CN102905527B - 烟碱型乙酰胆碱受体调节剂 - Google Patents

烟碱型乙酰胆碱受体调节剂 Download PDF

Info

Publication number
CN102905527B
CN102905527B CN201180013438.8A CN201180013438A CN102905527B CN 102905527 B CN102905527 B CN 102905527B CN 201180013438 A CN201180013438 A CN 201180013438A CN 102905527 B CN102905527 B CN 102905527B
Authority
CN
China
Prior art keywords
compound
alkyl
substituted
aryl
hydrogen
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
CN201180013438.8A
Other languages
English (en)
Chinese (zh)
Other versions
CN102905527A (zh
Inventor
N.T.扎维里
F.蒋
L.托尔
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.)
Astraea Therapeutics LLC
Original Assignee
Astraea Therapeutics 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 Astraea Therapeutics LLC filed Critical Astraea Therapeutics LLC
Publication of CN102905527A publication Critical patent/CN102905527A/zh
Application granted granted Critical
Publication of CN102905527B publication Critical patent/CN102905527B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/439Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
    • 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
    • A61P25/04Centrally acting analgesics, e.g. opioids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16Anti-Parkinson drugs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/18Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • 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
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/30Drugs for disorders of the nervous system for treating abuse or dependence
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/30Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/32Alcohol-abuse
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/30Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/34Tobacco-abuse
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/30Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/36Opioid-abuse
    • 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
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D451/00Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
    • C07D451/14Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing 9-azabicyclo [3.3.1] nonane ring systems, e.g. granatane, 2-aza-adamantane; Cyclic acetals thereof
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D519/00Heterocyclic 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

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Addiction (AREA)
  • Psychiatry (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
CN201180013438.8A 2010-01-11 2011-01-11 烟碱型乙酰胆碱受体调节剂 Active CN102905527B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US29404410P 2010-01-11 2010-01-11
US61/294044 2010-01-11
PCT/US2011/020881 WO2011085389A1 (en) 2010-01-11 2011-01-11 Nicotinic acetylcholine receptor modulators

Publications (2)

Publication Number Publication Date
CN102905527A CN102905527A (zh) 2013-01-30
CN102905527B true CN102905527B (zh) 2016-08-24

Family

ID=44258996

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201180013438.8A Active CN102905527B (zh) 2010-01-11 2011-01-11 烟碱型乙酰胆碱受体调节剂

Country Status (9)

Country Link
US (4) US9062042B2 (enExample)
EP (1) EP2523562B1 (enExample)
JP (1) JP5840143B2 (enExample)
CN (1) CN102905527B (enExample)
CA (1) CA2787063C (enExample)
IL (1) IL220839B (enExample)
MX (1) MX2012008082A (enExample)
RU (1) RU2560729C2 (enExample)
WO (1) WO2011085389A1 (enExample)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011085389A1 (en) 2010-01-11 2011-07-14 Astraea Therapeutics, Llc Nicotinic acetylcholine receptor modulators
CN110804051B (zh) * 2019-10-17 2020-10-20 杭州励德生物科技有限公司 一种格拉司琼中间体的制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101291931A (zh) * 2005-09-30 2008-10-22 欧加农股份有限公司 作为单胺再摄取抑制剂的9-氮杂双环[3.3.1]壬烷衍生物
WO2009058120A1 (en) * 2007-11-02 2009-05-07 Sri International Nicotinic acetylcholine receptor modulators

