JP5266216B2 - Ａｋｔプロテインキナーゼ阻害剤としてのヒドロキシル化およびメトキシル化されたシクロペンタ［ｄ］ピリミジン - Google Patents

Ａｋｔプロテインキナーゼ阻害剤としてのヒドロキシル化およびメトキシル化されたシクロペンタ［ｄ］ピリミジン Download PDF

Info

Publication number
JP5266216B2
JP5266216B2 JP2009518636A JP2009518636A JP5266216B2 JP 5266216 B2 JP5266216 B2 JP 5266216B2 JP 2009518636 A JP2009518636 A JP 2009518636A JP 2009518636 A JP2009518636 A JP 2009518636A JP 5266216 B2 JP5266216 B2 JP 5266216B2
Authority
JP
Japan
Prior art keywords
methyl
cyclopenta
dihydro
hydroxy
piperazin
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
JP2009518636A
Other languages
English (en)
Japanese (ja)
Other versions
JP2009542723A (ja
JP2009542723A5 (enExample
Inventor
イアン エス． ミッチェル，
ジェームス エフ． ブレーク，
ルイ スー，
ニコラス シー． カラン，
デンミン シャオ，
キース リー スペンサー，
ジョセフ アール． ベンシック，
チュン リャン，
ブライアン サフィナ，
ビロン チャン，
クリスティーヌ シャボー，
スティーブン ドゥー，
エリー エム． ウォレス，
アンナ エル． バンカ，
スティーブン ティー． シュラヒター，
Original Assignee
アレイ バイオファーマ、インコーポレイテッド
ジェネンテック， インコーポレイテッド
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=38686743&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=JP5266216(B2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by アレイ バイオファーマ、インコーポレイテッド, ジェネンテック， インコーポレイテッド filed Critical アレイ バイオファーマ、インコーポレイテッド
Publication of JP2009542723A publication Critical patent/JP2009542723A/ja
Publication of JP2009542723A5 publication Critical patent/JP2009542723A5/ja
Application granted granted Critical
Publication of JP5266216B2 publication Critical patent/JP5266216B2/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/06—Anti-spasmodics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic 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
    • C07D401/02—Heterocyclic 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
    • C07D401/12—Heterocyclic 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 chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic 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
    • C07D403/04—Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic 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
    • C07D403/12—Heterocyclic 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 chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Oncology (AREA)
  • Virology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Communicable Diseases (AREA)
  • Diabetes (AREA)
  • Pulmonology (AREA)
  • Epidemiology (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Reproductive Health (AREA)
  • Dermatology (AREA)
  • Obesity (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Molecular Biology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Rheumatology (AREA)
  • Hospice & Palliative Care (AREA)
  • Transplantation (AREA)
  • Child & Adolescent Psychology (AREA)
  • AIDS & HIV (AREA)
JP2009518636A 2006-07-06 2007-07-05 Ａｋｔプロテインキナーゼ阻害剤としてのヒドロキシル化およびメトキシル化されたシクロペンタ［ｄ］ピリミジン Active JP5266216B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US81871806P 2006-07-06 2006-07-06
US60/818,718 2006-07-06
PCT/US2007/072885 WO2008006040A1 (en) 2006-07-06 2007-07-05 Hydroxylated and methoxylated cyclopenta [d] pyrimidines as akt protein kinase inhibitors

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2013029956A Division JP5836294B2 (ja) 2006-07-06 2013-02-19 Ａｋｔプロテインキナーゼ阻害剤としてのヒドロキシル化およびメトキシル化されたシクロペンタ［ｄ］ピリミジン

Publications (3)

Publication Number Publication Date
JP2009542723A JP2009542723A (ja) 2009-12-03
JP2009542723A5 JP2009542723A5 (enExample) 2010-08-26
JP5266216B2 true JP5266216B2 (ja) 2013-08-21

Family

ID=38686743

Family Applications (4)

