Peptidyl nitril compounds as dipeptidyl peptidase I inhibitors
The invention relates to compounds of Formula (I) and their use as selective dipeptidyl peptidase I inhibitors, as well as pharmaceutical compositions comprising said compounds, and methods of treatment involving said compounds.
1. A compound of the formula (I)
wherein X 1 represents
wherein y represents 0, 1, 2, 3, 4, 5, 6, 7 or 8;
wherein Z represents O (oxygen);
when y is 1 or 2, then R 1 independently represents deuterium; halogen; hydroxyl; cyano; oxo (═O); mercapto; or C 1-3 -alkyl; which C 1-3 -alkyl is optionally substituted with at least one substituent selected from halogen, hydroxyl, cyano and mercapto;
or when y represents 3, 4, 5, 6, 7 or 8, then R 1 represents deuterium;
wherein R 2 represents —C 3-6 -cycloalkyl, —C 1-3 -alkyl-C 3-6 -cycloalkyl or —C 1-6 -alkyl, which —C 1-6 -alkyl is optionally substituted with at least one substituent selected from hydroxyl, cyano or amino; as well as pharmaceutically-acceptable salts thereof.
2. The compound according to claim 1 consisting of:
3. The compound according to claim 1 , wherein R 2 is —C 1-6 -alkyl, which —C 1-6 -alkyl is optionally substituted with at least one substituent selected from hydroxyl, cyano or amino.
4. The compound according to claim 1 , wherein R 2 is —C 1-6 -alkyl, preferably —C 1-3 -alkyl, more preferably methyl-, ethyl- or propyl-.
5. The compound according to claim 1 , wherein y represents 0, 1, 2, 3, or 4.
6. A pharmaceutical composition comprising a compound of the formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof, together with at least one pharmaceutically-acceptable adjuvant, carrier or diluent.
7. A method for treatment of a medical condition selected from the group selected from asthma, chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, alpha-1 antitrypsin deficiency, acute lung injury, acute respiratory distress syndrome, congestive heart failure, atherosclerosis, myocardial infarction, reperfusion injury, abdominal aortic aneurysms, diabetic cardiomyopathy, gout, pseudogout, respiratory syncytial virus infection, inflammatory bowel diseases, psoriasis, rheumatoid arthritis, multiple sclerosis, malaria, Alzheimer's disease or sepsis, said method comprising administering a pharmaceutically effective amount of a compound of formula (I) according to claim 1 .
8. The method according to claim 7 , wherein the medical condition is selected from the group selected from asthma, chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, alpha-1 antitrypsin deficiency, congestive heart failure, myocardial infarction, reperfusion injury, abdominal aortic aneurysms, diabetic cardiomyopathy, gout, pseudogout, respiratory syncytial virus infection, rheumatoid arthritis or sepsis.
9. The compound according to claim 1 , wherein y represents 0.
10. A pharmaceutical comprising a compound of the formula:
or a pharmaceutically acceptable salt thereof, together with at least one pharmaceutically-acceptable adjuvant, carrier or diluent.
11. The method of claim 7 , wherein a symptom of said medical condition is alleviated.
12. The method of claim 8 , wherein a symptom of said medical condition is alleviated.
13. A method for treatment of a medical condition selected from the group selected from asthma, chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, alpha-1 antitrypsin deficiency, acute lung injury, acute respiratory distress syndrome, congestive heart failure, atherosclerosis, myocardial infarction, reperfusion injury, abdominal aortic aneurysms, diabetic cardiomyopathy, gout, pseudogout, respiratory syncytial virus infection, inflammatory bowel diseases, psoriasis, rheumatoid arthritis, multiple sclerosis, malaria, Alzheimer's disease or sepsis, said method comprising administering a pharmaceutically effective amount of a compound according to claim 2 .
14. The method according to claim 11 , wherein the medical condition is selected from the group selected from asthma, chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, alpha-1 antitrypsin deficiency, congestive heart failure, myocardial infarction, reperfusion injury, abdominal aortic aneurysms, diabetic cardiomyopathy, gout, pseudogout, respiratory syncytial virus infection, rheumatoid arthritis or sepsis.
15. The method of claim 13 , wherein a symptom of said medical condition is alleviated.
16. The method of claim 14 , wherein a symptom of said medical condition is alleviated.