Family Cites Families (59)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5198447A (en) 1986-11-21 1993-03-30 Glaxo Group Limited Medicaments
US5200413A (en) 1987-01-05 1993-04-06 Beecham Group P.L.C. Indolyl carboxamides useful treating migraine, cluster headache, trigeminal neuralgia or emesis
US4835162A (en) 1987-02-12 1989-05-30 Abood Leo G Agonists and antagonists to nicotine as smoking deterents
EP0287196B1 (en) 1987-02-18 1994-11-23 Beecham Group Plc Indole derivatives, process for their preparation and pharmaceutical compositions containing them
DE3822792C2 (de) 1987-07-11 1997-11-27 Sandoz Ag Neue Verwendung von 5HT¶3¶-Antagonisten
US5223511A (en) 1987-09-23 1993-06-29 Boehringer Ingelheim Italia S.P.A. Benzimidazoline-2-oxo-1-carboxylic acid compounds useful as 5-HT receptor antagonists
EP0315390B1 (en) 1987-11-04 1994-07-20 Beecham Group Plc Novel 4-oxobenzotriazines and 4-oxoquinazolines
GB2236751B (en) 1989-10-14 1993-04-28 Wyeth John & Brother Ltd Heterocyclic compounds
US5446050A (en) 1989-11-17 1995-08-29 Pfizer Inc. Azabicyclo amides and esters as 5-HT3 receptor antagonists
JP3122671B2 (ja) 1990-05-23 2001-01-09 協和醗酵工業株式会社 複素環式化合物
JP3087763B2 (ja) * 1990-11-30 2000-09-11 三井化学株式会社 新規な複素環式化合物およびそれを含有する医薬組成物
US5491148A (en) 1991-04-26 1996-02-13 Syntex (U.S.A.) Inc. Isoquinolinone and dihydroisoquinolinone 5-HT3 receptor antagonists
PH30413A (en) 1992-03-26 1997-05-09 Boehringer Ingelheim Italia Crystalline forms of endo-2,3-dihydro-n-(8-methyl)-8-azabicyclo-(3,2,1)oct-3-yl)-2-oxo-1h-benzimidazole-1-carboxamides
US5280028A (en) 1992-06-24 1994-01-18 G. D. Searle & Co. Benzimidazole compounds
HUT74949A (en) 1993-09-10 1997-03-28 Cytomed Epibatidine and derivatives thereof as cholinergic receptor agonists and antagonists
US5399562A (en) 1994-02-04 1995-03-21 G. D. Searle & Co. Indolones useful as serotonergic agents
US6117889A (en) 1994-04-01 2000-09-12 University Of Virginia 7-Azabicyclo-[2.2.1]-heptane and -heptene derivatives as analgesics and anti-inflammatory agents
GB9410441D0 (en) 1994-05-25 1994-07-13 Erba Carlo Spa Azabicycloakyl derivatives of imidazo (1,5-a) indol-3-one and process for their preparation
CA2220768A1 (en) 1996-03-13 1997-09-18 Yale University Smoking cessation treatments using naltrexone and related compounds
EE04057B1 (et) 1997-05-30 2003-06-16 Neurosearch A/S 8-asabitsüklo[3,2,1]okt-2-eeni ja -oktaani derivaadid, nende valmistamismeetod, kasutamine ja farmatseutiline kompositsioon
WO1998054182A1 (en) 1997-05-30 1998-12-03 Neurosearch A/S 9-AZABICYCLO(3.3.1)NON-2-ENE AND NONANE DERIVATIVES AS CHOLINERGIC LIGANDS AT NICOTINIC ACh RECEPTORS
JP4570773B2 (ja) 1997-10-27 2010-10-27 ニューロサーチ、アクティーゼルスカブ ニコチン性アセチルコリンレセプターに於けるコリン作動性リガンドとしてのヘテロアリールジアザシクロアルカン
JP2002501891A (ja) 1998-01-29 2002-01-22 セプラコア インコーポレーテッド 光学的に純粋な(+)−ビュープロピオンの医薬用途
IT1303123B1 (it) 1998-10-13 2000-10-30 Rotta Research Lab Derivati basici di benz(e)isoindol-1-oni e pirrolo(3,4-c)chinolin-1-oni ad attivita' 5ht3 antagonista, loro preparazione ed
NZ510287A (en) 1998-11-27 2003-05-30 Neurosearch As 8-azabicyclo[3.2.1]oct-2-ene and -octane derivatives useful as cholinergic ligands at the nicotinic acetyl choline receptor
FR2788982B1 (fr) 1999-02-02 2002-08-02 Synthelabo Compositions pharmaceutiques contenant de la nicotine et leur application dans le sevrage tabagique
DE10045112A1 (de) 2000-09-11 2002-03-21 Merck Patent Gmbh Verwendung von Indolderivaten zur Behandlung von Erkrankungen des zentralen Nervensystems
IL158484A0 (en) 2001-04-18 2004-05-12 Euro Celtique Sa Nociceptin analogs
US7199147B2 (en) * 2001-06-12 2007-04-03 Dainippon Sumitomo Pharma Co., Ltd. Rho kinase inhibitors
AR036040A1 (es) 2001-06-12 2004-08-04 Upjohn Co Compuestos de heteroarilo multiciclicos sustituidos con quinuclidinas y composiciones farmaceuticas que los contienen
