The Nitrogen Is Part Of A Substituent Which Contains Additional Nonionically Bonded Nitrogen Patents (Class 546/106)
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Patent number: 10544100Abstract: The present invention relates to compounds of formulas III and V that are useful as pharmaceutical agents, particularly as autophagy inhibitors.Type: GrantFiled: June 8, 2018Date of Patent: January 28, 2020Assignees: Translational Genomics Research Institute, Van Andel Research InstituteInventors: Jeffrey Paul MacKeigan, Katie Renee Martin, Megan Lynne Goodall, Stephen T. Gately, Tong Wang
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Publication number: 20150005328Abstract: The present invention relates to non-charged oxime compounds which are acetyl cholinesterase (AChE) reactivators of inhibited AChE and which protect against organophosphate poisoning both peripherally and in the central nervous system. Also disclosed are pharmaceutical compositions and methods for preparing the reactivator compounds and associated intermediates.Type: ApplicationFiled: July 2, 2014Publication date: January 1, 2015Inventors: Stanton F. MCHARDY, Richard M. CORBETT, Donald M. MAXWELL, Michael W. TIDWELL, Bismarck CAMPOS, Christopher J. BEMBEN
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Patent number: 8841453Abstract: The invention relates to novel hybrid cholinesterase inhibitors containing the melatonin or its oxidation products unit and tetrahydroacridine unit linked via a carbamate bond. Due to the high selectivity of action, which is expressed with high ratio of IC50 for acetylcholinesterase inhibition to IC50 for butyrylcholinesterase inhibition ([IC50(AChE)]/[IC50(BChE)]), the novel compounds may be used in relief and/or treatment of the neurodegenerative diseases, among them the Alzheimer's disease.Type: GrantFiled: November 22, 2013Date of Patent: September 23, 2014Assignees: Uniwersytet Warszawski, Centrum Medyczne Ksztalcenia PodyplomowegoInventors: Anna Zawadzka, Zbigniew Czarnocki, Iwona Lozinska, Zuzanna Moleda, Miroslawa Panasiewicz
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Patent number: 8754078Abstract: The present invention relates to pyrroloquinolinyl-pyrrolidine-2,5-dione compounds in combination with chemotherapeutic agents. The present invention provides methods of treating a cell proliferative disorder, such as a cancer, by administering to a subject in need thereof a therapeutically effective amount of a pyrroloquinolinyl-pyrrole-2,5-dione compound or pyrroloquinolinyl-pyrrolidine-2,5-dione compound of the present invention and also administering a effective amount of a chemotherapeutic agent.Type: GrantFiled: February 7, 2013Date of Patent: June 17, 2014Assignee: ArQule, Inc.Inventors: Chiang J. Li, Mark A. Ashwell, Jason Hill, Magdi M. Moussa, Neru Munshi
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Publication number: 20140148451Abstract: The present invention relates to compounds of formulas III and V that are useful as pharmaceutical agents, particularly as autophagy inhibitors.Type: ApplicationFiled: May 9, 2012Publication date: May 29, 2014Applicants: Translational Genomics Research Institute, Van Andel Research InstituteInventors: Jeffrey Paul MacKeigan, Katie Renee Martin, Megan Lynne Goodall, Stephen Gately, Tong Wang
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Publication number: 20140080860Abstract: The invention relates to novel hybrid cholinesterase inhibitors containing the melatonin or its oxidation products unit and tetrahydroacridine unit linked via a carbamate bond. Due to the high selectivity of action, which is expressed with high ratio of IC50 for acetylcholinesterase inhibition to IC50 for butyrylcholinesterase inhibition ([IC50(AChE)]/[IC50(BChE)]), the novel compounds may be used in relief and/or treatment of the neurodegenerative diseases, among them the Alzheimer's disease.Type: ApplicationFiled: November 22, 2013Publication date: March 20, 2014Applicants: CENTRUM MEDYCZNE KSZTALCENIA PODYPLOMOWEGO, UNIWERSYTET WARSZAWSKIInventors: Anna Zawadzka, Zbigniew Czarnocki, Iwona Lozinska, Zuzanna Moleda, Miroslawa Panasiewicz
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Publication number: 20140066421Abstract: The present invention relates to non-charged oxime compounds which are acetyl cholinesterase (AChE) reactivators of inhibited AChE and which protect against organophosphate poisoning both peripherally and in the central nervous system. Also disclosed are pharmaceutical compositions and methods for preparing the reactivator compounds and associated intermediates.Type: ApplicationFiled: May 17, 2012Publication date: March 6, 2014Applicant: SOUTHWEST RESEARCH INSTITUTEInventors: Stanton F. McHardy, Richard M. Corbett, Donald M. Maxwell, Michael W. Tidwell, Bismarck Campos, Christopher J. Bemben
