Tricyclic derivatives as LTD4 antagonists

1. A compound of formula (I):

or pharmaceutically acceptable salts thereof, in any stereoisomeric form, or a mixture of any such compounds in any ratio, wherein:

from one to two of A 1 , A 2 , A 3 and A 4 are nitrogen atoms, the others being —CH— groups;

G 1 represents a group chosen from —CH 2 —O—, —CH 2 —CH 2 —, —CH═CH—, and —N(C1-C4 alkyl)-CH2;

G 2 represents a group chosen from —O—CH 2 —, —CH═CH—, and —CH 2 —CH 2 —;

n, m and p are independently 0, 1 or 2;

R 3 is hydrogen; R 2 and R 4 are chosen from halogen and C1-C4-alkyl;

Y represents an optionally substituted group chosen from alkyl, cycloalkyl, aryl, alkyl-cycloalkyl, cycloalkyl-alkyl, arylalkyl, alkylaryl, alkyl-cycloalkyl-alkyl, cycloalkyl-alkyl-cycloalkyl, alkyl-aryl-alkyl and aryl-alkyl-aryl;

Z represents a group chosen from a tetrazolyl group, a —COOR 5 group, a —CONR 5 R 5 group, a NHSO 2 R 5 group and a —CONHSO 2 R 5 group wherein R 5 is chosen from a hydrogen and an optionally substituted alkyl, aryl, cycloalkyl, heterocyclyl or heteroaryl.

2. A compound according to claim 1 wherein one of A 1 , A 2 , A 3 and A 4 is a nitrogen atom, the others being —CH— groups.

3. A compound according to claim 2 wherein A 1 is a nitrogen atom and A 2 , A 3 and A 4 are —CH— groups.

4. A compound according to claim 2 wherein A 4 is a nitrogen atom and A 1 , A 2 and A 3 are —CH— groups.

5. A compound according to claim 1 wherein G 1 is a —CH 2 O— group.

6. A compound according to claim 1 wherein G 2 is chosen from —OCH 2 — and —CH═CH—.

7. A compound according to claim 1 wherein p is 2 and each R 4 is a halogen atom.

8. A compound according to claim 7 wherein each R 4 is independently chosen from F and Cl.

9. A compound according to claim 1 wherein Y represents a group chosen from alkyl, alkyl-cycloalkyl-alkyl and alkylaryl said group being optionally substituted by one or more substituents chosen from halogens, hydroxy, alkoxy, amino, alkyl groups and haloalkyl.

10. A compound according to claim 9 wherein Y represents a group chosen —CH 2 CH 2 — and 2-cyclopropylpropyl.

11. A compound according to claim 1 chosen from:

3-{(7-[(6,7-difluoroquinolin-2-yl)methoxy]-5,11-dihydro[1]benzoxepino[3,4-b]pyrindin-5-yl)thio}propanoic acid,

{(7-[(6,7-difluoroquinolin-2-yl)methoxy]-5,11-dihydro[1]benzoxepino[3,4-b]pyrindin-5-yl)thio}acetic acid,

{(7-[(7-chloro,6-fluoroquinolin-2-yl)methoxy]-5,11-dihydro[1]benzoxepino[3,4-b]pyrindin-5-yl)thio}acetic acid,

3-{(7-[(7-chloro,6-fluoroquinolin-2-yl)methoxy]-5,11-dihydro[1]benzoxepino[3,4-b]pyrindin-5-yl)thio}propanoic acid,

[{(7-[(6,7-difluoroquinolin-2-yl)methoxy]-5,11-dihydro[1]benzoxepino[3,4-b]pyrindin-5-yl)thio}methyl]benzoic acid,

[{(7-[(7-chloro,6-fluoroquinolin-2-yl)methoxy]-5,11-dihydro[1]benzoxepino[3,4-b]pyrindin-5-yl)thio}methyl]benzoic acid,

1-{[(7-[(6,7-difluoroquinolin-2-yl)methoxy]-5,11-dihydro[1]benzoxepino[3,4-b]pyrindin-5-yl)thio]methyl}cyclopropyl acetic acid,

3-{(7-[(6,7-difluoroquinolin-2-yl)methoxy]-5,11-dihydro[1]benzoxepino[3,4-b]pyrindin-5-yl)thio}-2,2-dimethylpropanoic acid,

3-{(7-[(6,7-difluoroquinolin-2-yl)methoxy]-5,11-dihydro[1]benzoxepino[3,4-b]pyrindin-5-yl)thio}-3-methylbutanoic acid,

3-{(7-[(E)-2-(6,7-difluoroquinolin-2-yl)vinyl]-5,11-dihydro[1]benzoxepino[3,4-b]pyrindin-5-yl)thio}propanoic acid,

