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US-20260125399-A1 - Substituted Pyrazolo[3,4-b]pyridine Compounds and Methods of Use Thereof

US20260125399A1US 20260125399 A1US20260125399 A1US 20260125399A1US-20260125399-A1

Abstract

present disclosure relates, in part, to SARS-CoV-2 papain-like protease (PL pro ) inhibitors of Formula (I), pharmaceutical compositions thereof, and methods of using the same for promoting an antiviral effect in a subject and/or treating, preventing, and/or ameliorating a viral infection in a subject:

Inventors

  • Jun Wang
  • Bin Tan
  • Prakash Daulat Jadhav

Assignees

  • RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY

Dates

Publication Date
20260507
Application Date
20251107

Claims (20)

  1. 1 . A compound of Formula (I), or a salt, stereoisomer, or isotopically labeled derivative thereof: wherein: X 1 is selected from the group consisting of —N— and —C(R 5c )—; X 2 is selected from the group consisting of —N— and —C(R 5d )—; L 1 is selected from the group consisting of R 1 is selected from the group consisting of L 2 is selected from the group consisting of optionally substituted C 1 -C 6 alkylenyl, C 1 -C 6 heteroalkylenyl, optionally substituted C 3 -C 8 cycloalkylenyl, optionally substituted C 2 -C 8 heterocycloalkylenyl, optionally substituted C 6 -C 10 arylenyl, and optionally substituted C 2 -C 8 heteroarylenyl; Y 1 is selected from the group consisting of —O— and —N(R A )—; R 2a , R 2b , and R 2d are each independently selected from the group consisting of H, halogen, optionally substituted C 1 -C 6 alkyl, OR A , N(R A )(R B ), C(═O)R A , C(═O)OR A , C(═O)N(R A )(R B ), CN, and NO 2 ; R 3 is CH 3 ; R 4 is selected from the group consisting of H and optionally substituted C 1 -C 6 alkyl; R 5a , R 5b , R 5c , and R 5d , if present, are each independently selected from the group consisting of H, halogen, optionally substituted C 1 -C 6 alkyl, OR A , N(R A )(R B ), C(═O)R A , C(═O)OR A , C(═O)N(R A )(R B ), CN, and NO 2 ; R 6 is selected from the group consisting of optionally substituted C 2 -C 10 heteroaryl, CN, NO 2 , and a halogen; R 7 is selected from the group consisting of H and optionally substituted C 1 -C 6 alkyl; R 8a , R 8b , R 8c , and R 8d , if present, are each independently selected from the group consisting of H and optionally substituted C 1 -C 6 alkyl; R 9a and R 9b are each independently selected from the group consisting of H and optionally substituted C 1 -C 6 alkyl, or R 9a and R 9b combine with the nitrogen atom to which they are bound to form an optionally substituted C 2 -C 12 heterocycloalkyl; each occurrence of R A and R B , if present, is independently selected from the group consisting of H, C(═O)R C , C(═O)OR C , C(═O)N(R C )(R D ), optionally substituted C 1 -C 6 alkyl, optionally substituted C 3 -C 8 cycloalkyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 2 -C 6 heterocycloalkyl, optionally substituted C 7 -C 12 aralkyl, optionally substituted C 6 -C 10 aryl, and optionally substituted C 2 -C 12 heteroaryl; and R C and R D , if present, are each independently selected from the group consisting of H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 3 -C 8 cycloalkyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 2 -C 6 heterocycloalkyl, optionally substituted C 7 -C 12 aralkyl, optionally substituted C 6 -C 10 aryl, and optionally substituted C 2 -C 12 heteroaryl.
  2. 2 . The compound of claim 1 , wherein at least one of the following applies: (a) X 1 is N; (b) X 2 is N; (c) Y 1 is selected from the group consisting of —N(CH 3 )— and —O—.
  3. 3 . The compound of claim 1 , wherein R 8a , R 8b , R 8c , and R 8d , if present, are each independently selected from the group consisting of H and CH 3 .
  4. 4 . The compound of claim 1 , wherein L 1 is selected from the group consisting of:
  5. 5 . The compound of claim 1 , wherein L 2 is —(CH 2 ) 2 —.
  6. 6 . The compound of claim 1 , wherein one of the following applies: (a) R 9a and R 9b are each independently CH 3 ; or (b) R 9a and R 9b combine with the nitrogen atom to which they are bound to form a moiety selected from the group consisting of:
  7. 7 . The compound of claim 1 , wherein at least one of the following applies: (a) R 2a , R 2b , and R 2c are each independently H; (b) R 4 is H; and (c) R 5a , R 5b , R 5c , and R 5d , if present, are each independently H.
  8. 8 . The compound of claim 1 , wherein R 6 is selected from the group consisting of: wherein: R 10a , R 10b , R 10c , and R 10d , if present, are each independently selected from the group consisting of H, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 3 -C 8 cycloalkyl, optionally substituted C 2 -C 8 heterocycloalkyl, optionally substituted C 6 -C 10 aryl, optionally substituted C 2 -C 8 heteroaryl, OR A , N(R A )(R B ), CN, and NO 2 ; R 11 , if present, is selected from the group consisting of are each independently selected from the group consisting of H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 3 -C 8 cycloalkyl, optionally substituted C 2 -C 8 heterocycloalkyl, OR A , N(R A )(R B ), CN, and NO 2 ; and R 12a , R 12b , R 12c , R 12d , R 12e , R 12f , and R 12g , if present, are each independently selected from the group consisting of H and optionally substituted C 1 -C 6 alkyl.