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Patent number: 8518965Abstract: The present invention embraces bis-acridine and bis-quinoline intercalators having a bis(4-aminophenyl)ether tether, and diglycolate salts thereof, for selectively decreasing colon cancer and glial cell proliferation and preventing or treating colon cancers and gliomas.Type: GrantFiled: July 13, 2010Date of Patent: August 27, 2013Assignee: Trustees of Dartmouth CollegeInventors: Gordon W. Gribble, Dmitry A. Androsov
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Publication number: 20130178494Abstract: The present disclosure relates to new DNA-directed alkylating agents and water-soluble N-mustard agents with improved chemical stability and anti-tumor therapeutic efficacy.Type: ApplicationFiled: June 29, 2012Publication date: July 11, 2013Applicant: Academia SinicaInventors: Tsann-Long SU, Ting-Chao Chou, Te-Chuang Lee
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Publication number: 20130102627Abstract: The present disclosure is directed to compounds of Formula I: which are inhibitors of Haspin kinase and DYRK kinases. The compounds of the present disclosure, and compositions thereof, are useful in the treatment of disease related to Haspin kinase and DYRK kinase expression and/or activity.Type: ApplicationFiled: April 8, 2011Publication date: April 25, 2013Applicant: THE BRIGHAM AND WOMEN'S HOSPITAL, INC.Inventors: Jonathan Higgins, Gregory D. Cuny, Marcie Glicksman, Debasis Patnaik, Maxime Robin, Ross L. Stein, Jun Xian
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Publication number: 20130018180Abstract: Disclosed herein are a crystal of a human TOPII (hTOPII)-DNA binary complex, the method for preparing the same and the use thereof. The hTOPII-DNA binary complex includes an hTOPII portion that contains an hTOPII core domain (hTOPIIcore), and a synthetic double-stranded DNA in complex with the hTOPII portion. The synthetic double-stranded DNA has a first DNA strand comprising nucleotide positions 3 to 20 of the sequence of 5?-NNNCCGAGCNNNNGCTCGGNNN-3? (SEQ ID NO: 1), wherein N is any one of adenine, thymine, cytosine, or guanine, and a second DNA strand complementary to the first DNA strand.Type: ApplicationFiled: July 24, 2012Publication date: January 17, 2013Applicant: National Taiwan UniversityInventors: Nei-Li CHAN, Tsai-Kun Li, Chyuan-Chuan Wu, Ying-Ren Wang
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Publication number: 20120220537Abstract: N-substituted 9-aminoacridine and bis-acridino derivatives containing electron-withdrawing groups (EWG) or electron-donating groups (EDG), including amino acid residues, and one-pot methods for their synthesis are disclosed. The derivatives are potential candidates for cancer treatment.Type: ApplicationFiled: November 1, 2010Publication date: August 30, 2012Applicant: ARIEL-UNIVERSITY RESEARCH AND DEVELOPMENT COMPANY LTD.Inventor: Gary Gellerman
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Publication number: 20120165365Abstract: The present invention embraces bis-acridine and bis-quinoline intercalators having a bis(4-aminophenyl)ether tether, and diglycolate salts thereof, for selectively decreasing colon cancer and glial cell proliferation and preventing or treating colon cancers and gliomas.Type: ApplicationFiled: July 13, 2010Publication date: June 28, 2012Applicant: Trustees of Dartmouth CollegeInventors: Gordon W. Gribble, Dmitry A. Androsov
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Publication number: 20120022097Abstract: The present invention is bis-acridine or bis-quinoline intercalators having a modified bis(4-aminophenyl)ether tether to improve activity, selectivity, solubility and bioavailability of the antitumor compound.Type: ApplicationFiled: September 20, 2011Publication date: January 26, 2012Applicant: Trustees of Dartmouth CollegeInventors: Gordon W. Gribble, Justin M. Lopchuk
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Publication number: 20110318788Abstract: Provided are compounds comprising two DNA supramolecular binding molecules covalently joined by a linker group. Also provided are multisignal labeling reagents comprising (i) an oligomer of nucleotides or nucleotide analogs; (ii) a DNA supramolecular binding molecule noncovalently bound to the oligomer; and (iii) a first reactive group or a first partner of a first binding pair covalently bound to the oligomer. Additionally provided are methods of producing multisignal labeling reagents.Type: ApplicationFiled: March 14, 2011Publication date: December 29, 2011Applicant: ENZO LIFE SCIENCES, INC., C/O ENZO BIOCHEM, INC.Inventors: Jack Coleman, Elazar Rabbani, Jannis Stavrianopoulos, Praveen Pande