1-{[(7-[(E)-2-(6,7-difluoroquinolin-2-yl)vinyl]-5,11-dihydro[1]benzoxepino[3,4-b]pyrindin-5-yl)thio]methyl}cyclopropyl acetic acid,

{(7-[(E)-2-(6,7-difluoroquinolin-2-yl)vinyl]-5,11-dihydro[1]benzoxepino[3,4-b]pyrindin-5-yl)thio}acetic acid,

7-[(E)-2-(6,7-difluoroquinolin-2-yl)vinyl]-5-{[2-(1H-tetrazol-5-yl)ethyl]thio}-5,11-dihydro[1]benzoxepino[3,4-b]pyridine,

1,1,1-trifluoro-N-[2-({7-[(E)-2-(6,7-difluoroquinolin-2-yl)vinyl]-5,11-dihydro[1]benzoxepino[3,4-b]pyrindin-5-yl)thio)ethyl]methanesulfonamide,

1,1,1-trifluoro-N-[2-({7-[(6,7-difluoroquinolin-2-yl)methoxy]-5,11-dihydro[1]benzoxepino[3,4-b]pyrindin-5-yl)thio)ethyl]methanesulfonamide,

3-{(9-[(E)-2-(6,7-difluoroquinolin-2-yl)vinyl]-5,11-dihydro[1]benzoxepino[4,3-b]pyrindin-11-yl)thio}propanoic acid,

3-{(9-[(6,7-difluoroquinolin-2-yl)methoxy]-5,11-dihydro[1]benzoxepino[4,3-b]pyrindin-11-yl)thio}propanoic acid,

1-{[(9-[(6,7-difluoroquinolin-2-yl)methoxy]-5,11-dihydro[1]benzoxepino[4,3-b]pyrindin-11-yl)thio]methyl}cyclopropyl acetic acid,

7-[(6,7-difluoroquinolin-2-yl)methoxy]-5-{[2-(1H-tetrazol-5-yl)methyl]thio}-5,11-dihydro[1]benzoxepino[3,4-b]pyridine,

7-[(6,7-difluoroquinolin-2-yl)methoxy]-5-{[2-(1H-tetrazol-5-yl)ethyl]thio}-5,11-dihydro[1]benzoxepino[3,4-b]pyridine,

3-[7-(6,7-Difluoro-quinolin-2-ylmethoxy)-11-methyl-10,11-dihydro-5H-benzo[e]pyrido[2,3-b]azepin-5-ylsulfanyl]-propionic acid,

3-[7-(7-Chloro-6-fluoro-quinolin-2-ylmethoxy)-11-methyl-10,11-dihydro-5H-benzo[e]pyrido[2,3-b]azepin-5-ylsulfanyl]-propionic acid,

3-[9-chloro-7-(6,7-difluoro-quinolin-2-ylmethoxy)-5,11-dihydro[1]benzoxepino[3,4-b]pyridin-5-yl)thio]propanoic acid,

ethyl 3-[7-(6,7-difluoro-quinolin-2-ylmethoxy)-5,11-dihydro[1]benzoxepino[3,4-b]pyridin-5-yl)thio]propanoate,

3-[7-(6,7-difluoro-quinolin-2-ylmethoxy)-5,11-dihydro[1]benzoxepino[3,4-b]pyridin-5-yl)thio]propanamide,

3-[7-(6,7-difluoro-quinolin-2-ylmethoxy)-9-fluoro-5,11-dihydro[1]benzoxepino[3,4-b]pyridin-5-yl)thio]propanoic acid,

3-[7-(6,7-difluoro-quinolin-2-ylmethoxy)-9-methyl-5,11-dihydro[1]benzoxepino[3,4-b]pyridin-5-yl)thio]propanoic acid,

3-{(7-[(E)-2-(6,7-difluoroquinolin-2-yl)vinyl]-5,11-dihydro[1]benzoxepino[3,4-b]pyrindin-5-yl)thio}propanamide, and

ethyl 3-{(7-[(E)-2-(6,7-difluoroquinolin-2-yl)vinyl]-5,11-dihydro[1]benzoxepino[3,4-b]pyrindin-5-yl)thio}propanoate.

12. A process for the preparation of a compound of formula (I):

wherein A 1 , A 2 , A 3 , A 4 , G 1 , G 2 , R 2 , R 3 , R 4 Y and Z are as defined in claim 1 , which comprises reacting an alcohol of formula (III):

with a mercaptane of formula HS—Y—Z.

13. A compound of formula (III):

wherein A 1 , A 2 , A 3 , A 4 , G 1 , G 2 , R 2 , R 3 , R 4 Y and Z are as defined in claim 1 .

14. A pharmaceutical composition comprising a compound according to claim 1 and at least one pharmaceutically acceptable diluent or carrier.