The Hetero Ring Contains At Least Three Nitrogens Patents (Class 540/474)
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Patent number: 5874421Abstract: The present invention is directed to low molecular weight mimics of superoxide dismutase (SOD) represented by the formula: ##STR1## wherein R, R', R.sub.1, R'.sub.1, R.sub.2, R'.sub.2, R.sub.3, R'.sub.3, R.sub.4, R'.sub.4, R.sub.5, R'.sub.5, R.sub.6, R'.sub.6, R.sub.7, R'.sub.7, R.sub.8, R'.sub.8, R.sub.9, and R'.sub.9 and X, Y, Z and n are as defined herein, useful as therapeutic agents for inflammatory disease states and disorders, ischemic/reperfusion injury, stroke, atherosclerosis, hypertension and all other conditions of oxidant-induced tissue damage or injury.Type: GrantFiled: June 6, 1995Date of Patent: February 23, 1999Assignee: G. D. Searle & Co.Inventors: Dennis P. Riley, Randy H. Weiss, William L. Neuman, Anil S. Modak, Patrick J. Lennon, Karl W. Aston
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Patent number: 5874573Abstract: This invention involves synthesis and use of a class of compounds with chelation affinity and selectivity for first transition series elements. Administration of the free or conjugated compound, or physiological salts of the free or conjugated compound, results in decrease in the in vivo bioavailability of first transition series elements and/or removal from the body of first transition series elements and elements with similar chemical properties. These characteristics make such compounds useful in the management of diseases associated with a bodily excess of first transition series elements and elements with similar chemical properties. This invention demonstrates that such compounds inhibit mammalian, bacterial, and fungal cell replication and are therefore useful in the treatment of neoplasia, infection, inflammation, immune response, and in termination of pregnancy.Type: GrantFiled: June 24, 1996Date of Patent: February 23, 1999Assignee: Concat, Inc.Inventors: Harry S Winchell, Joseph Y Klein, Elliot D Simhon, Rosa L Cyjon, Ofer Klein, Haim Zaklad
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Patent number: 5871709Abstract: Tetraazacyclododecane compounds of general formula I ##STR1## in which E and Q are defined herein and their salts with inorganic and/or organic bases, amino acids or amino acid amides are valuable pharmaceutical agents.Type: GrantFiled: January 10, 1994Date of Patent: February 16, 1999Assignee: Schering AktiengesellschaftInventors: Heinz Gries, Hans-Joachim Weinmann, Johannes Platzek, Wolf-Rudiger Press, Hubert Vogler
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Patent number: 5869651Abstract: The invention relates to certain substituted derivatives of aminopolycarboxylic acids and metal chelates thereof. The compounds are particularly suitable for use as diagnostic agent. For example, the compounds can be used as radiodiagnostic agents, detoxification agents and contrast agents for diagnostic imaging processes. In particular, the high relaxivity paramagnetic metal chelates of substituted aminopolycarboxylic acids are especially suited for use as magnetic resonance imaging contrast agents.Type: GrantFiled: August 8, 1994Date of Patent: February 9, 1999Assignee: Nycomed SalutarInventors: Richard J. Himmelsbach, P.ang.l Rongved, Jo Klaveness, Per Strande, Harald Dugstad
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Patent number: 5853699Abstract: The disclosed metal complexes are suitable as contrast media for computer tomography of the liver and the biliary tracts.Type: GrantFiled: November 30, 1995Date of Patent: December 29, 1998Assignee: Schering AktiengesellschaftInventors: Franz-Karl Maier, Michael Bauer, Werner Krause, Ulrich Speck, Gabriele Schuhmann-Giampiere, Andreas Muhler, Thomas Balzer, Wolf-Rudiger Press
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Patent number: 5847121Abstract: Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, methods for radiometal labeling of biotin, as well as related compounds, are described. Articles of manufacture useful in pretargeting methods are also discussed.Type: GrantFiled: December 13, 1995Date of Patent: December 8, 1998Assignee: NeoRx CorporationInventors: Eric K. Yau, Louis J. Theodore, Linda M. Gustavson
