Patents Assigned to Nycomed Salutar, Inc.
  • Patent number: 6288224
    Abstract: Aziridines may be subjeted to a cyclooligomerization reaction to produce polyazacycloalkane compounds useful for example in the preparation of chelating agents for use in diagnostic imaging contrast agents. N-benzyl-aziridine in particular is useful as it can be cyclotetramerized and debenzylated to yield cyclen, a key intermediate in chelating agent preparation. The invention provides a particularly attractive route to production of N-benzyl and other N-arylmethyl aziridines of formula (I) where each R1 is independently hydrogen or a group AR and Ar is an optionally substituted phenyl group. The process comprises reacting a purified N-arylmethylethanolamine-sulphonate sulphonate ester with a base. N-aryimethyl-ethanolamine sulphonate ester of the formula R′NHCH2CH2OSO3H, wherein the N-arylmethyl group R′ is an N-(bisarylmethyl) or N-(triarylmethyl) group, as intermediates.
    Type: Grant
    Filed: April 10, 2000
    Date of Patent: September 11, 2001
    Assignees: Nycomed Salutar, Inc., University of Iowa Research Foundation
    Inventors: Janis Vasilevskis, John Varadarajan, Martha Garrity, Jere Douglas Fellmann, Louis Messerle, Gandara Amarasinghe
  • Patent number: 6048979
    Abstract: Aziridines may be subjected to a cyclooligomerization reaction to produce polyazacycloalkane compounds useful for example in the preparation of chelating agents for use in diagnostic imaging contrast agents. N-benzyl-aziridine in particular is useful as it can be cyclotetramerized and debenzylated to yield cyclen, a key intermediate in chelating agent preparation. The invention provides a particularly attractive route to production of N-benzyl and other N-arylmethyl aziridines of formula (I) where each R.sub.1 is independently hydrogen or a group AR and Ar is an optionally substituted phenyl group. The process comprises reacting a purified N-arylmethylethanolaminesulphonate ester with a base. N-arylmethyl-ethanolamine sulphonate ester of the formula R'NHCH.sub.2 CH.sub.2 OSO.sub.3 H, wherein the N-arylmethyl group R' is an N-(bisarylmethyl) or N-(triarylmethyl) group, as intermediates. In a further aspect, the invention provides compounds of formula (II) ##STR1## where Ar and R.sub.
    Type: Grant
    Filed: December 2, 1997
    Date of Patent: April 11, 2000
    Assignees: Nycomed Salutar, Inc., University of Iowa Foundation
    Inventors: Janis Vasilevskis, John Varadarajan, Martha Garrity, Jere Douglas Fellmann, Louis Messerle, Gandara Amarasinghe
  • Patent number: 6045821
    Abstract: The present invention relates to a liposomal agent comprising liposomes having bound to a membrane thereof a chelated diagnostically or therapeutically effective metal ion. The chelating agent binding the metal ion has a macrocyclic chelant moiety with, attached to a single ring atom thereof, a lipophilic membrane associating moiety.
    Type: Grant
    Filed: May 29, 1997
    Date of Patent: April 4, 2000
    Assignee: Nycomed Salutar, Inc.
    Inventors: Martha Garrity, John Varadarajan, Alan David Watson
  • Patent number: 6010681
    Abstract: The invention provides a blood pool contrast agent having an overall molecular weight of at least 10KD comprising a macrostructure which has bound thereto a plurality of opsonization inhibiting moieties and carries chelated ionic paramagnetic or heavy metal moieties, the chelant groups for said chelated moieties being macrocyclic where said macrostructure is liposomal.
    Type: Grant
    Filed: January 21, 1997
    Date of Patent: January 4, 2000
    Assignee: Nycomed Salutar, Inc.
    Inventors: Larry Margerum, Brian Campion, Jere Douglas Fellmann, Martha Garrity, John Varadarajan
  • Patent number: 5976493
    Abstract: The invention provides polychelant compounds which are useful for example in diagnostic imaging procedures and which are degradable in vivo to release excretable fragments. Such compounds conveniently are of the formula (I): R.sup.1 (X.sup.1 R.sup.2 ((X.sup.2).sub.p L).sub.n).sub.m (where X.sup.1 is a linker moiety metabolically cleavable to release R.sup.1 X.sup.3.sub.m and X.sup.4 R.sup.2 ((X.sup.2).sub.p L).sub.n fragments where X.sup.3 and X.sup.4 are the cleavage residues of X.sup.1 ; R.sup.1 X.sup.3.sub.m is a biotolerable polymer, preferably a substantially monodisperse polymer and especially one with a molecular weight below 40,000 D, particularly below 30,000 D and especially below 20,000 D, for example a first to sixth generation dendrimer; X.sup.4 R.sup.2 ((X.sup.2).sub.p L).sub.n is a polychelant fragment having a molecular weight below 40,000 D, preferably below 30,000 D, especially below 20,000 D, each such moiety preferably being the same; p is 0 or 1; X.sup.
