Plural Nitrogens In The Hetero Ring Patents (Class 540/469)
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Patent number: 6974872Abstract: The present invention discloses processes for preparing piperidine derivative compounds of the formulae: wherein n is 0 or 1; R1 is hydrogen or hydroxy; R2 is hydrogen; or, when n is 0, R1 and R2 taken together form a second bond between the carbon atoms bearing R1 and R2, provided that when n is 1, R1 and R2 are each hydrogen; R3 is —COOH or —COOR4; R4 is an alkyl or aryl moiety; A, B, and D are the substituents of their rings, each of which may be different or the same, and are selected from the group consisting of hydrogen, halogens, alkyl, hydroxy, alkoxy, and other substituents.Type: GrantFiled: August 5, 2002Date of Patent: December 13, 2005Assignee: AMR Technology, Inc.Inventors: Thomas E. D'Ambra, Garry M. Pilling
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Patent number: 6962992Abstract: The invention describes crown ether chelators, including crown ethers having the formula and aza-substituted and thia-substituted analogs thereof. These crown ethers are substituted by a dye moiety, a chemically reactive group, a conjugated substance, or a combination thereof. Chelators that are substituted by fluorescent dyes are particularly useful as indicators for metal cations, particularly Na+ and K+ ions, and particularly where binding of the target ion results in a change in the fluorescence properties of the indicator that can be correlated with the ion concentration. Methods are provided for utilizing reactive groups on the chelators for conjugation to dyes, lipids and polymers and methods for enhancing entry of the indicators into living cells.Type: GrantFiled: December 19, 2001Date of Patent: November 8, 2005Assignee: Molecullar Probes, Inc.Inventors: Vladimir V. Martin, Kyle R. Gee, Richard P. Haugland, Zhenjun Diwu
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Patent number: 6946552Abstract: A method of making chlorins comprises the steps of reacting (e.g. condensing) a dipyrrin western half intermediate with an eastern half intermediate to form a tetrahydrobilene, and then cyclizing the tetrahydrobilene to form a chlorin. Intermediates including tetrahydrobilenes useful in such reactions are also described.Type: GrantFiled: May 8, 2002Date of Patent: September 20, 2005Assignee: North Carolina State UniversityInventors: Jonathan S. Lindsey, Masahiko Taniguchi, Doyoung Ra, Guoning M, Thiagarajan Balasubramanian
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Patent number: 6919458Abstract: The present invention relates to a process for preparing piperidine derivative compounds of the formulae: wherein n is 0 or 1; R1 is hydrogen or hydroxy; R2 is hydrogen; or, when n is 0, R1 and R2 taken together form a second bond between the carbon atoms bearing R1 and R2, provided that when n is 1, R1 and R2 are each hydrogen; R3 is —COOH or —COOR4; R4 is an alkyl or aryl moiety; A, B, and D are the substituents of their rings, each of which may be different or the same, and are selected from the group consisting of hydrogen, halogens, alkyl, hydroxy, alkoxy, and other substituents, The process comprises providing a regiosomer of the following formula: wherein Z is —CG1G2G3, m is an integer from 1 to 6; Q and Y are the same or different and are selected from the group consisting of O, S, and NR5; G1, G2, and G3 are the same or different and are selected from the group consisting of OR8, SR8, and NR8R9; R6 and R7 are the same or different and are selected from the group consisting of hydrType: GrantFiled: August 5, 2002Date of Patent: July 19, 2005Assignee: AMR Technology, Inc.Inventors: Thomas E. D'Ambra, Garry M. Pilling