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Patent number: 5847227Abstract: A method for producing aryl alkyl hydroperoxides which comprises selectively oxidizing an aryl alkyl hydrocarbon having the formula: ##STR1## wherein P and Q are hydrogen or an alkyl and may be the same or different from each other; x is an integer of 1-3; and Ar is an aromatic hydrocarbon group having a valence of x, with an oxygen-containing gas in the presence of a transition metal complex which contains, as a ligand, a cyclic polyfunctional amine compound having at least three nitrogen atoms in the ring forming molecular chain or an open chain polyfunctional amine compound having at least three nitrogen atoms in the main chain of the molecule.Type: GrantFiled: February 27, 1996Date of Patent: December 8, 1998Assignee: Mitsui Petrochemical Industries, Ltd.Inventors: Terunori Fujita, Shigekazu Matsui, Toshihiro Takai, Hideto Matsuoka, Akifumi Kagayama, Hiroshi Kuroda, Masayasu Ishibashi, Hiroshi Iwasaki, Nobuya Hirokane
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Patent number: 5837202Abstract: An fluorescent metal-chelating amphiphile having the structure: ##STR1## wherein A is a hydrophobic fluorophore, X and Y are aliphatic hydrocarbons having from 9 to 25 carbon atoms, B is a hydrophilic spacer, C is a metal chelator, and L is either an ether or ester linkage.The fluorescent metal-chelating amphiphile is combined with a matrix lipid to form lipid-based sensors which provide fluorometric detection of metal ions in liquids.Type: GrantFiled: September 11, 1996Date of Patent: November 17, 1998Assignee: California Institute of TechnologyInventors: Frances H. Arnold, Darryl Y. Sasaki
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Patent number: 5834456Abstract: Polyazamacrocyclofluoromonoalkylphosphonic acid compounds are disclosed which form inert complexes with Gd, Mn, Fe or La ions. The complexes are useful as contrast agents for diagnostic purposes.Type: GrantFiled: February 23, 1996Date of Patent: November 10, 1998Assignees: The Dow Chemical Company, The University of TexasInventors: Garry E. Kiefer, A. Dean Sherry
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Patent number: 5831088Abstract: A .beta.,.beta.'-dihydroxy meso-substituted chlorin, bacteriochlorin or isobacteriochlorin compound having the formula (I) or (II): ##STR1## wherein M is a metal. A novel method for synthesizing the compound of formula (I) or (II) comprises the steps of:a. osmylating a .beta...beta.'-unsubstituted, meso-substituted porphyrin to form an osmate ester at the .beta.,.beta.'-position, andb. reducing the osmate ester to form the corresponding .beta.,.beta.'-dihydroxy meso-substituted chlorin, bacteriochlorin or isobacteriochlorin of formula (I) or (II).Type: GrantFiled: May 8, 1997Date of Patent: November 3, 1998Assignee: The University of British ColumbiaInventors: David Dolphin, Christian Bruckner
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Patent number: 5817807Abstract: Macrocyclic compounds having 1, 4, 8, 11-tetraazacyclotetradecanyl group, show good selectivity against HIV-1 and HIV-2, in in vitro tests are disclosed.Type: GrantFiled: June 6, 1996Date of Patent: October 6, 1998Assignee: Anormed Inc.Inventors: Gary J. Bridger, Sreenivasan Padmanabhan, Renato T. Skerlj, Pedro E. Hernandez-Abad, Milind P. Sant
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Patent number: 5808054Abstract: A compound of Formula I: ##STR1## wherein: Q represents identical alkyl groups, cycloalkyl groups having from 5 to 7 ring atoms, or aryl or heteroaryl groups having from 5 to 12 ring atoms andR represents identical hydrogen, alkyl, alcohol or carbonyl-containing groups;or a composition containing from 5 to 100 mole % by weight of the compound of Formula I. A novel method for synthesizing the compound of Formula I comprises the steps of:(a) reacting a compound of the formula:Q--CHO or Q--CH(OS)(OS')wherein Q is as defined above and S and S' are independently lower alkyl, an aryl group containing from 5 to 14 ring atoms, and --(CH.sub.2).sub.n -- where n=2-4, with an excess amount of a pyrrole in the presence of a catalytic amount of a strong Lewis or Bronsted acid;(b) removing any unreacted pyrrole or other solvents used by evaporation;(c) removing polymeric materials and removing the corresponding dipyrromethane by-product, leaving the compound of Formula I.Type: GrantFiled: March 7, 1996Date of Patent: September 15, 1998Assignee: QLT PhotoTherapeutics, Inc.Inventors: Christian Bruckner, Ross W. Boyle, David Dolphin
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Patent number: 5798089Abstract: 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: GrantFiled: January 17, 1997Date of Patent: August 25, 1998Assignee: Nycomed Salutar, Inc.Inventors: John Varadarajan, Alan David Watson, Arne Berg