    Type: Grant
    Filed: November 8, 1996
    Date of Patent: November 2, 1999
    Assignee: Nycomed Salutar, Inc.
    Inventors: Lawrence Margerum, Joan Carvalho, Martha Garrity, Jere Douglas Fellmann
  • Patent number: 5972307
    Abstract: This invention relates to dichelants, in particular compounds having two macrocyclic chelant groups linked by a bridge containing an ester or amide bond, especially compounds of formula Vb ##STR1## (wherein each X which may be the same or different is NZ, O or S, at least two Xs being NZ;each Z is a group R.sup.1 or a group CR.sup.1.sub.2 Y, at least one Z, and preferably 2 or 3 Zs, on each macrocyclic ring being a group CR.sup.1.sub.2 Y;each Y is a group CO.sub.2 H, PO.sub.3 H, SO.sub.3 H, CONR.sup.1.sub.2, CON(OR.sup.1)R.sup.1, CNS or CONR.sup.1 NR.sup.1.sub.2, preferably COOH;m is 0 or 1 or 2, preferably 1; each n is 2 or 3, preferably 2; q is 1 or 2, preferably 1;each R.sup.
    Type: Grant
    Filed: July 22, 1997
    Date of Patent: October 26, 1999
    Assignee: Nycomed Salutar, Inc.
    Inventors: Joan Carvalho, Alan D. Watson, Jere D. Fellmann, Michael Koo
  • Patent number: 5958373
    Abstract: The present invention provides a polychelant compound of formula (VII), (wherein each X which may be the same or different is NZ, O or S, at least two Xs being NZ; B is (CR.sup.1 Y) or --N(CR.sup.1.sub.2 Y)--; each Z is a group R.sup.1 or a group CR.sup.1.sub.2 Y, at least one Z being a group CR.sup.1.sub.2 Y; each Y is a group CO.sub.2 H, PO.sub.3 H, SO.sub.3 H, CONR.sup.1.sub.2, CON(OR.sup.1)R.sup.1, CNS or CONR.sup.1 NR.sup.1.sub.2 ; m is 0 or 1 or 2; each n is 2 or 3; q is 0 or 1 when B is (CR.sup.1 Y) and 2 when B is N(CR.sup.1.sub.2 Y); p is an integer having a value of at least 2; each R.sup.1 which may be the same or different is a hydrogen atom or an alkyl, aryl or aralkyl group optionally substituted by one or more hydroxy or alkoxy groups, or two R.sup.1 groups on ring atoms or in Z groups together represent a linker group L; each L which may be the same or different represents a bond or an organic linker group having a molecular weight of less than 1000 and salts and chelates thereof.
    Type: Grant
    Filed: June 13, 1996
    Date of Patent: September 28, 1999
    Assignee: Nycomed Salutar Inc.
    Inventors: Martha Garrity, Shaun Paul Crofts, Joan Carvalho, Per Strande, Harald Dugstad
  • Patent number: 5932190
    Abstract: An x-ray contrast medium containing a multinuclear complex of the formula (M.sub.6 (.mu..sub.3 B).sub.8 A.sub.v).sub.x L.sub.w, wherein M is Mo, W, Re Tc, V, Nb, Ta, Ru, or Fe; .mu..sub.3 B represent a tridentate bridging atom; A is a non-bridging atom; L is a ligand coordinately bonded to at least one M atom; x is a positive integer; and v and w are independently zero or positive integers.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: August 3, 1999
    Assignee: Nycomed Salutar, Inc.
    Inventors: Torsten Almen, Arne Berg, Michael Droege, Harald Dugstad, Jere D. Fellman, Sook-Hui Kim, Jo Klaveness, Scott M. Rocklage, Pal Rongved, Brent Segal, Alan D. Watson
  • Patent number: 5906994
    Abstract: A process for the preparation of multinuclear cluster compounds by reacting a metal carbonyl with iodine, and use of these clusters and clusters derived from them, in diagnostic imaging. Novel multinuclear cluster compounds are also disclosed.
    Type: Grant
    Filed: January 28, 1998
    Date of Patent: May 25, 1999
    Assignee: Nycomed Salutar, Inc.