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Patent number: 6890922Abstract: The 2-phenyl-substituted imidazotriazinones having short, unbranched alkyl radicals in the 9-position are prepared from the corresponding 2-phenyl-imidazotriazinones by chlorosulphonation and subsequent reaction with the amines. The compounds inhibit cGMP-metabolizing phosphodiesterases and are suitable for use as active compounds in pharmaceuticals, for the treatment of cardiovascular and cerebrovascular disorders and/or disorders of the urogenital system, in particular for the treatment of erectile dysfunction.Type: GrantFiled: February 12, 2003Date of Patent: May 10, 2005Assignee: Bayer Healthcare AGInventors: Maria Niewohner, Mazen Es-Sayed, Helmut Haning, Thomas Schenke, Karl-Heinz Schlemmer, Jörg Keldenich, Erwin Bischoff, Elisabeth Perzborn, Klaus Dembowsky, Peter Serno, Marc Nowakowski, Ulrich Niewöhner
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Patent number: 6869589Abstract: The present invention relates to cryptate compounds useful as chelating agents. In particular, the present invention relates to functionalized derivatives of certain cryptate compounds. These functionalized derivatives are suitable for use in radiolabelling and similar applications. The present invention also relates to a method for diagnosis or therapy of a disease utilizing functionalized derivatives of cryptase compounds.Type: GrantFiled: January 5, 2000Date of Patent: March 22, 2005Assignees: Australian Nuclear Science & Technology Organization, The Australian National UniversityInventors: Suzanne V. Smith, John M. Harrowfield, Nadine M. Di Bartolo, Alan McLeod Sargeson
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Patent number: 6846802Abstract: The present invention discloses novel macrocyclic compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such macrocycles as well as methods of using them to treat disorders associated with the HCV protease.Type: GrantFiled: April 3, 2001Date of Patent: January 25, 2005Assignee: Schering CorporationInventors: Kevin X. Chen, Ashok Arasappan, Srikanth Venkatraman, Tejal Parekh, Haining Gu, George F. Njoroge, Viyyoor Moopil Girijavallabhan, Ashit Ganguly, Anil Saksena, Edwin Jao, Nanhua Hugh Yao, Andrew Joseph Prongay, Vincent Stewart Madison, Bancha Vibulbhan
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Patent number: 6828327Abstract: This invention is directed to macroheterocyclic compounds useful as kinase or dual-kinase inhibitors, methods for producing such compounds and methods for treating or ameliorating a kinase or dual-kinase mediated disorder.Type: GrantFiled: December 6, 2001Date of Patent: December 7, 2004Assignee: Ortho-McNeil Pharmaceutical, Inc.Inventors: Gee-Hong Kuo, Han-Cheng Zhang, Catherine Prouty, Alan DeAngelis, Peter Connolly, William V. Murray, Lan Shen, Bruce Conway, Keith Demarest, Chandra R. Shah, Bruce E. Maryanoff, Kimberly B. White
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Publication number: 20040110820Abstract: Expanded porphyrin comprising substitutions for at least two NH groups by S, Se or Te are non-photoactive and are selective for binding G-quadruplexes characteristic of the c-MYC control region. Accordingly, these expanded porphyrins are useful to modulate the expression of genes controlled by the formation of c-MYC type G-quadruplexes, such as c-MYC itself.Type: ApplicationFiled: September 12, 2003Publication date: June 10, 2004Inventor: Laurence H. Hurley
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Publication number: 20040087788Abstract: A description follows of ligands having general formula (I) wherein R1, R2, R3, R4, R5, and R6, the same or different, are selected form hydrogen, halogen, C1-C10 alkyl, C6-C15 aryl optionally halogenated, or adjacent pairs of Ri groups (with i ranging from 1 to 6) are bound to each other to give cyclic hydrocarbon structures condensed with the thiophene or pyridine ring: R7 is selected from H, C1-C10 alkyl, C6-C15 aryl: R8 is selected from C1-C10 alkyl and C6-C15 aryl. The complexes of the above ligands with transition metals are also described.Type: ApplicationFiled: October 14, 2003Publication date: May 6, 2004Inventors: Claudio Bianchini, Anna Sommazzi, Giuseppe Mantovani, Roberto Santi, Francesco Masi
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Publication number: 20040010127Abstract: Novel methods, processes and metal complexes attached to a hypoxia-localizing moiety comprisingType: ApplicationFiled: November 16, 2001Publication date: January 15, 2004Inventors: Karen Linder, Adrian D. Nunn, David P. Nowotnik, Kondareddiar Ramalingam, Richard J. DiRocco, William L. Rumsey, John P. Pirro
