Farmitalia Carlo Erba S.p.a.

Farmitalia Carlo Erba

Societa' Farmaceutici Italia S.p.a.

Aldemio Temperilli

Sergio Mantegani

Luigi Bernardi

Patricia Salvati

Gabriella Traquandi

Enzo Brambilla

Laura Chiodini

Mauro Gobbini

Alessandro Rossi

Daniela Ruggieri

Germano Bosisio

Giuliana Arcari

Patrizia Ferrari

Enrico Di Salle

Lorenzo Pegrassi

Anna M Caravaggi

Maria A Cervini

Alfredo Glasser

Osvaldo Sapini

Daniel Ruggieri

Rosanna Eccel

Maurizio Foglio

Roberto Maj

t-alkyl eroline derivatives of formula I are produced ##STR1## wherein (R.sub.1 =H, OCH.sub.3 and R.sub.2 H) or (R.sub.1 +R.sub.2 =a ring bond and R.sub.3 =H, optionally substituted nicotinynoyl or 1-oxo-2-cyclopenten-3-yl); and their pharmaceutically acceptable salts. A process for the preparation of these derivatives from lysergol and a t-alkyl alcohol is also described, as are pharmaceutical compositions containing them.

t-alkyl ergoline derivatives

##STR1## Compounds I [R.sub.1 =H or C.sub.1 -C.sub.3 alkyl, R.sub.2 =an (alkyl-substituted) aminodeoxy or aminodideoxy or aminotrideoxy sugar residue of the D and L series, the glycosidic linkage being .alpha. or .beta.] and their pharmaceutically acceptable salts are useful as antihypertensive agents. Their preparation and use as well as pharmaceutical compositions containing them are also described.

Aminoglycoside steroids, a process for their preparation, their use and

##STR1## Compounds I (either R.sub.1 =OH, C.sub.1 -C.sub.4 alkoxy and R.sub.2 =H, C.sub.1 -C.sub.4 alkyl, or R.sub.1 +R.sub.2 =a chemical bond; R.sub.3 =an aminodeoxy or aminodideoxy or aminotrideoxy sugar residue of the D and L series, the glycosidic linkage being .alpha. or .beta.: and either R.sub.4 =OH and R.sub.5 =H or R.sub.4 +R.sub.5 =a chemical bond) and their pharmaceutically acceptable salts are useful as antihypertensive agents. Their preparation and use as well as pharmaceutical compositions containing them are also described.

Nor-cholanic acid derivatives, a process for their preparation, their

##STR1## Compounds I (either R.sub.1 =OH, C.sub.1 -C.sub.4 alkoxy and R.sub.2 =H, C.sub.1 -C.sub.4 alkyl, or R.sub.1 +R.sub.2 =a chemical bond; R.sub.3 =an aminodeoxy or aminodideoxy or aminotrideoxy sugar residue of the D and L series, the glycosidic linkage being .alpha. or .beta.) and their pharmaceutically acceptable salts are useful as antihypertensive agents. Their preparation and use as well as pharmaceutical compositions containing them are also described.

Pharmaceutical compounds of the formula ##STR1## wherein R is H or CH.sub.3, R.sub.1 is H or OCH.sub.3, R.sub.2 is a C.sub.1 -C.sub.4 hydrocarbon group and X is an organic group. Also disclosed is a process for the preparation of these compounds. The compounds have dopamine agonist or antagonist activity.

D-nor-7-ergoline derivatives having anti-Parkinson and antipsychosis

An ergoline derivative of the formula I: ##STR1## wherein R.sub.1 represents hydrogen or a methyl group; R.sub.2 represents hydrogen or a halogen atom, a methyl, cyano or phenyl group or an alkylthio group having from 1 to about 4 carbon atoms; R.sub.3 represents a hydrocarbon group having from 1 to about 4 carbon atoms; R.sub.4 represents hydrogen, a phenyl group or a hydrocarbon group having from 1 to about 4 carbon atoms; wherein either (a) R.sub.6 and R.sub.7 represent a valence bond or hydrogen atoms and R.sub.8 represents a hydrogen atom or a methoxy group, or (b) R.sub.6 represents a hydrogen atom and R.sub.7 and R.sub.8 taken together represent a valence bond; W represents an oxygen atom or an imino group; A represents a group of the formula CHR.sub.5, CH.dbd.CR.sub.5 or CH.sub.2 CHR.sub.5 wherein R.sub.5 represents a hydrogen atom or an alkyl group having from 1 to about 4 carbon atoms; X represents an oxygen or sulphur atom or an imino group; and n is 0, 1 or 2; or a pharmaceutically acceptable salt thereof.

