Title:
COMPOUNDS FOR TREATING POLYQ-RELATED NEURODEGENERATIVE DISORDERS
Document Type and Number:
WIPO Patent Application WO/2023/104170
Kind Code:
A1
Abstract:
One embodiment of the disclosure is a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof. The variables in Formula (I) are defined herein. Compounds of Formula (I) can be used to treat polyQ-related neurodegenerative disorders.
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Inventors:
YIN NING (US)
JI NAN (US)
JI NAN (US)
Application Number:
PCT/CN2022/137686
Publication Date:
June 15, 2023
Filing Date:
December 08, 2022
Export Citation:
Assignee:
HANGZHOU JIJING PHARMACEUTICAL TECH LIMITED (CN)
International Classes:
C07D209/34; A61K31/404; A61K31/4168; A61K31/4178; A61K31/422; A61K31/427; A61K31/437; A61K31/438; A61K31/4439; A61K31/497; A61K31/498; A61K31/501; A61K31/506; A61P25/00; A61P25/28; C07D401/12; C07D403/12; C07D405/12; C07D413/12; C07D413/14; C07D417/12; C07D471/04
Domestic Patent References:
| WO2020237025A1 | 2020-11-26 | |||
| WO2012119506A1 | 2012-09-13 | |||
| WO2006131186A1 | 2006-12-14 | |||
| WO2012178015A2 | 2012-12-27 | |||
| WO2009030270A1 | 2009-03-12 | |||
| WO2020182144A1 | 2020-09-17 |
Foreign References:
| CN113149890A | 2021-07-23 |
Other References:
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XU XIAN-KUAN ET AL: "Pd-Catalyzed Direct C-H Activation for the C5-Olefination of Methyleneindolinones", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 86, no. 10, 6 May 2021 (2021-05-06), pages 7288 - 7295, XP093027291, ISSN: 0022-3263, DOI: 10.1021/acs.joc.1c00637
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PARVEEN NAZIYA ET AL: "Palladium Nanoparticle-Catalyzed Stereoselective Domino Synthesis of All-Carbon Tetrasubstituted Olefin Containing Oxindoles via Carbopalladation/C-H Activation", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 85, no. 16, 5 August 2020 (2020-08-05), pages 10514 - 10524, XP093027306, ISSN: 0022-3263, DOI: 10.1021/acs.joc.0c00915
BISHT GIRISH SINGH ET AL: "Transition-Metal-Free Addition Reaction for the Synthesis of 3-(Aminobenzylidene/aminoalkylidene)indolin-2-ones and Its Synthetic Applications", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 84, no. 21, 26 September 2019 (2019-09-26), pages 13516 - 13527, XP093027410, ISSN: 0022-3263, DOI: 10.1021/acs.joc.9b01771
BISHT GIRISH SINGH ET AL: "Ru-Catalyzed dehydrogenative synthesis of antimalarial arylidene oxindoles", ORGANIC & BIOMOLECULAR CHEMISTRY, vol. 16, no. 39, 1 January 2018 (2018-01-01), pages 7223 - 7229, XP093027479, ISSN: 1477-0520, DOI: 10.1039/C8OB01852A
PARK SUNHWA ET AL: "Palladium-Catalyzed Tandem Approach to 3-(Diarylmethylene)oxindoles Using Microwave Irradiation", SYNLETT, vol. 26, no. 16, 12 August 2015 (2015-08-12), DE, pages 2296 - 2300, XP093027547, ISSN: 0936-5214, DOI: 10.1055/s-0035-1560091
