Title:
PYRROLIDINE COMPOUNDS AS HISTONE DEACETYLASE INHIBITORS
Document Type and Number:
WIPO Patent Application WO/2023/042914
Kind Code:
A1
Abstract:
Pyrrolidine compounds having an HDAC inhibition activity which are useful for treatment or prevention of diseases involving HDACs are provided. A compound of Formula [I], or a salt thereof, wherein R1 is an optionally substituted 6- to 10-membered aryl, etc.; a ring structure A is any one of the formulae (A1) to (A3) wherein ring groups G1 and G2 are each independently 6- to 10-membered aryl or 5- to 10-membered heteroaryl, which is optionally substituted with oxo; m and n are each independently an integer of 1 or 2; R21, R22, and R23 are each independent, each of which is independent when existing plurally, and are an optionally C1-6 alkyl, etc.; and p, q, and r are each independently an integer of 0 to 2.
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Inventors:
MIYAMURA SHIN (JP)
ISHIKAWA SHUNPEI (JP)
TAMAI TAICHI (JP)
NAGASE TSUYOSHI (JP)
KONDO KAZUMI (JP)
MORI YUKIKO (JP)
TAI KUNINORI (JP)
NAKAISHI YUICHIRO (JP)
KAWATO TATSUYA (JP)
SATO AKIMASA (JP)
HASHIMOTO TETSUYA (JP)
GOTO SHINTARO (JP)
BUCK ILDIKO MARIA (GB)
CONS BENJAMIN DAVID (GB)
HEIGHTMAN THOMAS DANIEL (GB)
SCHÖPF PATRICK (GB)
TAMANINI EMILIANO (GB)
WOOLFORD ALISON JO-ANNE (GB)
ISHIKAWA SHUNPEI (JP)
TAMAI TAICHI (JP)
NAGASE TSUYOSHI (JP)
KONDO KAZUMI (JP)
MORI YUKIKO (JP)
TAI KUNINORI (JP)
NAKAISHI YUICHIRO (JP)
KAWATO TATSUYA (JP)
SATO AKIMASA (JP)
HASHIMOTO TETSUYA (JP)
GOTO SHINTARO (JP)
BUCK ILDIKO MARIA (GB)
CONS BENJAMIN DAVID (GB)
HEIGHTMAN THOMAS DANIEL (GB)
SCHÖPF PATRICK (GB)
TAMANINI EMILIANO (GB)
WOOLFORD ALISON JO-ANNE (GB)
Application Number:
PCT/JP2022/034827
Publication Date:
March 23, 2023
Filing Date:
September 16, 2022
Export Citation:
Assignee:
OTSUKA PHARMA CO LTD (JP)
International Classes:
C07D401/12; A61K31/4025; A61P25/28; C07D401/14; C07D403/06; C07D403/14; C07D405/14; C07D409/12; C07D409/14; C07D417/14; C07D495/04
Domestic Patent References:
| WO2017007756A1 | 2017-01-12 | |||
| WO2021170658A1 | 2021-09-02 |
Foreign References:
| US20080306089A1 | 2008-12-11 | |||
| US20110230419A1 | 2011-09-22 |
Other References:
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GRAEFF, J: "Annual review of pharmacology and toxicology", vol. 53, 2013, article "The potential of HDAC inhibitors as cognitive enhancers", pages: 311 - 330
GUAN, S-J. ET AL.: "HDAC2 negatively regulates memory formation and synaptic plasticity", NATURE, vol. 459, 2009, pages 55 - 60, XP055054472, DOI: 10.1038/nature07925
SUNG, Y-M. ET AL.: "Mercaptoacetamide-based class II HDAC inhibitor lowers Abeta levels and improves learning and memory in a mouse model of Alzheimer's disease", EXP NEUROL, vol. 239, 2013, pages 192 - 201
CHOONG, C-J. ET AL.: "A novel histone deacetylase 1 and 2 isoform-specific inhibitor alleviates experimental Parkinson's disease", NEUROBIOL AGING, vol. 37, 2016, pages 103 - 16, XP029344328, DOI: 10.1016/j.neurobiolaging.2015.10.001
SIMONA SANNA, S. ET AL.: "HDACI inhibition ameliorates TDP-43-induced cell death in vitro and in vivo", CELL DEATH & DISEASE, vol. 11, no. 369, 2020
ROSSAERT, E. ET AL.: "Restoration of histone acetylation ameliorates disease and metabolic abnormalities in a FUS mouse model", ACTA NEUROPATHOLOGICA COMMUNICATIONS, vol. 7, no. 107, 2019
FEDE, E. D. ET AL.: "Exogenous and endogenous HDAC inhibitor effects in Rubinstein-Taybi syndrome models", BIORXIV, 1 April 2020 (2020-04-01)
GOTTESFELD, J. M. ET AL.: "Increasing frataxin gene expression with histone deacetylase inhibitors as a therapeutic approach for friedreich's ataxia", J NEUROCHEM, vol. 126, August 2013 (2013-08-01), pages 147 - 154, XP055383276, DOI: 10.1111/jnc.12302
