Bicyclic compound and use thereof for medical purposes

1. A compound represented by the formula (I):

wherein Z represents (1)-(CH 2 ) m —, (2)-(CH 2 ) n —CH═CH—, (3)-(CH 2 ) p -A-CH 2 — or (4) ring 1;

A represents an oxygen atom or a sulfur atom;

R 1 represents (1) COOH, (2) COOR 2 , (3) CH 2 OH or (4) CONR 3 R 4 ;

R 2 represents a C1-6 alkyl group which may be substituted with a hydroxyl group, ONO 2 or a C1-4 alkoxy group, R 3 and R 4 each independently represent a hydrogen atom, or a C1-4 alkyl group which may be substituted with ONO 2 ;

R 5 represents a halogen atom, a hydroxyl group or a C1-4 alkoxy group;

R 8 represents a hydrogen atom or a halogen atom;

R 9 represents

wherein the arrow represents a bonding site,

W 1 represents a C1-6 alkyl group which may be substituted with 1 to 5 substituents selected from the group consisting of (1) a hydroxyl group, (2) an oxo group, (3) a halogen atom, (4) a C1-4 alkyl group, (5) a C1-4 alkoxy group, (6) ring 2, (7) —O-ring 2 and (8) —S-ring 2;

W 2 represents a C2-6 alkenyl group, a C1-3 alkoxy group or an alkyl ether group having 1 to 3 carbon atoms, wherein said carbon atoms may be substituted with 1 to 5 substituents selected from the group consisting of (1) a hydroxyl group, (2) an oxo group, (3) a halogen atom, (4) a C1-4 alkyl group, (5) a C1-4 alkoxy group, (6) ring 2, (7) —O-ring 2 and (8) —S-ring 2;

W 3 represents a C1-6 alkyl group, a C1-3 alkoxy group or an alkyl ether group having 1 to 3 carbon atoms, wherein said carbon atoms may be substituted with 1 to 5 substituents selected from the group consisting of (1) a hydroxyl group, (2) an oxo group, (3) a halogen atom, (4) a C1-4 alkyl group, (5) a C1-4 alkoxy group, (6) ring 2, (7) —O-ring 2 and (8) —S-ring 2; R 10 represents a hydrogen atom or a halogen atom;

ring 1 and ring 2 each independently represent a C3-10 carbocyclic ring or a 3- to 10-membered heterocyclic ring which may be substituted with 1 to 5 substituents selected from the group consisting of (1) a halogen atom, (2) CF 3 , (3) OCF 3 , (4) a C1-4 alkoxy group, (5) a C1-4 alkyl group, (6) a hydroxyl group and (7) a nitrile group;

m represents an integer of 1 to 6;

n represents an integer of 1 to 4;

p represents an integer of 1 to 4:

represents a single bond or a double bond,

represents α configuration,

represents β configuration, and

represents α configuration, β configuration or an arbitrary mixture thereof, a salt thereof, a solvate thereof, or a prodrug thereof.

2. The compound according to claim 1 , wherein R 8 is a halogen atom, and R 9 is

wherein all symbols represent the same meanings as those described in claim 1 ; or R 8 is a hydrogen atom, and R 9 is

wherein all symbols represent the same meanings as those described in claim 1 , or a salt thereof, a solvate thereof, or a prodrug thereof.

3. The compound according to claim 2 , which is represented by the formula (I-1):

wherein all symbols represent the same meanings as those described in claim 2 , or a salt thereof, a solvate thereof, or a prodrug thereof.

4. The compound according to claim 1 , which is a compound selected from the group consisting of

(1) 4-{(3S,5aR,6R,7R,8aS)-7-hydroxy-6-[(1E,3S)-3-hydroxy-4-phenoxy-1-buten-1-yl]octahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(2) 4-{(3S,5aR,6R,7R,8aS)-7-hydroxy-6-[(1E,3R)-3-hydroxy-5-phenyl-1-penten-1-yl]octahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(3) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3R)-5-(3-fluorophenyl)-3-hydroxy-1-penten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(4) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3S)-5-(3-fluorophenyl)-3-hydroxy-1-penten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(5) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3R)-5-(4-fluorophenyl)-3-hydroxy-1-penten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(6) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3S)-5-(4-fluorophenyl)-3-hydroxy-1-penten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(7) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3R)-5-(2-fluorophenyl)-3-hydroxy-1-penten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(8) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3S)-5-(2-fluorophenyl)-3-hydroxy-1-penten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(9) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3R)-5-(3-chlorophenyl)-3-hydroxy-1-penten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(10) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3S)-5-(3-chlorophenyl)-3-hydroxy-1-penten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(11) 4-[(3S,5aR,6R,7R,8aS)-7-hydroxy-6-{ (1E,3R)-3-hydroxy-5-[3-(trifluoromethyl)phenyl]-1-penten-1-yl}octahydro-2H-cyclopenta[b]oxepin-3-yl]butanoic acid,

