Benzodipyrroles, processes for the preparation thereof and pharmaceutical compositions containing them

The present invention provides compounds of the general formula ##STR1## wherein the variables are as defined herein. The present invention also provides processes for the preparation thereof, pharmaceutical compositions containing them and intermediates for the preparation thereof.

The present invention is concerned with new benzodipyrroles, processes for 
the preparation thereof and pharmaceutical compositions containing them. 
The new benzodipyrroles according to the present invention are compounds of 
the general formula: 
##STR2## 
wherein R.sub.1 is a hydrogen atom or an alkyl, alkenyl or a cycloalkyl 
radical; R.sub.2 is a hydrogen atom, an alkyl or alkenyl radical, a cyano 
group, a carbonyl group substituted by hydroxyl, alkyl, alkoxy, amino, 
alkylamino, dialkylamino or hydrazino or together with R.sub.1 represents 
a cycloalkylene radical or R.sub.1 and R.sub.2 together form an alkylidene 
or cycloalkylidene radical; R.sub.3 is a hydrogen atom, a cyano group or 
an alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkylcarbonyl, 
alkoxycarbonyl, carboxyl, aminocarbonyl, alkylaminocarbonyl, 
dialkylaminocarbonyl or aryl radical; R.sub.4 is a hydrogen atom, an 
alkyl, trihalogenomethyl, cycloalkyl, hydroxyl, cyano, carboxyl, 
alkoxycarbonyl, alkylcarbonyl, aminocarbonyl, alkylaminocarbonyl or 
dialkylaminocarbonyl radical or a heterocyclic five-membered ring with 1 
to 4 heteroatoms or a heterocyclic six-membered ring with 1 to 5 
heteroatoms, the heteroatoms of the said five- and six-membered rings 
being the same or different and being nitrogen, oxygen or sulphur and one 
or more of the nitrogen atoms optionally carries an oxygen atom and the 
said five- and six-membered rings are optionally substituted by one or 
more alkyl, alkoxy, alkylthio, hydroxyl, nitro, amino, halogen or cyano 
groups or R.sub.4 is a phenyl ring of the general formula: 
##STR3## 
where R.sub.5, R.sub.6 and R.sub.7 are the same or different and each is a 
hydrogen atom or an alkanesulphonyloxy, trifluoromethanesulphonyloxy, 
alkanesulphonylamino, trifluoromethanesulphonylamino, 
N-alkyl-alkanesulphonylamino, N-alkyl-trifluoromethanesulphonylamino, 
alkylsulphenylmethyl, alkylsulphinylmethyl or alkylsulphonylmethyl radical 
or a carbonyl group substituted by hydroxyl, alkoxy, amino, alkylamino or 
dialkylamino or a sulphonyl group substituted by amino, alkylamino, 
dialkylamino or cyclic imino, whereby a methylene group in the 4-position 
can be replaced by a sulphur or oxygen atom, or an alkylcarbonylamino, 
aminocarbonylamino, alkylaminocarbonylamino radical, alkylthio, 
alkylsulphinyl or aklylsulphonyl radical, a nitro, halogen, amino or 
hydroxyl group, an alkyl, alkoxy, alkenyloxy, alkynyloxy, cyanoalkoxy, 
carboxyalkoxy, alkoxycarbonylalkoxy, dialkylamino, 1-imidazolyl, 
trifluoromethyl or cyano group and X is an oxygen or sulphur atom; the 
tautomers thereof and the physiologically acceptable salts thereof with 
inorganic and organic acids. 
Since the compounds of general formula (I), when R.sub.1 is not a hydrogen 
atom, possess an asymmetric carbon atom, the present invention also 
provides the opticallyactive forms and the racemic mixtures of these 
compounds. 
In the case of compounds of general formula (I), in which R.sub.4 is a 
hydroxyl group, the tautomeric forms of the following general formulae are 
also the subject of the present invention: 
##STR4## 
in which R.sub.1, R.sub.2 and R.sub.3 have the same meanings as above. 
The new compounds according to the present invention possess valuable 
pharmacological properties and, in particular, they increase the strength 
of the heart and/or have a blood pressure lowering action and/or influence 
the thrombocyte function and improve the microcirculation. 
In general formula (I) the substituents R.sub.1 and R.sub.2 can be the same 
or different and represent hydrogen, an alkyl, cycloalkyl or alkenyl 
radical, a cyano group or a carbonyl group substituted by hydroxyl, alkyl, 
alkoxy, amino, alkylamino, dialkylamino or hydrazino, in which each of the 
above-mentioned alkyl and alkenyl moieties can be straight-chained or 
branched and contain 1 to 6 or 2 to 6 carbon atoms, respectively, and the 
above-mentioned cycloalkyl moiety can contain 3 to 7 carbon atoms. 
Preferred in this sense for R.sub.1 and R.sub.2 are hydrogen, methyl, 
ethyl, isopropyl, 3-pentyl, allyl, cyclopentyl, cyclohexyl, cyano, acetyl, 
propionyl, methoxycarbonyl, ethoxycarbonyl, aminocarbonyl, 
methylaminocarbonyl, dimethylaminocarbonyl and hydrazinocarbonyl. 
R.sub.1 and R.sub.2, together with the carbon atom to which they are 
attached, can also form a cycloalkylene ring containing 3 to 7 carbon 
atoms and preferably a spirocyclopropyl, spirocyclobutyl, spirocyclopentyl 
or spirocyclohexyl radical. 
R.sub.1 and R.sub.2 can together also form an alkylidene or cycloalkylidene 
radical and preferably an isopropylidene radical. 
If R.sub.3 is a hydrogen atom or an alkyl, alkenyl, cycloalkyl or 
cycloalkenyl radical, then it is preferably a hydrogen atom, 
straight-chained or branched alkyl or alkenyl radical containing 1 to 7 or 
2 to 7 carbon atoms, respectively, or a cycloalkyl or cycloalkenyl radical 
containing 3 to 7 carbon atoms, R.sub.3 is preferably a hydrogen atom or a 
methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, 3-pentyl, allyl, 
but-2-enyl, cyclopentyl, cyclohexyl, cyclopentyl or cyclohexyl radical. 
If R.sub.3 is a cyano group or an alkylcarbonyl, alkoxycarbonyl, 
aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl or aryl radical, 
then the above-mentioned alkyl and alkoxy radicals contain up to 7 and 
preferably up to 5 carbon atoms. Besides cyano, carboxyl or phenyl, 
R.sub.3 is preferably acetyl, propionyl, methoxycarbonyl, ethoxycarbonyl, 
aminocarbonyl, methylaminocarbonyl or dimethylaminocarbonyl. 
If R.sub.4 is a hydrogen atom or an alkyl, trihalogenomethyl cycloalkyl, 
cycloalkenyl, hydroxyl, cyano, carboxyl, alkylcarbonyl, alkoxycarbonyl, 
alkylaminocarbonyl or dialkylaminocarbonyl radical, then the said alkyl 
and cycloalkyl radicals contain 1 to 7 and 3 to 7 carbon atoms, 
respectively. Preferred meanings for R.sub.4 include methyl, ethyl, 
isopropyl, n-butyl, trifluoromethyl, cyclopentyl, cyclohexyl, cyclopentyl, 
cyclohexenyl, hydroxyl, cyano, carboxyl, acetyl, propionyl, 
methoxycarbonyl, ethoxycarbonyl, aminocarbonyl, methylaminocarbonyl and 
dimethylaminocarbonyl. 
If R.sub.4 is a heterocyclic five-membered ring containing 1 to 4 
heteroatoms or a heterocyclic six-membered ring containing 1 to 5 
heteroatoms, the heteroatoms in the said five- and six-membered rings 
being the same or different and being nitrogen, oxygen or sulphur, one or 
more of the nitrogen atoms optionally carrying oxygen, then preferred 
radicals include pyrrole, furan, thiophene, pyrazole, imidazole, thiazole, 
oxazole, triazole, tetrazole, thiadiazole, oxadiazole, pyrazine, 
N,N-dioxypyrazine, pyrimidine, N,N-dioxypyrimidine, pyridazine, oxazine, 
thiazine, triazine, tetrazine, pyridyl and N-oxypyridyl. 
