The Nitrogen Is Part Of A Substituent Which Contains Additional Nonionically Bonded Nitrogen Patents (Class 546/106)
  • Patent number: 10544100
    Abstract: The present invention relates to compounds of formulas III and V that are useful as pharmaceutical agents, particularly as autophagy inhibitors.
    Type: Grant
    Filed: June 8, 2018
    Date of Patent: January 28, 2020
    Assignees: Translational Genomics Research Institute, Van Andel Research Institute
    Inventors: Jeffrey Paul MacKeigan, Katie Renee Martin, Megan Lynne Goodall, Stephen T. Gately, Tong Wang
  • Publication number: 20150005328
    Abstract: 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: Application
    Filed: July 2, 2014
    Publication date: January 1, 2015
    Inventors: Stanton F. MCHARDY, Richard M. CORBETT, Donald M. MAXWELL, Michael W. TIDWELL, Bismarck CAMPOS, Christopher J. BEMBEN
  • Patent number: 8841453
    Abstract: 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: Grant
    Filed: November 22, 2013
    Date of Patent: September 23, 2014
    Assignees: Uniwersytet Warszawski, Centrum Medyczne Ksztalcenia Podyplomowego
    Inventors: Anna Zawadzka, Zbigniew Czarnocki, Iwona Lozinska, Zuzanna Moleda, Miroslawa Panasiewicz
  • Patent number: 8754078
    Abstract: 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: Grant
    Filed: February 7, 2013
    Date of Patent: June 17, 2014
    Assignee: ArQule, Inc.
    Inventors: Chiang J. Li, Mark A. Ashwell, Jason Hill, Magdi M. Moussa, Neru Munshi
  • Publication number: 20140148451
    Abstract: The present invention relates to compounds of formulas III and V that are useful as pharmaceutical agents, particularly as autophagy inhibitors.
    Type: Application
    Filed: May 9, 2012
    Publication date: May 29, 2014
    Applicants: Translational Genomics Research Institute, Van Andel Research Institute
    Inventors: Jeffrey Paul MacKeigan, Katie Renee Martin, Megan Lynne Goodall, Stephen Gately, Tong Wang
  • Publication number: 20140080860
    Abstract: 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: Application
    Filed: November 22, 2013
    Publication date: March 20, 2014
    Applicants: CENTRUM MEDYCZNE KSZTALCENIA PODYPLOMOWEGO, UNIWERSYTET WARSZAWSKI
    Inventors: Anna Zawadzka, Zbigniew Czarnocki, Iwona Lozinska, Zuzanna Moleda, Miroslawa Panasiewicz
  • Publication number: 20140066421
    Abstract: 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: Application
    Filed: May 17, 2012
    Publication date: March 6, 2014
    Applicant: SOUTHWEST RESEARCH INSTITUTE
    Inventors: Stanton F. McHardy, Richard M. Corbett, Donald M. Maxwell, Michael W. Tidwell, Bismarck Campos, Christopher J. Bemben
  • Patent number: 8518965
    Abstract: 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: Grant
    Filed: July 13, 2010
    Date of Patent: August 27, 2013
    Assignee: Trustees of Dartmouth College
    Inventors: Gordon W. Gribble, Dmitry A. Androsov
  • Publication number: 20130178494
    Abstract: 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: Application
    Filed: June 29, 2012
    Publication date: July 11, 2013
    Applicant: Academia Sinica
    Inventors: Tsann-Long SU, Ting-Chao Chou, Te-Chuang Lee
  • Publication number: 20130102627
    Abstract: 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: Application
    Filed: April 8, 2011
    Publication date: April 25, 2013
    Applicant: THE BRIGHAM AND WOMEN'S HOSPITAL, INC.
    Inventors: Jonathan Higgins, Gregory D. Cuny, Marcie Glicksman, Debasis Patnaik, Maxime Robin, Ross L. Stein, Jun Xian
  • Publication number: 20130018180
    Abstract: 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: Application
    Filed: July 24, 2012
    Publication date: January 17, 2013
    Applicant: National Taiwan University
    Inventors: Nei-Li CHAN, Tsai-Kun Li, Chyuan-Chuan Wu, Ying-Ren Wang
  • Publication number: 20120220537
    Abstract: 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: Application
    Filed: November 1, 2010
    Publication date: August 30, 2012
    Applicant: ARIEL-UNIVERSITY RESEARCH AND DEVELOPMENT COMPANY LTD.
    Inventor: Gary Gellerman
  • Publication number: 20120165365
    Abstract: 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: Application
    Filed: July 13, 2010
    Publication date: June 28, 2012
    Applicant: Trustees of Dartmouth College
    Inventors: Gordon W. Gribble, Dmitry A. Androsov
  • Publication number: 20120022097
    Abstract: 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: Application
    Filed: September 20, 2011
    Publication date: January 26, 2012
    Applicant: Trustees of Dartmouth College
    Inventors: Gordon W. Gribble, Justin M. Lopchuk
  • Publication number: 20110318788
    Abstract: 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: Application
    Filed: March 14, 2011
    Publication date: December 29, 2011
    Applicant: ENZO LIFE SCIENCES, INC., C/O ENZO BIOCHEM, INC.
