Substituted pyrazoloazepin-8-ones and their use as phosphodiesterase inhibitors

1. A Compound of general formula (I)

wherein

R 1 and R 4 are independently selected from the group consisting of hydrogen and (C 1 -C 4 )alkyl;

R 2 and R 3 are independently selected from the group consisting of hydrogen and (C 1 -C 4 )alkyl; or R 2 and R 3 may together with the carbon atom to which they are attached form a cyclopropyl, cyclobutyl, cyclopentyl, oxetanyl, tetrahydrofuranyl or tetrahydropyranyl ring;

n=0, 1 or 2;

Q is selected from the group consisting of —O—C(O)—R 5 ;

R 5 is selected from the group consisting of (C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl, (4-7)-membered heterocycloalkyl heteroaryl and aryl, wherein said heteroaryl and aryl are optionally substituted with one or more substituents selected from R 6 , and wherein said (C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl and (4-7)-membered heterocycloalkyl are optionally substituted with one or more substituents selected from R 7 ;

R 6 consists of halogen, cyano, hydroxyl, (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl, —S(O) 2 R x , —S(O) 2 NR a R b , C(O)NR a R b , —C(O)OR a , —C(O)R x and —OR x ;

R 7 consists of halogen, hydroxyl, (C 1 -C 4 )alkyl, cyano, oxo, —C(O)NR a R b , —C(O)OR a , —C(O)R x , S(O) 2 R x , —OR x , —SR x , aryl and heteroaryl;

R x consist of (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl;

R a and R b are independently selected from the group consisting of hydrogen, (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl and phenyl(C 1 -C 4 )alkyl, or

R a and R b may together with the nitrogen atom to which they are attached form a 4-6 membered heterocycloalkyl, wherein said heterocycloalkyl is optionally substituted with one or more (C 1 -C 4 )alkyl or —C(O)R x ;

or a pharmaceutically acceptable salt, hydrate or solvate thereof.

2. A Compound of general formula (I) according to claim 1 wherein

R 1 and R 4 are independently selected from the group consisting of hydrogen and (C 1 -C 4 )alkyl;

R 2 and R 3 are independently selected from the group consisting of hydrogen and (C 1 -C 4 )alkyl;

n=0, 1 or 2;

Q is selected from the group consisting of —O—C(O)—R 5 ;

R 5 is selected from the group consisting of (C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl, a (4-6)-membered heterocycloalkyl, a (5-6)-membered heteroaryl and phenyl, wherein said (5-6)-membered heteroaryl and phenyl are optionally substituted with one or more substituents selected from R 6 , and wherein said (C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl and (4-6)-membered heterocycloalkyl are optionally substituted with one or more substituents selected from R 7 ;

R 6 consists of halogen, cyano, hydroxyl, (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl, —S(O) 2 R x , —S(O) 2 NR a R b , C(O)NR a R b , —C(O)R x and —OR x ;

R 7 consists of halogen, hydroxyl, (C 1 -C 4 )alkyl, cyano, oxo, —C(O)NR a R b , —C(O)OR a , —C(O)R x , —S(O) 2 R x , —OR x , —SR x , aryl and heteroaryl;

R x consist of (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl;

R a and R b are independently selected from the group consisting of hydrogen, (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl and phenyl(C 1 -C 4 )alkyl, or R a and R b may together with the nitrogen atom to which they are attached form a 4-6 membered heterocycloalkyl, wherein said heterocycloalkyl is optionally substituted with one or more (C 1 -C 4 )alkyl or —C(O)R x ;

or a pharmaceutically acceptable salt, hydrate or solvate thereof.

3. A Compound of general formula (I)

wherein

R 1 and R 4 are independently selected from the group consisting of hydrogen and (C 1 -C 4 )alkyl;

R 2 and R 3 are independently selected from the group consisting of hydrogen and (C 1 -C 4 )alkyl; or R 2 and R 3 may together with the carbon atom to which they are attached form a cyclopropyl, cyclobutyl, cyclopentyl, oxetanyl, tetrahydrofuranyl or tetrahydropyranyl ring;

n=0, 1 or 2;

Q is selected from the group consisting of —O—C(O)—R 5 ;

R 5 is selected from the group consisting of (C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl, (4-7)-membered heterocycloalkyl and aryl, wherein said aryl is optionally substituted with one or more substituents selected from R 6 , and wherein said (C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl and (4-7)-membered heterocycloalkyl are optionally substituted with one or more substituents selected from R 7 ;

