Plural Isoquinoline Ring Systems Attached Directly Or Indirectly To Each Other By Nonionic Bonding Patents (Class 546/140)
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Patent number: 6686351Abstract: Compounds that modulate the estrogen receptor (ER) are disclosed, as well as pharmaceutical compositions containing the same. In a specific embodiment, the compounds are selective modulators for ER-&bgr; over ER-&agr;. Methods are disclosed for modulating ER-&bgr; in cell and/or tissues expressing the same, including cells and/or tissue that preferentially express ER-&bgr;. More generally, methods for treating estrogen-related conditions are also disclosed, including conditions such as is breast cancer, testicular cancer, osteoporosis, endometriosis, cardiovascular disease, hypercholesterolemia, prostatic hypertrophy, prostatic carcinomas, obesity, hot flashes, skin effects, mood swings, memory loss, urinary incontinence, hairloss, cataracts, natural hormonal imbalances, and adverse reproductive effects associated with exposure to environmental chemicals.Type: GrantFiled: February 27, 2002Date of Patent: February 3, 2004Assignee: Signal Pharmaceuticals, Inc.Inventors: Shripad S. Bhagwat, Leah M. Gayo-Fung, Qi Chao
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Publication number: 20030220298Abstract: The present invention relates to the syntheses and structural elucidation of Combretastatin A1-Phosphate Prodrugs and Combretastatin B1-Phosphate Prodrugs and the utilization of those prodrugs in the treatment of neoplastic diseases. The prodrugs described herein have the structure: Combretastin A-1 Phosphate Prodrug (I) and Combretastin B-1 Phosphate Prodrug (II).Type: ApplicationFiled: October 25, 2002Publication date: November 27, 2003Inventors: George R. Pettit, John W. Lippert
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Patent number: 6645957Abstract: The invention relates to compounds represented by the following general formula (1): wherein A is an aromatic compound which may be substituted, or the like, B is a nitrogen atom or CH, X is a lower alkylene group which may be substituted, or the like, Y is a single bond or the like; Z is a divalent residue of benzene which may be substituted, or the like, and m and n are independently an integer of 1 to 4, and medicines comprising such a compound. These compounds have an excellent inhibitory effect on the production of an IgE antibody and are hence useful as antiallergic agents and the like.Type: GrantFiled: June 19, 2002Date of Patent: November 11, 2003Assignee: Kowa Co., Ltd.Inventors: Hiroyuki Ishiwata, Seiichi Sato, Mototsugu Kabeya, Soichi Oda, Yukio Hattori, Makoto Suda, Manabu Shibasaki, Hiroshi Nakao, Takao Nagoya
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Antimalarial naphthylisoquinoline alkaloids and pharmaceutical compositions and medical uses thereof
Patent number: 6627641Abstract: The present invention provides antimalarial pharmaceutical compositions containing antimalarial naphthylisoquinoline alkaloids or antimalarial derivatives thereof, useful new antimalarial naphthylisoquinoline alkaloid derivatives, methods for obtaining such derivatives, and methods of using such antimalarial compounds for the prevention of malaria infections in mammals and for treating mammals with malarial infections. The antimalarial compounds of the present invention inhibit the reproduction and cytopathicity of Plasmodium sp. parasites in vitro and in vivo.Type: GrantFiled: April 16, 1997Date of Patent: September 30, 2003Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Guido François, Gerhard Bringmann, J. David Phillipson, Michael R. Boyd, Laurent Aké Assi, Christoph Schneider, Georges Timperman -
Patent number: 6617335Abstract: This invention relates to the preparation of bis-isoquinoline derivatives of general formula (I) and salts thereof, which possesses multi-drug resistance (MDR) reversal activities. Drug compositions and formulations comprising bis-isoquinoline derivatives of general formula (I) and salts thereof are provided for use as sensitivity enhancers in cancer chemotherapy. Methods for inhibiting MDR by treatment with bis-isoquinoline derivatives are also provided.Type: GrantFiled: May 2, 2002Date of Patent: September 9, 2003Assignee: Kanghong USA, Inc.Inventors: Fengpeng Wang, Li Wang, Jinsong Yang, Donglin Chen, Xixian Jian
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Patent number: 6593322Abstract: Compounds that modulate the estrogen receptor (ER) are disclosed, as well as pharmaceutical compositions containing the same. In a specific embodiment, the compounds are selective for ER-&bgr; over ER-&agr;. Methods are disclosed for modulating ER-&bgr; in cell and/or tissues expressing the same, including cells and/or tissue that preferentially ER-&bgr;. Methods for treating estrogen-related conditions are also disclosed, including conditions such as is breast cancer, testicular cancer, osteoporosis, endometriosis, cardiovascular disease, hypercholesterolemia, prostatic hypertrophy, prostatic carcinomas, obesity, hot flashes, skin effects, mood swings, memory loss, urinary incontinence, hairloss, cataracts, natureal hormonal imbalances, and adverse reproductive effects associated with exposure to environmental chemicals.Type: GrantFiled: September 21, 2000Date of Patent: July 15, 2003Assignee: Signal Pharmaceuticals, Inc.Inventors: Shripad S. Bhagwat, Leah Marie Gayo-Fung, Bernd M. Stein, Qi Chao, Anthony R. Gangloff, Jeffrey A. McKie, Kenneth D. Rice