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Publication number: 20030096989Abstract: A method of making chlorins comprises the steps of reacting (e.g. condensing) a dipyrrin western half intermediate with an eastern half intermediate to form a tetrahydrobilene, and then cyclizing the tetrahydrobilene to form a chlorin. Intermediates including tetrahydrobilenes useful in such reactions are also described.Type: ApplicationFiled: May 8, 2002Publication date: May 22, 2003Inventors: Jonathan S. Lindsey, Masahiko Taniguchi, Doyoung Ra, Guoning Mo, Thiagarajan Balasubramanian
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Patent number: 6562823Abstract: The present invention is directed to peptidomimetic piperazine-containing macrocyclic compounds which inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.Type: GrantFiled: June 28, 2001Date of Patent: May 13, 2003Assignee: Merck & Co., Inc.Inventors: Christopher J. Dinsmore, Jeffrey M. Bergman, Samuel L. Graham, Diem N. Nguyen, Gerald E. Stokker, Theresa M. Williams, C. Blair Zartman
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Patent number: 6559143Abstract: There is provided compounds of formula I, wherein R1, R2, R3, R4, R41 to R46, A, B and G have meanings given in the description, which are useful in the prophylaxis and in the treatment of arrhythmias, in particular atrial and ventricular arrhythmias.Type: GrantFiled: October 16, 2000Date of Patent: May 6, 2003Assignee: AstraZeneca ABInventors: Annika Björe, Magnus Björsne, Kurt-Jürgen Hoffmann, Fritiof Pontén, Gert Strandlund, Peder Svensson, Michael Wilsterman
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Patent number: 6552187Abstract: A process for the preparation of compounds of formula (I), which process comprises reacting a compound of formula (II), in an inert organic solvent, optionally in the presence of a base, with a compound of formula (IV), (IVa) or (IVb), and optionally converting the resulting compound of formula (I) wherein G is a metal ion equivalent or an ammonium cation, by salt conversion into the corresponding salt of formula (I) wherein G is a sulfonium or phosphonium cation, or by treatment with a Brönsted acid into the corresponding compound of formula (I) wherein G is hydrogen, and ‘in situ’ conversion of compounds of formula (I) with an electrophile of formula (XII) or (XIId) G0—L (XII) or R32—N═C═X3 (XIId), optionally in the presence of an acid-binding agent or a catalyst, to the compounds of formula (Ia).Type: GrantFiled: November 29, 2001Date of Patent: April 22, 2003Assignee: Syngenta Crop Protection, Inc.Inventors: Thomas Maetzke, René Mutti, Henry Szczepanski
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Patent number: 6534506Abstract: The present invention is directed to peptidomimetic macrocyclic compounds which inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.Type: GrantFiled: April 6, 2001Date of Patent: March 18, 2003Assignee: Merck & Co., Inc.Inventors: Diem N. Nguyen, Craig A. Stump, Theresa M. Williams
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Patent number: 6444824Abstract: The present invention relates to a method for preparing piperidine derivative compounds by converting, with a piperidine compound, regioisomers having the formula: where Z is and where m is 1 or 3-6; Q and Y are the same or different and are selected from the group consisting of O, S, and NR5; R6 and R7 are the same or different and are selected from the group consisting of hydrogen, an alkyl moiety, an aryl moiety, OR8, SR8, and NR8R9; and R5, R8, and R9 are the same or different and are selected from the group consisting of hyrogen, an alkyl moiety, and an aryl moiety.Type: GrantFiled: August 9, 2000Date of Patent: September 3, 2002Assignee: Albany Molecular Research, Inc.Inventors: Thomas E. D'Ambra, Garry M. Pilling
