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US-20260125421-A1 - ANTIVIRAL COMPOUNDS

US20260125421A1US 20260125421 A1US20260125421 A1US 20260125421A1US-20260125421-A1

Abstract

The invention provides viral protease inhibitors having the general formula (I) wherein the variables are as described herein, compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds.

Inventors

  • David James Edmonds
  • Chungen Liang
  • HongYing Yun
  • Bo Zhang
  • Xiufang Zheng

Assignees

  • HOFFMANN-LA ROCHE INC.

Dates

Publication Date
20260507
Application Date
20231010
Priority Date
20221012

Claims (20)

  1. 1 . A compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein: L is C 1 -C 6 -alkyl; R 1 is selected from C 3 -C 10 -cycloalkyl, halo-C 3 -C 10 -cycloalkyl, C 6 -C 14 -aryl, 3- to 14-membered heteroaryl, C 1 -C 6 -alkyl, and halo-C 1 -C 6 -alkyl; R 2 is selected from hydrogen, C 3 -C 10 -cycloalkyl, C 3 -C 10 -cycloalkyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-C 3 -C 10 -cycloalkyl, C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-S—C 1 -C 6 -alkyl, 3- to 14-membered heteroaryl, (3- to 14-membered heteroaryl)-C 1 -C 6 -alkyl, C 6 -C 14 -aryl, and C 6 -C 14 -aryl-C 1 -C 6 -alkyl; R 3a , R 3b , R 4a , and R 4b are each independently selected from hydrogen, halogen, C 1 -C 6 -alkyl, and halo-C 1 -C 6 -alkyl; or R 3a and R 3b , taken together with the carbon atom to which they are attached, form a C 3 -C 10 -cycloalkyl; and R 4a and R 4b are each independently selected from hydrogen and C 1 -C 6 -alkyl; wherein said C 3 -C 10 -cycloalkyl is optionally substituted with 1 to 2 C 1 -C 6 -alkyl substituents; or R 4a and R 4b , taken together with the carbon atom to which they are attached, form a C 3 -C 10 -cycloalkyl; and R 3a and R 3b are each independently selected from hydrogen and C 1 -C 6 -alkyl; wherein said C 3 -C 10 -cycloalkyl is optionally substituted with 1 to 2 C 1 -C 6 -alkyl substituents; or R 3a and R 4a , taken together with the carbon atoms to which they are attached, form a C3-C 10 -cycloalkyl; and R 3b and R 4b are each independently selected from hydrogen and C 1 -C 6 -alkyl; wherein said C 3 -C 10 -cycloalkyl is optionally substituted with 1 to 2 C 1 -C 6 -alkyl substituents; R 5 is selected from fluoro and chloro; R 6 is selected from hydrogen, chloro, and acyl; R 7a and R 7b are both C 1 -C 6 -alkyl, R 7c and R 7d are both selected from hydrogen and C 1 -C 6 -alkyl; or R 7a , R 7b and R 7d are hydrogen and R 7c is C 1 -C 6 -alkyl; or R 7a is C 1 -C 6 -alkyl, R 7b is hydrogen, and R 7c and R 7d are both selected from hydrogen and C 1 -C 6 -alkyl; or R 7a and R 7b , taken together with the carbon atom to which they are attached, form a C 3 -C 10 -cycloalkyl and R 7c and R 7d are both selected from hydrogen and C 1 -C 6 -alkyl; or R 7a and R 7d , taken together with the carbon atoms to which they are attached, form a C 3 -C 10 -cycloalkyl and R 7b and R 7c are both selected from hydrogen and C 1 -C 6 -alkyl.
  2. 2 . The compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is halo-C 3 -C 10 -cycloalkyl or halo-C 1 -C 6 -alkyl.
  3. 3 . The compound of formula (I) according to claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from 1-fluorocyclopropyl, 2,2-difluorocyclopropyl, CHClF, and CHF 2 .
  4. 4 . The compound of formula (I) according to claim 3 , or a pharmaceutically acceptable salt thereof, wherein R 1 is 1-fluorocyclopropyl or 2,2-difluorocyclopropyl.
  5. 5 . The compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is C 1 -C 6 -alkyl.
  6. 6 . The compound of formula (I) according to claim 5 , or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from tert-butyl, 1-methylpropyl, and 1-ethylpropyl.
  7. 7 . The compound of formula (I) according to claim 6 , or a pharmaceutically acceptable salt thereof, wherein R 2 is tert-butyl or 1-methylpropyl.
  8. 8 . The compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein: R 3a and R 4a , taken together with the carbon atoms to which they are attached, form a C3-C 10 -cycloalkyl; and R 3b and R 4b are both hydrogen; wherein said C 3 -C 10 -cycloalkyl is optionally substituted with 1 to 2 C 1 -C 6 -alkyl substituents.
  9. 9 . The compound of formula (I) according to claim 8 , or a pharmaceutically acceptable salt thereof, wherein: R 3a and R 4a , taken together with the carbon atoms to which they are attached, form a cyclopropyl or a cyclopentyl; and R 3b and R 4b are both hydrogen; wherein said cyclopropyl or cyclopentyl is optionally substituted with 1 to 2 methyl substituents.
  10. 10 . The compound of formula (I) according to claim 9 , or a pharmaceutically acceptable salt thereof, wherein the group is selected from
