CA2777114C - Hydroxyl, keto, and glucuronide derivatives of 3-(4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl)-3-cyclopentylpropanenitrile - Google Patents

Hydroxyl, keto, and glucuronide derivatives of 3-(4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl)-3-cyclopentylpropanenitrile Download PDF

Info

Publication number
CA2777114C
CA2777114C CA2777114A CA2777114A CA2777114C CA 2777114 C CA2777114 C CA 2777114C CA 2777114 A CA2777114 A CA 2777114A CA 2777114 A CA2777114 A CA 2777114A CA 2777114 C CA2777114 C CA 2777114C
Authority
CA
Canada
Prior art keywords
cyclopentylpropanenitrile
pyrrolo
pyrazol
pyrimidin
keto
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
CA2777114A
Other languages
English (en)
French (fr)
Other versions
CA2777114A1 (en
Inventor
James D. Rodgers
Adam Shilling
Argyrios G. Arvanitis
Stacey Shepard
Laurine G. Galya
Mei Li
Frank M. Nedza
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.)
Incyte Holdings Corp
Original Assignee
Incyte Holdings Corp
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 Incyte Holdings Corp filed Critical Incyte Holdings Corp
Publication of CA2777114A1 publication Critical patent/CA2777114A1/en
Application granted granted Critical
Publication of CA2777114C publication Critical patent/CA2777114C/en
Active 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A61K31/4155—1,2-Diazoles non 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
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • 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
    • 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
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • 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
    • 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
    • A61P17/06—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
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • 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
    • A61P25/28—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
    • 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
    • A61P3/08—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
    • A61P31/12—Antivirals
    • 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
    • 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
    • A61P37/06—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
    • 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
    • A61P5/00—Drugs for disorders of the endocrine 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
    • 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
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/26—Acyclic or carbocyclic radicals, substituted by hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
    • C07H17/02—Heterocyclic radicals containing only nitrogen as ring hetero atoms

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Diabetes (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Endocrinology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Neurosurgery (AREA)
  • Hematology (AREA)
  • Dermatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Oncology (AREA)
  • Rheumatology (AREA)
  • Cardiology (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Pain & Pain Management (AREA)
  • Communicable Diseases (AREA)
  • Reproductive Health (AREA)
  • Urology & Nephrology (AREA)
  • Virology (AREA)
CA2777114A 2009-10-09 2010-10-08 Hydroxyl, keto, and glucuronide derivatives of 3-(4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl)-3-cyclopentylpropanenitrile Active CA2777114C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US25038709P 2009-10-09 2009-10-09
US61/250,387 2009-10-09
US31621810P 2010-03-22 2010-03-22
US61/316,218 2010-03-22
PCT/US2010/052011 WO2011044481A1 (en) 2009-10-09 2010-10-08 Hydroxyl, keto, and glucuronide derivatives of 3-(4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl)-3-cyclopentylpropanenitrile

Publications (2)

Publication Number Publication Date
CA2777114A1 CA2777114A1 (en) 2011-04-14
CA2777114C true CA2777114C (en) 2018-10-23

Family

ID=43037845

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2777114A Active CA2777114C (en) 2009-10-09 2010-10-08 Hydroxyl, keto, and glucuronide derivatives of 3-(4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl)-3-cyclopentylpropanenitrile

Country Status (13)

Country Link
US (3) US8486902B2 (enExample)
EP (1) EP2486041B1 (enExample)
JP (3) JP5946768B2 (enExample)
KR (3) KR20180126619A (enExample)
CN (2) CN102596960B (enExample)
BR (1) BR112012008267B1 (enExample)
CA (1) CA2777114C (enExample)
EA (1) EA021478B1 (enExample)
ES (1) ES2435491T3 (enExample)
MX (1) MX2012004180A (enExample)
PL (1) PL2486041T3 (enExample)
PT (1) PT2486041E (enExample)
WO (1) WO2011044481A1 (enExample)

