CN104918939B - 人磷脂酰肌醇3-激酶δ的嘌呤抑制剂 - Google Patents

人磷脂酰肌醇3-激酶δ的嘌呤抑制剂 Download PDF

Info

Publication number
CN104918939B
CN104918939B CN201380070648.XA CN201380070648A CN104918939B CN 104918939 B CN104918939 B CN 104918939B CN 201380070648 A CN201380070648 A CN 201380070648A CN 104918939 B CN104918939 B CN 104918939B
Authority
CN
China
Prior art keywords
methyl
oxy
ethyl
purine
pyrrolidin
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
CN201380070648.XA
Other languages
English (en)
Chinese (zh)
Other versions
CN104918939A (zh
Inventor
A.A.阿查布
M.D.阿尔特曼
Y.邓
T.古兹
S.卡塔
J.D.卡茨
J.L.梅索特
H.周
M.麦克戈万
M.P.克里斯托弗
Y.加西亚
N.J.安东尼
F.X.弗拉德拉利纳斯
C.穆
S.张
R.张
K.C.冯
X.冷
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 Sharp and Dohme LLC
Original Assignee
Merck Sharp and Dohme LLC
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 Sharp and Dohme LLC filed Critical Merck Sharp and Dohme LLC
Publication of CN104918939A publication Critical patent/CN104918939A/zh
Application granted granted Critical
Publication of CN104918939B publication Critical patent/CN104918939B/zh
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • 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
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
    • C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
    • C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
    • C07D473/28—Oxygen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
    • C07D473/28—Oxygen atom
    • C07D473/30—Oxygen atom attached in position 6, e.g. hypoxanthine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
    • C07D473/36—Sulfur atom
    • C07D473/38—Sulfur atom attached in position 6
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Pulmonology (AREA)
  • Rheumatology (AREA)
  • Transplantation (AREA)
  • Pain & Pain Management (AREA)
  • Dermatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CN201380070648.XA 2012-11-16 2013-11-15 人磷脂酰肌醇3-激酶δ的嘌呤抑制剂 Expired - Fee Related CN104918939B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201261727416P 2012-11-16 2012-11-16
US61/727416 2012-11-16
PCT/CN2013/001394 WO2014075392A1 (en) 2012-11-16 2013-11-15 Purine inhibitors of human phosphatidylinositol 3-kinase delta

Publications (2)

Publication Number Publication Date
CN104918939A CN104918939A (zh) 2015-09-16
CN104918939B true CN104918939B (zh) 2018-08-28

Family

ID=50730541

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201380070648.XA Expired - Fee Related CN104918939B (zh) 2012-11-16 2013-11-15 人磷脂酰肌醇3-激酶δ的嘌呤抑制剂

Country Status (11)

Country Link
US (1) US9730940B2 (enExample)
EP (1) EP2920171B1 (enExample)
JP (1) JP6297582B2 (enExample)
KR (1) KR20150082613A (enExample)
CN (1) CN104918939B (enExample)
AU (1) AU2013347538B2 (enExample)
BR (1) BR112015011148A8 (enExample)
CA (1) CA2891009A1 (enExample)
MX (1) MX2015006191A (enExample)
RU (1) RU2658006C2 (enExample)
WO (1) WO2014075392A1 (enExample)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW201444821A (zh) 2013-03-13 2014-12-01 Janssen Pharmaceutica Nv 經取代之哌啶化合物及其作為食慾素受體調節劑之用途
TWI621618B (zh) 2013-03-13 2018-04-21 比利時商健生藥品公司 經取代２－氮雜雙環類及其作為食慾素受體調控劑之用途
TW201444849A (zh) 2013-03-13 2014-12-01 Janssen Pharmaceutica Nv 經取代的7-氮雜雙環類及其作為食慾激素受體調節劑之用途
NZ720092A (en) 2013-12-05 2019-05-31 Pfizer Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides
US10100047B2 (en) * 2014-03-06 2018-10-16 Shanghai Haiyan Pharmaceutical Technology Co., Ltd. Piperidine derivatives as orexin receptor antagonist
CN104030998B (zh) * 2014-06-05 2015-11-18 华东师范大学 4-多氟烷基-4，5-二取代异噁唑衍生物及其制备方法
WO2016020784A1 (en) 2014-08-05 2016-02-11 Pfizer Inc. N-acylpyrrolidine ether tropomyosin-related kinase inhibitors
AU2015314851B2 (en) 2014-09-11 2020-01-02 Janssen Pharmaceutica Nv Substituted 2-azabicycles and their use as orexin receptor modulators
JP6783230B2 (ja) * 2014-10-10 2020-11-11 ジェネンテック， インコーポレイテッド ヒストンデメチラーゼのインヒビターとしてのピロリドンアミド化合物
EP3411375B1 (en) * 2016-02-04 2020-08-05 Chiesi Farmaceutici S.p.A. Pyrazole derivatives as phosphoinositide 3-kinases inhibitors
WO2017166104A1 (en) * 2016-03-30 2017-10-05 Merck Sharp & Dohme Corp. Purine inhibitors of human phosphatidylinositol 3-kinase delta
ES2872003T3 (es) * 2016-09-14 2021-11-02 Janssen Pharmaceutica Nv Inhibidores espirobicíclicos de la interacción de menina-MLL
US10494370B2 (en) 2017-08-16 2019-12-03 Bristol-Myers Squibb Company Toll-like receptor 7 (TLR7) agonists having a pyridine or pyrazine moiety, conjugates thereof, and methods and uses therefor
MX2022007652A (es) 2019-12-19 2022-09-23 Janssen Pharmaceutica Nv Derivados espiráncos sustituidos de cadena lineal.
CN113620976B (zh) * 2020-05-09 2023-09-26 中国医学科学院药物研究所 噻唑并嘧啶类化合物及其制备方法、用途和药物组合物
CN117203212A (zh) * 2021-03-29 2023-12-08 株式会社钟化 (2-甲基嘧啶-5-基)硼酸衍生物的制造方法
CN113072480B (zh) * 2021-04-13 2022-09-30 常州佳德医药科技有限公司 一种手性(-)-5-氮杂螺[2.4]庚烷-7-醇、制备方法及应用
WO2024083237A1 (en) * 2022-10-20 2024-04-25 Impact Therapeutics (Shanghai) , Inc Substituted heteroaryl bicyclic compounds as usp1 inhibitors and the use thereof

