Title:
FERROPTOSIS INHIBITOR AND USE THEREFOR
Document Type and Number:
WIPO Patent Application WO/2023/085420
Kind Code:
A1
Abstract:
The present invention provides a means whereby it is possible to clarify the mechanism of manifestation of symptoms, an illness, or dysfunction caused by mitochondrial dysfunction and prevent or treat symptoms, an illness, or dysfunction relating to the same mechanism of manifestation. One embodiment of the present invention relates to a ferroptosis inhibitor containing a compound represented by formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof as an active ingredient. Another embodiment of the present invention relates to a medicine that contains the ferroptosis inhibitor as an active ingredient and is for use in the prevention or treatment of symptoms, an illness, or dysfunction relating to ferroptosis. Yet another embodiment of the present invention relates to a compound represented by formula (I-1), a salt thereof, or a solvate thereof.
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Inventors:
OSAKA HITOSHI (JP)
MIYAUCHI AKIHIKO (JP)
JINBO ERIKO (JP)
KOBAYASHI MIZUKI (JP)
MIYAUCHI AKIHIKO (JP)
JINBO ERIKO (JP)
KOBAYASHI MIZUKI (JP)
Application Number:
PCT/JP2022/042198
Publication Date:
May 19, 2023
Filing Date:
November 14, 2022
Export Citation:
Assignee:
UNIV JICHI MEDICAL (JP)
International Classes:
C07D221/18; A61K31/473; A61K31/4741; A61P1/16; A61P3/00; A61P3/10; A61P5/00; A61P9/10; A61P11/00; A61P13/02; A61P13/12; A61P25/00; A61P25/14; A61P25/16; A61P25/28; A61P27/02; A61P31/04; A61P43/00; C07D491/06
Domestic Patent References:
| WO2007134485A1 | 2007-11-29 | |||
| WO2015015248A1 | 2015-02-05 | |||
| WO2019093379A1 | 2019-05-16 |
Foreign References:
| CN112494491A | 2021-03-16 | |||
| JP2013517301A | 2013-05-16 | |||
| CN101966228A | 2011-02-09 | |||
| CN101407520A | 2009-04-15 | |||
| CN110772517A | 2020-02-11 |
Other References:
CANNON G, SMITH ROBERT V, MODIRI ALI, SOOD S PAUL, BORGMAN ROBERT J, ALEEM MOHD A, , : "Centrally Acting Emetics. 5. Preparation and Pharmacology of 10-Hydroxy-11-methoxyaporphine (Isoapocodeine). In Vitro Enzymatic Methylation of Apomorphine1Ĵ", JOURNAL OF MEDICINAL CHEMISTRY, vol. 15, no. 3, 1 March 1972 (1972-03-01), pages 273 - 276, XP093065431
DANYU LI; BING LIU; YUMEI FAN; MING LIU; BIHUI HAN; YANXIU MENG; XIAO XU; ZHIYUAN SONG; XIAOPENG LIU; QIANG HAO; XIANGLIN DUAN; AK: "Nuciferine protects against folic acid‐induced acute kidney injury by inhibiting ferroptosis", BRITISH JOURNAL OF PHARMACOLOGY, WILEY-BLACKWELL, UK, vol. 178, no. 5, 10 February 2021 (2021-02-10), UK , pages 1182 - 1199, XP071081679, ISSN: 0007-1188, DOI: 10.1111/bph.15364
WANG, HONG-MEI; MA, YUN-SHU; HUANG, QIU-YAN; KONG, SHU-JUN; WANG, HUI: "Effect of isocorydine on arrhythmia in rats induced by myocardial ischemia/reperfusion injury", ZHONGGUO YAOLIXUE TONGBAO - CHINESE PHARMACOLOGICAL BULLETIN, LINCHUANG YAOLI YANJIUSUO, HEFEI, CN, vol. 32, no. 9, 1 January 2016 (2016-01-01), CN , pages 1268 - 1272, XP009546216, ISSN: 1001-1978
TANG, DEPING ET AL.: "Dicranostiga leptopodu (Maxim.) Fedde extracts attenuated CCl4-induced acute liver damage in mice through increasing anti-oxidative enzyme activity to improve mitochondrial function", BIOMEDICINE & PHARMACOTHERAPY, vol. 85, 1 January 2017 (2017-01-01), pages 763 - 771, XP009546219
JANG YOON YOUNG, SONG JIN HO, SHIN YONG KYOO, HAN EUN SOOK, LEE CHUNG SOO: "Protective effect of boldine on oxidative mitochondrial damage in streptozotocin-induced diabetic rats", PHARMACOLOGICAL RESEARCH, ELSEVIER, AMSTERDAM, NL, vol. 42, no. 4, 1 October 2000 (2000-10-01), AMSTERDAM, NL, pages 361 - 371, XP093065439, ISSN: 1043-6618, DOI: 10.1006/phrs.2000.0705
