Title:
BRAIN-TARGETING PRODRUG FOR AMPA RECEPTOR SYNERGIST, AND PHARMACEUTICAL APPLICATIONS
Document Type and Number:
WIPO Patent Application WO/2017/177896
Kind Code:
A1
Abstract:
Disclosed in the present invention are a compound represented by formula (I), a geometric or optical isomer, a pharmaceutically acceptable salt, a solvate or a polymorph thereof. Also disclosed in the present invention is a composition of the compound represented by formula (I), the geometric or optical isomer, the pharmaceutically acceptable salt, the solvate or the polymorph thereof. Also disclosed in the present invention are applications of the compound represented by formula (I), the geometric or optical isomer, the pharmaceutically acceptable salt, the solvate or the polymorph thereof in diseases related to glutamic acid hypofunction, neurodegenerative diseases, and respiratory depression diseases or symptoms, and especially applications in the diseases or symptoms related to an AMPA receptor.
Inventors:
LI SONG (CN)
ZHOU XINBO (CN)
XIAO DIAN (CN)
ZHONG WU (CN)
XIAO JUNHAI (CN)
ZHENG ZHIBING (CN)
LI XINGZHOU (CN)
XIE YUNDE (CN)
WANG XIAOKUI (CN)
ZHOU XINBO (CN)
XIAO DIAN (CN)
ZHONG WU (CN)
XIAO JUNHAI (CN)
ZHENG ZHIBING (CN)
LI XINGZHOU (CN)
XIE YUNDE (CN)
WANG XIAOKUI (CN)
Application Number:
PCT/CN2017/080083
Publication Date:
October 19, 2017
Filing Date:
April 11, 2017
Export Citation:
Assignee:
INST PHARMACOLOGY & TOXICOLOGY ACAD MILITARY MEDICAL SCIENCES PLA CHINA (CN)
International Classes:
A61K31/4245; C07D271/12; A61K31/7056; A61P11/00; A61P25/00; A61P25/16; A61P25/18; A61P25/28; C07D413/12; C07H1/00; C07H13/04
Domestic Patent References:
| WO2008143963A1 | 2008-11-27 |
Foreign References:
| CN101742911A | 2010-06-16 | |||
| CN1785972A | 2006-06-14 | |||
| US5747492A | 1998-05-05 | |||
| US6030968A | 2000-02-29 | |||
| US5736543A | 1998-04-07 | |||
| US20020055508A1 | 2002-05-09 | |||
| US20020099050A1 | 2002-07-25 | |||
| CN101742911A | 2010-06-16 |
Other References:
XIAO DIAN: "Design, Synthesis and Biological Evaluation of Brain-Targeted Thiamine Disulfide Prodrugs of Ampakine Compound LCX001", MOLECULES, vol. 21, no. 4, 488, 14 April 2016 (2016-04-14), pages 1 - 14, XP055602333, ISSN: 1420-3049
ZHAO YI: "Design, synthesis and biological evaluation of brain targeting L-ascorbic acid prodrugs of ibuprofen with ''lock-in'' function", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 82, 2 June 2014 (2014-06-02), pages 314 - 323, XP028872871, ISSN: 0223-5234