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Patent number: 5789586Abstract: A method for preparing functionalized derivatives of organic or inorganic compounds and tetrapyrrolic compounds in particular, all of which compounds have at least one sulfonic acid group, by first preparing a sulfonyl halide intermediate of the compound then reacting the intermediate with a second compound having a reactive hydroxyl or amine group to yield the desired sulfonylamide or sulfonic esters thereof. The method may be used to produce a variety of photosensitive compounds having different functionality. For example, sulfonamide or sulfonic ester reaction products of the tetrapyrrolic compounds or other photosensitive organic molecules may exhibit an enhanced ability to localize at a particular target site for phototherapy.Type: GrantFiled: July 7, 1997Date of Patent: August 4, 1998Assignee: PDT Pharmaceuticals, Inc.Inventor: Byron Robinson
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Patent number: 5780622Abstract: A novel 5,15-diarylbenzochlorin-7-one compound having the formula (I) or (II): ##STR1## wherein M is a metal. A novel method for synthesizing the compound of formula (I) comprises the steps of:a. cyclizing a meso-(formylvinyl) 5,15-diarylporphyrin to form a cyclization reaction mixture, andb. oxidizing said reaction mixture to form the 5,15-diarylbenzochlorin-7-one of formula (I).A novel method for synthesizing the compound of formula (II) comprises the cyclizing and oxidizing steps listed above and, either prior to or after the oxidizing step, adding the step of demetallating the compound.Type: GrantFiled: August 11, 1997Date of Patent: July 14, 1998Assignee: The University of British ColumbiaInventors: David Dolphin, Ross Boyle
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Patent number: 5770730Abstract: A method for the preparation of an imide derivative of purpurin by reacting hexylamine with a chlorin or bacteriochlorin having a macrocycle with a six-membered anhydride ring fused thereto, said macrocycle containing a and b rings which may be saturated or unsaturated at R.sub.4 to R.sub.11 positions of the rings and which R.sub.4 and R.sub.11, positions may contain at least one group selected from the group consisting of hydrogen, hydroxy, formyl, substituted and unsubstituted alkyl, alkoxy, alkenyl, aryl and aryloxy wherein carbon containing groups may be substituted with a substituent selected from, hydroxy, phosphoro, carboxy, halo, sulfo, amino and ether, to obtain a purpurin derivative; and reacting the purpurin derivative with a carbodiimide to obtain the imide derivative of purpurin. The invention further includes novel imides made by the method.Type: GrantFiled: March 8, 1996Date of Patent: June 23, 1998Assignee: Health Research, Inc.Inventors: Ravindra K. Pandey, Andrei N. Kozyrev, Thomas J. Dougherty
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Patent number: 5760191Abstract: A metal chelate comprising a compound having the following formula and one or more metal ions which metal ions are a radionucleotide or a paramagnetic metal ion: ##STR1##Type: GrantFiled: February 22, 1995Date of Patent: June 2, 1998Assignee: Nycomed Imaging ASInventors: Robert A. Snow, Daniel J. Delecki, Chandra R. Shah
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Patent number: 5756065Abstract: A group conjugates having a functionalized polyaminocarboxylate chelant that form complexes with rare earth-type metal ions, covalently attached to an antibody or antibody fragment, can be used for therapeutic and/or diagnostic purposes.Type: GrantFiled: February 15, 1995Date of Patent: May 26, 1998Assignee: The Dow Chemical CompanyInventors: David A. Wilson, Joseph R. Garlich, William A. Fordyce, R. Keith Frank, Jaime Simon, William F. Goeckler, Roberta C. Cheng, William J. Kruper, Kenneth McMillan
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Patent number: 5756726Abstract: Novel texaphyrin compounds having improved functionalization are described. Metal complexes of these compounds are active as photosensitizers for the generation of singlet oxygen and thus are potentially useful for treatments performed with singlet oxygen. Several of the metallotexaphyrin complexes absorb light in the physiologically important range of 690-880 nm. The complexes form long-lived triplet states and thus may act as efficient photosensitizers for generation of singlet oxygen.Type: GrantFiled: June 6, 1995Date of Patent: May 26, 1998Assignees: Pharmacyclics, Inc., Board of Regents, The University of Texas SystemInventors: Gregory W. Hemmi, Jonathan L. Sessler, Tarak D. Mody
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Patent number: 5756727Abstract: The chiral manganese-triazonone complex of the general formula (I) is disclosed:?Mn.sub.u (L).sub.V (OR).sub.W (.mu.-O).sub.X (.mu.OAc).sub.y !X.sub.z(I)The complex is useful industrially to prepare chiral compounds.Type: GrantFiled: June 28, 1996Date of Patent: May 26, 1998Assignee: Hoechst AGInventors: Matthias Beller, Ahmed Tafesh, Richard Walter Fischer, Bernd Scharbert