WEI-LUEN CHANG ; SHOEI-SHENG LEE ; MING-JAI SU: "Attenuation of Post-ischemia Reperfusion Injury by Thaliporphine and Morphine in Rat Hearts", JOURNAL OF BIOMEDICAL SCIENCE, KLUWER ACADEMIC PUBLISHERS, DO, vol. 12, no. 4, 1 July 2005 (2005-07-01), Do , pages 611 - 619, XP019272208, ISSN: 1423-0127, DOI: 10.1007/s11373-005-7401-2
LEE A. S., CHEN W. P., KUO Y. L., HO Y. J., LEE S. S., SU M. J.: "Thaliporphine Preserves Cardiac Function of Endotoxemic Rabbits by Both Directly and Indirectly Attenuating NFκB Signaling Pathway", PLOS ONE, vol. 7, no. 6, 25 June 2012 (2012-06-25), pages e39174, XP093065442, DOI: 10.1371/journal.pone.0039174
DAJAS-BAILADOR FEDERICO A, ASENCIO MARCELO, BONILLA CAROLINA, SCORZA MA.CECILIA, ECHEVERRY CAROLINA, REYES-PARADA MIGUEL, SILVEIRA: "Dopaminergic pharmacology and antioxidant properties of pukateine, a natural product lead for the design of agents increasing dopamine neurotransmission", GENERAL PHARMACOLOGY., PERGAMON PRESS, OXFORD., GB, vol. 32, no. 3, 1 March 1999 (1999-03-01), GB , pages 373 - 379, XP093065447, ISSN: 0306-3623, DOI: 10.1016/S0306-3623(98)00210-9
HE, X. WANG, D. ZHANG, X. LI, A. GU, X. DING, F. ZHOU, J.: "Prolonged modulation of FGF-2 expression in astrocytic cultures induced by O,O'-diacetyl-apomorphine", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, ELSEVIER, AMSTERDAM NL, vol. 369, no. 3, 27 February 2008 (2008-02-27), Amsterdam NL , pages 824 - 829, XP022572192, ISSN: 0006-291X, DOI: 10.1016/j.bbrc.2008.02.082
SORIANO-CASTELL DAVID; CURRAIS ANTONIO; MAHER PAMELA: "Defining a pharmacological inhibitor fingerprint for oxytosis/ferroptosis", FREE RADICAL BIOLOGY & MEDICINE, ELSEVIER INC, US, vol. 171, 16 May 2021 (2021-05-16), US , pages 219 - 231, XP086635686, ISSN: 0891-5849, DOI: 10.1016/j.freeradbiomed.2021.05.023
HEDBERG MARTIN H., JANSEN JOHANNA M., NORDVALL GUNNAR, HJORTH STEPHAN, UNELIUS LENA, JOHANSSON ANETTE M.: "10-Substituted 11-Oxygenated ( R )-Aporphines: Synthesis, Pharmacology, and Modeling of 5-HT 1A Receptor Interactions", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 39, no. 18, 1 January 1996 (1996-01-01), US , pages 3491 - 3502, XP093065452, ISSN: 0022-2623, DOI: 10.1021/jm960188q
MIYAUCHI, AKIHIKO ET AL. : "Drug candidates for mitochondrial disease by anti-ferroptosis effect", NIHON SHōNIKA GAKKAI ZASSHI = JOURNAL OF JAPAN PEDIATRIC SOCIETY, JAPAN PEDIATRIC SOCIETY, JP, vol. 126, no. 2, 1 February 2022 (2022-02-01), JP , pages 231, XP009546214, ISSN: 0001-6543
MIYAUCHI, AKIHIKO ET AL.: "S2-2-T2-2 Mitochondrial therapies using apomorphine ferroptosis", PROGRAM AND ABSTRACTS OF THE 20TH ANNUAL MEETING OF THE JAPANESE SOCIETY OF MITOCHONDRIAL RESEARCH AND MEDICINE; TOKYO, JAPAN; DECEMBER 9-10, 2021, vol. 20, 29 July 2022 (2022-07-29) - 10 December 2021 (2021-12-10), XP009546612
DANYU LI; BING LIU; YUMEI FAN; MING LIU; BIHUI HAN; YANXIU MENG; XIAO XU; ZHIYUAN SONG; XIAOPENG LIU; QIANG HAO; XIANGLIN DUAN; AK: "Nuciferine protects against folic acid‐induced acute kidney injury by inhibiting ferroptosis", BRITISH JOURNAL OF PHARMACOLOGY, WILEY-BLACKWELL, UK, vol. 178, no. 5, 10 February 2021 (2021-02-10), UK , pages 1182 - 1199, XP071081679, ISSN: 0007-1188, DOI: 10.1111/bph.15364
WANG, HONG-MEI; MA, YUN-SHU; HUANG, QIU-YAN; KONG, SHU-JUN; WANG, HUI: "Effect of isocorydine on arrhythmia in rats induced by myocardial ischemia/reperfusion injury", ZHONGGUO YAOLIXUE TONGBAO - CHINESE PHARMACOLOGICAL BULLETIN, LINCHUANG YAOLI YANJIUSUO, HEFEI, CN, vol. 32, no. 9, 1 January 2016 (2016-01-01), CN , pages 1268 - 1272, XP009546216, ISSN: 1001-1978