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Patent number: 6441164Abstract: Wurster's crown ligands comprise a macrocyclic ligand such as a crown ether in which a hetero atom is substituted with a 1,4-phenylenediamine group. The phenylenediamine group is covalently bound to the macrocyclic ligand by one or both of the amine nitrogens, the amine nitrogen thereby substituting for the hetero atom of the macrocyclic ligand. The resulting compounds are redox active. Methods of making and using the compounds are also disclosed.Type: GrantFiled: July 12, 2001Date of Patent: August 27, 2002Assignee: East Carolina UniversityInventor: John W. Sibert
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Publication number: 20020107181Abstract: The present invention discloses novel macrocyclic compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such macrocycles as well as methods of using them to treat disorders associated with the HCV protease.Type: ApplicationFiled: April 3, 2001Publication date: August 8, 2002Inventors: Kevin X. Chen, Ashok Arasappan, Srikanth Venkatraman, Tejal Parekh, Haining Gu, F. George Njoroge, Viyyoor Moopil Girijavallabhan, Ashit Ganguly, Anil Saksena, Edwin Jao, Nanhua Hugh Yao, Andrew Joseph Prongay, Vincent Stewart Madison, Bancha Vibulbhan
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Patent number: 6413963Abstract: Conformationally constrained compounds which mimic the secondary structure of reverse-turn regions of biologically active peptides and proteins are disclosed. Such reverse-turn mimetics have utility in the treatment of cell adhesion-indicated diseases, such as multiple sclerosis, atherosclerosis, asthma and inflammatory bowel disease.Type: GrantFiled: December 19, 2000Date of Patent: July 2, 2002Assignee: Molecumetics, Ltd.Inventors: Michael Kahn, Masakatsu Eguchi, Hwa-Ok Kim, Marcin Stasiak
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Patent number: 6413964Abstract: The present invention is directed to peptidomimetic macrocyclic compounds of the formula A: wherein W is a heterocycle, V is a heterocycle or aryl moiety and Z1 is a suitably substituted aryl or heterocycle moiety. The instant compounds inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.Type: GrantFiled: January 9, 2001Date of Patent: July 2, 2002Inventors: S. Jane deSolms, Suzanne C. MacTough, Anthony W. Shaw
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Patent number: 6410534Abstract: The present invention is directed to peptidomimetic macrocyclic compounds which inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.Type: GrantFiled: June 29, 1999Date of Patent: June 25, 2002Assignee: Merck & Co., Inc.Inventors: Christopher J. Dinsmore, Ian M. Bell, Douglas C. Beshore, Theresa M. Williams
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Patent number: 6391900Abstract: The present invention discloses new cytotoxic tris(oxazole)-containing macrolides having the formula: wherein X represents a lower alkyl; R1 and R2 represent hydrogen or lower alkyl; R3a represents hydrogen, and R3b represents or R3a and R3b together represent oxygen; R4 represents hydrogen, lower alkoxy or lower alkyl; R5 represents hydrogen, carbamoyl, or lower alkanoyl; R6a represents hydrogen, and R6b represents hydroxy, or R6a and R6b together represent oxygen; R7 represents hydrogen, lower alkyl, or hydroxymethyl; R8 represents lower alkoxy or lower alkyl; Y1 represents hydrogen or methyl, and y2 represents hydrogen, or Y1 and Y2 together represent a double bond. Also disclose are methods for treating mammals using the macrolides and pharmaceutical preparations including the macrolides.Type: GrantFiled: January 12, 2001Date of Patent: May 21, 2002Assignee: Instituto Biomar S.A.Inventors: Tatsuo Higa, Dolores Garcia Gravalos, Jose Luis Fernandez Puentes
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Patent number: 6359130Abstract: The present invention is directed to novel fused aryl and heteroaryl bridged indenopyrrolocarbazoles which are useful, inter alia, as therapeutic agents. The invention is also directed to methods for making and using the bridged indenopyrrolocarbazoles.Type: GrantFiled: May 17, 2000Date of Patent: March 19, 2002Assignee: Cephalon, Inc.Inventors: Jasbir Singh, Robert L. Hudkins, John P. Mallamo, Theodore L. Underiner, Rabindranath Tripathy