AR036041A1 (es) 2001-06-12 2004-08-04 Upjohn Co Compuestos aromaticos heterociclicos sustituidos con quinuclidina y composiciones farmaceuticas que los contienen
US7642278B2 (en) 2001-07-03 2010-01-05 Novartis Vaccines And Diagnostics, Inc. Indazole benzimidazole compounds
BR0212477A (pt) 2001-09-12 2004-08-24 Upjohn Co 7-aza[2.2.1] bicicloheptanos substituìdos para o tratamento de doenças
US6951849B2 (en) 2001-10-02 2005-10-04 Acadia Pharmaceuticals Inc. Benzimidazolidinone derivatives as muscarinic agents
MXPA04003007A (es) 2001-10-02 2004-07-15 Upjohn Co Compuestos azabiciclico sustituidos condensados con heteroarilo para el tratamiento de enfermedades.
US6849620B2 (en) 2001-10-26 2005-02-01 Pfizer Inc N-(azabicyclo moieties)-substituted hetero-bicyclic aromatic compounds for the treatment of disease
MXPA04004464A (es) 2001-11-08 2004-08-11 Upjohn Co Compuestos de heteroarilo sustituido con azabiciclo para el tratamiento de enfermedades.
WO2003042210A1 (en) 2001-11-09 2003-05-22 Pharmacia & Upjohn Company Azabicyclic-phenyl-fused-heterocyclic compounds and their use as alpha7 nachr ligands
US6852716B2 (en) 2002-02-15 2005-02-08 Pfizer Inc Substituted-aryl compounds for treatment of disease
WO2003070731A2 (en) 2002-02-19 2003-08-28 Pharmacia & Upjohn Company Azabicyclic compounds for the treatment of disease
WO2003070732A1 (en) 2002-02-19 2003-08-28 Pharmacia & Upjohn Company Fused bicyclic-n-bridged-heteroaromatic carboxamides for the treatment of disease
US7176198B2 (en) 2002-08-01 2007-02-13 Pfizer Inc. 1H-pyrazole and 1H-pyrrole-azabicyclic compounds for the treatment of disease
JP2006506395A (ja) 2002-11-01 2006-02-23 ファルマシア・アンド・アップジョン・カンパニー・エルエルシー CNS疾患の治療のための、α7ニコチンアゴニスト活性及び5HT3アンタゴニスト活性を有する化合物
AU2003283648A1 (en) 2002-12-06 2004-06-30 Pharmacia & Upjohn Company Llc Compounds as radioligands for the diagnosis of disease
PT1678172E (pt) 2003-10-15 2010-03-03 Targacept Inc Composições farmacêuticas e métodos para alívio da dor e tratamento de perturbações do sistema nervoso central
WO2005060947A2 (en) 2003-12-19 2005-07-07 Sri International Agonist and antagonist ligands of the nociceptin receptor
BRPI0417323A (pt) 2003-12-22 2007-03-27 Memory Pharm Corp indóis, 1h-indazóis, 1,2-benzisoxazóis, e 1,2-benzisotiazóis, composto, composição farmacêutica e usos dos mesmos
JP2007534692A (ja) 2004-04-22 2007-11-29 メモリー・ファーマシューティカルズ・コーポレイション インドール、1h−インダゾール、1,2−ベンズイソキサゾール、1,2−ベンゾイソチアゾール、ならびにその調製および使用
DE602005027452D1 (de) 2004-05-07 2011-05-26 Memory Pharm Corp 1h-indazole, benzothiazole, 1,2-benzisoxazole, 1,2-benzisothiazole und chromone und deren herstellung und verwendungen
EP1831215A1 (en) 2004-11-23 2007-09-12 Ranbaxy Laboratories Limited Pyrido[2,3-d]pyrimidines as anti-inflamatory agents
US7868017B2 (en) * 2005-09-30 2011-01-11 N.V. Organon 9-azabicyclo[3.3.1]nonane derivatives
BRPI0616667B1 (pt) * 2005-10-06 2017-07-18 Nippon Soda Co. , Ltd. Compounds of cyclical amine or salts thereof or non-oxides thereof, and agents for control of fever
BRPI0716069A2 (pt) 2006-08-07 2013-09-17 Albany Molecular Res Inc composto, composiÇço farmacÊutica, e, mÉtodo para tratar um distérbio
GB0719644D0 (en) * 2007-10-05 2007-11-14 Cancer Rec Tech Ltd Therapeutic compounds and their use
US8697722B2 (en) 2007-11-02 2014-04-15 Sri International Nicotinic acetylcholine receptor modulators
WO2009067579A1 (en) 2007-11-21 2009-05-28 Abbott Laboratories Biaryl substituted azabicyclic alkane derivatives as nicotinic acetylcholine receptor activity modulators
PL2356113T3 (pl) 2008-11-14 2015-06-30 Bayer Ip Gmbh Heterocyklicznie podstawione związki arylowe jako inhibitory HIF
EP2415765A4 (en) 2009-03-30 2012-08-15 Astellas Pharma Inc PYRIMIDINE COMPOUND
WO2011085389A1 (en) 2010-01-11 2011-07-14 Astraea Therapeutics, Llc Nicotinic acetylcholine receptor modulators