Application Number Title Priority Date Filing Date
JP2009518636A Active JP5266216B2 (ja) 2006-07-06 2007-07-05 Ａｋｔプロテインキナーゼ阻害剤としてのヒドロキシル化およびメトキシル化されたシクロペンタ［ｄ］ピリミジン
JP2013029956A Active JP5836294B2 (ja) 2006-07-06 2013-02-19 Ａｋｔプロテインキナーゼ阻害剤としてのヒドロキシル化およびメトキシル化されたシクロペンタ［ｄ］ピリミジン
JP2013133983A Pending JP2013177470A (ja) 2006-07-06 2013-06-26 Ａｋｔプロテインキナーゼ阻害剤としてのヒドロキシル化およびメトキシル化されたシクロペンタ［ｄ］ピリミジン
JP2014188238A Withdrawn JP2014231530A (ja) 2006-07-06 2014-09-16 Ａｋｔプロテインキナーゼ阻害剤としてのヒドロキシル化およびメトキシル化されたシクロペンタ［ｄ］ピリミジン

Family Applications After (3)

Application Number Title Priority Date Filing Date
JP2013029956A Active JP5836294B2 (ja) 2006-07-06 2013-02-19 Ａｋｔプロテインキナーゼ阻害剤としてのヒドロキシル化およびメトキシル化されたシクロペンタ［ｄ］ピリミジン
JP2013133983A Pending JP2013177470A (ja) 2006-07-06 2013-06-26 Ａｋｔプロテインキナーゼ阻害剤としてのヒドロキシル化およびメトキシル化されたシクロペンタ［ｄ］ピリミジン
JP2014188238A Withdrawn JP2014231530A (ja) 2006-07-06 2014-09-16 Ａｋｔプロテインキナーゼ阻害剤としてのヒドロキシル化およびメトキシル化されたシクロペンタ［ｄ］ピリミジン

Country Status (34)

Country Link
EP (4) EP2399909B1 (enExample)
JP (4) JP5266216B2 (enExample)
KR (5) KR101578877B1 (enExample)
CN (2) CN102816124A (enExample)
AR (3) AR061842A1 (enExample)
AT (1) ATE524447T1 (enExample)
AU (1) AU2007269060B2 (enExample)
BR (3) BRPI0713923B8 (enExample)
CA (2) CA2836316A1 (enExample)
CL (1) CL2007001993A1 (enExample)
CO (1) CO6150161A2 (enExample)
CR (1) CR10600A (enExample)
CY (1) CY1112117T1 (enExample)
DK (2) DK2402325T3 (enExample)
ES (3) ES2372774T3 (enExample)
HR (1) HRP20110908T1 (enExample)
HU (1) HUE026237T2 (enExample)
IL (2) IL196028A (enExample)
IN (1) IN2014KN02886A (enExample)
MA (1) MA31655B1 (enExample)
MX (4) MX377920B (enExample)
MY (1) MY147364A (enExample)
NO (1) NO342346B1 (enExample)
NZ (3) NZ610633A (enExample)
PL (2) PL2049501T3 (enExample)
PT (1) PT2049501E (enExample)
RS (1) RS52212B (enExample)
RU (2) RU2478632C2 (enExample)
SG (4) SG185980A1 (enExample)
SI (2) SI2402325T1 (enExample)
TW (2) TWI402266B (enExample)
UA (1) UA95641C2 (enExample)
WO (1) WO2008006040A1 (enExample)
ZA (1) ZA200900070B (enExample)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013091670A (ja) * 2006-07-06 2013-05-16 Array Biopharma Inc Ａｋｔプロテインキナーゼ阻害剤としてのヒドロキシル化およびメトキシル化されたシクロペンタ［ｄ］ピリミジン