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Patent number: 7910739Abstract: The invention provides compounds of formula: which have a tacrine moiety connected to an heterocyclic moiety through a linker. Through careful selection of the substituents and the linker, the activity and selectivity towards acetylcholinesterase can be modulated. The compounds show potent AChE inhibition activities together with modifications in the ?-amyloid aggregation properties by binding simultaneously to the catalytic and peripheral AChE sites. They are useful in the treatment of AChE mediated diseases, such as the Alzheimer's disease.Type: GrantFiled: July 9, 2004Date of Patent: March 22, 2011Assignee: Noscira, S.A.Inventors: Ana Martinez Gil, Isabel Dorronsoro Diaz, Laura Rubio Arrieta, Diana Alonso Gordillo, Ana Fuertes Huerta, Susana Morales-Alcelay, Maria Del Monte Millan, Esther Garcia Palomero, Paola Usan Egea, Celia De Austria, Miguel Medina Padilla, Pilar Munoz Ruiz
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Publication number: 20110062429Abstract: Disclosed is an organic electroluminescent device (organic EL device) that is improved in the luminous efficiency, fully secured of the driving stability, and of a simple structure and also disclosed is a compound for organic EL device useful for the said device. The compound for organic EL device is, for example, an indolocarbazole derivative represented by the following general formula (3). The organic EL device comprises a light-emitting layer disposed between an anode and a cathode piled one upon another on a substrate and the said light-emitting layer comprises a phosphorescent dopant and the aforementioned indolocarbazole derivative as a host material. In general formula (3), L is an aromatic heterocyclic group of a fused-ring structure with a valence of (n+1), Ar1 to Ar3 each is an alkyl group, an aralkyl group, or a substituted or unsubstituted aromatic hydrocarbon or aromatic heterocyclic group, and n is an integer of 0-5.Type: ApplicationFiled: April 30, 2009Publication date: March 17, 2011Inventors: Takahiro Kai, Masaki Komori, Toshihiro Yamamoto
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Publication number: 20110044940Abstract: The present invention relates to novel Heterocyclic Ether or Thioether Derivatives, compositions comprising the Heterocyclic Ether or Thioether Derivatives, and methods for using the Heterocyclic Ether or Thioether Derivatives for treating or preventing a proliferative disorder, an anti-proliferative disorder, inflammation, arthritis, a central nervous system disorder, a cardiovascular disease, alopecia, a neuronal disease, an ischemic injury, a viral infection, a fungal infection, or a disorder related to the activity of a protein kinase.Type: ApplicationFiled: October 27, 2008Publication date: February 24, 2011Inventors: Gerald W. Shipps, JR., Matthew Richards, Cliff C. Cheng, Xiaohua Huang
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Publication number: 20100317842Abstract: The present application discloses methods for identifying inhibitors with high binding-affinity for the carbonic anhydrase-IX (CA-IX) enzyme using click chemistry and uses the candidates thereof as positron emission tomography (PET) imaging agents.Type: ApplicationFiled: August 25, 2010Publication date: December 16, 2010Applicant: SIEMENS MEDICAL SOLUTIONS USA, INC.Inventors: Hartmuth C. Kolb, Joseph C. Walsh, Dhanalakshmi Kasi, Vani P. Mocharla, Bing Wang, Umesh B. Gangadharmath, Brian A. Duclos, Kai Chen, Wei Zhang, Gang Chen, Henry Clifton Padgett, Farhad Karimi, Peter J.H. Scott, Zhiyong Gao, Qianwa Liang, Thomas Lee Collier, Tieming Zhao, Chunfang Xia
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Patent number: 7825279Abstract: Novel fused ring dicationic anti-protozoan compounds. Representative protozoan species include but are not limited to Trypanosoma brucei rhodesiense (T.b.r.) and Plasmodium falciparum. Prodrugs of these compounds can be used as an oral treatment for malaria and human African trypanosomiasis.Type: GrantFiled: November 18, 2004Date of Patent: November 2, 2010Assignees: The University of North Carolina at Chapel Hill, Georgia State University Research Foundation, Inc.Inventors: David W. Boykin, Richard R. Tidwell, W. David Wilson, Reto Brun, Reem K. Arafa, Chad E. Stephens
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Patent number: 7605265Abstract: Novel heterodimers of tetrahydroacridines and tetrahydroquinolinones are disclosed. The heterodimers are capable of acting as both acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. The heterodimers may be used to improve cognitive defects via treatment or prevention in both humans and non-humans.Type: GrantFiled: January 22, 2007Date of Patent: October 20, 2009Assignee: Biotechnology Research Corporation Ltd.Inventors: Nancy Y Ip, Fanny Chui Fun Ip, Yueqing Hu, Yifan Han, Sookja Kim Chung
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Publication number: 20090069301Abstract: Provided herein are novel sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, chemotherapeutic induced neuropathy, neuropathy associated with an ischemic event, polyglutamine diseases, ocular diseases and/or disorders, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.Type: ApplicationFiled: March 3, 2006Publication date: March 12, 2009Applicant: Sirtris Pharmaceuticals, Inc.Inventors: Michael Milburn, Jill Milne, Jean Bemis, Joseph J. Nunes, Roger Xie, Karl D. Normington
