Granted Patent B2

US 12,630,538 · App. 18/347,099 · Granted May 19, 2026

Inventors: Koen Vandyck (Paal, BE); Dorothée Alice Marie-Eve Bardiot (Leuven, BE); Pierre Jean-Marie Bernard Raboisson (Wavre, BE); Leonid Beigelman (San Mateo, CA); Antitsa Dimitrova Stoycheva (Half Moon Bay, CA); Sandro Boland (Leuven, BE); Arnaud Didier Marie Marchand (Leuven, BE)

Assignees: Aligos Therapeutics, Inc.; Katholieke Universiteit Leuven

C07D403/12A61P31/14

Abstract

Claims (42)

1 . A compound of Formula (I), or a pharmaceutically acceptable salt thereof, having the structure:

wherein:

Ring A 1 is selected from the group consisting of,

 and wherein Ring A 1 is optionally substituted with one or more moieties independently selected from the group consisting of ═O, ═CH 2 , deuterium, halogen, hydroxy, an unsubstituted C 1-4 alkyl, an unsubstituted C 1-4 haloalkyl, an unsubstituted C 2-4 alkenyl and an unsubstituted or a substituted C 3-6 monocyclic cycloalkyl;

R 1 is selected from the group consisting of cyano, an unsubstituted or a substituted C 2-5 alkynyl, an unsubstituted or a substituted acyl, an unsubstituted or a substituted ketoamide, —CH(OH)—(S(═O) 2 —O—), —CH(OH)((P═O)(OR 6 ) 2 ) and —C(═O) CH 2 —O—((P═O)(OR 7 ) 2 );

each R 6 and each R 7 are independently hydrogen, an unsubstituted C 1-6 alkyl, an unsubstituted C 2-6 alkenyl, an unsubstituted C 1-6 haloalkyl, an unsubstituted or a substituted aryl or an unsubstituted or a substituted aryl(C 1-4 alkyl);

R 2 is hydrogen, deuterium or halogen;

R 3 is an unsubstituted or a substituted monocyclic nitrogen-containing heterocyclyl(C 1-4 alkyl), an unsubstituted or a substituted bicyclic nitrogen-containing heterocyclyl(C 1-4 alkyl) or an unsubstituted or a substituted monocyclic nitrogen-containing heteroaryl(C 1-4 alkyl);

R 4 is hydrogen, deuterium or halogen;

R 5 is;

R 8 is selected from the group consisting of an unsubstituted or a substituted C 2-6 alkyl, an unsubstituted or a substituted C 2-6 alkenyl, an unsubstituted or a substituted C 2-6 alkynyl, an unsubstituted or a substituted monocyclic C 3-6 cycloalkyl, an unsubstituted or a substituted bicyclic C 5-8 cycloalkyl, an unsubstituted or a substituted monocyclic 4- to 6-membered heterocyclyl and an unsubstituted monocyclic C 3-6 cycloalkyl (CH 2 )—,

wherein when the C 2-6 alkyl is substituted, the C 2-6 alkyl is substituted 1, 2, 3 or 4 times with a substituent independently selected from the group consisting of halogen, cyano, an unsubstituted or a substituted monocyclic C 3-6 cycloalkyl, an unsubstituted C 1-4 alkoxy and an unsubstituted C 1-4 haloalkoxy, or the C 2-6 alkyl is substituted 1 to 13 times with deuterium;

wherein when the C 2-6 alkenyl, the C 2-6 alkynyl, the monocyclic C 3-6 cycloalkyl, the bicyclic C 5-8 cycloalkyl and the monocyclic 4- to 6-membered heterocyclyl are substituted, the C 2-6 alkenyl, the C 2-6 alkynyl, the monocyclic C 3-6 cycloalkyl, the bicyclic C 5-8 cycloalkyl and the monocyclic 4- to 6-membered heterocyclyl are substituted 1, 2, 3 or 4 times with a substituent independently selected from the group consisting of halogen, an unsubstituted C 1-4 alkyl, an unsubstituted C 2-4 alkenyl, an unsubstituted C 2-4 alkynyl, an unsubstituted C 1-4 haloalkyl, an unsubstituted or a substituted monocyclic C 3-6 cycloalkyl and an unsubstituted C 1-4 alkoxy; and

R 9 is an unsubstituted or a substituted alkoxy.

2 . The compound of claim 1 , wherein R 1 is cyano.

