Abstract: The invention relates to crystalline lithium complexes of N-(1-hydroxymethyl-2,3-dihydroxypropyl)-1,4,7-triscarboxymethyl-1,4,7,10 tetraazacyclododecane, their production and the recovery of the salt-free gadolinium complex of N-(1-hydroxymethyl-2,3-dihydroxypropyl)-1,4,7-triscarboxymethyl-1,4,7,10 tetraazacyclododecane from the latter without the use of ion exchangers.

Abstract: Novel metal-chelate complexes comprising aminocarboxylate ligands including substituted aromatic amide moieties, such as those having the formula wherein R13, A1, R1 and R2 are as defined herein, are disclosed.

Abstract: The present invention is drawn to novel antiviral compounds, pharmaceutical compositions and their use. More specifically this invention is drawn to derivatives of monocyclic polyamines which have activity in standard tests against HIV- or FIV-infected cells as well as other biological activity related to binding of ligands to chemokine receptors that medicate a number of mammalian embryonic developmental processes.

Abstract: The present invention is directed, in general, to a method for making high yields of functionalized cyclic or acyclic tertiary amine-containing compounds, termed active esters, the functionalized compounds themselves, and diagnostic or therapeutic systems incorporating such compounds. Ester groups are attached to all but one of its Nitrogen atoms of the tertiary amine-containing compound. Therefore, an active agent, in the presence of coupling agent, attaches to the remaining amine via a carboxylate group attached to the amine, to produce high yields of the active ester. The active ester is then combined with a biomolecule, to produce high yields of a bioconjugated product. A metal ion may be chelated to the bioconjugated product to produce a chelating agent for use in either diagnostic or therapeutic applications.

Abstract: The present invention is directed, in general, to a method for making high yields of functionalized cyclic or acyclic tertiary amine-containing compounds, termed active esters, the functionalized compounds themselves, and diagnostic or therapeutic systems incorporating such compounds. Ester groups are attached to all but one of its Nitrogen atoms of the tertiary amine-containing compound. Therefore, an active agent, in the presence of coupling agent, attaches to the remaining amine via a carboxylate group attached to the amine, to produce high yields of the active ester. The active ester is then combined with a biomolecule, to produce high yields of a bioconjugated product. A metal ion may be chelated to the bioconjugated product to produce a chelating agent for use in either diagnostic or therapeutic applications.

Abstract: The metal complexes of general formula I 1

Abstract: A process for producing compound 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8] hexacosa,4,6,13,15,21,23-hexaene (2) and then compound 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosane (1) from compound (2) is described. The process uses a reaction between triaminoethylamine and glyoxal in the presence of water, alcohol and tertiary amine at low temperature to produce compound 2. Then compound 1 is produced from compound 2 by reduction with an alkali metal containing ammonia as the reductant. The compounds are aza cryptands which are used to bind metals and the like for electrides, and in alkalides, medicine and water treatment, for instance.

Abstract: The invention concerns a racemic compound of the pair of enantiomers of formula (III) wherein R represents an alkyl group or a phenyl group optionally substituted.

Abstract: The present invention provides an &agr;-particle-emitting radioisotope chelation complex comprising 225Actinium (225Ac) and 1,4,7,10,13,16-hexaazacyclohexadecane-N,N′,N′,N′,N′,N′-hexaacetic acid (HEHA) (225Ac-HEHA). Also provided is a bifunctional HEHA, and a bifunctional 225Ac-HEHA. The bifunctional HEHA and the bifunctional 225Ac-HEHA can be conjugated to a targeting agent. In view of the above, the present invention provides a method of making HEHA and methods of making a bifunctional HEHA, including a conjugate thereof Also provided are a method of treating disease, a method of treating cancer, a method of decontaminating a sample from 225Ac, a method of decontaminating a person who has been externally contaminated with 225Ac, and a method of detoxifying a person who has internalized 225Ac.