R 6 consists of halogen, cyano, hydroxyl, (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl, —S(O) 2 R x , —S(O) 2 NR a R b , and —OR x ;

R 7 consists of halogen, hydroxyl, cyano, —C(O)NR a R b , —C(O)OR a , aryl and heteroaryl;

R x is (C 1 -C 6 )alkyl;

R a and R b are independently selected from the group consisting of hydrogen, (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl and phenyl(C 1 -C 4 )alkyl, or

R a and R b may together with the nitrogen atom to which they are attached form a 4-6 membered heterocycloalkyl, wherein said heterocycloalkyl is optionally substituted with one or more (C 1 -C 4 )alkyl; or

a pharmaceutically acceptable salt, hydrate or solvate thereof.

4. A Compound according to claim 1 wherein all of R 1 , R 2 , R 3 , R 4 are hydrogen, n is 1, and R 5 is phenyl optionally substituted with one or two of R 6 .

5. A Compound according to claim 1 selected from the group consisting of

(i) 3-(1-Ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-(methylsulfamoyl)benzoate (Compound 101),

(ii) 3-(1-Ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-(dimethylsulfamoyl)benzoate (Compound 102),

(iii) 3-(1-Ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-methylsulfonylbenzoate (Compound 103);

or a pharmaceutically acceptable salt, hydrate or solvate thereof.

6. A Compound according to claim 1 selected from the group consisting of:

(i) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-methylpropanoate

(ii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl cyclopentanecarboxylate

(iii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-ethylbutanoate

(iv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl benzoate

(v) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-methylbenzoate

(vi) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-fluorobenzoate

(vii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-fluorobenzoate

(viii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-cyanobenzoate

(ix) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-cyanobenzoate

(x) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3,4-dimethylbenzoate

(xi) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2,4-dimethylbenzoate

(xii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-ethylbenzoate

(xiii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-methoxybenzoate

(xiv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-methoxybenzoate

(xv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-fluoro-4-methyl-benzoate

(xvi) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-fluoro-2-methyl-benzoate

(xvii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 5-fluoro-2-methyl-benzoate

(xviii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-fluoro-2-methyl-benzoate

(xix) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-chlorobenzoate

(xx) (3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3,4-difluorobenzoate

(xxi) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2,3-difluorobenzoate

(xxii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2,5-difluorobenzoate

(xxiii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2,6-difluorobenzoate

(xxiv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-acetyl benzoate

(xxv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-acetyl benzoate

(xxvi) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-cyano-5-fluoro-benzoate

(xxvii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-cyano-4-fluoro-benzoate

(xxviii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 5-cyano-2-fluoro-benzoate

(xxix) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-cyano-3-fluoro-benzoate

(xxx) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-methoxy-3-methyl-benzoate

(xxxi) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-methoxy-4-methyl-benzoate

(xxxii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-fluoro-4-methoxy-benzoate

(xxxiii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-fluoro-3-methoxy-benzoate

(xxxiv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-fluoro-5-methoxy-benzoate

(xxxv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-fluoro-4-methoxy-benzoate

(xxxvi) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-fluoro-3-methoxy-benzoate

(xxxvii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-fluoro-2-methoxy-benzoate

(xxxviii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-fluoro-6-methoxy-benzoate

(xxxix) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-chloro-4-methyl-benzoate

(xl) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-chloro-2-methyl-benzoate

(xli) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 5-chloro-2-methyl-benzoate

(xlii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-(difluoromethyl)benzoate

(xliii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-chloro-5-fluoro-benzoate

(xliv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-chloro-5-fluoro-benzoate

(xlv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-chloro-3-fluoro-benzoate

(xlvi) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-chloro-3-fluoro-benzoate

(xlvii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-chloro-2-fluoro-benzoate

(xlviii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 5-chloro-2-fluoro-benzoate

(xlix) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-chloro-6-fluoro-benzoate

(l) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-chloro-2-fluoro-benzoate

(li) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-chloro-4-fluoro-benzoate

(lii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-chloro-3-methoxy-benzoate

(liii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-chloro-5-methoxy-benzoate

(liv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-chloro-3-methoxy-benzoate

(lv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-chloro-4-methoxy-benzoate

(lvi) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-chloro-2-methoxy-benzoate

(lvii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 5-chloro-2-methoxy-benzoate

(lviii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-chloro-2-methoxy-benzoate

(lix) (3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-(trifluoromethyl)benzoate

(lx) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-methylsulfonylbenzoate

(lxi) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-methylsulfonylbenzoate

