JP6276769B2 - Parpインヒビターとしてのキナゾリノン誘導体 - Google Patents

Parpインヒビターとしてのキナゾリノン誘導体 Download PDF

Info

Publication number
JP6276769B2
JP6276769B2 JP2015533466A JP2015533466A JP6276769B2 JP 6276769 B2 JP6276769 B2 JP 6276769B2 JP 2015533466 A JP2015533466 A JP 2015533466A JP 2015533466 A JP2015533466 A JP 2015533466A JP 6276769 B2 JP6276769 B2 JP 6276769B2
Authority
JP
Japan
Prior art keywords
compound
formula
methyl
compounds
pharmaceutically acceptable
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
JP2015533466A
Other languages
English (en)
Japanese (ja)
Other versions
JP2015535831A5 (enExample
JP2015535831A (ja
Inventor
ドルシュ,ディーター
ブッフシュタラー,ハンス−ペーター
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck Patent GmbH
Original Assignee
Merck Patent GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Merck Patent GmbH filed Critical Merck Patent GmbH
Publication of JP2015535831A publication Critical patent/JP2015535831A/ja
Publication of JP2015535831A5 publication Critical patent/JP2015535831A5/ja
Application granted granted Critical
Publication of JP6276769B2 publication Critical patent/JP6276769B2/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72Quinazolines; Hydrogenated quinazolines
    • C07D239/86Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
    • C07D239/88Oxygen atoms
    • C07D239/91Oxygen atoms with aryl or aralkyl radicals attached in position 2 or 3
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541Non-condensed thiazines containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/10Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/10Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/10Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/10Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Immunology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
JP2015533466A 2012-09-26 2013-08-27 Parpインヒビターとしてのキナゾリノン誘導体 Active JP6276769B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP12006707 2012-09-26
EP12006707.9 2012-09-26
PCT/EP2013/002577 WO2014048532A1 (en) 2012-09-26 2013-08-27 Quinazolinone derivatives as parp inhibitors

Publications (3)

Publication Number Publication Date
JP2015535831A JP2015535831A (ja) 2015-12-17
JP2015535831A5 JP2015535831A5 (enExample) 2016-10-20
JP6276769B2 true JP6276769B2 (ja) 2018-02-07

Family

ID=47002492

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2015533466A Active JP6276769B2 (ja) 2012-09-26 2013-08-27 Parpインヒビターとしてのキナゾリノン誘導体

Country Status (16)