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Patent number: 6329376Abstract: The present invention is directed to peptidomimetic piperazine-containing macrocyclic compounds which inhibit a prenyl-protein transferase (FTase) and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.Type: GrantFiled: October 26, 1999Date of Patent: December 11, 2001Assignee: Merck & Co., Inc.Inventor: Jeffrey M. Bergman
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Publication number: 20010047095Abstract: Wurster's crown ligands comprise a macrocyclic ligand such as a crown ether in which a hetero atom is substituted with a 1,4-phenylenediamine group. The phenylenediamine group is covalently bound to the macrocyclic ligand by one or both of the amine nitrogens, the amine nitrogen thereby substituting for the hetero atom of the macrocyclic ligand. The resulting compounds are redox active. Methods of making and using the compounds are also disclosed.Type: ApplicationFiled: July 12, 2001Publication date: November 29, 2001Inventor: John W. Sibert
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Patent number: 6316436Abstract: The present invention is directed to compounds which inhibit prenyl-protein transferase and particularly, the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.Type: GrantFiled: December 7, 1999Date of Patent: November 13, 2001Assignee: Merck & Co., Inc.Inventors: S. Jane deSolms, Anthony W. Shaw
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Patent number: 6294525Abstract: Conformationally constrained compounds which mimic the secondary structure of reverse-turn regions of biologically active peptides and proteins having the following structure are disclosed: wherein A, R1, R2, R2a, R3, R3a and R4 are as defined herein. Such compounds have utility over a wide range of fields, including use as diagnostic and therapeutic agents. In particular, compounds of this invention are useful in pharmaceutical compositions as anti-inflammatory agents. Libraries containing the compounds of this invention are also disclosed, as well as methods for screening the same to identify biologically active members.Type: GrantFiled: September 1, 1999Date of Patent: September 25, 2001Assignee: Molecumetics Ltd.Inventors: Marcin Stasiak, Michael Kahn
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Patent number: 6291447Abstract: Novel granulatimide compounds and pharmaceutical formulations thereof are provided.Type: GrantFiled: February 26, 1999Date of Patent: September 18, 2001Assignees: The University of British Columbia, Kinetek Pharmaceuticals, Inc.Inventors: Raymond Andersen, Michel Roberge, Jasbinder Sanghera, Daniel Leung, Edward Piers, Roberto GS Berlinck, Robert Britton
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Patent number: 6225306Abstract: A biphenyl derivative represented by the following general formula (1) and a pharmaceutically acceptable salt thereof: [In the formula (1), A represents a single bond, —CH2—, —CO—, —CS— or —SO2—; B represents a single bond or —CH2—; R1 represents a hydrogen atom, —OH, —NR11R12 (wherein R11 and R12 each independently represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms), —OCOCH3, or a halogen atom; R2 represents a hydrogen atom or R1 and R2 form a group ═O together; R3 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; provided that in the formula, the absolute configuration of the position a may be either R or S]. The compound of the present invention has considerably high safety and efficacy and is useful as, in particular, a vasopressin receptor antagonist.Type: GrantFiled: September 30, 1999Date of Patent: May 1, 2001Assignee: Wakamoto Pharmaceutical Co., Ltd.Inventors: Yasuhiro Ohtake, Akira Naito, Kenji Naito, Hidehiko Matsukawa, Yoshiaki Saito, Hatsunori Toyofuku
