Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ester doai
Patent
1996-11-25
1998-04-07
Raymond, Richard L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Ester doai
514538, 514620, 514651, 558422, 560 45, 564165, 564352, 564353, 564354, A61K 31135, A61K 31445, C07C21714, C07C21718
Patent
active
057365687
DESCRIPTION:
BRIEF SUMMARY
The present application has been filed under 35 U.S.C. .sctn. 371 and is based on PCT/EP 95/00626, filed Feb. 20, 1995.
This invention relates to novel substituted 2-(aminoalkoxy)phenylalkylamine compounds having therapeutic activity useful in treating conditions associated with inflammation, allergy, rheumatism, neurological damage or the immune system, to therapeutic compositions containing these novel compounds and to processes for preparing these novel compounds.
It is believed that, in response to an inflammatory stimulus, phospholipase enzymes are activated leading to the release of arachidonic acid from phospholipids. Existing non-steroidal anti-inflammatory agents (NSAIA) are believed to act primarily by blocking the conversion of this released arachidonic acid into prostaglandins via the cyclo-oxygenase pathway of the arachidonic acid cascade. Many existing NSAIA are unsuitable for use by asthmatics. We have found a series of compounds which act to block the release of arachidonic acid from phospholipids. These compounds are indicated as useful antiinflammatory compounds with a potentially broader spectrum of activity than existing NSAIA, and potentially fewer gastro-intestinal side-effects. In addition the compounds may be useful in the treatment of asthma.
Amides and sulphonamides of formula A ##STR2## in which R.sub.1 is alkyl, cycloalkyl or aryl; R.sub.2 is acyl or sulphonyl ; R.sub.3 is alkylamino, dialkylamino or a nitrogen containing heterocyclic group; A.sub.1 is a saturated bond or an alkylene group having 1 to 4 carbon atoms and A.sub.2 is an alkylene group having 2 to 5 carbon atoms, are disclosed as having antiinflammatory activity in U.S. Pat. No. 4,064,125, U.S. Pat. No. 4,127,606 and U.S. Pat. No. 4,122,255. In these documents compounds of formula A in which R.sub.2 represents hydrogen are disclosed as chemical intermediates. There is no hint or suggestion that these intermediates have any biological activity.
Compounds of formula B ##STR3## in which R.sub.1 is alkyl, cycloalkyl or aryl; R.sub.2 is acyl or sulphonyl; R.sub.3 is alkylamino, dialkylamino or a nitrogen containing heterocyclic group; A.sub.1 is a saturated bond or an alkylene group having 1 to 4 carbon atoms; A.sub.2 is an alkylene group having 2 to 5 carbon atoms and R.sub.4 is alkoxy, are disclosed as having antiinflammatory activity in U.S. Pat. No. 4,156,079 and U.S. Pat. No. 4,199,528. Compounds of formula B in which R.sub.2 represents hydrogen are disclosed as chemical intermediates in these documents. There is no hint or suggestion that these intermediates have any biological activity.
Compounds of formula C ##STR4## in which R.sub.1 is alkoxycarbonyl, amido or substituted amido; R.sub.2 is acyl or sulphonyl; R.sub.3 is alkylamino, dialkylamino or a nitrogen containing heterocyclic group; A.sub.1 is an alkylene group having 2 to 5 carbon atoms and n is 1, 2 or 3, are disclosed as having antiinflammatory activity in U.S. Pat. No. 4,098,789.
Compounds of formula D ##STR5## in which R.sub.1 is alkyl, cycloalkyl or aryl; A.sub.1 is a saturated bond or an alkylene group having 1 to 4 carbon atoms; A.sub.2 is an alkylene group having 2 to 5 carbon atoms and R.sub.4 is alkoxy are disclosed as useful intermediates in U.S. Pat. No. 4,214,081.
Compounds of formula E ##STR6## in which R.sub.1 and R.sub.2 independently represent inter alia hydrogen, lower alkyl, cycloalkyl or aralkyl; X represents inter alia --O--; m is an integer from 2 to 4 inclusive; n is 0, 1 or 2 and ALK denotes a straight or branched alkylene chain of 1 to 6 carbon atoms, are claimed as chemical intermediates in GB 1,604,675. 2(4-Aminobutoxy)-N,N-dimethylbenzenemethanamine is exemplified. There is no suggestion that these compounds possess any pharmacological activity.
Dimethylaminomethyl 2-dimethylaminomethyl-4-methylphenyl ether is disclosed as a chemical intermediate in Chem. Pharm. Bull. 10(1), 15-20 (1972). as by-products in Helv. Chim. Acta 46, 1696 (1963).
U.S. Pat. No. 3,047,628 discloses that 2-(dilower alkylamino-lower alkoxy) benzylamines ar
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Rafferty Paul
Tometzki Gerald Bernard
Knoll Aktiengesellschaft
Raymond Richard L.
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