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1. WO2006100119 - DERIVATIVES OF IMIDAZO (1,2-A) PYRIDINE USEFUL AS MEDICAMENTS FOR TREATING GASTROINTESTINAL DISEASES

Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

[ EN ]

Claims

1. A compound of formula (T)



(I)

wherein X is NH, NR7 or O;
Rl is H, C1-4 alkyl, CH2CN, CH2NH2, C3-6cycloalkyl, C3-6cycloalkylC1-4alkyl, Q- 4alkoxy, C2-6alkenyl, C2-6alkenyloxyC1-4alkyl, C2-6alkynyl, hydroxyC1-4alkyl, C1- 4alkoxyC1-4alkyl, hydxoxyC1-4alkoxyC1-4alkyl, fluoroC1-4alkyl, C^ealkynyloxyQ. 4alkyl, C1-4alkylsulphonylC1-4alkyl or NR8R9, where each of R8 and R9, which may be the same or different, are H or C1-4alkyl or, together with the nitrogen to which they are attached, form a 5- or 6- membered heterocyclic group containing 0 to 3 further heteroatoms selected from N, O and S;
R2 is C1-4alkyl, NH2, C3-6cycloalkyl, C3-6cycloalkylC1-4alkyl, C1-4alkoxy, C2-6alkenyl, hydroxyC1-4alkyl, C1-4alkoxyC1-4alkyl, hydroxyC1-4alkoxyC1-4alkyl, cyanoC1-4alkyl, haloC1-4alkyl or aminocarboxyC1-4alkyl;
R3 is H or C1-4alkyl;
R4 and R5, which may be the same or different, are H, C1-4alkyl, OH, halogen, C1- 4alkoxy, NR14R15 where each of R14 and R15, which may be the same or different, are H or C1-4alkyl, NHCONRl ORl 1 or OCONRlORl 1 where each of RlO and Rl 1, which may be the same or different, are H or C^ancyl or, together with the nitrogen to which they are attached, form a 5- or 6- membered heterocyclic group containing 0 to 3 further heteroatoms selected from N, O and S;
or R3 and R4 together with the interconnecting atoms form a 5- or 6- membered carbocyclic group or a heterocyclic group containing 1 heteroatom selected from N, O and S, which carbocyclic or heterocyclic group is optionally substituted with one group selected from the group consisting of C1-4alkyl, OH, OC1-4alkyl, halogen and NRl 6Rl 7 where each of Rl 6 and Rl 7, which may be the same or different, are H or C1-4alkyl;
R6 is H, C1-4alkyl, halogen, OH, NHCO2C1 -4alkyl, NR18R19 where each of R18 and Rl 9, which may be the same or different, are H or C1-4alkyl;

R7 is C1-4alkyl;
or R4 and R7 together with the interconnecting atoms form a 5- to 7- membered heterocyclic group containing 0 or 1 former heteroatoms selected from N, O and S, which heterocyclic group is optionally substituted with one group selected from the group consisting of C1-4alkyl, OH, OC1-4alkyl, halogen and NR20R21 where each of R20 and R21, which may he the same or different, are H or C1-4alkyl;
and
Ar is aryl, or a 5- or 6- membered monocyclic, or a 7- to 12- membered bicyclic, heteroaryl group (containing 1 to 4 heteroatoms selected from N, O and S) which aryl or heteroaryl group is independently optionally substituted with 1, 2, 3 or 4 groups selected from the group consisting of halogen, hydroxy, oxo, cyano, C1-4alkyl, C1. 4alkoxy, hydroxyC1-4alkyl, hydroxyC1-4alkoxy, haloC1-4alkyl, haloC1-4alkoxy, arylCμ 4alkoxy, C1-4alkylthio, C1-4alkoxyC1-4alkyl, C3-6cycloalkylC1-4alkoxy, C1-4alkanoyl, C1-4alkylsulfonyl, C1-4alkylsulfonyloxy, C1-4alkylsulfonylC1-4alkyl, arylsulfonyl, arylsulfonyloxy, aryloxysulfonyl, arylsulfonylC^alkyl, Q^alkylsulfonamidod-4alkyl, C1-4alkylamidoC1-4alkyl, arylsulfonamido, arylcarboxamido,
arylsulfonamidoC1-4alkyl, arylcarboxamidoC1-4alkyl, arylaminosulfonyl,
arylaminocarbonyl, aroyl, aroylC1-4alkyl, arylC1-4alkanoyl, NR12R13 and
CONR12R13, where each of R12 and R13, which may be the same or different, are H, C1-4 alkyl, hydroxyC1-4alkyl, alkoxyC1-4alkyl, C3-6cycloalkyl, C3-6CyClOaIkVlC1- 4alkyl or, together with the nitrogen to which they are attached, form a 5- or 6-membered heterocyclic group containing a further heteroatom selected from N, O or S; -or a pharmaceutically acceptable salt thereof;
with the proviso that the compound is not:
l-(8-{[(4-fluoroρhenyl)methyl]oxy}-2-methylimidazo[l,2-α]pyridin-6-yl)-2(lH)-pyridinone.