Alkyl, alkoxy and alkylthio substituents in the heterocyclic five- and 
six-membered rings can contain up to 6 and preferably up to 4 carbon 
atoms. Preferred radicals include methyl, ethyl, methoxy, ethoxy, 
methylthio and ethylthio radicals. Halogen is to be understood to be 
fluorine, chlorine or bromine, chlorine being preferred. 
If R.sub.4 means a phenyl ring of general formula (II), then the alkyl 
moiety of the substituents mentioned in the case of R.sub.5, R.sub.6 and 
R.sub.7 contains up to 5 and preferably up to 4 carbon atoms. Preferred 
radicals in this sense include, for example, methanesulphonyloxy, 
ethanesulphonyloxy, n-propanesulphonyloxy, isopropanesulphonyloxy, 
trifluoromethanesulphonyloxy, methylsulphenylmethyl, ethylsulphenylmethyl, 
n-propylsulphenylmethyl, methylsulphinylmethyl, ethylsulphinylmethyl, 
methylsulphonymethyl, ethylsulphonylmethyl, n-propylsulphonylmethyl, 
methanesulphonylamino, ethanesulphonylamino, n-propanesulphonylamino, 
trifluoromethanesulphonylamino, N-methyl-methanesulphonylamino, 
N-ethylmethanesulphonylamino, N-methyl-ethanesulphonylamino, 
N-ethyl-ethanesulphonylamino, N-isopropyl-ethanesulphonylamino, 
N-methyl-n-propanesulphonylamino, N-n-propyl-n-propanesulphonylamino, 
N-methyl-trifluoromethanesulphonylamino, 
N-ethyl-trifluoromethanesulphonylamino, 
N-isopropyl-trifluoromethanesulphonylamino, methoxycarbonyl, 
ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, methylaminocarbonyl, 
ethylaminocarbonyl, dimethylaminocarbonyl, di-(n-propyl)-aminocarbonyl, 
N-methyl-ethylaminocarbonyl, trifluoromethyl, methylaminosulphonyl, 
ethylaminosulphonyl, n-propylaminosulphonyl, n-butylaminosulphonyl, 
n-pentylaminosulphonyl, dimethylaminosulphonyl, diethylaminosulphonyl, 
di-(n-propyl)-aminosulphonyl, N-methylisopropylaminosulphonyl, 
acetylamino, propionylamino, methylaminocarbonylamino, 
ethylaminocarbonylamino, propylaminocarbonylamino, methyl, ethyl, propyl, 
methoxy, ethoxy, propyloxy, allyloxy, but-2-enyloxy, but-3-enyloxy, 
pent-2-enyloxy, propargyloxy, but-2-ynyloxy, but-3-ynyloxy, 
cyanomethyloxy, cyanoethyloxy, methoxycarbonylmethyloxy, 
methoxycarbonylethyloxy, methylthio, ethylthio, methylsulphinyl, 
ethylsulphinyl, methylsulphonyl and ethylsulphonyl radicals. 
In the case of sulphonyl groups which can be substituted by imino groups, 
the morpholino, pyrrolidino, piperidino and hexamethyleneiminosulphonyl 
radicals are preferred. 
R.sub.5 is especially a hydrogen atom or an alkylsulphonyloxy, 
trifluoromethylsulphonyloxy, alkylsulphenylmethyl, alkylsulphinylmethyl, 
alkylsulphonylmethyl, alkylsulphonylamino, N-alkyl-alkylsulphonylamino, 
trifluoromethylsulphonylamino or N-alkyl-trifluoromethylsulphonylamino 
radical, a carbonyl group substituted by hydroxy, alkoxy, amino, 
alkylamino or dialkylamino or a sulphonyl group substituted by amino, 
dialkylamino or morpholino, wherein the alkyl moieties can contain 1 or 2 
carbon atoms, or a nitro, cyano or alkylaminosulphonyl radical with 1-4 
carbon atoms, an alkylcarbonylamino, aminocarbonylamino or 
N-alkyl-aminocarbonylamino radical, an alkylthio, alkylsulphinyl or 
alkylsulphonyl radical, whereby the alkyl moieties can contain 1 or 2 
carbon atoms, a halogen, amino, hydroxy, dialkylamino, alkyl, alkoxy, 
alkenyloxy or alkynyloxy radical preferably with 1-3 carbon atoms, a 
cyanomethyloxy or methoxycarbonylmethyloxy radical, a trifluoromethyl 
radical or a 1-imidazolyl radical; R.sub.6 is especially a hydrogen atom 
or an alkyl radical with 1-3 carbon atoms or an alkoxy or dialkylamino 
radical with 1 or 2 carbon atoms in the alkyl moieties or a halogen atom 
and R.sub.7 is preferably a hydrogen atom or a methoxy radical. 
The phenyl radical (II) can contain up to 3 of the above substituents. 
Preferred monosubstituted phenyl compounds are the hydroxy, C.sub.1 
-C.sub.3 alkyl, C.sub.1 -C.sub.3 alkoxy, allyloxy, propargyloxy, 
cyanomethyloxy, methoxycarbonylmethyloxy, halogeno, nitro, cyano, 
aminocarbonyl, methoxycarbonyl, amino, C.sub.2 -C.sub.6 dialkylamino, 
C.sub.1 -C.sub.3 alkylthio, C.sub.1 -C.sub.3 alkylsulphinyl, C.sub.1 
-C.sub.3 alkylsulphonyl, C.sub.1 -C.sub.3 alkylsulphonyloxy and the 
1-imidazolyl compounds, the substituent being in the 2-, 3- or 4-position. 
Preferred disubstituted compounds contain as substituents 
alkanesulphonyloxy, trifluoromethylsulphonyloxy, alkylsulphenylmethyl, 
alkylsulphinylmethyl, alkylsulphonylmethyl, alkylsulphonylamino, 
N-alkyl-alkylsulphonylamino, trifluoromethylsulphonylamino or 
N-alkyl-trifluoromethylsulphonylamino radicals, a carbonyl group 
substituted by hydroxy, alkoxy, amino, alkylamino or dialkylamino or a 
sulphonyl group substituted by amino, dialkylamino or morpholino, an 
alkylaminosulphonyl, alkylcarbonylamino, aminocarbonylamino or 
N-alkyl-aminocarbonylamino radical, a hydroxy, alkyl, alkoxy, allyloxy, 
propargyloxy, cyanomethoxy, methoxycarbonylmethoxy, cyano, halogen, nitro, 
amino, dialkylamino, alkylthio, alkylsulphinyl, alkylsulphonyl, or 
1-imidazolyl group, the two substituents being the same or different and 
being in the 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-position but preferably 
in the 2,4-2,5- or 3,4-position and the above-mentioned alkyl radicals, 
alone or in combination with other radicals, can contain up to 3 carbon 
atoms. 
A preferred trisubstituted phenyl radical is the 3,4,5-trimethoxyphenyl 
radical. 
For X, an oxygen or sulphur atom is preferred. 
