Richter Gedeon Vegyeszeti Gyar Rt

Gyorgy Kalaus

Csaba Szantay

Lajos Szabo

Laszlo Szporny

Egon Karpati

Tibor Keve

Lajos Dancsi

Janos Sapi

Janos Kreidl

Ferenc Drexler

Andras Nemes

Maria Farkas Nee Kirjak

Laszlo Czibula

Gyorgy Visky

Bela Kiss

Eva Palosi

Elemer Ezer

Bela Stefko

Arpad Kiraly

Lilla Forgach

Maria Zajer Nee Balazs

Judit M Meszaros Nee Brill

Bela Rosdy

Gyongyver Kiraly Nee Soos

Gyorgy Hajos

Erzsebet Lapis

Istvan Laszlovszky

Janos Galambos

Zsolt Szombathelyi

Katalin Csomor

Aniko Gere

Katalin Nogradi

Lilla Forgacs

Tibor Acs

Istvan Hegedus

Csaba Kuthi

Ida Deutsch Nee Juhasz

Zsuzsanna Aracs Nee Tischler

Bela Benke

Lajor Szabo

Maria Gazdac

Krisztina Mihalyfi

Laszlo Cibula

Maria Farkas Nee Kirlyak

Lajos Szbao

Mari Zajer Nee Balazs

Ferenc Vezekenyi

Lajos Szaho

Zsuzsanna Gyulai

Kalman Graf

Katalin Horvath Nee Berki

Kalmam Gaf

New intermediate compounds are disclosed of the formula I, ##STR1## wherein R.sub.1 and R.sub.2 are independently alkyl having 1 to 4 carbon atoms, or acid-addition salts thereof of formula Ib, ##STR2## wherein X represents an acid residue, and a process for the preparation of the intermediate compounds.

Racemic and optically active octahydro-indolo(2,3-a) tetrahydropyranyl

The invention relates to the new (-)-1.beta.-ethyl-1.alpha.-hydroxymethyl-1,2, 3,4,6,7,12,12b.alpha.-octa-hydroindolo[2,3-a] quinolizine of the formula (I) ##STR1## and acid addition salts thereof. According to another aspect of the invention there is provided a process for the preparation of the compound of formula (I) and acid addition salts thereof by resolution of the corresponding racemic compound and optionally by subsequent hydrolysis and/or salt formation. The compound of formula (I) shows a remarkable peripheral vasodilating and antihypoxial activity. Pharmaceutical compositions comprising it as active ingredient are also within the scope of the invention.

(-)-1.beta.-ethyl-1.alpha.-hydroxymethyl-1,2,3,4,6,7,12,

The invention relates to new eburnane derivatives of the formula (I) ##STR1## wherein R.sup.1 is alkyl having from 1 to 6 carbon atoms, and acid addition salts thereof. The invention further relates to a process for the preparation of these compounds and pharmaceutical compositions containing them. Compounds of formula (I) show remarkable CNS-activity and are useful intermediates in the preparation of other, pharmaceutically active compounds.

Eburnane derivatives, process for their preparation and pharmaceutical

The invention relates to racemic or optically active eburnane derivatives of the formula (I), ##STR1## wherein R represents an alkyl group having 1 to 6 carbon atoms,

The invention relates to optically active or racemic eburnane-oxime ethers of the formulae (Ia) and/or ##STR1## wherein R represents an alkyl group having 1 or 2 carbon atoms,

Eburnane oxime ethers

The invention relates to racemic or optically active E-homo-eburnane derivatives of the formula /I/, ##STR1## wherein R.sup.1 and R.sup.2 independently represent an alkyl group having 1 to 6 carbon atoms,

E-Homo-eburnane derivatives, process for their preparation, and

A process is disclosed for the preparation of racemic cis or trans apovincaminic acid esters of the formula (I) ##STR1## and the corresponding optically active derivatives of the formulae (Ia) ##STR2## wherein R.sup.1 and R.sup.2 are identical or different alkyl groups having 1 to 6 carbon atoms. Apovincaminic acid alkyl esters are well-known vasodilating compounds.

Apovincaminic acid esters

The invention relates to a new process for the preparation of eburnamonine derivatives of the general Formula I ##STR1## (wherein R.sup.1 is an alkyl group having 1-6 carbon atoms) and optical and geometrical isomers thereof which comprises reacting a hydroxyimino-octahydro-indolo[2,3-a]quinolizine derivative of the general Formula II ##STR2## (wherein R.sup.1 is as stated above and R.sup.2 stands for an alkyl group having 1-6 carbon atoms being identical with or different from R.sup.1, or a hydrogen atom) or an acid addition salt thereof in an organic protic solvent or solvent mixture with an inorganic base, optionally under the addition of water or an aqueous mineral acid, at a temperature between 60.degree. C. and 200.degree. C. The compounds of the present invention are known drugs having blood pressure decreasing and cerebral vasodilatatory effect. The advantage of the process of the present invention is that it is readily feasible on industrial scale too, provides isomer-free pure products with high yield and requires the use of readily available simple starting materials.

Process for the preparation of eburnamonine derivatives

The invention relates to a new process for the preparation of apovincaminic acid esters. More particularly, the invention concerns a process for preparing racemic and optionally active vincaminic acid esters of the formula (I) ##STR1## in which R.sup.1 and R.sup.2 independently stand for alkyl having from one to 6 carbon atoms, and 14-epimers thereof. According to the invention an octahydroindolo[2,3-a]quinolizine-oxime ester of the formula (II) ##STR2## in which R.sup.1 and R.sup.2 have the same meaning as defined above, is reacted with an aqueous solution of sulfurous acid or a salt thereof at a temperature of 80.degree. to 110.degree. C. and the 14-epimeric mixture obtained is epimerized or separated in a known manner and if desired, the racemic vincaminic acid esters are resolved. The valuable, pharmaceutically active compounds of the formula (I) can be prepared according to the invention in a considerably improved yield and the undesired side reactions can be suppressed and/or the by-products can easily be converted into other pharmaceutically active materials.

Process for the preparation of vincaminic acid esters

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 new polycyclic compounds substituted on the A-ring. More particularly, the invention concerns new polycyclic compounds of the formula (I) ##STR1## wherein R.sup.1 is methoxy or halogen and

Polycyclic compounds substituted on the A-ring, pharmaceutical

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

The invention relates to the new apovincaminol-3',4',5'-trimethoxy-benzoate and acid addition salts thereof. The new compound may be prepared by reacting apovincaminol or an acid addition salt thereof with 3,4,5-trimethoxy benzoic acid or a reactive derivative thereof capable of acylation and if desired converting the compound thus obtained into an acid addition salt. The new compound of the present invention can be used in therapy in the treatment of skin diseases attached to pathological cell proliferation and in the propylaxis of such diseases.

Apovincaminol derivative and compositions and methods utilizing it for

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Budapest, Hungary

Gyorgy Kalaus