  9. 9 . The compound of claim 8 , wherein at least one of the following applies: (a) R 10a , R 10b , R 10c , and R 10d are each independently selected from the group consisting of H, CH 3 , CF 3 , OCH 3 , NH 2 , CN, (b) R 11 is selected from the group consisting of H, CH 3 , CD 3 , CH 2 CH 3 , CHF 2 , CF 3 , CH(CH 3 ) 2 , C(CH 3 ) 3 , CH 2 CF 3 , (CH 2 ) 2 F, (CH 2 ) 2 OH, (CH 2 ) 2 CN, (CH 2 ) 2 OCH 3 , CH 2 N(CH 3 ) 2 , and (c) R 12a , R 12b , R 12c , R 12d , R 12e , R 12f , and R 12g are each independently selected from the group consisting of H.
  10. 10 . The compound of claim 1 , wherein R 6 is selected from the group consisting of:
  11. 11 . The compound of claim 1 , wherein R 7 is selected from the group consisting of CH 3 and CH(CH 3 ) 2 .
  12. 12 . The compound of claim 1 , which is selected from the group consisting of: N-(1-(6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; 2-methyl-N-(1-(1-methyl-6-(2-methylthiazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; 2-methyl-N-(1-(1-methyl-6-(2-methylthiazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(3,6-dihydro-2H-pyran-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(3,6-dihydro-2H-pyran-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; 2-methyl-N-(1-(1-methyl-6-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; 2-methyl-N-(1-(1-methyl-6-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; 2-methyl-N-(1-(1-methyl-6-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; 2-methyl-N-(1-(1-methyl-6-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-chloro-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-chloro-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-cyclopropyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-cyclopropyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(tert-butyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(tert-butyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-isopropyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-isopropyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; 2-methyl-N-(1-(1-methyl-6-(1-methyl-1H-pyrazol-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; 2-methyl-N-(1-(1-methyl-6-(1-methyl-1H-pyrazol-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-ethyl-1H-pyrazol-3-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-ethyl-1H-pyrazol-3-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; 2-methyl-N-(1-(1-methyl-6-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; 2-methyl-N-(1-(1-methyl-6-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; 2-methyl-N-(1-(1-methyl-6-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-5-(6-methyl-3,6-diazabicyclo[3.1.1]heptan-3-yl)benzamide; 2-methyl-N-(1-(1-methyl-6-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-5-((1R,5S)-6-methyl-3,6-diazabicyclo[3.1.1]heptan-3-yl)benzamide; 2-methyl-5-(methyl(2-morpholinoethyl)amino)-N-(1-(1-methyl-6-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)benzamide; 5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)benzamide; 2-methyl-N-(1-(1-methyl-6-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-5-(4-methylpiperazin-1-yl)benzamide; 5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (R)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (S)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; 5-(2-(dimethylamino)ethoxy)-N-(1-(6-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; (R)-5-(2-(dimethylamino)ethoxy)-N-(1-(6-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; (S)-5-(2-(dimethylamino)ethoxy)-N-(1-(6-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; 5-(2-(dimethylamino)ethoxy)-N-(1-(6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; (R)-5-(2-(dimethylamino)ethoxy)-N-(1-(6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; (S)-5-(2-(dimethylamino)ethoxy)-N-(1-(6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; N-(1-(6-(1,5-dimethyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; (R)—N-(1-(6-(1,5-dimethyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; (S)—N-(1-(6-(1,5-dimethyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; 5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-methyl-1H-pyrazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (R)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-methyl-1H-pyrazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (S)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-methyl-1H-pyrazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; 5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(thiazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (R)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(thiazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (S)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(thiazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; 5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (R)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (S)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; 