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Publication number: 20030119870Abstract: The invention relates to compounds of formulae 1Type: ApplicationFiled: October 29, 2002Publication date: June 26, 2003Inventors: Alexander Alanine, Bernd Buettelmann, Marie-Paule Heitz Neidhart, Emmanuel Pinard, Rene Wyler
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Patent number: 6576642Abstract: Compounds having the formula (1): wherein A is a phenyl, naphthyl, dihydronaphthyindeny, pyridyl, indolyl,isoindolyl, quinolyl or isoquinolyl group which are optionally substituted; X is optionally substituted alicyclic, aromatic, imino or heterocyclic groups or —S— or —O—; Y is a single bond or an alkylene group; Z is an unsubstituted aliphatic group or divalent residue of benzene or pyridine, which is optionally substituted; anis hydrogen, lower alkyl, cycloalkyl, aryl or aralkyl; with certain provisos. These compounds exhibit an inhibitory effect on the production of IgE antibodies and are, hence, useful as antiallergic agents.Type: GrantFiled: May 17, 2001Date of Patent: June 10, 2003Assignee: Kowa Co., Ltd.Inventors: Hiroyuki Ishiwata, Mototsugu Kabeya, Masami Shiratsuchi, Yukio Hattori, Hiroshi Nakao, Takao Nagoya, Seiichi Sato, Soichi Oda, Makoto Suda, Manabu Shibasaki
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Publication number: 20030044845Abstract: Novel multi-binding compounds (agents) are disclosed which bind cell membrane transporters including ion channels, molecular transporters and ion pumps. The compounds of this invention comprise from 2 to 10 ligands each of which can bind to such cellular transporters to modulate the biological processes/functions thereof. Each of the ligands is covalently attached to a linker (framework) to provide for a multi-binding compound. The linker is selected such that the multi-binding compound exhibits increased modulation of the biological processes/functions of the transporter as compared to the aggregate of the individual ligand units made available for binding to the transporter.Type: ApplicationFiled: February 13, 2002Publication date: March 6, 2003Inventors: Thomas E. Jenkins, Burton G. Christensen, John H. Griffin, J. Kevin Judice
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Publication number: 20020143014Abstract: Provided herein are compounds of the formula (I): 1Type: ApplicationFiled: March 6, 2002Publication date: October 3, 2002Inventors: James P. Beck, Matt A. Curry, Mark A. Smith
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Patent number: 6436923Abstract: Compounds that modulate the estrogen receptor (ER) are disclosed, as well as pharmaceutical compositions containing the same. In a specific embodiment, the compounds are selective modulators for ER-&bgr; over ER-&agr;. Methods are disclosed for modulating ER-&bgr; in cell and/or tissues expressing the same, including cells and/or tissue that preferentially express ER-&bgr;. More generally, methods for treating estrogen-related conditions are also disclosed, including conditions such as is breast cancer, testicular cancer, osteoporosis, endometriosis, cardiovascular disease, hypercholesterolemia, prostatic hypertrophy, prostatic carcinomas, obesity, hot flashes, skin effects, mood swings, memory loss, urinary incontinence, hairloss, cataracts, natural hormonal imbalances, and adverse reproductive effects associated with exposure to environmental chemicals.Type: GrantFiled: March 17, 2000Date of Patent: August 20, 2002Assignee: Signal Pharmaceuticals, Inc.Inventors: Shripad S. Bhagwat, Leah M. Gayo-Fung, Bernd M. Stein, Qi Chao, Anthony R. Gangloff, Jeffrey A. McKie, Kenneth D. Rice
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Patent number: 6433177Abstract: It is here described a new process for the synthesis of (S)-N-tertbutyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide wherein the N-carboxy anhydride of formula is treated with tert-butylamine in an organic inert solvent, preferably toluene, at a temperature of between −80 and −30° C.Type: GrantFiled: January 6, 2000Date of Patent: August 13, 2002Assignee: Clariant LSM Italia S.P.A.Inventors: Pietro Bellani, Aldo Banfi
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Patent number: 6384028Abstract: &bgr;-alanine compounds or a pharmaceutically acceptable salt thereof, which is useful as a glycoprotein IIB/IIIa antagonist, inhibitor of blood platelet aggregation and inhibitor of the binding of fibrinogen to blood platelet; a composition containing the same, a process for the preparation of the compound, and a process for the treatment of diseases caused by thrombus formation, for example, are provided.Type: GrantFiled: September 10, 1997Date of Patent: May 7, 2002Assignee: Fujisawa Pharmaceutical Co., Ltd.Inventors: Mitsuru Ohkubo, Fumie Takahashi, Toshio Yamanaka, Masayuki Kato
