Certain (2S)-N-[(1 s)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamides as dipeptidyl peptidase 1 inhibitors

1. A hydrate of a compound of formula (I),

wherein the compound of formula (I) has a pIC 50 value of from about 7.00 to about 8.6, in a dipeptidyl transferase 1 (DPP1) inhibition assay, and wherein,

R 1 is

R 2 is hydrogen, F, Cl, Br, OSO 2 C 1-3 alkyl, or C 1-3 alkyl;

R 3 is 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 a azetidine, pyrrolidine or piperidine ring; or

R 1 is

X is O, S or CF 2 ;

Y is O or S;

Q is CH or N;

R 6 is 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 tetrapydropyran; and

R 7 is hydrogen, F, Cl or CH 3 .

2. The hydrate of claim 1 , wherein R 1 is

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 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 hydrate 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 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 hydrate of claim 1 , wherein,

R 1 is

5. The hydrate of claim 4 , wherein,

X is O;

R 6 is C 1-3 alkyl; and

R 7 is hydrogen;

or a pharmaceutically acceptable salt thereof.

6. The hydrate of claim 1 , wherein,

R 1 is

X is O;

R 6 is C 1-3 alkyl, wherein said C 1-3 alkyl is optionally substituted by 1, 2 or 3 F; and

R 7 is hydrogen.

7. The hydrate of claim 1 , wherein,

R 1 is

X is O;

R 6 is C 1-3 alkyl; and

R 7 is hydrogen.

8. The hydrate of claim 1 , wherein the compound of formula (I) is selected from the group consisting of:

(2S)-N-[(1S)-1-Cyano-2-(4′-cyanobiphenyl-4-yl)ethyl]-1,4-oxazepane-2-carboxamide;

(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;

(2S)-N-{(1S)-1-Cyano-2-[4-(3,7-dimethyl-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl)phenyl]ethyl}-1,4-oxazepane-2-carboxamide;

4′-[(2S)-2-Cyano-2-{[(2S)-1,4-oxazepan-2-ylcarb onyl] amino ethyl]biphenyl-3-yl methanesulfonate;

(2S)-N-{(1S)-1-Cyano-2-[4-(3-methyl-1,2-benzoxazol-5-yl)phenyl]ethyl}-1,4-oxazepane-2-carboxamide;

(2S)-N-{(1S)-1-Cyano-2-[4 ‘-(trifluoromethyl)biphenyl-4-yl]ethyl-1,4-oxazepane-2-carboxamide;

(2S)-N-[(1S)-1-Cyano-2-(3’,4′-difluorobiphenyl-4-yl)ethyl]-1,4-oxazepane-2-carboxamide;

(2S)-N-415)-1-Cyano-2-[4-(6-cyanopyridin-3-yl)phenyl]ethyl-1,4-oxazepane-2-carboxamide;

(2S)-N-{(1S)-1-Cyano-2-[4-(4-methyl-3-oxo-3,4-dihydro-2H-1,4-benzothiazin-6-yl)phenyl]ethyl 1-1,4-oxazepane-2-carboxamide;

(2S)-N-{(1S)-1-Cyano-2-[4-(3-ethyl-7-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl)phenyl]ethyl 1-1,4-oxazepane-2-carboxamide;

(2S)-N-R 1S)-1-Cyano-2-{4-[3-(2-hydroxy-2-methylpropyl)-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl]phenyl ethyl]-1,4-oxazepane-2-carboxamide;

(2S)—N-[(1S)-1-Cyano-2-{4-[3-(2,2-difluoroethyl)-7-fluoro-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl]phenyl ethyl]-1,4-oxazepane-2-carboxamide;

(2S)—N-[(1S)-1-Cyano-2-(4-{3 [2-(dimethylamino)ethyl]-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl}phenyl)ethyl]-1,4-oxazepane-2-carboxamide;

(2S)-N-{(1S)-1-Cyano-2-[4-(3,3-difluoro-1-methyl-2-oxo-2,3-dihydro-1H-indol-6-yl)phenyl]ethyl 1-1,4-oxazepane-2-carboxamide;

(2S)-N-{(1S)-1-Cyano-2-[4-(7-fluoro-3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl)phenyl]ethyl 1-1,4-oxazepane-2-carboxamide;

(2S)-N-{(1S)-1-Cyano-2-[4-(3-ethyl-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl)phenyl] ethyl 1-1,4-oxazepane-2-carboxamide;

(2S)—N-[(1S)-1-Cyano-2-{4-[3-(cyclopropylmethyl)-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl]phenyl ethyl]-1,4-oxazepane-2-carboxamide;

(2S)—N—R 1S)-1-Cyano-2-{4-[3-(2-methoxyethyl)-2-oxo-2,3-dihydro-1,3-benzothiazol-5-yl]phenyl ethyl]-1,4-oxazepane-2-carboxamide;