Abstract: The present invention relates to phosphate-binding compounds that find use in binding, detecting and isolating phosphorylated target molecules including the subsequent identification of target molecules that interact with phosphorylated target molecules or molecules capable of being phosphorylated. A binding solution is provide that comprises a phosphate-binding compound, an acid and a metal ion wherein the metal ion simultaneously interacts with an exposed phosphate group on a target molecule and the metal chelating moiety of the phosphate-binding compound forming a bridge between the phosphate-binding compound and a phosphorylated target molecule resulting in a ternary complex. The binding solution of the present invention finds use in binding and detecting immobilized and solubilized phosphorylated target molecules, isolation of phosphorylated target molecules from a complex mixture and aiding in proteomic analysis wherein kinase and phosphatase substrates and enzymes can be identified.

Abstract: The present invention relates to novel bifunctional chelates that are based on asymmetrical cyclen derivatives. The chelates contain either three acetates and one methylphosphonic arm or three acetates and one methylphosphonic arm enabling to link the chelate through P-alkyl within phosphoric acid derivative or through P—O-alkyl within phosphonic derivative to any organic back-bone suited for targeting. Suitable targeting moieties are monoclonal antibodies, their fragments and recombinant derivatives such as single chain antibodies, diabodies, triabodies, humanized, human or chimeric variants but also peptides, aptamers, spiegelmers, nucleotides, anti sense oligomers and conventional small molecules. These novel bifunctional chelates are suited for the production of kits for the routine labelling of targeting moieties to be used in radiotherapy with radiometals such as Yttrium-90, or for Magnetic Resonance Imagining (MRI) using Gadolinium.

Abstract: An improved method of synthesizing a macrocyclic tetraamido compound includes protecting the amino portion of an amino carboxylic acid to form a protected amino carboxylic acid; exposing the protected amino carboxylic acid to a first solvent, preferably a hydrocarbon solvent, such as toluene or 1,2-dichloroethane, dichloromethane, dibromomethane and 1,2-dibromoethane. The carboxylic acid portion of the protected amino carboxylic acid is then converted to an activated carboxylic acid by one of esterification or acid halide formation, to form a protected amino activated carboxylic acid derivative. The protected amino activated carboxylic acid derivative is reacted with a diamine in the presence of a second solvent, such as THF or ,2-dichloroethane, dichloromethane, dibromomethane and 1,2-dibromoethane, to form a protected diamide diamine intermediate.

Abstract: A multivalently interactive molecular assembly having a plurality of functional groups or ligands, in which a ratio between Rh and Rg expressed as Rh/Rg is 1.0 or less. Here, Rh is a hydrodynamic radius calculated from dynamic light scattering (DLS) assay performed in aqueous solution; and Rg is a radius of gyration determined based on the Zimm plot generated using data obtained by static light scattering (SLS) assay.

Abstract: 1,4,7,10-Tetrazacyclododecanes carrying a side chain terminating in a group capable of reacting with an antibody, and their complexes with a di- or tripositive metal having a coordination number of 6 or more can be used to prepare imaging agents. Typical metals are indium, copper, lead, bismuth, yttrium, terbium, gadolinium, and scandium. The compounds can be reacted with a monoclonal or polyclonal antibody or antibody fragment to target the metal to a specific type of tissue.

Abstract: The present invention relates to a novel sulfonamide derivatives and novel intermediates thereof, preparation thereof, and a pharmaceutical composition comprising the same, and more particularly, to novel sulfonamide derivatives and intermediates thereof that are used as angiogenesis controlling material and that can inhibit overexpression of matrix metalloproteinase that decomposes protein constituents in extracellular and basement membranes of connective tissues, and preparation methods thereof, and a pharmaceutical composition comprising the same.

Abstract: Metal chelates capable of exhibiting an immobilized relativity between about 60 and 200 mM−1s−1/metal atom are useful as magnetic resonance imaging agents.

Abstract: The present invention is drawn to novel antiviral compounds, pharmaceutical compositions and their use. More specifically this invention is drawn to derivatives of monocyclic polyamines which have activity in standard tests against HIV-infected cells as well as other biological activity related to binding of ligands to chemokine receptors that mediate a number of mammalian embryonic developmental processes.

Abstract: An ammonium selective ionophore for use in ion selective electrodes.

Abstract: A composition and method is disclosed for providing a magnetic resonance imaging contrast agent that is sensitive to pH, the compound and salts thereof including, a tetraaza base having a spacer at each of the amide groups, and a proton exchange attached to each of the spacer molecules, wherein the proton exchange group groups mediate proton exchange with water molecules that are trapped within the tetraaza base molecule.