LEE HYUN JU ET AL: "An expedient synthesis of 3-alkylideneoxindoles by Ti(OiPr)4/pyridine-mediated Knoevenagel condensation", TETRAHEDRON LETTERS, ELSEVIER, AMSTERDAM , NL, vol. 55, no. 6, 4 January 2014 (2014-01-04), pages 1183 - 1187, XP028820564, ISSN: 0040-4039, DOI: 10.1016/J.TETLET.2013.12.097
PAL ABHISHEK ET AL: "Bis-arylidene Oxindoles as Anti-Breast-Cancer Agents Acting via the Estrogen Receptor", CHEMMEDCHEM COMMUNICATIONS, vol. 9, no. 4, 31 January 2014 (2014-01-31), DE, pages 727 - 732, XP093027561, ISSN: 1860-7179, DOI: 10.1002/cmdc.201400003
LV KAI ET AL: "Synthesis and in vitro antitumor activity of 1-(3-dimethylamino)propyl indolin-2-one derivatives", MEDICINAL CHEMISTRY RESEARCH, vol. 22, no. 4, 13 July 2012 (2012-07-13), US, pages 1723 - 1729, XP093027574, ISSN: 1054-2523, Retrieved from the Internet DOI: 10.1007/s00044-012-0170-3
DONG GUANG ET AL: "Synthesis of 3-(Diarylmethylene)oxindoles via a Palladium-Catalyzed One-Pot Reaction: Sonogashira-Heck-Suzuki-Miyaura Combined Reaction", SYNLETT, vol. 24, no. 15, 13 August 2013 (2013-08-13), DE, pages 1993 - 1997, XP093027577, ISSN: 0936-5214, DOI: 10.1055/s-0033-1339690
MARTIN ARTHUIS ET AL: "Synthesis and Structure-Activity Relationships of Constrained Heterocyclic Analogues of Combretastatin A4", CHEMMEDCHEM COMMUNICATIONS, vol. 6, no. 9, 5 September 2011 (2011-09-05), DE, pages 1693 - 1705, XP055471332, ISSN: 1860-7179, DOI: 10.1002/cmdc.201100154
CANTAGREL GUILLAUME ET AL: "Iron Trichloride-Promoted Cyclization of o -Alkynylaryl Isocyanates: Synthesis of 3-(Chloromethylene)oxindoles", ORGANIC LETTERS, vol. 11, no. 19, 9 September 2009 (2009-09-09), US, pages 4262 - 4265, XP093027618, ISSN: 1523-7060, DOI: 10.1021/ol9014877
MIURA TOMOYA ET AL: "Rhodium-Catalyzed Borylative Cyclization of 2-Alkynylaryl Isocyanates with Bis(pinacolato)diboron", ORGANIC LETTERS, vol. 10, no. 9, 11 April 2008 (2008-04-11), US, pages 1743 - 1745, XP093027639, ISSN: 1523-7060, DOI: 10.1021/ol800380t
MIURA TOMOYA ET AL: "Stereoselective Synthesis of 3-Alkylideneoxindoles by Palladium-Catalyzed Cyclization Reaction of 2-(Alkynyl)aryl Isocyanates with Organoboron Reagents", ORGANIC LETTERS, vol. 10, no. 21, 7 October 2008 (2008-10-07), US, pages 4887 - 4889, XP093027645, ISSN: 1523-7060, DOI: 10.1021/ol801844w
CHEUNG WING S. ET AL: "A Tandem Heck-Carbocyclization/Suzuki-Coupling Approach to the Stereoselective Syntheses of Asymmetric 3,3-(Diarylmethylene)indolinones", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 70, no. 9, 1 April 2005 (2005-04-01), pages 3741 - 3744, XP093027663, ISSN: 0022-3263, DOI: 10.1021/jo050016d
WANG, NEUROSCIENCE, vol. 371, 2018, pages 138 - 154
MENZIES ET AL., BRAIN, vol. 133, 2010, pages 93 - 104
COSTA MD, BRAIN, vol. 139, no. 11, 2016, pages 2891 - 2908
LESLEY JONES ET AL.: "DNA repair in the trinucleotide repeat disorders", LANCET NEUROL, vol. 16, 2017, pages 88 - 96, XP029836611, DOI: 10.1016/S1474-4422(16)30350-7