Families Citing this family (53)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8063050B2 (en) * 2006-07-06 2011-11-22 Array Biopharma Inc. Hydroxylated and methoxylated pyrimidyl cyclopentanes as AKT protein kinase inhibitors
WO2008006039A1 (en) 2006-07-06 2008-01-10 Array Biopharma Inc. Dihydrothieno pyrimidines as akt protein kinase inhibitors
DE602007011628D1 (de) * 2006-07-06 2011-02-10 Array Biopharma Inc Dihydrofuropyrimidine als akt-proteinkinaseinhibitoren
RU2481336C2 (ru) 2006-07-06 2013-05-10 Эррэй Биофарма Инк. Циклопента(d)пиримидины в качестве ингибиторов протеинкиназ акт
US20110135569A1 (en) 2007-03-20 2011-06-09 Peak Biosciences Inc. Method for therapeutic administration of radionucleosides
US8846683B2 (en) 2007-07-05 2014-09-30 Array Biopharma, Inc. Pyrimidyl cyclopentanes as Akt protein kinase inhibitors
MX2009014013A (es) 2007-07-05 2010-01-28 Array Biopharma Inc Pirimidil ciclopentanos como inhibidores de la proteina cinasa akt.
US9409886B2 (en) 2007-07-05 2016-08-09 Array Biopharma Inc. Pyrimidyl cyclopentanes as AKT protein kinase inhibitors
CA2692502C (en) 2007-07-05 2016-03-01 Array Biopharma Inc. Pyrimidyl cyclopentanes as akt protein kinase inhibitors
CN104876921A (zh) 2008-01-09 2015-09-02 阵列生物制药公司 作为AKT蛋白激酶抑制剂的5H-环戊二烯并[d]嘧啶
US8853216B2 (en) * 2008-01-09 2014-10-07 Array Biopharma, Inc. Hydroxylated pyrimidyl cyclopentane as AKT protein kinase inhibitor
US8835434B2 (en) * 2008-01-09 2014-09-16 Array Biopharma, Inc. Hydroxylated pyrimidyl cyclopentanes as akt protein kinase inhibitors
TW200940542A (en) 2008-01-09 2009-10-01 Array Biopharma Inc Pyrimidyl cyclopentanes as AKT protein kinase inhibitors
EP2655619A4 (en) * 2010-12-23 2014-10-22 Genentech Inc COMBINATION THERAPY FROM AUTOPHAGIA AND HEMMER FOR THE TREATMENT OF NEOPLASMS
FI2694072T4 (fi) * 2011-04-01 2024-09-30 Genentech Inc Akt-inhibiittoriyhdisteen ja abirateronin yhdistelmä käytettäväksi terapeuttisissa hoidoissa
TR201815685T4 (tr) 2011-04-01 2018-11-21 Genentech Inc Kanser tedavisi için akt ve mek inhibe edici bileşiklerin kombinasyonları.
SG194050A1 (en) * 2011-04-01 2013-11-29 Genentech Inc Biomarkers for predicting sensitivity to cancer treatments
ES2588878T3 (es) * 2012-05-17 2016-11-07 Array Biopharma, Inc. Proceso para preparar compuestos de ciclopentilpirimidina hidroxilada
LT2858989T (lt) * 2012-05-17 2020-08-10 Genentech, Inc. Akt inhibuojančio pirimidinil-ciklopentano junginio amorfinė forma, jo kompozicijos ir būdai
EP2850200A1 (en) 2012-05-17 2015-03-25 Genentech, Inc. Process of making hydroxylated cyclopentapyrimidine compounds and salts thereof
BR112014028585B1 (pt) 2012-05-17 2020-12-22 Genentech , Inc processo para fabricação de aminoácidos, e seus intermediários
ES2582557T3 (es) * 2012-05-17 2016-09-13 Array Biopharma, Inc. Proceso para la preparación de compuestos hidroxilados de ciclopentilpirimidina
WO2014068070A1 (en) 2012-10-31 2014-05-08 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for preventing antiphospholipid syndrome (aps)
MX2015007054A (es) 2012-12-07 2016-01-12 Gen Hospital Corp Combinaciones de un compuesto inhibidor de pi3k/akt con un compuesto inhibidor de her3/egfr, y métodos de uso.
JP6340162B2 (ja) * 2012-12-20 2018-06-06 日東電工株式会社 アポトーシス誘導剤
CN112898210B (zh) 2013-11-15 2025-02-21 豪夫迈·罗氏有限公司 用于制备嘧啶基环戊烷化合物的方法