Especially preferred compounds of general formula (I) are those in which 
R.sub.1 and R.sub.2 are the same and signify methyl or ethyl radicals or 
R.sub.1 and R.sub.2 are different and signify hydrogen atoms or methyl, 
ethyl, isopropyl, cyclopentyl, cyano, acetyl, methoxycarbonyl, 
ethoxycarbonyl, aminocarbonyl or hydrazinocarbonyl radicals or R.sub.1 and 
R.sub.2 represent a spirocyclopentyl ring when R.sub.1 and R.sub.2, 
together with the carbon atom to which they are attached, form a 
cycloalkyl ring, R.sub.3 is hydrogen atom or a methyl, ethyl, isopropyl, 
n-butyl, allyl, cyclohexyl, cyclopentyl, cyano, ethoxycarbonyl or phenyl 
radical, R.sub.4 is a methyl, ethyl, isopropyl, trifluoromethyl, 
cyclopentyl, hydroxyl, cyano, acetyl, carboxyl, ethoxycarbonyl, 
aminocarbonyl, methylaminocarbonyl or dimethylaminocarbonyl radical or 
R.sub.4 is a pyrrole, furan, thiophene, pyrazole, imidazole, thiazole, 
oxazole, triazole, tetrazole, thiadiazole, oxadiazole, pyridine, 
N-oxypyridine, pyrazine, N,N-dioxypyrazine, pyrimidine, 
N,N-dioxypyrimidine, pyridazine, oxazine, thiazine, triazine or tetrazine 
radical, as well as the methyl, ethyl, methoxy, ethoxy, methylthio, 
ethylthio and chlorine substituted derivatives thereof, or R.sub.4 is a 
phenyl radical of general formula (II) in which R.sub.5 is a hydrogen atom 
or a methanesulphonyloxy, trifluoromethanesulphonyl, 
methanesulphonylamino, trifluoromethanesulphonylamino, 
methanesulphonylmethylamino, trifluoromethanesulphonylmethylamino, 
methylsulphenylmethyl, methylsulphinylmethyl, methylsulphonylmethyl, 
aminocarbonyl, aminosulphonyl, methylaminosulphonyl, 
dimethylaminosulphonyl, acetylamino, methylthio, methylsulphonyl, 
hydroxyl, methyl, methoxy, propargyloxy, cyanomethoxy, 
methoxycarbonylmethoxy, cyano, chloro, nitro, amino, dimethylamino, 
trifluoromethyl or 1-imidazolyl radical, R.sub.6 is a hydrogen atom or 
methyl, methoxy, dimethylamino or chlorine and R.sub.7 is a hydrogen atom 
or a methoxy radical and X is an oxygen atom. 
The compounds of general formula (I) can be prepared by methods known from 
the literature for the synthesis of indoles and oxindoles. In this regard, 
reference is made to: 
(a) P. L. Julian, E. W. Meyer and H. C. Printy, in R. C. Elderfield (ed.), 
Heterocyclic Compounds, Vol. 1, pp. 1-231, pub. John Wiley & Sons, New 
York, 1952 
(b) R. K. Brown, in W. J. Houlihan (ed.), Heterocyclic Compounds, Vol. 25, 
part I, pp. 227-537, pub. John Wiley & Sons, New York, 1972. 
However, the synthesis routes shown in the following schemes 1, 2 and 3 are 
especially advantageous. 
##STR5## 
As can be seen from scheme 1, the compounds of general formula (III), which 
are known from the literature (cf. in this regard Federal Republic of 
Germany Patent Specifications Nos. P 34 17 643.8 and P 34 46 417.4), in 
which R.sub.1, R.sub.2 and X have the above given meanings, can be 
diazotised and the diazonium salt reduced to a hydrazine (IV). By reaction 
of the hydrazine with a compound of the general formula: 
EQU R.sub.4 COCH.sub.2 R.sub.3 (V), 
in which R.sub.3 and R.sub.4 have the above-given meanings, there is 
obtained a hydrazone (VI) which can be cyclised by a Fischer indole 
synthesis to give a compound of general formula (I). On the other hand, a 
hydrazone of general formula (VI) can also be obtained by reacting a 
diazonium salt of an amine (III) in a Japp-Klingemann reaction with a 
compound of general formula (VII), R.sub.3 and R.sub.4 having the 
above-given meanings and Y being a residue activating the methine group. 
This residue can be, for example, an aldehyde, ketone, ester, carboxylic 
acid or nitrile. The azo compound obtained as intermediate in the reaction 
mixture is, without isolation, saponified directly to give a hydrazone. 
The diazotisation of the amines (III) is preferably carried out under 
neutral or acidic conditions in a polar solvent, such as water, methanol, 
ethanol, glacial acetic acid, hydrochloric acid, sulphuric acid or 
phosphoric acid, at a temperature of from -70.degree. to +50.degree. C. 
and preferably of from -5.degree. to +10.degree. C. For the diazotisation, 
there is preferably used an inorganic salt or an organic ester of nitrous 
acid, for example sodium nitrite, potassium nitrite or amyl nitrite. 
The reduction of the diazonium salts is usually carried out in the 
above-mentioned solvents at a temperature of from -50.degree. C. to the 
boiling point of the solvent used by preferably at a temperature of from 
0.degree. to 80.degree. C., whereby as reducing agent, there can be used 
an alkali metal sulphite, sulphur dioxide, a dithionite, stannous 
chloride, zinc dust, iron, sodium amalgam, triphenylphosphines or an 
endiol. An electrochemical reduction can also be used. 
The reaction of the hydrazines with compounds of general formula (V) can be 
carried out in a solvent, such as water, alcohol, benzene, toluene, 
dioxan, dimethylformamide, diethyl ether or tetrahydrofuran, at a 
temperature of from -80.degree. C. to the boiling point of the solvent 
used. The addition of an inorganic or organic acid, such as hydrochloric 
acid, sulphuric acid, phosphoric acid or acetic acid, has also proved to 
be advantageous. 
The Japp-Klingemann reaction is advantageously carried out in the solvents 
in which the above-described diazotisation can be carried out. Thus, these 
are especially water, methanol, ethanol, glacial acetic acid, hydrochloric 
acid, sulphuric acid or phosphoric acid, the temperature used being from 
-50.degree. C. to +80.degree. C. but preferably from 0.degree. to 
25.degree. C. The following saponification can be carried out thermally or 
after the addition of an acid or base, for example aqueous sodium or 
potassium hydroxide solution, hydrochloric acid, sulphuric acid, 
phosphoric acid or glacial acetic acid, at a temperature up to the boiling 
point of the solvent. 
The Fischer indole synthesis of the hydrazones (VI) is carried out without 
a solvent or in a solvent, such as alcohol, nitrobenzene, acetic acid, 
xylene, cumol or toluene, thermally or in the presence of an acidic 
catalyst which, however, can also be used as solvent, whereby there can be 
used hydrochloric acid, sulphuric acid, phosphoric acid, polyphosphoric 
acid, glacial acetic acid, formic acid, zinc chloride, boron trifluoride, 
a cation exchanger, sulphosalicylic acid or a polyphosphate ester, at a 
temperature of from 0.degree. C. to the boiling point of the solvent used. 
The hydrazones (VI) can also be prepared from the amines (III) according to 
the following scheme 2: 
##STR6## 
The reaction of compounds (III) with halogenoacetic acid esters (X), in 
which halogen is fluorine, chlorine, bromine or iodine but is preferably 
bromine, is advantageously carried out in a polar or non-polar solvent, 
for example methylene chloride, toluene, dioxan, alcohols or 
dimethylformamide, at a temperature of from -50.degree. C. and the boiling 
point of the solvent and preferably at a temperature of from 25.degree. to 
100.degree. C. 
The esters so obtained can be saponified according to well-known processes, 
for example with an inorganic base, such as sodium hydroxide, potassium 
hydroxide, sodium hydrogen carbonate or potassium hydrogen carbonate, in a 
protic solvent, such as water or alcohol, or with an inorganic or organic 
acid, such as hydrochloric acid, sulphuric acid, glacial acetic acid, 
phosphoric acid or polyphosphoric acid, optionally with the addition of a 
solvent, such as water or alcohol. 
The nitrosation of the acids obtained to give compounds of general formula 
(VIII) is preferably carried out under neutral to acidic conditions in a 
polar solvent, such as water, methanol, ethanol, glacial acetic acid, 
hydrochloric acid, sulphuric acid or phosphoric acid, at a temperature of 
from -70.degree. to +50.degree. C. and preferably of from -5.degree. to 
+10.degree. C. The for nitrosation, there is preferably used an inorganic 
salt or an organic ester or nitrous acid, for example sodium or potassium 
nitrite or amyl nitrite. 
The reaction of the N-nitroso-carboxylic acids (VIII) to give the syndnones 
(IX) is carried out in an inert solvent, for example dioxan, diethyl 
ether, tetrahydrofuran or toluene, with a water-removing agent, for 
example acetic anhydride, propionic acid anhydride, sulphuric acid, 
phosphoric acid, phosphorus pentachloride or phosphorus trichloride, at a 
temperature of from -50.degree. C. to the boiling point of the solvent but 
preferably at a temperature of from 25.degree. to 100.degree. C. 