3 . The compound of claim 1 , wherein Ring A 1 is an unsubstituted

a substituted

substituted with one or more moieties independently selected from the group consisting of ═O, ═CH 2 , deuterium, halogen, hydroxy, an unsubstituted C 1-4 alkyl, an unsubstituted C 1-4 haloalkyl, an unsubstituted C 2-4 alkenyl and an unsubstituted or a substituted C 3-6 monocyclic cycloalkyl, an unsubstituted

or a substituted

substituted with one or more moieties independently selected from the group consisting of ═O, ═CH 2 , deuterium, halogen, hydroxy, an unsubstituted C 1-4 alkyl, an unsubstituted C 1-4 haloalkyl, an unsubstituted C 2-4 alkenyl and an unsubstituted or a substituted C 3-6 monocyclic cycloalkyl.

4 . The compound of claim 1 , wherein Ring A 1 is selected from the group consisting of

and wherein Ring A 1 is optionally substituted with one or more moieties independently selected from the group consisting of ═O, ═CH 2 , deuterium, halogen, hydroxy, an unsubstituted C 1-4 alkyl, an unsubstituted C 1-4 haloalkyl, an unsubstituted C 2-4 alkenyl and an unsubstituted or a substituted C 3-6 monocyclic cycloalkyl.

5 . The compound of claim 1 , wherein Ring A 1 is selected from the group consisting of:

6 . The compound of claim 1 , wherein R 8 is an unsubstituted C 2-6 alkyl.

7 . The compound of claim 6 , wherein R 5 is selected from the group consisting of:

8 . The compound of claim 1 , wherein R 3 is an unsubstituted or a substituted monocyclic nitrogen-containing heterocyclyl(C 1-4 alkyl).

9 . The compound of claim 8 , wherein the monocyclic nitrogen-containing heterocyclyl(C 1-4 alkyl) is azepan-2-one(C 1-4 alkyl), imidazolidin-2-one(C 1-4 alkyl), tetrahydropyrimidin-2-one(C 1-4 alkyl), pyrrolidin-2-one(C 1-4 alkyl), piperidin-2-one(C 1-4 alkyl), pyrazolidin-3-one(C 1-4 alkyl), oxazolidin-4-one(C 1-4 alkyl), 1,4-oxazepan-3-one(C 1-4 alkyl) or morpholin-3-one(C 1-4 alkyl).

10 . The compound of claim 1 , wherein R 3 is

wherein each m1 is independently 1, 2, 3 or 4.

11 . The compound of claim 1 , wherein R 3 is selected from the group consisting of

12 . The compound of claim 1 , wherein R 3 is

13 . The compound of claim 1 , wherein R 2 is hydrogen; and R 4 is hydrogen.

14 . The compound of claim 1 , wherein the compound is selected from the group consisting of:

or a pharmaceutically acceptable salt of any of the foregoing.

15 . The compound of claim 1 , wherein the compound is selected from the group consisting of:

or a pharmaceutically acceptable salt of any of the foregoing.

16 . A pharmaceutical composition comprising an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and excipient.

17 . A method for treating a coronavirus infection in a subject identified as suffering from the coronavirus infection comprising administering to the subject identified as suffering from the coronavirus infection an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

18 . The method of claim 17 , further comprising administering an additional agent selected from the group consisting of an ACE inhibitor, an anticoagulant, an anti-inflammatory, an ARB, an ASO, a Covid-19 convalescent plasma, an entry inhibitor, an H 2 pump antagonist, an H-conducting channel, an HIV protease inhibitor, an HMG-CoA reductase inhibitor, an immune globulin, an immunosuppressant, an immunotherapeutic agent, a neuraminidase inhibitor, a nucleoside inhibitor, a nucleoside analog inhibitor, a polymerase inhibitor, a protease inhibitor, an siRNA, a statin, a tissue plasminogen activator, an antibiotic, an antimicrobial and a vaccine.

19 . A method for treating a picornavirus or a norovirus infection in a subject identified as suffering from the picornavirus infection or the norovirus infection comprising administering to the subject identified as suffering from the picornavirus infection or the norovirus infection an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

20 . A method for inhibiting a coronavirus protease comprising contacting a cell infected with a coronavirus with an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound of claim 1 , or a pharmaceutically acceptable salt thereof, selectively inhibits the coronavirus protease compared to a host protease.

21 . The method of claim 20 , wherein the compound of formula (I) selectively inhibits the coronavirus protease over the host protease that is selected from the group consisting of Cathepsin L, Cathepsin B, Cathepsin D, Cathepsin K, Leukocyte Elastase, Chymotrypsin, Trypsin, Thrombin, Pepsin, Caspase 2, Elastase and Calpain.

Assignments (3)

Continuity (2)

References Cited (387)