(2S)—N—R 1S)-1-Cyano-2-{442-oxo-3-(propan-2-yl)-2,3-dihydro-1,3-benzoxazol-5-yl]phenyl ethyl]-1,4-oxazepane-2-carboxamide;

(2S)-N-{(1S)-1-Cyano-2-[4-(4-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)phenyl]ethyl 1-1,4-oxazepane-2-carboxamide;

(2S)-N-[(1S)-1-Cyano-2-{4-[3-(2-methoxyethyl)-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl]phenyl ethyl]-1,4-oxazepane-2-carboxamide;

(2S)-N-{(1S)-1-Cyano-2[4-(5-cyanothiophen-2-yl)phenyflethyl 1-1,4-oxazepane-2-carboxamide;

(2S)-N-R1S)-2-(4′-Carbamoyl-3′-fluorobiphenyl-4-yl)-1-cyanoethyl]-1,4-oxazepane-2-carboxamide;

(2S)-N-{(1S)-1-Cyano-2-[4-(1-methyl-2-oxo-1,2-dihydroquinolin-7-yl)phenyl]ethyl-1,4-oxazepane-2-carboxamide;

(2S)-N-R 15)-1-Cyano-2-4-[2-oxo-3-(tetrahy dro-2H-pyran-4-ylmethyl)-2,3-dihydro-1,3-benzoxazol-5-yl]phenyl ethyl]-1,4-oxazepane-2-carboxamide;

(2S)-N-{(1S)-2-[4-(7-Chloro-3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl)phenyl]-1-cyanoethyl 1-1,4-oxazepane-2-carboxamide;

(2S)-N-[(1S)-1-Cyano-2-14-[3-(2,2-difluoroethyl)-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl]phenyl ethyl]-1,4-oxazepane-2-carboxamide;

(2S)-N-[(1S)-1-Cyano-2-{4-[2-oxo-3-(2,2,2-trifluoroethyl)-2,3-dihydro-1,3-benzoxazol-5-yl]phenyl ethyl]-1,4-oxazepane-2-carboxamide;

(2S)-N-{(1S)-1-Cyano-2-[4-(3-methyl-2-oxo-2,3-dihydro-1,3-benzothiazol-5-yl)phenyl]ethyl}-1,4-oxazepane-2-carboxamide;

(2S)-N-{(1S)-1-Cyano-2[4′-(methyl sulfonyl)biphenyl-4-yl] ethyl 1-1,4-oxazepane-2-carboxamide;

(2S)-N{(1S)-2-[4′-(Azetidin-1-yl sulfonyl)biphenyl-4-yl]-1-cyanoethyl}-1,4-oxazepane-2-carboxamide;

(2S)-N-R15′)-1-Cyano-2-(4′-fluorobiphenyl-4-yl)ethyl]-1,4-oxazepane-2-carboxamide;

(2S)-N-{(1S)-2-[4-(1,3-Benzothiazol-5-yl)phenyl]-1-cyanoethyl -1,4-oxazepane-2-carboxamide;

(2S)-N-R1S)-1-Cyano-2-(4′-cyanobiphenyl-4-yl)ethyl]-1,4-oxazepane-2-carboxamide; or

(2S)-N-{(1S)-1-Cyano-2-[4-(4-methyl-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-yl)phenyl] ethyl 1-1,4-oxazepane-2-carboxamide;

and pharmaceutically acceptable salts thereof.

9. The hydrate of claim 1 which is (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:

10. A pharmaceutical composition comprising the hydrate of claim 1 , and a pharmaceutically acceptable adjuvant, diluent or carrier.

11. A pharmaceutical composition comprising the hydrate of claim 9 , and a pharmaceutically acceptable adjuvant, diluent or carrier.

12. A method for treating an obstructive disease of the airway, comprising orally administering to a patient in need thereof, the pharmaceutical composition of claim 10 .

13. A method for treating an obstructive disease of the airway, comprising orally administering to a patient in need thereof, the pharmaceutical composition of claim 11 .

14. The method of claim 12 , wherein the obstructive disease of the airway is bronchiectasis.

15. The method of claim 12 , wherein the obstructive disease of the airway is cystic fibrosis.

16. The method of claim 12 , wherein the obstructive disease of the airway is asthma.

17. The method of claim 12 , wherein the obstructive disease of the airway is chronic obstructive pulmonary disease (COPD).

18. The method of claim 13 , wherein the obstructive disease of the airway is bronchiectasis.

19. The method of claim 13 , wherein the obstructive disease of the airway is cystic fibrosis.

20. The method of claim 13 , wherein the obstructive disease of the airway is asthma.

21. The method of claim 13 , wherein the obstructive disease of the airway is chronic obstructive pulmonary disease (COPD).