Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1997-05-12
1999-10-12
Daus, Donald G.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
5462777, 5462774, 546111, 546119, 546113, 546139, 546152, 5462757, 544333, 544362, 544373, 5483601, 548452, 514256, 514272, 514253, 514292, 514303, 514300, 514307, 514314, 514339, 514415, A61K 3144, C07D20922
Patent
active
059655828
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to N-benzylindole- and benzopyrazole derivatives having anti-asthmatic, anti-allergic, anti-inflammatory and immunomodulating effects.
2. Background Information
Indole derivatives have many uses as synthetic building blocks for the synthesis of drugs, for example the drugs indomethacin and acemethacin have an N-substituted indole skeleton.
Indomethacin is the prototype of compounds having a predominantly anti-inflammatory and anti-rheumatic effect.
An indazole derivative that can be cited is the substance bendazac which has an anti-inflammatory effect; the synthesis of the substance, IUPAC name [(1-benzyl-1H-indazole-3-yl)oxy]acetic acid, is described in US PS 3 470 194.
DE-OS 42 25 756 and EP 392 317 describe benzimidazoles which constitute angiotensin antagonists, in particular angioterlsin-II antagonists.
DE-OS 27 31 647 describes 1,3-benzothiolanes and their pharmaceutically useful salts.
Colantti (Chim. Ther 6(5), 367-79) describe indole derivatives which have coccidiostatic properties.
Clark et al (J. Med. Chem, 36 (18), 264-57) describe 1H-indole-3-carboxamides substituted by quinuclidyl radicals and derivatives at the acid amide nitrogen. These compounds are 5HT.sub.3 antagonists and can, for example, be used as anti-emetics.
EP 490 263 describes N-methyl-indole derivatives as 5-HT-antagonists.
EP 485 962 describes N-methyl-indole derivatives as S.sub.3 -receptor antagonists.
WO 88/5432 describes N-alkyl substituted 3-indole-carboxylic acid derivatives as diuretics and cardiovascularly active substances.
WO 93/2062 also describes N-alkyl-substituted 3-indole carboxylic acid amides, in which the amide nitrogen is substituted by a heterocyclic system, such as a tetrazole ring or a substituted tetrazole ring.
EP 580 502 describes 3-(hydroxybenzylidenyl)-indoline-2-one-derivatives with an anti-inflammatory, analgesic, anti-arteriosclerotic and anti-asthmatic effect. The compounds, which can be present as an E/Z-isomer mixture, inhibit LTB.sub.4 synthesis.
The compounds carry various substituents at the indoline nitrogen; there is a keto- or thioketo group at the 2-carbon atom of the indoline ring.
SUMMARY OF THE INVENTION
It is the object of the invention to provide novel compounds which have an anti-asthmatic, anti-allergic, anti-inflammatory and immunemodulating effect; processes are also described for the preparation of the compounds and of drugs that can be obtained from the compounds.
The object of the invention therefore comprises compounds of the general formula 1 ##STR2## having the following meanings: R.sup.1 =hydrogen, (C.sub.1 -C.sub.6)alkyl, where the alkyl group can be straight-chained or branched and can be substituted once or several times by halogen, phenyl, which for its part can be substituted once or several times by halogen, (C.sub.1 -C.sub.6)alkyl, (C.sub.3 -C.sub.7)cycloalkyl, carboxyl groups, esterified carboxyl groups, trifluoromethyl groups, trichloromethyl groups, hydroxyl groups, methoxy groups, ethoxy groups, benzyloxy groups, benzyl groups or benzoyl groups, 2- or 3-thienyl, 2-quinolyl, 2-, 3- or 4-pyridyl which, for its part, can be substituted once or several times by halogen, (C.sub.1 -C.sub.4)alkyl groups or (C.sub.1 -C.sub.4)alkoxy groups, (C.sub.3 -C.sub.7)cycloalkyl, aryl, for example phenyl or naphthyl, heteroaryl, for example 2-, 3- or 4-pyridyl, 2- or 8-quinolyl, 2-thienyl or 1,3 or 8 isoquinolyl, where aryl or heteroaryl can be substituted once or several times by halogen, (C.sub.1 -C.sub.4)alkyl, (C.sub.1 -C.sub.4)alkoxy, hydroxy, thiol groups, thioether groups (C.sub.1 -C.sub.4)alkanoyl groups, CN, --COOH, --CF.sub.3, NO.sub.2, (C.sub.1 -C.sub.3)alkoxycarbonyl, an amino group of the general formula ##STR3## or aroyl, with aryl in the meaning stated. R.sup.2 and R.sup.3 can be the same or different and can represent hydrogen, (C.sub.1 -C.sub.6)alkyl, straight-chained or branched, (C.sub.3 -C.sub.7)cycloalkyl, (C.sub.1 -C.sub.6)alkanoyl, (C.sub.1 -C.sub.6)alkoxy, halogen, benzyloxy, h
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Emig Peter
Fleischhauer Ilona
Fouchard Fabienne
Kutscher Bernhard
Lebaut Guillaume
Asta Medica Aktiengesellschaft
Daus Donald G.
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