Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1997-04-09
1999-07-27
Bernhardt, Emily
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
544295, 544364, 544367, 544369, 544370, 544298, 544315, 544319, 5462837, 548127, 548129, 548182, 548213, 548225, 548228, 548229, 5482632, 548144, 548251, 548255, 5483111, A61K 31495, C07D40514, C07D40714
Patent
active
059290757
DESCRIPTION:
BRIEF SUMMARY
The present invention concerns novel compounds of formula (I), pharmaceutical compositions comprising said compounds, the preparation thereof as well as the use as a medicine in the treatment of hyperlipidemia.
The causal relationship between hypercholesterolemia, particularly that associated with increased plasma concentrations of low density lipoproteins (LDL) and very low density lipoprotein (VLDL) remnants, and premature atherosclerosis has gained widespread acceptance over the last few years. The consensus that treatment of hypercholesterolemia has therapeutic benefit has become widely accepted by both physicians and the public. A limited number of drugs are available for the treatment of hyperlipidemia. The primary agents used for the management of hyperlipidemia included bile acid sequestrants, fibrates, nicotinic acid and HMG Co A-reductase inhibitors. The inconvenience of administration and gastro-intestinal side-effects of available bile acid sequestrants make compliance a major problem. The fibrates have only limited usefulness in the treatment for certain types of hypercholesterolemia. Treatment with nicotinic acid encompasses side-effects and toxicity problems. The HMG Co A-reductase inhibitors already form a first line treatment of familiar hypercholesterolemia. However there still remains a need for new lipid lowering agents for that act preferably via other mechanisms than the above mentioned drugs.
EP-0,006,711-A, published on Sep. 9, 1980, discloses heterocyclic derivatives of (4-phenylpiperazin-1-yl-aryloxymethyl-1,3-dioxolan-2-yl)-methyl-1H-imidazo les and 1H-1,2,4-triazoles having antifungal properties. The presently claimed compounds differ therefrom by the presence of a sulfur atom adjacent to the Het-moiety and by their pharmacological profile, in particular their apolipoprotein B synthesis inhibiting activity. The present invention provides novel compounds of formula ##STR2## the N-oxides, the stereochemically isomeric forms thereof, and the pharmaceutically acceptable acid addition salts, wherein A and B taken together form a bivalent radical of formula: replaced by C.sub.1-6 alkyl; in the bivalent radicals of formula (c), (d), (e), (f), one or two hydrogen atoms may be replaced by C.sub.1-6 alkyl; alkyl substituted with hydroxy, oxo, C.sub.3-6 cycloalkyl or aryl; pyridine substituted with one or two substituents selected from C.sub.1-6 alkyl, hydroxy, C.sub.1-6 alkyloxy, trihalomethyl, amino, mono- or di(C.sub.1-6 alkyl)amino or aryl; pyrimidine; pyrimidine substituted with one or two substituents selected from C.sub.1-6 alkyl, hydroxy, C.sub.1-6 alkyloxy, trihalomethyl, amino, mono- or di(C.sub.1-6 alkyl)-amino or aryl; tetrazole; tetrazole substituted with C.sub.1-6 alkyl or aryl; triazole; triazole substituted with one or two substituents selected from C.sub.1-6 alkyl, hydroxy, C.sub.1-6 alkyloxy, trihalomethyl, amino, mono- or di(C.sub.1-6 alkyl)-amino; thiadiazole; thiadiazole substituted with one or two substituents selected from C.sub.1-6 alkyl, hydroxy, C.sub.1-6 alkyloxy, trihalomethyl, amino, mono- or di(C.sub.1-6 alkyl)amino; oxadiazole substituted with one or two substituents selected from C.sub.1-6 alkyl, hydroxy, C.sub.1-6 alkyloxy, trihalomethyl, amino, mono- or di(C.sub.1-6 alkyl)amino; imidazole; imidazole substituted with one or two substituents selected from C.sub.1-6 alkyl, hydroxy, C.sub.1-6 alkyloxy, trihalomethyl, amino, mono- or di(C.sub.1-6 alkyl)amino; thiazole; thiazole substituted with one or two substituents selected from C.sub.1-6 alkyl, hydroxy, C.sub.1-6 alkyloxy, trihalomethyl, amino, mono- or di(C.sub.1-6 alkyl)amino; oxazole; oxazole substituted with one or two substituents selected from C.sub.1-6 alkyl, hydroxy, C.sub.1-6 alkyloxy, trihalomethyl, amino, mono- or di(C.sub.1-6 alkyl)amino;
The heterocyclic radical "Het" is bound to the sulfur atom via a carbon atom.
As used in the foregoing definitions halo is generic to fluoro, chloro, bromo and iodo; C.sub.1-6 alkyl defines straight and branched chain saturated hydrocarbon radicals having from
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Montserrat, Chemical Abstracts, vol. 106, No. 67321 (1987).
Chemical Abstract, vol. 106, No. 9, 67321f, Mar. 2, 1987, (Inke S.A.).
Montserrat CA, 106,67320e, Mar. 2, 1987 (Ineke S.A.).
Backx Leo Jacobus Jozef
de Chaffoy de Courcelles Didier Robert Guy Gabriel
Heeres Jan
Hendrickx Robert Jozef Maria
Van der Eycken Luc Alfons Leo
Bernhardt Emily
Ciambrone Coletti Ellen
Janssen Pharmaceutica N.V.
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