Claims
- 1-14. (canceled)
- 15. A compound of formula (I)
- 16. The compound of formula (I) as defined in claim 15, wherein B is —CH2—CH═CH— or —CH2-(cyclopropyl)-, said groups being non-substituted or substituted by one or more halogens or (C1-C4)-alkyl; Ar1 is phenyl, or a physiologically acceptable salt thereof.
- 17. The compound of formula (I) as defined in claim 15 having the formula (IA):
- 18. The compound of formula (I) as defined in claim 15 having the formula (IB):
- 19. The compound of formula (I) as defined in claim 15, wherein R2 and R3 are fluorine or chlorine, X is CH or N and Ar3 is phenyl, non-substituted or substituted by R8 as defined in claim 1, or a physiologically acceptable addition salt thereof.
- 20. The compound of formula (I) as defined in claim 15, wherein R1 is hydrogen or, methyl or ethyl, non-substituted or substituted by F, OH, NH2, (C1-C6)-alkyloxy, (C1-C6)-alkylamino, pyrrolidino, 2-oxopyrrolidino or di-(C1-C6)-alkylamino group, or a physiologically acceptable addition salt thereof.
- 21. The compound of formula (I) as defined in claim 15, wherein Ar3 is phenyl, non-substituted or substituted by R8, representing —Cl, —F, CN, —CF3, —OCF3, —OH, —NH2, (C1-C6)-alkyloxy, (C1-C6)-alkylamino, or di-(C1-C6)-alkylamino or a heterocycle chosen from:
- 22. The compound of formula (I) as defined in claim 15 selected from the group consisting of:
alpha-[[[2-[3-(4-chlorophenyl)-2(E)-propenyl]-1,2,3,4-tetrahydro-6-isoquinolinyl]oxy]methyl]-alpha-(2,4-dichlorophenyl)-1H-imidazol-1-ethanol; alpha-(2,4-dichlorophenyl)-alpha-[[4-[[[methyl(3-phenyl-2(E)-propenyl)]amino]methyl]phenoxy]methyl]-1H-imidazol-1-ethanol; alpha-(2,4-difluorophenyl)-alpha-[[4-[[methyl(3-phenyl-2(E)-propenyl)amino]methyl]phenoxy]methyl]-1 H-1,2,4-triazol-1-ethanol; alpha-[[[2-[3-(4-chlorophenyl)-2(E)-propenyl]-1,2,3,4-tetrahydro-6-isoquinolinyl]oxy]methyl]-alpha-(2,4-difluorophenyl)-1H-1,2,4-triazol-1-ethanol; and alpha-(2,4-difluorophenyl)-alpha-[[4-[[(2-aminoethyl)[3-(4-chlorophenyl)-2(E)-propenyl]amino]methyl]phenoxy]methyl]-1H-imidazol-1-ethanol.
- 23. A process for the preparation of a compound of formula (IA) as defined in claim 17 comprising:
reacting a compound of formula (II) 25wherein X and Ar1 are as defined in claim 17, with a compound of formula (IIIa): 26wherein R1, B, R5 and Ar3 are as defined in claim 17, in a basic medium, to obtain the corresponding compound of formula (IA) as defined in claim 17.
- 24. A process for the preparation of a compound of formula (IB) as defined in claim 18 comprising:
reacting a compound of formula (II) 27wherein X and Ar1 are as defined in claim 18, with a compound of formula (IIIa) or (IIIb) 28wherein B, R5 and Ar3 are as defined in claim 18, in a basic medium, to obtain the corresponding compound of formula (IB) as defined in claim 18.
- 25. A process for the preparation of a compound of formula (I) as defined in claim 15 comprising:
reacting a compound of formula (II): 29with a compound of formula (III′), HO—C6H4—CHO, in the presence of a base, the phenyl being non-substituted or substituted by R5 to obtain a compound of formula (IIA): 30reacting compound of formula (IIA) with an amine of formula, R1—NH2, R1 being as defined in claim 15, the reactive functions of which are optionally protected, followed by a reduction reaction in the presence of a reducing agent such as NaBH3CN or BH3.pyridine, to obtain a compound of formula (IIB) 31reacting compound of formula (IIB)
either with a derivative of formulaOHC—CH═CH—C6H4—R8 or OHC—(Cyclopropyl)—C6H4—R8 followed by a reduction reaction in the presence of a reducing agent such as NaBH3CN or BH3.pyridine or with a compound of formula:AcO—CH2—CH═CH—C6H4—R8in the presence of a palladium derivative to obtain the following compounds of formula (IAA) or (IAB): 32wherein X, Ar1, R1, and R8are as defined in claim 15.