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101291931A (zh) * 2005-09-30 2008-10-22 欧加农股份有限公司 作为单胺再摄取抑制剂的9-氮杂双环[3.3.1]壬烷衍生物
WO2009058120A1 (en) * 2007-11-02 2009-05-07 Sri International Nicotinic acetylcholine receptor modulators

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
A structural model of agonist binding to the α3β4 neuronal nicotinic receptor;Valeria Costa et al;《British Journal of Pharmacology》;20031231;第140卷(第5期);第921-931页 *
Synthesis and structural and conformational study of some amines derived from the norgranatane system;M.J.Fernandez et al;《Journal of Molecular Structure》;19910101;第246卷(第3/04期);第360页 Scheme 1 *

Also Published As

Publication number Publication date
US20170224665A1 (en) 2017-08-10
IL220839A0 (en) 2012-08-30
US9062042B2 (en) 2015-06-23
US10085975B2 (en) 2018-10-02
EP2523562B1 (en) 2019-01-02
US20150148541A1 (en) 2015-05-28
RU2012129257A (ru) 2014-02-20
EP2523562A1 (en) 2012-11-21
US9670198B2 (en) 2017-06-06
CN102905527A (zh) 2013-01-30
EP2523562A4 (en) 2013-04-17
RU2560729C2 (ru) 2015-08-20
CA2787063C (en) 2018-11-27
JP2013516496A (ja) 2013-05-13
MX2012008082A (es) 2013-02-07
US20180318270A1 (en) 2018-11-08
US20110172264A1 (en) 2011-07-14
JP5840143B2 (ja) 2016-01-06
IL220839B (en) 2018-07-31
CA2787063A1 (en) 2011-07-14
WO2011085389A1 (en) 2011-07-14

Similar Documents

Publication Publication Date Title
US7001900B2 (en) Azabicyclic compounds for the treatment of disease
JP6856532B2 (ja) エルゴリン化合物およびその使用
MX2013015373A (es) Nuevos analogos de fluoroergolina.
JP7821835B2 (ja) ピペリジニルノシセプチン受容体化合物
AU2012382929A1 (en) Novel cabergoline derivatives
US20240059664A1 (en) Piperidinyl Nociceptin Receptor Compounds
JP2016503795A (ja) 新規メチセルジド誘導体
AU2013361343A1 (en) Fluoroergoline derivatives and uses thereof
CN102905527B (zh) 烟碱型乙酰胆碱受体调节剂
AU2016209490B2 (en) Isoergoline compounds and uses thereof
HK40117531A (en) Piperidinyl nociceptin receptor compounds

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant