Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Patent
1993-06-21
1995-08-29
Robinson, Allen J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
514331, 514352, 514357, 514398, 514400, 514406, 514411, 514416, 514538, 514548, 514562, 514564, 514602, 546232, 546309, 546312, 5483401, 5483717, 548444, 548470, 548558, A61K 3118
Patent
active
054460654
DESCRIPTION:
BRIEF SUMMARY
The present invention concerns new amines of the general formula I ##STR3## in which R.sub.1 signifies an aryl, aralkyl or an aralkenyl group, the aryl radical of which can be substituted one or more times by halogen, cyano, alkyl, trifluoromethyl, alkoxy, alkylthio, trifluoromethoxy, hydroxyl or carboxyl, m a whole from 1 to 3, n a whole number from 1 to 5, R.sub.2 hydrogen, an alkyl, aralkyl or acyl group, Q a bond or an oxygen atom, R.sub.3 hydrogen or a lower alkyl group which is possibly terminally substituted by carboxyl or by a hydroxyl group and R.sub.4 hydrogen, a lower alkyl group with 1-4 C-atoms, which is possibly terminally substituted by carboxyl or hydroxyl, a possibly substituted phenyl, heteroaryl, cycloalkyl or acyl group or a group ##STR4## in which R.sub.5 represents a straight-chained or branched alkyl chain with 1-4 C-atoms, which is possibly terminally substituted by carboxyl, alkoxycarbonyl, aminocarbonyl, hydroxyl, mercapto, alkylthio or imidazolyl, and Y a carboxyl, an alkoxycarbonyl, aminocarbonyl or cyano, formyl, hydroxymethyl, aminomethyl or an ortho ester group, whereby R.sub.3 and R.sub.4 can also be component of a 5- or 6-membered saturated or unsaturated possibly substituted heterocycle with 1-4 heteroatoms which can be annellated with further ring compounds via one or more bonds.
Thus, the subject of the invention are sulphonamide group-containing phenylalkylamines and phenoxyalkylamines.
The invention includes compounds of the general formula I in which the sulphonamidoalkyl radical stands not only in ortho but also in meta or para position to the radical --Q--(CH.sub.2).sub.2 --NR.sub.3 R.sub.4. The meta and the para position are especially preferred.
If the compounds of the general formula I contain asymmetric carbon atoms, then not only the pure optical isomers (enantiomers) but also their mixture/racemates are contained in the claim.
For the case that the compounds I contain carboxyl groups, their physiologically acceptable salts, esters and amides are also claimed.
Such compounds have hitherto not been described. There are only two publications concerning disulphonamides of the phenylalkylamine type: D. B. Baird et al. Soc. Perkin Trans. 1, No. 8 (1973), 832 and J. H. Wood and R. E. Gibson, Am. Soc. 71 (1949), 393. In neither of the two cited works is a pharmacological action described.
The subject of previous patents/publications were only sulphonamide group-containing phenoxycarboxylic acids, as well as their esters and amides, furthermore phenylalkylcarboxylic acids, as well as their esters and amides, phenoxyalkylcarboxylic acid amides with amino acids as amine component, as well as sulphonamide group-containing tetrazole compounds. In principle, all these compounds contain an acid function. Therefore, it was surprising that the acid function can be replaced by a basic amine function without therein being observed a loss of the pharmacological activity observed in the case of the acid compounds.
The new compounds of the general formula I show an excellent antagonistic action towards thromboxane A.sub.2, as well as against prostaglandin endoperoxides. They inhibit the activation of blood platelets and of other blood cells and prevent the constriction of the smooth musculature of bronchi and blood vessels, as well as the contraction of mesangium cells and of similar cells with contractile properties.
This action makes them valuable remedies for the treatment of cardiovascular diseases, such as acute heart and brain infarct, cerebral and coronary ischaemia, migraine, peripheral arterial occlusive diseases, as well as venous and arterial thromboses. Furthermore, their early use can favourably influence the appearance of organ damages in the case of shock patients. Furthermore, they are suitable for the prevention of thrombocyte and leukocyte depositions in the case of interventions with an extracorporeal circulation and in the case of haemodialysis. Their addition to thrombocyte concentrates stabilises the blood platelets and thus increases the storability of the pr
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Beckh Hansjorg
Doerge Liesel
Stegmeier Karlheinz
Witte Ernst-Christian
Boehringer Mannheim GmbH
Burn Brian M.
Robinson Allen J.
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