- 26. A method for the treatment of a fungal disease comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of the formula (I):
- 27. The method as defined in claim 26 wherein said fungal disease is caused by Candida albicans, Candida glabrata, krusei, tropicalis, pseudotropicalis, parapsilosis, Aspergillus, Aspergillus flavus, Aspergillus niger, Cryptococcus neoformans, Microsporum canis, Trichophyton rubrun or Trichophyton mentagrophyte.
- 28. The method as defined in claim 26 wherein said fungal disease is selected from the group consisting of candidoses, cryptococcoses, bronchopulmonary and pulmonary aspergilloses and invasive aspergilloses in immunodeficient individuals.
- 29. The method as defined in claim 28 wherein said candidoses is selected from the group consisting of digestive, urinary, vaginal and cutaneous candidoses.
- 30. The method as defined in claim 28 wherein said cryptococcoses is selected from the group consisting of neuromeningeal, pulmonary and cutaneous cryptococcoses.
- 31. The method as defined in claim 26 wherein said compound is selected from the group consisting of:
alpha-[[[2-[3-(4-chlorophenyl)-2(E)-propenyl]-1,2,3,4-tetrahydro-6-isoquinolinyl]oxy]methyl]-alpha-(2,4-dichlorophenyl)-1H-imidazol-1-ethanol; alpha-(2,4-dichlorophenyl)-alpha-[[4-[[[methyl(3-phenyl-2(E)-propenyl)]amino]methyl]phenoxy]methyl]-1H-imidazol-1-ethanol; alpha-(2,4-difluorophenyl)-alpha-[[4-[[methyl(3-phenyl-2(E)-propenyl)amino]methyl]phenoxy]methyl]-1H-1,2,4-triazol-1-ethanol; alpha-[[[2-[3-(4-chlorophenyl)-2(E)-propenyl]-1,2,3,4-tetrahydro-6-isoquinolinyl]oxy]methyl]-alpha-(2,4-difluorophenyl)-1H-1,2,4-triazol-1-ethanol; and alpha-(2,4-difluorophenyl)-alpha-[[4-[[(2-aminoethyl)[3-(4-chlorophenyl)-2(E)-propenyl]amino]methyl]phenoxy]methyl]-1H-imidazol-1-ethanol.
- 32. A pharmaceutical composition comprising at least one compound of formula (I) as defined in claim 1 or an enantiomer, a stereoisomer, a tautomer or a mixture thereof, or a physiologically acceptable salt, a solvate or a derivative thereof, or a prodrug thereof in combination with one or more pharmaceutically acceptable carriers.
- 33. The composition as defined in claim 32 wherein said compound is selected from the group consisting of:
alpha-[[[2-[3-(4-chlorophenyl)-2(E)-propenyl]-1,2,3,4-tetrahydro-6-isoquinolinyl]oxy]methyl]-alpha-(2,4-dichlorophenyl)-1H-imidazol-1-ethanol; alpha-(2,4-dichlorophenyl)-alpha-[[4-[[[methyl(3-phenyl-2(E)-propenyl)]amino]methyl]phenoxy]methyl]-1H-imidazol-1-ethanol; alpha-(2,4-difluorophenyl)-alpha-[[4-[[methyl(3-phenyl-2(E)-propenyl)amino]methyl]phenoxy]methyl]-1H-1,2,4-triazol-1-ethanol; alpha-[[[2-[3-(4-chlorophenyl)-2(E)-propenyl]-1,2,3,4-tetrahydro-6-isoquinolinyl]oxy]methyl]-alpha-(2,4-difluorophenyl)-1H-1,2,4-triazol-1-ethanol; and alpha-(2,4-difluorophenyl)-alpha-[[4-[[(2-aminoethyl)[3-(4-chlorophenyl)-2(E)-propenyl]amino]methyl]phenoxy]methyl]-1H-imidazol-1-ethanol.
- 34. A compound of formula:
Priority Claims (1)
Number |
Date |
Country |
Kind |
01/05959 |
May 2001 |
FR |
|
Parent Case Info
[0001] This application is a National Stage of International application No. PCT/FR02/01,519, filed May 02, 2002; which claims the benefit of priority of French Patent Application No. 01/05,959, filed May 04, 2001.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
PCT/FR02/01519 |
5/2/2002 |
WO |
|