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Patent number: 6331630Abstract: The present invention provides new naphthylisoquinoline derivatives. In particular, the present invention furthermore provides novel dimeric arylisoquinoline alkaloids comprised of coupled first and second arylisoquinoline monomers. Monomeric and dimeric compounds of the present invention have medically useful properties, such as antimicrobial properties, more specifically such as antimalarial and antiviral properties. Monomeric compounds of the present invention are also useful as building blocks or intermediates for synthesis of novel dimeric arylisoquinoline alkaloids. Monomeric and dimeric compounds of the present invention may be obtained in substantially pure form by total synthesis, partial synthesis, or derivatization from known synthetic or naturally occurring compounds, and by isolation and purification from plants of the Dioncophyllaceae and Ancistrocladaceae families.Type: GrantFiled: March 16, 2000Date of Patent: December 18, 2001Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Gerhard Bringmann, Michael R. Boyd, Matthias Wenzel
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Patent number: 6274594Abstract: Novel isoquinoline derivatives and methods of using them to treat various neurological indications are disclosed.Type: GrantFiled: May 16, 2000Date of Patent: August 14, 2001Assignee: SmithKline Beecham p.l.c.Inventors: Steven Coulton, Roderick Alan Porter, Mervyn Thompson
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Patent number: 6242450Abstract: This invention provides 5-HT1f antagonists of Formula I: where AR1, AR2, R, and R′ are as defined in the specification.Type: GrantFiled: June 17, 1999Date of Patent: June 5, 2001Assignee: Eli Lilly and CompanyInventors: Daniel James Koch, Lee Alan Phebus, Vincent Patrick Rocco, Tammy Joy Sajdyk
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Patent number: 6187789Abstract: Ultrashort acting neuromuscular blocking agents of Formula (I) which are useful as skeletal muscle relaxants during emergency intubation procedures, routine surgery and post-operative settings are disclosed, wherein: X is a halogen; h is from 1 to 2; Y is hydrogen or methoxy; Z1 and Z2 are methyl; W1 and W2 are carbon; and A is a pharmaceutically acceptable anion.Type: GrantFiled: January 19, 2000Date of Patent: February 13, 2001Assignees: Glaxo Wellcome Inc., Cornell Research Foundation Inc.Inventors: Eric Cleveland Bigham, Grady Evan Boswell, John Joseph Savarese, Roy Archibald Swaringen, Jr., Sanjay Shashikant Patel, Eric Eugene Boros, Robert Anthony Mook, Jr., Vincente Samano
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Patent number: 6177445Abstract: Ultra short acting neuromuscular blocking agents of Formula (I) which are useful as skeletal muscle relaxants during emergency intubation procedures, routine surgery and post-operative settings are disclosed, wherein q and t are independently from 0 to 4; X1 and X2 are independently halogen; ha and hb are independenity from 0 to 2; Z1 and Z2 are indepentdently hydrogen, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl with the proviso that Z1 and Z2 are not both hydrogen; Y1, Y2, and Y3 and Y4 are independently hydrogen, halogen or C1-3 alkoxy; m and p are independently 1 to 6; n and r are independently 0 to 4; with the proviso the if ha and hb are both 0, then r is 0 and n is 0 to 2; R1 to R14 are independently hydrogen, halogen, C1-3 alkoxy, or R2 and R3 together with the carbon atoms to which they are bonded, R5 and R6 together with the carbon atoms to which they are bonded, R9 and R10 together with the carbon atoms to which they are bonded, R12 and R13 together with the carbon atoms to which they are bonded, mayType: GrantFiled: December 22, 1999Date of Patent: January 23, 2001Assignees: Glaxo Wellcome Inc., Cornell Research Foundation Inc.Inventors: Eric Cleveland Bigham, Grady Evan Boswell, John Joseph Savarese, Roy Archibald Swaringen, Jr., Sanjay Shashikant Patel, Eric Eugene Boros, Robert Anthony Mook, Jr., Vincente Samano
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Patent number: 6174901Abstract: Selected novel substituted pyridine and pyridazine compounds are effective for prophylaxis and treatment of diseases, such as TNF-&agr;, IL-1&bgr;, IL-6 and/or IL-8 mediated diseases, and other maladies, such as cancer, pain and diabetes. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving inflammation, cancer, pain, diabetes and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.Type: GrantFiled: December 18, 1998Date of Patent: January 16, 2001Assignee: Amgen Inc.Inventors: Nathan B. Mantlo, Chan-Kou Hwang, Ulrike D. Spohr
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Patent number: 6156767Abstract: There are disclosed compounds of formula (I) ##STR1## and pharmaceutically acceptable salts thereof which are useful as antagonists of GnRH and as such may be useful for the treatment of a variety of sex-hormone related and other conditions in both men and women.Type: GrantFiled: May 22, 1998Date of Patent: December 5, 2000Assignee: Merck & Co., Inc.Inventors: Mark Goulet, Matthew J. Wyvratt, Jr., Peter Lin, Lin Chu, Narindar N. Girotra
