Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1997-09-30
1999-09-14
Higel, Floyd D.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
514398, 5483235, C07D23332, C07D23370, A61K 31415
Patent
active
059525100
DESCRIPTION:
BRIEF SUMMARY
The present invention concerns 1,3dihydro1-(phenylalkenyl)-2H-imidazol-2-one derivatives having PDE IV and cytokine inhibiting activity and their preparation; it further relates to compositions comprising them, as well as their use as a medicine.
WO 94/12461, WO 94/20455 and WO 94/14800 generically disclose a number of 1-(phenylalkenyl)-2-hydroxy-imidazole derivatives as selective inhibitors of phosphodiesterase type IV (PDE IV).
Unexpectedly, particular 1,3-dihydro-1-(phenylalkenyl)-2H-imidazol-2-one derivatives show improved PDE IV inhibiting activity over the art compounds. In addition, the compounds of the present invention were found to display cytokine inhibiting activity. In view of these pharmacological properties, the present compounds have therapeutical utility in the treatment of disease states related to an abnormal enzymatic or catalytic activity of PDE IV, and/or disease states related to a physiologically detrimental excess of cytokines, in particular allergic, atopic and inflammatory diseases.
The present invention concerns 1,3-dihydro-1-(phenylalkenyl)-2H-imidazol-2-one derivatives having the formula ##STR2## the N-oxide forms, the pharmaceutically acceptable acid or base addition salts and the stereochemically isomeric forms thereof, wherein: difluoromethyl; trifluoromethyl; C.sub.3-6 cycloalkyl; a saturated 5-, 6- or 7-membered heterocycle containing one or two heteroatoms selected from C.sub.1-10 alkyl substituted with one or two substituents each independently selected from aryl, pyridinyl, thienyl, furanyl, C.sub.3-7 cycloalkyl and a saturated 5-, 6- or 7-membered heterocycle containing one or two heteroatoms selected from oxygen, sulfur or nitrogen; aryl or C.sub.1-6 alkyl substituted with aryl, cyano, carboxyl or C.sub.1-6 alkyloxycarbonyl; aryl or C.sub.1-6 alkyl substituted with aryl, cyano, carboxyl or C.sub.1-6 alkyloxycarbonyl; alkyl; alkyloxycarbonyl; C.sub.1-6 alkyl substituted with one or two substituents selected from the group consisting of hydroxy, C.sub.1-4 alkyloxy, C.sub.1-4 alkyloxycarbonyl, mono- and di(C.sub.1-4 alkyl)amino, aryl and Het; C.sub.3-6 alkenyl; C.sub.3-6 alkenyl substituted with aryl; piperidinyl; piperidinyl substituted with C.sub.1-4 alkyl or arylC.sub.1-4 alkyl; C.sub.1-6 alkylsulfonyl or arylsulfonyl; selected from halo, hydroxy, C.sub.1-4 alkyl, C.sub.1-4 alkyloxy, C.sub.3-6 cycloalkyl, trifluoromethyl, amino, nitro, carboxyl, C.sub.1-4 alkyloxycarbonyl and C.sub.1-4 alkylcarbonylamino; alkyl or arylC.sub.1-4 alkyl; piperazinyl; piperazinyl substituted with C.sub.1-4 alkyl or arylC.sub.1-4 alkyl; pyridinyl; pyridinyl substituted with C.sub.1-4 alkyl; furanyl; furanyl substituted with C.sub.1-4 alkyl; thienyl or thienyl substituted with C.sub.1-4 alkyl or C.sub.1-4 alkylcarbonylamino.
Some of the compounds of formula (I) may also exist in their tautomeric forms. Such forms although not explicitly indicated in the above formula are intended to be included within the scope of the present invention.
In R.sup.1 and R.sup.2, the saturated 5-, 6- or 7-membered heterocycles containing one or two heteroatoms selected from oxygen, sulfur or nitrogen may suitably be selected from heterocycles such as, for example, tetrahydrofuranyl, dioxolanyl, pyrrolidinyl, morpholinyl, piperidinyl, piperazinyl and tetrahydropyranyl. Said heterocyclic radicals are attached to the C.sub.1-10 alkyl radical by any carbon atom or, where appropriate, by a nitrogen atom.
As used in the foregoing definitions the term halo is generic to fluoro, chloro, bromo and iodo; the term C.sub.1-4 alkyl is meant to include straight chained or branched saturated hydrocarbons having from 1 to 4 carbon atoms such as, for example, methyl, ethyl, 1-methylethyl, 1,1-dimethylethyl, propyl, 2-methylpropyl and butyl; the term C.sub.1-6 alkyl is meant to include C.sub.1-4 alkyl and the higher homologues thereof having 5 to 6 carbon atoms such as, for example, 2-methylbutyl, pentyl and hexyl; the term C.sub.3-6 alkenyl defines straight and branch chained hydrocarbon radicals containing one double bond an
REFERENCES:
patent: 3551417 (1970-12-01), Symon et al.
patent: 5494927 (1996-02-01), Cetenko et al.
patent: 5677464 (1997-10-01), Itoh et al.
Andrés-Gil José Ignacio
Diels Gaston Stanislas Marcella
Fernandez-Gadea Francisco Javier
Freyne Eddy Jean Edgard
Appollina Mary A.
Higel Floyd D.
Janssen Pharmaceutica N.V.
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