Bracco Imaging S.p.a.

Bracco International Bv

Giovanna Lux

Pier Lucio Anelli

Marino Brocchetta

Fulvio Uggeri

Luciano Lattuada

Enrico Cappelletti

Michele Serleti

Herv&eacute; Tournier

Milena Gabellini

Massimo Visigalli

Christoph De Haen

Pierfrancesco Morosini

Ornella Gazzotti

Giuseppe Manfredi

Daniela Palano

A process for the preparation of (S)-N,N'-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5-[(2-hydroxy-1-oxo-propyl)amino]-2,4,6-triiodo-1,3-benzendicarboxamide (iopamidol) starting from 5-amino-N,N&#x2032;-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-2,4,6-triiodo-1,3-benzenedicarboxamide (II) which process comprises a) reacting the compound of formula (II) with a suitable protecting agent, to give a compound of formula (III) wherein R is a group of formula A or B wherein Ris a hydrogen atom, a C&#xf7;Cstraight or branched alkoxy group, Ris hydrogen, a C&#xf7;Cstraight or branched alkoy group and R3 ?is a C&#xf7;Cstraight or branched alkyl group, a trifuoromethyl or a trichloromethyl group; b) acylating the amino group in position 5 of the intermediate compound of formula (III), by reaction with a (S)-2-(acetyloxy)propanoyl chloride to give a compound of formula (IV) wherein R is as defined above; and c) removing all the acyl groups present in the compound of formula (IV) under basic conditions, with prior cleavage of the cyclic protections of the hydroxy groups in the carboxamido substituents under acidic conditions, when R is a group of formula A carboxamido hydroxy groups under acidic conditions. The invention also refers to the new intermediates of formula (III) and (IV) wherein &#x2014;R is a group A.

Process for the preparation of iopamidol and the new intermediates therein

The invention relates to a process for the preparation of a compound of formula (I), wherein R represents a 2,3-dihydroxy-1-propyl or a 1,3-dihydroxy-2-propyl radical, via direct amidation of a dialkyl ester of 5-amino-1,3-benzenedicarboxylic acid of formula (V), wherein Rrepresents a straight or branched (C-C)-alkyl group, with at least the stoichiometric amount of an amine of formula HNR.

Process for the preparation of N,N-substituted 5-amino-1,3-benzenedicarboxamides

A process for the preparation of (S)-N,N'-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5-[(2-hydroxy-1-oxo-propyl)amino]-2,4,6-triiodo-1,3-benzendicarboxamide (iopamidol) starting from 5-amino-N,N&#x2032;-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-2,4,6-triiodo-1,3-benzenedicarboxamide (II) which process comprises a) reacting the compound of formula (II) with a suitable protecting agent, to give a compound of formula (III) wherein R is a group of formula A or B wherein Ris a hydrogen atom, a C&#xf7;Cstraight or branched alkoxy group, Ris hydrogen, a C&#xf7;Cstraight or branched alkoxy group and R3 ?is a C&#xf7;Cstraight or branched alkyl group, a trifuoromethyl or a trichloromethyl group; b) acylating the amino group in position 5 of the intermediate compound of formula (III), by reaction with a (S)-2-(acetyloxy)propanoyl chloride to give a compound of formula (IV) wherein R is as defined above; and c) removing all the acyl groups present in the compound of formula (IV) under basic conditions, with prior cleavage of the cyclic protections of the hydroxy groups in the carboxamido substituents under acidic conditions, when R is a group of formula A carboxamido hydroxy groups under acidic conditions. The invention also refers to the new intermediates of formula (III) and (IV) wherein &#x2014;R is a group A.

Process for the preparation of iopamidol and the new intermediated therein

Substituted polycarboxylic ligand molecules and corresponding metal complexes of said ligands, preferably paramagnetic metals complexes for generating responses in the field of magnetic resonance imaging (MRI) The paramagnetic complexes of the polycarboxylic ligands possess advantageous tensioactive properties and are useful as MRI contrast media in formulations for investigating the blood pool.

Amphipatic polycarboxylic chelates and complexes with paramagnetic metals as MRI contrast agents

Blood pool imaging contrast agents containing paramagnetic bi- and tri-valent metal ion chelates of bile acid conjugates with molecules having chelating activity are used in magnetic resonance imaging of the vascular system and particularly the coronaries.

Use of bile acid conjugates, derivatives thereof with metal complexes as blood pool agents for nuclear magnetic resonance diagnostics

Substituted polycarboxylic ligand molecules and corresponding metal complexes of said ligands, preferably paramagnetic metals complexes for generating responses in the field of magnetic resonance imaging (MRI). The paramagnetic complexes of the polycarboxylic ligands possess advantageous tensioactive properties and are useful as MRI contrast media in formulations for investigating the blood pool.

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Milan, Italy

Giovanna Lux