5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1H-pyrazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (R)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1H-pyrazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (S)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1H-pyrazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; N-(1-(6-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; (R)—N-(1-(6-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; (S)—N-(1-(6-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; N-(1-(6-(1-cyclopropyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; (R)—N-(1-(6-(1-cyclopropyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; (S)—N-(1-(6-(1-cyclopropyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; 5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (R)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (S)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; 5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(5-(pyrrolidin-1-ylmethyl)thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (R)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(5-(pyrrolidin-1-ylmethyl)thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (S)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(5-(pyrrolidin-1-ylmethyl)thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; 5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; 5-(2-(dimethylamino)ethoxy)-2-methyl-N-((1R)-1-(1-methyl-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; 5-(2-(dimethylamino)ethoxy)-2-methyl-N-((1S)-1-(1-methyl-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; 5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (R)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (S)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; N-(1-(6-(1H-indazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; (R)—N-(1-(6-(1H-indazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; (S)—N-(1-(6-(1H-indazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; N-(1-(6-chloro-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; (R)—N-(1-(6-chloro-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; (S)—N-(1-(6-chloro-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; 5-(2-(dimethylamino)ethoxy)-N-(1-(6-(1-isopropyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; (R)-5-(2-(dimethylamino)ethoxy)-N-(1-(6-(1-isopropyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; (S)-5-(2-(dimethylamino)ethoxy)-N-(1-(6-(1-isopropyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; N-(1-(6-(1-cyclobutyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; (R)—N-(1-(6-(1-cyclobutyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; (S)—N-(1-(6-(1-cyclobutyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; 5-(2-(dimethylamino)ethoxy)-N-(1-(6-(1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; (R)-5-(2-(dimethylamino)ethoxy)-N-(1-(6-(1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; (S)-5-(2-(dimethylamino)ethoxy)-N-(1-(6-(1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; 5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-methyl-1H-pyrazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (R)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-methyl-1H-pyrazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (S)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-methyl-1H-pyrazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; 5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-(trifluoromethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (R)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-(trifluoromethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (S)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-(trifluoromethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; 5-(2-(dimethylamino)ethoxy)-N-(1-(6-(6-(4-hydroxypiperidin-1-yl)pyridin-3-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; (R)-5-(2-(dimethylamino)ethoxy)-N-(1-(6-(6-(4-hydroxypiperidin-1-yl)pyridin-3-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; (S)-5-(2-(dimethylamino)ethoxy)-N-(1-(6-(6-(4-hydroxypiperidin-1-yl)pyridin-3-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; 5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(2-oxo-1,2-dihydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (R)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(2-oxo-1,2-dihydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (S)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(2-oxo-1,2-dihydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; 5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(2-(pyrrolidin-1-yl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (R)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(2-(pyrrolidin-1-yl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (S)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(2-(pyrrolidin-1-yl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; N-(1-(6-(1H-indazol-6-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; (R)—N-(1-(6-(1H-indazol-6-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; (S)—N-(1-(6-(1H-indazol-6-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; 5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1′-methyl-1H,1′H-[5,6′-bipyrazolo[3,4-b]pyridin]-4′-yl)ethyl)benzamide; (R)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1′-methyl-1H,1′H-[5,6′-bipyrazolo[3,4-b]pyridin]-4′-yl)ethyl)benzamide; (S)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1′-methyl-1H,1′H-[5,6′-bipyrazolo[3,4-b]pyridin]-4′-yl)ethyl)benzamide; 