Istituto Luso Farmaco D'italia

A. Menarini Industrie Farmaceutiche Riunite S.r.l.

Menarini Ricerche S.p.a.

A. Menarini Industrie Farmaceutiche Riunite

Enzo Perrotta

Maria Altamura

Federico Maria Arcamone

Carlo Alberto Maggi

Vittorio Pestellini

Danilo Giannotti

Giuseppe Cascio

Sandro Giuliani

Piero Sbraci

Basic monocyclic compounds having general formula (I) useful as NK-2 antagonists are described, processes for their preparation and pharmaceutical compositions containing them are also described.

Basic monocyclic compounds having Nk2 antagonist action, processes for their preparation, and formulations containing them

Process for the preparation of 2-halomethyl-penems (I) comprising (a) reacting an acetoxy-(protected hydroxyethyl)-2-azetidinone (III) with a 2-halothioacetic acid to form a 3-haloacetylthioazetidinone (V), (b) reacting (V) with oxalyl chloride to give an intermediate (VII), acylated on the beta-lactamic nitrogen, and (c) cyclizing (VII) in the presence of an organic phosphate or phosphonite to produce the corresponding 2-halomethyl-penem (I).

Process for the preparation of 2-halomethyl-penems and their use for the

Penem derivatives of general formula (I), below, and pharmaceutically acceptable salts thereof are disclosed. ##STR1## wherein: R.sub.1 is H, C.sub.1 -C.sub.6 alkoxy, C.sub.3 -C.sub.7 cycloalkyl, or an optionally protected C.sub.1 -C.sub.6 hydroxyalkyl; R.sub.2 is a free or esterified carboxyl group or a carboxylate anion; R.sub.3 is H or C.sub.1 -C.sub.6 alkyl; R.sub.4 is H, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 hydroxyalkyl, C.sub.1 -C.sub.6 mercaptoalkyl, C.sub.1 -C.sub.6 aminoalkyl, C.sub.1 -C.sub.6 alkyl substituted by a quaternary ammonium group, C.sub.1 -C.sub.6 carboxyalkyl, cycloalkyl, aryl, arylalkyl, heterocyclyl-alkyl optionally substituted, saturated or unsaturated heterocycle, or R.sub.3 and R.sub.4 are linked together to form a heterocyclic ring having 3-7 atoms; R.sub.5 and R.sub.6 independently are H, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 hydroxyalkyl, C.sub.1 -C.sub.6 mercaptoalkyl, C.sub. -C.sub.6 aminoalkyl, alkenyl, cycloalkyl, aryl, arylalkyl, alkylaryl, heterocyclyl-alkyl, C.sub.1 -C.sub.6 alkyl carboxyamide, or R.sub.5 and R.sub.6 are taken together to form a heterocyclic ring having 3-7 atoms, and n is an intiger from 1 to 3.

Penem derivatives, their preparation and pharmaceutical compositions

Growing community of inventors

Florence, Italy

Enzo Perrotta