FAN WEI: "Design, synthesis and biological evaluation of brain-specific glucosyl thiamine disulfide prodrugs of naproxen", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 46, no. 9, 20 May 2011 (2011-05-20), pages 3651 - 3661, XP028278261, ISSN: 0223-5234, DOI: doi:10.1016/j.ejmech.2011.05.029
ISHIKURA TOYOAKI: "Drug delivery to the brain. DOPA prodrugs based on a ring-closure reaction to quaternary thiazolium compounds", INTERNATIONAL JOURNAL OF PHARMACEUTICS, vol. 116, no. 1, 1 January 1995 (1995-01-01), pages 51 - 63, XP000575531, ISSN: 0378-5173
MONAGHAN ET AL., BRAIN RESEARCH, vol. 324, 1984, pages 160 - 164
PAARMANN ET AL., JOURNAL OF NEUROCHEMISTRY, vol. 74, 2000, pages 1335 - 1345
ARAI; LYNCH, BRAIN RESEARCH, vol. 598, 1992, pages 173 - 184
GRANGER ET AL., SYNAPSE, vol. 15, 1993, pages 326 - 329
STAUBLI ET AL., PNAS, vol. 91, 1994, pages 777 - 781
ARAI ET AL., BRAIN RES., vol. 638, 1994, pages 343 - 346
STAUBLI ET AL., PNAS, vol. 91, 1994, pages 11158 - 11162
SHORS ET AL., NEUROSCI. LET., vol. 186, 1995, pages 153 - 156
LARSON ET AL., J. NEUROSCI., vol. 15, 1995, pages 8023 - 8030
GRANGER ET AL., SYNAPSE, vol. 22, 1996, pages 332 - 337
ARAI ET AL., JPET, vol. 278, 1996, pages 627 - 638
LYNCH ET AL., INTERNAT. CLIN. PSYCHOPHARM., vol. 11, 1996, pages 13 - 19
LYNCH ET AL., EXP. NEUROLOGY, vol. 145, 1997, pages 89 - 92
INGVAR ET AL., EXP. NEUROLOGY, vol. 146, 1997, pages 553 - 559
HAMPSON ET AL., J. NEUROSCI., vol. 18, 1998, pages 2748 - 2763
PORRINO ET AL., PLOS BIOL, vol. 3, no. 9, 2006, pages 1 - 14
CERRO; LYNCH, NEUROSCIENCE, vol. 49, 1992, pages 1 - 6
WHITLOCK ET AL., SCIENCE, vol. 313, 2006, pages 1093 - 1097
PASTALKOVA ET AL., SCIENCE, vol. 313, 2006, pages 1141 - 1144
REX ET AL., J. NEUROPHYSIOL., vol. 96, 2006, pages 677 - 685
REN ET AL., AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, vol. 174, 2006, pages 1384 - 1391
LAUTERBORN ET AL., J. NEUROSCI., vol. 20, 2000, pages 8 - 21
LAUTERBORN ET AL., JPET, vol. 307, 2003, pages 297 - 305
MACKOWIAK ET AL., NEUROPHARMACOLOGY, vol. 43, 2002, pages 1 - 10
O'NEILL ET AL., EUR. J. PHARMACOL., vol. 486, 2004, pages 163 - 174
KENT ET AL., MOL. PSYCHIATRY., vol. 10, 2005, pages 939 - 943
RIIKONEN ET AL., J. CHILD NEUROL., vol. 18, 2003, pages 693 - 697
CHANG ET AL., NEURON, vol. 49, 2006, pages 341 - 348
"NEUROSCIENCE", 1997, SINAUER ASSOCIATES, INC.
"DSM IV", article "Diagnostic and Statistical Manual of Mental Disorders", pages: 317 - 391
"DSM IV", article "Diagnostic and Statistical Manual of Mental Disorders"
"Remington's Pharmaceutical Sciences", 1985, MACK PUB. CO.