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Patent number: 6080839Abstract: The invention relates to a novel labeling reactant, suitable for labeling of a biospecific binding reactant using solid-phase synthesis. The invention further concerns new labeling methods. The novel labeling reactant has the formula (I) ##STR1## wherein -A- is a bivalent aromatic structure capable of absorbing light or energy and transferring the excitation energy to a lanthanide ion after the product made by the said solid-phase synthesis has been released from the used solid support, deprotected and converted to a lanthanide chelate;-G- is a bridge replacing a hydrogen atom in A;R is a protected amino acid residue --CH(NHX)COOH, where X is a transient protecting group, or its active ester, where said ester is e.g. an N-hydroxysuccinimido, p-nitrophenol or pentafluorophenol ester; andR' is --COOR'" where R'" is an alkyl of 1 to 4 carbon atoms, phenyl or benzyl, which phenyl or benzyl can be substituted or unsubstituted.Type: GrantFiled: June 25, 1998Date of Patent: June 27, 2000Assignee: Wallac OyInventors: Harri Takalo, Jari Hovinen, Veli-Matti Mukkala, Paivi Liitti, Heikki Mikola
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Patent number: 6048867Abstract: A method of therapy wherein there is administered to a person in need of such therapy a pharmacologically effective amount of a rupununine having the formula: ##STR1##Type: GrantFiled: August 12, 1996Date of Patent: April 11, 2000Inventor: Conrad Gorinsky
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Patent number: 5965730Abstract: A pyridine derivative of the formula (I): ##STR1## wherein A is group of the following formulae: ##STR2## (R.sup.1 and R.sup.2 are each H, or protected or unprotected OH, R.sup.31, R.sup.41 and R.sup.42 are protected or unprotected hydroxymethyl, R.sup.32 is H, lower alkyl, or protected or unprotected hydroxymethyl, R.sup.33 is substituted or unsubstituted lower alkyl, and the dotted line means the presence or absence of a double bond), R.sup.5 and R.sup.6 are H, or protected or unprotected amino, or both combine together with the adjacent nitrogen to form substituted or unsubstituted heterocycle, or a pharmaceutically acceptable salt thereof, these compounds showing excellent bronchoconstriction inhibitory activity and/or anti-inflammatory activity of airway, and being useful in the prophylaxis or treatment of asthma.Type: GrantFiled: December 4, 1997Date of Patent: October 12, 1999Assignee: Tanabe Seiyaku Co., Ltd.Inventors: Tatsuzo Ukita, Masakatsu Sugahara, Katsuo Ikezawa, Hideo Kikkawa, Kazuaki Naito
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Patent number: 5863929Abstract: This invention relates to a compound of the Formula IX--C(O)--Y--G--R I(wherein X, Y, G and R have the values defined in the description), or a pharmaceutically acceptable salt thereof, processes and intermediates for the preparation of such a compound or salt, pharmaceutical compositions comprising such a compound or salt and methods of their use as thrombin inhibitors, coagulation inhibitors and agents for the treatment of thromboembolic disorders.Type: GrantFiled: June 20, 1997Date of Patent: January 26, 1999Assignee: Eli Lilly and CompanyInventors: Valentine Joseph Klimkowski, Aaron Leigh Schacht, Michael Robert Wiley
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Patent number: 5789594Abstract: The present invention provides methods of preparing dimeric naphthylisoquinoline alkaloids by coupling together two monomeric naphthylisoquinoline alkaloids, each of which may be the same or different, and one, both, or neither of which may possess a C-8' to C-5 naphthalene/isoquinoline linkage, to form homodimers or heterodimers, including the antiviral michellamines. The present invention also provides new, medically useful homodimeric and heterodimeric naphthylisoquinoline compounds and derivatives thereof.Type: GrantFiled: July 1, 1996Date of Patent: August 4, 1998Assignee: The United States of America as represented by the Secretary of the Department of Health and Human ServicesInventors: Gerhard Bringmann, Sven Harmsen, Michael R. Boyd
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Patent number: 5786482Abstract: The present invention provides a method of preparing dimeric arylisoquinoline alkaloids by coupling two isoquinoline building blocks, which may be the same or different, together with a symmetrical or nonsymmetrical biaryl building block to form homodimers or heterodimers, including the antiviral michellamines. The present invention also provides new, medically useful homodimeric and heterodimeric arylisoquinoline compounds and derivatives thereof.Type: GrantFiled: September 24, 1996Date of Patent: July 28, 1998Assignees: The United States of America as represented by the Department of Health and Human Services, The Trustees of Boston CollegeInventors: Gerhard Bringmann, Michael R. Boyd, Roland Gotz, T. Ross Kelly
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Patent number: 5741789Abstract: A series of hetero-oxy alkanamines are effective pharmaceuticals for the treatment of conditions related to or affected by the reuptake of serotonin and by the serotonin 1.sub.A receptor. The compounds are particularly useful for alleviating the symptoms of nicotine and tobacco withdrawal, and for the treatment of depression and other conditions for which serotonin reuptake inhibitors are used.Type: GrantFiled: June 6, 1995Date of Patent: April 21, 1998Assignee: Eli Lilly and CompanyInventors: David J. Hibschman, Joseph H. Krushinski, Jr., Kurt Rasmussen, Vincent P. Rocco, John M. Schaus, Dennis C. Thompson