(lxii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-sulfamoylbenzoate

(lxiii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-sulfamoylbenzoate

(lxiv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-methyl-5-(trifluoromethyl)benzoate

(lxv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-methyl-3-(trifluoromethyl)benzoate

(lxvi) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-fluoro-3-(trifluoromethyl)benzoate

(lxvii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-fluoro-4-(trifluoromethyl)benzoate

(lxviii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-fluoro-2-(trifluoromethyl)benzoate

(lxix) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-fluoro-5-(trifluoromethyl)benzoate

(lxx) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-fluoro-5-(trifluoromethyl)benzoate

(lxxi) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 5-fluoro-2-(trifluoromethyl)benzoate

(lxxii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-fluoro-4-(trifluoromethyl)benzoate

(lxxiii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-ethylsulfonylbenzoate

(lxxiv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-ethylsulfonylbenzoate

(lxxv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-(methylsulfamoyl)benzoate

(lxxvi) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-methoxy-3-(trifluoromethyl)benzoate

(lxxvii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 5-methoxy-2-(trifluoromethyl)benzoate

(lxxviii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-methoxy-2-(trifluoromethyl)benzoate

(lxxix) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-methoxy-5-(trifluoromethyl)benzoate

(lxxx) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-methoxy-4-(trifluoromethyl)benzoate

(lxxxi) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-chloro-2-(trifluoromethyl)benzoate

(lxxxii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-chloro-3-(trifluoromethyl)benzoate

(lxxxiii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-chloro-4-(trifluoromethyl)benzoate

(lxxxiv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 5-chloro-2-(trifluoromethyl)benzoate

(lxxxv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-chloro-4-(trifluoromethyl)benzoate

(lxxxvi) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-chloro-3-(trifluoromethyl)benzoate

(lxxxvii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-chloro-5-(trifluoromethyl)benzoate

(lxxxviii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-chloro-5-(trifluoromethyl)benzoate

(lxxxix) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-isopropylsulfonylbenzoate

(xc) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-isopropylsulfonylbenzoate

(xci) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-cyclopentylsulfonylbenzoate

(xcii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-pyrrolidin-1-ylsulfonylbenzoate

(xciii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-pyrrolidin-1-ylsulfonylbenzoate

(xciv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2,4-bis(trifluoromethyl)benzoate

(xcv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3,4-bis(trifluoromethyl)benzoate

(xcvi) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-morpholinosulfonylbenzoate

(xcvii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-morpholinosulfonylbenzoate

(xcviii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-(4-acetylpiperazin-1-yl)sulfonylbenzoate

(xcix) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-(4-acetylpiperazin-1-yl)sulfonylbenzoate

(c) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-carbamoylbenzoate

(ci) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-(methylcarbamoyl)benzoate

(cii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-(dimethylcarbamoyl)benzoate

(ciii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-(pyrrolidine-1-carbonyl)benzoate

(civ) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-(piperidine-1-carbonyl)benzoate

(cv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-(morpholine-4-carbonyl)benzoate

(cvi) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-(4-methylpiperazine-1-carbonyl)benzoate

(cvii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 4-(4-acetylpiperazine-1-carbonyl)benzoate

(cviii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-carbamoylbenzoate

(cix) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-(methylcarbamoyl)benzoate

(cx) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-(dimethylcarbamoyl)benzoate

(cxi) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-(pyrrolidine-1-carbonyl)benzoate

(cxii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-(piperidine-1-carbonyl)benzoate

(cxiii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-(morpholine-4-carbonyl)benzoate

(cxiv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-(4-methylpiperazine-1-carbonyl)benzoate

(cxv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-(4-acetylpiperazine-1-carbonyl)benzoate

(cxvi) 4-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)butyl 2-methyl propanoate

(cxvii) 4-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)butyl cyclopentanecarboxylate

(cxviii) 4-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)butyl 4-methylbenzoate

(cxix) 4-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)butyl 4-fluorobenzoate

(cxx) 4-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)butyl 4-methoxybenzoate

(cxxi) 4-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)butyl 4-acetylbenzoate

(cxxii) 4-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)butyl 4-carbamoylbenzoate

(cxxiii) 4-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)butyl 4-(methylcarbamoyl)benzoate

(cxxiv) 4-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)butyl 4-(dimethylcarbamoyl)benzoate

(cxxv) 4-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)butyl 4-methylsulfonylbenzoate

(cxxvi) 4-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)butyl 4-(methylsulfamoyl)benzoate

