Richter Gedeon Vegyeszeti Gyar Rt

Karola Jovanovics

Kalman Szasz

Csaba Lorincz

Eszter Dezseri

Laszlo Nemeth

Emil Bittner

Zsuzsa Relle

Bela Kellner

Lajos Dancsi

Csaba Szantay

Lajos Szabo

Sandor Gorog

Bela Szarvady

Eszter Deszeri

Laszlo Szporny

Eva Palosi

Egon Karpati

Gyorgy Fekete

Lajos Kovacs

Katalin Nogradi

Sandor Eckhardt

Janos Sugar

Katalin Honty

Gyorgy Dobo

Maria Bolyos

Aron Szollosy

Jozsef Tamas

Zsuzsa Relle Nee Somfai

A process for the preparation of diindole-alkaloids, especially new compounds corresponding to vinblastine or leurosine, in which the N-methyl group is replaced by an N--CH.sub.2 --O--R group wherein R is lower alkyl, having antitumor properties. The starting materials are subjected to oxidation by chromic acid or an alkali metal dichromate at temperatures from -90.degree. C. to -30.degree. C. and preferably below -45.degree. C. where the new compounds are to be produced, a lower alkanol being present in this case.

Process for the preparation of bis-indole alkaloids and acid-addition

A process for the preparation of diindolealkaloids, especially new compounds corresponding to vinblastine or leurosine, in which the N-methyl group is replaced by an N--CH.sub.2 --OC.sub.2 H.sub.5 group having antitumor properties. The starting compounds are subjected to oxidation by chromic acid or an alkali metal dichromate at temperatures from -90.degree. C. to -30.degree. C. but preferably below about -45.degree. C. when the new compounds are to be produced, ethanol being present in this case.

Bis-indole-alkaloid

N-formylleurosine or a pharmaceutically effective salt is used in human therapy for treatment of lymphoma, leukemia or Hodgkins Disease.

Method of treatment using new leurosine derivatives

Multiple myeloma in human patients is treated by administering N-formylleurosine or its sulfate salt.

New leurosine derivatives of the general formula (1), ##STR1## wherein R stands for hydrogen or formyl, or pharmaceutically acceptable acid addition salts thereof were prepared by oxidizing leurosine or an acid addition salt thereof, optionally formylating the thus-obtained product and then separating, and, if desired, converting any of the free bases into its acid addition salt.

N-Formyl leurosine derivatives in a dosage form effective for treating

A mixture of minor diindole alkaloids from Vinca-containing vinblastine and 4-deacetoxy-vinblastine vines, are separated by subjecting the mixture to a deacetylation to correct the vinblastine to deacetyl-vinblastine prior to chromatographic separation of said mixture in a single stage.

Process for separating pharmaceutically active diindole alkaloids

A process for the preparation of alkaloids of the leurosine type having the formula I ##STR1## and the acid addition salts thereof. In the formula I R is hydrogen or methyl. The compounds prepared according to the invention are known compounds showing cytostatic activity.

Process for the preparation of alkaloids of the leurosine type

Leurosine derivatives of the formula (I), ##STR1## wherein R is hydrogen or formyl, or pharmaceutically acceptable acid addition salts thereof were prepared by oxidizing leurosine or an acid addition salt thereof, optionally formylating the thus-obtained product and then separating, and, if desired, converting any of the free bases into its acid addition salt. The new compounds of the invention possess strong cytostatic activity, and can be used in the human therapy with great advantage.

N-formyl and N-desmethyl leurosine derivatives

Tumor inhibiting alkaloids are recovered from Vinca Rosea L. by a method which comprises extracting the dried leaves with a solvent selected from the group consisting of an alkanol having 1 to 5 carbon atoms, a mixture of an alkanol having 1 to 5 carbon atoms and a dilute, aqueous solution, benzene and benzene homologs; subsequently purifying the alkaloid extract obtained by a phase-change method between immiscible solvents, precipitating the main amount of dimeric alkaloids in form of their sulphuric acid addition salts, isolating leurosine, vincistine, vinblastine, desacetoxy-vinblastine, N-desmethyl-vinblastine and desacetyl-vinblastine from the salt mixture obtained, and then completing the separation and isolation of the remaining alkaloids by separation and isolation by adjusting the pH-value of the mother liquor, after precipitation and removal of the salt mixture, to 5.5 to 10, extracting the solution with a water-immiscible organic solvent and separating vindoline, catharantine, 3',4' -anhydrovinblastine and leurosine from the extract by chromatography, extracting vindoline in the pH-range of 2.5 to 3.5 and catharantine 3',4'-anhydrovinblastine and leurosine in the pH-range of 5 to 6 with benzene or a benzene homologue, from the mother liquor obtained when isolating the salt mixture, and separating a mixture of leurosine and 3',4'-anhydrovinblastine by crystallization, epoxidizing this mixture with an oxygen source, or separating the mixture into its components by chromatography, and subsequently epoxidizing the 3',4'-anhydrovinblastine component to leurosine, and isolating catharantine remaining from the mother liquor obtained when separating the crystalline mixture, or separating the extract containing catharantine, 3',4'-anhydrovinblastine and leurosine into its components by chromatography.

Process for the isolation of alkaloid components from the plant Vinca

A process is disclosed for the separation and recovery of vinblastine and leurosine from a mixture of diindole alkaloids obtained by extraction of the plant, Vinca rosea L.

Process for the preparation of diindole alkaloids or of the acid

A heart and vasotropic pharmaceutical of the formula: ##STR1## wherein R represents a hydrogen atom or an acyl group, preferably a C.sub.1-15 alkylcarbonyl, C.sub.2-6 alkenylcarbonyl, or a phenyl- (C.sub.1-5)-alkylcarbonyl group or a benzoyl group optionally substituted with halogen, trihalomethyl, C.sub.1-4 or nitro And pharmaceutically acceptable acid addition and quaternary salts thereof.

Growing community of inventors

Budapest, Hungary

Karola Jovanovics