5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (R)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (S)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; N-(1-(6-(6-cyanopyridin-3-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; (R)—N-(1-(6-(6-cyanopyridin-3-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; (S)—N-(1-(6-(6-cyanopyridin-3-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; N-(1-(6-(2-aminopyrimidin-5-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; (R)—N-(1-(6-(2-aminopyrimidin-5-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; (S)—N-(1-(6-(2-aminopyrimidin-5-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-5-(2-(dimethylamino)ethoxy)-2-methylbenzamide; 5-(2-(dimethylamino)ethoxy)-N-(1-(6-(2-methoxypyridin-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; (R)-5-(2-(dimethylamino)ethoxy)-N-(1-(6-(2-methoxypyridin-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; (S)-5-(2-(dimethylamino)ethoxy)-N-(1-(6-(2-methoxypyridin-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; 5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-methyl-1H-imidazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (R)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-methyl-1H-imidazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (S)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-methyl-1H-imidazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; 5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (R)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (S)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; 5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (R)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (S)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; 5-(2-(dimethylamino)ethoxy)-N-(1-(6-(1-(2-fluoroethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; (R)-5-(2-(dimethylamino)ethoxy)-N-(1-(6-(1-(2-fluoroethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; (S)-5-(2-(dimethylamino)ethoxy)-N-(1-(6-(1-(2-fluoroethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; 5-(2-(dimethylamino)ethoxy)-N-(1-(6-(5-methoxythiophen-2-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; (R)-5-(2-(dimethylamino)ethoxy)-N-(1-(6-(5-methoxythiophen-2-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; (S)-5-(2-(dimethylamino)ethoxy)-N-(1-(6-(5-methoxythiophen-2-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)-2-methylbenzamide; 5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (R)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; (S)-5-(2-(dimethylamino)ethoxy)-2-methyl-N-(1-(1-methyl-6-(1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl)benzamide; N-(1-(6-(1-cyclopentyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-cyclopentyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1S,5R)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-cyclopentyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(2-cyanoethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(2-cyanoethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(2-cyanoethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1S,5R)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1,5-dimethyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1,5-dimethyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1S,5R)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1,5-dimethyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; 2-methyl-N-(1-(1-methyl-6-(1-(methyl-d3)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; 2-methyl-N-(1-(1-methyl-6-(1-(methyl-d3)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; 2-methyl-N-(1-(1-methyl-6-(1-(methyl-d3)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-5-((1S,5R)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(6-methyl-3,6-diazabicyclo[3.1.1]heptan-3-yl)benzamide; N-(1-(6-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-6-methyl-3,6-diazabicyclo[3.1.1]heptan-3-yl)benzamide; N-(1-(6-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1S,5R)-6-methyl-3,6-diazabicyclo[3.1.1]heptan-3-yl)benzamide; N-(1-(6-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(6-methyl-3,6-diazabicyclo[3.1.1]heptan-3-yl)benzamide; N-(1-(6-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-6-methyl-3,6-diazabicyclo[3.1.1]heptan-3-yl)benzamide; N-(1-(6-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1S,5R)-6-methyl-3,6-diazabicyclo[3.1.1]heptan-3-yl)benzamide; N-(1-(6-(1-(fluoromethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(6-methyl-3,6-diazabicyclo[3.1.1]heptan-3-yl)benzamide; N-(1-(6-(1-(fluoromethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-6-methyl-3,6-diazabicyclo[3.1.1]heptan-3-yl)benzamide; N-(1-(6-(1-(fluoromethyl)-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1S,5R)-6-methyl-3,6-diazabicyclo[3.1.1]heptan-3-yl)benzamide; N-(1-(1-isopropyl-6-(1-methyl-1H-pyrazol-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(1-methyl-1H-pyrazol-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(1-methyl-1H-pyrazol-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-