PL3197875T3 (pl) 2014-09-26 2020-03-31 F. Hoffmann-La Roche Ag Sposoby wytwarzania związków (cyklopentylo[d]pirymidyn-4-ylo)piperazynowych
CN109789141B (zh) 2016-08-10 2022-08-26 豪夫迈·罗氏有限公司 包含Akt蛋白激酶抑制剂的药物组合物
MX2019004950A (es) 2016-10-28 2019-09-26 Icahn School Med Mount Sinai Composiciones y metodos para tratar el cancer mediado por el potenciador del homologo zeste 2.
JP2021515013A (ja) * 2018-03-06 2021-06-17 アイカーン スクール オブ メディスン アット マウント シナイ セリンスレオニンキナーゼ（ａｋｔ）分解／破壊化合物および使用方法
JP2021527666A (ja) 2018-06-21 2021-10-14 アイカーン スクール オブ メディスン アット マウント シナイ Ｗｄ４０反復ドメインタンパク質５（ｗｄｒ５）分解／破壊化合物および使用の方法
WO2020010204A1 (en) 2018-07-05 2020-01-09 Icahn School Of Medicine At Mount Sinai Protein tyrosine kinase 6 (ptk6) degradation / disruption compounds and methods of use
EP3897612A1 (en) 2018-12-19 2021-10-27 Genentech, Inc. Treatment of breast cancer using combination therapies comprising an akt inhibitor, a taxane, and a pd-l1 inhibitor
BR112021011894A2 (pt) 2018-12-21 2021-09-08 Daiichi Sankyo Company, Limited Composição farmacêutica
US12617784B2 (en) 2019-01-29 2026-05-05 Nanjing Chia Tai Tianqing Pharmaceutical Co., Ltd. AKT inhibitor
WO2020201073A1 (en) 2019-03-29 2020-10-08 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for the treatment of keloid, hypertrophic scars and/or hyperpigmentation disorders
JP7667742B2 (ja) 2019-04-09 2025-04-23 ダナ－ファーバー キャンサー インスティテュート，インコーポレイテッド Ａｔｐ競合性ａｋｔ阻害剤ｇｄｃ－００６８とｅ３リガーゼリガンドとの結合によるａｋｔの分解および使用方法
CN114423463B (zh) 2019-05-06 2025-09-26 西奈山伊坎医学院 作为hpk1的降解剂的异双功能化合物
JP2023520140A (ja) * 2020-03-17 2023-05-16 江蘇恒瑞医薬股▲ふん▼有限公司 縮合二環系誘導体、その調製方法及びその医薬的応用
US12103924B2 (en) 2020-06-01 2024-10-01 Icahn School Of Medicine At Mount Sinai Mitogen-activated protein kinase kinase (MEK) degradation compounds and methods of use
CN120887837A (zh) 2020-06-16 2025-11-04 豪夫迈·罗氏有限公司 用于制备羟基化环戊基嘧啶化合物的方法
US12673061B2 (en) 2020-07-22 2026-07-07 Nanjing Chia Tai Tianqing Pharmaceutical Co., Ltd. Unit dosage composition of AKT inhibitor
EP4186902A4 (en) 2020-07-22 2024-06-05 Nanjing Chia Tai Tianqing Pharmaceutical Co., Ltd. DIHYDROPYRIDO[2,3-D]PYRIMIDINONE DERIVATIVE SALT, PREPARATION METHOD AND USE THEREOF
TWI750905B (zh) * 2020-11-19 2021-12-21 財團法人國家衛生研究院 噻唑化合物作為蛋白質激酶抑制劑
KR102689151B1 (ko) * 2021-09-06 2024-07-29 연세대학교 산학협력단 Akt 신호경로 억제제를 유효성분으로 포함하는 아토피피부염의 예방 또는 치료용 조성물
WO2023043869A1 (en) * 2021-09-15 2023-03-23 Teva Pharmaceuticals International Gmbh Solid state forms of ipatasertib citrate
CN113788834B (zh) * 2021-09-18 2022-11-29 河南奥思恩医药科技有限公司 2,4-二氯-6,7-二氢-5H-吡咯并[3,4-d]嘧啶盐酸盐的制备方法
WO2023109540A1 (zh) * 2021-12-17 2023-06-22 中国医药研究开发中心有限公司 具有akt激酶抑制活性的杂环化合物及其制备方法和医药用途
CN119278041A (zh) 2022-03-31 2025-01-07 阿斯利康(瑞典)有限公司 用于治疗癌症的与akt抑制剂组合的表皮生长因子受体（egfr）酪氨酸激酶抑制剂
WO2024083716A1 (en) 2022-10-17 2024-04-25 Astrazeneca Ab Combinations of a serd for the treatment of cancer
JP2025539034A (ja) 2022-11-11 2025-12-03 アストラゼネカ・アクチエボラーグ 癌の治療のための併用療法
WO2024160843A1 (en) 2023-01-31 2024-08-08 F. Hoffmann-La Roche Ag Mutant ketoreductase with increased ketoreductase activity as well as methods and uses involving the same
EP4643858A1 (en) 2024-04-29 2025-11-05 Institut National de la Santé et de la Recherche Médicale Methods and pharmaceutical composition for the treatment of uterine disease