    Inventors: Jack Coleman, Elazar Rabbani, Jannis Stavrianopoulos, Praveen Pande
  • Patent number: 7910739
    Abstract: 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: Grant
    Filed: July 9, 2004
    Date of Patent: March 22, 2011
    Assignee: 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
  • Publication number: 20110062429
    Abstract: 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: Application
    Filed: April 30, 2009
    Publication date: March 17, 2011
    Inventors: Takahiro Kai, Masaki Komori, Toshihiro Yamamoto
  • Publication number: 20110044940
    Abstract: 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: Application
    Filed: October 27, 2008
    Publication date: February 24, 2011
    Inventors: Gerald W. Shipps, JR., Matthew Richards, Cliff C. Cheng, Xiaohua Huang
  • Publication number: 20100317842
    Abstract: 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: Application
    Filed: August 25, 2010
    Publication date: December 16, 2010
    Applicant: 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
  • Patent number: 7825279
    Abstract: 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: Grant
    Filed: November 18, 2004
    Date of Patent: November 2, 2010
    Assignees: 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
  • Patent number: 7605265
    Abstract: 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: Grant
    Filed: January 22, 2007
    Date of Patent: October 20, 2009
    Assignee: Biotechnology Research Corporation Ltd.
    Inventors: Nancy Y Ip, Fanny Chui Fun Ip, Yueqing Hu, Yifan Han, Sookja Kim Chung
  • Publication number: 20090069301
    Abstract: 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: Application
    Filed: March 3, 2006
    Publication date: March 12, 2009
    Applicant: Sirtris Pharmaceuticals, Inc.
    Inventors: Michael Milburn, Jill Milne, Jean Bemis, Joseph J. Nunes, Roger Xie, Karl D. Normington
  • Publication number: 20080176889
    Abstract: This invention relates to 9-anilinoacridine alkylating agents, their synthesis and their use in pharmaceutical compositions for treating diseases.
    Type: Application
    Filed: March 12, 2004
    Publication date: July 24, 2008
    Inventors: Tsann-Long Su, Ting-Chao Chou
  • Publication number: 20080153867
    Abstract: 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: Application
    Filed: December 17, 2007
    Publication date: June 26, 2008
    Inventors: Josephus H.M. Lange, Cornelis G. Kruse, Belal Shadid
  • Patent number: 6869974
    Abstract: 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: Grant
    Filed: April 11, 2000
    Date of Patent: March 22, 2005
    Assignee: Nicox S.A.
    Inventor: Piero Del Soldato
  • Patent number: 6821983
    Abstract: This invention relates to 9-anilinoacridine compounds, and more particularly to their synthesis and their use in pharmaceutical compositions for treating diseases.
    Type: Grant
    Filed: July 30, 2003
    Date of Patent: November 23, 2004
    Assignee: Academia Sinica
    Inventors: Tsann-Long Su, Jang-Yang Chang, Ting-Chao Chou
  • Publication number: 20040198765
    Abstract: This invention relates to 9-anilinoacridine compounds, and more particularly to their synthesis and their use in pharmaceutical compositions for treating diseases.
    Type: Application
    Filed: July 30, 2003
    Publication date: October 7, 2004
    Inventors: Tsann-Long Su, Jang-Yang Chang, Ting-Chao Chou
  • Patent number: 6620936
    Abstract: 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 al
    Type: Grant
    Filed: May 16, 2001
    Date of Patent: September 16, 2003
    Assignee: Samjin Pharmaceutical Co., Ltd.
    Inventors: Eui-Hwan Cho, Sun-Gan Chung, Sun-Hwan Lee, Ho-Seok Kwon, Dong-Wook Kang, Jeong-Ho Joo
  • Patent number: 6489336
    Abstract: 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: Grant
    Filed: November 2, 2001
    Date of Patent: December 3, 2002
    Assignee: 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
  • Publication number: 20020111491
    Abstract: 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 alkylcar
    Type: Application
    Filed: May 16, 2001
    Publication date: August 15, 2002
    Applicant: Samjin Pharmaceutical Co., Ltd.
    Inventors: Eui-Hwan Cho, Sun-Gan Chung, Sun-Hwan Lee, Ho-Seok Kwon, Dong-Wook Kang, Jeong-Ho Joo
  • Patent number: 6262104
    Abstract: 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: Grant
    Filed: June 5, 1998
    Date of Patent: July 17, 2001
    Assignee: SmithKline Beecham p.l.c.