The sydnones (IX) can be decomposed under acidic conditions to give the 
hydrazines (IV) which can be take up in situ with the ketones (V) to give 
the hydrazones (VI). As acid for the saponification of the syndones, there 
can be used an inorganic acid, for example, hydrochloric acid, sulphuric 
acid, phosphoric acid or polyphosphoric acid, or an organic acid, such as 
glacial acetic acid, at a temperature of from -70.degree. to +100.degree. 
C., and preferably of from 0.degree. to 70.degree. C. 
Alternatively to schemes 1 and 2, the compounds of general formula (I) can 
also be prepared by the oxindole synthesis according to the following 
scheme 3 (cf. P. L. Julian, E. W. Meyer and H. C. Printy in R. C. 
Elderfield (ed.), Heterocyclic Compounds, Vol. 3, pub. John Wiley & Sons, 
New York, 1952, pp. 128-142). 
Hinsberg synthesis: reaction of aromatic amines with the bisulphite 
addition compounds of ketones 
Brunner synthesis: cyclisation of aromatic amines via the hydrazide to the 
oxindoles 
Stelle synthesis: cyclisation of aromatic amines via an amide to the 
oxindole. 
##STR7## 
The oxindole synthesis of compounds of general formula (III) to give 
compounds of general formula (I) only applies to the case in which R.sub.4 
is a hydroxyl group. Some of the compounds of general formula (XI) are new 
and these compounds can be prepared by processes known from the 
literature. 
Compounds of general formula (I) can also be subsequently converted into 
other compounds of general formula (I). This applies, for example: 
(a) For the oxidation of a five- or six-membered ring with one or more 
nitrogen atoms to give the corresponding N-oxides. The oxidation is 
preferably carried out with one or more equivalents of the oxidation agent 
used, for example with hydrogen peroxide in glacial acetic acid, 
trifluoroacetic acid or in formic acid, at a temperature of 20.degree. to 
100.degree. C. or in acetone at a temperature of from 0.degree. to 
60.degree. C., with a per acid, such as performic acid or m-chlorobenzoic 
acid, in glacial acetic acid, trifluoroacetic acid, methylene chloride or 
chloroform, at a temperature of from 0.degree. to 60.degree. C. 
(b) For the preparation of compounds of general formula (I), in which 
R.sub.4 is a radical of general formula (II) and R.sub.5 is an 
alkylsulphinyl, alkylsulphonyl, alkylsulphinylmethyl or 
alkylsulphonylmethyl radical, by subsequent oxidation of a compound of the 
general formula: 
##STR8## 
wherein R.sub.1, R.sub.2, R.sub.3, R.sub.6, R.sub.7 and X have the same 
meanings as above and R'.sub.5 is an alkylthio or alkylsulphenylmethyl 
radical with, in each case, up to 3 carbon atoms in the alkyl moiety. 
The oxidation is preferably carried out in a solvent or solvent mixture, 
for example in water, water/pyridine, acetone, glacial acetic acid, dilute 
sulphuric acid or trifluoroacetic acid, depending upon the oxidation agent 
used, preferably at a temperature of from -80.degree. to +100.degree. C. 
For the preparation of an alkylsulphinyl or alkylsulphinylmethyl compound 
of general formula (I), the oxidation is preferably carried out with an 
equivalent of the oxidation agent used, for example with hydrogen peroxide 
in glacial acetic acid, trifluoroacetic acid or formic acid, at a 
temperature of from 0.degree. to 20.degree. C. or in acetone at 0.degree. 
to 60.degree. C., with a per acid, such as performic acid in glacial 
acetic acid or trifluoroacetic acid at 0.degree. to 50.degree. C. or with 
m-chloroperbenzoic acid in methylene chloride or chloroform at -20.degree. 
to +60.degree. C., with sodium metaperiodate in aqueous methanol or 
ethanol at -15.degree. to +25.degree. C., with bromine in glacial acetic 
acid or aqueous acetic acid, with N-bromosuccinimide in ethanol, with 
tert.-butyl hypochloride in methanol at -80.degree. to -30.degree. C., 
with iodobenzodichloride in aqueous pyridine at 0.degree. to 50.degree. 
C., with nitric acid in glacial acetic acid at 0.degree. to 20.degree. C., 
with chromic acid in glacial acetic acid or in acetone at 0.degree. to 
20.degree. C., and with sulphuryl chloride in methylene chloride at 
-70.degree. C., the thioether chlorine complex hereby obtained preferably 
being hydrolysed with aqueous ethanol. 
For the preparation of an alkylsulphonyl or alkylsulphonylmethyl compound 
of general formula (I), the oxidation is preferably carried out with one 
or with two equivalents of the oxidation agent used, for example hydrogen 
peroxide in glacial acetic acid, trifluoroacetic acid or in formic acid, 
at 20.degree. to 100.degree. C. or in acetone at 0.degree. to 60.degree. 
C., with a per acid, such as performic acid or m-chloroperbenzoic acid, in 
glacial acetic acid, trifluoroacetic acid, methylene chloride or 
chloroform at 0.degree. to 60.degree. C., with nitric acid in glacial 
acetic acid at 0.degree. to 20.degree. C., with chromic acid or potassium 
permanganate in glacial acetic acid, water/sulphuric acid or in acetone at 
0.degree. to 20.degree. C. 
(c) For the preparation of compounds of general formula (I), in which 
R.sub.4 is a radical of general formula (II) and R.sub.5 is an 
alkanesulphonyloxy, trifluoromethanesulphonyloxy, alkanesulphonylamino, 
N-alkyl-alkanesulphonylamino, trifluoromethanesulphonylamino or 
N-alkyl-trifluoromethanesulphonylamino radical, by the subsequent reaction 
of a compound of the general formula: 
##STR9## 
wherein R.sub.1, R.sub.2, R.sub.3, R.sub.6, R.sub.7 and X have the same 
meanings as above and R".sub.5 is a hydroxyl or amino group or an 
N-alkylamino radical with up to 3 carbon atoms in the alkyl moiety, with a 
sulphonic acid of the general formula: 
EQU R.sub.8 --SO.sub.2 OH (XIV) 
wherein R.sub.8 is an alkyl radical containing up to 3 carbon atoms or a 
trifluoromethyl radical, in the presence of a water-removing agent and/or 
a reagent activating the acid or the amine or with reactive derivatives 
thereof. 
The reaction is preferably carried out in a solvent or solvent mixture, 
such as methylene chloride, diethyl ether, tetrahydrofuran, dioxan or 
benzene, optionally in the presence of an acid-binding agent, such as 
sodium carbonate, triethylamine or pyridine, whereby the latter two can 
simultaneously serve as solvent, in the presence of an acid-activating or 
water-removing agent, such as thionyl chloride or phosphorus 
pentachloride, but preferably with a reactive derivative of a compound of 
general formula (XIV), for example with an anhydride or halide thereof, 
for example methanesulphonic acid chloride or ethanesulphonic acid 
chloride, preferably at a temperature of from 0.degree. to 100.degree. C., 
for example at a temperature of from ambient temperature to 50.degree. C. 
(d) For the preparation of compounds of general formula (I), in which 
R.sub.4 is a radical of general formula (II) and R.sub.2 and/or R.sub.3 is 
a carbonyl or sulphonyl group substituted by an amino, alkylamino, 
dialkylamino or hydrazino group, by the subsequent reaction of a compound 
of the general formula: 
##STR10## 
in which R.sub.1, R.sub.3, R.sub.6 R.sub.7 and X have the above-given 
meanings and R'.sub.2 and/or R'".sub.5 is a carboxyl or hydroxylsulphonyl 
group, or a reactive derivative thereof, for example an ester or acid 
chloride, with hydrazine or an amine of the general formula: 
EQU R.sub.9 --NH--R.sub.10 (XVI) 
wherein R.sub.9 and R.sub.10 can be the same or different and are hydrogen 
atoms or alkyl radicals containing up to 5 carbon atoms, or with a 
reactive derivative thereof if R'.sub.2 and/or R"'.sub.5 represents a 
carboxyl or hydroxylsulphonyl group. 
