Sigma-tau Industrie Farmaceutiche Riunite S.p.a.

Fabio Giannessi

Maria Ornella Tinti

Francesco De Angelis

Domenico Misiti

Orlando Ghirardi

Mauro Marzi

Patrizia Minetti

Arduino Arduini

Piero Chiodi

Roberto Cozzolino

Natalina Dell'Uomo

Roberto Castagnani

Maria Laura Bolognesi

Emanuela Tassoni

Pompeo Pessotto

Carlo Scolastico

Nazareno Scafetta

Maurizio Botta

Paolo De Witt

Tiziana Brunetti

Ida Bernabei

Anna Floriana Sciarroni

Carlo Sclolastico

Pederico Corelli

Ferdinando Maria Milazzo

Monica Bandera

Compounds having reversible inhibiting activity of carnitine palmitoyl-transferase

Compounds of formula (I)wherein the groups are as defined in the description are disclosed. The compounds of formula (I) are endowed with reversible inhibiting activity of carnitine palmitoyl-transferase and are useful in the preparation of medicaments useful in the pathologies related to a hyperactivity of carnitine palmitoyl-transferase, such as hyperglycemia, diabetes and pathologies related thereto, heart failure, ischemia.

The use is described of derivatives of &#x3b1;-phenylthiocarboxylic and &#x3b1;-phenyloxycarboxylic acids with formula (i): in which the substituents have the meanings described in the text, for the preparation of a medicine for the prophylaxis and treatment of diabetes, particularly type 2 diabetes, its complications, the various forms of insulin resistance, and hyperlipidaemias 

Use of &#x3b1;-phenylthiocarboxylic and &#x3b1;-phenyloxycarboxylic acids with serum-glucose-lowering and serum-lipid-lowering activity

Formula (I) compounds are described where the groups are as identified in the text, and their use as medicines, particularly as anti-diabetes, serum glucose-lowering and anti-obesity agents. They are useful for the prophylaxis and treatment of diabetes, particularly type 2 diabetes, and its complications, syndrome X, the various forms of insulin resistance, and hyperlipidaemias, as well as for the treatment of obesity.

Variously substituted derivatives of guanidine, and their use as medicines with anti-diabetes and/or anti-obesity activity

Synthesis of (R) and (S)-aminocarnitine, (R) and (S)-4-phosphonium-3-amino-butanoate, (R) and (S) 3,4-diaminobutanoic acid, and their derivatives starting from D- and L-aspartic acid

Synthesis of (R) and (S) -aminocarnitine and their derivatives starting from D- and L-aspartic acid

R-(&minus;)-carnitine is prepared by (a) conversion of (S)-3-hydroxy-4-butyrolactone &lsqb;1&rsqb; to alkyl (S)-4-halogen-3-hydroxy-butyrate &lsqb;2&rsqb; by reaction with a linear or branched C,-C,alcohol (b), substitution of a CN group for the halogen of compound &lsqb;2&rsqb; to yield the alkyl ester of (R)-4-cyano-3-hydroxybutyric acid &lsqb;3&rsqb;, (c) conversion of alkyl ester &lsqb;3&rsqb; to yield (R)-4-cyano-3-hydroxybutyramide &lsqb;4&rsqb;, (d) cyclization of compound &lsqb;4&rsqb; to yield (R)-5-(cyanomethyl)-2-oxazolidone &lsqb;5&rsqb; via conversion of the amide function to isocyanate, (e) hydrolysis of compound &lsqb;5&rsqb; to yield (R)-4-amino-3-hydroxybutyric acid &lsqb;6&rsqb;, and finally (f) methylation of the amino group of compound &lsqb;6&rsqb; to yield the end product (R)-carnitine.

Process for the preparation of R-(-)-carnitine

A process is disclosed for producing (R)-3-hydroxy-4-butyrolactone from its enantiomer, (S)-3-hydroxy-4-butyrolactone. The (R)-enantiomer can be advantageously utilized in several organic synthesis and industrial processes, such as e.g. GABOB and (R)-carnitine preparation.

Process for producing (R)-3-hydroxy-4-butyrolactone useful for preparing

A process for producing (S)-.beta.-hydroxy-.gamma.-butyrolactone, a versatile intermediate used in several organic syntheses, from (S)-carnitine which is an unexpensive waste-product obtained from the production of (R)-carnitine by the resolution of racemic mixtures, is disclosed.

Process for the preparation of (S)-.beta.-hydroxy-.gamma.-butyrolactone

The present invention relates to a proces for manufacturing L-(-)-carnitine from D-(+)-carnitine or a derivative thereof. D-(+)-carnitine is esterified in order to protect the carboxyl group and subsequently converted to an acyl derivative. The acyl derivative is then converted to a lactone of L-(-)-carnitine. Finally, the lactone is reopened to obtain L-(-)-carnitine.

Process for manufacturing L-(-)-carnitine from a waste product having

L-(-)-carnitine is prepared from D-(+)-carnitinamide by (a) reacting D-(+)-carnitinamide in an acid medium with a straight or branched chain aliphatic alcohol thereby forming D-(+)-carnitine ester, (b) acylating the D-(+)-carnitine ester with an anhydride R.sub.2 O, thereby forming an acylated ester intermediate, (c) acid hydrolyzing the ester group of the acyl carnitine ester thereby obtaining acyl D-(+)-carnitine, (d) lactonizing the acyl D-(+)-carnitine to a lactone of L-(-)-carnitine, and (e) reacting the lactone with base thereby forming L-(-)-carnitine.

Process for manufacturing L(-)-carnitine from a waste product having

A process for producing aminocarnitine is described, wherein methanesulfonylcarnitine is converted to a lactone which is reacted with an azide to give azidocarnitine. The catalytic hydrogenation of azidocarnitine gives aminocarnitine.

Process for producing R-aminocarnitine and S-aminocarnitine

A Process for Preparing L-(-)-carnitine is disclosed which comprises acylating D-(+)-carnitinenitrile or D-(+)-carnitineamide to their respective acyl derivatives which, via acid hydrolysis, yield D-(+)-carnitine which is converted to the lactone of L-(-)-carnitine. The lactone when in base yields L-(-)-carnitine.

Growing community of inventors

Rome, Italy

Fabio Giannessi