Bracco Industria Chimica, S.p.a.

Dibra S.p.a.

Merck Patent Gesellschaft MIT Beschrankter Haftung

Syntex LLC

Bracco Chimica S.p.a.

Bracco Industria Chimica Societa Per Azioni

Savac Ag

Ernst Felder

Davide Pitre

Fulvio Uggeri

Luciano Fumagalli

Giorgio Vittadini

Pier Lucio Anelli

Michael Romer

Giorgio Ripa

Christoph De Haen

Hartmut Hartner

Mario Virtuani

Andrea Beltrami

Hans Bardonner

Hans Zutter

Marco Lolli

Carlo Distaso

Carlo Musu

David E Pitre

Giorio Vittadini

Maria Zingales, Deceased

Wolfgang Fruhstorfer

Paramagnetic chelates for nuclear magnetic resonance diagnosis

A process for the preparation, separation and purification of (6S) and (6R) diastereomers of folinic acid salts with at least dibasic amines is disclosed, which process comprises the hydrolysis of (6RS)-5,10-methenyl-5,6,7,8-tetrahydrofolic acid chloride hydrochloride with an at least dibasic amine and the subsequent separation of the diasteromeric salts.

Process for the preparation and separation of diastereomeric salts of

Aqueous injectable formulations useful for radiodiagnosis comprising

Comounds having the formula ##STR1## wherein: a is 2 or 3; b is an integer from 0 to 4;

Paramagnetic chelates

Macrocyclic derivatives of 1,4,7,10-tetraazacyclododecane of general formula (I) hereinbelow, wherein A is a group of formula (II) hereinbelow, in which R is H or alkyl or optionally substituted benzyl or a H(OCH.sub.2 CH.sub.2).sub.1-4-, Me(OCH.sub.2 CH.sub.2).sub.1-4-, or Et(OCH.sub.2 CH.sub.2).sub.1-4- group, X or O--R.sub.1, in which R.sub.1 is H or alkyl, hydroxyalkyl, alkoxyalkyl, alkoxyhydroxyalkyl or a polyoxaalkyl group or X is --NR.sub.2 R.sub.3, in which R.sub.2 and R.sub.3 are H or alkyl, hydroxyalkyl, alkoxyalkyl or alkoxyhydroxyalkyl, and B.sub.1, B.sub.2 and B.sub.3 have the same meanings as A or are H or a group of formula (III) hereinbelow, in which R.sub.4 is H or alkyl, Y is a O--R.sub.5 group, wherein R.sub.5 is H or alkyl, hydroxyalkyl, alkoxyalkyl, alkoxyhydroxyalkyl or a polyoxaalkyl group, or Y is a --NR.sub.6 R.sub.7 group, wherein R.sub.6 and R.sub.7 are H or alkyl, hydroxyalkyl, alkoxyalkyl, or alkoxyhydroxyalkyl, said derivatives optionally being salified, and the complex salts thereof, are used as pharmaceuticals and/or diagnostic agents. ##STR1##

Macrocyclic chelating agents and chelates thereof

A process for the production of hydroxyamines of the formula I

Process for the preparation of hydroxyamines

Compounds suitable for NMR imaging having the formula: ##STR1## wherein a is 2 or 3;

Paramagnetic chelates useful for NMR imaging

Barium sulfate suitable for the preparation of radiographic contrast agents of increased flowability and density is obtained by a high temperature treatment at 700.degree. to 1,200.degree. C. and preferably at 800.degree. to 1,000.degree. C. The barium sulfate so sintered is distinguished by a bulk density of 2.5 to 3 g/ml and its aqueous suspension, containing 200 g of barium sulfate per 100 ml, is distinguished by a viscosity of no more than 1,000 mPas. Radiographic contrast agents containing at least 200 g of sintered barium sulfate per 100 ml are outstandingly suitable for the difficult double contrast visualization of the stomach and gastric mucosa.

Process for the preparation of barium sulfate of increased flowability

Compounds for use in non-ionic X-ray contrasting materials having the formula ##STR1## in which (H0).sub.2-3 alkyl is 1,3-dihydroxyisopropyl, 2,3-dihydroxypropyl or 1,3-dihydroxy-2-hydroxymethylisopropyl,

Derivatives of 2,4,6-triiodo-isophthalic acid, processes for their

Novel, radio-opaque compounds comprising water-soluble bis-[N-{3,5-bis-(hydroxyalkylaminocarbonyl)-2,4,6-triiodo-phenyl}-N-(.alph a.-hydroxyacyl)-amino]-alkanes are disclosed for use as X-ray contrast agents. These compounds are relatively simple to synthesize, possess low toxicity and have good stability as well as resistance to hydrolysis. Methods for preparation and use of the compounds are also disclosed.

New derivatives of 2,4,6-triiodo-isophthalic acid, proceses for their

3-Alkoxy-2-alkyl-propionic acid derivatives are prepared by catalytic hydrogenation of the acrylic acid analogs. The latter are obtained by CO treatment of lower alkyl esters of alkanoic acids having 3-6 carbon atoms in the presence of alkali metal methylate and condensation of the resulting 2-formylalkanoic acids or their alkali metal enolates with compounds of the formula X--(CH.sub.2).sub.m --Z wherein X is Cl, Br, or OH, and Z is Cl, Br, I, alkyl- or arylsulfonyl, or OH.

Method of preparing a 3-alkoxy-2-alkyl-propionic acid ester derivative

The subject of the invention is a process for resolving mixtures of (+)- and (-)-6-methoxy-.alpha.-methyl-2-naphthaleneacetic acid into the enantiomers thereof, characterized in that N-methyl-D-glucamine [=1-deoxy-1-(methylamino)-D-glucitol] is used as the resolving agent, so that the 6-methoxy-.alpha.-methyl-2-naphthaleneacetic acid is converted into the corresponding diastereoisomeric N-methyl-D-glucamine salt pair which, because of very different solubilities, can be separated easily and completely with high yield.

Process for the resolution of (+)- and

.alpha., .omega.-BIS-[5-(DIHYDROXYALKYL) AMINOCARBONYL-3-HYDROXYACYL-AMINO-2,4,6-TRIIODO-BENZOYL-AMINO]-OXAALKANE COMPOUNDS OF THE FORMULA ##STR1## wherein R.sub.1 is ##STR2## R and R' are hydrogen or methyl, R.sub.2 is dihydroxyalkyl having 3 or 4 carbon atoms,

Water-soluble, non-ionizing, radiopaque compounds and contrast

Compounds of the formula ##STR1## wherein R is (C.sub.m H.sub.2m O.sub.n)--OH, m being 2, 3, or 4, and n being 0 or 1, are effective and well tolerated as X-ray contrast agents in lymphography, hepatography, bronchography, cystography, and hysterosalpingography.

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Riva S. Vitale, Switzerland

Ernst Felder