Family Cites Families (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3773919A (en) 1969-10-23 1973-11-20 Du Pont Polylactide-drug mixtures
NL7112938A (enExample) * 1970-09-30 1972-04-05
US5543523A (en) 1994-11-15 1996-08-06 Regents Of The University Of Minnesota Method and intermediates for the synthesis of korupensamines
WO1998030546A1 (en) * 1997-01-08 1998-07-16 F. Hoffmann-La Roche Ag TRICYCLIC BENZO[e]ISOINDOLES AND BENZO[h]ISOQUINOLINES
ES2152902B1 (es) * 1999-07-27 2001-08-16 Medichem Sa Procedimiento de obtencion de venlafaxina
HU228668B1 (hu) * 2000-08-18 2013-05-28 Millennium Pharmaceuticals Kináz inhibitor kinazolin-származékok és az ezeket tartalmazó gyógyszerkészítmények
AU2001290912A1 (en) * 2000-09-15 2002-03-26 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
CA2443135C (en) * 2001-03-30 2010-07-13 Allan R. Moorman Pharmaceutically active compounds and methods of use
ATE424388T1 (de) * 2001-12-06 2009-03-15 Merck & Co Inc Mitotische kinesinhemmer
MXPA04007191A (es) * 2002-01-23 2005-03-31 Bayer Pharmaceuticals Corp Derivados de pirimidina como inhibidores de rho-quinasa.
TW200306819A (en) * 2002-01-25 2003-12-01 Vertex Pharma Indazole compounds useful as protein kinase inhibitors
AU2004293026B2 (en) * 2003-11-21 2012-01-19 Array Biopharma Inc. AKT protein kinase inhibitors
EP1751133B1 (en) * 2004-04-28 2010-04-14 Vertex Pharmaceuticals Incorporated Compositions useful as inhibitors of rock and other protein kinases
WO2005113762A1 (en) 2004-05-18 2005-12-01 Pfizer Products Inc. CRYSTAL STRUCTURE OF PROTEIN KINASE B-α (AKT-1) AND USES THEREOF
JP2008538102A (ja) * 2005-03-03 2008-10-09 ザ バーナム インスティテュート フォー メディカル リサーチ バーチャルドッキングアプローチを適用したプロテインキナーゼｂ阻害剤のスクリーニング方法並びにそれにより見出された化合物及び組成物
WO2008006039A1 (en) * 2006-07-06 2008-01-10 Array Biopharma Inc. Dihydrothieno pyrimidines as akt protein kinase inhibitors
UA95641C2 (xx) * 2006-07-06 2011-08-25 Эррей Биофарма Инк. Гідроксильовані піримідильні циклопентани як інгібітори акт протеїнкінази$гидроксилированные пиримидильные циклопентаны как ингибиторы акт протеинкиназы
RU2481336C2 (ru) * 2006-07-06 2013-05-10 Эррэй Биофарма Инк. Циклопента(d)пиримидины в качестве ингибиторов протеинкиназ акт

