Richter Gedeon Vegyeszeti Gyar Rt

Lajos Dancsi

Csaba Szantay

Lajos Szabo

Tibor Keve

Gyorgy Kalaus

Ferenc Drexler

Laszlo Szporny

Egon Karpati

Eszter Dezseri

Gyorgy Fekete

Karola Jovanovics

Csaba Lorincz

Sandor Eckhardt

Janos Sugar

Katalin Honty

Sandor Gorog

Janos Sapi

Tibor Acs

Sandor Kerpel-Fronius

Bela Szarvady

Ivan Hindi

Janos Galambos

Kalman Szasz

Lajos Kovacs

Katalin Nogradi

Tibor Cs

Gyorgy Dobo

Krisztina Mihalyfi

Zsuzsanna Relle Nee Somfa

Lajos Szbao

Ferenc Vezekenyi

Zsuzsa Relle Nee Somfai

Jozsef Tamas

Aron Szollosy

Maria Gazdac

Gyoorgy Kalaus

Zsuzsanna Relle Nee Somfai

The invention relates to new cytostatic compound, process for their preparation and pharmaceutical compositions containing them. More particularly, there are provided new compounds of the general formula ##STR1## in which R.sup.4 is .beta.-hydroxyl and

N-Desmethyl-N-(allyloxymethyl)-vinblastine and antileukemic and

New salts of the formula XIIIa and XIIIb are disclosed ##STR1## wherein R.sup.2, R.sup.3 and R.sup.5 are each C.sub.1 to C.sub.6 alkyl and A.sup.- is an anion of a pharmaceutically acceptable acid. Furthermore new compounds of the formula XIVa and XIVb are disclosed: ##STR2## wherein R.sup.2 and R.sup.3 are as defined above. The new salts and compounds are intermediates in the preparation of 10-bromo-vincaminic acid esters. In addition the new salts and compounds have the ability to increase blood circulation and to decrease blood flow resistance in an animal subject while at the same time maintaining a steady pulse rate and blood pressure.

9-Bromo-hexahydro- and octahydro-indolo[2,3 a]quinolizines and use for

The invention relates to new hydroxyamino-eburnane derivatives of the general formula (I), ##STR1## wherein R.sup.1 and R.sup.2 each stand for a C.sub.1-6 alkyl group, as well as to pharmaceutically acceptable acid addition salts and optically active isomers of these compounds. These new compounds can be applied as peripheral vasodilatating agents or can be converted into other compounds, e.g. vincamine and apovincamine derivatives, of valuable therapeutical effects. The compounds of the general formula (I) are prepared according to the invention by reacting a hexahydro-indoloquinolisinium derivative of the general formula (II), ##STR2## wherein R.sup.2 is as defined above and X stands for an acid residue, with a methylenemalonic acid diester derivative of the general formula (III), ##STR3## wherein R.sup.1 is as defined above, subjecting the resulting product to catalytic hydrogenation, treating the resulting product with an alkali, and reacting the resulting octahydroindoloquinolisine monoester derivative with a nitrosating agent in an acidic medium.

Hexahydroindoloquinolizinium and octahydroindoloquinolizine esters, and

The invention relates to a new process for the preparation of alkoxyvincaminic acid esters of the formula (I) ##STR1## and/or alkoxyapovincaminic acid esters of the formula (II) ##STR2## wherein R.sup.1, R.sup.2 and R.sup.3 independently stand for alkyl groups having from one to 6 carbon atoms. The compounds of the formulae (I) and (II) are pharmaceutically active, thus some of them show psychostimulant activity.

1.alpha.-Ethyl-1.beta.-(2'-alkoxy

A novel process for preparing 10-bromo-vincaminic acid esters and homologous compounds of the general formula ##STR1## wherein R.sup.1 and R.sup.2 each stand for a C.sub.1-6 alkyl group is disclosed. All the intermediate products are new and exhibit valuable therapeutical effect on the blood circulation.

Cis-10-bromo-E-homoeburnanes

Process for preparation of cytostatic compounds

The invention concerns a new process for the preparation of apovincaminic acid ester derivatives of the general formula (I) ##STR1## wherein R.sup.1 and R.sup.2 independently represent an alkyl group having 1 to 6 carbon atoms,

Process for the preparation of apovincaminic acid ester derivatives

The invention relates to new halovincamone derivatives of the general formula (I), ##STR1## wherein R is a C.sub.1-6 alkyl group and X is halogen, and pharmaceutically acceptable acid addition salts and optically active isomers thereof. These compounds possess valuable vasodilating effect, and can be applied to advantage in the therapy. The new compounds defined above are prepared according to the invention so that a single epimer or an epimeric mixture of a racemic or optically active halogenated 14-oxo-15-hydroxy-E-homoeburnane derivative of the general formula (II), ##STR2## wherein R and X are as defined above, or an acid addition salt thereof is treated with an oxidizing agent, and, if desired, the resulting compound of the general formula (I) is converted into its pharmaceutically acceptable acid addition salt and/or resolved.