Abstract: Tertrapyrrolic macrocycles selected from 5,10,15,20-tetraaryl-porphyrins and 5,10,15-triaryl-corrloes, wherein said aryl radical is a carboaryl, a heteroaryl or a mixed carboaryl-heteroaryl radical and at least two of said aryl radicals are positively charged, inhibit growth factor (e.g. bFGF, VEGF) receptor tyrosine kinase activity, and are useful for inhibition of cell proliferation mediated by growth factor receptor tyrosine kinase activity for example for inhibition of angiogenesis, or vascular smooth muscle cell proliferation in disorders including atherosclerosis, hyperthrophic heart failure and postsurfical restenosis, and of cell proliferation and migration in the treatment of primary tumors and metastasis. Some of the 5,10,15,20-tetraaryl-prophyrins are novel compounds.

Abstract: A new class of polychelants, their chelates with metal ions and their physiologically acceptable salts, useful, either as they are or in association or formulation with other components, for diagnostic imaging as general or specific contrast agents for specific tissues, organs or body compartments.

Abstract: Formula (I) compounds are described where the groups are as defined here below, processes for their preparation, and their uses for the preparation of conjugates with radionuclides for use in human and animal therapy and diagnostics, particularly for the diagnosis and therapy of pathological conditions such as tumours.

Abstract: This invention relates to macrocyclic chelants comprised of one or two heteroatom-containing bridges, compositions containing them and their use in medicine, particularly in diagnostic imaging and radiotherapy. This invention relates especially to the use of metal chelates of the macrocyclic chelants as metallopharmaceuticals in Magnetic Resonance Imaging (MRI) and radiopharmaceuticals. This invention also relates to macrocyclic chelants as bifunctional chelating agents (BFC's) for the labeling of biologically active targeting molecules such as proteins, peptides, peptidomimetics, and non-peptide receptor ligands, with metal ions and radioisotopes.

Abstract: Disclosed are guanidine and biguanidine derivatives which have anti-viral and anti-bacterial activity. Also disclosed are pharmaceutical compositions containing such compounds as an active ingredient, and anti-viral and anti-bacterial methods utilizing such compounds.

Abstract: Metal chelates capable of exhibiting an immobilized relativity between about 60 and 200 mM−1s−1/metal atom are useful as magnetic resonance imaging agents. Additionally, a compound which is useful as a metal-chelating ligand has the following formula: wherein Q is a 4- to an 8-membered carbocyclic ring which may be fully or partially saturated; t is an integer from 2 to 16; each R group is independently hydrogen, —OH, —CH2—A, —OCH2CH(OH)CH2—A or a functional group capable of forming a conjugate with a biomolecule, provided that at least two of the R groups are selected from —CH2—A or —OCH2CH(OH)CH2—A; and A is a moiety capable of chelating a metal atom.

Abstract: Perfluoroalkyl-containing complexes with polar radicals of general formula I (K)1-G-(Z-Rf)m(R)p  (I) in which R means the polar radical, Rf means a perfluorinated carbon chain, K is a metal complex, and Z represents a linker group, are suitable for intravenous lymphography, for tumor diagnosis and for infarction and necrosis imaging.

Abstract: Methods to elevate white blood cell counts in animal subjects using compounds of formula (1) are disclosed.

Abstract: The present invention is drawn to novel antiviral compounds, pharmaceutical compositions and their use. More specifically this invention is drawn to derivatives of monocyclic polyamines which have activity in standard tests against HIV- or FIV-infected cells as well as other biological activity related to binding of ligands to chemokine receptors that mediate a number of mammalian embryonic developmental processes.

Abstract: The present invention provides certain non-symmetric tripyrranes; that is, tripyrranes that do not contain a mirror plane of symmetry perpendicular to the plane containing the tripyrrane. Further, the invention includes texaphyrin compounds and sapphyrin compounds, as well as other polypyrrolic macrocycles, prepared using tripyrranes of Formula I as a precursor. These macrocycles are characterized by a tripyrrolic portion of the macrocyclic ring having substituents that cause the heterocycle to lack a plane of symmetry perpendicular to the plane of the macrocycle.

Abstract: Substituted 1,4,7-triazacyclononane-N,N′,N″-triacetic acid compounds with a pendant donor amino group, metal complexes thereof, compositions thereof, and methods of use in diagnostic imaging and treatment of a cellular disorder.

