# US 5,344,639 A · Contrast agent for NMR imaging comprising peptide structures > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,344,639 A - Document ID: US5344639A - Status: Granted - Kind: A - Application number: 07/719,715 - Filed: 1991-06-26 - Granted: 1994-09-06 - Earliest claimed: 1990-06-26 - Assignees: Medgenix Group S.A. - Inventors: Kwok W. Chiu; Wassif Hussain; John R. Thornback - Web page: https://patentgrep.com/patent/US5344639A ## CPC - C07K 5/022: {containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2} - Y10T 436/24: Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION ## Abstract The present invention relates to a contrast agent for NMR imaging constituted by a complex between a chelating agent and paramagnetic metal cations, wherein said complex corresponds to the formula I: ##STR1## or a physiologically acceptable salt of this complex, in which formula: n and n' are whole numbers from 1 to 4 R.sub.1 -R.sub.7 are selected from among H, a halogen, alkyl, alkoxy, aryl, alkenyl, and cycloalkyl groups; with the alkyl groups being optionally substituted by halogen, alkoxy, alkyl, nitrile, nitro or amino; >C(R.sub.6, R.sub.7) can in addition represent >C=O; the three substituents Y are identical or different and represent H or an ionic equivalent of a divalent or trivalent paramagnetic metal cation or of a physiologically acceptable cation derived from an inorganic or organic base, with the condition that at least two of the substituents Y represent ionic equivalents of paramagnetic metal cations. ## Claims ### Claim 1 A complex between a chelating agent and a paramagnetic metal cation, having the formula: ##STR15## or a physiologically acceptable salt of this complex, wherein n and n' are the same or different and are selected from the group consisting of whole numbers of from 1 to 4; each R.sub.1, R.sub.2, R.sub.4 and R.sub.5 are the same or different and are selected from the group consisting of H, halogen and C.sub.1-4 alkyl, the C.sub.1-4 alkyl being optionally substituted by halogen; R.sub.3 is hydrogen; >C(R.sub.6, R.sub.7) is >C=O; the three substituents Y are the same or different and represent H or the cation ionic equivalent of a trivalent paramagnetic metal cation or the anionic equivalent of a physiologically acceptable cation derived from an inorganic or organic base, at least two of the substituents Y representing ionic equivalents of cations of paramagnetic metals. ### Claim 2 (depends on 1) A complex according to claim 1, wherein the paramagnetic metal is selected from among divalent or trivalent ions of transition metals and lanthanides. ### Claim 3 (depends on 2) A complex according to claim 2, wherein the paramagnetic metal is selected from among Co.sup.2+, Mn.sup.2+, Cu.sup.2+, Cr.sup.3+, Fe.sup.2+, Fe.sup.3+, Eu.sup.2+, Gd.sup.3+, Dy.sup.3+ and Ho.sup.3+. ### Claim 4 (depends on 1) A complex according to claim 1, having the formula II ##STR16## or a physiologically acceptable acid salt of formula ##STR17## in which X.sup.- is the anion derived from an acid of formula HX, in which formulae Y represents an ionic equivalent of a trivalent paramagnetic metal; n, n', R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 have the previously given meanings. ### Claim 5 (depends on 4) A complex according to claim 4 wherein X.sup.- represents Cl.sup.-, Br.sup.-, F.sup.-, I.sup.-, C.sub.n H.sub.2n+1 COO.sup.-, C.sub.6 H.sub.5 COO.sup.-, or C.sub.n F.sub.2n+1 COO.sup.-. ### Claim 6 (depends on 1) A complex according to claim 1, wherein R.sub.1 =R.sub.2 =R.sub.4 =R.sub.5 =H. ### Claim 7 (depends on 1) A complex according to claim 1, wherein n=n'=1. ### Claim 8 (depends on 4) A complex according to claim 4, wherein X.sup.- =CF.sub.3 COO.sup.-. ### Claim 9 (depends on 1) A complex according to claim 1, wherein the paramagnetic metal is the Gadolinium Gd.sup.3+ ion. ### Claim 10 (depends on 1) A contrast agent for NMR imaging comprising a complex according to claim 1 and a physiologically acceptable carrier. ### Claim 11 A chelating agent with a peptide structure which can form complexes with metals and has the formula: ##STR18## or a physiologically acceptable salt thereof, wherein n and n' are the same or different and are selected from the group consisting of whole numbers from 1 to 4; each R.sub.1, R.sub.2, R.sub.4 and R.sub.5 are the same or different and are selected from the group consisting of H, halogen and C.sub.1-4 alkyl, the C.sub.1-4 alkyl being optionally substituted by halogen; R.sub.3 is hydrogen; and >C(R.sub.6, R.sub.7) is >C=O. ### Claim 12 (depends on 11) Chelating agent according to claim 11, said agent having the formula ##STR19## wherein X.sup.- is derived from an HX acid.