Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1997-03-31
1998-09-15
Grumbling, Matthew V.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514249, 514250, 514258, 514259, 514261, 514262, 514263, 514264, 514265, 514267, 544284, 544279, 544256, 544280, 544278, 544264, 544265, 544266, 544267, 544268, 544269, 544270, 544271, 544272, 544255, 544262, 544249, 544236, 544250, 544251, 544254, 544257, 544258, 544259, 544260, 544261, C07D40302, C07D40314, A61K 31505, A61K 31495
Patent
active
058078541
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a new series of pyrimidone derivatives of general formula I having potent antifungal activity. The invention also relates to a process for their preparation, to pharmaceutical compositions containing them and to their use for the treatment of fungal diseases.
1. Description of the Prior Art
The compounds of the present invention are antifungal agents belonging to the azole class, whose mechanism of action is based on the inhibition of the biosynthesis of ergosterol, the main sterol present in fungi membranes. Other antifungal agents having this mechanism of action have been reported in the literature and some of them are already being used in therapy. Some of them are administered topically in the treatment of fungal infections in skin, vagina and nails. More recently discovered compounds are used orally in the treatment of systemic and organ mycoses, such as systemic candidiasis, aspergillosis, criptococcal meningitis, coccidioidomycosis, paracoccidioidomycosis, histoplasmosis, chromoblastomycosis, sporotrichosis, and blastomycosis.
However, given the worrying rise in fungal infections, specially among immunocompromised patients (such as AIDS patients or cancer patients undergoing chemotherapy) and the emergence of pathogens resistant to some of the commonly used antifungal agents, the present medical situation is by no means satisfactory and new orally active products which are more potent, have a broader spectrum of antifungal activity and which are effective against certain mycoses (such as aspergillosis) for which no effective treatment is currently available are urgently needed.
2. Description of the Invention
The present invention relates to new pyrimidone derivatives of general formula I ##STR2## as racemates, diastereomer mixtures or as pure enantiomers, wherein: Ar represents phenyl or phenyl substituted with one or more halogen and/or trifluoromethyl groups; R.sub.2 form a C.sub.2 -C.sub.4 polymethylene chain; haloalkyl, or cyclopropyl; one or more of the ring atoms are selected from the group consisting of N, O and S, which rings can be optionally fused to a benzene ring or to a 5- or 6-membered heterocyclic ring containing one or more heteroatoms selected from N, O and S, and wherein A can be unsubstituted or have 1, 2, 3 or 4 substituents W in any of the rings; C.sub.1 -C.sub.4 haloalkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 haloalkoxy, halogen, nitro, cyano, hydroxy, benzyloxy, hydroxymethyl, a group --NR.sub.4 R.sub.5, a group --CONR.sub.4 R.sub.5, a group --CH.sub.2 --OCO--R.sub.4, a group --CO--R.sub.4, a group --COO--R.sub.4, a group --SO.sub.z R.sub.6, a group --C(.dbd.NR.sub.4)NHR.sub.7, a group --C(.dbd.NR.sub.7)OR.sub.4, and additionally one of the groups W can also represent 1-pyrrolyl, 1-imidazolyl, 1H-1,2,4-triazol-1-yl, 5-tetrazolyl (optionally substituted with C.sub.1 -C.sub.4 alkyl), 1-pyrrolidinyl, 4-morpholinyl, 4-morpholinyl-N-oxide, a group --X--R.sub.8, or a group of formula (i)-(iv): ##STR3## wherein R represents hydrogen, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.6 cycloalkyl or aryl C.sub.1-4 alkyl, wherein aryl represents phenyl or phenyl substituted with one or more C.sub.1 -C.sub.4 alkyl, halogen, C.sub.1 -C.sub.4 haloalkyl, C.sub.1 -C.sub.4 alkoxy or C.sub.1 -C.sub.4 haloalkoxy groups; cycloalkyl, a group --COR.sub.4 or a group --COCF.sub.3 ; NHR.sub.4, --SO.sub.2 R.sub.4, --OR.sub.4, --OCCOR.sub.4 or --(C.sub.1-4 alkyl)--NH.sub.2 ; --C(.dbd.O)--; groups R.sub.9 ; C.sub.1 -C.sub.4 haloalkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 haloalkoxy, halogen, nitro, cyano, a group --NR.sub.4 R.sub.5, a group --CONR.sub.4 R.sub.5, a group --CH.sub.2 --OCO--R.sub.4, a group --CO--R.sub.4, a group --COO--R.sub.4, a group --SO.sub.z R.sub.6, a group --C(.dbd.NR.sub.4)NHR.sub.7, a group --C(.dbd.NR.sub.7)OR.sub.4, a group of formula (iv) or R.sub.9 represents a phenyl group (optionally substituted with a group C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 haloalkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 haloalkoxy, halo
Anguita Manuel
Bartroli Javier
Turmo Enric
Grumbling Matthew V.
J. Uriah & Cia. S.A.
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