2. A compound according to claim 1 wherein the Ar group is a 5- or 6-membered monocyclic or 7- to 12-membered bicyclic heteroaryl group and is attached to the imidazopyridine core through a carbon atom of the Ar ring.

3. A compound according to claim 1 wherein the Ar group is a 5- or 6-membered monocyclic or 7- to 12-membered bicyclic heteroaryl group and is attached to the imidazopyridine core through a nitrogen atom of the Ar ring.

4. A compound according to claim 1 wherein Ar is phenyl, napthyl, pyridinyl, pyrimidinyl, thiazolyl, pyridazinyl, pyrazinyl, oxazolyl, triazolyl, tetrazolyl, imidazolyl, pyrazolyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazinyl, isothiazolyl, isoxazolyl, quinoxalinyl, quinazolinyl, pyridopyrazinyl, benzoxazolyl, benzimidazolyl, naphthyridinyl, quinolinyl, benzofuranyl, benzothienyl, indolyl, benzothiazolyl, oxazolyl[4,5-b]pyridiyl, pyridopyrimidinyl or isoquinolinyl.

5. A compound according to claim 4 wherein Ar is selected from phenyl, pyridinyl, pyrimidinyl, pyridazmyl, pyrazinyl, oxazolyl, furanyl, oxadiazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, imidazolyl, thienyl, methylpyridinyl, methyloxypyridinyl, carboxamidopyridinyl, aminopyridinyl, pyridinonyl,
methylpyridinonyl cyanopyridinonyl, chloropyridinonyl, pyrazolonyl,
methylpyrazolyl, hydroxymethylpyrazolyl, pyrimidinonyl, pyrimidinedionyl, dimethylpyriniidinedionyl and pyridazinonyl.

6. A compound according to any one of claims 1 to 5 wherein the optional substituents for Ar are C1-4alkyl, C1-4alkoxy, carboxamide, oxo, cyano, amino or hydroxyC1-4alkyl.

7. A compound according to any one of claims 1 to 6 wherein X is NH or O.

8. A compound according to claim 7 wherein X is NH.

9. A compound according to claim 7 wherein X is O.

10. A compound according to any one of claims 1 to 9 wherein Rl is C1-4 alkyl, CH2CN, C1-4alkoxy, hydroxyC1-4alkyl or C1-4alkoxyC1-4alkyl.

11. A compound according to any one of claims 1 to 10 wherein R2 is Q^alkyl.

12. A compound according to claim 11 wherein Rl and R2 are both methyl.

13. A compound according to any one of claims 1 to 12 wherein R3 is H.

14. A compound according to any one of claims 1 to 13 wherein R4 is H, Ci-4alkyl or halogen.

15. A compound according to any one of claims 1 to 14 wherein R5 is H, C1-4alkyl or halogen.

16. A compound according to claim 15 wherein R4 and R5 are not both H.

17. A compound according to any one of claims 1 to 16 wherein R6 is H, C1-4alkyl or halogen.

18. A compound according to claim 17 wherein R4 and R5 are both methyl and R6 is H.

19. A compound according to claim 17 wherein R4 is methyl, R5 is ethyl and R6 is H.

20. A compound according to any one of claims 1 to 7 wherein X is NH or O; R3 is H; Rl, R2, R4 and R5 are all methyl; and R6 is H.