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Patent number: 5733931Abstract: The present invention provides a cyclohexanediurea derivative, inclusive of its salt, represented by the following formula (I): ##STR1## wherein R.sup.1 and R.sup.2 are the same or different and they each represent a straight-chain or branched alkyl group having at least 3 carbons, a cycloalkyl group, a cycloalkyl group having a bridge head, a furyl group, a furyl lower alkyl group or an aralkyl group, A.sub.1 and A.sub.2 are the same or different and they each represent a phenyl, pyridyl, quinolyl, isoquinolyl or indolyl group which may have substituents; a process for production thereof; an intermediate thereof; pharmaceutical use, a method for treatment and use thereof.Type: GrantFiled: March 8, 1996Date of Patent: March 31, 1998Assignee: Nissin Food Products Co., Ltd.Inventors: Toshihiro Yamada, Yoichi Nobuhara, Ichinari Takagi, Shiho Furumoto, Kazuhiro Kobayashi, Kiyohito Ikemoto
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Patent number: 5684154Abstract: A process of producing atracurium besylate that substantially reduces the level of impurities in the final product and avoids the repeated use of ether is provided. In accordance with such a process, N, N'-4,10-dioxa-3,11-dioxotridecylene-1,13-bis-tetrahydropapaverine (Compound 1), methyl benzenesulfonate and a catalytic amount of an insoluble base in a solvent are combined to form a reaction mixture that is maintained for a period of time sufficient for atracurium besylate formation. The reaction mixture is then filtered to remove the insoluble base and the atracuriurn besylate is precipitated.Type: GrantFiled: February 16, 1996Date of Patent: November 4, 1997Assignee: Abbott LaboratoriesInventors: Steven A. Chamberlin, Ashok V. Bhatia, Deborah A. Davis, Keith A. Drengler
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Patent number: 5656632Abstract: Disclosed are compounds of the formula ##STR1## or the pharmaceutically acceptable salts thereof wherein the 6-membered A ring may be optionally substituted with up to four groups independently selected from halogen, hydroxy, lower alkyl, or lower alkoxy;Ar represents optionally substituted aryl or heteroarylZ represents carbon or nitrogen provided thatwhere Z is carbon, R.sub.11 represents hydrogen, halogen, hydroxy, lower alkyl, or lower alkoxy, or phenyl optionally substituted with one or two groups selected from hydrogen, halogen, hydroxy, lower alkyl, or lower alkoxy; andwhere Z is nitrogen, R.sub.11 represents an electron pair;R.sub.5 is hydrogen or lower alkyl;L and m represent integers;n is 0, or an integer;R.sub.12 and R.sub.Type: GrantFiled: June 5, 1995Date of Patent: August 12, 1997Assignee: Neurogen CorporationInventors: Xiao-shu He, Brian de Costa, Jan W. F. Wasley
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Patent number: 5654432Abstract: The present invention provides new antiviral compounds, i.e., michellamines and derivatives and pharmacologically acceptable salts thereof, methods for isolating such antiviral compounds from a plant species of the genus Ancistrocladus, antiviral compositions containing such antiviral compounds, and methods of using such antiviral compounds for treating patients with viral infections. The antiviral compounds of the present invention inhibit the reproduction and cytopathicity of human acquired immunodeficiency viruses.Type: GrantFiled: June 1, 1995Date of Patent: August 5, 1997Assignee: The United States of America, as represented by the Department of Health and Human ServicesInventors: Michael R. Boyd, John H. Cardellina, II, Kirk P. Manfredi, John W. Blunt, Lewis K. Pannell, James B. McMahon, Robert J. Gulakowski, Gordon M. Cragg, Gerhard Bringmann, Duncan Thomas, Johnson Jato
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Patent number: 5637708Abstract: Agents having the structure,U--CH.sub.2 --V--CH.sub.2 --W,and agents having the structure,U--CH.sub.2 --V--CH.sub.2 --W--X--Y--Z,where U, W, and Z are double fused aromatic rings, V is a single six-membered aromatic ring with a hydroxyl group constituent, X is a polar group, and Y is a positively charged group, are disclosed. The double fused aromatic rings can be a five-membered aromatic ring, or a six-membered aromatic ring, fused to a six-membered aromatic ring; the double fused aromatic rings can comprise heteroatoms. The agents can be used as capsid stabilizing or antiviral agents.Type: GrantFiled: June 2, 1995Date of Patent: June 10, 1997Assignee: President and Fellows of Harvard CollegeInventors: James M. Hogle, Martin Karplus, Diane Joseph-McCarthy
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Patent number: 5629430Abstract: Trifluoromethylpyrroloindolecarboxylic acid ester derivatives, and optical isomers and pharmaceutically acceptable salts thereof are provided which are represented by the general formula (1): ##STR1## or the general formula (2): ##STR2## The compounds are antineoplastic agents which are selective to cancer cells, effective also to solid cancer, and less toxic.Type: GrantFiled: June 14, 1995Date of Patent: May 13, 1997Assignees: Kyorin Pharmaceutical Co., Ltd., Sagami Chemical Research CenterInventors: Shiro Terashima, Yasumichi Fukuda, Yasuo Oomori
