Certain (2S)-N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamides as dipeptidyl peptidase 1 inhibitors
The present disclosure relates to certain (2S)—N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), that inhibit dipeptidyl peptidase 1 (DPP1) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.
1. A method for treating an obstructive disease of the airway due to a coronavirus or influenza infection in a patient in need thereof, comprising, administering to the patient, an effective amount of a compound of formula (I)
or a pharmaceutically acceptable salt thereof, wherein,
R 2 is selected from hydrogen, F, Cl, Br, OSO 2 C 1-3 alkyl, or C 1-3 alkyl;
R 3 is selected from hydrogen, F, Cl, Br, CN, CF 3 , SO 2 C 1-3 alkyl, CONH 2 or SO 2 NR 4 R 5 ,
wherein R 4 and R 5 together with the nitrogen atom to which they are attached form an azetidine, pyrrolidine or piperidine ring; or
R 1 is selected from
X is selected from O, S or CF 2 ;
Y is selected from O or S;
Q is selected from CH or N;
R 6 is selected from C 1-3 alkyl, wherein said C 1-3 alkyl is optionally substituted by 1, 2 or 3 F and optionally by one substituent selected from OH, OC 1-3 alkyl, N(C 1-3 alkyl) 2 , cyclopropyl, or tetrahydropyran; and
R 7 is selected from hydrogen, F, Cl or CH 3 .
2. The method of claim 1 , wherein R 1 is selected from
X is selected from O, S or CF 2 ;
Y is selected from O or S;
Q is selected from CH or N;
R 6 is selected from C 1-3 alkyl, wherein said C 1-3 alkyl is optionally substituted by 1, 2 or 3 F and optionally by one substituent selected from OH, OC 1-3 alkyl, N(C 1-3 alkyl) 2 , cyclopropyl, or tetrahydropyran; and
R 7 is selected from hydrogen, F, Cl or CH 3 .
3. The method of claim 1 , wherein
R 1 is
X is selected from O, S or CF 2 ;
Y is selected from O or S;
R 6 is selected from C 1-3 alkyl, wherein said C 1-3 alkyl is optionally substituted by 1, 2 or 3 F and optionally by one substituent selected from OH, OC 1-3 alkyl, N(C 1-3 alkyl) 2 , cyclopropyl, or tetrahydropyran; and
R 7 is selected from hydrogen, F, Cl or CH 3 .
4. The method of claim 1 , wherein
R 1 is
X is O;
R 6 is C 1-3 alkyl, wherein said C 1-3 alkyl optionally substituted by 1, 2 or 3 F; and
R 7 is hydrogen.
5. The method of claim 1 , wherein
R 1 is
6. The method of claim 4 , wherein
R 1 is
X is O;
R 6 is C 1-3 alkyl; and
R 7 is hydrogen.
7. The method of claim 1 , wherein the compound of formula (I) is (2S)--N-{(1S)-1-cyano-2-[4-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-5-y-1)phenyl]ethyl}-1,4-oxazepane-2-carboxamide
or a pharmaceutically acceptable salt thereof.
8. The method of claim 7 , wherein the compound of formula (I) is (2S)--N-{(1S)-1-cyano-2-[4-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-5-y-1)phenyl]ethyl}-1,4-oxazepane-2-carboxamide.
9. The method of claim 1 , wherein the obstructive disease of the airway is due to a coronavirus infection.
10. The method of claim 1 , wherein the obstructive disease of the airway is due to an influenza infection.
11. The method of claim 2 , wherein the obstructive disease of the airway is due to a coronavirus infection.
12. The method of claim 2 , wherein the obstructive disease of the airway is due to an influenza infection.
13. The method of claim 3 , wherein the obstructive disease of the airway is due to a coronavirus infection.
14. The method of claim 3 , wherein the obstructive disease of the airway is due to an influenza infection.
15. The method of claim 4 , wherein the obstructive disease of the airway is due to a coronavirus infection.
16. The method of claim 4 , wherein the obstructive disease of the airway is due to an influenza infection.
17. The method of claim 5 , wherein the obstructive disease of the airway is due to a coronavirus infection.
18. The method of claim 5 , wherein the obstructive disease of the airway is due to an influenza infection.
19. The method of claim 6 , wherein the obstructive disease of the airway is due to a coronavirus infection.
20. The method of claim 6 , wherein the obstructive disease of the airway is due to an influenza infection.
21. The method of claim 7 , wherein the obstructive disease of the airway is due to a coronavirus infection.
22. The method of claim 7 , wherein the obstructive disease of the airway is due to an influenza infection.
23. The method of claim 8 , wherein the obstructive disease of the airway is due to a coronavirus infection.
24. The method of claim 8 , wherein the obstructive disease of the airway is due to an influenza infection.
25. The method of claim 9 , wherein the coronavirus is a SARS coronavirus.
26. The method of claim 11 , wherein the coronavirus is a SARS coronavirus.
27. The method of claim 13 , wherein the coronavirus is a SARS coronavirus.
28. The method of claim 15 , wherein the coronavirus is a SARS coronavirus.
29. The method of claim 17 , wherein the coronavirus is a SARS coronavirus.
30. The method of claim 19 , wherein the coronavirus is a SARS coronavirus.
31. The method of claim 21 , wherein the coronavirus is a SARS coronavirus.
32. The method of claim 23 , wherein the coronavirus is a SARS coronavirus.
33. The method of claim 9 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
34. The method of claim 10 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
35. The method of claim 11 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
36. The method of claim 12 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
37. The method of claim 13 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
38. The method of claim 14 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
39. The method of claim 15 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
40. The method of claim 16 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
41. The method of claim 17 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
42. The method of claim 18 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
43. The method of claim 19 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
44. The method of claim 20 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
45. The method of claim 21 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
46. The method of claim 22 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
47. The method of claim 23 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
48. The method of claim 24 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
49. The method of claim 25 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
50. The method of claim 26 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
51. The method of claim 27 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
52. The method of claim 28 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
53. The method of claim 29 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
54. The method of claim 30 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
55. The method of claim 31 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
56. The method of claim 32 , wherein the obstructive disease of the airway is acute respiratory distress syndrome (ARDS).
57. The method of claim 1 , wherein the compound is present in a sterile solution, suspension or emulsion.
58. The method of claim 57 , wherein administering comprises parenteral administration.
59. The method of claim 58 , wherein the parenteral administration is intravenous, subcutaneous, intramuscular, intravascular or infusion administration.
60. The method of claim 59 , wherein the parenteral administration is intravenous administration.