PINTO A ET AL: "Palladium-catalyzed domino N-arylation/carbopalladation/C-H functionalization: three-component synthesis of 3-(diarylmethylene)oxindoles", TETRAHEDRON LETTERS, ELSEVIER, AMSTERDAM , NL, vol. 50, no. 26, 1 July 2009 (2009-07-01), pages 3602 - 3605, XP026120568, ISSN: 0040-4039, [retrieved on 20090316], DOI: 10.1016/J.TETLET.2009.03.086
SONG R J ET AL: "Selective synthesis of 3-methyleneindolin-2-ones by one-pot multicatalytic processes", TETRAHEDRON LETTERS, ELSEVIER, AMSTERDAM , NL, vol. 50, no. 27, 8 July 2009 (2009-07-08), pages 3912 - 3916, XP026127404, ISSN: 0040-4039, [retrieved on 20090422], DOI: 10.1016/J.TETLET.2009.04.066
MAREK LUKÁS ET AL: "Synthesis of ( Z )-3-[amino(phenyl)methylidene]-1,3-dihydro-2 H -indol-2-ones using an Eschenmoser coupling reaction", BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY, vol. 17, 12 February 2021 (2021-02-12), pages 527 - 539, XP093027279, Retrieved from the Internet
XU XIAN-KUAN ET AL: "Pd-Catalyzed Direct C-H Activation for the C5-Olefination of Methyleneindolinones", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 86, no. 10, 6 May 2021 (2021-05-06), pages 7288 - 7295, XP093027291, ISSN: 0022-3263, DOI: 10.1021/acs.joc.1c00637
KUMAR KRISHNA ET AL: "Catalytic enantioselective synthesis of chiral 4-hydroxy 4'-substituted pyrazolones by the vinylogous aldol reaction of pyrazole-4,5-diones with 3-alkylidene-2-oxindoles", NEW JOURNAL OF CHEMISTRY, vol. 45, no. 31, 1 January 2021 (2021-01-01), GB, pages 13747 - 13750, XP093027294, ISSN: 1144-0546, DOI: 10.1039/D0NJ05886F
JAISWAL MANISH K. ET AL: "Enantioselective vinylogous aldol reaction of acylphosphonates with 3-alkylidene oxindoles", ORGANIC & BIOMOLECULAR CHEMISTRY, vol. 19, no. 36, 1 January 2021 (2021-01-01), pages 7861 - 7866, XP093027299, ISSN: 1477-0520, DOI: 10.1039/D1OB00140J
PARVEEN NAZIYA ET AL: "Palladium Nanoparticle-Catalyzed Stereoselective Domino Synthesis of All-Carbon Tetrasubstituted Olefin Containing Oxindoles via Carbopalladation/C-H Activation", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 85, no. 16, 5 August 2020 (2020-08-05), pages 10514 - 10524, XP093027306, ISSN: 0022-3263, DOI: 10.1021/acs.joc.0c00915
BISHT GIRISH SINGH ET AL: "Transition-Metal-Free Addition Reaction for the Synthesis of 3-(Aminobenzylidene/aminoalkylidene)indolin-2-ones and Its Synthetic Applications", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 84, no. 21, 26 September 2019 (2019-09-26), pages 13516 - 13527, XP093027410, ISSN: 0022-3263, DOI: 10.1021/acs.joc.9b01771
BISHT GIRISH SINGH ET AL: "Ru-Catalyzed dehydrogenative synthesis of antimalarial arylidene oxindoles", ORGANIC & BIOMOLECULAR CHEMISTRY, vol. 16, no. 39, 1 January 2018 (2018-01-01), pages 7223 - 7229, XP093027479, ISSN: 1477-0520, DOI: 10.1039/C8OB01852A
PARK SUNHWA ET AL: "Palladium-Catalyzed Tandem Approach to 3-(Diarylmethylene)oxindoles Using Microwave Irradiation", SYNLETT, vol. 26, no. 16, 12 August 2015 (2015-08-12), DE, pages 2296 - 2300, XP093027547, ISSN: 0936-5214, DOI: 10.1055/s-0035-1560091
