Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1998-10-06
2000-12-05
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514219, 540543, 540554, 540555, 540576, 540578, A61K 3155, C07D22314, C07D25500, C07D24300, C07D49822
Patent
active
061567477
DESCRIPTION:
BRIEF SUMMARY
This invention concerns substituted tetracyclic isoxazolidine derivatives having antipsychotic, cardiovascular and gastrokinetic activity and their preparations; it further relates to compositions comprising them, as well as their use as a medicine.
U.S. Pat. No. 4,039,558 discloses pyrrolidinodibenzo-azepine, -oxazepine, -thiazepine and -diazepine derivatives having antihistamine, sedative and antidepressant properties. EP-A-0,421,823 describes dibenzopyrazino- or benzo-pyrido-pyrazino-azepine derivatives having anti-allergic and anti-asthmatic activities. The present compounds differ therefrom by the presence of an isoxazolidine ring, and by their pharmacological properties.
This invention concerns compounds of formula (I) ##STR3## the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein: C.sub.1-6 alkylcarbonyl; trihalomethylcarbonyl; C.sub.1-6 alkyl substituted with hydroxy, C.sub.1-6 alkyloxy, carboxyl, C.sub.1-6 alkylcarbonyloxy, C.sub.1-6 alkyloxycarbonyl or aryl; or R.sup.1 and R.sup.2 taken together with the nitrogen atom to which they are attached may form a morpholinyl ring or a radical of formula: ##STR4## wherein: R.sup.9, R.sup.10, R.sup.11 and R.sup.12 each independently are hydrogen, halo, trihalomethyl, or C.sub.1-6 alkyl; or C.sub.1-6 alkyl; or alkanediyl; trihalomethylcarbonyl; C.sub.1-6 alkyloxycarbonyl; aryl; di(aryl)methyl; C.sub.1-6 alkyl substituted with hydroxy, C.sub.1-6 alkyloxy, carboxyl, C.sub.1-6 alkylcarbonyloxy, C.sub.1-6 alkyloxycarbonyl or aryl; trihalomethoxy, carboxyl, nitro, amino, mono- or di(C.sub.1-6 alkyl)amino, C.sub.1-6 alkylcarbonylamino, aminosulfonyl, mono- or di(C.sub.1-6 alkyl)aminosulfonyl, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy, C.sub.1-6 alkylcarbonyl or C.sub.1-6 alkyloxycarbonyl; trihalomethoxy, carboxyl, nitro, amino, mono- or di(C.sub.1-6 alkyl)amino, C.sub.1-6 alkylcarbonylamino, aminosulfonyl, mono- or di(C.sub.1-6 alkyl)aminosulfonyl, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy, C.sub.1-6 alkylcarbonyl or C.sub.1-6 alkyloxycarbonyl; wherein alkyl, trihalomethyl, C.sub.1-6 alkyloxy or R.sup.6 and R.sup.7 taken together may form methylene; mono- or di(cyano)methylene; a bivalent radical of formula --(CH.sub.2).sub.2 --, --(CH.sub.2).sub.3 --, --(CH.sub.2).sub.4 --, --(CH.sub.2).sub.5 --, --O--(CH.sub.2).sub.2 --O--, --O--(CH.sub.2).sub.3 --O--; or, together with the carbon atom to which they are attached, a carbonyl; arylcarbonyl, arylC.sub.1-6 alkylcarbonyl, C.sub.1-6 alkylsulfonyl, arylsulfonyl or arylC.sub.1-6 alkylsulfonyl; ##STR5## independently represents a bivalent aromatic heterocycle wherein the heterocycle may be selected from the group consisting of pyrrole, pyrrazole, imidazole, triazole, furane, thiophene, isoxazole, oxazole, isothiazole, thiazole, pyridine, pyridazine, pyrimidine, pyrazine and triazine; or one of the two bivalent aromatic heterocycles in the compounds of formula (1) may be 1,2-benzenediyl; and from halo, hydroxy, C.sub.1-6 alkyl and trihalomethyl.
In the foregoing definitions C.sub.1-6 alkyl defines straight and branch chained saturated hydrocarbon radicals having from 1 to 6 carbon atoms such as, for example, methyl, ethyl, propyl, butyl, 1-methylpropyl, 1,1-dimethylethyl, pentyl, hexyl; C.sub.4-5 alkanediyl defines bivalent straight and branch chained saturated hydrocarbon radicals having from 4 to 5 carbon atoms such as, for example, 1,4-butanediyl, 1,5-pentanediyl; halo is generic to fluoro, chloro, bromo and iodo. The term monocyanomethylene stands for a radical of formula .dbd.CHCN, and dicyanomethylene for a radical of formula .dbd.C(CN).sub.2. The term halomethyl is meant to include mono-, di-, and trihalomethyl. Examples of halomethyl are fluoromethyl, difluoromethyl and 15 particularly trifluoromethyl. In case R.sup.6 and R.sup.7 taken together form a bivalent radical of formula --(CH.sub.2).sub.2 --, --(CH.sub.2).sub.3 --, --(CH.sub.2).sub.4 --, --(CH.sub.2).sub.5 --, --O--(CH.sub.2).sub.2 --O--or --O--(CH.sub.2).sub.3 --O--, the compounds of formula (I) a
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Andrés-Gil José Ignacio
Fernandez-Gadea Francisco Javier
Martinez-Jimenez Pedro
Sipido Victor Karel
Appollina Mary
Coleman Brenda
Janssen Pharmaceutica N.V.
Shah Mukund J.
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