JP5584696B2 - Mmp−13阻害剤として有用なヘテロアリールジアミド化合物 - Google Patents

Mmp−13阻害剤として有用なヘテロアリールジアミド化合物 Download PDF

Info

Publication number
JP5584696B2
JP5584696B2 JP2011536394A JP2011536394A JP5584696B2 JP 5584696 B2 JP5584696 B2 JP 5584696B2 JP 2011536394 A JP2011536394 A JP 2011536394A JP 2011536394 A JP2011536394 A JP 2011536394A JP 5584696 B2 JP5584696 B2 JP 5584696B2
Authority
JP
Japan
Prior art keywords
alkyl
compound
formula
mmol
phenyl
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.)
Expired - Fee Related
Application number
JP2011536394A
Other languages
English (en)
Japanese (ja)
Other versions
JP2012509262A (ja
JP2012509262A5 (Direct
Inventor
ファロー,ニール・アレクサンダー
ガオ,ドンホン・エイ
ハイム−リーター,アレクサンダー
スミス・キーナン,ラナ・ルイーズ
リャン,シュアン
テイラー,スティーブン・ジョン
ヴェレンゾーン,ベルント
ヴィーデンマイヤー,ディーター
ション,ツァオミン
ツァン,チァン
シュライヤー,サビーネ
Original Assignee
ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング
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 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング filed Critical ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング
Publication of JP2012509262A publication Critical patent/JP2012509262A/ja
Publication of JP2012509262A5 publication Critical patent/JP2012509262A5/ja
Application granted granted Critical
Publication of JP5584696B2 publication Critical patent/JP5584696B2/ja
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • C07D407/10—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 carbon chain containing aromatic rings
    • 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
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • 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
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • 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
    • 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
    • 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
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • 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
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • 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
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D407/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D411/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms
    • C07D411/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D411/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and 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
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Immunology (AREA)
  • Vascular Medicine (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pain & Pain Management (AREA)
  • Oncology (AREA)
  • Urology & Nephrology (AREA)
  • Hospice & Palliative Care (AREA)
  • Biomedical Technology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Furan Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
JP2011536394A 2008-11-17 2009-11-05 Mmp−13阻害剤として有用なヘテロアリールジアミド化合物 Expired - Fee Related JP5584696B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US11521608P 2008-11-17 2008-11-17
US61/115,216 2008-11-17
PCT/US2009/063343 WO2010056585A2 (en) 2008-11-17 2009-11-05 Heteroaryl diamide compounds useful as mmp-13 inhibitors

Publications (3)

Publication Number Publication Date
JP2012509262A JP2012509262A (ja) 2012-04-19
JP2012509262A5 JP2012509262A5 (Direct) 2012-12-20
JP5584696B2 true JP5584696B2 (ja) 2014-09-03

Family

ID=41395988

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2011536394A Expired - Fee Related JP5584696B2 (ja) 2008-11-17 2009-11-05 Mmp−13阻害剤として有用なヘテロアリールジアミド化合物

Country Status (5)

Country Link
US (1) US8637550B2 (Direct)
EP (1) EP2346831B1 (Direct)
JP (1) JP5584696B2 (Direct)
CA (1) CA2743146A1 (Direct)
WO (1) WO2010056585A2 (Direct)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2739488A1 (en) 2008-10-15 2010-04-22 Boehringer Ingelheim International Gmbh Fused heteroaryl diamide compounds useful as mmp-13 inhibitors
US8785489B2 (en) 2008-10-17 2014-07-22 Boehringer Ingelheim International Gmbh Heteroaryl substituted indole compounds useful as MMP-13 inhibitors
CA2743146A1 (en) 2008-11-17 2010-05-20 Boehringer Ingelheim International Gmbh Heteroaryl diamide compounds useful as mmp-13 inhibitors
DK2909181T3 (da) * 2012-10-16 2017-11-20 Tolero Pharmaceuticals Inc PKM2-modulatorer og fremgangsmåder til anvendelse deraf
EP3941463A1 (en) 2019-03-22 2022-01-26 Sumitomo Dainippon Pharma Oncology, Inc. Compositions comprising pkm2 modulators and methods of treatment using the same
AU2020417293A1 (en) 2020-01-03 2022-09-01 Berg Llc Polycyclic amides as UBE2K modulators for treating cancer