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0421819A1 (en) * 1989-10-06 1991-04-10 The Wellcome Foundation Limited Therapeutic nucleosides

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5670501A (en) 1994-09-01 1997-09-23 Discovery Therapeutics, Inc. N-substituted 9-alkyladenines
KR100785363B1 (ko) * 2000-04-25 2007-12-18 이코스 코포레이션 인간 포스파티딜-이노시톨 3-키나제 델타의 억제제
EP2682397B1 (en) * 2000-07-21 2017-04-19 Gilead Sciences, Inc. Prodrugs of phosphonate nucleotide analogues and methods for selecting and making same
SE0300456D0 (sv) * 2003-02-19 2003-02-19 Astrazeneca Ab Novel compounds
KR20060021881A (ko) * 2003-06-12 2006-03-08 노보 노르디스크 에이/에스 호르몬 민감성 리파제의 억제제로서의 사용을 위한 치환된피페리딘 카르바메이트
EP1751159A2 (en) 2004-04-28 2007-02-14 Cv Therapeutics, Inc. Purine derivatives as a1 adenosine receptor antagonists
US8008307B2 (en) * 2006-08-08 2011-08-30 Millennium Pharmaceuticals, Inc. Heteroaryl compounds useful as inhibitors of E1 activating enzymes
BRPI0715176A8 (pt) * 2006-08-08 2018-04-10 Millennium Pharm Inc compostos de heteroarila utéis como inibidores de enzimas de ativação e1
WO2010005558A2 (en) * 2008-07-07 2010-01-14 Xcovery, Inc. Pi3k isoform selective inhibitors
US8759359B2 (en) 2009-12-18 2014-06-24 Incyte Corporation Substituted heteroaryl fused derivatives as PI3K inhibitors
MX2012015143A (es) * 2010-06-30 2013-07-03 Amgen Inc Compuestos heterociclicos que contienen nitrogeno como inhibidores de pi3k delta.
UA112517C2 (uk) * 2010-07-06 2016-09-26 Новартіс Аг Тетрагідропіридопіримідинові похідні
ES2612503T3 (es) * 2010-09-14 2017-05-17 Exelixis, Inc. Compuestos 9H-purina como inhibidores de PI3K-delta y métodos para su preparación
AU2011302196B2 (en) * 2010-09-14 2016-04-28 Exelixis, Inc. Inhibitors of PI3K-delta and methods of their use and manufacture
CN102838600A (zh) * 2011-06-24 2012-12-26 山东亨利医药科技有限责任公司 苯基喹唑啉类PI3Kδ抑制剂

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0421819A1 (en) * 1989-10-06 1991-04-10 The Wellcome Foundation Limited Therapeutic nucleosides