Abstract: The invention relates to novel magnetic resonance imaging contrast agents.

Abstract: A complex of a radiometal or paramagnetic metal ion with a metal chelating agent such as a diaminedioxime has attached thereto a substituent of formula —(Y)m—A—NHR, can function as a substrate for the fibrin-stabilizing Factor XIIIa. The complex is useful for the diagnosis or therapy of thrombosis, embolism, atherosclerosis, inflammation or cancer.

Abstract: 1,4,7,10-Tetraazacyclodecane, a precursor for the synthesis of macrocylic chelating agents for metal ions such as gadolinium, is prepared efficiently as a highly pure product on an industrial scale.

Abstract: The invention relates to ligands or complexes useful as catalysts for catalytically bleaching substrates with atmospheric oxygen, and as catalysts in the of treatment of textiles such as laundry fabrics whereby bleaching by atmospheric oxygen is catalysed after the treatment.

Abstract: The invention relates to conjugates that consist of macrocyclic metal complexes with biomolecules and their production. The conjugates are suitable as contrast media in NMR diagnosis and radiodiagnosis as well as as agents for radiotherapy. High relaxivity is achieved by a special liganding of macrocyclic compounds, and a fine-tuning of the relaxivity is made possible.

Abstract: Perfluoroalkyl-containing complexes with sugar radicals of general formula I in which R represents a monosaccharide or oligosaccharide radical that is bonded via the 1-OH position or 1-SH position, Rf means a perfluorinated carbon chain, K is a metal complex, and Y and Z represent linker groups, are suitable for intravenous lymphography, for tumor diagnosis and for infarction and necrosis imaging.

Abstract: The invention relates to substituted N-Aliphatic-N-Aromatic tertiary-Heteroalkylamine compounds useful as inhibitors of cholesteryl ester transfer protein (CETP; plasma lipid transfer protein-I) and compounds, compositions and methods for treating atherosclerosis, dyslipidemia, and other coronary artery disease.

Abstract: The present invention aims to provide cyclic peptide derivatives having motilin receptor antagonist activity or the like and useful as pharmaceuticals.

Abstract: Novel meso-aryl substituted expanded porphyrins comprising of alternate arrangement of more than six of pyrrole units bridged by a methine group whose hydrogen is substituted with Ar-group; and their synthetic method. Ar-group is either a 2,6-substituted phenyl group which can possess a substituent at the other 3, 4, and 5 positions, or 9-anthryl group which can possess a substituent at the other positions of the anthracence, or a cyclohexyl group which can possess a substituent at the other positions of the cyclohexyl group. The substituents at the 2 and 6 positions mentioned above can be selected independently from halogen atom or lower alkyl group of carbon number 1 to 4, substituents at 3-5 positions, 9-anthryl group and cyclohexyl group can be selected independently from the group consisting of substituted or non-substituted alkyl of carbon number 5 or 6, substituted or non-substituted aryl group, besides above mentioned substituents at 2 and 6 positions. Each Ar-group can be different.

Abstract: A formulation and method for therapeutic treatment of in mammals using certain metals or particle-emitting radionuclides complexed with tetraazamacrocyclic ligands are described.

Abstract: The present invention provides novel radiopharmaceuticals useful for the diagnosis of infection and inflammation, reagents and kits useful for preparing the radiopharmaceuticals, methods of imaging sites of infection and/or inflammation in a patient, and methods of diagnosing diseases associated with infection or inflammation in patients in need of such diagnosis. The radiopharmaceuticals bind in vivo to the leukotriene B4 (LTB4) receptor on the surface of leukocytes which accumulate at the site of infection and inflammation. The reagents provided by this invention are also useful for the treatment of diseases associated with infection and inflammation.

Abstract: The invention relates to macrocyclic metal complexes and their production and use for the production of conjugates with biomolecules. The conjugates are suitable as contrast media in NMR diagnosis and radiodiagnosis as well as for radiotherapy. High relaxivity is achieved by a special liganding of macrocyclic compounds, and a fine-tuning of the relaxivity is made possible.