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013091670A (ja) * 2006-07-06 2013-05-16 Array Biopharma Inc Ａｋｔプロテインキナーゼ阻害剤としてのヒドロキシル化およびメトキシル化されたシクロペンタ［ｄ］ピリミジン

Also Published As

Publication number Publication date
PL2402325T3 (pl) 2016-01-29
KR20140093291A (ko) 2014-07-25
BR122013028005B1 (pt) 2021-04-06
TW201332994A (zh) 2013-08-16
SG10201802127UA (en) 2018-04-27
HRP20110908T1 (hr) 2012-02-29
JP2013091670A (ja) 2013-05-16
SG188905A1 (en) 2013-04-30
AR061842A1 (es) 2008-09-24
ZA200900070B (en) 2010-03-31
JP5836294B2 (ja) 2015-12-24
HK1160638A1 (en) 2012-08-10
KR101178672B1 (ko) 2012-09-07
UA95641C2 (xx) 2011-08-25
CN101578273A (zh) 2009-11-11
WO2008006040A1 (en) 2008-01-10
KR101495408B1 (ko) 2015-02-25
BRPI0713923B1 (pt) 2020-09-29
RS52212B (sr) 2012-10-31
EP2049501A1 (en) 2009-04-22
MX377920B (es) 2025-03-11
NO342346B1 (no) 2018-05-07
IN2014KN02886A (enExample) 2015-05-08
KR20090030333A (ko) 2009-03-24
HUE026237T2 (en) 2016-06-28
CN101578273B (zh) 2012-11-14
AR109424A2 (es) 2018-11-28
DK2049501T3 (da) 2011-12-12
BRPI0713923A2 (pt) 2013-07-02
BRPI0713923B8 (pt) 2021-05-25
IL196028A0 (en) 2009-09-01
MX366319B (es) 2019-07-05
EP2966065A2 (en) 2016-01-13
ATE524447T1 (de) 2011-09-15
EP2402325B1 (en) 2015-08-26
TW200817373A (en) 2008-04-16
CN102816124A (zh) 2012-12-12
EP2399909A1 (en) 2011-12-28
ES2372774T3 (es) 2012-01-26
JP2009542723A (ja) 2009-12-03
EP2399909B1 (en) 2015-08-26
KR20150051240A (ko) 2015-05-11
CA2656622C (en) 2017-09-12
CR10600A (es) 2009-02-20
EP2966065A3 (en) 2016-03-02
TWI402266B (zh) 2013-07-21
CO6150161A2 (es) 2010-04-20
CA2656622A1 (en) 2008-01-10
PT2049501E (pt) 2011-12-30
MX337843B (es) 2016-03-22
NZ573732A (en) 2012-03-30
KR101578877B1 (ko) 2016-02-22
SI2049501T1 (sl) 2012-01-31
DK2402325T3 (en) 2015-12-07
ES2554228T3 (es) 2015-12-17
PL2049501T3 (pl) 2012-02-29
MX2008016202A (es) 2009-02-11
BR122013028012B8 (pt) 2021-05-25
JP2014231530A (ja) 2014-12-11
ES2554252T3 (es) 2015-12-17
RU2009103900A (ru) 2010-08-20
AU2007269060A1 (en) 2008-01-10
EP2402325A2 (en) 2012-01-04
CY1112117T1 (el) 2015-11-04
RU2478632C2 (ru) 2013-04-10
EP2049501B1 (en) 2011-09-14
MX2019008117A (es) 2019-09-04
SG184706A1 (en) 2012-10-30
RU2012155606A (ru) 2014-06-27
MY147364A (en) 2012-11-30
NZ597647A (en) 2013-08-30
HK1160134A1 (en) 2012-08-10
KR20130141717A (ko) 2013-12-26
AU2007269060B2 (en) 2014-02-20
MA31655B1 (fr) 2010-09-01
IL241705A0 (en) 2015-11-30
NZ610633A (en) 2014-12-24
BR122013028012B1 (pt) 2021-04-06
SI2402325T1 (sl) 2015-12-31
BR122013028005B8 (pt) 2021-05-25
AR093810A2 (es) 2015-06-24
IL196028A (en) 2017-02-28
KR20130029364A (ko) 2013-03-22
CA2836316A1 (en) 2008-01-10
CL2007001993A1 (es) 2008-06-20
NO20090581L (no) 2009-04-06
JP2013177470A (ja) 2013-09-09
HK1126768A1 (en) 2009-09-11
EP2402325A3 (en) 2012-06-13
SG185980A1 (en) 2012-12-28

Similar Documents

Publication Publication Date Title
JP5836294B2 (ja) Ａｋｔプロテインキナーゼ阻害剤としてのヒドロキシル化およびメトキシル化されたシクロペンタ［ｄ］ピリミジン
JP5268904B2 (ja) Ａｋｔプロテインキナーゼ阻害剤としてのシクロペンタ［ｄ］ピリミジン
JP5231411B2 (ja) Ａｋｔプロテインキナーゼ阻害剤としてのジヒドロチエノピリミジン
US20250152588A1 (en) Hydroxylated and methoxylated pyrimidyl cyclopentanes as akt protein kinase inhibitors
JP5231410B2 (ja) Ａｋｔプロテインキナーゼ阻害剤としてのジヒドロフロピリミジン
HK1160638B (en) Hydroxylated cyclopenta[d]pyrimidines as akt protein kinase inhibitors
HK1160134B (en) Hydroxylated cyclopenta[d]pyrimidines as akt protein kinase inhibitors

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20100702

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20100702

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20110620

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20120920

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20121219

A602 Written permission of extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A602

Effective date: 20121227

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20130118

A602 Written permission of extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A602

Effective date: 20130125

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20130219

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A821

Effective date: 20130219

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: 20130405

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20130502

R150 Certificate of patent or registration of utility model

Ref document number: 5266216

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

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

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