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Patent number: 5756728Abstract: An improved process for preparing 1,1'-?1,4-phenylenebis-(methylene)!-bis-1,4,8,11-tetraazacyclotetradecane comprising the selective functionalization of an acyclic tetraamine, and subsequent dimerization and hydrolyzation/tosylation to obtain a 1,4-phenylenebis-methylene bridged hexatosyl acyclic precursor in a first step, the cyclization of said precursor to obtain a hexatosyl cyclam dimer in a second step, and the detosylation of said cyclam dimer in a third step followed by basification to obtain the desired 1,1'-?1,4-phenylenebis-(methylene)!-bis-1,4,8,11-tetraazacyclotetradecane.Type: GrantFiled: December 30, 1996Date of Patent: May 26, 1998Assignee: Johnson Matthey Public Limited CompanyInventors: David Xu, Prasad Kapa, Oljan Repic, Thomas J. Blacklock
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Patent number: 5747000Abstract: The invention relates to the use of macrocyclic metal complexes that consist of a complexing agent of formula I and at least one metal ion of an element of atomic numbers 21-29, 42, 44 or 57-70 ##STR1## in which n, R.sup.1, R.sup.2, R.sup.3 and A are as set forth in the specification, are useful as temperature sensors.Type: GrantFiled: March 8, 1996Date of Patent: May 5, 1998Assignee: Schering AktiengesellschaftInventors: Johannes Platzek, Bernd Raduchel, Ulrich Niedballa, Hanns-Joachim Weinmann, Hans Bauer, Klaus Roth
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Patent number: 5744598Abstract: Purified imines of porphyrins, chlorins, bateriochlorins, chlorophylls, bacteriochlorophylls, purpurins, reduced purpurins, verdins, Diels Alder adducts, benzochlorins and metal complexes of the foregoing imines are disclosed. The formulas of the benzochlorinimines and of the benzochlorinimine metal complexes are set forth below: ##STR1## In specific examples, M in the metal complexes is a copper cation that is complexed with two of the nitrogens of the benzochlorinimine R' and R"" are methyl, and R1 through R8 are ethyl.Type: GrantFiled: April 29, 1996Date of Patent: April 28, 1998Assignees: University of Toledo, Medical College of OhioInventors: Dimitris Skalkos, Steven H. Selman, James A. Hampton, Alan R. Morgan
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Patent number: 5739323Abstract: A group of functionalized polyaminocarboxamide modified chelators, such as 1,4 7,10-tetraaza-1-N-(1-carboxy-3-(4-aminophenyl)propyl)-7-N-(1-carboxymethyl )bis-4,10-N,N-(carboxamidomethyl)cyclododecane and 1,4 7,10-tetraaza-1-N-(1-carboxy-3-(4-aminophenyl)propyl)bis-4,7-N,N-(1-carbox ymethyl)-10-N-(carboxamidomethyl)cyclododecane are disclosed. These modified chelators are capable of forming complexes with rare earth-type metal ions. When the complexes are covalently attached to an antibody or antibody fragment, they can be used in therapeutic and diagnostic applications.Type: GrantFiled: April 13, 1995Date of Patent: April 14, 1998Assignee: The Dow Chemical CompanyInventors: William J. Kruper, Jr., William A. Fordyce, A. Dean Sherry
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Patent number: 5731299Abstract: The present invention relates to phosphonsulfonates and the pharmaceutically-acceptable salts and esters thereof, having the following structure according to formula (I): ##STR1## The present invention further relates to pharmaceutical compositions containing a safe and effective amount of a compound of the present invention, and pharmaceutically-acceptable excipients. Finally, the present invention relates to methods for treating or preventing pathological conditions characterized by abnormal calcium and phosphate metabolism in humans or other mammals, including treating or preventing osteoporosis and arthritis, especially rheumatoid arthritis and osteoarthritis. This method comprises administering to a human or other mammal in need of such treatment of a safe and effective amount of a compound or composition of the present invention.Type: GrantFiled: May 7, 1993Date of Patent: March 24, 1998Assignee: The Procter & Gamble CompanyInventors: Frank Hallock Ebetino, Allan Vincent Bayless, Susan Mary Dansereau
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Patent number: 5723456Abstract: A method for treating endothelial cell dysfunction, such as associated with cardiovascular disease are disclosed, particularly using the isozyme selective PKC inhibitor, (S)-3,4-?N,N'-1,1'-((27"-ethoxy)-3'"(O)-4'"-(N,N-dimethylamino)-butane)-bi s-(3,3'-indolyl)!-1(H)-pyrrole-2,5-dione hydrochloride salt.Type: GrantFiled: June 13, 1996Date of Patent: March 3, 1998Assignee: Eli Lilly & CompanyInventors: Michael R. Jirousek, William Francis Heath, Jr., Douglas Kirk Ways, Lawrence E. Stramm