The reaction is preferably carried out in a solvent or solvent mixture, 
such as methylene chloride, ethanol, chloroform, carbon tetrachloride, 
diethyl ether, tetrahydrofuran, dioxan, benzene, toluene, acetonitrile or 
dimethylformamide, optionally in the presence of an agent activating the 
acid or removing water, for example in the presence of ethyl 
chloroformate, thionyl chloride, phosphorus trichloride, phosphorus 
pentoxide, N,N'-dicyclohexylcarbodiimide/N-hydroxysuccinimide, 
N,N'-carbonyldiimidazole or N,N'-thionyldiimidazole or 
triphenylphosphine/carbon tetrachloride, or of an agent activating the 
hydrazino or amino group, for example phosphorus trichloride, and 
optionally in the presence of an inorganic base, such as sodium carbonate, 
or of a tertiary organic base, such as triethylamine or pyridine, which 
can simultaneously serve as a solvent, at a temperature of from 
-25.degree. to +250.degree. C. but preferably at a temperature of from 
-10.degree. C. to the boiling point of the solvent used. Furthermore, 
water formed during the reaction can be separated off by azeotropic 
distillation, for example by heating with toluene on a water separator, or 
by the addition of a drying agent, such as anhydrous magnesium sulphate or 
of a molecular sieve. 
However, the reaction is carried out especially advantageously in an 
appropriate halide, for example the carboxylic acid sulphonic acid 
chloride, and hydrazine or an appropriate amine, whereby these can 
simultaneously sere as solvent, at a temperature of from 0.degree. to 
50.degree. C. 
(e) For the preparation of compounds of general formula (I), in which 
R.sub.3 is a cyano group, by the subsequent reaction of a compound of 
general formula (I), in which R.sub.1, R.sub.2, R.sub.4 and X have the 
above-given meanings and R.sub.3 is a hydrogen atom, with 
N-carbonylsulphamoyl chloride, which can also be called chlorosulphonyl 
isocyanate, in an appropriate solvent according to known processes (Chem. 
Ber., 100, 2719/1967; Synthesis, 1978, 374 and J. Chem. Soc., Perkin I, 
1978, 1117). 
The reaction is preferably carried out in a solvent which is inert under 
the reaction conditions, for example water, methanol, ethanol, n-butanol, 
dioxan, acetonitrile, nitromethane, pyridine, dimethylformamide or 
methylene chloride, optionally in the presence of an acid-binding agent. 
The reactions are carried out with ice cooling, at ambient temperature or 
with warming, optionally under a protective gas atmosphere. 
(f) For the preparation of compounds of general formula (I), in which 
R.sub.3 and R.sub.4 are carboxyl, alkoxycarbonyl or aminocarbonyl groups 
or R.sub.4 is a radical of general formula (II), R.sub.5 being a carboxyl, 
alkoxycarbonyl, aminocarbonyl, alkoxycarbonylalkoxy or carboxyalkoxy 
radical, by subsequent alcoholysis and/or hydrolysis of compounds of 
general formula (I), in which R.sub.3 and R.sub.4 are a cyano group or 
R.sub.4 is a radical of general formula (II), R.sub.5 being a cyano or 
cyanoalkoxy group. 
The subsequent alcoholysis and/or hydrolysis is preferably carried out 
either in the presence of an acid, such as hydrochloric acid, sulphuric 
acid, phosphoric acid or trichloroacetic acid, or in the presence of a 
base, such as sodium hydroxide or potassium hydroxide, in an appropriate 
solvent, such as water, water/methanol, ethanol, water/ethanol, 
water/isopropanol or water/dioxane, at a temperature of from -10.degree. 
to +120.degree. C., for example at a temperature between ambient 
temperature and the boiling point of the reaction mixture. 
(g) For the preparation of compounds of general formula (I), in which X is 
a sulphur atom, by the subsequent introduction of the sulphur atom into 
compounds of general formula (I), in which R.sub.1, R.sub.2, R.sub.3 and 
R.sub.4 have the above-given meanings and X is an oxygen atom. 
The reaction is carried out with reagents known from the literature which 
transfer the sulphur atom, for example with phosphorus pentasulphide, it 
being preferable to use 1 to 5 moles but more preferably 1 mold of 
phosphorus pentasulphide in an appropriate solvent. The solvent can be, 
for example, tetrahydrofuran, dioxan, benzene, toluene or pyridine, the 
reaction temperature being from 25.degree. to 125.degree. C. 
However, it is preferred to use pyridine with a reaction period of from 1 
to 10 hours and preferably of 5 hours, depending upon the reaction 
components. 
Furthermore, the compounds obtained of general formula (I) can, if desired, 
be subsequently converted into their physiologically acceptable 
acid-addition salts with organic and inorganic acids. As acids for this 
purpose, there can be used, for example, hydrochloric acid, hydrobromic 
acid, sulphuric acid, phosphoric acid, fumaric acid, succinic acid, 
tartaric acid, citric acid, lactic acid, maleic acid or methanesulphonic 
acid. 
As already mentioned hereinbefore, the new compounds of general formula(I), 
the tautomers thereof and the physiologically acceptable acid-addition 
salts thereof possess, with a long period of action, superior 
pharmacological properties, especially a blood pressure lowering and/or 
positive inotropic action and/or influence the thrombocyte function and 
improve the microcirculation. 
For the preparation of pharmaceutical compositions, the compounds of 
general formula (I) are mixed in known manner with appropriate 
pharmaceutical carrier substances and formed, for example, into tablets or 
dragees or, with the addition of appropriate adjuvants, are suspended or 
dissolved in water or an oil, for example olive oil. 
The new compounds according to the present invention of general formula (I) 
and the salts thereof can be administered enterally or parenterally in 
liquid or solid form. As injection medium it is preferred to use water 
which contains the additives usual in the case of injection solutions, 
such as stabilising agents, solubilising agents or buffers. 
Additives of this type include, for example, tartrate and citrate buffers, 
ethanol, complex formers (such as ethylenediamine-tetraacetic acid and the 
nontoxic salts thereof) and high molecular weight polymers (such as liquid 
polyethylene oxide) for viscosity regulation. Solid carrier materials 
include, for example, starch, lactose, mannitol, methyl cellulose, talc, 
highly dispersed silicic acids, high molecular weight fatty acids (such as 
stearic acid), gelatine, agar-agar, calcium phosphate, magnesium stearate, 
animal and vegetable fats and solid high molecular weight polymers (such 
as polyethylene glycols). Compositions suitable for oral administration 
can, if desired, contain flavouring and sweetening agents. 
The compounds according to the present invention are usually administered 
in amounts of from 10 to 500 mg. per day, referred to a body weight of 75 
kg. It is preferred to administer 1 to 2 tablets with an active material 
content of 5 to 200 mg. two or three times a day. The tablets can also be 
retarded in which case only 1 or 2 tablets with 10 to 500 mg. of active 
material have to be given once per day. The active material can also be 
administered by injection 1 to 8 times a day or by continuous infusion, in 
which case amounts of 5 to 200 mg./day normally suffice. 
