Granted Patent
B2
US 12,747,230 · App. 17/247,000 · Granted Sep 29, 2026
Inhibitors of cysteine proteases and methods of use thereof
Inventors:
Lee D. Arnold (Rancho Santa Fe, CA); Uri Lopatin (Berkeley, CA); Walter Keung (Encinitas, CA)
Assignee:
Pardes Biosciences, Inc.
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Abstract
The disclosure provides compounds with warheads and their use in treating medical diseases or disorders, such as viral infections. Pharmaceutical compositions and methods of making various compounds with warheads are provided. The compounds are contemplated to inhibit proteases, such as the 3C, CL- or 3CL-like protease.
Claims (27)
1 . A compound represented by Formula I:
or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
R 25 is —C(O)R 1 ,
R 1 is 4-7 membered heterocyclyl, wherein R 1 is optionally substituted by one, two or three substituents each selected from R a ,
R 2 is C 6 -C 14 aryl, wherein R 2 is optionally substituted by one, two or three substituents each selected from R 5 ;
wherein C 6 -C 14 aryl may optionally be fused with one or more carbocyclyl or heterocyclyl groups, and wherein C 6 -C 14 aryl designates the number of carbon atoms in the aryl ring system;
R 3 is 5-6 membered monocyclic heteroaryl, wherein the 5-6 membered monocyclic heteroaryl contains at least one ring nitrogen and may have one, two or three optional substituents each selected from R a ;
R 3a is selected from the group consisting of hydrogen and C 1 -C 6 alkyl;
R 4 is selected from the group consisting of C 3 -C 10 cycloalkyl and C 1 -C 6 alkyl-(C 6 -C 14 aryl), wherein the C 3 -C 10 cycloalkyl is optionally substituted by one, two or three substituents each selected from R a ;
R 4a is hydrogen;
R 5 is independently selected, for each occurrence, from the group consisting of halogen, SF 5 , C 1 -C 6 alkyl, C 3 -C 10 cycloalkyl, and C 6 -C 14 aryl;
R a is independently selected, for each occurrence, from the group consisting of halogen, hydroxyl, cyano, —OR aa , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, and C 1 -C 6 alkoxy; and
R aa is C 1 -C 6 haloalkyl.
2 . The compound of claim 1 , wherein R 1 is a warhead selected from the group consisting of:
3 . The compound of claim 1 , wherein R 2 is selected from the group consisting of:
4 . The compound of claim 1 , wherein R 3 is selected from the group consisting of:
5 . The compound of claim 1 , wherein R 3a is selected from the group consisting of hydrogen and CH 3 .
6 . The compound of claim 1 , wherein R 4 is selected from the group consisting of:
7 . The compound of claim 1 , wherein R 5 is selected from the group consisting of:
8 . A protease inhibitor compound selected from the group consisting of:
or a pharmaceutically acceptable salt or stereoisomer thereof.
9 . A protease inhibitor compound selected from the group consisting of:
10 . A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient.
11 . The pharmaceutical composition of claim 10 , further comprising a second active agent.
12 . A method of ameliorating or treating a viral infection in a patient in need thereof, comprising administering to the patient a therapeutically effective amount a compound of claim 1 .
13 . A method of ameliorating or treating SARS-CoV-2 (COVID-19) in a patient in need thereof, comprising administering to the patient a therapeutically effective amount a compound of claim 1 .
14 . The method of claim 13 , further comprising administering an additional anti-viral therapeutic.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Oct 29, 2025
From: ARNOLD, LEE D.; LOPATIN, URI; KEUNG, WALTER
To: PARDES BIOSCIENCES, INC.
Reel/Frame 072722/0317 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 16, 2021
From: ARNOLD, LEE D.; LOPATIN, URI; KEUNG, WALTER
To: PARDES BIOSCIENCES, INC.
Reel/Frame 056567/0567 →
Continuity (7)
Continuation
PCTUS2021027780
· Apr 16, 2021
Provisional Application
63111248
· Nov 9, 2020
Provisional Application
63067666
· Aug 19, 2020
Provisional Application
63039290
· Jun 15, 2020
Provisional Application
63031357
· May 28, 2020
Provisional Application
63012039
· Apr 17, 2020
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