Bracco Imaging S.p.a.

Roberta Napolitano

Luciano Lattuada

Valeria Boi

Massimo Visigalli

Giovanni Battista Giovenzana

Federica Buonsanti

Silvio Aime

Alberto Fringuello Mingo

Federico Crivellin

Magnus Karlsson

Pernille Rose Jensen

Mathilde H Lerche

Fabio Tedoldi

Zsolt Baranyai

Giovanni Valbusa

Lorena Pizzuto

Giuseppe Marazzi

Laura Orio

Elisa Battistini

Andrea Ferraris

Nicole Guidolin

Daniela Imperio

Francesco Blasi

Roberta Fretta

Luigi Miragoli

Claudia Cabella

Laura Galimberti

Sonia Colombo Serra

Andrea Banin

Chiara Brioschi

Frederica Buonsanti

The present invention relates to the field of optical imaging. More particularly, it relates to compounds of the cyanine family with near-infrared emission characterized by improved physico-chemical and biological properties and to conjugates with biological ligands thereof. The invention also relates to the use of these compounds as optical diagnostic agents in imaging or therapy of solid tumors, to the methods for their preparation and to the compositions comprising them.

Near-infrared cyanine dyes and conjugates thereof

The present invention relates to the RRR/SSS pair of enantiomers of the of Gd(PCTA-tris-glutaric acid), the single enantiomers of the pair, the pharmaceutically acceptable salts thereof, their amide derivatives, and compositions comprising at least 50% of these compounds.

Gadolinium bearing PCTA-based contrast agents

The present invention relates to the field of optical imaging. More particularly, it relates to compounds of the cyanine family with near-infrared emission characterized by improved physico-chemical and biological properties and to conjugates with biological ligands thereof. The invention also relates to the use of these compounds as optical diagnostic agents in imaging or therapy of solid tumors, to the methods for their preparation and to the compositions comprising them. The compounds have formula (I), formula (I), wherein X is direct bond or —O—; Y is a group selected from linear or branched C1-C6 alkyl, C3-C7 cycloalkyl and heterocyclyl, substituted by at least two hydroxyl groups; R1 and R2 are each independently a linear or branched C1-C6 alkyl substituted by a group selected from —SO3H, —COOH, —CONH2 and —COO—C1-C6 alkyl; and R3 is hydrogen, —SO3H or a linear or branched C1-C6 alkyl substituted by —COOH or —CONH—Y, wherein Y is a group selected from linear or branched C1-C6 alkyl, C3-C7 cycloalkyl and heterocyclyl, substituted by at least two hydroxyl groups.

The present invention relates to the calcium complex of (4RS)(4-carboxy-5,8,11-tris(carboxymethyl)-1-phenyl oxa-5,8,11-triazatridecan-13-oato(5-))pentahydrogen (BOPTA) in the form of a salt, to the process for its preparation and to a formulation comprising said salt.

Calcium BOPTA complex

The present invention relates to new class of dimeric macrocycles capable of chelating paramagnetic metal ions, their chelated complexes with metal ions and the use thereof as contrast agents, particularly suitable for Magnetic Resonance Imaging (MRI) analysis.

Dimeric contrast agents

The present invention relates to new class of functionalized macrocycles capable of chelating paramagnetic metal ions, their chelated complexes with metal ions and the use thereof as contrast agents, particularly suitable for Magnetic Resonance Imaging (MRI) analysis.

Contrast agents

The present invention relates to new class of functionalized polyazamacrocycles including at least one phosphonic or phosphinic group linked to a nitrogen atom of the macrocyclic cage, and capable of chelating paramagnetic metal ions, their chelated complexes with metal ions and the use thereof as contrast agents, particularly suitable for Magnetic Resonance Imaging (MRI) analysis.

The present invention relates to new class of dimeric macrocycles capable of chelating paramagnetic metal ions, their chelated complexes with the paramagnetic metal ions and the use thereof as contrast agents, particularly suitable for Magnetic Resonance Imaging (MRI) analysis.

1-C-1,1-Bis(acetoxy(methyl))-2,2'-cyclopropane of formula (I): The compound can be hyperpolarized and used as a contrast agent inC Magnetic Resonance diagnostic technique (C-MR) for the diagnosis of tumor.

Hyperpolarized 1-13C-1,1-bis(acetoxy(methyl))-2,2'-cyclopropane as metabolic marker for MR

The present invention discloses a process for recovery of a boronic acid of formula R&#x2014;B(OH), wherein Ris selected from the group consisting of C-Clinear or branched alkyl, C-Ccycloalkyl, and Caryl, optionally substituted with a group selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, t-butyl, and phenyl, comprising admixing the boronic acid with a water-immiscible organic solvent in a weight ratio between the boronic acid and the water-immiscible organic solvent from 1:10 to 1:20, adding an aqueous solution to a final pH of neutral, and partitioning the boronic acid into an organic water-immiscible phase and recovery of the organic water-immiscible phase.

Process for the recovery of a boronic acid

The present invention discloses a process for the preparation of Iopamidol of formula (II) and comprising the following steps: a) reacting the Compound (I) wherein X is OR2 or R3, and wherein R2 and R3 are a Ci-C6 linear or branched alkyl, C3-C6 cycloalkyl, C6 aryl, optionally substituted with a group selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, t-butyl and phenyl, with the acylating agent (S)-2-(acetyloxy)propanoyl chloride in a reaction medium to provide the acetyloxy derivative of Compound (I); b) hydrolyzing the intermediate from step a) with an aqueous solution at a pH comprised from 0 to 7, by adding water or a diluted alkaline solution such as sodium hydroxide or potassium hydroxide, freeing the hydroxyls from the boron-containing protective groups, obtaining the N&#x2014;(S)-2-(acetyloxy)propanoyl derivative of Compound (II); c) alkaline hydrolysis to restore the (S)-2-(hydroxy)propanoyl group and to obtain Iopamidol (II) and optional recovery of the boron derivative from the solution obtained in step b). The boron-containing protective group is versatile, efficient and recyclable. A one-pot synthesis, without intermediate isolation is provided, leading to a decreasing of recovered and recycled solvents and a significant increasing in the yield, representing a significant advantage in terms of cost-effectiveness of the entire process and environmental awareness. 

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Albiano d'Ivrea, Italy

Roberta Napolitano