Preferred compounds according to the present invention, apart from the 
compounds described in the Examples, include the following and the 
tautomers thereof: 
3,3-dimethyl-6-(pyrrol-2-yl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 7H)-one 
3,3-dimethyl-6-(thiazol-4-yl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 
7H)-one 
3,3-dimethyl-6-(1,2,4-triazol-3-yl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 
7H)-one 
3,3-dimethyl-6-(5-carboxy-1,2,3-triazol-4-yl)-benzo[1,2-b:5,4-b']dipyrrol(1 
H, 3H, 7H)-one 
3,3-dimethyl-6-(5-methylthio-1,3,4-oxadiazol-2-yl)-benzo[1,2-b:5,4-b']dipyr 
rol-2-(1H, 3H, 7H)-one 
3,3-dimethyl-6-(1,2,5-thiadiazol-3-yl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1H, 
3H, 7H)-one 
3,3-dimethyl-6-(pyrimidin-5-yl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 
7H)-one 
3,3-dimethyl-6-(pyrazin-2-yl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 
7H)-one 
3,3-dimethyl-6-(N-oxy-4-pyridyl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 
7H)-one 
3,3-dimethyl-6-(4-nitrophenyl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 
7H)-one 
3,3-dimethyl-6-(4-methylthiophenyl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 
7H)-one 
3,3-dimethyl-6-(4-amino-phenyl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 
7H)-one 
3,3-dimethyl-6-(4-methylsulphenyl-2-methoxyphenyl)-benzo[1,2-b:5,4-b']dipyr 
rol-2-(1H, 3H, 7H)-one 
3,3-dimethyl-6-(4-methylsulphinyl-2-methoxyphenyl)-benzo[1,2-b:5,4-b']dipyr 
rol-2-(1H, 3H, 7H)-one 
3,3-dimethyl-6-(4-methylsulphonyl-2-methoxyphenyl)-benzo[1,2-b:5,4']dipyrro 
l-2-(1H, 3H, 7H)-one 
3,3-dimethyl-6-(4-methylsulphonyloxy-2-methoxyphenyl)-benzo[1,2-b:5,4-b']di 
pyrrol-2-(1H, 3H, 7H)-one 
3,3,5,6-tetramethylbenzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 7H)-one 
3,3,5-trimethylbenzo[12-b:5,4-b']dipyrrol-2-(1H, 3H, 7H)-one 
3,3,6-trimethyl-5-cyanobenzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 7H)-one 
3,3,6-trimethyl-5-aminocarbonylbenzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 
7H)-one 
3,3,6-trimethyl-5-ethoxycarbonylbenzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 
7H)-one 
3,3-dimethyl-6-trifluoromethylbenzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 
7H)-one 
3,3-dimethyl-6-(cyclohexen-1-yl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 
7H)-one 
3,3-dimethyl-6-cyclopropylbenzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 7H)-one 
3,3-dimethyl-6-cyanobenzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 7H)-one 
3,3-dimethyl-6-acetylbenzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 7H)-one 
3,3-dimethyl-5,6-diphenylbenzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 7H)-one 
3,3-dimethyl-6-(3,4,5-trimethoxyphenyl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1H, 
3H, 7H)-one 
3,3-diethyl-6-(4-dimethylaminophenyl)-benzo-1,2-b:5,4-b']dipyrrol-2-(1H, 
3H, 7H)-one 
3,3-diethyl-6-(2-hydroxy-5-pyrimidinyl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1H, 
3H, 7H)-one 
3,3-diethyl-6-(4-pyrimidinyl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 
7H)-one 
3,3-diethyl-6-(3-hydroxy-6-pyridazinyl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1H, 
3H, 7H)-one 
6'-(2-methyl-4-oxazolyl)-spiro[cyclopentan-2,3'-benzo[1',2'-b:5',4'-b]dipyr 
rol]-2'-(1H', 3'H, 7'H)-one 
6'-(2-chloro-4-pyridyl)-spiro[cyclopentan-1,3'-benzo[1',2'-b:5',4'-b']dipyr 
rol]-2'-(1'H, 3'H, 7'H)-one 
6'-(2-methyl-4-pyridyl)-spiro[cyclopentan-1,3'-benzo[1',2'-b:5',4'-b']dipyr 
rol]-2'-(1'H, 3'H, 7'H)-one 
3-isopropyliden-6-(2-pyridyl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 
7H)-one 
3-methyl-3-ethoxycarbonyl-5-methyl-6-phenylbenzo[1,2-b:5,4-b']dipyrrol-2-(1 
H, 3H, 7H)-one 
3-methyl-3-ethoxycarbonyl-6-(4-trifluoromethylsulphonyl-2-methoxyphenl)-ben 
zo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 7H)-one 
2-methoxyphenyl)-benzo[1,2-b:5,4-b']dpyrrol-2-(1H, 3H, 7H)-one 
3-methyl-3-ethoxycarbonyl-6-(4-morpholinylsulphonyl-2-methoxyphenyl)-benzo[ 
1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 7H)-one 
3-methyl-6-(2-furanyl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 7H)-one 
3-methyl-6-(imidazol-4-yl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 7H)-one 
3-methyl-6-(2,4-dimethoxyphenyl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 
7H)-one 
3-methyl-6-(2-methoxy-4-aminosulphonylphenyl)-benzo[1,2-b:5,4-b']dipyrrol-2 
-(1H, 3H, 7H)-one 
3-methyl-6-(2-methoxy-4-methylsulphonylaminophenyl)-benzo[1,2-b:5,4-b']dipy 
rrol-2-(1H, 3H, 7H)-one 
3-methyl-6-(2-methoxy-4-methylsulphenymethylphenyl)-benzo[1,2-b:5,4-b']dipy 
rrol-2-(1H, 3H, 7H)-one 
3-methyl-6-(2-methoxy-4-methylsulphinylmethylphenyl)-benzo[1,2-b:5,4-b']dip 
yrrol-2-(1H, 3H, 7H)-one 
3-methyl-6-(2-methoxy-4-methylsulphonylmethylphenyl)-benzo[1,2-b:5,4-b']dip 
yrrol-2-(1H, 3H, 7H)-one 
3-ethyl-6-(2-methoxy-4-cyanomethyloxyphenyl)-benzo[1,2-b:5,4-b']dipyrrol-2- 
(1H, 3H, 7H)-one 
3-ethyl-6-(2-methoxy-4-propargyloxyphenyl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1 
H, 3H, 7H)-one 
3-ethyl-6-(4-pyridyl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 7H)-one 
7-cyclopentyl-6-(4-pyridyl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 7H)-one 
3,3,5-trimethylbenzo[1,2-b:5,4-b']dipyrrol-2,6-(1H, 3H, 5H, 7H)-dione.

The following Examples are given for the purpose of illustrating the 
present invention: 
EXAMPLE 1 
3,3-Dimethyl-6-(4-pyridyl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 7H)-one 
(a) 6.8 g. (38 mmole) 6-amino-3,3-dimethylindolin-2-one are dissolved in 
125 ml. 50% sulphuric acid and 2.8 g. (40.6 mmole) sodium nitrite, 
dissolved in 25 ml. water, added dropwise thereto at a temperature below 
5.degree. C. After 15 minutes, 0.5 g. urea is added thereto and stirring 
continued for 15 minutes. 26.35 g. (116.8 mmole) Stannous chloride 
dihydrate, dissolved in 20 ml. concentrated hydrochloric acid, are added 
dropwise thereto at 5.degree. C. After 2 hours, the solution is mixed with 
6.9 g. (57 mmole) 4-acetylpyridine, stirred for 2 hours at 25.degree. C., 
the residue is filtered off with suction, suspended in water, neutralised 
with aqueous ammonia solution and filtered off with suction. There are 
obtained 8.5 g. (76% are theory) 
4-acetylpyridine(3,3-dimethyl-2-oxoindoline-6-hydrazone); m.p. 
272.degree.-274.degree. C. 
(b) 8.3 g. (28.2 mmole) of the hydrazone thus obtained are stirred with 50 
ml. polyphosphoric acid under an atmosphere of nitrogen for 6 hours at an 
oil bath temperature of 110.degree.-120.degree. C. The cooled reaction 
mixture is worked up with ice water and the suspension is neutralised with 
concentrated aqueous ammonia solution and filtered off with suction. The 
residue is recrystallised from methanol/methylene chloride. There are 
obtained 5.18 g. (66% of theory) of the title compound; m.p. &gt;300.degree. 
C. 
The following compounds are obtained analogously to Example 1: 
______________________________________ 
yield m.p. .degree.C. 
designation (%) (solvent) 
______________________________________ 
Example 1.1 
3,3-dimethyl-6-(3-pyridyl)-benzo- 
24 305 
[1,2-b:5,4-b']dipyrrol-2-(1H,3H, 
methanol 
7H)-one .times. 1 mole methanol from 
3-acetylpyridin-(3,3-dimethyl-2- 
oxoindolin-6-hydrazone) as 
crude product 
Example 1.2 
3,3-dimethyl-6-(pyridazin-4-yl)- 
33 330 
benzo[1,2-b:5,4-b']dipyrrol-2- 
methanol 
(1H,3H,7H)-one .times. 1 mole methanol 
from 
4-acetyl-pyridazin-(3,3-dimethyl- 
2-oxoindolin-6-hydrazone); m.p. 