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Patent number: 5714604Abstract: A novel process for the preparation of azamacrocyclic or acyclic aminophosphonate ester derivatives is disclosed. The process concerns the reaction of an appropriate azamacrocyclic or acyclic primary or secondary amine with trialkyl phosphite and paraformaldehyde.Type: GrantFiled: May 6, 1993Date of Patent: February 3, 1998Assignee: The Dow Chemical CompanyInventor: Garry E. Kiefer
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Patent number: 5712396Abstract: .alpha.-Phosphonosulfonate compounds are provided which inhibit the enzyme squalene synthetase and thereby inhibit cholesterol biosynthesis. These compounds have the formula ##STR1## wherein R.sup.2 is OR.sup.5 or R.sup.5a ; R.sup.3 and R.sup.5 are independently H, alkyl, arylalkyl, aryl or cycloalkyl; R.sup.5a is H, alkyl, arylalkyl or aryl; R4 is H, alkyl, aryl, arylalkyl, or cycloalkyl;, Z is H, halogen, lower alkyl or lower alkenyl; and R.sup.1 is a lipophilic group which contains at least 7 carbons and is alkyl, alkenyl, alkynyl, mixed alkenyl-alkynyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, cycloheteroalkyl, cycloheteroalkylalkyl; as further defined above; including pharmaceutically acceptable salts and or prodrug esters of the phosphonic (phosphinic) and/or sulfonic acids.Type: GrantFiled: July 5, 1994Date of Patent: January 27, 1998Inventors: David R. Magnin, Scott A. Biller, John K. Dickson, Jr., R. Michael Lawrence, Richard B. Sulsky
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Patent number: 5712389Abstract: Poly(amino acid) derivatives, which are chelating agents of paramagnetic metal ions, in which at least 3 of the donor nitrogen atoms carry identical or different substituents, of formulaCH (R.sub.1) --X,in which X represents CO.sub.2 R.sub.a, CONR.sub.b R.sub.c or P(R.sub.d)O.sub.2 H and R.sub.a, R.sub.b and R.sub.c, which are identical or different, represent H or optionally hydroxylated (C.sub.1 -C.sub.8)alkyl, R.sub.d represents OH, (C.sub.1 -C.sub.8)alkyl or (C.sub.1 -C.sub.8)alkoxy and R.sub.1 represents a hydrophilic group with a molecular weight greater than 200 containing at least 3 oxygen atoms, with the proviso that at least 3 of the X groups are optionally salified acid functional groups.Type: GrantFiled: February 28, 1997Date of Patent: January 27, 1998Assignee: Guerbet S.A.Inventors: Dominique Meyer, Olivier Rousseaux, Michel Schaefer, Christian Simonot
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Patent number: 5708166Abstract: This invention relates to novel compounds able to chelate paramagnetic bi- or trivalent metal ions, their chelates with said metal ions and their use as contrast agents in magnetic resonance imaging (MRI).Type: GrantFiled: January 14, 1997Date of Patent: January 13, 1998Assignee: Dibra S.p.A.Inventors: Fulvio Uggeri, Pier Lucio Anelli, Giuseppe Manfredi, Marino Brocchetta, Franco Fedeli
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Patent number: 5705637Abstract: The present invention relates to tribenzylcyclen compounds of formula I ##STR1## (where R is hydrogen, or a C.sub.1-12 alkyl group optionally substituted by hydroxy, alkoxy or aryl groups or R is an amphiphilic aralkyl group comprising a N, S, O or P interrupted C.sub.2-25 alkylene chain, e.g. a polyalkylene oxide chain or R provides a bridge to a second tribenzylcyclen group, but with the proviso that R is other than benzyl; X is CHR.sub.1, or where R is hydrogen two X groups may each represent CO groups; and R.sub.1 is hydrogen, a C.sub.1-6 alkyl group optionally substituted by hydroxy, alkoxy or carboxy groups or an aralkyl group having 1 to 6 carbons in the alkyl moiety and optionally. substituted in the aryl moiety by alkyl, alkoxy, hydroxy or isothiocyanate groups). These compounds are useful in the preparation of DO3A, N-substituted-1,4,7,10-tetraazacyclododecane-N',N",N'"-triacetic acids, and the phosphonic acid analogs.Type: GrantFiled: February 3, 1997Date of Patent: January 6, 1998Assignee: Nycomed Imaging ASInventors: Lisa Schultze, Alan Ray Bulls
