyclic C5-9 cycloalkenyl, or phenyl, with optional substitution. R1 is selected from cyano, C2-5 alkynyl, ketoamide, N-sulfonamido, and phosphate/prodrug-like motifs, while R2 and R4 are hydrogen, deuterium, or halogen. R3 is selected from C-amido and nitrogen-containing heteroaryl or heterocyclyl groups, and R6 and R7 can independently vary or together form an optionally substituted 4-9 membered ring system containing O, N, or S.
The disclosure also presents embodiments and examples within the same structural space, including compounds characterized by stereochemical variants and LC-MS data. The compounds are presented as members of the defined Formula (I) scaffold and as anti-viral compounds with the same ring topology and substituent constraints.
Claims Coverage
The consolidated claim set includes one independent compound claim for Formula (I) and additional independent use claims for coronavirus infection treatment and selective coronavirus protease inhibition. Overall, the claim coverage centers on the Formula (I) scaffold with defined Z1-Z3, Ring A1, and R1-R7 substituent choices, together with therapeutic and mechanism-of-action uses.
Formula (I) compound scaffold and pharmaceutically acceptable salts
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, defined by Z1 as C(=O) or CH(CF3), Z2 as O, S, or NR8 with R8 as H or an unsubstituted C1-4 alkyl, Z3 as N or C with the limitation that when Z3 is N then R5 is absent, and Ring A1 as an unsubstituted or substituted azetidine, pyrrolidine, or piperidine optionally substituted with R_x groups and connected to a cyclic moiety in fused-fashion or spiro-fashion.
Ring A1 connected to a cyclic moiety
The azetidine, pyrrolidine, and piperidine are connected to a cyclic moiety selected from monocyclic C3-7 cycloalkyl, bicyclic C5-9 cycloalkyl, monocyclic C3-7 cycloalkenyl, bicyclic C5-9 cycloalkenyl, or phenyl, with optional substitution.
Defined substituent set for R1 through R7
R1 is selected from cyano, C2-5 alkynyl, ketoamide, N-sulfonamido, and phosphate/prodrug-like motifs; R2 and R4 are hydrogen, deuterium, or halogen; R3 is selected from C-amido and nitrogen-containing heteroaryl or heterocyclyl groups; and R6 and R7 are independently selected or together form an optionally substituted 4-9 membered ring system containing O, N, or S.
Coronavirus infection treatment by administering Formula (I) compound
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 inhibition of coronavirus protease versus host protease
A method that inhibits a coronavirus protease by contacting a coronavirus-infected cell with a compound of Formula (I), or a pharmaceutically acceptable salt thereof, that selectively inhibits the coronavirus protease versus a host protease.
The claims define a broad Formula (I) compound class with a fused- or spiro-connected Ring A1 system and enumerated substituent constraints, and further extend to methods of treating coronavirus infection and selectively inhibiting a coronavirus protease versus a host protease.
Stated Advantages
Treats a coronavirus infection.
Inhibits a coronavirus protease selectively versus a host protease.
Inhibits and can be used to treat coronaviruses.
Inhibits and can be used to treat rhinoviruses.
Documented Applications
Treatment of coronavirus infections by administering an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, to a subject in need.
Inhibition of a coronavirus protease by contacting a coronavirus-infected cell with a compound of Formula (I), or a pharmaceutically acceptable salt thereof, with selective inhibition versus a host protease.
Treating coronavirus and rhinovirus.
Use in pharmaceutical compositions comprising compounds of Formula (I) with a pharmaceutically acceptable carrier, excipient, or diluent for treatment or inhibition of viral replication.
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