N-oxide ergolines as antihypertensive agents

t-Alkyl ergoline derivatives of formula I are produced ##STR1## wherein (R.sub.1 =H, OCH.sub.3 and R.sub.2 =H) or (R.sub.1 +R.sub.2 =a ring bond and R.sub.3 =H, optionally substituted nicotinoyl or 1-oxo-2-cyclopenten-3-yl); and their pharmaceutically acceptable salts. A process for the preparation of these derivatives from lysergol and a t-alkyl alcohol is also described, as are pharmaceutical compositions containing them.

1-t-butyl ergolines useful in the treatment of cerebral insufficiency

Ergoline derivatives of the formula I ##STR1## wherein R.sub.1 represents a hydrogen atom or a methyl group; R.sub.2 represents a hydrogen atom or a methoxy group;

Ergolinyl heterocycles for the treatment of Parkinson's disease and

Compounds of the formula I: ##STR1## wherein R.sub.1 =H, CH.sub.3 ; m=0,1; R.sub.2 =R.sub.3 =H or R.sub.2, R.sub.3 =bond, R.sub.4 =C.sub.1 -C.sub.4 hydrocarbon, n=1 or 2 and their pharmaceutically acceptable salts are antihypertensive agents. Their preparation and pharmaceutical compositions containing them are also described.

Tetracyclic indole derivatives for treating hypertension

Ergoline Esters having the formula (I) ##STR1## in which R.sub.1 =H or CH.sub.3 ; R.sub.2 =C.sub.1 -C.sub.4 hydrocarbon; R.sub.3 =H or OCH.sub.3 ; R.sub.4 =H or halogen; R.sub.5 =C.sub.1 -C.sub.4 alkyl and their pharmaceutically acceptable salts are active at the central nervous system level. A process for their preparation is described.

Ergoline esters

Ergoline derivatives of the formula I ##STR1## wherein R.sub.1 =H,CH.sub.3 ; R.sub.2 =H, halogen, CH.sub.3, CN, C.sub.1 -C.sub.4 alkylthio or phenylthio; R.sub.3 =C.sub.1 -C.sub.4 hydrocarbon; R.sub.4 =H, OCH.sub.3 ; R.sub.5 =H and R.sub.6 =--CH.dbd.CH--CONHR.sub.7 or R.sub.5 and R.sub.6 =.dbd.CH--CONHR.sub.7 ; R.sub.7 =2-thiazolyl, 3-pyridazinyl, 1,3,4-thiadiazol-2-yl or 4-pyrimidinyl group optionally substituted, and pharmaceutically acceptable salts thereof, display activity on the Central Nervous System and are useful as antiprolactinic agents. Their preparation and pharmaceutical compositions containing them are also described.

Ergoline compounds useful as antiparkinson agents

The invention relates to ergoline derivatives having the general formula (I): ##STR1## where R=H, CH.sub.3 ; R.sub.1 =H, halogen, CH.sub.3, phenylthio, C.sub.1 -C.sub.4 alkylthio; R.sub.2 =H, CH.sub.3 O, and R.sub.3 =H or R.sub.2 +R.sub.3 =chemical bond; R.sub.4 =C.sub.1 -C.sub.4 hydrocarbon; R.sub.5, R.sub.6, R.sub.8, R.sub.9 independently=H, C.sub.1 -C.sub.4 alkyl, or R.sub.5, R.sub.8 independently=H, C.sub.1 -C.sub.4 alkyl and R.sub.6 +R.sub.9 =CH.sub.2 CH.sub.2, CH.sub.2 CH.sub.2 CH.sub.2 ; R.sub.7 =H, C.sub.1 -C.sub.4 alkyl, phenyl, NR'R'; R',R' independently=H, C.sub.1 -C.sub.4 alkyl, acyl or NR'R'=heterocyclic ring; W=0, H.sub.2 ; n=0, 1, 2, and their pharmaceutically acceptable salts, these compounds exhibiting antihypertensive activity making them useful anxiolytic and antipsychotic agents. A process for their preparation and pharmaceutical compositions containing them are also described.