240.degree. C. 
Example 1.3 
3,3-dimethyl-6-[4-(1H--imidazol- 
23 &gt;340 
1-yl)-phenyl]-benzo[1,2-b: 
5,4-b']dipyrrol-2-(1H,3H,7H)- methanol 
one from 
4-(1H--imidazol-1-yl)-aceto- 
phenone-(3,3-dimethyl-2-oxo- 
indolin-6-hydrazone) as crude 
product 
Example 1.4 
3-methyl-6-(4-pyridyl)-benzo- 
7.5 &gt;330 
[1,2-b:5,4-b']dipyrrol-2-(1H, methanol 
3H,7H)-one from 
4-acetylpyridin-(3-methyl-2- 
oxoindolin-6-hydrazone); 
m.p. 267-270.degree. C. 
Example 1.5 
3-methyl-6-(3-pyridyl)-benzo- 
14 330-31 
[1,2-b:5,4-b']dipyrrol-2-(1H, 
3H,7H)-one from 
3-acetylpyridine-(3-methyl-2- 
oxoindoline-6-hydrazone) as 
crude product 
______________________________________ 
EXAMPLE 2 
3,3-Dimethyl-6-(4-cyanophenyl)-benzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 
7H)-one.times.1.5 dichloromethane. 
The title compound is obtained analogously to Example 1 from 4.4 g. (13.8 
mmole) 4-cyanoacetophenone(3,3-dimethyl2-2-oxoindoline-6-hydrazone) (m.p. 
242.degree. C.). The purification of the 3.7 g. of crude product obtained 
is carried out by column chromatography over silica gel (elution agent: 
methylene chloride/methanol 95:5 v/v). Yield 0.25 g. (6% of theory); m.p. 
&gt;310.degree. C. 
The following compounds are obtained analogously to Example 2: 
______________________________________ 
yield m.p. .degree.C. 
designation (%) (solvent) 
______________________________________ 
Example 2.1 
3,3,6-trimethylbenzo[1,2-b: 
12.5 255 
5,4-b']dipyrrol-2-(1H,3H,7H)- 
methanol 
one from 
acetone-(3,3-dimethyl-2-oxo- 
indoline-6-hydrazone); m.p. 
150.degree. C. 
Example 2.2 
3,3,5-trimethyl-6-(4-pyridyl)- 
17.9 &gt;300 
benzo[1,2-b:5,4-b']dipyrrol-2- 
methanol 
(1H,3H,7H)-one from 
4-propionylpyridine-(3,3- 
dimethyl-2-oxoindoline-6- 
hydrazone); m.p. &gt; 300.degree. C. 
______________________________________ 
EXAMPLE 3 
3,3-Dimethyl-6-(2-thienyl)-benzo[1,2-b:5,4-b']-dipyrrol-2-(1H, 3H, 7H)-one 
Analogously to Example 1, 6.8 g. (38 mmole) 
6-amino-3,3-dimethylindolin-2-one are diazotised and reduced. Into the 
solution are added dropwise 10.9 g. (85 mmole) 2-acetylthiophene and the 
oil which separates out is taken up in methylene chloride, dried and 
evaporated. As crude product, there are obtained 11.2 g. 
2-acetylthiophene-(3,3-dimethyl-2-oxoindoline-6-hydrazone) which is 
further reacted without purification. 
11 g. of the residue are treated with 50 g. polyphosphoric acid analogously 
to Example 1. Purification takes place by column chromatography (elution 
agent: methylene chloride/ethyl acetate 5:1 v/v). Yield 0.6 g. (5.6% of 
theory); m.p. 265.degree.-270.degree. C., after recrystallisation from 
ethanol. 
EXAMPLE 4 
3,3-Dimethyl-6-phenylbenzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 
7H)-one.times.0.5 mole water.times.0.14 mole ethyl acetate 
3.06 g. (17.4 mmole) 6-Amino-3,3-dimethylindoline-2-one are diazotised and 
reduced analogously to Example 1. Into the solution is added dropwise 0.6 
g. (5 mmole) acetophenone and the reaction mixture further stirred for 3 
hours at 25.degree. C. The oil which separates out is separated off, 
worked up with water and subsequently boiled with heptane. The crude 
product obtained, acetophenone-(3,3-dimethyl-2-oxoindoline-6-hydrazone), 
is, without further purification, cyclised according to Example 1 and 
purified according to Example 2 over silica gel (elution agent: ethyl 
acetate). There is obtained 0.16 g. (11.6% of theory, referred to the 
amount of acetophenone used) of the title compound; m.p. 
270.degree.-273.degree. C. 
The following compounds are obtained in a manner analogously to that 
described in Example 4; 
______________________________________ 
yield 
designation (%) m.p. .degree.C. 
______________________________________ 
Examp1e 4.1 
3,3-dimethyl-6-(4-methoxy- 
3 273-276 
phenyl)-benzo[1,2-b:5,4-b']- 
dipyrrol-2-(1H,3H,7H)-one .times. 
0.75 mole water from 
4-methoxyacetophenone-(3,3- 
dimethyl-2-oxoindoline-6- 
hydrazone) 
Example 4.2 
3,3-dimethyl-6-(4-methyl- 
8.6 278-281 
phenyl)-benzo[1,2-b:5,4-b']- 
dipyrrol-2-(1H,3H,7H)-one .times. 
0.5 mole water .times. 0.17 mole 
ethyl acetate from 
4-methylacetophenone-(3,3- 
dimethyl-2-oxoindoline-6- 
hydrazone) 
Example 4.3 
3,3-dimethyl-6-(4-chlorophenyl)- 
5.2 261-263 
benzo[1,2-b:5,4-b']dipyrrol-2- 
(1H,3H,7H)-one .times. 1.5 mole water 
.times. 0.2 mole ethyl acetate from 
4-chloroacetophenon-(3,3- 
dimethyl-2-oxoindoline-6- 
hydrazone 
Example 4.4 
3,3-dimethyl-6-(2-hydroxyphenyl)- 
0.3 250-255 
benzo[1,2-b:5,4-b']dipyrrol-2- 
(1H,3H,7H)-one from 
2-hydroxyacetophenone-(3,3- 
dimethyl-2-oxoindoline-6- 
hydrazone 
______________________________________ 
EXAMPLE 5 
3,3-Diethyl-6-ethoxycarbonylbenzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 7H)-one 
6 g. (34 mmole) 6-amino-3,3-dimethylindolin-2-one are dissolved in 160 ml. 
2N hydrochloric acid and 2.51 g. (36.4 mmole) sodium nitrite, dissolved in 
20 ml. water, added dropwise thereto at a temperature below 0.degree. C. 
After 15 minutes, at the same temperature, 23.59 g. (104 mmole) stannous 
chloride dihydrate, dissolved in 70 ml. 2N hydrochloric acid, are added 
dropwise thereto. After 30 minutes, the solution is mixed at 0.degree. C. 
with 5.58 g. (48 mmole) ethyl pyruvate and further stirred for 3 hours at 
25.degree. C. The residue obtained is filtered off with suction, again 
suspended in water and neutralised with aqueous ammonia solution and 
filtered off with suction. There are obtained, as crude product, 11.2 g. 
ethyl pyruvate-(3,3-dimethyl2-oxoindoline-6-hydrazone) (m.p. 
284.degree.-290.degree. C.) which is further reacted without purification. 
11.3 g. of the above crude product are cyclised in polyphosphoric acid 
analogously to Example 1. Purification is carried out by column 
chromatography on silica gel (elution agent: methylene chloride/ethanol 
95:5 v/v). Yield 0.45 g. (referred to the amount of amine used); m.p. 
313.degree.-315.degree. C. after recrystallisation from ethanol. 