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Patent number: 5602168Abstract: Disclosed are compounds of the formula ##STR1## or the pharmaceutically acceptable salts thereof wherein the 6-membered A ring may be optionally substituted with up to four groups independently selected from halogen, hydroxy, lower alkyl, or lower alkoxy;Ar represents optionally substituted aryl or heteroarylZ represents carbon or nitrogen provided thatwhere Z is carbon, R.sub.11 represents hydrogen, halogen, hydroxy, lower alkyl, or lower alkoxy, or phenyl optionally substituted with one or two groups selected from hydrogen, halogen, hydroxy, lower alkyl, or lower alkoxy; andwhere Z is nitrogen, R.sub.11 represents an electron pair;R.sub.5 is hydrogen or lower alkyl;L and m represent integers;n is 0, or an integer;R.sub.12 and R.sub.Type: GrantFiled: June 5, 1995Date of Patent: February 11, 1997Assignee: Neurogen CorporationInventors: Xiao-shu He, Brian de Costa, Jan W. F. Wasley
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Patent number: 5578729Abstract: The present invention provides a method of preparing dimeric arylisoquinoline alkaloids by coupling two isoquinoline building blocks, each of which may be the same or different, together with a symmetrical or nonsymmetrical biaryl building block to form homodimers or heterodimers, including the antiviral michellamines. The present invention also provides new, medically useful homodimeric and heterodimeric arylisoquinoline compounds and derivatives thereof.Type: GrantFiled: December 23, 1994Date of Patent: November 26, 1996Assignees: The United States of America as represented by the Department of Health and Human Services, The Trustees of Boston CollegeInventors: Gerhard Bringmann, Michael R. Boyd, Roland G otz, T. Ross Kelly
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Patent number: 5571919Abstract: The present invention provides methods of preparing dimeric naphthylisoquinoline alkaloids by coupling together two monomeric naphthylisoquinoline alkaloids, each of which may be the same or different, and one, both, or neither of which may possess a C-8' to C-5 naphthalene/isoquinoline linkage, to form homodimers or heterodimers, including the antiviral michellamines. The present invention also provides new, medically useful homodimeric and heterodimeric naphthylisoquinoline compounds and derivatives thereof.Type: GrantFiled: July 22, 1994Date of Patent: November 5, 1996Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Gerhard Bringmann, Sven Harmsen, Michael R. Boyd
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Patent number: 5556978Abstract: 1R-cis, 1'R-cis isomer of a 2',2'-(3,11-dioxo-4,10-dioxatridecylene)-bis-(1,2,3,4-tetrahydro-6,7-dimet hoxy-2-methyl-1-veratrylisoquinolinium) salt, substantially free from other geometrical and optical isomers thereof. The 1R-cis,1'R-cis isomer has been found to have an advantageous combination of pharmacological properties, notably greater neuromuscular blocking potency, weaker histamine-releasing potency, and at equivalent levels of neuromuscular blockade, fewer potential adverse effects on the autonomic nervous system (sympathetic and parasympathetic blockade), in comparison with the known mixture of geometrical and optical isomers.Type: GrantFiled: March 28, 1995Date of Patent: September 17, 1996Assignee: Glaxo Wellcome Inc.Inventors: Derek A. Hill, Geoffrey L. Turner
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Patent number: 5527811Abstract: Compounds represented by the formula: ##STR1## wherein the ring A and the ring B each stand for an optionally substituted benzene ring; Ar stands for an optionally substituted aryl group or an optionally substituted heterocyclic group; Q stands for an oxygen atom or a sulfur atom; R stands for a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group or an optionally substituted amino group; X stands for --O-- or --NR.sup.1 -- wherein R.sup.1 stands for a hydrogen atom or an optionally substituted hydrocarbon group; Y stands for --O--, --NR.sup.2 -- wherein R.sup.2 stands for a hydrogen atom or an optionally substituted hydrocarbon group, or a bond; m denotes 1, 2 or 3, and n denotes 0, 1 or 2, and salts thereof which have excellent calcium- or substance P receptor-antagonistic activity, being useful for treating a cerebralvascular disorder in mammals such as cerebralischemia, cerebral edema and neuronal damage, their production and use.Type: GrantFiled: July 13, 1994Date of Patent: June 18, 1996Assignee: Takeda Chemical Industries, Ltd.Inventors: Hideaki Natsugari, Tetsuji Imamoto, Yuzo Ichimori
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Patent number: 5514694Abstract: A novel class of peptide .alpha.-ketoamides useful for selectively inhibiting serine proteases, selectively inhibiting cysteine proteases, generally inhibiting all serine proteases, and generally inhibiting all cysteine proteases, having the formula Y--CO--AA.sup.2 --AA.sup.1 --CO--NH--X. Processes for the synthesis of peptidyl .alpha.-ketoamide derivatives.Type: GrantFiled: June 24, 1993Date of Patent: May 7, 1996Assignee: Georgia Tech Research CorpInventors: James C. Powers, Zhaozhao Li, Girish S. Patil, Der-Lun Chu