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU6396600A (en) * 1999-08-04 2001-03-05 Chemrx Advanced Technologies, Inc. Solid phase synthesis of oxa- and thiazoles
US6849660B1 (en) 2000-08-01 2005-02-01 Isis Pharmaceuticals, Inc. Antimicrobial biaryl compounds
JP2006506326A (ja) 2002-05-14 2006-02-23 アキシーズ ファーマシューティカルズ インク. システインプロテアーゼ阻害剤
CA2506114A1 (en) 2002-12-05 2004-06-24 Axys Pharmaceuticals, Inc. Cyanomethyl derivatives as cysteine protease inhibitors
US7384970B2 (en) 2003-03-24 2008-06-10 Irm Llc Inhibitors of cathepsin S
US7109243B2 (en) * 2003-03-24 2006-09-19 Irm Llc Inhibitors of cathepsin S
EP1493739A1 (fr) * 2003-07-03 2005-01-05 Warner-Lambert Company LLC Dérivés thiophényliques d'aminoacides, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent
UA94412C2 (en) * 2005-07-11 2011-05-10 Уайет Glutamate aggrecanase inhibitors
CA2739488A1 (en) 2008-10-15 2010-04-22 Boehringer Ingelheim International Gmbh Fused heteroaryl diamide compounds useful as mmp-13 inhibitors
US8785489B2 (en) 2008-10-17 2014-07-22 Boehringer Ingelheim International Gmbh Heteroaryl substituted indole compounds useful as MMP-13 inhibitors
CA2743146A1 (en) 2008-11-17 2010-05-20 Boehringer Ingelheim International Gmbh Heteroaryl diamide compounds useful as mmp-13 inhibitors

Also Published As

Publication number Publication date
US20110275625A1 (en) 2011-11-10
JP2012509262A (ja) 2012-04-19
WO2010056585A3 (en) 2010-11-25
EP2346831A2 (en) 2011-07-27
WO2010056585A2 (en) 2010-05-20
EP2346831B1 (en) 2015-01-07
US8637550B2 (en) 2014-01-28
CA2743146A1 (en) 2010-05-20

Similar Documents

Publication Publication Date Title
EP2340243B1 (en) Heteroaryl substituted indole compounds useful as mmp-13 inhibitors
JP5216912B2 (ja) Ccr1受容体拮抗薬としてのインダゾール化合物
JP7046968B2 (ja) 2-(置換フェニルヘテロ)芳香族カルボン酸系fto阻害剤、その製造方法およびその使用
AU2004255342B2 (en) Benzenesulfonylamino compounds and pharmaceutical compositions containing these compounds
JP6511450B2 (ja) Wnt経路のモジュレーターとしてのマレイミド誘導体
BRPI0414548B1 (pt) derivados de 2-piridona como inibidores de elastase de neutrófilo e seu uso
KR20120047211A (ko) Cb2 수용체를 선택적으로 조절하는 화합물
JP2012509262A (ja) Mmp−13阻害剤として有用なヘテロアリールジアミド化合物
JP2023553291A (ja) Trpm3媒介性障害を治療するためのアリール誘導体
WO2009140101A2 (en) Imidazopyridine compounds useful as mmp-13 inhibitors
US8338367B2 (en) Fused heteroaryl diamide compounds useful as MMP-13 inhibitors
JP4571075B2 (ja) アミド型カルボキサミド誘導体
US6727266B2 (en) Substituted tryptophan derivatives
CN113166148B (zh) 作为cdk-hdac双通路抑制剂的杂环化合物
ES2375633T3 (es) Derivado de pirimidinilisoxazol.
KR20250036737A (ko) Trpm3 매개 장애를 치료하기 위한 새로운 유도체
WO2025215121A1 (en) Hedgehog acyltransferase inhibitors
JP5529131B2 (ja) キマーゼ阻害薬
GB2640329A (en) Hedgehog acyltransferase inhibitors
TW202132282A (zh) 基質金屬蛋白酶(mmp)抑制劑及其使用方法
JP4218388B2 (ja) ベンゾフラン誘導体
JP2003513959A (ja) カルボキサミド置換ベンゾイミダゾール誘導体、それらの調製方法及び医薬組成物としてのそれらの使用
JPH06298759A (ja) ベンゾピラン化合物

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20121102

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20121102

A977 Report on retrieval

Free format text: JAPANESE INTERMEDIATE CODE: A971007

Effective date: 20140203

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20140212

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20140507

A602 Written permission of extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A602

Effective date: 20140514

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20140610

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: 20140708

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20140718

R150 Certificate of patent or registration of utility model

Ref document number: 5584696

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

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

LAPS Cancellation because of no payment of annual fees