(cxxvii) 4-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)butyl 4-(dimethylsulfamoyl)benzoate

(cxxviii) 4-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)butyl 4-(morpholine-4-carbonyl)benzoate

(cxxix) 2-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)ethyl cyclopentanecarboxylate

(cxxx) 2-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)ethyl 4-methylbenzoate

(cxxxi) 2-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)ethyl 4-methylsulfonylbenzoate

(cxxxii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]3-methoxypropanoate

(cxxxiii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]3-hydroxycyclobutanecarboxylate

(cxxxiv) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]3-methylsulfanylpropanoate

(cxxxv) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]4-methylbenzoate

(cxxxvi) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]2-methylbenzoate

(cxxxvii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]3-methylbenzoate

(cxxxviii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]3-fluorobenzoate

(cxxxix) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]2-fluorobenzoate

(cxl) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]4-fluorobenzoate

(cxli) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]4-hydroxycyclohexanecarboxylate

(cxlii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]4-hydroxycyclohexanecarboxylate

(cxliii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]4-ethylbenzoate

(cxliv) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]4-methoxybenzoate

(cxlv) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]3-methoxybenzoate

(cxlvi) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]2-methoxybenzoate

(cxlvii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]3-methylsulfonylpropanoate

(cxlviii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]4-acetylbenzoate

(cxlix) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]3-acetylbenzoate

(cl) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]4-methylsulfonylbenzoate

(cli) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]3-ethylsulfonylbenzoate

(clii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]4-ethylsulfonylbenzoate

(cliii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]4-(methylsulfamoyl)benzoate

(cliv) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]3-isopropylsulfonylbenzoate

(clv) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]4-isopropylsulfonylbenzoate

(clvi) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]4-(dimethylsulfamoyl)benzoate

(clvii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]4-cyclopentylsulfonylbenzoate

(clviii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]3-pyrrolidin-1-ylsulfonylbenzoate

(clix) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]3-morpholinosulfonylbenzoate

(clx) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]4-morpholinosulfonylbenzoate

(clxi) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]3-(4-acetylpiperazin-1-yl)sulfonylbenzoate

(clxii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]4-(4-acetylpiperazin-1-yl)sulfonylbenzoate

(clxiii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]4-carbamoylbenzoate

(clxiv) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]4-(methylcarbamoyl)benzoate

(clxv) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]4-(dimethylcarbamoyl)benzoate

(clxvi) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]4-(pyrrolidine-1-carbonyl)benzoate

(clxvii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]4-(piperidine-1-carbonyl)benzoate

(clxviii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]4-(morpholine-4-carbonyl)benzoate

(clxix) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]4-(4-methylpiperazine-1-carbonyl)benzoate

(clxx) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]4-(4-acetylpiperazine-1-carbonyl)benzoate

(clxxi) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]3-carbamoylbenzoate

(clxxii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]3-(methylcarbamoyl)benzoate

(clxxiii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]3-(dimethylcarbamoyl)benzoate

(clxxiv) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]3-(pyrrolidine-1-carbonyl)benzoate

(clxxv) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]3-(piperidine-1-carbonyl)benzoate

(clxxvi) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]3-(morpholine-4-carbonyl)benzoate

(clxxvii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]3-(4-methylpiperazine-1-carbonyl)benzoate

(clxxviii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]3-(4-acetylpiperazine-1-carbonyl)benzoate

(clxxix) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]3-methoxypropanoate

(clxxx) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]3-methylsulfanylpropanoate

(clxxxi) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-methylbenzoate

(clxxxii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]2-methylbenzoate

(clxxxiii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]3-methylbenzoate

(clxxxiv) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]3-fluorobenzoate

(clxxxv) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-fluorobenzoate

(clxxxvi) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]2-fluorobenzoate

(clxxxvii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-hydroxycyclohexanecarboxylate

(clxxxviii)[3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-ethylbenzoate

(clxxxix) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]3-methoxybenzoate

(cxc) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-methoxybenzoate

(cxci) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]2-methoxybenzoate

(cxcii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]3-methylsulfonylpropanoate

(cxciii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-acetylbenzoate

(cxciv) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]3-acetylbenzoate

(cxcv) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-methylsulfonylbenzoate

(cxcvi) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-ethylsulfonylbenzoate

(cxcvii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]3-ethylsulfonylbenzoate

(cxcviii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-(methylsulfamoyl)benzoate

(cxcix) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]3-isopropylsulfonylbenzoate