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Patent number: 5698674Abstract: The present invention provides a triheterocyclic peptide having first, second, and third 5-member heterocyclic moieties having the following formula CR.sub.3 CONH--Q.sup.1 --CONH--Q.sup.2 --CONH--Q.sup.3 -CONH--(CR.sub.3).sub.S --B, wherein Q.sup.1 is selected from a group consisting of: ##STR1## wherein Q.sup.2 is selected from a group consisting of: ##STR2## wherein Q.sup.3 is selected from a group consisting of: ##STR3## wherein at least one of A and Z is other than C; wherein A is C, N, O, or S; wherein B is N(CR.sub.3).sub.n or C(NH.sub.2).sub.2 ; wherein n is an integer from 2 to 10; wherein P is H, a lower alkyl or a halogen; wherein Q1, Q2, and Q3 are the same or different; wherein R is H, a lower alkyl group; wherein S is an integer from 1 to 10; wherein X' represents CR.sub.3, (CR.sub.2).sub.n --NRY, or (CR.sub.2).sub.n --CR.sub.2 Y; wherein X" represents CR.sub.3, (CR.sub.2).sub.n --NRY, or (CR.sub.2).sub.n --CR.sub.2 Y; wherein X'" represents CR.sub.3, (CR.sub.2).sub.n --NRY, or (CR.sub.2).sub.Type: GrantFiled: April 13, 1994Date of Patent: December 16, 1997Assignee: The Regents of the University of CaliforniaInventors: Thomas C. Bruice, Kenneth A. Browne, Gong-Xin He
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Patent number: 5684135Type: GrantFiled: May 26, 1995Date of Patent: November 4, 1997Assignee: Celltech Therapeutics LimitedInventors: David Parker, Nigel Robert Arnold Beeley, Thomas Andrew Millican
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Patent number: 5684149Abstract: The present invention provides the first examples of metal complexes that show catalytic behavior in RNA transesterification under physiological relevant conditions i.e., 37.degree. C. and neutral pH. The metal complexes are catalytically active and kinetically inert to metal ion dissociation.The metal complexes are formed by the union of a central metal ion with a non-metallic ion or molecule. The metal ion comprises copper, zinc, cobalt, nickel, palladium, lead, iridium, maganese, iron, molybdenum, vanadium, titanium, ruthenium, bismuth, cadmium, yttrium, magnesium, rhodium, uranium, the transition metals and the Lanthanide metals. The non-metallic ion comprises a ligand or complexing agent. The preferred ligand is one which strongly chelates lanthanides, and more preferably, forms a cationic complex of the lanthanides.Type: GrantFiled: February 17, 1995Date of Patent: November 4, 1997Assignee: Research Foundation of State University of New YorkInventor: Janet R. Morrow
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Patent number: 5677446Abstract: The present invention relates to tribenzylcyclen compounds of formula I ##STR1## (where R is hydrogen, or a C.sub.1-12 alkyl group optionally substituted by hydroxy, alkoxy or aryl groups or R is an amphiphilic aralkyl group comprising a N, S, O or P interrupted C.sub.2-25 alkylene chain, e.g. a polyalkylene oxide chain or R provides a bridge to a second tribenzylcyclen group, but with the proviso that R is other than benzyl; X is CHR.sub.1, or where R is hydrogen two X groups may each represent CO groups; and R.sub.1 is hydrogen, a C.sub.1-6 alkyl group optionally substituted by hydroxy, alkoxy or carboxy groups or an aralkyl group having 1 to 6 carbons in the alkyl moiety and optionally. substituted in the aryl moiety by alkyl, alkoxy, hydroxy or isothiocyanate groups). These compounds are useful in the preparation of DO3A, N-substituted-1,4,7,10-tetraazacyclododecane-N',N",N"'-triacetic acids, and the phosphonic acid analogs.Type: GrantFiled: June 7, 1995Date of Patent: October 14, 1997Assignee: Nycomed Imaging ASInventors: Lisa Schultze, Al Ray Bulls
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Patent number: 5656756Abstract: A novel 5,15-diarylbenzochlorin-7-one compound having the formula (I) or (II): ##STR1## wherein M is a metal. A novel method for synthesizing the compound of formula (I) comprises the steps of:a. cyclizing a meso-(formylvinyl) 5,15-diarylporphyrin to form a cyclization reaction mixture, andb. oxidizing said reaction mixture to form the 5,15-diarylbenzochlorin-7-one of formula (I).A novel method for synthesizing the compound of formula (II) comprises the cyclizing and oxidizing steps listed above and, either prior to or after the oxidizing step, adding the step of demetallating the compound.Type: GrantFiled: April 29, 1994Date of Patent: August 12, 1997Assignee: The University of British ColumbiaInventors: David Dolphin, Ross Boyle
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Patent number: 5653960Type: GrantFiled: September 23, 1994Date of Patent: August 5, 1997Assignee: Celltech Therapeutics LimitedInventors: David Parker, Nigel Robert Arnold Beeley
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Patent number: 5652361Abstract: A group of functionalized polyaminocarboxylate chelants that form complexes with rare earth-type metal ions are disclosed. The complexes, covalently attached to an antibody or antibody fragment, can be used for therapeutic and/or diagnostic purposes.Type: GrantFiled: March 8, 1993Date of Patent: July 29, 1997Assignee: The Dow Chemical CompanyInventors: Jaime Simon, Joseph R. Garlich, Garry E. Kiefer, Kenneth McMillan, Richard Keith Frank, William F. Goeckeler, William A. Fordyce, Roberta C. Cheng, William J. Kruper, Jr., Sharon Baughman, David A. Wilson