21. A compound according to claim 20 wherein X is NH or O; R3 is H; Rl, R2, R4 and R5 are all methyl; R6 is H; and Ar is pyridinonyl, pyrazolyl or triazolyl.

22. A compound according to claim 17 wherein R6 is fluoro.

23. A compound according to claim 16 wherein R4 and R5 is fluoro, chloro or bromo and the other is H.

24. A compound according to claim 16 wherein R4 and R5 are both fluoro.

25. A compound according to any one of claims 1 to 7 wherein X is NH or O; R3 is H; Rl and R2 are both methyl; R6 is H or fluoro; one of R4 and R5 is chloro and the other is H.

26. A compound according to claim 25 wherein X is NH or O; R3 is H; Rl and R2 are both methyl; R6 is H or fluoro; one of R4 and R5 is chloro and the other is H; and Ar is pyridinonyl, pyrazolyl or triazolyl.

27. A compound according to any one of claims 1 to 7 wherein X is NH or O; R3 is H; Rl and R2 are both methyl; R6 is fluoro; and R4 and R5 are both methyl.

28. A compound according to claim 27 wherein X is NH or O; R3 is H; Rl and R2 are both methyl; R6 is fluoro; R4 and R5 are both methyl; and Ar is pyridinonyl, pyrazolyl or triazolyl.

29. A compound according to claim 1 which is the compound of any one of examples 1 to 135.

30. A compound according to any one of claims 1 to 29, or a pharmaceutically acceptable salt thereof, for use in human or veterinary medicine.

31. Use of a compound of formula (I) as defined in any one of claims 1 to 29, or a pharmaceutically acceptable salt thereof, for the treatment of diseases or disorders where an acid pump antagonist (APA) is required.

32. Use according to claim 31 wherein the disease or disorder where an acid pump antagonist (APA) is required is a gastrointestinal disease or disorder associated with an imbalance in gastric acid.

33. Use according to claim 32 wherein the gastrointestinal disease or disorder is selected from gastric or duodenal ulcer, gastritis, gastro-oesophageal reflux disease (GERD), and Zoller-Ellison Syndrome or diseases and disorders where gastric antisecretory effect is desirable for example in patients with gastrinomas and acute upper gastrointestinal bleeding.

34. Use of a compound of formula (I) as defined in any one of claims 1 to 29, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment or prophylaxis of diseases or disorders where an antagonist of a human acid pump is required.

35. Use according to claim 34 wherein the disease or disorder where an acid pump antagonist (APA) is required is a gastrointestinal disease or disorder associated with an imbalance in gastric acid.

36. Use according to claim 35 wherein the gastrointestinal disease or disorder is selected from gastric or duodenal ulcer, gastritis, gastro-oesophageal reflux disease (GERD), and Zoller-Ellison Syndrome or diseases and disorders where gastric antisecretory effect is desirable for example in patients with gastrinomas and acute upper gastrointestinal bleeding.

37. A method of treating or preventing diseases or disorders where an acid pump antagonist (APA) is required, which comprises administering to a subject in need thereof an effective amount of a compound of formula (I) as defined in any one of claims 1 to 29, or a pharmaceutically acceptable salt thereof.

38. A method according to claim 37 wherein the disease or disorder where an acid pump antagonist (APA) is required is a gastrointestinal disease or disorder associated with an imbalance in gastric acid.

39. A method according to claim 38 wherein the gastrointestinal disease or disorder is selected from gastric or duodenal ulcer, gastritis, gastro-oesophageal reflux disease (GERD), and Zoller-Ellison Syndrome or diseases and disorders where gastric antisecretory effect is desirable for example in patients with gastrinomas and acute upper gastrointestinal bleeding.
40. A pharmaceutical composition comprising a compound of formula (I) as defined in any one of claims 1 to 29, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.