3-oxo-piperazin-1-yl-ergolines exhibiting antidopaminergic activity

Compounds of formula I: ##STR1## wherein R.sub.1 represents a hydrogen atom or a methyl group; R.sub.2 represents a hydrogen or halogen atom or a methyl, cyano, C.sub.1 -C.sub.4 alkylthio or phenylthio group; R.sub.7 and R.sub.8 represent hydrogen atoms and R.sub.3 represents a hydrogen atom or a methoxy group, or R.sub.7 represents a hydrogen atom and R.sub.3 and R.sub.8 taken together represent a bond, or R.sub.3 represents a hydrogen atom or a methoxy group and R.sub.7 and R.sub.8 taken together represent a bond; R.sub.4 represents a hydrocarbon group having from 1 to 4 carbon atoms; R.sub.5 represents a hydrogen atom or a hydrocarbon group having from 1 to 4 carbon atoms or a phenyl group; X represents an oxygen or sulphur atom or an imino group, R.sub.9 represents a hydrogen atom and B represents a cyano, a C.sub.2 -C.sub.5 alkoxycarbonyl or carbamoyl group, or R.sub.9 and B taken together represent a ##STR2## group wherein W represents an oxygen atom or an imino group; A represents a group of the formula CHR.sub.6, CH.sub.2 --CHR.sub.6 or CH.dbd.CR.sub.6 group wherein R.sub.6 represents a hydrogen atom or a C.sub.1 -C.sub.4 alkyl group; and n is 0, 1 or 2; and their pharmaceutically acceptable salts are disclosed, along with the use of these compounds as antiprolactinic and antihypertensive agents. The preparation of these compounds and pharmaceutical compositions containing them are also described.

Ergolines exhibiting protactin secretion inhibition activity

Ergoline derivatives of formula: ##STR1## wherein n=0,1,2; R.sub.1 =H, CH.sub.3 ; R.sub.2 =H, CH.sub.3, halogen; R.sub.3 =H, OCH.sub.3 ; R.sub.4 =hydrocarbon group and R.sub.5 is a residue of general formula II, III, IV, V, VI, VII: ##STR2## wherein R.sub.6 =H, Cl, OCH.sub.3, NR.sub.11 R.sub.12, wherein R.sub.11 and R.sub.12 =H, lower alkyl; phenyl or are bonded together to form a heterocyclic ring, R.sub.7, R.sub.8 and R.sub.9 and R.sub.10 =H or C.sub.1 -C.sub.3 alkyl, with the proviso that if R.sub.5 is of formula II and R.sub.2 =R.sub.7 =R.sub.8 =H, then R.sub.4 is not methyl or n is not 0. Pharmaceutically acceptable acid addition salts are also provided. A method for their preparation is also provided. The compounds have anti-depressive, anti-hypertensive and antiprolactin activity.

8-pyridazinylcarbamoyl ergolines

There are provided ergoline compounds of the formula: ##STR1## wherein R.sub.1 is a hydrogen atom or a methyl group; R.sub.2 is a hydrogen or halogen atom, a methyl or thiomethyl group; R.sub.3 is a hydrogen atom or a methoxy group; R.sub.4 is a hydrocarbon group having from 1 to 4 carbon atoms; n is 1 or 2; each of R.sub.5 and R.sub.6 independently is a hydrogen atom, an alkyl group having from 1 to 3 carbon atoms, or a phenyl or hydroxy or alkoxy group having from 1 to 4 carbon atoms, and X is an oxygen atom or a group of the formula NR.sub.7 wherein R.sub.7 is selected from the group consisting of a hydrogen atom, an alkyl having from 1 to 4 carbon atoms and a phenyl group, or a group of the formula N.dbd.C--R.sub.8 wherein the carbon atom is positioned between the nitrogen atoms in the ring and R.sub.8 is an amino, substituted amino, methyl, phenyl, thiomethyl or mercapto group. The compounds have antihypertensive and antiprolactin activity.

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Milan, Italy

Aldemio Temperilli