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Patent number: 6211359Abstract: The invention relates to a triaza-cryptand of the general Formula I wherein a is selected from the group consisting of 0 and 1, b and c independently are selected from the group consisting of 0 and 1, with the proviso that not both of b and c are 0, d is selected from the group consisting of 1, 2 and 3, e and f independently are selected from the group consisting of 0 and 1, with the proviso that not both of e and f are 0, R1 and R2 are either hydrogen or form an alkyl(C1-C4) benzene ring or an alkoxy(C1C4) benzene ring together with C1 and C2, wherein C2 is the para position, R3 and R2 are either hydrogen or form an alkyl(C1-C4) benzene ring or an alkoxy(C1-C4) benzene ring together with C3 and C4, wherein C3 is the para position, R5 and R6 are either hydrogen or form a benzene ring or a naphtalene ring together with C5 and C6, R7 and R8 are either hydrogen or form an alkyl(C1-C4) benzene ring or an alkoxy(C1-C4) benzene ring together with C7 and C8, wherein C8 is the para position,Type: GrantFiled: August 17, 1999Date of Patent: April 3, 2001Assignee: AVL Medical InstrumentsInventors: Huarui He, Mark Alan Mortellaro, Marco Jean Pierre Leiner
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Patent number: 6177551Abstract: The present invention provides for substituted metal chelating compounds in which at least two of the chelating atoms are nitrogen which are directly attached to aromatic rings and one or more of those nitrogen atoms has attached thereto a substituent other than hydrogen, and methods for making and using these compounds.Type: GrantFiled: May 12, 1999Date of Patent: January 23, 2001Assignee: NeoRx CorporationInventor: Sudhakar Kasina
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Patent number: 6156282Abstract: The invention relates to new calixarenes of formula: ##STR1## in which R.sup.1 represents a crown ether chain that includes at least two aryl or cycloalkyl rings,R.sup.2 is a hydroxyl or alkoxy group, or the two R.sup.2 groups together form a crown ether chain such as R.sup.1, and R.sup.3 represents a hydrogen atom or an alkyl group. The calixarenes are used to selectively extract caesium from aqueous solutions that notably have high concentrations of sodium.Type: GrantFiled: January 27, 1999Date of Patent: December 5, 2000Assignee: Commissariat a l'Energie AtomiqueInventors: Jean-Fran.cedilla.ois Dozol, Veronique Lamare, Christophe Bressot, Rocco Ungaro, Alessandro Casnati, Jacques Vicens, Zouhair Asfari
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Patent number: 6117861Abstract: This invention provides novel bis-indolylmaleimide macrocycle derivatives of the formula: ##STR1## and solvates thereof. The invention further provides the preparation, pharmaceutical formulations and the methods of use for inhibiting Protein Kinase C in mammals.Type: GrantFiled: December 7, 1999Date of Patent: September 12, 2000Assignee: Eli Lilly and CompanyInventors: Gary Lowell Engel, Nagy Alphonse Farid, Margaret Mary Faul, Michael Robert Jirousek, Lori Ann Richardson, Leonard Larry Winneroski, Jr.
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Patent number: 6107482Abstract: Novel macrocyclic compounds are constructed to include large cyclic structures that are interrupted by at least one ring system. Each interrupting ring system includes two bridgehead atoms. Bridgehead atoms are bonded to one or more bridges that interconnect one or more ring systems thereby forming a large cyclic structure. Located in each bridge are two or more nitrogenous moieties that are derivatized with chemical functional groups. The ring systems can include further nitrogenous moieties, either as ring atoms or on pendant groups attached to the ring. These can also be derivatized with chemical functional groups. The totality of the chemical functional groups imparts certain conformational and other properties to the macrocyclic compounds. In accordance with certain embodiments of the invention, libraries of such macrocyclic compounds are prepared utilizing permutations and combinations of the chemical functional groups and the nitrogenous moieties to build complexity into the library.Type: GrantFiled: September 19, 1997Date of Patent: August 22, 2000Assignee: Isis Pharmaceuticals, Inc.Inventors: Phillip Dan Cook, Haoyun An, Charles J. Guinosso, Pei-Pei Kung, Allister S. Fraser