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
Experimental Evaluation of Potential Anticancer Agents I. Quantitative Therapeutic Evaluation of Certain Purine Analogs;FRANK M. SCHABEL et al.;《Cancer Research》;19610630;第21卷;690-699 *
Inhibition of Purine Ribonucleotide and Phosphoribosyl Pyrophosphate Synthesis by 6-CycIopentylthio-9-hydroxymethylpurine and Structurally Related Compounds;Camilla M. Smith et al.;《Cancer Research》;19740331;第34卷;463-467 *
Lipid-Soluble Derivatives of 6-Mercaptopurine;CARROLL TEMPLE et al.;《J. Med. Chem.》;19680131;第11卷;41-44 *
Novel 8-arylated purines as inhibitors of glycogen synthase kinase;Nada Ibrahim et al.;《European Journal of Medicinal Chemistry》;20100428;第45卷;3389-3393 *
RN 159627-91-5;ACS;《STN-Registry》;19941216;1 *
RN 159627-92-6;ACS;《STN-Registry》;19941216;1 *
Some Cyclization Reactions of 6-Mercaptopurine with Expected Biological Activity;A.Y. HASSAN;《Asian Journal of Chemistry》;20101231;第22卷(第1期);689-698 *

Also Published As

Publication number Publication date
CN104918939A (zh) 2015-09-16
US20150353552A1 (en) 2015-12-10
KR20150082613A (ko) 2015-07-15
WO2014075392A1 (en) 2014-05-22
AU2013347538A1 (en) 2015-05-07
EP2920171A4 (en) 2016-06-22
JP2015537010A (ja) 2015-12-24
US9730940B2 (en) 2017-08-15
EP2920171A1 (en) 2015-09-23
RU2658006C2 (ru) 2018-06-19
CA2891009A1 (en) 2014-05-22
EP2920171B1 (en) 2018-08-29
AU2013347538B2 (en) 2017-04-27
MX2015006191A (es) 2015-08-10
BR112015011148A2 (pt) 2017-07-11
BR112015011148A8 (pt) 2019-10-01
RU2015122895A (ru) 2017-01-10
JP6297582B2 (ja) 2018-03-20

Similar Documents

Publication Publication Date Title
CN104918939B (zh) 人磷脂酰肌醇3-激酶δ的嘌呤抑制剂
CN104918940B (zh) 人磷脂酰肌醇3‑激酶δ的嘌呤抑制剂
CN109983001B (zh) 作为变构shp2抑制剂的2,5-双取代型3-甲基吡嗪及2,5,6-三取代型3-甲基吡嗪
EP3154976B1 (en) Purine inhibitors of human phosphatidylinositol 3-kinase delta
ES2683309T3 (es) Cicloalquilnitrilpirazolpiridonas como inhibidores de janus cinasa
KR20170068585A (ko) 야누스 키나제 억제제로서의 에틸 N-Boc 피페리디닐 피라졸로 피리돈
CN105189508B (zh) 作为janus激酶抑制剂的环烷基腈吡唑并吡啶酮
WO2022134641A1 (zh) 芳香杂环类化合物、药物组合物及其应用
TW202241914A (zh) 吡唑并噻唑羧醯胺及其作為ｐｄｇｆｒ抑制劑之用途
JP2016514709A (ja) ヤヌスキナーゼ阻害剤としてのジェミナル置換シアノエチルピラゾロピリドン
CN105189497A (zh) 作为janus激酶抑制剂的n-(2-氰基杂环基)吡唑并吡啶酮
ES2415430T3 (es) 3-Aminociclopentanocarboxamidas como moduladores de receptores de quimioquinas
CN115873000B (zh) 异喹啉酮类及喹唑啉酮类化合物及其组合物和用途
EP3313397A1 (en) Purine inhibitors of human phosphatidylinositol 3-kinase delta
CN116802184A (zh) 吡唑并噻唑甲酰胺及其作为pdgfr抑制剂的用途
BR122024024795A2 (pt) 3-metil pirazinas 2,5-dissubstituídas e 3-metil pirazinas 2,5,6- trissubstituídas, composição farmacêutica e seus usos como inibidores de shp2 alostéricos
BR112019000494B1 (pt) 3-metil pirazinas 2,5-dissubstituídas e 3-metil pirazinas 2,5,6- trissubstituídas, composição farmacêutica e seus usos como inibidores de shp2 alostéricos
KR20150130310A (ko) 야누스 키나제 억제제로서의 같은자리 치환된 시아노에틸피라졸로 피리돈
CN105189498A (zh) 作为janus激酶抑制剂的孪位取代的氰基乙基吡唑并吡啶酮

Legal Events

Date Code Title Description
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20180828

Termination date: 20201115

CF01 Termination of patent right due to non-payment of annual fee