(12) 4-[(3S,5aR,6R,7R,8aS)-7-hydroxy-6-{ (1E,3S)-3-hydroxy-5-[3-(trifluoromethyl)phenyl]-1-penten-1-yl}octahydro-2H-cyclopenta[b]oxepin-3-yl]butanoic acid,

(13) 4-[(3S,5aR,6R,7R,8aS)-7-hydroxy-6-{ (1E,3S)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]-1-buten-1-yl}octahydro-2H-cyclopenta[b]oxepin-3-yl]butanoic acid,

(14) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3S)-4-(2-fluorophenoxy)-3-hydroxy-1-buten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(15) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3S)-4-(3-fluorophenoxy)-3-hydroxy-1-buten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(16) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3S)-4-(4-fluorophenoxy)-3-hydroxy-1-buten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(17) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3S)-5-cyclohexyl-3-hydroxy-1-penten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(18) 4-{(3S,5aR,6R,7R,8aS)-7-hydroxy-6-[(3S)-3-hydroxy-4-phenoxybutyl]octahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(19) 4-{(3S,5aR,6R,7R,8aS)-7-hydroxy-6-[(3S)-3-hydroxy-5-phenylpentyl]octahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(20) 4-{(3S,5aR,6R,7R,8aS)-6-[(3S)-5-(3-fluorophenyl)-3-hydroxypentyl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(21) 4-{(3S,5aR,6R,7R,8aS)-6-[(3R)-5-(3-fluorophenyl)-3-hydroxypentyl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(22) 4-{(3S,5aR,6R,7R,8aS)-6-[(3S)-5-(4-fluorophenyl)-3-hydroxypentyl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(23) 4-{(3S,5aR,6R,7R,8aS)-6-[(3R)-5-(4-fluorophenyl)-3-hydroxypentyl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(24) 4-{(3S,5aR,6R,7R,8aS)-6-[(3S)-5-(2-fluorophenyl)-3-hydroxypentyl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(25) 4-{(3S,5aR,6R,7R,8aS)-6-[(3R)-5-(2-fluorophenyl)-3-hydroxypentyl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(26) 4-{(3S,5aR,6R,7R,8aS)-6-[(3S)-5-(3-chlorophenyl)-3-hydroxypentyl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(27) 4-{(3S,5aR,6R,7R,8aS)-6-[(3R)-5-(3-chlorophenyl)-3-hydroxypentyl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(28) 4-[(3S,5aR,6R,7R,8aS)-7-hydroxy-6-{(3S)-3-hydroxy-5-[3-(trifluoromethyl)phenyl]pentyl}octahydro-2H-cyclopenta[b]oxepin-3-yl]butanoic acid,

(29) 4-[(3S,5aR,6R,7R,8aS)-7-hydroxy-6-{(3R)-3-hydroxy-5-[3-(trifluoromethyl)phenyl]pentyl}octahydro-2H-cyclopenta[b]oxepin-3-yl]butanoic acid,

(30) 4-[(3S,5aR,6R,7R,8aS)-7-hydroxy-6-{(3R)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]butyl}octahydro-2H-cyclopenta[b]oxepin-3-yl]butanoic acid,

(31) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E)-3-fluoro-4-phenoxy-1-buten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(32) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E)-4-(3-chlorophenoxy)-1-buten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(33) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E)-4-(2-fluorophenoxy)-1-buten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(34) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E)-4-(3-fluorophenoxy)-1-buten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(35) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E)-4-(2,5-difluorophenoxy)-1-buten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(36) 4-{(3S,5aR,6R,7R,8aS)-7-hydroxy-6-[(1E)-4-hydroxy-6-phenyl-1-hexen-1-yl]octahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(37) 4-[(3S,5aR,6R,7R,8aS)-7-hydroxy-6-(4-phenoxybutyl)octahydro-2H-cyclopenta[b]oxepin-3-yl]butanoic acid,

