Nitrogen-containing cyclic ligands

{
  "publication_number": "US5049667A",
  "country": "US",
  "kind": "A",
  "title": "Nitrogen-containing cyclic ligands",
  "abstract": "The subject of the invention is nitrogen-containing cyclic ligands and metal complexes formed by these ligands, the uses of these complexes as magnetic resonance imaging (MRI) agents, as X-ray contrast agents and as chemical shift reagents in vivo.",
  "claims": [
    "1. A ligand having the formula: ##STR44## in which R 1 represents a radical of the formula: ##STR45## R 6 being selected from the group consisting of C 1 -C 18 alkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 polyhydroxyalkyl and a group of the formula: ##STR46## R 11 being selected from the group consisting of C 1 -C 8 alkylene, R 7 being selected from the group consisting of hydrogen, C 1 -C 14 alkyl, C 1 -C 6 hydroxyalkyl and C 1 -C 6 polyhydroxyalkyl, m=0 or 1, R 2, R 3, R 4, identical or different represent a radical of the formula ##STR47## R 8 and R 9, identical or different, being selected from hydrogen, C 1 -C 14 alkyl, C 1 -C 6 hydroxyalkyl and C 1 -C 6 polyhydroxyalkyl, p=1 or 2, n=0, 1 or 2 and R 5 is selected from the group consisting of hydrogen, C 1 -C 14 alkyl, C 1 -C 6 hydroxyalkyl and C 1 -C 6 polyhydroxyalkyl, and Z is selected from the group consisting of oxygen and a group of the formula: >N--R.sub.10 R 10 being selected from the group consisting of hydrogen, C 1 -C 14 alkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 4 polyhydroxyalkyl, a group of the formula ##STR48## R 5 having the meaning given previously R 13, R 14, R 15 and R 16, identical or different being selected from the group consisting of hydroxy and a group of the formula ##STR49## R 17 and R 18, identical or different being selected from the group consisting of hydrogen, C 1 -C 14 alkyl, C 1 -C 6 hydroxyalkyl and C 1 -C 6 polyhydroxyalkyl, as well as salts thereof.",
    "2. A ligand of the formula: ##STR50## in which R 1 represents a radical of the formula: ##STR51## R 6 being selected from the group consisting of C 1 -C 14 alkyl, C 1 -C 4 hydroxyalkyl, C 1 -C 4 polyhydroxyalkyl and a group of the formula: ##STR52## R 11 being selected from the group consisting of C 1 -C 8 alkylene, R 7 being selected from the group consisting of hydrogen, C 1 -C 14 alkyl, C 1 -C 4 hydroxyalkyl, C 1 -C 4 polyhydroxyalkyl, m=0 or 1, R 2, R 3, R 4, identical or different, represent a radical of the formula: ##STR53## R 8 and R 9, identical or different, being selected from hydrogen, C 1 -C 14 alkyl, C 1 -C 4 hydroxyalkyl and C 1 -C 4 polyhydroxyalkyl, p=1 or 2, n=0, 1 or 2 and R 5 is selected from the group consisting of hydrogen, C 1 -C 4 alkyl, C 1 -C 4 hydroxyalkyl and C 1 -C 4 polyhydroxyalkyl, and Z is selected from the group consisting of oxygen and a group of the formula: >N--R.sub.10 R 10 being selected from the group consisting of hydrogen, C 1 -C 14 alkyl, C 1 -C 4 hydroxyalkyl and C 1 -C 4 polyhydroxyalkyl, a group of the formula ##STR54## R 5 having the meaning given previously, as well as the salts thereof.",