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Patent number: 5650133Abstract: 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: GrantFiled: April 12, 1994Date of Patent: July 22, 1997Assignee: Nycomed SalutarInventors: Joan Carvalho, Alan D. Watson, Jere D. Fellmann, Michael David Koo
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Patent number: 5648485Abstract: A .beta.,.beta.'-dihydroxy meso-substituted chlorin, bacteriochlorin or isobacteriochlorin compound having the formula (I) or (II): ##STR1## wherein M is a metal. A novel method for synthesizing the compound of formula (I) or (II) comprises the steps of:a. osmylating a .beta...beta.'-unsubstituted, meso-substituted porphyrin to form an osmate ester at the .beta.,.beta.'-position, andb. reducing the osmate ester to form the corresponding .beta.,.beta.'-dihydroxy meso-substituted chlorin, bacteriochlorin or isobacteriochlorin of formula (I) or (II).Type: GrantFiled: October 26, 1994Date of Patent: July 15, 1997Assignee: University of British ColumbiaInventors: David Dolphin, Christian Bruckner
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Patent number: 5648063Abstract: A diagnostic medium contains at least one physiologically well tolerated complex salt comprising an anion of a complexing acid and one or more central ion or ions of an element with an atomic number of 21 to 29, 42, 44 or 57 to 83 and, optionally, one or more physiologically biocompatible cation or cations of an inorganic and/or organic base or amino acid, optionally, with additives customary in galenic formulations, dissolved or suspended in an aqueous medium.Type: GrantFiled: August 4, 1993Date of Patent: July 15, 1997Assignee: Schering AktiengesellschaftInventors: Heinz Gries, Douwe Rosenberg, Hanns-Joachim Weinmann, Ulrich Speck, Wolfgang Mutzel, Georg-Alexander Hoyer, Heinrich Pfeiffer, deceased, Franz-Josef Renneke
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Patent number: 5641878Abstract: Fluorescent dyes which are free of aggregation and serum binding are provided. These dyes are suitable for applications such as fluorescence immunoassays, in vivo imaging and in vivo tumor therapy. The dyes are particularly useful in fluorescence immunoassays of biological samples containing serum. Such dyes have two polyoxyhydrocarbyl moities, one located on either side of a planar molecular structure such as a porphyrin derivative, azaporphyrin derivative, corrin derivative, sapphyrin derivative or porphycene derivative.Type: GrantFiled: November 2, 1994Date of Patent: June 24, 1997Assignee: Diatron CorporationInventors: Walter B. Dandliker, Mao-Lin Hsu
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Patent number: 5639879Abstract: A simple method for the synthesis of 1,4,7, 10-tetraazacyclododecane N,N'N",N'"-tetraacetic acid and 1,4,8,11-tetraazacyclotetradecane N,N',N",N'"-tetraacetic acid involves cyanomethylating 1,4,7, 10-tetraazacyclododecane or 1,4,8,11-tetraazacyclotetradecane to form a tetranitrile and hydrolyzing the tetranitrile. These macrocyclic compounds are functionalized through one of the carboxylates and then conjugated to various biological molecules including monoclonal antibodies. The resulting conjugated molecules are labeled with radiometals for SPECT and PET imaging and for radiotherapy.Type: GrantFiled: February 2, 1995Date of Patent: June 17, 1997Assignee: Associated Universities, Inc.Inventors: Ronnie C. Mease, Leonard F. Mausner, Suresh C. Srivastava
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Patent number: 5637578Abstract: The present invention is directed to low molecular weight mimics of superoxide dismutase (SOD) represented by the formula: ##STR1## wherein R, R', R.sub.1, R'.sub.1, R.sub.2, R'.sub.2, R.sub.3, R'.sub.3, R.sub.4, R'.sub.4, R.sub.5, R'.sub.5, R.sub.6, R'.sub.6, R.sub.7, R'.sub.7, R.sub.8, R'.sub.8, R.sub.9, and R'.sub.9 and X, Y, Z and n are as defined herein, useful as therapeutic agents for inflammatory disease states and disorders, ischemic/reperfusion injury, stroke, atherosclerosis, hypertension and all other conditions of oxidant-induced tissue damage or injury.Type: GrantFiled: May 16, 1995Date of Patent: June 10, 1997Inventors: Dennis P. Riley, Randy H. Weiss, William L. Neuman, Anil S. Modak, Patrick J. Lennon, Karl W. Aston