chloro-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-chloro-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-chloro-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1S,5R)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1S,5R)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1S,5R)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1S,5R)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(1-isopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(1-isopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(1-isopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(2-cyanoethyl)-1H-pyrazol-4-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(2-cyanoethyl)-1H-pyrazol-4-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(2-cyanoethyl)-1H-pyrazol-4-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1S,5R)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(1-methyl-1H-pyrazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(1-methyl-1H-pyrazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(1-methyl-1H-pyrazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1S,5R)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(tert-butyl)-1H-pyrazol-4-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(tert-butyl)-1H-pyrazol-4-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(tert-butyl)-1H-pyrazol-4-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1S,5R)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1S,5R)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(fluoromethyl)-1H-pyrazol-4-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(fluoromethyl)-1H-pyrazol-4-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-(fluoromethyl)-1H-pyrazol-4-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1S,5R)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-cyclobutyl-1H-pyrazol-4-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-cyclobutyl-1H-pyrazol-4-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1-cyclobutyl-1H-pyrazol-4-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1S,5R)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(1-(methyl-d3)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(1-(methyl-d3)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(1-(methyl-d3)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1S,5R)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1,5-dimethyl-1H-pyrazol-4-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1,5-dimethyl-1H-pyrazol-4-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(6-(1,5-dimethyl-1H-pyrazol-4-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1S,5R)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(3-methylisothiazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(3-methylisothiazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(3-methylisothiazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1S,5R)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(1-methyl-1H-1,2,3-triazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(1-methyl-1H-1,2,3-triazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(1-methyl-1H-1,2,3-triazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1S,5R)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(2-methyl-2H-1,2,3-triazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(2-methyl-2H-1,2,3-triazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(2-methyl-2H-1,2,3-triazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1S,5R)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(1-methyl-1H-1,2,4-triazol-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; N-(1-(1-isopropyl-6-(1-methyl-1H-1,2,4-triazol-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide; and N-(1-(1-isopropyl-6-(1-methyl-1H-1,2,4-triazol-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropyl)-2-methyl-5-((1S,5R)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)benzamide.
  13. 13 . A pharmaceutical composition comprising at least one compound of claim 1 and a pharmaceutically acceptable carrier.
  14. 14 . The pharmaceutical composition of claim 13 , further comprising at least one antiviral agent, optionally wherein the antiviral agent is a protease inhibitor, and optionally wherein the antiviral agent is selected from the group consisting of nirmatrelvir, ensitrelvir, molnupiravir, VV116, and remdesivir.
  15. 15 . A method for promoting an antiviral effect in a subject, the method comprising administering at least one compound of claim 1 or a pharmaceutical composition thereof.
  16. 16 . The method of claim 15 , wherein the method further comprises administering to the subject at least one antiviral agent, optionally wherein the antiviral agent is a protease inhibitor, and optionally wherein the antiviral agent is selected from the group consisting of nirmatrelvir, ensitrelvir, molnupiravir, VV116, and remdesivir.
  17. 17 . A method for inhibiting a papain-like protease in a subject, the method comprising administering to the subject at least one compound of claim 1 or a pharmaceutical composition thereof.
  18. 18 . A method for treating, preventing, or ameliorating a viral infection in a subject, the method comprising administering to the subject at least one compound of claim 1 or a pharmaceutical composition thereof.