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Publication number: 20080176889Abstract: This invention relates to 9-anilinoacridine alkylating agents, their synthesis and their use in pharmaceutical compositions for treating diseases.Type: ApplicationFiled: March 12, 2004Publication date: July 24, 2008Inventors: Tsann-Long Su, Ting-Chao Chou
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Publication number: 20080153867Abstract: Embodiments of this invention relate to compounds having a combination of cannabinoid-CB1 antagonism and cholinesterase inhibition, to pharmaceutical compositions comprising these compounds, to methods for preparing these compounds, methods for preparing novel intermediates useful for the synthesis of these compounds, and methods for preparing compositions comprising these compounds. The invention also relates to methods of treating Alzheimer's disease, cognitive disorders, memory disorders, dementia, attention deficit disorder, traumatic brain injury, drug dependence, addiction or substance abuse by administering a pharmaceutical composition comprising these compounds to a patient in need thereof. A compound with a combination of cannabinoid-CB1 antagonism and cholinesterase inhibition is a compound of formula (1) wherein the symbols have the meanings given in the specification.Type: ApplicationFiled: December 17, 2007Publication date: June 26, 2008Inventors: Josephus H.M. Lange, Cornelis G. Kruse, Belal Shadid
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Patent number: 6869974Abstract: Compounds or their salts having general formulas (I) and (II): wherein s is an integer equal to 1 or 2, A is the radical of a drug that satisfies certain pharmacological tests, C and C1 are bivalent radicals, and precursors of the radicals B and B1 satisfy certain pharmacological tests.Type: GrantFiled: April 11, 2000Date of Patent: March 22, 2005Assignee: Nicox S.A.Inventor: Piero Del Soldato
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Patent number: 6821983Abstract: This invention relates to 9-anilinoacridine compounds, and more particularly to their synthesis and their use in pharmaceutical compositions for treating diseases.Type: GrantFiled: July 30, 2003Date of Patent: November 23, 2004Assignee: Academia SinicaInventors: Tsann-Long Su, Jang-Yang Chang, Ting-Chao Chou
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Publication number: 20040198765Abstract: This invention relates to 9-anilinoacridine compounds, and more particularly to their synthesis and their use in pharmaceutical compositions for treating diseases.Type: ApplicationFiled: July 30, 2003Publication date: October 7, 2004Inventors: Tsann-Long Su, Jang-Yang Chang, Ting-Chao Chou
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Patent number: 6620936Abstract: The present invention relates to new 9-aminoacridine derivatives of general formula (I), wherein A is hydrogen or (II) (wherein X is oxygen or sulfur, R1, R2, R3, R4 and R5 are independently hydrogen, halogen, nitro, amino, hydroxy, C1-C4 lower alkylhydroxy, C1-C4 lower alkylamino, C1-C8 alkyl, C1-C4 lower alkoxy or C1-C4 lower alkyloxycarbonyl and m and n are independently an integer of 0, 1 or 2), R6, R7, R8 and R9 are independently C1-C8 alkyl or C1-C4 lower alkoxy, and Y is hydrogen, amino, —N═CHR′(wherein R′ is hydrogen, benzyl, C1-C8 alkyl or C1-C6 lower alkylamino), (III) (wherein R″ is hydrogen, benzyl, C1-C8 alkyl or C1-C6 lower alkylamino, and R′″ is hydrogen, benzyl, C1-C8 alkyl or amino protecting group) or (IV) (wherein, X is as defined above, R1′, R2′, R3′, R4′ and R5′ are independently hydrogen, halogen, nitro, amino, hydroxy, C1-C4 lower alkylhydroxy, C1-C4 lower alkylamino, C1-C8 alkyl, C1-C4 lower alkoxy or C1-C4 lower alType: GrantFiled: May 16, 2001Date of Patent: September 16, 2003Assignee: Samjin Pharmaceutical Co., Ltd.Inventors: Eui-Hwan Cho, Sun-Gan Chung, Sun-Hwan Lee, Ho-Seok Kwon, Dong-Wook Kang, Jeong-Ho Joo
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Patent number: 6489336Abstract: A phenothiazine, acridan, acridone oxime, acridone hydrazone and dibenzodiazepine derivative represented by formula (I) effective against diseases in which histamine, leukotrienes, etc. participate and effective in preventing or treating diseases in which chemical mediators such as histamine and leukotrienes participate, for example, asthma, allergic rhinitis, atopic dermatitis, urticaria, hay fever, gastrointestinal allergy and food allergy.Type: GrantFiled: November 2, 2001Date of Patent: December 3, 2002Assignee: Eisai Co., Ltd.Inventors: Mitsuaki Miyamoto, Tatsuya Yoshiuchi, Keizo Sato, Makoto Kaino, Masayuki Tanaka, Motohiro Soejima, Katsuhiro Moriya, Yoshinori Sakuma, Koji Yamada, Kokichi Harada, Yukio Nishizawa, Seiichi Kobayashi, Makoto Okita, Koichi Katayama