    Inventors: John D. Franolic, Jeffrey R. Long, Richard H. Holm, Michael Droege, Shannan Downey
  • Patent number: 5834020
    Abstract: The invention provides a dendrimeric compound comprising a dendrimeric bioactive moiety with linked thereto a plurality of diagnostically or therapeutically active moieties characterized in that the molecular skeleton of said compound contains at least one biodegradable cleavage site such that on cleavage thereof said active moieties are released in renally excretable form.
    Type: Grant
    Filed: January 21, 1997
    Date of Patent: November 10, 1998
    Assignee: Nycomed Salutar, Inc.
    Inventors: Larry Margerum, Brian Campion, Jere Douglas Fellmann, Martha Garrity
  • Patent number: 5804161
    Abstract: Compounds of formula (I)?M.sub.6 Q.sub.8 B.sub.n L.sub.6-n !.sup.xwhere M is Re or Rh;each Q is a bridging atom selected from O, S, Se and Te;B is a monovalent non-bridging atom or moiety;L is a PR.sub.3 group in which R is C.sub.1-6 alkyl or aryl, optionally substituted on the alkyl or aryl group by one or more water-solubilizing groups such as an amine or hydroxidy group, or the three R groups together form a C.sub.6-10 trivalent group which may also contain up to three nitrogen or oxygen atoms;n is an integer from 0 to 6;and x is an integer from -2 to +4, representing the overall charge of the cluster, which when non-zero is accompanied by one or more counter ions of equal and balancing charge, and contrast media, particularly X-ray contrast media, containing them.
    Type: Grant
    Filed: August 26, 1996
    Date of Patent: September 8, 1998
    Assignee: Nycomed Salutar Inc.
    Inventors: Jeffrey R. Long, Xhiping Xheng, Richard H. Holm, Shi-Bao Yu, Michael Droege, William A. Sanderson
  • Patent number: 5798089
    Abstract: The invention provides amphiphilic compounds of the formula (I) Ch--(--L--Ar--(--AH).sub.n).sub.m (where Ch is a hydrophilic chelant moiety or a salt or a chelate thereof); each L is an optionally oxo substituted C.sub.2-25 -alkylene linker wherein at least one CH.sub.2 moiety is replaced by a group X.sup.1 (e.g. L may include a chain sequence, an X.sup.1 (CH.sub.2 CH.sub.2 X.sup.1).sub.u (where u is a positive integer) such as X.sup.1 (CH.sub.2 CH.sub.2 X.sup.1).sub.u, CH.sub.2 X.sup.1 CH.sub.2 CH.sub.2 X.sup.1 CH.sub.2 CH.sub.2 X.sup.1, CH.sub.2 X.sup.1 CH.sub.2 CH.sub.2 X.sup.1 CH.sub.2 CH.sub.2 X.sup.1 CH.sub.2 CH.sub.2 X.sup.1, etc.), and wherein L is optionally interrupted by a metabolizable group M but with the provisos that the terminus of L adjacent Ch is CH.sub.2 and that the terminus of L adjacent Ar is X.sup.1 or a CH.sub.2 group adjacent or separated by one CH.sub.2 from a group X.sup.1 (thus, for example the L--Ar linkage may be L.sup.1 --X.sup.1 --Ar, L.sup.1 --CH.sub.2 --Ar, L.sup.1 --X.sup.
    Type: Grant
    Filed: January 17, 1997
    Date of Patent: August 25, 1998
    Assignee: Nycomed Salutar, Inc.
    Inventors: John Varadarajan, Alan David Watson, Arne Berg
  • Patent number: 5717121
    Abstract: A process for the preparation of multinuclear cluster compounds by reacting a metal carbonyl with iodine, and use of these clusters and clusters derived from them, in diagnostic imaging. Novel multinuclear cluster compounds are also disclosed.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: February 10, 1998
    Assignee: Nycomed Salutar, Inc.
    Inventors: John D. Franolic, Jeffrey R. Long, Richard H. Holm, Michael Droege, Shannan Downey
  • Patent number: 5688486
    Abstract: Compounds including tight molecular meshes, preferably curved in one or two directions, such as fullerenes and met-cars, can be used as carriers for diagnostic or therapeutic agents, especially diagnostic contrast agents.
    Type: Grant
    Filed: October 31, 1994
    Date of Patent: November 18, 1997
    Assignee: Nycomed Salutar, Inc.