TANG, DEPING ET AL.: "Dicranostiga leptopodu (Maxim.) Fedde extracts attenuated CCl4-induced acute liver damage in mice through increasing anti-oxidative enzyme activity to improve mitochondrial function", BIOMEDICINE & PHARMACOTHERAPY, vol. 85, 1 January 2017 (2017-01-01), pages 763 - 771, XP009546219
JANG YOON YOUNG, SONG JIN HO, SHIN YONG KYOO, HAN EUN SOOK, LEE CHUNG SOO: "Protective effect of boldine on oxidative mitochondrial damage in streptozotocin-induced diabetic rats", PHARMACOLOGICAL RESEARCH, ELSEVIER, AMSTERDAM, NL, vol. 42, no. 4, 1 October 2000 (2000-10-01), AMSTERDAM, NL, pages 361 - 371, XP093065439, ISSN: 1043-6618, DOI: 10.1006/phrs.2000.0705
WEI-LUEN CHANG ; SHOEI-SHENG LEE ; MING-JAI SU: "Attenuation of Post-ischemia Reperfusion Injury by Thaliporphine and Morphine in Rat Hearts", JOURNAL OF BIOMEDICAL SCIENCE, KLUWER ACADEMIC PUBLISHERS, DO, vol. 12, no. 4, 1 July 2005 (2005-07-01), Do , pages 611 - 619, XP019272208, ISSN: 1423-0127, DOI: 10.1007/s11373-005-7401-2
LEE A. S., CHEN W. P., KUO Y. L., HO Y. J., LEE S. S., SU M. J.: "Thaliporphine Preserves Cardiac Function of Endotoxemic Rabbits by Both Directly and Indirectly Attenuating NFκB Signaling Pathway", PLOS ONE, vol. 7, no. 6, 25 June 2012 (2012-06-25), pages e39174, XP093065442, DOI: 10.1371/journal.pone.0039174
DAJAS-BAILADOR FEDERICO A, ASENCIO MARCELO, BONILLA CAROLINA, SCORZA MA.CECILIA, ECHEVERRY CAROLINA, REYES-PARADA MIGUEL, SILVEIRA: "Dopaminergic pharmacology and antioxidant properties of pukateine, a natural product lead for the design of agents increasing dopamine neurotransmission", GENERAL PHARMACOLOGY., PERGAMON PRESS, OXFORD., GB, vol. 32, no. 3, 1 March 1999 (1999-03-01), GB , pages 373 - 379, XP093065447, ISSN: 0306-3623, DOI: 10.1016/S0306-3623(98)00210-9
HE, X. WANG, D. ZHANG, X. LI, A. GU, X. DING, F. ZHOU, J.: "Prolonged modulation of FGF-2 expression in astrocytic cultures induced by O,O'-diacetyl-apomorphine", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, ELSEVIER, AMSTERDAM NL, vol. 369, no. 3, 27 February 2008 (2008-02-27), Amsterdam NL , pages 824 - 829, XP022572192, ISSN: 0006-291X, DOI: 10.1016/j.bbrc.2008.02.082
SORIANO-CASTELL DAVID; CURRAIS ANTONIO; MAHER PAMELA: "Defining a pharmacological inhibitor fingerprint for oxytosis/ferroptosis", FREE RADICAL BIOLOGY & MEDICINE, ELSEVIER INC, US, vol. 171, 16 May 2021 (2021-05-16), US , pages 219 - 231, XP086635686, ISSN: 0891-5849, DOI: 10.1016/j.freeradbiomed.2021.05.023
HEDBERG MARTIN H., JANSEN JOHANNA M., NORDVALL GUNNAR, HJORTH STEPHAN, UNELIUS LENA, JOHANSSON ANETTE M.: "10-Substituted 11-Oxygenated ( R )-Aporphines: Synthesis, Pharmacology, and Modeling of 5-HT 1A Receptor Interactions", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 39, no. 18, 1 January 1996 (1996-01-01), US , pages 3491 - 3502, XP093065452, ISSN: 0022-2623, DOI: 10.1021/jm960188q
MIYAUCHI, AKIHIKO ET AL. : "Drug candidates for mitochondrial disease by anti-ferroptosis effect", NIHON SHōNIKA GAKKAI ZASSHI = JOURNAL OF JAPAN PEDIATRIC SOCIETY, JAPAN PEDIATRIC SOCIETY, JP, vol. 126, no. 2, 1 February 2022 (2022-02-01), JP , pages 231, XP009546214, ISSN: 0001-6543
MIYAUCHI, AKIHIKO ET AL.: "S2-2-T2-2 Mitochondrial therapies using apomorphine ferroptosis", PROGRAM AND ABSTRACTS OF THE 20TH ANNUAL MEETING OF THE JAPANESE SOCIETY OF MITOCHONDRIAL RESEARCH AND MEDICINE; TOKYO, JAPAN; DECEMBER 9-10, 2021, vol. 20, 29 July 2022 (2022-07-29) - 10 December 2021 (2021-12-10), XP009546612
Attorney, Agent or Firm:
HIRAKI & ASSOCIATES (JP)
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