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Patent number: 5462963Abstract: The present invention involves photoprotective compositions which are useful for topical application to prevent damage to skin caused by acute or chronic exposure to ultraviolet light comprising chelating agents having the structure: ##STR1## wherein each --R.sup.1 is independently selected from the group consisting of alkyl, aryl, heteroaryl and heterocycle, or the --R.sup.1 's are covalently bonded together to form a cyclic alkyl or heterocyclic ring; --R.sup.2 and --R.sup.3 are --OR.sup.4, in which case there is no bond or a polar bond between --R.sup.2 and the nitrogen covalently bonded to --R.sup.3, each --R.sup.4 being independently selected from the group consisting of hydrogen, alkyl and aryl, except that both --R.sup.4 's are not methyl when both --R.sup.1 's are furyl; or --R.sup.2 is --O-- and is covalently bonded to the nitrogen which is covalently bonded to --R.sup.3, and --R.sup.3 is --O-- (there being a + charge on the nitrogen to which it is bonded) or nil;wherein the .alpha.Type: GrantFiled: August 2, 1991Date of Patent: October 31, 1995Assignee: The Procter & Gamble CompanyInventors: Rodney D. Bush, Donald L. Bissett
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Patent number: 5455251Abstract: The present invention provides new antiviral compounds, i.e., michellamines and derivatives and pharmacologically acceptable salts thereof, methods for isolating such antiviral compounds from a plant species of the genus Ancistrocladus, antiviral compositions containing such antiviral compounds, and methods of using such antiviral compounds for treating patients with viral infections. The antiviral compounds of the present invention inhibit the reproduction and cytopathicity of human acquired immunodeficiency viruses.Type: GrantFiled: April 19, 1993Date of Patent: October 3, 1995Assignee: The United States of America as represented by the Secretary of the Department of Health and Human ServicesInventors: Michael R. Boyd, John H. Cardellina, II, Kirk P. Manfredi, John W. Blunt, Lewis K. Pannell, James B. McMahon, Robert J. Gulakowski, Gordon M. Cragg, Gerhard Bringmann, Duncan Thomas, Johnson Jato
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Patent number: 5453510Abstract: 1R-cis,1'R-cis isomer of a 2',2'-(3,11-dioxo-4,10-dioxatridecylene)-bis(1,2,3,4-tetrahydro-6, 7-dimethoxy-2-methyl-1-veratrylisoquinolium) said, substantially free from other geometrical and optical isomers thereof. The 1R-cis,1'R-cis isomer has been found to have an advantageous combination of pharmacological properties, notably greater neuromuscular blocking potency, weaker histamine-releasing potency, and at equivalent levels of neuromuscular blockade, fewer potential adverse effects on the autonomic nervous system (sympathetic and parasympathetic blockage), in comparison with the known mixture of geometrical and optical isomers.Type: GrantFiled: July 10, 1992Date of Patent: September 26, 1995Assignee: Burroughs Wellcome Co.Inventors: Derek A. Hill, Geoffrey L. Turner
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Patent number: 5416093Abstract: Thrombin inhibitors represented by the formula ##STR1## as provided wherein A is e.g. phenylglycyl, and phenylalanyl, .alpha.-methylphenylalanine and .alpha.-methylphenylglycine wherein the amino group is preferably substituted with lower alkyl alkanoyl or lower alkoxycarbonyl, or a bicyclo group e.g. 1,2,3,4-tetrahydroisoquinolin-1-yl or -3-yl and perhydroisoquinolin-1-yl or -3-yl. Also provided are a method for inhibiting clot formation in man and animals, pharmaceutical formulations useful in the method and intermediates for the inhibitors.Type: GrantFiled: August 13, 1993Date of Patent: May 16, 1995Assignee: Eli Lilly and CompanyInventor: Robert T. Shuman
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Patent number: 5416094Abstract: Described are guanidinocarbonyl isoquinolines of the formula I, ##STR1## wherein R(1) is hydrogen, (amino) (cyclo) (aryl)alk(en)yl (heteroaryl); R(2) is hydrogen, halogen, alkyl, or aryl; G is a radical of the formula VII: ##STR2## X(2), X(3) and X(4) are hydrogen, halogen, nitro, amino, alkyl, sulfonamide, (mono) (di) (lower alkyl) (amino), benzyloxy, hydroxy; X(1) hydrogen, oxygen, sulfur and NR(7)R(8), and their pharmaceutically acceptable salts; described is also a process for their preparation, their use as medicaments, and medicaments containing them for treating congestive heart failure, and arrhythmic conditions as well as cardioprotective agents in mammals.Type: GrantFiled: September 24, 1993Date of Patent: May 16, 1995Assignee: Hoechst AktiengesellschaftInventors: Bansi Lal, Ramesh Gidwani, Ramanujam Rajagopalan, Radha Panicker, Chinnakulandai Sankar, Hans-Jochen Lang, Heinrich Englert, Wolfgang Scholz