EXAMPLE 6 
3,3-Dimethyl-6-carboxybenzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 
7H)-one.times.1 mole ethanol 
0.5 g (1.8 mmole) of the ester obtained in Example 5 is stirred in 5 ml. 2N 
aqueous sodium hydroxide solution and 2.5 ml. ethanol for 1 hour at 
60.degree. C. The ethanol is subsequently distilled off and the remaining 
solution is treated with charcoal and acidified with 2N hydrochloric acid. 
The residue is recrystallised from ethanol/methylene chloride. Yield: 82%; 
m.p. 304.degree. C. 
EXAMPLE 7 
3,3-Dimethyl-6-aminocarbonylbenzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 
7H)-one.times.0.3 mole ethanol 
1.6 g. (6.55 mmole) of the carboxylic acid obtained in Example 6 are 
stirred for 3 hours with 16 ml. thionyl chloride at 60.degree. C. Excess 
thionyl chloride is subsequently distilled off and the residue is mixed, 
while cooling, with 20 ml. concentrated aqueous ammonia solution. After 24 
hours at 25.degree. C., the precipitate is filtered off with suction and 
recrystallised from ethanol. Yield 0.18 g. (11% of theory); m.p. 
294.degree.-296.degree. C. 
EXAMPLE 8 
3,3-Dimethylbenzo[1,2-b:6,5,4-b']dipyrrol-2,6-(1H, 3H, 5H, 
7H)-dione.times.0.5 mole isopropanol.times.0.75 mole water 
(a) 5.0 g. (27 mmole) 6-aminooxoindole (Helv. Chim. Acta, 20, 373/1937) are 
suspended in 80 ml. dichloromethane, mixed with 6.45 g. (63 mmole) 
triethylamine and 6.8 g (29 mmole) .alpha.-bromoisobutyric acid bromide 
added dropwise thereto at 5.degree. C. After stirring for 3 hours at 
25.degree. C., the solvent is distilled off and the residue is worked up 
with water and filtered off with suction. There are obtained 4.2 g. (52.4% 
of theory) .alpha.-bromo-N-(2-oxoindolin-6-yl)-isobutyric acid amide; m.p. 
211.degree.-212.degree. C. 
(b) 3.2 g. (10.8 mmole) of the above amide are well mixed with 7.1 g. 
aluminium trichloride and heated for 5 hours, while stirring, to 
160.degree. C. The cooled residue is worked up with water and a little 2N 
hydrochloric acid and filtered off with suction. The precipitate is 
purified over silica gel (elution agent: methylene chloride/methanol 96:4 
v/v). Yield 0.27 g. (11.7% of theory); m.p. 280.degree.-282.degree. C., 
after recrystallisation from isopropanol. 
EXAMPLE 9 
6'-(4-Pyridyl)-spiro(cyclopentane-1,3'-benzo[1',2'-b:5',4'-b']dipyrrol)-2'- 
(1'H, 3'H, 7'H)-one 
4 g. (20 mmole) 6'-aminospiro(cyclopentan-1,3'-indoline)-2'-one are 
introduced into 50 ml. concentrated hydrochloric acid, cooled to 0.degree. 
C. and 1.5 g. (21.5 mmole) sodium nitrite, dissolved in 5 ml. water, added 
dropwise thereto. After 15 minutes, 13.5 g. (60 mmole) stannous chloride, 
dissolved in 10 ml. concentrated hydrochloric acid, are added dropwise 
thereto at 0.degree. C. After 2 hours at 25.degree. C., 2.2 g. (18 mmole) 
4-acetylpyridine are added thereto and the precipitate is filtered off 
with suction after 3 hours and washed with a little water. As crude 
product, there are obtained 6.7 g. 
4-acetylpyridine-(2'-oxospiro(cyclopentane-1,3'-indoline)-6'-hydrazone 
hydrochloride, which is further reacted without purification. 
6.7 g. of the crude product are slowly introduced, while stirring, into 70 
ml. polyphosphoric acid at 120.degree. C. After 2 hours at this 
temperature, the reaction mixture is poured on to ice, neutralised with 
aqueous ammonia solution and filtered off with suction. Purification takes 
place by column chromatography (elution agent: methylene chloride/methanol 
saturated with ammonia 20:1 v/v). Yield 0.7 g. (11.5% of theory, referred 
to the amount of amine used); m.p. 326.degree.-329.degree. C., after 
recrystallisation from ethanol. 
EXAMPLE 10 
3,3,6-Trimethyl-5-phenylbenzo[1,2-b:5,4-b']dipyrrol-2-(1H, 3H, 7H)-one. 
Analogously to Example 5, 4 g. (22.7 mmole) 
6-amino-3,3-dimethylindolin-2-one are diazotised and reduced. 
Subsequently, 3 g. (22.3 mole) phenylacetone are added thereto and the 
reaction mixture further stirred for 18 hours at 25.degree. C. The oil 
which separates out is shaken out several times with methylene chloride, 
evaporated and the residue worked up with cyclohexane and filtered off 
with suction. The solid residue is again dissolved in methylene chloride, 
washed twice with aqueous sodium hydrogen carbonate solution and once with 
water, dried with anhydrous sodium sulphate with the addition of charcoal 
and crystallised from methylene chloride. Yield 1.25 g. (19% of theory); 
m.p. 233.degree.-235.degree. C. 
Pharmaceutical Activity 
Male Sprague-Dawley rats weighing between 350 and 450 g were narcotized by 
intraperitoneal injection of a barbiturate and fitted with instrumentation 
for the examinations as follows: 
A pressure measuring catheter (Miller Mikrotip.TM./diameter 0.5 mm) was 
inserted through the arteria carotis dextra into the left ventricle. The 
pressure inside the left ventricle was continually registered through this 
catheter. The signal from this Mikrotip was electronically differentiated 
and (dp/dt).sub.60 --the slope of the pressure-time curve at a pressure of 
60 mmHg--was taken as a measure for the inotropy. 
A polypropylene catheter was bound in a vena jugularis for the intravenous 
injection of the test substances. 
A further polypropylene catheter was inserted through an arteria femoralis 
into the abdominal aorta for the direct measurement of the arterial blood 
pressure. 
The ECG was traced with subcutaneous insertion electrodes. 
During the preparation of the animal and during the entire test period the 
rate were fixed on an electrically heated and thermostated operating 
table. 
Procedure 
The test substances were always introduced by intravenous injection, with 
an injection volume, per injection, of 1 ml/kg body weight. In intervals 
of 10 min each, doses increasing from 0.01 to 30 mg of the test substances 
were intravenously injected. In this way dose effect curves for the 
measured parameters for the investigated substances were obtained. From 
the measured data, using a regression calculation, equipotent doses for 
the positively inotropic effect .DELTA. (dp/dt).sub.60 were calculated. In 
addition, as criterion for the effectiveness of the substances, the 
maximum effect obtained maximal increase of (dp/dt).sub.60 and its 
corresponding dose were determined. The table that follows shows the 
equipotent doses (DE.sub.1,5 =the dose in mg/kg that leads to an increase 
of (dp/dt).sub.60 of 1.5 mHg/sec) and the maximal effectiveness (W.sub.max 
=the maximal increase of (dp/dt).sub.60. 
______________________________________ 
Substance 
ED.sub.1,5 mHg/sec 
W.sub.max 
from Exp. 
[mg/kg i.v.] [mHg/sec] [mg/kg i.v.] 
______________________________________ 
1. 0,16 3,4 3,0 
1.1 -- &gt;1,0 &gt;3,0 
1.2 -- &gt;1,4 &gt;3,0 
1.3 -- 0,6 0,3 
1.4 -- &gt;0,3 &gt;3,0 
2.1 -- &gt;0,8 &gt;3,0 
3. *i.d. tested + 1,5 
4. *i.d. tested + 0,9 
8. 0,1 2,0 0,3 
______________________________________ 
*intraduodenal dosage of 50 mg/kg. 
It will be understood that the specification and examples are illustrative 
but not limitative of the present invention and that other embodiments 
within the spirit and scope of the invention will suggest themselves to 
those skilled in the art.