Country Link
US (1) US9388142B2 (enExample)
EP (1) EP2900643B1 (enExample)
JP (1) JP6276769B2 (enExample)
KR (1) KR102200628B1 (enExample)
CN (1) CN104662006B (enExample)
AR (1) AR092670A1 (enExample)
AU (1) AU2013324681B2 (enExample)
BR (1) BR112015006524A8 (enExample)
CA (1) CA2886000C (enExample)
ES (1) ES2654464T3 (enExample)
IL (1) IL237840A (enExample)
MX (1) MX362855B (enExample)
RU (1) RU2650107C2 (enExample)
SG (1) SG11201502120XA (enExample)
WO (1) WO2014048532A1 (enExample)
ZA (1) ZA201502838B (enExample)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SI2794627T1 (sl) 2011-12-22 2019-02-28 Alios Biopharma, Inc. Substituirani nukleozidi, nukleotidi in njihovi analogi
DK2822656T3 (en) 2012-03-07 2017-01-30 Inst Of Cancer Research: Royal Cancer Hospital (The) 3-aryl-5-substituted-isoquinolin-1-one compounds and their therapeutic use
US9441007B2 (en) 2012-03-21 2016-09-13 Alios Biopharma, Inc. Substituted nucleosides, nucleotides and analogs thereof
USRE48171E1 (en) 2012-03-21 2020-08-25 Janssen Biopharma, Inc. Substituted nucleosides, nucleotides and analogs thereof
PL2861611T3 (pl) 2012-05-25 2017-08-31 Janssen Sciences Ireland Uc Nukleozydy uracylowe spirooksetanu
ES2865402T3 (es) 2012-12-21 2021-10-15 Janssen Biopharma Inc 4'-fluoronucleósidos, 4'-fluoronucleótidos y análogos de los mismos para el tratamiento del VHC
CN105722835B (zh) 2013-09-11 2018-07-31 癌症研究协会:皇家癌症医院 3-芳基-5-取代的-异喹啉-1-酮化合物及它们的疗法应用
JP6899323B2 (ja) 2014-10-14 2021-07-07 ラ ホーヤ インスティテュート オブ アレルギー アンド イミュノロジー 低分子量タンパク質チロシンホスファターゼの阻害剤、及びその使用
WO2017156350A1 (en) 2016-03-09 2017-09-14 K-Gen, Inc. Methods of cancer treatment
CN107286169B (zh) * 2016-04-05 2020-11-24 北京四环制药有限公司 端锚聚合酶抑制剂
CN106432103A (zh) * 2016-09-14 2017-02-22 信阳师范学院 一种喹唑酮类化合物及其制备方法
EP3619210A4 (en) * 2017-05-01 2020-12-02 Sanford Burnham Prebys Medical Discovery Institute LOW MOLECULAR WEIGHT PROTEIN TYROSINE PHOSPHATASE (LMPTP) INHIBITORS AND ASSOCIATED USES
EP3733186B1 (en) * 2017-12-27 2024-12-04 Japanese Foundation For Cancer Research Novel dihydroquinazolinone compound or pharmacologically acceptable salt, and cell growth inhibitor
WO2019131794A1 (ja) * 2017-12-27 2019-07-04 公益財団法人がん研究会 抗がん剤
WO2021037868A1 (en) * 2019-08-28 2021-03-04 F. Hoffmann-La Roche Ag Novel quinazoline compounds for the treatment and prophylaxis of hepatitis b virus disease
WO2025111705A1 (en) * 2023-11-30 2025-06-05 Waverley Pharma Inc. Quinazolinone derivatives as poly (adp ribose) polymerase 1 (parp-1) inhibitors
WO2025221809A1 (en) * 2024-04-16 2025-10-23 Eluciderm Inc. 2-aryl-quinazolin-4(3h)-one inhibitors for the treatment of diseases

Family Cites Families (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3046871A1 (de) * 1980-12-12 1982-07-22 Dr. Karl Thomae Gmbh, 7950 Biberach Neue chinazolinone, ihre herstellung und ihre verwendung als arzneimittel
EP0054132B1 (de) 1980-12-12 1984-10-10 Dr. Karl Thomae GmbH Neue Pyrimidinone, ihre Herstellung und Arzneimittel mit einem Gehalt an diesen Stoffen
GB9404485D0 (en) 1994-03-09 1994-04-20 Cancer Res Campaign Tech Benzamide analogues
GB9624482D0 (en) 1995-12-18 1997-01-15 Zeneca Phaema S A Chemical compounds
BR9707495A (pt) 1996-02-13 1999-07-27 Zeneca Ltd Derivado de quinazolina processo para a preparação do mesmo composição farmacêutica e processo para a produç o de um efeito antiangiogênico e/ou de redução de permeabilidade vascular em um animal de sangue quente
JP4464466B2 (ja) 1996-03-05 2010-05-19 アストラゼネカ・ユーケイ・リミテッド 4―アニリノキナゾリン誘導体
GB9718972D0 (en) 1996-09-25 1997-11-12 Zeneca Ltd Chemical compounds
GB9702701D0 (en) * 1997-02-01 1997-04-02 Univ Newcastle Ventures Ltd Quinazolinone compounds
GB9714249D0 (en) 1997-07-08 1997-09-10 Angiogene Pharm Ltd Vascular damaging agents
EP1020445B1 (en) 1997-10-02 2008-08-13 Eisai R&D Management Co., Ltd. Fused pyridine derivatives
GB9900334D0 (en) 1999-01-07 1999-02-24 Angiogene Pharm Ltd Tricylic vascular damaging agents
GB9900752D0 (en) 1999-01-15 1999-03-03 Angiogene Pharm Ltd Benzimidazole vascular damaging agents
IL152682A0 (en) 2000-05-31 2003-06-24 Astrazeneca Ab Indole derivatives with vascular damaging activity
JP2004502766A (ja) 2000-07-07 2004-01-29 アンギオジェン・ファーマシューティカルズ・リミテッド 血管損傷剤としてのコルヒノール誘導体
CA2410562A1 (en) 2000-07-07 2002-01-31 Angiogene Pharmaceuticals Limited Colchinol derivatives as angiogenesis inhibitors
WO2004014873A1 (ja) * 2002-08-09 2004-02-19 Kyorin Pharmaceutical Co., Ltd. 4-置換キナゾリン-8-カルボン酸アミド誘導体とその薬理上許容される付加塩
CA2600868A1 (en) * 2005-03-09 2006-09-21 Merck & Co., Inc. Quinazolinone t-type calcium channel antagonists
ATE542799T1 (de) 2007-03-08 2012-02-15 Janssen Pharmaceutica Nv Chinolinonderivate als parp und tank-inhibitoren
NZ595747A (en) * 2009-03-18 2015-06-26 Resverlogix Corp Novel quinazolinones and related compounds for use as anti-inflammatory agents
TWI499418B (zh) 2009-05-21 2015-09-11 Nerviano Medical Sciences Srl 異喹啉-1(2h)-酮衍生物
PL2611300T3 (pl) 2010-09-03 2016-10-31 Podstawione skondensowane pochodne dihydropirymidynonów