ZHONGBO HUA; LIU HE; WU BO; WANG YAPING: "Synthesis and crystal structure of N-cyclopropylmethyl-7a-[(R)-1-hydroxyl-1-methyl-3-(2-thienyl)propyl]-6,14-endoethano-6,7,8,9-tetrahydrodemethylthebaine", CHINESE JOURNAL OF ORGANIC CHEMISTRY, vol. 25, no. 2, 2005, pages 210 - 212, XP009508418
See also references of EP 3444240A4
ZHAO YI: "Design, synthesis and biological evaluation of brain targeting L-ascorbic acid prodrugs of ibuprofen with ''lock-in'' function", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 82, 2 June 2014 (2014-06-02), pages 314 - 323, XP028872871, ISSN: 0223-5234
FAN WEI: "Design, synthesis and biological evaluation of brain-specific glucosyl thiamine disulfide prodrugs of naproxen", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 46, no. 9, 20 May 2011 (2011-05-20), pages 3651 - 3661, XP028278261, ISSN: 0223-5234, DOI: doi:10.1016/j.ejmech.2011.05.029
ISHIKURA TOYOAKI: "Drug delivery to the brain. DOPA prodrugs based on a ring-closure reaction to quaternary thiazolium compounds", INTERNATIONAL JOURNAL OF PHARMACEUTICS, vol. 116, no. 1, 1 January 1995 (1995-01-01), pages 51 - 63, XP000575531, ISSN: 0378-5173
MONAGHAN ET AL., BRAIN RESEARCH, vol. 324, 1984, pages 160 - 164
PAARMANN ET AL., JOURNAL OF NEUROCHEMISTRY, vol. 74, 2000, pages 1335 - 1345
ARAI; LYNCH, BRAIN RESEARCH, vol. 598, 1992, pages 173 - 184
GRANGER ET AL., SYNAPSE, vol. 15, 1993, pages 326 - 329
STAUBLI ET AL., PNAS, vol. 91, 1994, pages 777 - 781
ARAI ET AL., BRAIN RES., vol. 638, 1994, pages 343 - 346
STAUBLI ET AL., PNAS, vol. 91, 1994, pages 11158 - 11162
SHORS ET AL., NEUROSCI. LET., vol. 186, 1995, pages 153 - 156
LARSON ET AL., J. NEUROSCI., vol. 15, 1995, pages 8023 - 8030
GRANGER ET AL., SYNAPSE, vol. 22, 1996, pages 332 - 337
ARAI ET AL., JPET, vol. 278, 1996, pages 627 - 638
LYNCH ET AL., INTERNAT. CLIN. PSYCHOPHARM., vol. 11, 1996, pages 13 - 19
LYNCH ET AL., EXP. NEUROLOGY, vol. 145, 1997, pages 89 - 92
INGVAR ET AL., EXP. NEUROLOGY, vol. 146, 1997, pages 553 - 559
HAMPSON ET AL., J. NEUROSCI., vol. 18, 1998, pages 2748 - 2763
PORRINO ET AL., PLOS BIOL, vol. 3, no. 9, 2006, pages 1 - 14
CERRO; LYNCH, NEUROSCIENCE, vol. 49, 1992, pages 1 - 6
WHITLOCK ET AL., SCIENCE, vol. 313, 2006, pages 1093 - 1097
PASTALKOVA ET AL., SCIENCE, vol. 313, 2006, pages 1141 - 1144
REX ET AL., J. NEUROPHYSIOL., vol. 96, 2006, pages 677 - 685
REN ET AL., AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, vol. 174, 2006, pages 1384 - 1391
LAUTERBORN ET AL., J. NEUROSCI., vol. 20, 2000, pages 8 - 21
LAUTERBORN ET AL., JPET, vol. 307, 2003, pages 297 - 305
MACKOWIAK ET AL., NEUROPHARMACOLOGY, vol. 43, 2002, pages 1 - 10
O'NEILL ET AL., EUR. J. PHARMACOL., vol. 486, 2004, pages 163 - 174
KENT ET AL., MOL. PSYCHIATRY., vol. 10, 2005, pages 939 - 943
RIIKONEN ET AL., J. CHILD NEUROL., vol. 18, 2003, pages 693 - 697
CHANG ET AL., NEURON, vol. 49, 2006, pages 341 - 348
"NEUROSCIENCE", 1997, SINAUER ASSOCIATES, INC.
"DSM IV", article "Diagnostic and Statistical Manual of Mental Disorders", pages: 317 - 391
"DSM IV", article "Diagnostic and Statistical Manual of Mental Disorders"
"Remington's Pharmaceutical Sciences", 1985, MACK PUB. CO.
ZHONGBO HUA; LIU HE; WU BO; WANG YAPING: "Synthesis and crystal structure of N-cyclopropylmethyl-7a-[(R)-1-hydroxyl-1-methyl-3-(2-thienyl)propyl]-6,14-endoethano-6,7,8,9-tetrahydrodemethylthebaine", CHINESE JOURNAL OF ORGANIC CHEMISTRY, vol. 25, no. 2, 2005, pages 210 - 212, XP009508418
See also references of EP 3444240A4
Attorney, Agent or Firm:
CCPIT PATENT AND TRADEMARK LAW OFFICE (CN)
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