Process for the preparation of halovincamone derivatives

The invention relates to new hydroxyamino-eburnane derivatives of the general formula (I), ##STR1## wherein R.sup.1 and R.sup.2 each stand for a C.sub.1-6 alkyl group, as well as to pharmaceutically acceptable acid addition salts and optically active isomers of these compounds. These new compounds can be applied as peripheral vasodilatating agents or can be converted into other compounds, e.g. vincamine and apovincamine derivatives of valuable therapeutical effects. The compounds of the general formula (I) are prepared according to the invention by reacting a hexahydro-indoloquinolisinium derivative of the general formula (II), ##STR2## wherein R.sup.2 is as defined above and X stands for an acid residue, with a methylenemalonic acid diester derivative of the general formula (III), ##STR3## wherein R.sup.1 is as defined above, subjecting the resulting product to catalytic hydrogenation, treating the resulting product with an alkali, and reacting the resulting octahydroindoloquinolisine monoester derivative with a nitrosating agent in an acidic medium.

Process for the preparation of hydroxyamino-eburnane derivatives and

The invention relates to new, racemic or optically active, halogenated 15-hydroxy-E-homoeburnane derivatives of the formulae (Ia) and/or (Ib), ##STR1## wherein R is a C.sub.1-6 alkyl group and X is halogen, and acid addition salts thereof. These compounds are biologically active, furthermore they can be applied as intermediates in the synthesis of other pharmaceutically active substances.

Halogenated 15-hydroxy-E-homoeburane derivatives

The invention is directed to 1-alkyl-9-bromohexagydro indoloquinolizium salts and a method for their use to increase blood circulation and decrease in blood vessel resistance.

1-Alkyl-9-bromohexahydroindolo quinolizium salts and use thereof to

A process for the preparation of 15-hydroxyimino-E-homoeburnane derivatives of the formula (I), ##STR1## wherein X.sup.1 stands for hydrogen or halogen and

Process for the preparation of 15-hydroxyimino-E-homoeburnane and

The invention relates to new 10-halo-E-homoeburnane derivatives of the general formula (I), ##STR1## wherein R.sup.2 is a C.sub.1-6 alkyl group and X is halogen, and epimers, optically active derivatives and pharmaceutically acceptable acid addition salts thereof. These substances exert vasodilating effects and can be applied to advantage in the therapy. The new compounds are prepared so that a racemic or optically active 9-halo-octahydroindoloquinolisine derivative of the general formula (II), ##STR2## wherein R.sup.2 and X are as defined above and R.sup.1 is a C.sub.1-6 alkyl group, or an acid addition salt thereof is treated with a strong base, and, if desired, the 15-epimers of the resulting compound having the general formula (I) are separated from each other, and/or, if desired, the resulting substance is converted into its pharmaceutically acceptable acid addition salt and/or resolved.

10-halo-E-homoeburnane derivatives, a process for the preparation

The invention relates to new, racemic or optically active, halogenated 15-hydroxy-E-homoeburnane derivatives of the general formula (Ia) and/or (Ib), ##STR1## wherin R is a C.sub.1-6 alkyl group and X is halogen, and acid addition salts thereof. These compounds are biologically active, furthermore they can be applied as intermediates in the synthesis of other pharmaceutically active substances. The compounds of the general formulae (Ia) and (Ib) are prepared by halogenating the respective racemic or optically active 15-hydroxy-E-homoeburnane derivative of the general formula (II), wherein R is as defined above. ##STR2##

Process for the preparation of halogenated 15-hydroxy-E-homoeburnane

A novel process for preparing 11-bromo-vincaminic acid esters of the general formula ##STR1## wherein R.sup.1 and R.sup.2 each stand independently from each other for a C.sub.1-6 alkyl group, comprising the steps of treating a 1-alkyl-1-alkoxycarbonylethyl-octahydroindolo-quinolisine of the general formula ##STR2## wherein R.sup.2 is as defined above and R.sup.3 stands for a C.sub.1-6 alkyl group, with a brominating agent and treating the resulting isomeric mixture of the bromo-derivatives with an alkaline agent or treating the corresponding 14-oxo-E-homo-eburnane being unsubstituted in ring A with a brominating agent and nitrosating the resulting 11-bromo-14-oxo-E-homo-eburnane of the general formula ##STR3## wherein R.sup.2 is as defined above, then subjecting the resulting 11-bromo-14-oxo-15-hydroxyimino-E-homoeburnanes to deoxyimination and treating the 14,15-dioxo-derivatives obtained with a base in an alcohol of the general formula R.sup.1 OH, wherein R.sup.1 is as defined above. All the intermediate products are novel and exhibit a therapeutical protecting effect against cerebral hypoxy.

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Budapest, Hungary

Lajos Dancsi