    Inventors: Giulio Dondio, Silvano Ronzoni
  • Patent number: 6262265
    Abstract: 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: Grant
    Filed: June 18, 1999
    Date of Patent: July 17, 2001
    Assignee: Microgenics Corporation
    Inventors: Riaz Rouhani, Gerald F. Sigler
  • Patent number: 6248750
    Abstract: 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: Grant
    Filed: March 24, 2000
    Date of Patent: June 19, 2001
    Assignee: Hoechst Roussel Pharmaceuticals
    Inventors: Gregory Michael Shutske, Kevin James Kapples
  • Patent number: 6242459
    Abstract: 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: Grant
    Filed: July 2, 1999
    Date of Patent: June 5, 2001
    Assignee: SmithKline Beecham Corporation
    Inventors: William E. Bondinell, Valerie A. Reader, Thomas Wen Fu Ku
  • Patent number: 6207673
    Abstract: 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: Grant
    Filed: March 12, 1997
    Date of Patent: March 27, 2001
    Assignees: The University of North Carolina at Chapel Hill, Yale University
    Inventors: Kuo-Hsiung Lee, Yung-Chi Cheng, Xin Guo, Kenneth F. Bastow, Hui-Kang Wang
  • Patent number: 6197825
    Abstract: 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: Grant
    Filed: May 28, 1998
    Date of Patent: March 6, 2001
    Assignee: Florida International University
    Inventor: David Alan Becker
  • Patent number: 6194403
    Abstract: 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: Grant
    Filed: September 9, 1999
    Date of Patent: February 27, 2001
    Assignee: Unitech Pharmaceuticals, Inc.
    Inventors: Ming-Kuan Hu, Jiajiu Shaw
  • Patent number: 6187787
    Abstract: 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: Grant
    Filed: February 15, 2000
    Date of Patent: February 13, 2001
    Assignee: Trustees of Dartmouth College
    Inventors: Gordon W. Gribble, Gary D. Jaycox, Michael Mosher
  • Patent number: 6093725
    Abstract: 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: Grant
    Filed: January 6, 1998
    Date of Patent: July 25, 2000
    Assignee: Cerus Corporation
    Inventors: David Cook, John E. Merritt, Aileen Nerio, Henry Rapoport, Adonis Stassinopoulos, Susan Wollowitz, Jan Matejovic
  • Patent number: 6083988
    Abstract: 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: Grant
    Filed: September 4, 1997
    Date of Patent: July 4, 2000
    Inventor: David Alan Becker
  • Patent number: 6075144
    Abstract: 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: Grant
    Filed: June 13, 1994
    Date of Patent: June 13, 2000
    Assignee: Hoechst Marion Roussel, Inc.
    Inventors: Gregory Michael Shutske, Kevin James Kapples
  • Patent number: 5939428
    Abstract: 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: Grant
    Filed: May 4, 1998
    Date of Patent: August 17, 1999
    Assignee: National Health Research Institutes
    Inventors: Tsann-Long Su, Ting-Chao Chou, Felicia Y.-H. Wu, Cheng-Wen Wu
  • Patent number: 5886185
    Abstract: 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: Grant
    Filed: November 20, 1997
    Date of Patent: March 23, 1999
    Assignee: Development Center for Biotechnoloy
    Inventors: Shan-Yen Chou, Shan-Shue Wang, Chin-Fen Lee, Wei-Kun Yin, Shyh-Fong Chen
  • Patent number: 5672707
    Abstract: "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: Grant
    Filed: October 29, 1993
    Date of Patent: September 30, 1997
    Assignee: 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
  • Patent number: 5602142
    Abstract: 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: Grant
    Filed: December 21, 1994
    Date of Patent: February 11, 1997
    Assignee: Evanston Hospital Corporation
    Inventors: Maria V. Papadopoulou-Rosenzweig, William D. Bloomer
  • Patent number: 5569763
    Abstract: 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: Grant
    Filed: March 10, 1995
    Date of Patent: October 29, 1996
    Assignee: Kabushiki Kaisha Toshiba
    Inventor: Yoshiaki Kawamonzen
  • Patent number: 5536728
    Abstract: 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: Grant
    Filed: December 8, 1994
    Date of Patent: July 16, 1996
    Assignee: Mitsubishi Chemical Corporation
    Inventors: Kunihiro Ninomiya, deceased, Ken-ichi Saito, Mamoru Sugano, Akihiro Tobe, Yasuhiro Morinaka, Tomoko Bessho, Haruko Harada
  • Patent number: 5512667
    Abstract: 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: Grant
    Filed: February 3, 1993
    Date of Patent: April 30, 1996
    Inventors: Michael W. Reed, Rich B. Meyer, Jr.
  • Patent number: 5478837
    Abstract: 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: Grant
    Filed: June 7, 1994
    Date of Patent: December 26, 1995
    Assignee: University of Southern California
    Inventors: Kathleen E. Rodgers, Gere S. Dizerega
  • Patent number: 5354864
    Abstract: 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: Grant
    Filed: May 21, 1992
    Date of Patent: October 11, 1994
    Assignee: Sloan-Kettering Institute for Cancer Research
    Inventors: Kyoichi A. Watanabe, Grazyna Ciszewska, Tsann-Long Su, Ting-Chao Chou