(cc) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-isopropylsulfonylbenzoate

(cci) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-(dimethylsulfamoyl)benzoate

(ccii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-cyclopentylsulfonylbenzoate

(cciii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]3-pyrrolidin-1-ylsulfonylbenzoate

(cciv) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-pyrrolidin-1-ylsulfonylbenzoate

(ccv) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]3-morpholinosulfonylbenzoate

(ccvi) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-morpholinosulfonylbenzoate

(ccvii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-[benzyl(methyl)sulfamoyl]benzoate

(ccviii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]3-(4-acetylpiperazin-1-yl)sulfonylbenzoate

(ccix) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-(4-acetylpiperazin-1-yl)sulfonylbenzoate

(ccx) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-carbamoylbenzoate

(ccxi) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-(methylcarbamoyl)benzoate

(ccxii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-(dimethylcarbamoyl)benzoate

(ccxiii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-(pyrrolidine-1-carbonyl)benzoate

(ccxiv) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-(piperidine-1-carbonyl)benzoate

(ccxv) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-(morpholine-4-carbonyl)benzoate

(ccxvi) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-(4-methylpiperazine-1-carbonyl)benzoate

(ccxvii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]4-(4-acetylpiperazine-1-carbonyl)benzoate

(ccxviii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]3-carbamoylbenzoate

(ccxix) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]3-(methylcarbamoyl)benzoate

(ccxx) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]3-(dimethylcarbamoyl)benzoate

(ccxxi) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]3-(pyrrolidine-1-carbonyl)benzoate

(ccxxii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]3-(piperidine-1-carbonyl)benzoate

(ccxxiii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]3-(morpholine-4-carbonyl)benzoate

(ccxxiv) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]3-(4-methylpiperazine-1-carbonyl)benzoate

(ccxxv) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]3-(4-acetylpiperazine-1-carbonyl)benzoate,

or a pharmaceutically acceptable salt, hydrate or solvate thereof.

7. A compound according to claim 1 selected from the group consisting of:

(i) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl oxazole-4-carboxylate

(ii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl tetrahydrofuran-3-carboxylate

(iii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 1-methylpyrazole-3-carboxylate

(iv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 1-methylpyrazole-4-carboxylate

(v) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 1-methylimidazole-4-carboxylate

(vi) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-methyloxazole-4-carboxylate

(vii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-methyloxazole-5-carboxylate

(viii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl isothiazole-5-carboxylate

(ix) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl isothiazole-4-carboxylate

(x) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl thiazole-4-carboxylate

(xi) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl thiazole-5-carboxylate

(xii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl tetrahydropyran-4-carboxylate

(xiii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-methylpyrimidine-5-carboxylate

(xiv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 1-ethyl pyrazole-3-carboxylate

(xv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 1,5-dimethylpyrazole-3-carboxylate

(xvi) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 1-ethyl pyrazole-4-carboxylate

(xvii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-ethyloxazole-4-carboxylate

(xviii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 1-acetylazetidine-3-carboxylate

(xix) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 3-methylisothiazole-5-carboxylate

(xx) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-methylthiazole-4-carboxylate

(xxi) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-methylthiazole-5-carboxylate

(xxii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 1-methylpiperidine-4-carboxylate

(xxiii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl tetrahydrothiopyran-4-carboxylate

(xxiv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2,6-dimethylpyridine-4-carboxylate

(xxv) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 5-ethyl-1-methyl-pyrazole-3-carboxylate

(xxvi) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 2-ethylthiazole-4-carboxylate

(xxvii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 1-acetylpiperidine-4-carboxylate

(xxviii) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 1,1-dioxothiane-4-carboxylate

(xxix) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl] 1-methoxycarbonylpiperidine-4-carboxylate

(xxx) 3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)propyl 1-(dimethylcarbamoyl)piperidine-4-carboxylate

(xxxi) 4-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)butyl tetrahydrofuran-3-carboxylate

(xxxii) 4-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)butyl 2-methyloxazole-4-carboxylate

(xxxiii) 4-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)butyl 2-methyloxazole-5-carboxylate

(xxxiv) 4-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)butyl isothiazole-4-carboxylate

(xxxv) 4-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)butyl thiazole-4-carboxylate

(xxxvi) 4-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)butyl tetrahydropyran-4-carboxylate

(xxxvii) 4-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)butyl 2-methylpyrimidine-5-carboxylate

(xxxviii) 4-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)butyl 1,5-dimethylpyrazole-3-carboxylate