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Publication number: 20020111491Abstract: The present invention relates to new 9-aminoacridine derivatives of general formula (I), wherein A is hydrogen or (II) (wherein X is oxygen or sulfur, R1, R2, R3, R4 and R5 are independently hydrogen, halogen, nitro, amino, hydroxy, C1-C4 lower alkylhydroxy, C1-C4 lower alkylamino, C1-C8 alkyl, C1-C4 lower alkoxy or C1-C4 lower alkyloxycarbonyl and m and n are independently an integer of 0, 1 or 2), R6, R7, R8 and R9 are independently C1-C8 alkyl or C1-C4 lower alkoxy, and Y is hydrogen, amino, -N═CHR′(wherein R′ is hydrogen, benzyl, C1-C8 alkyl or C1-C6 lower alkylamino), (III) (wherein R″ is hydrogen, benzyl, C1-C8 alkyl or C1-C6 lower alkylamino, and R′″ is hydrogen, benzyl, C1-C8 alkyl or amino protecting group) or (IV) (wherein, X is as defined above, R1′, R2′, R3′, R4′ and R5′ are independently hydrogen, halogen, nitro, amino, hydroxy, C1-C4 lower alkylhydroxy, C1-C4 lower alkylamino, C1-C8 alkyl, C1-C4 lower alkoxy or C1-C4 lower alkylcarType: ApplicationFiled: May 16, 2001Publication date: August 15, 2002Applicant: Samjin Pharmaceutical Co., Ltd.Inventors: Eui-Hwan Cho, Sun-Gan Chung, Sun-Hwan Lee, Ho-Seok Kwon, Dong-Wook Kang, Jeong-Ho Joo
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Patent number: 6262265Abstract: Novel chemical analogs are disclosed for the essential heroin metabolite 6-O-acetyl morphine (6MAM). The analogs optionally can be made to contain protein reactive groups, and can be used to form protein conjugates, fluorescently labeled compounds, and solid-phase adsorbants. The proteins conjugates can be used in turn to raise antibodies reactive with 6MAM and having a low cross-reactivity with the closely related opiates, morphine and codeine. The antibodies can be used in combination with labeled analogs in exquisitely sensitive immunoassays suitable for testing for heroin abuse.Type: GrantFiled: June 18, 1999Date of Patent: July 17, 2001Assignee: Microgenics CorporationInventors: Riaz Rouhani, Gerald F. Sigler
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Patent number: 6262104Abstract: Compounds, or solvates or salts thereof, of formula (I): selective delta opioid agonists and antagonists and may be of therapeutic utility as analgesics, immunosuppressants to prevent rejection in organ transplant and skin graft, anti-allergic and anti-inflammatory agents, brain cell protectants, agents for treating drug and alcohol abuse, gastritis, diarrhoea, cardiovascular and respiratory diseases, cough, mental illness, epilepsy and, in general, agents for the treatment of those pathological conditions which, customarily, can be treated with agonists and antagonists of the delta opioid receptor.Type: GrantFiled: June 5, 1998Date of Patent: July 17, 2001Assignee: SmithKline Beecham p.l.c.Inventors: Giulio Dondio, Silvano Ronzoni
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Patent number: 6248750Abstract: There are disclosed compounds having the formula wherein n is 1-4; X is hydrogen, loweralkyl, cycloalkyl, loweralkoxy, halogen, hydroxy, nitro, trifluoromethyl, formyl, loweralkylcarbonyl, arylcarbonyl, —SH, loweralkylthio, —NHCOR2 or —NR3R4 where R2 is hydrogen or loweralkyl, and R3 and R4 are independently hydrogen, loweralkyl or cycloalkyl; R is hydrogen, loweralkyl or loweralkylcarbonyl; and R1 is hydrogen, loweralkyl, aryl, diloweralkylaminoloweralkyl, arylloweralkyl, furylloweralkyl, thienylloweralkyl, pyridinylloweralkyl, diarylloweralkyl, oxygen-bridged arylloweralkyl or oxygen-bridged diarylloweralkyl; stereo, optical and geometrical isomers thereof, and pharmaceutically acceptable acid addition salts thereof which are useful for enhancing memory.Type: GrantFiled: March 24, 2000Date of Patent: June 19, 2001Assignee: Hoechst Roussel PharmaceuticalsInventors: Gregory Michael Shutske, Kevin James Kapples
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Patent number: 6242459Abstract: This invention relates to substituted bis-acridines and related compounds which are ligands, in particular, antagonists of the CCR5 receptor. In addition, this invention relates to the treatment and prevention of disease states mediated by CCR5, including, but not limited to, asthma and atopic disorders, rheumatoid arthritis, atherosclerosis, psoriasis, auto immune diseases such as multiple sclerosis, and inflammatory bowel disease, all in mammals, by the use of substituted bis-acridines and related compounds which are CCR5 receptor antagonists. Also, since CCR5 is a co-receptor for the entry of HIV into cells, selective receptor ligands may be useful in the treatment of HIV infection.Type: GrantFiled: July 2, 1999Date of Patent: June 5, 2001Assignee: SmithKline Beecham CorporationInventors: William E. Bondinell, Valerie A. Reader, Thomas Wen Fu Ku