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Patent number: 5340811Abstract: Disclosed is a sulfonamide derivative represented by following formula (I) and a medicine for the treatment of asthma comprising the sulfonamide derivative as an active ingredient which exhibits bronchodilation effect. ##STR1## wherein X represents a quinoline residue represented by formula (II) or an isoquinoline residue represented by formula (III) ##STR2## where R.sup.1 is a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group, or ##STR3## where R.sup.2 is a hydrogen atom or a hydroxyl group, and wherein: when X is quinoline residue (II), n is zero or 1, in which,when n is zero, R.sup.4 is an unsubstituted or substituted diazacycloalkyl group, andwhen n is 1, R.sup.3 is a hydrogen atom or a lower alkyl group and R.sup.4 is an unsubstituted or substituted aralkylamino group or an unsubstituted or substituted diazacycloalkyl group; andwhen X is isoquinoline residue (III), n is 1, in which, R.sup.3 is a hydrogen atom or a lower alkyl group and R.sup.Type: GrantFiled: July 17, 1990Date of Patent: August 23, 1994Assignee: Asahi Kasei Kogyo Kabushiki KaishaInventors: Akiro Kajihara, Shiro Miyoshi
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Patent number: 5334600Abstract: The compounds of the formula ##STR1## wherein R represents hydrogen, lower alkyl, aryl, biaryl, C.sub.3 -C.sub.7 -cycloalkyl, aryl-lower alkyl, aryl-lower alkenyl, aryl-lower alkynyl, aryloxy-lower alkyl, arylthio-lower alkyl, C.sub.3 -C.sub.7 -cycloalkyl-lower alkyl, biaryl-lower alkyl, aryl-C.sub.3 -C.sub.7 -cycloalkyl, aryl-C.sub.3 -C.sub.7 -cycloalkyl-lower alkyl or aryloxy-aryl-lower alkyl; and aryl represents carbocyclic or heterocyclic aryl; Z represents C.sub.1 -C.sub.3 -alkylene or vinylene, each unsubstituted or substituted by lower alkyl; Y represents SO.sub.2 (sulfonyl) or CO (carbonyl); A represents .sub.0 (oxygen), S (sulfur), or a direct bond; B represents lower alkylene; or B represents lower alkenylene or lower alkynylene provided that A represents a direct bond; X represents oxygen or sulfur, R.sub.Type: GrantFiled: February 1, 1993Date of Patent: August 2, 1994Assignee: Ciba-Geigy CorporationInventors: John H. Van Duzer, Dennis M. Roland
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Patent number: 5266700Abstract: Process employing bipyridyls as inks, of the general formula ##STR1## in which R, R' are, for example, alkyl and R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 are, for example hydrogen or alkyl radicals, or R.sup.1 and R.sup.2 or R.sup.2 and R.sup.3, and/or R.sup.4 and R.sup.5 or R.sup.5 and R.sup.6 together with the pyridine ring form in isoquinoline or quinoline ring system.Type: GrantFiled: December 31, 1991Date of Patent: November 30, 1993Assignee: Riedel-De-HaenInventors: Heinz Langhals, Christoph Naumann
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Patent number: 5250692Abstract: A water-soluble methine compound represented by the following general formula (I): ##STR1## wherein Z.sub.1 and Z.sub.2, which may be the same or different, each represents a non-metallic atomic group required for forming a 5-membered or 6-membered nitrogen-containing heterocyclic ring; R.sub.1 and R.sub.2, which may be the same or different, each represents an alkyl group; Q.sub.1 and Q.sub.2 each represents an atomic group required, in combination, for forming a 4-thiazolidinone ring, a 5-thiazolidinone ring, a 4-imidazolidinone ring, a 4-oxazolidinone ring, a 5-oxazolidinone ring, a 5-imidazolidinone ring or a 4-dithiolanone ring; L.sub.1, L.sub.2, L.sub.3, L.sub.4 and L.sub.5, which may be the same or different, each represents a methine group; R represents a hydrogen atom, an alkyl group, an aryl group or a heterocyclic group; m represents 1 or 2; i and h each represents 0 or 1; l represents 1 or 2; and j and k each represents 0, 1, 2 or 3.Type: GrantFiled: April 18, 1991Date of Patent: October 5, 1993Assignee: Fuji Photo Film Co., Ltd.Inventors: Keizo Koya, Toshinao Ukai, Haruo Takei
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Patent number: 5245034Abstract: Novel quinoline sulfonamino derivatives having a vessel smooth muscle relaxation activity as well as a platelet agglutination inhibitory activity and inhibitory activity to protein kinase A, myosin light chain kinase, proteinkinase C, and calmodulindependent proteinkinase II, but having little action or cardio function; a process for the production of the derivatives, and a pharmaceutical composition containing the derivative.Type: GrantFiled: March 23, 1992Date of Patent: September 14, 1993Assignee: Kiroyoshi HidakaInventors: Hiroyoshi Hidaka, Tomohiko Ishikawa, Masatoshi Hagiwara, Tsutomu Inoue, Kenji Naitoh, Osamu Sakuma, Masayuki Yuasa, Tadashi Morita, Tadashi Toshioka, Isao Umezawa, Takashi Inaba
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Patent number: 5244895Abstract: An anti-ulcer agent contains a compound expressed by the following general formula 1: ##STR1## where, R.sub.1 is hydrogen atom or an alkyl group having 1 or 2 carbon atoms with or without substitution, R.sub.2 and R.sub.3 are resp. hydrogen atom or form oxo group together, R.sub.4 is hydrogen atom or methyl group or isoquinoline sulfonyl group, n is 2 or 3, A is N--R.sub.5 or CH--R.sub.5, R.sub.5 is phenyl group with or without substitution or benzyloxycarbonyl group with or without substitution, or a physiologically allowable acid added salt thereof as the active component.Type: GrantFiled: May 15, 1992Date of Patent: September 14, 1993Assignee: Hiroyoshi HidakaInventors: Hiroyoshi Hidaka, Tomohiko Ishikawa