  11. 11 . The compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein L is CH 2 .
  12. 12 . The compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is fluoro and R 6 is chloro.
  13. 13 . The compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein: R 7a and R 7b are both C 1 -C 6 -alkyl and R 7c and R 7d are both hydrogen; or R 7a and R 7d , taken together with the carbon atoms to which they are attached, form a C 3 -C 10 -cycloalkyl and R 7b and R 7c are both hydrogen; or R 7a is C 1 -C 6 -alkyl and R 7b , R 7c and R 7d are all hydrogen; or R 7a and R 7b , taken together with the carbon atom to which they are attached, form a C 3 -C 10 -cycloalkyl and R 7c and R 7d are both hydrogen.
  14. 14 . The compound of formula (I) according to claim 13 , or a pharmaceutically acceptable salt thereof, wherein: R 7a and R 7b are both methyl and R 7c and R 7d are both hydrogen; or R 7a and R 7d , taken together with the carbon atoms to which they are attached, form a cyclopropyl and R 7b and R 7c are both hydrogen; or R 7a is methyl and R 7b , R 7c and R 7d are all hydrogen; or R 7a and R 7b , taken together with the carbon atom to which they are attached, form a cyclopropyl and R 7c and R 7d are both hydrogen.
  15. 15 . The compound of formula (I) according to claim 14 , or a pharmaceutically acceptable salt thereof, wherein R 7a and R 7b are both methyl and R 7c is hydrogen.
  16. 16 . The compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof, selected from: N-[(1S,2S)-1-[(1R,2S,5S)-2-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2-methyl-butyl]-1-fluoro-cyclopropanecarboxamide; N-[(1S,2S)-1-[(1R,2S,5S)-2-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3R)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2-methyl-butyl]-1-fluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3R)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; rac-(1S)-2,2-difluoro-N-[(1S)-2,2-dimethyl-1-[(3S,3aS,6aR)-3-[[(5,5-dimethyl-2-oxo-pyrrolidin-3-yl)methyl-[(2R)-2-chloro-2-fluoro-acetyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]propyl]cyclopropanecarboxamide; N-[(1S,2S)-1-[(1R,2S,5S)-2-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2-methyl-butyl]-1-fluoro-cyclopropanecarboxamide; N-[(1S,2S)-1-[(1R,2S,5S)-2-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3R)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2-methyl-butyl]-1-fluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(1R,2S,5S)-2-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3R)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(1R,2S,5S)-2-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(1R,2S,5S)-2-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3R)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(1R,2S,5S)-2-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3R)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3R)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2-ethyl-butyl]-2,2-difluoro-acetamide; N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2-ethyl-butyl]-2,2-difluoro-acetamide; N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3R)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2-ethyl-butyl]-2,2-difluoro-acetamide; N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2-ethyl-butyl]-2,2-difluoro-acetamide; N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3R)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-acetamide; N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-acetamide; N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3R)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-acetamide; N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-acetamide; (1S)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3R)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-acetamide; N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2-ethyl-butyl]-2,2-difluoro-acetamide; N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3R)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2-ethyl-butyl]-2,2-difluoro-acetamide; (2R)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2-ethyl-butyl]-2-chloro-2-fluoro-acetamide; N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3R)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-acetamide; N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-acetamide; N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2-ethyl-butyl]-2,2-difluoro-acetamide; (2S)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2-ethyl-butyl]-2-chloro-2-fluoro-acetamide; (2R)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2-chloro-2-fluoro-acetamide; (2S)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2-chloro-2-fluoro-acetamide; (2R)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2-chloro-2-fluoro-acetamide; (2S)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2-chloro-2-fluoro-acetamide; N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3R)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2-ethyl-butyl]-2,2-difluoro-acetamide; N-[(1S,2S)-1-[(1R,2S,5S)-2-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3R)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2-methyl-butyl]-1-fluoro-cyclopropanecarboxamide; (2R)-2-chloro-N-[(1S)-1-[(1R,2S,5S)-2-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2,2-dimethyl-propyl]-2-fluoro-acetamide; (1S)—N-[(1S)-1-[(1R,2S,5S)-2-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (2S)-2-chloro-N-[(1S)-1-[(1R,2S,5S)-2-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2,2-dimethyl-propyl]-2-fluoro-acetamide; (1S)—N-[(1S)-1-[(1R,2S,5S)-2-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(1R,2S,5S)-2-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3R)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(6S)-5-oxo-4-azaspiro[2.4]heptan-6-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(6R)-5-oxo-4-azaspiro[2.4]heptan-6-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3S,5S)-5-methyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3R,5S)-5-methyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3R,5R)-5-methyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3S,5R)-5-methyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(1R,2S,5S)-2-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3R,5S)-5-methyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(1R,2S,5S)-2-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3R,5R)-5-methyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(1R,2S,5S)-2-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3 S,5S)-5-methyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(1R,2S,5S)-2-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3S,5R)-5-methyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(1R,4S,5R)-3-oxo-2-azabicyclo[3.1.0]hexan-4-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(1S,4S,5S)-3-oxo-2-azabicyclo[3.1.0]hexan-4-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(1R,4S,5R)-3-oxo-2-azabicyclo[3.1.0]hexan-4-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(1R,4R,5R)-3-oxo-2-azabicyclo[3.1.0]hexan-4-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(1S,4S,5S)-3-oxo-2-azabicyclo[3.1.0]hexan-4-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; and (1S)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(1R,4R,5R)-3-oxo-2-azabicyclo[3.1.0]hexan-4-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide.
  17. 17 . The compound of formula (I) according to claim 16 , or a pharmaceutically acceptable salt thereof, selected from: N-[(1S,2S)-1-[(1R,2S,5S)-2-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2-methyl-butyl]-1-fluoro-cyclopropanecarboxamide; N-[(1S,2S)-1-[(1R,2S,5S)-2-[[[(2R)-2-chloro-2-fluoro-acetyl]-[[(3R)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2-methyl-butyl]-1-fluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; (1S)—N-[(1S)-1-[(3S,3aS,6aR)-3-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3R)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-2,2-dimethyl-propyl]-2,2-difluoro-cyclopropanecarboxamide; rac-(1S)-2,2-difluoro-N-[(1S)-2,2-dimethyl-1-[(3S,3aS,6aR)-3-[[(5,5-dimethyl-2-oxo-pyrrolidin-3-yl)methyl-[(2R)-2-chloro-2-fluoro-acetyl]amino]carbamoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]propyl]cyclopropanecarboxamide; N-[(1S,2S)-1-[(1R,2S,5S)-2-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3S)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2-methyl-butyl]-1-fluoro-cyclopropanecarboxamide; and N-[(1S,2S)-1-[(1R,2S,5S)-2-[[[(2S)-2-chloro-2-fluoro-acetyl]-[[(3R)-5,5-dimethyl-2-oxo-pyrrolidin-3-yl]methyl]amino]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2-methyl-butyl]-1-fluoro-cyclopropanecarboxamide.
  18. 18 . A process of manufacturing a compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof, comprising reacting a compound of formula (XI) wherein R 1 , R 2 , R 3a , R 3b , R 4a , R 4b , R 7a , R 7b , R 7c , and L are as defined in claim 1 ; with a compound of formula (XI-1), wherein R 5 and R 6 are as defined in claim 1 and LG 2 is a leaving group; in the presence of a coupling reagent and a base, to form said compound of formula (I).
  19. 19 - 20 . (canceled)
  20. 21 . A pharmaceutical composition comprising a compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