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Patent number: 6207673Abstract: The present invention provides covalent conjugates of topoisomerase I and topoisomerase II inhibitors. Such compounds have a structure according to formula I: TI—L—TII (I) wherein: TI is a topoisomerase I inhibitor such as a camptothecin group; TII is a topoisomerase II inhibitor such as an amsacrine, ellipticine, epipodophyllotoxin, or anthracycline antibiotic group; and L is a linking group. The compounds are useful for inhibiting topoisomerase I and II enzymes, for promoting cellular differentiation, and for treating cancer.Type: GrantFiled: March 12, 1997Date of Patent: March 27, 2001Assignees: The University of North Carolina at Chapel Hill, Yale UniversityInventors: Kuo-Hsiung Lee, Yung-Chi Cheng, Xin Guo, Kenneth F. Bastow, Hui-Kang Wang
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Patent number: 6197825Abstract: The present invention relates to chromotropic nitrone spin trapping agents, methods of making these agents, compositions comprising same, and methods of their use. In particular, azulenyl nitrones of the present invention are effective agents for trapping free radical species and find use as efficient antioxidants in physicochemical and biological systems. Accordingly, the invention also relates to spin adducts formed from the combination of azulenyl nitrones with free radicals. The compounds of the present invention are readily prepared from available starting materials and find further use in assays and in a number of diagnostic, prophylactic and therapeutic applications, including but not limited to the alleviation, modulation and inhibition of the negative effects of carbon-centered or oxygen-centered radical species and other products of oxidation. Moreover, the combination adducts may be calorimetrically detected and, optionally, isolated and characterized to obtain valuable information (e.g.Type: GrantFiled: May 28, 1998Date of Patent: March 6, 2001Assignee: Florida International UniversityInventor: David Alan Becker
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Patent number: 6194403Abstract: A series of tacrine derivatives has be synthesized and disclosed. These tacrine derivatives were claimed to be new and be useful for the treatment of Alzheimer's disease alone or in combination with other drugs for Alzheimer's disease. These tacrine derivatives may be formulated into suitable pharmaceutical dosage forms for the treatment of Alzheimer's disease.Type: GrantFiled: September 9, 1999Date of Patent: February 27, 2001Assignee: Unitech Pharmaceuticals, Inc.Inventors: Ming-Kuan Hu, Jiajiu Shaw
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Patent number: 6187787Abstract: A series of bis-acridinyl DNA intercalating agents with anticancer cell activity represented by formula (I), where Z is a linear arrangement of multiple aromatic rings, containing at least three aromatic rings, or at least two alicyclic rings, said rings being linked in a 1,4 or 1,3 manner are provided. Methods of inhibiting cancer cells and treating patients having cancer with these agents are also provided.Type: GrantFiled: February 15, 2000Date of Patent: February 13, 2001Assignee: Trustees of Dartmouth CollegeInventors: Gordon W. Gribble, Gary D. Jaycox, Michael Mosher
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Patent number: 6093725Abstract: Compounds and methods for inactivating pathogens in materials are described, including compositions and methods for inactivating pathogens in biological materials such as red blood cell preparations and plasma. The compounds and methods may be used to treat materials intended for in vitro or in vivo use, such as clinical testing or transfusion. The compounds are designed to specifically bind to and react with nucleic acid, and then to degrade to form breakdown products. The degradation reaction is preferably slower than the reaction with nucleic acid.Type: GrantFiled: January 6, 1998Date of Patent: July 25, 2000Assignee: Cerus CorporationInventors: David Cook, John E. Merritt, Aileen Nerio, Henry Rapoport, Adonis Stassinopoulos, Susan Wollowitz, Jan Matejovic
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Patent number: 6083988Abstract: The present invention relates to chromotropic nitrone spin trapping agents, methods of making these agents, compositions comprising same, and methods of their use. In particular, azulenyl nitrones of the present invention are effective agents for trapping free radical species and find use as efficient antioxidants in physicochemical and biological systems. Accordingly, the invention also relates to spin adducts formed from the combination of azulenyl nitrones with free radicals. The compounds of the present invention are readily prepared from available starting materials and find further use in assays and in a number of diagnostic, prophylactic and therapeutic applications, including but not limited to the alleviation, modulation and inhibition of the negative effects of carbon-centered or oxygen-centered radical species and other products of oxidation. Moreover, the combination adducts may be calorimetrically detected and, optionally, isolated and characterized to obtain valuable information (e.g.Type: GrantFiled: September 4, 1997Date of Patent: July 4, 2000Inventor: David Alan Becker