(38) 4-{(3S,5aR,6R,7R,8aS)-7-hydroxy-6-[(1E)-3-hydroxy-1-decen-1-yl]octahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(39) 4-{(3S,5aR,6R,7R,8aS)-7-hydroxy-6-[(1E)-3-hydroxy-5-(5-methyl-2-furyl)-1-penten-1-yl]octahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(40) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E)-5-cyclopentyl-3-hydroxy-1-penten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(41) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E)-3-(1-benzofuran-2-yl)-3-hydroxy-1-propen-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(42) 4-{(3S,5aR,6R,7R,8aS)-7-hydroxy-6-[(1E)-3-hydroxy-5-(3-hydroxyphenyl)-1-penten-1-yl]octahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(43) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E)-3,3-difluoro-5-phenyl-1-penten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(44) 4-[(3S,5aR,6R,7R,8aS)-6-(3,3-difluoro-5-phenylpentyl)-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl]butanoic acid,

(45) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E)-5-cyclopentyl-3,3-difluoro-1-penten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(46) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E)-5-cyclohexyl-3,3-difluoro-1-penten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(47) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E)-3,3-difluoro-1-octen-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid, and isomers thereof,

or a salt thereof, a solvate thereof, or a prodrug thereof.

5. The compound according to claim 2 , which is a compound selected from the group consisting of

(1) 4-[(3S,5aR,6S,7R,8aS)-7-hydroxy-6-({[(2E)-3-phenyl-2-propen-1-yl]oxy}methyl)octahydro-2H-cyclopenta[b]oxepin-3-yl]butanoic acid,

(2) 4-{(3S,5aR,6R,7R,8aS)-7-hydroxy-6-[2-(2-phenylethoxyl)ethyl]octahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(3) 4-[(3S,5aR,6S,7R,8aS)-7-hydroxy-6-(3-hydroxy-5-phenyl-1-pentyn-1-yl)octahydro-2H-cyclopenta[b]oxepin-3-yl]butanoic acid,

(4) 4-{(3S,5aR,6R,7R,8aS)-6-[(2E)-1-fluoro-4-phenoxy-2-buten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(5) 4-{(3S,5aR,6R,7R,8aS)-7-hydroxy-6-[(1E)-3-hydroxy-8-methyl-1,7-nonadien-1-yl]octahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(6) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E)-4-(benzyloxy)-3-hydroxy-1-buten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(7) 4-{(3S,5aR,6R,7R,8aS)-7-hydroxy-6-[(1E)-3-hydroxy-1,7-octadien-1-yl]octahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(8) 4-{(3S,5aR,6R,7R,8aS)-7-hydroxy-6-[(1E,6Z)-3-hydroxy-1,6-nonadien-1-yl]octahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(9) 4-{(3S,5aR,6R,7R,8aS)-7-hydroxy-6-[(1E)-3-hydroxy-4,8-dimethyl-1,7-nonadien-1-yl]octahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(10) 4-{(3S,5aR,6R,8aS)-7,7-difluoro-6-[(1E)-3-hydroxy-1-octen-1-yl]octahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(11) 4-{(3S,5aR,6R,8aS)-7,7-difluoro-6-[(1E)-3-hydroxy-5-phenyl-1-penten-1-yl]octahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid,

(12) 4-{(3S,5aR,6R,7R,8aS)-6-[(1E)-3,3-difluoro-8-methyl-1,7-nonadien-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoic acid, and isomers thereof,

or a salt thereof, a solvate thereof, or a prodrug thereof.

6. A pharmaceutical composition comprising the compound, or a salt thereof, a solvate thereof, or a prodrug thereof described in claim 2 and a pharmaceutically acceptable diluent or excipient.

7. A method of treating an ocular disease, comprising administering an effective amount of the compound, or a salt thereof, a solvate thereof, or a prodrug thereof described in claim 2 to a mammal.

8. A pharmaceutical composition comprising the compound, or a salt thereof, a solvate thereof, or a prodrug thereof described in claim 1 and a pharmaceutically acceptable diluent or excipient.