New derivatives of 2,4,6-triiodo-isophthalic acid, proceses for their synthesis and X-ray contrasting materials containing these

• US 4,348,377 A
• Filed: 07/30/1980
• Issued: 09/07/1982
• Est. Priority Date: 08/09/1979
• Status: Expired due to Term

• Current Assignee: Bracco International B.V. (Bracco SPA)
• Original Assignee: Bracco Industria Chimica S.p.A.
• Inventors: Felder, Ernst, Pitre, Davide
• Primary Examiner(s): Phillips, Delbert R.
• Application Number:
  US06/173,765
• Time in Patent Office: 769 Days
• Field of Search: 424/5, 564/153
• US Class Current: 424/9.452
• CPC Class Codes: C07C 233/00 Carboxylic acid amides

Abstract

Novel, radio-opaque compounds comprising water-soluble bis-[N-{3,5-bis-(hydroxyalkylaminocarbonyl)-2,4,6-triiodo-phenyl}-N-(.alpha.-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.

Claims

1. Bis-[N-{3,5-bis-(hydroxyalkylaminocarbonyl)-2,4,6-triiodo-phenyl}-N-(α

-hydroxyacyl]-alkanes having the formula (I) ##STR5## wherein (HO)_2-3 alkyl is 1,3-dihydroxyisopropyl, 2,3-dihydroxypropyl, or 1,3-dihydroxy-2-hydroxymethylisopropyl,

R is hydrogen or methyl, and

alkylene is a bivalent alkylene residue with 2 to 10 carbon atoms which may be substituted by hydroxy functions, or a mono-, di-or poly-oxa-alkylene residue with 4 to 12 carbon atoms, which may be substituted by hydroxy functions.

2. The compound of claim 1 wherein the alkylene is

3. Bis-[N-{3,5-bis(dihydroxypropylaminocarbonyl)-2,4,6-triiodo-phenyl}-N-(α

-hydroxyacyl)-amino]-alkanes having the formula (I) ##STR6## in which (HO)₂ C₃ H₅ --is 1,3-dihydroxyisopropyl or 2,3-dihydroxypropyl,

R is hydrogen or methyl, and

alkylene is a bivalent alkylene residue with 2 to 10 carbon atoms which may be substituted by hydroxy functions, or a mono-, di- or poly-oxa-alkylene residue with 4 to 12 carbon atoms which may also be substituted by hydroxy functions.

4. The compound of claim 3 wherein the alkylene is

5. An X-ray contrasting composition comprising a pharmacologically acceptable carrier and a radio-opaque effective amount of bis-[N-{3,5-bis-(hydroxyalkylaminocarbonyl)-2,4,6,-triiodo-phenyl}-N-(.alpha.-hydroxyacyl)-amino]-alkane having the formula (I) ##STR7## wherein (HO)_2-3 alkyl is 1,3-dihydroxyisopropyl, 2,3-dihydroxypropyl or 1,3-dihydroxy-2-hydroxymethylisopropyl,

R is hydrogen or methyl, and

alkylene is a bivalent alkylene residue with 2 to 10 carbon atoms which may be substituted by hydroxy functions, or a mono-, di-, or poly-oxa-alkylene residue with 4 to 12 carbon atoms which may be substituted by hydroxy functions.

6. In a method for enhancement of the visualization of vessels in a patient wherein an X-ray contrasting composition is injected into the vessel, the improvement which comprises said X-ray contrasting composition comprising a radio-opaque effective amount of ##STR8## wherein (HO)_2-3 alkyl is 1,3-dihydroxyisopropyl, 2,3-dihydroxypropyl, or 1,3-dihydroxy-2-hydroxymethylisopropyl,

R is hydrogen or methyl, and

alkylene is a bivalent alkylene residue with 2 to 10 carbon atoms which may be substituted by hydroxy functions, or a mono-, di- or poly-oxa-alkylene residue with 4 to 12 carbon atoms which may be substituted by hydroxy functions,

and a carrier.

7. 1,3-bis[N-{3,5-bis-(2,3-dihydroxypropylaminocarbonyl)-2,4,6-triiodo-phenyl}-N-hydroxyacetyl-amino]-propane.