Duphar International Research Bv

Derk Hamminga

Ineke Van Wijngaarden

Wouter Wouters

Hans H Haeck

Johannes W Jansen

Ineke Van Wigngaarden

The invention relates to a group of new 8,9-annelated-.beta.-carbolines and 8,9-annelated-3,4-dihydro-.beta.-carbolines having interesting fibrinolytic properties. In particular the compounds can be used as orally active fibrinolytics. The compounds have the general formulae 1 and 2 ##STR1## wherein R.sub.2 +R.sub.3 together with the carbon atom and the nitrogen atom to which they are bound and the intermediate carbon atom constitute a heterocyclic group consisting of 5-10 ring atoms.

8,9-annelated-.beta.-carbolines and 8,9-annelated

New 8,9-annelated-1,2,3,4-tetrahydro-.beta.-carboline derivatives of the formula ##STR1## wherein R.sub.1 -R.sub.7 are as defined herein; and pharmaceutically acceptable salts and prodrugs thereof. A method of dissolving blood clots using this compound and a pharmaceutical composition having fibrinolytic activity comprising this compound are also part of the present invention.

8,9-anellated-1,2,3,4-tetrahydro-.beta.-carboline derivatives

The present invention concerns 3,4-annelated benzimidazol-2(1H)-one 1-carboxylic acid derivatives of the formula ##STR1## wherein R.sub.0, Z, A, B and C are as defined herein. Such derivatives are useful in the treatment of symptoms which are caused by over-excitation of 5-hydroxytryptamine receptors.

3,4-annelated benzimidazol-2-(1H)-one 1-carboxylic acid derivatives

The invention relates to a group of new annelated indolo [3,2-c] lactam derivatives of the formula ##STR1## having an antagonistic activity on 5-HT receptors. The compounds can be used for the treatment of symptoms which are caused by excessive stimulation of said receptors in the gastrointestinal system, the central nervous system, the cardiovascular system, the respiratory system, and for alleviating or preventing withdrawal symptoms which are induced by abuse of drugs.

Annelated indolo [3,2,-C]lactams

1,7-Annelated esters and amides of indolecarboxylic acids having formula 2, ##STR1## wherein R.sub.1 is halogen;

1,7-annelated indolecarboxylic acid esters and amides

The present invention is concerned with compounds of formula 1 ##STR1## wherein R.sub.0 is alkyl, alkoxy or alkylthio having 1-4 carbon atoms, hydroxy, halogen,

Substituted 3,4-annelated benzimidazol-2(1H)-ones

The invention relates to a group of new 3-N substituted carbamoyl-indole derivatives of the formula ##STR1## having an antagonistic activity on 5-HT receptors. The compounds can be used for the treatment of symptoms which are caused by excessive stimulation of said receptors in the gastrointestinal system, the central nervous system, the cardiovascular system, the respiratory system, and for alleviating or preventing withdrawal symptoms which are induced by abuse of drugs.

New 3-N substituted carbamoyl-indole derivatives

The invention relates to new 8,9-annelated-1,2,3,4-tetrahydro-.beta.-carboline derivatives of the formula ##STR1## wherein the symbols have the following meanings: R.sub.1 is hydrogen, straight or branched alkyl having 1-6 C-atoms, fluorinated or hydroxylated alkyl having 1-6 C-atoms;

8,9-aneallated-1,2,3,4-tetrahydro-.beta.-carboline derivatives

The invention relates to a new group of 8,9-annelated-1,2,3,4-tetrahydro-.beta.-carbolines of the formula ##STR1## and the salts and prodrugs thereof. The meanings of R.sub.1, n, Z, R.sub.2, R.sub.3, and R.sub.4 are defined within the body of the specification. It has been found that the compounds have good fibrinolytic properties and can be used in particular as orally active fibrinolytics.

8,9-annelated-1,2,3,4-tetrahydro-.beta.-carboline derivatives

Annelated indoleketones with an imidazolylalkyl substituent having the formula (2): ##STR1## wherein R.sub.1 is alkyl or alkoxy having 1-4 C-atoms, hydroxy, halogen, trifluoromethyl, a group R.sub.5 R.sub.6 N or R.sub.5 R.sub.6 -N-CO, wherein R.sub.5 and R.sub.6 are hydrogen or alkyl having 1-4 C-atoms or wherein R.sub.5 R.sub.6 N is a saturated 5-6 ring, and n has the value 0, 1 or 2;

Annelated indoleketones with an imidazolylalkyl substituent

The present invention is concerned with compounds of formula 1: ##STR1## wherein R.sub.1 is straight or branched alkyl having 1-4 C-atoms, halogen or cyano;

Substituted 1H-indazole-3-carboxamides

The invention relates to new 1,7-annelated esters and amides of indolecarboxylic acids having general formula 2, ##STR1## wherein the symbols have the meanings given in the specification. The compounds and their salts are very strong and selective antagonists of 'neuronal' 5-hydroxytryptamine (5-HT) receptors, and can be used for the treatment of symptoms which are caused by over-stimulation of these receptors.

1,7-annelated indolecarboxylic acid esters and -amides

The invention relates to a group of new substituted 1,7-annelated 1H-indazole derivatives being strong and selective antagonists of 'neuronal' 5-hydroxytryptamine (5-HT) receptors. The compounds can be represented by general formula 1: ##STR1##

Certain substituted 1,7-annelated 1h-indazoles being selective

The invention relates to a group of new substituted 1,7-annelated 1H-indazole derivatives being strong and selective antagonists of 'neuronal' 5-hydroxytryptamine (5-HT) receptors.

Substituted 1,7-annelated 1H-indazoles

The invention relates to new anellated indole derivatives of general formula 2, ##STR1## wherein p1 R.sub.0 is alkyl or alkoxy having 1-4 C-atoms, phenylalkoxy having 1-3 C-atoms in the alkoxy group, hydroxy, halogen, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, or a group R.sub.7 S(O).sub.p, wherein R.sub.7 is alkyl having 1-4 C-atoms and p has the value 0, 1 or 2, or R.sub.0 is a group R.sub.8 R.sub.9 N, R.sub.8 R.sub.9 N--CO--CH.sub.2 -- or R.sub.8 R.sub.9 --N--CO wherein R.sub.8 and R.sub.9 are hydrogen or alkyl having 1-4 C-atoms or R.sub.8 R.sub.9 N forms a saturated 5- or 6-membered ring and n has the value 0, 1 or 2, Z together with the carbon atom and nitrogen atom to which Z is bound and the intermediate carbon atom, forms a heterocyclic group consisting of 5-8 ring atoms, in which, in addition to the nitrogen atom already present, a --CO--group or a second hetero atom from the group N, O, S, S-O or SO.sub.2 may be present, which ring may be substituted with 1-3 alkyl groups having 1-4 C-atoms, a phenyl group or a spiroalkyl group (C.sub.2 -C.sub.5), or which ring may be anellated with a saturated or non-saturated carbocyclic or heterocyclic ring which consists of 5- or 6-ring atoms and which may be substituted with halogen, alkyl or alkoxy having 1-4 C-atoms, and

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Derk Hamminga