TANG, Y. ET AL.: "Inhibiting histone deacetylase 2 (HDAC2) promotes functional recovery from stroke", J AM HEART ASSOC, vol. 6, no. 10, 5 October 2017 (2017-10-05)
ZHANG, S. ET AL.: "Class I histone deacetylase (HDAC) inhibitor CI-994 promotes functional recovery following spinal cord injury", CELL DEATH & DISEASE, vol. 9, 2018
YANG, W-B. ET AL.: "Increased activation of HDAC 1/2/6 and Spl underlies therapeutic resistance and tumor growth in glioblastoma", NEURO ONCOL, vol. 22, no. 10, 14 October 2020 (2020-10-14), pages 1439 - 1451
OUYANG, B. ET AL.: "Normalizing HDAC2 levels in the spinal cord alleviates thermal and mechanical hyperalgesia after peripheral nerve injury and promotes GAD65 and KCC2 expression", FRONTIERS IN NEUROSCIENCE, vol. 13, 2019, pages 346
ROSSAERT, E. ET AL.: "HDAC6 inhibitors: Translating genetic and molecular insights into a therapy for axonal CMT", BRAIN RESEARCH, vol. 1733, 2020, pages 146692, XP086065771, DOI: 10.1016/j.brainres.2020.146692
IBI, D. ET AL.: "Antipsychotic-induced Hdac2 transcription via NF-kB leads to synaptic and cognitive side effects", NATURE NEUROSCIENCE, vol. 20, no. 9, 2017, pages 1247 - 1259
LOGAN, R. W. ET AL.: "Valproate reverses mania-like behaviors in mice via preferential targeting of HDAC2", MOLECULAR PSYCHIATRY, 24 November 2020 (2020-11-24)
SHETTY, M. G. ET AL.: "Histone deacetylase 2 selective inhibitors: A versatile therapeutic strategy as next generation drug target in cancer therapy", PHARMACOLOGICAL RESEARCH, vol. 170, 2021, pages 105695 - 105707, XP086714471, DOI: 10.1016/j.phrs.2021.105695
WEST, A. C. ET AL.: "New and emerging HDAC inhibitors for cancer treatment", J CLIN INVEST, vol. 124, no. 1, 2014, pages 30 - 39
YANG, YE ET AL.: "Rational design of selective HDAC2 inhibitors for liver cancer treatment: computational insights into the selectivity mechanism through molecular dynamics simulations and QM/MM calculation", PHYSICAL CHEMISTRY CHEMICAL PHYSICS, vol. 23, 2021, pages 17576 - 17590
GRYDER, B. E. ET AL.: "Targeted Cancer Therapy: Giving Histone Deacetylase Inhibitors All They Need to Succeed", FUTURE MED. CHEM., vol. 4, 2012, pages 505 - 524
MOTTAMAL, M. ET AL.: "Histone Deacetylase Inhibitors in Clinical Studies as Templates for New Anticancer Agents", MOLECULES, vol. 20, 2015, pages 3898 - 3941, XP055887261, DOI: 10.3390/molecules20033898
"Comprehensive Organic Transformations", 1989, CHEMICAL SOCIETY OF JAPAN
P. G. M. WUTST. W. GREENE: "Greene's Protective Groups in Organic Synthesis", 2006
SHIGERU OOBASHIGENOBU YANO: "Kagakusha no tame no Kiso-Koza 12 X-ray crystallography", 1999
WALDEMAR ADAMRAINER T. FELCHANTU R. SAHA-MOLLERCONG-GUI ZHAO, TETRAHEDRON: ASYMMETRY, vol. 9, 1998, pages 397 - 401
YUANMING ZHUYONG TUHONGWU YUYIAN SHI, TETRAHEDRON LETT., vol. 29, 1988, pages 2437 - 2440
GRAEFF, J: "Annual review of pharmacology and toxicology", vol. 53, 2013, article "The potential of HDAC inhibitors as cognitive enhancers", pages: 311 - 330
GUAN, S-J. ET AL.: "HDAC2 negatively regulates memory formation and synaptic plasticity", NATURE, vol. 459, 2009, pages 55 - 60, XP055054472, DOI: 10.1038/nature07925
SUNG, Y-M. ET AL.: "Mercaptoacetamide-based class II HDAC inhibitor lowers Abeta levels and improves learning and memory in a mouse model of Alzheimer's disease", EXP NEUROL, vol. 239, 2013, pages 192 - 201
CHOONG, C-J. ET AL.: "A novel histone deacetylase 1 and 2 isoform-specific inhibitor alleviates experimental Parkinson's disease", NEUROBIOL AGING, vol. 37, 2016, pages 103 - 16, XP029344328, DOI: 10.1016/j.neurobiolaging.2015.10.001