Abstract: Polyamines containing at least two nitrogen atoms monosubstituted with pendant arms capable of coordinating metal cations, or with precursors of such pendant arms, all nitrogen atoms of the polyamines except two being fully substituted and the remaining two bearing one H atom each, are cyclized by reaction with a bridging agent that contains two sites that each bear a reactive group capable of undergoing a nucleophilic attack by one of the two N-H groups on the polyamine. Unlike the prior art, cyclization occurs in preference over polymerization of the polyamine, even in reaction mixtures in which the polyamine is at high concentration. A process is also disclosed whereby linear polyamines in which the terminal amine groups are primary amines are substituted with methylenephosphonate ester groups, with one such substituent on each nitrogen atom of the polyamine.

Abstract: Fluorescent chelates of lanthanide, terbium, europium and dysprosium with tetraazamacrocyclic compounds are discussed which can be used as fluorescent in vitro or in vivo diagnostic agents. These chelates are tissue specific imaging agents for soft tissue cancers.

Abstract: Actinium-225 (225Ac) complexes with functionalized chelants of the formula (I) wherein; each Q is independently hydrogen or ((CHR5)pCO2R; Q1 is hydrogen or (CHR5)wCO2R; each R independently is hydrogen, benzyl or C1-C4 alkyl; with the proviso that at least two of the sum of Q and Q1 must be other than hydrogen, each R5 independently is hydrogen; C1-C4 alkyl or (C1-C2 alkyl)phenyl; X and Y are each independently hydrogen or may be taken with an adjacent X and Y to form an additional carbon—carbon bond; n is 0 or 1; m is an integer from 0 to 10 inclusive; p is 1 or 2; r is 0 or 1; w is 0 or 1; with the proviso that n is only 1 when X and/or Y form an additional carbon to carbon bond, and the sum of r and w is 0 or 1; L is a linker/spacer group covalently bonded to, and replaces one hydrogen atom of one of the carbon atoms to which it is joined, said linker/spacer group being represented by the formula (1) wherein s is an integer of 0 or 1; t is an integer of 0 to 20 inclusive; R1 is an electrophilie or nu

Abstract: The present invention describes novel compounds of the formula: (Q)d—Ln—Ch, useful for the diagnosis and treatment of cancer, methods of imaging tumors in a patient, and methods of treating cancer in a patient. The present invention also provides novel compounds useful for monitoring therapeutic angiogenesis treatment and destruction of new angiogenic vasculature. The pharmaceuticals are comprised of a targeting moiety that binds to a receptor that is upregulated during angiogenesis, an optional linking group, and a therapeutically effective radioisotope or diagnostically effective imageable moiety. The imageable moiety is a gamma ray or positron emitting radioisotope, a magnetic resonance imaging contrast agent, an X-ray contrast agent, or an ultrasound contrast agent.

Abstract: Cyclic to Synthetic pseudopeptide derivatives of osteogenic growth polypeptide (OGP) and OGP(10-14) which are capable of enhancing bone cell proliferation and bone formation. Pharmaceutical composition comprising as active ingredient at least one pseudopeptide derivative of the invention and to the use of these pseudopeptide derivatives in the preparation of a pharmaceutical composition for stimulating the formation of osteoblastic or fibroblastic cells, enhancing bone formation in osteopenic pathological conditions, repairing fractures, healing wounds, grafting of intraosseous implants, reversing bone loss in osteoporosis and other conditions requiring enhanced bone cells formation.

Abstract: A novel compound which can be used in the field of separation and purification of gases is disclosed. The compound can be incorporated into a silica gel incorporating polyazacycloalkane structural units for separating a predetermined gas from a mixture of gases. The mixture of gases is brought into contact with a metallated hybrid gel under conditions which make possible the absorption of the gas to be separated, followed by a phase of desorption of the attached gas, and the recovery of the gas.

Abstract: Disclosed are compounds which are conjugates of (a) a moiety capable of localizing in the cells of a tumor or atheroma and (b) a moiety capable of catalyzing the production of reactive oxygen species from a cellular metabolite. The disclosed compounds which are useful for treating atheroma, tumors and other neoplastic tissue.

Abstract: Compounds of formula (I) and (II) wherein the R, R1, R2, R3 and R4 groups have the meanings defined in the disclosure, are useful chelants for metal ions. The complexes of compounds (I) and (II) with paramagnetic ions are useful as contrast agents for M.R.I. imaging.