LEE HYUN JU ET AL: "An expedient synthesis of 3-alkylideneoxindoles by Ti(OiPr)4/pyridine-mediated Knoevenagel condensation", TETRAHEDRON LETTERS, ELSEVIER, AMSTERDAM , NL, vol. 55, no. 6, 4 January 2014 (2014-01-04), pages 1183 - 1187, XP028820564, ISSN: 0040-4039, DOI: 10.1016/J.TETLET.2013.12.097
PAL ABHISHEK ET AL: "Bis-arylidene Oxindoles as Anti-Breast-Cancer Agents Acting via the Estrogen Receptor", CHEMMEDCHEM COMMUNICATIONS, vol. 9, no. 4, 31 January 2014 (2014-01-31), DE, pages 727 - 732, XP093027561, ISSN: 1860-7179, DOI: 10.1002/cmdc.201400003
LV KAI ET AL: "Synthesis and in vitro antitumor activity of 1-(3-dimethylamino)propyl indolin-2-one derivatives", MEDICINAL CHEMISTRY RESEARCH, vol. 22, no. 4, 13 July 2012 (2012-07-13), US, pages 1723 - 1729, XP093027574, ISSN: 1054-2523, Retrieved from the Internet
DONG GUANG ET AL: "Synthesis of 3-(Diarylmethylene)oxindoles via a Palladium-Catalyzed One-Pot Reaction: Sonogashira-Heck-Suzuki-Miyaura Combined Reaction", SYNLETT, vol. 24, no. 15, 13 August 2013 (2013-08-13), DE, pages 1993 - 1997, XP093027577, ISSN: 0936-5214, DOI: 10.1055/s-0033-1339690
MARTIN ARTHUIS ET AL: "Synthesis and Structure-Activity Relationships of Constrained Heterocyclic Analogues of Combretastatin A4", CHEMMEDCHEM COMMUNICATIONS, vol. 6, no. 9, 5 September 2011 (2011-09-05), DE, pages 1693 - 1705, XP055471332, ISSN: 1860-7179, DOI: 10.1002/cmdc.201100154
CANTAGREL GUILLAUME ET AL: "Iron Trichloride-Promoted Cyclization of o -Alkynylaryl Isocyanates: Synthesis of 3-(Chloromethylene)oxindoles", ORGANIC LETTERS, vol. 11, no. 19, 9 September 2009 (2009-09-09), US, pages 4262 - 4265, XP093027618, ISSN: 1523-7060, DOI: 10.1021/ol9014877
MIURA TOMOYA ET AL: "Rhodium-Catalyzed Borylative Cyclization of 2-Alkynylaryl Isocyanates with Bis(pinacolato)diboron", ORGANIC LETTERS, vol. 10, no. 9, 11 April 2008 (2008-04-11), US, pages 1743 - 1745, XP093027639, ISSN: 1523-7060, DOI: 10.1021/ol800380t
MIURA TOMOYA ET AL: "Stereoselective Synthesis of 3-Alkylideneoxindoles by Palladium-Catalyzed Cyclization Reaction of 2-(Alkynyl)aryl Isocyanates with Organoboron Reagents", ORGANIC LETTERS, vol. 10, no. 21, 7 October 2008 (2008-10-07), US, pages 4887 - 4889, XP093027645, ISSN: 1523-7060, DOI: 10.1021/ol801844w
CHEUNG WING S. ET AL: "A Tandem Heck-Carbocyclization/Suzuki-Coupling Approach to the Stereoselective Syntheses of Asymmetric 3,3-(Diarylmethylene)indolinones", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 70, no. 9, 1 April 2005 (2005-04-01), pages 3741 - 3744, XP093027663, ISSN: 0022-3263, DOI: 10.1021/jo050016d
WANG, NEUROSCIENCE, vol. 371, 2018, pages 138 - 154
MENZIES ET AL., BRAIN, vol. 133, 2010, pages 93 - 104
COSTA MD, BRAIN, vol. 139, no. 11, 2016, pages 2891 - 2908
LESLEY JONES ET AL.: "DNA repair in the trinucleotide repeat disorders", LANCET NEUROL, vol. 16, 2017, pages 88 - 96, XP029836611, DOI: 10.1016/S1474-4422(16)30350-7
Attorney, Agent or Firm:
KING & WOOD MALLESONS (CN)
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