(xxxix) 4-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)butyl 2,6-dimethylpyridine-4-carboxylate

(xl) 4-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)butyl 1-acetylpiperidine-4-carboxylate

(xli) 2-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)ethyl isothiazole-4-carboxylate

(xlii) 2-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)ethyl tetrahydropyran-4-carboxylate

(xliii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl] oxazole-4-carboxylate

(xliv) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl] 1-methylpyrazole-3-carboxylate

(xlv) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl] 1-methylpyrazole-4-carboxylate

(xlvi) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl] 1-methylimidazole-4-carboxylate

(xlvii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]2-methyloxazole-4-carboxylate

(xlviii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]2-methyloxazole-5-carboxylate

(xlix) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl] isothiazole-5-carboxylate

(l) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl] isothiazole-4-carboxylate

(li) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl] thiazole-4-carboxylate

(lii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl] thiazole-5-carboxylate

(liii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl] tetrahydropyran-4-carboxylate

(liv) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]2-methylpyrimidine-5-carboxylate

(lv) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]1,5-dimethylpyrazole-3-carboxylate

(lvi) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]2-methylthiazole-4-carboxylate

(lvii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]2-methylthiazole-5-carboxylate

(lviii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl] 1-methyl piperidine-4-carboxylate

(lix) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl]2,6-dimethylpyridine-4-carboxylate

(lx) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl] 1-acetylpiperidine-4-carboxylate

(lxi) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl] 1-methoxycarbonylpiperidine-4-carboxylate

(lxii) [(2R)-3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2-methyl-propyl] 1-(dimethylcarbamoyl)piperidine-4-carboxylate

(lxiii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl] oxazole-4-carboxylate

(lxiv) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl] 1-methylpyrazole-3-carboxylate

(lxv) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl] 1-methylpyrazole-4-carboxylate

(lxvi) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl] 1-methylimidazole-4-carboxylate

(lxvii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]2-methyloxazole-4-carboxylate

(lxviii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]2-methyloxazole-5-carboxylate

(lxix) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl] isothiazole-5-carboxylate

(lxx) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl] isothiazole-4-carboxylate

(lxxi) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl] thiazole-4-carboxylate

(lxxii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl] thiazole-5-carboxylate

(lxxiii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl] tetrahydropyran-4-carboxylate

(lxxiv) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]2-methylpyrimidine-5-carboxylate

(lxxv) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]1,5-dimethylpyrazole-3-carboxylate

(lxxvi) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]2-methylthiazole-4-carboxylate

(lxxvii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]2-methylthiazole-5-carboxylate

(lxxviii) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl] 1-methylpiperidine-4-carboxylate

(lxxix) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]2,6-dimethylpyridine-4-carboxylate

(lxxx) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl] 1-acetylpiperidine-4-carboxylate

(lxxxi) [3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl] 1-methoxycarbonylpiperidine-4-carboxylate

(lxxxii)[3-(1-ethyl-8-oxo-spiro[6,7-dihydro-4H-pyrazolo[3,4-c]azepine-5,4′-tetrahydropyran]-3-yl)-2,2-dimethyl-propyl]1-(dimethylcarbamoyl)piperidine-4-carboxylate,

or a pharmaceutically acceptable salt, hydrate or solvate thereof.

8. A pharmaceutical composition comprising a Compound according to claim 1 together with one or more pharmaceutically acceptable vehicles or excipients or one or more pharmaceutically acceptable carriers.

9. The pharmaceutical composition according to claim 8 further comprising one or more other therapeutically active compounds.

10. A method for treatment or alleviation of a disease or a disorder or a condition responsive to PDE4 inhibitory activity, comprising administering to a subject in need thereof a therapeutically effective amount of a Compound according to claim 1 .

11. A method of treating or ameliorating one or more dermal diseases or conditions, comprising administering to a person suffering from at least one of said diseases an effective amount of one or more Compounds according to according to claim 1 .

12. The method according to claim 11 , wherein the dermal disease or condition is selected from the group consisting of proliferative and inflammatory skin disorders, dermatitis, atopic dermatitis, seborrheic dermatitis, contact dermatitis, psoriasis, cancer, epidermal inflammation, alopecia, alopecia areata, skin atrophy, steroid induced skin atrophy, skin ageing, photo skin ageing, acne, urticaria, pruritis, and eczema.

13. A method of treating or ameliorating one or more dermal diseases or conditions, comprising administering to a person suffering from at least one of said diseases an effective amount of the pharmaceutical composition according to claim 8 .