Farmitalia Carlo Erba S.r.l.

Pharmacia & Upjohn

Farmitalia Carlo Erba

Pharmacia Corporation

Societa' Farmaceutici Italia

Franco Zarini

Angelo Bedeschi

Ilaria Candiani

Walter Cabri

Giovanni Franceschi

Marco Alpegiani

Ettore Perrone

Sergio Penco

Costantino D Bruna

Federico Maria Arcamone

Maurizio Foglio

Laura Capolongo

Giorgio Palamidessi

Costantino Della Bruna

Carlo Battistini

Aurora Sanfilippo

Daniela Jabes

Giuseppe Mazzini

Giuseppina Visentin

Giovanna Schioppacassi

Constantino Della Bruna

Process for the preparation of 9-amino camptothecin

9,10 disubstituted camptothecin derivatives with antitumor activity

Hexacyclic camptothecin analogues, and process for preparing them

The present invention relates to compounds of the following formulas: ##STR1## which are endowed with antitumor activity. The invention also relates to methods of treating tumors using these compounds.

Substituted camptothecin derivatives and process for their preparation

Method for the preparation of 9-amino camptothecin

The present invention relates to new camptothecin derivatives which display antitumor activity. The present invention also provides processes for their preparation as well as pharmaceutical compositions containing the same.

Camptothecin derivatives and process for their preparation

A process for preparing 9-amino camptothecin comprising the steps of: (1) reacting a compound of formula (III) ##STR1## wherein the hydroxy group on ring A is in the 10- or 12-position, with a nitrating agent, to form the corresponding 9-nitro compound; (2) converting the 9-nitro compound into a corresponding compound of formula (V) ##STR2## wherein XO is a group that can be removed reductively; and (3) reductively removing the XO group and reducing the nitro group of the compound of formula (V), to form the 9-amino camptothecin, a known antitumor compound. The present invention also includes compound having the above formula (V) and their 9-amino analogs, which have antitumor activity.

The present invention relates to new camptothecin derivatives of the formula (I) ##STR1## wherein B is a group B' or B' ##STR2## wherein each of (x) and (y) is a single or double bond. The present invention also provides processes for their preparation as well as pharmaceutical compositions containing the same.

Penem derivatives

The present invention relates the removal of t-butyldimethylsilyl protecting groups in the preparation of penems which are useful antibiotics. The invention provides a process for preparing a compound of the formula I: ##STR1## wherein R is a free or protected hydroxy or amino group or an alkoxy, acyloxy or an optionally substituted carbamoyloxy group, and R.sub.1 is selected from:

Hydroxy protecting group removal in penems

Antibacterial penems of formula (I), where R represents a hydrogen atom or a hydroxy protecting group, are prepared by reacting a .beta.-lactam of formula (II) with an oxalyl halide in an inert solvent in the presence of an organic or inorganic base or an acid scavenger to produce a compound of formula (III), wherein X is a halogen atom, treating the resultant compound of formula (III) with a 1,3-dioxolen-2-one of formula (IV), wherein Y is a hydroxy group, in the presence of molecular sieves or an organic or inorganic base to produce a compound of formula (V), and cyclizing the compound of formula (V) in the presence of a trialkylphosphite to provide the penems of formula (I).

Process for penems

There is provided a process for preparing a compound of formula (I) ##STR1## wherein R is H or a hydroxy protecting group, R.sub.2 is an organic residue and R.sub.3 is H or a nitrogen protecting group, which process comprises reacting together a compound of formula (II) ##STR2## wherein R.sub.1 is a C.sub.1 -C.sub.4 alkyl or a phenyl group, R and R.sub.3 are as defined above, a compound of formula (III) ##STR3## wherein R.sub.2 is as defined above and X is a cation or a silicon-containing residue, and a salt of a group IIa, IIb or transition element. The compounds of formula (I) are intermediates in the synthesis of penem antibiotics.

(1'R,3S,4R)4-acylthio azetidinones

The invention provides a process for the preparation of ergoline derivatives of the formula I ##STR1## the process comprising reacting an ergoline amide of the formula II with an isocyanate of formula III ##STR2## in presence of a metal catalyst and of a phosphorus compound. The compounds of the formula I are useful antiprolactinic and antiparkinson agents.

Process for the preparation of ergoline derivatives

A substantially (.gtoreq.95%) optically pure (5R,6S,1'R) penem of formula ##STR1## and the pharmaceutically acceptable salts and the ester prodrugs thereof, are endowed with antibacterial activity.

Methoxymethyl penem compounds

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Settimo Milanese, Italy

Franco Zarini