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Patent number: 6069114Abstract: Compounds of the formula (I) and their salts ##STR1## in which R.sup.1 to R.sup.6, Y.sup.1, to Y.sup.2, Y.sup.3, m and n are as defined in claim 1 are suitable as herbicides and plant growth regulators. They can be prepared analogously to known processes using intermediates of the formula (V) (cf. claim 6).Type: GrantFiled: February 25, 1997Date of Patent: May 30, 2000Assignee: Hoechst Schering AgrEvo GmbHInventors: Klaus Lorenz, Klemens Minn, Lothar Willms, Klaus Bauer, Hermann Bieringer, Christopher Rosinger
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Patent number: 6057440Abstract: 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: November 14, 1997Date of Patent: May 2, 2000Assignee: Eli Lilly and CompanyInventors: William F. Heath, Jr., Michael R. Jirousek, John H. McDonald, III, Christopher J. Rito
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Patent number: 6001999Abstract: The invention relates to a compound having the general Formula I in which one of the groups R.sub.1,R.sub.2,R.sub.3,R.sub.4,R.sub.5,R.sub.6 and R.sub.7 represents an ionophoric moiety and the remaining groups each independently are hydrogen, a lipophilic or hydrophilic group or a reactive group for coupling to a polymer or a biomolecule, or R.sub.2 forms an aromatic ring system together with R.sub.3 and R.sub.5 forms an aromatic ring system together with R.sub.6.the compound of the invention is useful as a luminescence indicator for cations.Type: GrantFiled: May 27, 1998Date of Patent: December 14, 1999Assignee: AVL Medical InstrumentsInventors: Otto S. Wolfbeis, Jorg Daub, Thomas Gareis, Matthias Kollmannsberger, Stefan Heinl, Tobias Werner, Christian Huber, Andrei Boila-Gockel, Marco Jean Pierre Leiner
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Patent number: 5981558Abstract: DC107 derivatives represented by formula (I) or pharmaceutically acceptable salts thereof which have antimicrobial activity and antitumor activity are provided: ##STR1## wherein R.sup.1 represents hydrogen, lower alkoxyalkyl, aralkyloxyalkyl, lower alkoxyalkoxyalkyl, lower alkoxyalkoxyalkoxyalkyl, aralkyl, tetrahydropyranyl, COR.sup.4, or the like; R.sup.2 represents hydrogen or COR.sup.6 ; R.sup.3 represents --CH.sub.2 OCOR.sup.7, phthalimidomethyl, or the like; and W represents oxygen or NR.sup.8 (wherein R.sup.8 represents hydroxy, lower alkoxy, lower alkenyloxy, aralkyloxy, substituted or unsubstituted arylsulfonylamino, or lower alkoxycarbonylamino).Type: GrantFiled: August 13, 1998Date of Patent: November 9, 1999Assignee: Kyowa Hakko Kogyo Co., Ltd.Inventors: Hitoshi Arai, Yutaka Kanda, Hiroyuki Yamaguchi, Tadashi Ashizawa, Chikara Murakata, Shun-ichi Ikeda, Tatsuya Tamaoki
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Patent number: 5958782Abstract: A fluorescent ionophoric compound is disclosed that includes a complexing moiety, such as a cryptand or crown-ether portion, and a fluorescing moiety such as a coumarin portion. The coumarin portion may be substituted at the 3-position with an electron withdrawing or polarizable group such as a substituted aromatic group or a substituted heterocyclic group having a heteroatom in at least one of its alpha positions. The compound, which exhibits good photostability, can be incorporated into cation-sensing composite structures by means of convenient points of covalent attachment.Type: GrantFiled: February 27, 1997Date of Patent: September 28, 1999Assignee: Minnesota Mining and Manufacturing CompanyInventors: James G. Bentsen, Shih-Hung Chou, Elisa M. Cross, Kurt J. Halverson, John E. Trend, Cary A. Kipke, Masao Yafuso, Sanjay L. Patil
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Patent number: 5948907Abstract: The present invention provides for the reaction of optionally substituted indole-3-acetamides with optionally substituted methyl indole-3-glyoxyl reagent to prepare potent PKC inhibitors.Type: GrantFiled: May 19, 1998Date of Patent: September 7, 1999Assignee: Eli Lilly and CompanyInventors: Margaret Mary Faul, Leonard Larry Winneroski, Jr.