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Patent number: 6075144Abstract: There are disclosed compounds having the formula ##STR1## wherein n is 1-4; X is hydrogen, loweralkyl, cycloalkyl, loweralkoxy, halogen, hydroxy, nitro, trifluoromethyl, formyl, loweralkylcarbonyl, arylcarbonyl, --SH, loweralkylthio, --NHCOR.sub.2 or --NR.sub.3 R.sub.4 where R.sub.2 is hydrogen or loweralkyl, and R.sub.3 and R.sub.4 are independently hydrogen, loweralkyl or cycloalkyl; R is hydrogen, loweralkyl or loweralkylcarbonyl; and R.sub.1 is hydrogen, loweralkyl, aryl, diloweralkylaminoloweralkyl, arylloweralkyl, furylloweralkyl, thienylloweralkyl, pyridinylloweralkyl, diarylloweralkyl, oxygen-bridged arylloweralkyl or oxygen-bridged diarylloweralkyl; stereo, optical and geometrical isomers thereof, and pharmaceutically acceptable acid addition salts thereof which are useful for enhancing memory.Type: GrantFiled: June 13, 1994Date of Patent: June 13, 2000Assignee: Hoechst Marion Roussel, Inc.Inventors: Gregory Michael Shutske, Kevin James Kapples
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Patent number: 5939428Abstract: The invention provides a compound of the following formula: ##STR1## wherein R.sup.1 is C.sub.1-6 alkyl; or phenyl;R.sup.2 is hydrogen;an acyl group of the formula --COR.sup.a wherein R.sup.a is C.sub.1-6 alkyl or phenyl; oran acetylalkylcarbonyl group of the formula --CO(CH.sub.2).sub.n COCH.sub.3 wherein n=1-3; andR.sup.3 and R.sup.4 are substituents at different position(s) of the acridine ring (i.e. C-1'-C-8'), and R.sup.3 and R.sup.4 may be the same or different and independently represent:hydrogen;C.sub.1-6 alkyl;C.sub.1-6 alkyloxy;a nitro group;an amino group of the formula --NR.sup.b R.sup.c wherein R.sup.b and R.sup.c may be the same or different and independently represent hydrogen or C.sub.1-6 alkyl;an aminoalkylamino group of the formula --NH(CH.sub.2).sub.n NR.sup.d R.sup.e wherein R.sup.d and R.sup.e may be the same or different and independently represent hydrogen, C.sub.1-6 alkyl, a hydroxyalkyl group of the formula --(CH.sub.2).sub.n OH wherein n=1-3, or C.sub.Type: GrantFiled: May 4, 1998Date of Patent: August 17, 1999Assignee: National Health Research InstitutesInventors: Tsann-Long Su, Ting-Chao Chou, Felicia Y.-H. Wu, Cheng-Wen Wu
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Patent number: 5886185Abstract: A series of novel polyamine-linked acridine dimers and derivatives thereof are described. The polyamine-linked acridine dimers and derivatives are potential anti-cancer agents.Type: GrantFiled: November 20, 1997Date of Patent: March 23, 1999Assignee: Development Center for BiotechnoloyInventors: Shan-Yen Chou, Shan-Shue Wang, Chin-Fen Lee, Wei-Kun Yin, Shyh-Fong Chen
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Patent number: 5672707Abstract: "Derivatives of 9-aminoacridine characterized by psychothropic, antiamnestic and lipid-regulating activities".New chemical compounds derived of 9-aminoacridine with a general formula are presented: ##STR1## where R=H or CH.sub.3 R.sup.1 =H, CH.sub.3, or BrR.sup.2 =H, CH.sub.3R.sup.3 =--C.sub.1 -C.sub.5 alkyl phenylmethyl, substituted phenylmethyl or diethylaminoethylX=C=O, or CHOH, Y=CH.sub.2 orX+Y=CH=CHand their salts with organic and inorganic acids.The target compounds were obtained by a reaction of substituted nitriles of anthranilic acid with dimedone and subsequent cyclization of intermediate enaminonitriles to the corresponding 9-amino-3,4-dihydroacridine-1(2H)-ones. The reduction of the compounds or their alkylated or aralkylated at 9-aminogroupe derivatives results in corresponding alkanols, which on dehydratation give 9-amino-3,4-dihydroacridines.Type: GrantFiled: October 29, 1993Date of Patent: September 30, 1997Assignee: Vserossiisky Nauchny Tsentr Po Bezopasnosti Biologicheski Aktivnykh veschestv (Vntsbav)Inventors: Yury Valentinovich Burov, Sergei Borisovich Goncharenko, Tatyana Nikolaevna Robakidze, Jury Nikolaevich Portnov, Ljubov Vladislavovna Kadysheva, Ilmar Kharievich Penke, Eduard Maximovich Peganov, Svetlana Alexeevna Sukhanova, Galina Vasilievna Tananova, Anatoly Evgenievich Voronin, Anatoly Alexeevich Kotlobai, Yanis Fritsevich Oshis, Lidia Evgenievna Pchelintseva
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Patent number: 5602142Abstract: Hypoxia selective cytotoxins having the structural formula ##STR1## wherein D, E, F and G, independently, are carbon or nitrogen, with the proviso that three or more of D, E, F and G are carbon; R.sub.1 and R.sub.2, independently, are selected from the group consisting of methyl, halo, hydro, trifluoromethyl, methoxy, cyano, and methylsulfo; R.sub.3 and R.sub.4, independently, are selected from the group consisting of methyl, ethyl, phenyl, naphthyl, tertiary butyl, halo, halomethylene, hydro, trifluoromethyl, cyano and methylsulfo, or R.sub.3 and R.sub.4 taken together are a substituted or unsubstituted five or six-membered nonaromatic ring system; n is an integer 1 through 5; X is carbon or nitrogen; and Z is a physiologically acceptable anion, are disclosed. The compounds are useful as radiosensitizers or chemosensitizers, especially in the treatment of cancer patients.Type: GrantFiled: December 21, 1994Date of Patent: February 11, 1997Assignee: Evanston Hospital CorporationInventors: Maria V. Papadopoulou-Rosenzweig, William D. Bloomer