  19. 19 . The method of claim 18 , wherein the viral infection is caused by a coronavirus, optionally wherein the coronavirus is SARS-CoV-2, and optionally wherein the viral infection is COVID-19.
  20. 20 . The method of claim 18 , wherein the subject is a mammal, optionally wherein the mammal is a human.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Patent Application No. 63/717,703, filed Nov. 7, 2024, which is incorporated herein by reference in its entirety. STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT This invention was made with government support under U19AI171110 awarded by the National Institutes of Health. The government has certain rights in the invention. BACKGROUND The COVID-19 pandemic is by far the worst pandemic since the 1918 Spanish flu. The etiological agent of COVID-19 is SARS-CoV-2, a single-stranded positive sense RNA virus that belongs to the beta coronavirus genus. Two additional coronaviruses within the same genus, SARS-CoV, and MERS-CoV, have caused epidemics in humans with mortality rates of 9.6% and 34.3%, respectively. Although SARS-CoV-2 has a lower mortality rate of 2.1% compared to SARS-CoV and MERS-CoV, it has led to a far greater death toll due to its higher transmission. SARS-CoV-2 differs from SARS-CoV and MERS-CoV in that it has a long incubation time after the initial infection (1 to 2 weeks), and a large percentage of infected patients continue to shed the virus while being asymptomatic, presenting a daunting task for surveillance and containment. Three mRNA vaccines, which were developed by Pfizer/BioNTech, Moderna, and Johnson and Johnson, have been approved by FDA in the United States. For small molecule antivirals, remdesivir received FDA approval on Oct. 22, 2020. Although the polymerase of SARS-CoV-2 has proof-reading function, it continues to mutate at a rate about 10−6 per site per cycle. Several variants have already emerged and widely circulated among humans since the beginning of the pandemic. Therefore, there is a dire need for additional antivirals with a novel mechanism of action. Antivirals are not substituents of vaccines, but rather an important complement that can be used for the treatment of infection from both wild-type (WT) and variant viruses. Among the viral proteins that have been actively pursued as SARS-CoV-2 antiviral drug targets, the main protease (Mpro) and papain-like protease (PLUpro) are the most promising ones. Mpro and PLpro are involved in the proteolytic digestion of the viral polyproteins pp1a and pp1ab, yielding individual functional viral proteins for the replication complex formation. PLpro cleaves at three sites with the recognition sequence “LXGG↓XX” PLpro has been shown to play additional roles in dysregulating host immune response and impairing the host type I interferon antiviral effect through its deubiquitinating and deISG15ylating (interferon-induced gene 15) activities, respectively. SARS-CoV-2 PLUpro cleaves ISG15 and polyubiquitin modifications from cellular proteins, and inhibition of PLpro led to the accumulation of ISG15-conjugates and poly-ubiquitin-conjugates. While SARS-CoV PLpro prefers ubiquitinated substrates, SARS-CoV-2 PLpro prefers the ISGlyated proteins as substrates. PLpro is part of a membrane anchored multi-domain protein named non-structural protein 3 (nsp-3), an essential component of the replicase-transcriptase complex. The pleiotropic roles of SARS-CoV-2 PLUpro make it a promising antiviral drug target. Substantial morbidity and mortality associated with COVID-19 infection is caused by cytokine storm, and suppressing host immune response using dexamethasone and baricitinib has been shown to provide therapeutic benefits in the treatment of severe infections. Significant progress has been made in developing SARS-CoV-2 Mpro inhibitors. In comparison, PLpro represents a more challenging drug target, and GRL0617 remains one of the most potent PLpro inhibitors reported to date despite several high-throughput screening and medicinal chemistry optimization campaigns. GRL0617 was originally developed as a deubiquitinase inhibitor and was later identified as a SARS-CoV PLpro inhibitor through a high-throughput screening. As SARS-CoV-2 and SARS-CoV PLpro share a sequence identity of 83% and similarity of 90%, GRL0617 was also repurposed for SARS-CoV-2 PLpro and it was reported to inhibit SARS-CoV-2 PLpro with IC50 values of around 2 μM and SARS-CoV-2 viral replication with EC50 values around 20 μM from multiple studies. There is thus a need in the art for SARS-CoV-2 antiviral agents that can be used alone or in combination with other drugs (e.g., protease inhibitors). The present disclosure addresses this need. BRIEF SUMMARY OF THE INVENTION The disclosure provides a compound of Formula (I), or a salt, stereoisomer, or isotopically labeled derivative thereof: wherein: X1 is selected from the group consisting of —N— and —C(R5c)—;X2 is selected from the group consisting of —N— and —C(R5d)—;L1 is selected from the group consisting of R1 is selected from the group consisting of L2 is selected from the group consisting of optionally substituted C1-C6 alkylenyl, C1-C6 heteroalkylenyl, optionally substituted C3-C8 cycloalkyleny