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Patent number: 5948906Abstract: The invention discloses fluorescent chelator compounds that are especially useful to monitor and measure cytosolic concentrations of alkali metal cations such as Na.sup.+, K.sup.+, and Li.sup.+. The new compounds are comprised of: (1) crown ethers (that may or may not have substituent groups attached to the core carbons, but will always contain at least one core nitrogen) that are linked via the core nitrogen(s) to at least one (2) fluorophore that contains an additional heteroaromatic liganding center. In the currently preferred dye, SBFI, the core compound is crown ether 1,7-diaza-4,10,13-trioxacyclopentadecane and the heteroaromatic fluorophores are benzofurans that are linked to isophthalate groups. Selectivities for Na.sup.+ over K.sup.+ of about 20 are observed, resulting in effective dissociation constants for Na.sup.+ of about 20 mM against a background of 120 mM K.sup.+. Increasing ?Na.sup.Type: GrantFiled: July 27, 1992Date of Patent: September 7, 1999Assignee: The Regents of the University of CaliforniaInventors: Roger Yonchien Tsien, Akwasi Minta
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Patent number: 5821365Abstract: 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: November 14, 1997Date of Patent: October 13, 1998Assignee: Eli Lilly and CompanyInventors: Michael R. Jirousek, John H. McDonald, III, Christopher J. Rito
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Patent number: 5786352Abstract: Novel compounds of the following general formula or salts thereof. ##STR1## wherein Ring M is a heterocyclic ring having --N.dbd.C<, --CO--N< or --CS--N< as the partial structure --X . . . Y<; R.sup.a and R.sup.b are bonded to each other to form Ring A, or they are the same or different and represent, independently, a hydrogen atom or a substituent on the Ring M; Ring A and Ring B represent, independently, an optionally substituted homocyclic or heterocyclic ring, and at least one of them is optionally substituted heterocyclic ring; Ring C is optionally substituted homocyclic or heterocyclic ring; Ring Z is an optionally substituted ring; and n represents an integer of from 1 to 6, or a salt thereof, which has an excellent tachykinin receptor antagonistic effect, and their production, and pharmaceutical compositions.Type: GrantFiled: March 25, 1996Date of Patent: July 28, 1998Assignee: Takeda Chemical Industries, Ltd.Inventors: Hideaki Natsugari, Takenori Ishimaru, Takayuki Doi, Yoshinori Ikeura, Chiharu Kimura
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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: 5739322Abstract: This invention provides novel bis-indolemaleimide macrocycle derivatives of the formula: ##STR1## wherein R1, R2, 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: March 20, 1997Date of Patent: April 14, 1998Assignee: Eli Lilly and CompanyInventors: William F. Heath, Jr., Michael R. Jirousek, John H. McDonald, III, Christopher J. Rito
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Patent number: 5721272Abstract: This invention provides compounds of the formula: ##STR1## The invention further provides the use of this compound to prepare N,N'-bridged bisindolylmaleimides. Furthermore, the invention provides pharmaceutical formulations and the methods of use for inhibiting Protein Kinase C in mammals.Type: GrantFiled: November 18, 1996Date of Patent: February 24, 1998Assignee: Eli Lilly and CompanyInventors: Margaret Mary Faul, Christine Ann Krumrich, Leonard Larry Winneroski, Jr.
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Patent number: 5710145Abstract: This invention provides novel bis-indolylmaleimide macrocycle derivatives of the formula: ##STR1## and solvates thereof. The invention further provides the preparation, pharmaceutical formulations and the methods of use for inhibiting Protein Kinase C in mammals.Type: GrantFiled: November 18, 1996Date of Patent: January 20, 1998Assignee: Eli Lilly and CompanyInventors: Gary Lowell Engel, Nagy Alphonse Farid, Margaret Mary Faul, Michael Robert Jirousek, Lori Ann Richardson, Leonard Larry Winneroski, Jr.
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Patent number: 5677445Abstract: A compound of formula ##STR1## where the two R.sup.2 groups, taken together, represent the atoms necessary to complete a macrocyclic ring structure containing at least one heteroatom coordinating site and at least one alkylene group forming part of the ring structure; R.sup.3 represents hydrogen, alkyl, alkoxy, alkylthio, alkylamino, alkylformamido, aryl, aryloxy, heterocyclyl or a protein reactive group; and R.sup.4 represents hydrogen or a protein reactive group, provided that at least one of the R.sup.4 groups is a protein reactive group, and salts, complexes and protein conjugates thereof.Type: GrantFiled: December 15, 1995Date of Patent: October 14, 1997Assignee: Nycomed Imaging ASInventors: John L. Toner, David A. Hilborn, Bruce J. Murray, Timothy Z. Hossain
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Patent number: 5665877Abstract: The present invention provides a novel synthesis of the compounds of Formula (I): ##STR1## The compounds are produced in high yield and without utilizing expensive chromatographic separations. The synthesis is particularly advantageous because it is stereoselective.Type: GrantFiled: May 17, 1996Date of Patent: September 9, 1997Assignee: Eli Lilly and CompanyInventors: Margaret M. Faul, Michael R. Jirousek, Leonard L. Winneroski, II