    "3. A ligand having the formula: ##STR55## in which R 1 represents a radical of the formula: ##STR56## R 6 being selected from the group consisting of C 1 -C 18 alkyl, C 1 -C 6 hydroxyalkyl and C 1 -C 6 polyhydroxyalkyl, R 7 being selected from the group consisting of hydrogen, C 1 -C 14 alkyl, C 1 -C 6 hydroxyalkyl and C 1 -C 6 polyhydroxyalkyl, m=0 or 1 R 2, R 3, R 4, identical or different represent a radical of the formula ##STR57## R 8 and R 9, identical or different, being selected from hydrogen, C 1 -C 14 alkyl, C 1 -C 6 hydroxyalkyl and C 1 -C 6 polyhydroxyalkyl, R 5 is selected from the group consisting of hydrogen, C 1 -C 14, alkyl, C 1 -C 6 hydroxyalkyl and C 1 -C 6 polyhydroxyalkyl, and R 13, R 14, R 15, R 16 identical or different being selected from the group consisting of hydroxy and a group of the formula ##STR58## R 17 and R 18, identical or different, being selected from the group consisting of hydrogen, C 1 -C 14 alkyl, C 1 -C 6 hydroxyalkyl and C 1 -C 6 polyhydroxyalkyl, at least one group R 13, R 14, R 15 and R 16 being a group of the formula ##STR59## as well as salts thereof.",
    "4. A compound as claimed in claim 2 which is 2,6-dimethyl-1,4,7,10-tetraazacyclododecane-N,N',N\",N'\"-tetraacetic acid.",
    "5. A compound as claimed in claim 2 which is 2-hexyl-1,4,7,10-tetraazacyclododecane-N,N',N\",N'\"-tetraacetic acid.",
    "6. A compound as claimed in claim 1 which is 2-methyl-1,4,7,10-tetraazacyclododecane-N,N',N\",N'\"-tetraacetic acid.",
    "7. A compound as claimed in claim 2 which is 2-hydroxymethyl-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid.",
    "8. A compound as claimed in claim 2 which is 2-hydroxymethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid.",
    "9. A compound as claimed in claim 2 which is 2-hydroxyethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid.",
    "10. A compound as claimed in claim 3 which is monopropionamide of 2-methyl-1,4,7,10-tetraazacyclododecane-N,N',N\",N'\"-tetraacetic acid.",
    "11. Ligands having the formula: ##STR60## in which R 1 represents a radical of the formula: ##STR61## R 6 being selected from the group consisting of C 1 -C 14 alkyl, C 1 -C 3 hydroxyalkyl, C 1 -C 3 polyhydroxyalkyl, R 7 being selected from the group consisting of hydrogen, C 1 -C 14 alkyl, C 1 -C 3 hydroxyalkyl, C 1 -C 3 polyhydroxyalkyl, m=1 or 2, R 2, R 3, R 4, identical or different, represent a radical of the formula: ##STR62## R 8 and R 9, identical or different, being selected from hydrogen, C 1 -C 14 alkyl, C 1 -C 3 hydroxyalkyl and C 1 -C 3 polyhydroxyalkyl, p=1 or 2, n=0, 1 or 2 and R 5 is selected from the group consisting of hydrogen, C 1 -C 3 alkyl, C 1 -C 3 hydroxyalkyl and C 1 -C 3 polyhydroxyalkyl, and Z is a group of the formula: >N--R.sub.10 R 10 being a group of the formula ##STR63## R 5 having the meaning given previously, and the salts thereof.",
    "12. Ligands having the formula: ##STR64## in which R 1 represents a radical of the formula: ##STR65## R 6 being methyl, R 7 being hydrogen, m=1 or 2, R 2, R 3, R 4, identical or different, represent a radical of the formula: ##STR66## R 8 and R 9, identical or different, being selected from hydrogen, methyl and C 1 -C 4 hydroxyalkyl, p=1 or 2, n=0, 1 or 2 and R 5 is hydrogen, and Z is a group of the formula: >N--R.sub.10 R 10 being a group of the formula ##STR67## R 5 having the meaning given previously, and the salts thereof."
  ],
  "cpc": [
    "C07D 259/00",
    "A61K 49/06",
    "A61K 51/04",
    "A61K 51/0482",
    "C07D 257/02",
    "Y10T 436/24"
  ],
  "assignees": [
    "GUERBET SA"
  ],
  "filing_date": "1989-10-16",
  "publication_date": "1991-09-17",
  "grant_date": "1991-09-17",
  "priority_date": "1987-04-14",
  "application_number": "US-42159289-A",
  "family_id": "26225919",
  "citations": [
    "EP0255471A1",
    "JPS60202869A",
    "US3485818A",
    "US4168265A",
    "US4702998A",
    "US4880008A"
  ]
}