    Inventors: Alan D. Watson, Jo Klaveness, Gene C. Jamieson, Jere D. Fellmann, Nils B. Vogt
  • Patent number: 5614168
    Abstract: The invention relates to the use as contrast enhancing agents in medical imaging, especially X-ray imaging, of multinuclear complexes, i.e. complexes, such as those of W202 (U20) 2, in which the complexed entity comprises at least two contrast enhancing atoms.
    Type: Grant
    Filed: December 22, 1994
    Date of Patent: March 25, 1997
    Assignee: Nycomed Salutar Inc.
    Inventors: Arne Berg, Torsten Alm en, Klaus D. Krautwurst, Sook-Hui Kim, P.ang.l Rongved, Jo Klaveness, Harald Dugstad
  • Patent number: 5556968
    Abstract: Macrocyclic chelating agents, optionally possessing more than one macrocyclic ring having at least two peptide linkages within the macrocyclic skeleton. The chelating agents are used for the preparation of paramagnetic metal chelates for use as MRI contrast agents.
    Type: Grant
    Filed: May 7, 1993
    Date of Patent: September 17, 1996
    Assignee: Nycomed Salutar, Inc.
    Inventors: Joan F. Carvalho, Shaun P. Crofts, John Varadarajan
  • Patent number: 5554748
    Abstract: There are provided polychelants and their metal chelates which are useful in diagnostic imaging and in radiotherapy and which comprise a plurality of macrocyclic chelant moieties, e.g. DOTA residues, conjugated to a polyamine backbone molecule, e.g. polylysine. To produce a site-specific polychelate, one or more of the macrocyclic chelant carrying backbone molecules may be conjugated to a site-directed macromolecule, e.g. a protein. For example, adducts of a macrocyclic chelant can be formed by the process of (a) dispersing a carboxylic macrocyclic chelant in a polar, anhydrous solvent, (b) adding a base with a pKa sufficient to remove all carboxyl protons to create an amine salt of the chelant soluble in the solvent, (c) chilling the reaction mixture to between about 5.degree. C. and 55.degree. C.
    Type: Grant
    Filed: December 30, 1993
    Date of Patent: September 10, 1996
    Assignee: Nycomed Salutar, Inc.
    Inventors: Paul F. Sieving, Alan D. Watson
  • Patent number: 5482699
    Abstract: An imaging contrast medium comprising a physiologically tolerable multinuclear complex (as defined in claim 1) is disclosed. The multinuclear complex contains at least two, but preferably three or more contrast enhancing atoms. For X-ray or ultrasound imaging techniques heavy metal atoms are used to enhance contrast, whereas in Magnetic Resonance Imaging paramagnetic metal atoms are contrast enhancing. Molybdenum and tungsten are preferred contrast enhancing atoms. The medium may also be used therapeutically.
    Type: Grant
    Filed: September 24, 1993
    Date of Patent: January 9, 1996
    Assignee: Nycomed Salutar Inc.
    Inventors: Torsten Almen, Arne Berg, C. Allen Chang, Michael Droege, Harald Dugstad, Jere D. Fellman, Sook-Hui Kim, Jo Klaveness, Scott M. Rocklage, Pal Rongved, Brent Segal, Alan D. Watson
  • Patent number: 5458869
    Abstract: The invention relates to the use as contrast enhancing agents in medical imaging, especially X-ray imaging, of multinuclear complexes, i.e. complexes, such as those of W2O2 (u2O)2, in which the complexed entity comprises at least two contrast enhancing atoms.
    Type: Grant
    Filed: November 24, 1992
    Date of Patent: October 17, 1995
    Assignee: Nycomed Salutar Inc.
    Inventors: Arne Berg, Torsten Almen, Klaus D. Krautwurst, Sook-Hui Kim, Pal Rongved, Jo Klaveness, Harald Dugstad
  • Patent number: 5446145
    Abstract: There are disclosed polychelant compounds, that is multi-site metal chelating agents, and chelates formed therewith. The polychelants and especially their paramagnetic metal, heavy metal or radioactive metal polychelates are particularly suitable for use in diagnostic imaging, heavy metal detoxification or radiotherapy. The polychelants have a linear or branched oligomeric structure comprising alternating chelant and linker moieties bound together by amide or ester moieties the carbonyl groups whereof being adjacent the chelant moieties, each polychelant comprising at least two said chelant moieties capable of complexing a metal ion.
    Type: Grant
    Filed: July 7, 1993
    Date of Patent: August 29, 1995
    Assignee: Nycomed Salutar, Inc.
    Inventors: David B. Love, William C. Dow, Richard J. Himmelsbach, Alan D. Watson, Scott M. Rocklage