Also Published As

Publication number Publication date
EP2900643B1 (en) 2017-09-27
BR112015006524A8 (pt) 2019-08-20
IL237840A (en) 2017-05-29
WO2014048532A1 (en) 2014-04-03
AR092670A1 (es) 2015-04-29
CA2886000C (en) 2020-11-10
HK1210777A1 (en) 2016-05-06
US20150239850A1 (en) 2015-08-27
KR102200628B1 (ko) 2021-01-08
US9388142B2 (en) 2016-07-12
MX2015003570A (es) 2015-06-22
ES2654464T3 (es) 2018-02-13
CN104662006A (zh) 2015-05-27
AU2013324681B2 (en) 2017-08-10
JP2015535831A (ja) 2015-12-17
CA2886000A1 (en) 2014-04-03
SG11201502120XA (en) 2015-04-29
AU2013324681A1 (en) 2015-05-07
RU2650107C2 (ru) 2018-04-09
EP2900643A1 (en) 2015-08-05
CN104662006B (zh) 2017-10-24
MX362855B (es) 2019-02-20
RU2015115576A (ru) 2016-11-20
BR112015006524A2 (pt) 2017-07-04
KR20150063474A (ko) 2015-06-09
ZA201502838B (en) 2017-11-29

Similar Documents

Publication Publication Date Title
JP6276769B2 (ja) Parpインヒビターとしてのキナゾリノン誘導体
JP6333450B2 (ja) (アザ−)イソキノリノン誘導体
JP6097820B2 (ja) ピロロトリアジノン誘導体
JP6096879B2 (ja) 二環式ピラジノン誘導体
JP6116592B2 (ja) Tankおよびparpのインヒビターとしてのテトラヒドロ−キナゾリノン誘導体
JP6382964B2 (ja) フタラジン誘導体
HK1210777B (en) Quinazolinone derivatives as parp inhibitors
HK1209106B (en) (aza-)isoquinolinone derivatives
HK1202551B (en) Tetrahydro-quinazolinone derivatives as tank and parp inhibitors
HK1205740B (en) Pyrrolotriazinone derivatives
HK1203961B (en) Bicyclic pyrazinone derivatives

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20160826

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20160826

A977 Report on retrieval

Free format text: JAPANESE INTERMEDIATE CODE: A971007

Effective date: 20170615

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20170628

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20170928

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20171023

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20171204

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20171214

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20180112

R150 Certificate of patent or registration of utility model

Ref document number: 6276769

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250