Farmitalia Carlo Erba S.r.l.

Farmitalia Carlo Erba S.p.a.

Pharmacia & Upjohn S.p.a.

Farmitalia Carlo Erba

Carlo Erba S.p.a.

Pharmacia Italia S.p.a.

Pharmacia S.p.a.

Ettore Perrone

Marco Alpegiani

Giovanni Franceschi

Angelo Bedeschi

Pierluigi Bissolino

Franco Zarini

Giuseppe Cassinelli

Maurizio Foglio

Giuliano Nannini

Piergiuseppe Orezzi

Giuseppe Meinardi

Daniela Jabes

Carlo Confalonieri

Gisella Monti

Alberta Bianchi

Dino Severino

Angelo Forgione

Costantino D Bruna

Paolo Carminati

Francesca Abrate

Riccardo Corigli

Costantino Della Bruna

Walter Cabri

Sergio Mantegani

Stephen Hanessian

Enrico Pesenti

Marcello Marchi

Paolo Cremonesi

Giuseppe Mazzini

Matteo D'Anello

Giovanni Francheschi

Maria Francesca Abrate

Franco Giudici

Ferruccio Casabuona

Constantino Della Bruna

Silvio Grasso

Francesco Di Matteo

Massimiliano Palladino

Vincenzo Rizzo

Marina Lombroso

Giuseppina Visentin

Compounds which are 3-arylsulfonyl-2-methyl propanoic acid derivatives of formula (I): wherein X is HO&mdash;NH&mdash; or HO&mdash;, R1 is selected from phenyl, 4-chlorophenyl, 4-florophenyl, 4-cyanophenyl, benzamido (i.e., &mdash;NH&mdash;CO-Ph) and benzamido substituted on the terminal phenyl ring by C -C alkyl, fluoro, chloro, cyano or C alkoxy; R is selected from (a) &mdash;S&mdash;Ar or &mdash;S&mdash;CH &mdash;Ar wherein Ar is an aromatic moiety; (b) &mdash;O&mdash;Ar wherein Ar is as defined above; (c) &mdash;S-Het or &mdash;S&mdash;CH -Het wherein Het is a heterocyclic ring; and (d) 2,5-dioxo-1-imidazolidinyl or 2,4-dioxo-1-imidazolinyl; and the pharmaceutically acceptable salts thereof; have potent and selective inhibitory activity against matrix metalloproteinases (MMPs) and can thus be used in the treatment and prevention of diseases mediated by MMPs.

3-Arylsulfonyl-2 (substituted methyl) propanoic acid derivatives as matrix metalloproteinase inhibitors

A compound, which is an amine derivative of formula (I) wherein W is &mdash;CNHOH or &mdash;COOH: R and R are each hydrogen or an organic residue, R is an organic group, Q is a secondary or tertiary acyclic or cyclic amido group, and the pharmaceutically acceptable salts, solvates and hydrates thereof, are inhibitors of matrix metalloproteinases (MMPs) and of the release of tumor necrosis factor-alpha (TNF) from cells. They are therefore useful in the prevention, control and treatment of diseases in which MMPs or TNF are involved, especially tumoral and inflammatory diseases. Processes for their preparation and pharmaceutical compositions containing them are also described.

Matrix metalloproteinase inhibitors

Cephem derivatives as anti-metastatic agents

2-acyloxycephem derivatives

Tricyclic cefem sulphones

Penem derivatives

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

Process for preparing penem esters

There are provided compounds I ##STR1## wherein A is a hydrogen atom or an organic group,

1,1-dioxo-cephem-4-carbothiolic acid derivatives

.beta.-lactam derivatives of the cephem sulphone type

There is provided a process for preparing a compound of the formula (I): ##STR1## wherein R.sub.1 is an organic residue, R.sub.2 is a hydrogen or a chlorine atom, a methoxy, ethoxy or an acetoxy group, and n represents 0, 1 or 2. The process comprises reacting a compound of the formula (II): ##STR2## wherein R.sub.2 and n are as defined above, with an inorganic or organic nitrite, in an alcohol R.sub.1 OH, wherein R.sub.1 is as defined above, or in a mixture R.sub.1 OH-organic solvent in the presence of an inorganic or organic acid. The compounds of the formula (I) are known intermediates in the synthesis of human leucocyte elastase inhibitors (HLE).

Process for the preparation of 7 alpha-alkoxycephem derivatives

Compounds of the formula I ##STR1## wherein R' is a free or esterified carboxy group or a carboxylate anion and R.sup.2 is an organic group have beta-lactamase inhibition activity. A process for the preparation of the same and pharmaceutical compositions containing these compounds are provided.

Inhibition of .beta.lactamase with 6 .beta.-(substituted

6-substituted penem esters of formula (I): ##STR1## wherein R.sub.1 is halogen or a C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, phenyl, phenoxy, benzyl or sulphonyloxy group; R.sub.2 is a C.sub.1 -C.sub.4 alkyl, benzyl diphenylmethyl ##STR2## group where A is C.sub.1 -C.sub.4 alkyl, benzyl, p-nitrobenzyl or p-methoxybenzyl; and R.sub.3 is an organic radical, are elastase inhibitors and thereby useful antiinflammatory and antidegenerative agents.

6-substituted penem esters as anti-inflammatory and anti-degenerative

Compounds of formulae Ia and Ib ##STR1## wherein A is hydrogen atom or an organic residue, R.sup.1 is halogen atom, or an organic group, R.sup.2 is hydrogen or halogen atom, C.sub.1 -C.sub.4 alkyl or alkoxy group, R.sup.3 is hydrogen atom, C.sub.1 -C.sub.4 alkyl or alkoxy group, benzyl or a methylene group and R.sub.4 is an organic residue are disclosed. Compounds (Ia) and (Ib) are endowed with elastase inhibitory activity. A two-step process for their preparation starting from the corresponding 4-carboxy cephem or 3-carboxy penam is also provided.

Beta-lactam derivatives of the 4-acylcephem sulphone and 3-acylpenam

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Boffalora Ticino, Italy

Ettore Perrone