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. Crystal form C of (2S)—N-{(1S)-1-cyano-2-[4-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl)phenyl]ethyl}-1,4-oxazepane-2-carboxamide:
having X-ray powder diffraction peaks (° 2Θ) at 9.0±0.1, 14.0±0.1, 16.0±0.1, 16.4±0.1 and 21.0±0.1.
2. The crystal form C of (2S)—N-{(1S)-1-cyano-2-[4-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl)phenyl]ethyl}-1,4-oxazepane-2-carboxamide of claim 1 , having X-ray powder diffraction peaks (° 2Θ) at 7.8±0.1, 14.4±0.1, 17.9±0.1, 18.9±0.1 and 19.6±0.1.
3. A pharmaceutical composition comprising the crystal form C of (2S)—N-{(1S)-1-cyano-2-[4-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl)phenyl]ethyl}-1,4-oxazepane-2-carboxamide of claim 1 , and a pharmaceutically acceptable adjuvant, diluent or carrier.
4. A pharmaceutical composition comprising the crystal form C of (2S)—N-{(1S)-1-cyano-2-[4-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl)phenyl]ethyl}-1,4-oxazepane-2-carboxamide of claim 2 , and a pharmaceutically acceptable adjuvant, diluent or carrier.
5. A method for treating an obstructive disease of the airway, comprising orally administering to a patient in need thereof, the pharmaceutical composition of claim 3 .
6. A method for treating an obstructive disease of the airway, comprising orally administering to a patient in need thereof, the pharmaceutical composition of claim 4 .
7. The method of claim 5 , wherein the obstructive disease of the airway is bronchiectasis.
8. The method of claim 5 , wherein the obstructive disease of the airway is cystic fibrosis.
9. The method of claim 5 , wherein the obstructive disease of the airway is asthma.
10. The method of claim 5 , wherein the obstructive disease of the airway is chronic obstructive pulmonary disease (COPD).
11. The method of claim 6 , wherein the obstructive disease of the airway is bronchiectasis.
12. The method of claim 6 , wherein the obstructive disease of the airway is cystic fibrosis.
13. The method of claim 6 , wherein the obstructive disease of the airway is asthma.
14. The method of claim 6 , wherein the obstructive disease of the airway is chronic obstructive pulmonary disease (COPD).