Description

FIELD OF THE INVENTION The present invention relates to peptidomimetic compounds that act as viral protease inhibitors. The invention further relates to methods of preparing and using such compounds. BACKGROUND OF THE INVENTION In December 2019, a new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), caused an outbreak of the novel coronavirus disease COVID-19, which has spread to more than 200 countries with over 9 million confirmed cases and over 479,133 confirmed deaths worldwide as of Jun. 26, 2020 (WHO COVID-19 situation report-157). The WHO declared the coronavirus outbreak a public health emergency of international concern. Currently, there are no clinically effective vaccine or specific antiviral drug available for the prevention and treatment of SARS-CoV-2 infections. Coronaviruses (CoVs) are enveloped, positive-sense, single-stranded RNA viruses. Seven human coronaviruses (HCoVs) have been so far identified, namely HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, SARS coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and the novel coronavirus (SARS-CoV-2). While SARS-CoV, MERS-CoV, and SARS-CoV-2 are highly pathogenic, the others generally cause mild to moderate upper-respiratory tract illness and contribute to 15%-30% cases of common colds in human adults. The RNA genome of SARS-CoV-2 is about 30 kilobases in length shares approximately 80% sequence identity with SARS-CoV (Zhou P. et al. “A pneumonia outbreak associated with a new coronavirus of probable bat origin.” Nature 579(7798): 270-273, 2020). It consists six major open-reading frames (ORFs). ORF 1a/b, which is about two thirds of the whole genome length, directly translates two polyproteins, pp1a and pp1ab, which encodes 16 nonstructural proteins (nsps) to form the replication transcription complex. Nsp3, which encodes papain-like protease (PLpro), and nsp5, which encodes 3-chymotrypsin-like cysteine protease (3CLpro, also known as main protease, Mpro), are essential for processing these polyproteins. 3CLpro cleaves the polyprotein at 11 distinct sites to generate various nsps that are important for viral replication. Accordingly, inhibitors that block the cleavage function of 3CLpro could inhibit virus replication. In addition, 3CLpro is highly conserved between SARS-CoV and SARS-CoV-2 (96% sequence identity), as well as the other human coronaviruses. Furthermore, no human proteases with a similar cleavage specificity is known. These desired properties make 3CLpro one of the most attractive targets against coronavirus infections. SUMMARY OF THE INVENTION In a first aspect, the present invention provides compounds of formula (I) wherein the variables are as defined herein. In further aspects, the present invention provides processes for manufacturing the compounds of formula (I) described herein, pharmaceutical compositions comprising the same and methods of using the same. DETAILED DESCRIPTION OF THE INVENTION Definitions Features, integers, characteristics, compounds, chemical moieties or groups described in conjunction with a particular aspect, embodiment or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein, unless incompatible therewith. All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive. The invention is not restricted to the details of any foregoing embodiments. The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed. The term “alkyl” refers to a mono- or multivalent, e.g., a mono- or bivalent, linear or branched saturated hydrocarbon group of 1 to 6 carbon atoms (“C1-6-alkyl”), e.g., 1, 2, 3, 4, 5, or 6 carbon atoms. In other embodiments, the alkyl group contains 1 to 3 carbon atoms, e.g., 1, 2 or 3 carbon atoms. Some non-limiting examples of alkyl include methyl, ethyl, propyl, 2-propyl (isopropyl), n-butyl, iso-butyl, sec-butyl, tert-butyl, and 2,2-dimethylpropyl. Particularly preferred, yet non-limiting examples of alkyl are methyl, tert-butyl, and 2,2-dimethylpropyl. The term “halogen” or “halo” refers to fluoro (F), chloro (Cl), bromo (Br), or iodo (I). Preferably, the term “halogen” or “halo” refers to fluoro (F), chloro (Cl) or bromo (Br). Particularly preferred, yet non-limiting examples of “halogen” or “halo” are fluoro (F) and chloro (Cl). The term “cycloalkyl” as used herein refers to a saturated or partly unsaturated monocyclic or bicyclic hydrocarbon group of 3 to 10 ring carbon atoms (“C3-10-cycloalkyl”). In some preferred embodime