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Patent number: 5630997Abstract: The present invention relates to a new polyazamacrocyclic compound or a salt thereof and its uses as a tissue specific chelator. The compound has the formula ##STR1## where x is 2, 3 or a combination of p 2(s) and q 3(s) where p +q=y;y is 3 or 4;R is (CH.sub.2).sub.z P(.dbd.O)OR.sup.1 OR.sup.2 ;R.sup.1 is H or CH.sub.3 ;R.sup.2 is C.sub.n H.sub.1+2n ;n is 4 to 6;z is 1 to 3.In one important embodiment, this compound may be complexed with a metal to be a polyazamacrocyclic compound-metal complex having the formula ##STR2## where r is 2 or 3; andM is a metal ion, including a lanthanide, a heavy metal, or a radionuclide metal.Type: GrantFiled: November 8, 1994Date of Patent: May 20, 1997Assignees: Board of Regents, The University of Texas System, Dow Chemical CompanyInventors: A. Dean Sherry, Garry E. Kiefer
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Patent number: 5630996Abstract: Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, methods for radiometal labeling of biotin and for improved radiohalogenation of biotin, as well as related compounds, are described. Also, clearing agents, anti-ligand-targeting moiety conjugates, target cell retention enhancing moieties and additional methods are discussed.Type: GrantFiled: September 16, 1993Date of Patent: May 20, 1997Assignee: NeoRx CorporationInventors: John M. Reno, Louis J. Theodore, Linda M. Gustavson
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Patent number: 5631368Abstract: The present invention relates to tribenzylcyclen compounds of formula I ##STR1## (where R is hydrogen, or a C.sub.1-12 alkyl group optionally substituted by hydroxy, alkoxy or aryl groups or R is an amphiphilic aralkyl group comprising a N, S, O or P interrupted C.sub.2-25 alkylene chain, e.g. a polyalkylene oxide chain or R provides a bridge to a second tribenzylcyclen group, but with the proviso that R is other than benzyl; X is CHR.sub.1, or where R is hydrogen two X groups may each represent CO groups; and R.sub.1 is hydrogen, a C.sub.1-6 alkyl group optionally substituted by hydroxy, alkoxy or carboxy groups or an aralkyl group having 1 to 6 carbons in the alkyl moiety and optionally substituted in the aryl moiety by alkyl, alkoxy, hydroxy or isothiocyanate groups). These compounds are useful in the preparation of DO3A, N-substituted-1,4,7,10-tetraazacyclododecane-N',N",N"'-triacetic acids, and the phosphonic acid analogs.Type: GrantFiled: June 7, 1995Date of Patent: May 20, 1997Assignee: Nycomed Imaging ASInventors: Lisa Schultze, Alan R. Bulls
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Patent number: 5622945Abstract: The present invention is directed to the synthesis and use of novel macrocyclic compounds, based upon a new class of expanded porphyrins, termed rubyrins. Disclosed herein is the structure and synthesis of a prototypical rubyrin and various substituted rubyrin analogues, conjugates and compositions. Rubyrin itself is characterized by the presence of six pyrrolic subunits contained within a fully aromatic 26 .pi.-electron macrocyclic framework and by UV/VIS absorption bands that are very red-shifted as compared to those of other porphyrins or pentapyrrolic expanded porphyrins. The rubyrin-type class of compounds is further characterized by an ability to undergo facile protonation at the pyrrolic nitrogens and, once protonated, by an ability to form complexes with anions such as nucleotide-containing compounds. Rubyrin-based compounds are useful as, for example, anion chelators and receptors and as transporters for various anionic compounds including antiviral agents. In addition to the 26 .pi.Type: GrantFiled: January 4, 1995Date of Patent: April 22, 1997Assignee: Board of Regents, The University of Texas SystemInventors: Jonathan L. Sessler, Takashi Morishima, Steven J. Weghorn
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Patent number: 5622688Abstract: This invention relates to novel compounds able to chelate paramagnetic bi- or trivalent metal ions, their chelates with said metal ions and their use as contrast agents in magnetic resonance imaging (MRI).Type: GrantFiled: May 24, 1995Date of Patent: April 22, 1997Assignee: Dibra S.p.A.Inventors: Fulvio Uggeri, Pier L. Anelli, Giuseppe Manfredi, Marino Brocchetta, Franco Fedeli
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Patent number: 5621098Abstract: This invention provides novel bis-indolemaleimide macrocycle derivatives of the formula: ##STR1## wherein R.sub.1, R.sub.2, X, W, and Y are as defined in the specification. The invention further provides the preparation, pharmaceutical formulations and the methods of use for inhibiting Protein Kinase C in mammals.Type: GrantFiled: June 1, 1995Date of Patent: April 15, 1997Assignee: Eli Lilly and CompanyInventors: William F. Heath, Jr., Michael R. Jirousek, John H. McDonald, III, Christopher J. Rito