Alfa Wassermann S.p.a.

Alfa Wasserman S.p.a.

Alfa Wassernann S.p.a.

Silvano Piani

Egidio Marchi

Gianfranco Tamagnone

Claudia Baldazzi

Maria R Milani

Fabrizio Ungarelli

Goffredo Rosini

Raul R Alpino

Aldo Roda

Maria Barbanti

Gianfranco Cainelli

Stefano Saguatti

Eleonora Romagnoli

Marinella Fantuz

The present invention refers to compounds having a benzopyranic structure of general formula I ##STR1## wherein R represents a hydrogen atom or an acyl group, useful as intermediates in the synthesis of vitamin E and of other compounds having benzopyranic structure endowed with properties inhibiting the formation of organic peroxides and therefore having antioxidizing activity, and to the process for their preparation.

3,4-Dihydro-2-iodomethyl-2,5,7,8-tetramethyl-2H-1-benzopyrans

An amide of formula ##STR1## and its pharmacologically acceptable organic or inorganic salt shows a metabolic stability, both enteric and hepatic, greater than that of the corresponding bile acids conjugated with glycine or taurine physiologically present in the enterohepatic circulation. The pharmacological activity of the compounds of formula I or their pharmacologically acceptable organic or inorganic salt makes the use effective for the therapy of biliary calculosis from cholesterol and in every pathology caused by cholestasis like chronic hepatitis from cholestasis, primitive biliary cirrhosis and juvenile hepatopathy associated with cystic fibrosis.

Bile acids derivatives useful in the therapy of the biliary calculosis

Lactones of formula ##STR1## and their pharmacologically acceptable salts endowed with antioxiding and hypolipidaemic properties and that show the capability to prevent and/or to delay the oxidative modification of the lipoproteins by competing with the chain of propagation of the lipidic peroxidation by means of an effective scavenging of the peroxylic radicals. The compounds object of the present invention are useful in the treatment of the atherosclerosis and of many correlated vascular pathologies, like ischaemic cardiopathies (angina pectoris and myocardial infarction), cerebral thrombosis and peripheral arteriopathies, because the high plasma levels of lipids and the oxidative modifications of the low density lipoproteins (LDL) represent crucial events in the pathogenesis of the atherosclerosis.

Lactones with antioxidising and hypolipidaemic activity useful in the

This invention refers to heterocyclic compounds of general formula ##STR1## and their pharmacologically accepted salts. The derivatives described in this invention are active in the gastro-intestinal apparatus; in particular, they have prokinetic effects, in other words they create specific stimulation on gastro-intestinal motility, facilitating the passage of the contents of the alimentary tract, and possess anti-emetic qualities, without side effects involving the central nervous system.

Heterocyclic compounds active in gastro-intestinal pathologies

New heparin and heparan sulfate derivatives having antithrombotic activity, also endowed with reduced haemorrhagic and anticoagulant activity, are obtained by nucleophilic addition to heparin and heparan sulfate derivatives containing 2,3-anhydrogulonic acid residues. The compounds have the formula IV ##STR1## The glycosaminoglycan derivatives obtained through this treatment show a structural modification in the unit of .alpha.-L-iduronic acid 2-O-sulfate with the partial or total selective substitution of the O-sulfate group in position 2 with a nucleophilic residue. The structural modifications produce an improvement of the biological properties of the heparin and heparan sulfate, substantially keeping the antithrombotic activity while diminishing the haemorragic effect in vivo and the anticoagulant activity in vitro.

Semi-synthetic glycosaminoglycans with heparin or heparan structure of

A process for the synthesis of glycosaminoglycans in which one of the .alpha.-L-iduronic-2-O-sulfate acid saccharide units, which is characteristic of glycosaminoglycans with heparin or heparan structure, has undergone a structural modification, entirely or in part, with transformation into .alpha.-L-galacturonic acid substituted in position 3 with nucleophilic groups, is described. The process is carried out by treating glycosaminoglycans having heparin or heparan structure with a nucleophilic reagent in alkaline solution.

Process for the synthesis of glycosaminoglycans containing

A process for the synthesis of glycosaminoglycans with heparin or heparan structure modified in position 2 of the .alpha.-L-iduronic-2-O-sulfate acid in which the sulfate group is, entirely or in part, substituted with a nucleophilic group, is described. The process is carried out by treating glycosaminoglycans having heparin or heparan structure with a nucleophilic reagent in alkaline solution.

Process for the synthesis of glycosaminoglycans with heparin or heparan

New heparinic derivatives having anticalculous activity, devoid of the anticoagulant and antithrombotic activity characteristic of the heparins, obtained by treating commercial or purified or low molecular weight heparins in a basic medium, optionally in the presence of alkali metal salts and of a reducing agent. The heparinic derivatives obtained through this treatment show significant chemical-physical characteristics, in particular they present a .sup.13 C-NMR spectrum different from that of the starting heparins especially in the zone between 102 and 92 p.p.m. with a characteristic signal at 101.3 p.p.m., a specific rotatory power at 546 nm between about +15.degree. and about +40.degree. in aqueous solution, a sulfur content between about 6% and about 9%, a sulfate/carboxyl ratio between about 1.20 and about 1.70 and a content of free amino groups between about 0.4% and about 2.1%. These heparin derivatives can be useful in the treatment of the nephrolithiases.

Heparin derivatives and process for their preparation

New heparin derivatives having antithrombotic activity, also endowed with reduced hemorrhagic and anticoagulant activity, obtained by treating in a basic medium heparins of various origin, optionally in the presence of alkali metal salts and of a reducing agent. The heparin derivatives obtained through this treatment show peculiar chimico-physical characteristics, like new signals at about 53 and 54 p.p.m. in the .sup.13 C-NMR spectrum and an increase of the specific rotatory power, compared to that of the starting heparins, to values between +50.degree. to +90.degree.. Said structural modifications produce an improvement of the biological properties of the heparin, substantially keeping the antithrombotic activity while diminishing the hemorrhagic effect in vivo and the anticoagulant activity in vitro.

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Bologna, Italy

Silvano Piani