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Patent number: 5569763Abstract: Hydrazone compound useful as an excellent organic nonlinear optical material and a highly sensitive coloring chelation agent, represented by the following formula (1): ##STR1## wherein Ar is a substituted or an non-substituted 2-imidazolyl group, a 4-imidazolyl group, 3-pyrazolyl group, 3-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 2-quinolyl, 1-isoquinolyl, 3-isoquinolyl, 1-phthalazinyl, 2-quinazolinyl, 2-benzimidazolyl, 2-benzothiazolyl, or 2-thiazolyl group,R.sup.1 is a nitro group, cyano group or trifluoromethyl group,R.sup.2 is a nitro group, cyano group, trifluoromethyl group or a halogen atom, or a substituted or an non-substituted alkyl group,R.sup.3 is a hydrogen atom, andn is an integer from 0 to 3.Type: GrantFiled: March 10, 1995Date of Patent: October 29, 1996Assignee: Kabushiki Kaisha ToshibaInventor: Yoshiaki Kawamonzen
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Patent number: 5536728Abstract: A novel 4-acylaminopyridine derivative represented by the following formula (I) is disclosed. ##STR1## The 4-acylaminopyridine derivative of the present invention is useful as a medicine for treating disturbances of memory such as senile dementia and Alzheimer's disease, since it has an action of directly activating malfunctioned cholinergic neuron.Type: GrantFiled: December 8, 1994Date of Patent: July 16, 1996Assignee: Mitsubishi Chemical CorporationInventors: Kunihiro Ninomiya, deceased, Ken-ichi Saito, Mamoru Sugano, Akihiro Tobe, Yasuhiro Morinaka, Tomoko Bessho, Haruko Harada
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Patent number: 5512667Abstract: Oligonucleotides having a low molecular weight tail molecules joined to the 3' terminus of the oligonucleotide via a linking molecule of the structure:Z is ##STR1## wherein ##STR2## m and m' are positive integers less than 11, n is 0 or 1 and Q is a connecting group, are synthesized by selectively reacting three independent functional groups on the linking molecule, i.e., an amine, a primary hydroxyl and a secondary hydroxyl, in a stepwise manner. A tail molecule R is first connected to the amino functionality of the linking molecule. Next the linking molecule-tail molecule combination is attached to a solid state support via the secondary hydroxyl group. The oligonucleotide is systematically stepwise synthesized beginning on the primary hydroxyl group followed by release of the oligonucleotide having the low molecular weight tailed joined to its 3' terminus from the solid state support.Type: GrantFiled: February 3, 1993Date of Patent: April 30, 1996Inventors: Michael W. Reed, Rich B. Meyer, Jr.
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Patent number: 5478837Abstract: Compositions and methods for prevention of adhesion formation, whereby an effective amount of quinacrine as active agent is administered for a period of time sufficient to permit tissue repair. The active agent is preferably administered in conjunction with a delivery vehicle (e.g., microcapsules, microspheres, lipid-based systems, viscous instillates and absorbable mechanical barriers) useful for maintaining local concentrations of the compound at an effective level.Type: GrantFiled: June 7, 1994Date of Patent: December 26, 1995Assignee: University of Southern CaliforniaInventors: Kathleen E. Rodgers, Gere S. Dizerega
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Patent number: 5354864Abstract: The present invention provides a compound having the structure: ##STR1## wherein R.sup.1 and R.sup.2 are independently the same or different and are hydrogen, an acetyl group; an acyl group having the formula --CO(CH.sub.2).sub.n COCH.sub.3, wherein n=1-3; --CO(CH.sub.2).sub.n COOM, wherein n=1-4 and M is hydrogen, Na or K; or --(CH.sub.2).sub.n COOR, wherein n=1-4 and R is hydrogen, Na, K or an alkyl group having 1 to 5 carbon atoms; a hydroxyalkyl group having the formula --(CH.sub.2).sub.n CH.sub.2 OH, wherein n=1-4; a halo alkyl group having the formula --(CH.sub.2).sub.n CH.sub.2 X, wherein n=1-4 and X is a chloro, bromo, or iodo group; a metal sulfonate (--SO.sub.3 M) wherein M is Na or K; a metal sulfinate (--SO.sub.2 M) wherein M is Na or K; a alkyl sulfonate (--SO.sub.3 R) wherein R is an alkyl group having 1 to 4 carbon atoms such as methyl, ethyl, n-propyl or i-propyl; an alkylsulfonyl group (--SO.sub.Type: GrantFiled: May 21, 1992Date of Patent: October 11, 1994Assignee: Sloan-Kettering Institute for Cancer ResearchInventors: Kyoichi A. Watanabe, Grazyna Ciszewska, Tsann-Long Su, Ting-Chao Chou