SIMONA SANNA, S. ET AL.: "HDACI inhibition ameliorates TDP-43-induced cell death in vitro and in vivo", CELL DEATH & DISEASE, vol. 11, no. 369, 2020
ROSSAERT, E. ET AL.: "Restoration of histone acetylation ameliorates disease and metabolic abnormalities in a FUS mouse model", ACTA NEUROPATHOLOGICA COMMUNICATIONS, vol. 7, no. 107, 2019
FEDE, E. D. ET AL.: "Exogenous and endogenous HDAC inhibitor effects in Rubinstein-Taybi syndrome models", BIORXIV, 1 April 2020 (2020-04-01)
GOTTESFELD, J. M. ET AL.: "Increasing frataxin gene expression with histone deacetylase inhibitors as a therapeutic approach for friedreich's ataxia", J NEUROCHEM, vol. 126, August 2013 (2013-08-01), pages 147 - 154, XP055383276, DOI: 10.1111/jnc.12302
TANG, Y. ET AL.: "Inhibiting histone deacetylase 2 (HDAC2) promotes functional recovery from stroke", J AM HEART ASSOC, vol. 6, no. 10, 5 October 2017 (2017-10-05)
ZHANG, S. ET AL.: "Class I histone deacetylase (HDAC) inhibitor CI-994 promotes functional recovery following spinal cord injury", CELL DEATH & DISEASE, vol. 9, 2018
YANG, W-B. ET AL.: "Increased activation of HDAC 1/2/6 and Spl underlies therapeutic resistance and tumor growth in glioblastoma", NEURO ONCOL, vol. 22, no. 10, 14 October 2020 (2020-10-14), pages 1439 - 1451
OUYANG, B. ET AL.: "Normalizing HDAC2 levels in the spinal cord alleviates thermal and mechanical hyperalgesia after peripheral nerve injury and promotes GAD65 and KCC2 expression", FRONTIERS IN NEUROSCIENCE, vol. 13, 2019, pages 346
ROSSAERT, E. ET AL.: "HDAC6 inhibitors: Translating genetic and molecular insights into a therapy for axonal CMT", BRAIN RESEARCH, vol. 1733, 2020, pages 146692, XP086065771, DOI: 10.1016/j.brainres.2020.146692
IBI, D. ET AL.: "Antipsychotic-induced Hdac2 transcription via NF-kB leads to synaptic and cognitive side effects", NATURE NEUROSCIENCE, vol. 20, no. 9, 2017, pages 1247 - 1259
LOGAN, R. W. ET AL.: "Valproate reverses mania-like behaviors in mice via preferential targeting of HDAC2", MOLECULAR PSYCHIATRY, 24 November 2020 (2020-11-24)
SHETTY, M. G. ET AL.: "Histone deacetylase 2 selective inhibitors: A versatile therapeutic strategy as next generation drug target in cancer therapy", PHARMACOLOGICAL RESEARCH, vol. 170, 2021, pages 105695 - 105707, XP086714471, DOI: 10.1016/j.phrs.2021.105695
WEST, A. C. ET AL.: "New and emerging HDAC inhibitors for cancer treatment", J CLIN INVEST, vol. 124, no. 1, 2014, pages 30 - 39
YANG, YE ET AL.: "Rational design of selective HDAC2 inhibitors for liver cancer treatment: computational insights into the selectivity mechanism through molecular dynamics simulations and QM/MM calculation", PHYSICAL CHEMISTRY CHEMICAL PHYSICS, vol. 23, 2021, pages 17576 - 17590
GRYDER, B. E. ET AL.: "Targeted Cancer Therapy: Giving Histone Deacetylase Inhibitors All They Need to Succeed", FUTURE MED. CHEM., vol. 4, 2012, pages 505 - 524
MOTTAMAL, M. ET AL.: "Histone Deacetylase Inhibitors in Clinical Studies as Templates for New Anticancer Agents", MOLECULES, vol. 20, 2015, pages 3898 - 3941, XP055887261, DOI: 10.3390/molecules20033898
"Comprehensive Organic Transformations", 1989, CHEMICAL SOCIETY OF JAPAN
P. G. M. WUTST. W. GREENE: "Greene's Protective Groups in Organic Synthesis", 2006
SHIGERU OOBASHIGENOBU YANO: "Kagakusha no tame no Kiso-Koza 12 X-ray crystallography", 1999
WALDEMAR ADAMRAINER T. FELCHANTU R. SAHA-MOLLERCONG-GUI ZHAO, TETRAHEDRON: ASYMMETRY, vol. 9, 1998, pages 397 - 401
YUANMING ZHUYONG TUHONGWU YUYIAN SHI, TETRAHEDRON LETT., vol. 29, 1988, pages 2437 - 2440
Attorney, Agent or Firm:
YAMAO, Norihito et al. (JP)
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