Families Citing this family (69)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103214484B (zh) 2005-12-13 2016-07-06 因塞特控股公司 作为两面神激酶抑制剂的杂芳基取代的吡咯并[2,3-b]吡啶和吡咯并[2,3-b]嘧啶
CL2008001709A1 (es) 2007-06-13 2008-11-03 Incyte Corp Compuestos derivados de pirrolo [2,3-b]pirimidina, moduladores de quinasas jak; composicion farmaceutica; y uso en el tratamiento de enfermedades tales como cancer, psoriasis, artritis reumatoide, entre otras.
HUE029236T2 (en) 2007-06-13 2017-02-28 Incyte Holdings Corp (R) -3- (4- (7H-Pyrrolo [2,3-d] pyrimidin-4-yl) -1H-pyrazol-1-yl) -3-cyclopentylpropanenitrile Crystalline salts of Janus kinase inhibitor
CL2009001884A1 (es) * 2008-10-02 2010-05-14 Incyte Holdings Corp Uso de 3-ciclopentil-3-[4-(7h-pirrolo[2,3-d]pirimidin-4-il)-1h-pirazol-1-il)propanonitrilo, inhibidor de janus quinasa, y uso de una composición que lo comprende para el tratamiento del ojo seco.
PE20211639A1 (es) 2009-01-15 2021-08-24 Incyte Holdings Corp Procesos para preparar inhibidores de jak y compuestos intermediarios relacionado
MY156727A (en) * 2009-05-22 2016-03-15 Incyte Corp N-(hetero)aryl-pyrrolidine derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines and pyrrol-3-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors
EP2432472B1 (en) 2009-05-22 2019-10-02 Incyte Holdings Corporation 3-[4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl]octane- or heptane-nitrile as jak inhibitors
TW201113285A (en) * 2009-09-01 2011-04-16 Incyte Corp Heterocyclic derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors
MX2012004180A (es) * 2009-10-09 2012-07-17 Incyte Corp Derivados de hidroxil, ceto y glucuronido de 3-(4-7h-pirrolo[2,3-d ]pirimidin-a-il)-1h-pirazol-1-il)-3-ciclopentilpropanonitrilo.
CA2790070C (en) * 2010-02-18 2018-03-06 Incyte Corporation Cyclobutane and methylcyclobutane derivatives as janus kinase inhibitors
EP3354652B1 (en) 2010-03-10 2020-05-06 Incyte Holdings Corporation Piperidin-4-yl azetidine derivatives as jak1 inhibitors
AR084691A1 (es) 2010-05-21 2013-06-05 Incyte Corp Formulacion de uso topico para un inhibidor de jak y metodo para tratar trastorno de la piel
WO2012068440A1 (en) 2010-11-19 2012-05-24 Incyte Corporation Heterocyclic-substituted pyrrolopyridines and pyrrolopyrimidines as jak inhibitors
CA2818542A1 (en) 2010-11-19 2012-05-24 Incyte Corporation Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as jak inhibitors
WO2012112847A1 (en) 2011-02-18 2012-08-23 Novartis Pharma Ag mTOR/JAK INHIBITOR COMBINATION THERAPY
MY165963A (en) 2011-06-20 2018-05-18 Incyte Holdings Corp Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as jak inhibitors
CA2844507A1 (en) 2011-08-10 2013-02-14 Novartis Pharma Ag Jak pi3k/mtor combination therapy
TW201313721A (zh) 2011-08-18 2013-04-01 Incyte Corp 作為ｊａｋ抑制劑之環己基氮雜環丁烷衍生物
UA111854C2 (uk) 2011-09-07 2016-06-24 Інсайт Холдінгс Корпорейшн Способи і проміжні сполуки для отримання інгібіторів jak
CA3131037A1 (en) 2011-11-30 2013-06-06 Emory University Antiviral jak inhibitors useful in treating or preventing retroviral and other viral infections
TW201406761A (zh) 2012-05-18 2014-02-16 Incyte Corp 做爲ｊａｋ抑制劑之哌啶基環丁基取代之吡咯并吡啶及吡咯并嘧啶衍生物
CA2879603A1 (en) 2012-07-27 2014-01-30 Ratiopharm Gmbh Oral dosage forms for modified release comprising ruxolitinib
JP6359546B2 (ja) 2012-11-01 2018-07-18 インサイト・ホールディングス・コーポレイションＩｎｃｙｔｅ Ｈｏｌｄｉｎｇｓ Ｃｏｒｐｏｒａｔｉｏｎ Ｊａｋ阻害薬としての三環式縮合チオフェン誘導体
TWI761825B (zh) 2012-11-15 2022-04-21 美商英塞特控股公司 盧梭利替尼之緩釋性劑型
US20160123982A1 (en) 2013-02-04 2016-05-05 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for assaying jak2 activity in red blood cells and uses thereof
MX384910B (es) 2013-03-06 2025-03-14 Incyte Holdings Corp Procesos e intermedios para hacer un inhibidor de jak.
PE20200527A1 (es) 2013-05-17 2020-03-09 Incyte Corp Derivados del bipirazol como inhibidores jak
SG11201600815WA (en) 2013-08-07 2016-03-30 Incyte Corp Sustained release dosage forms for a jak1 inhibitor
BR112016025427A2 (pt) 2014-04-30 2017-08-15 Incyte Corp processos de preparação de um inibidor de jak1 e formas do mesmo
WO2015184305A1 (en) 2014-05-30 2015-12-03 Incyte Corporation TREATMENT OF CHRONIC NEUTROPHILIC LEUKEMIA (CNL) AND ATYPICAL CHRONIC MYELOID LEUKEMIA (aCML) BY INHIBITORS OF JAK1
JP6149810B2 (ja) * 2014-06-13 2017-06-21 株式会社島津製作所 代謝物解析システム及び代謝物解析方法
RS62713B1 (sr) 2014-08-11 2022-01-31 Acerta Pharma Bv Terapeutske kombinacije btk inhibitora i bcl-2 inhibitora
HRP20220738T1 (hr) 2014-08-11 2022-08-19 Acerta Pharma B.V. Terapijske kombinacije inhibitora btk, inhibitora pd-1 i/ili inhibitora pd-l1
US20170224819A1 (en) 2014-08-11 2017-08-10 Acerta Pharma B.V. Therapeutic Combinations of a BTK Inhibitor, a PI3K Inhibitor, a JAK-2 Inhibitor, and/or a CDK 4/6 Inhibitor
CN105777754B (zh) * 2014-12-16 2019-07-26 北京赛林泰医药技术有限公司 吡咯并嘧啶化合物
US10435428B2 (en) 2015-11-24 2019-10-08 Theravance Biopharma R&D Ip, Llc Prodrugs of a JAK inhibitor compound for treatment of gastrointestinal inflammatory disease
CN107513067A (zh) * 2016-06-16 2017-12-26 北京赛林泰医药技术有限公司 含有取代环戊基的吡咯并嘧啶化合物
CN107759623B (zh) * 2016-08-23 2020-08-14 苏州旺山旺水生物医药有限公司 Jak抑制剂的中间体及其制备方法
WO2018165250A1 (en) 2017-03-08 2018-09-13 Theravance Biopharma R&D Ip, Llc Glucuronide prodrugs of tofacitinib
WO2018167283A1 (en) 2017-03-17 2018-09-20 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for the diagnosis and treatment of pancreatic ductal adenocarcinoma associated neural remodeling
EP3610264A1 (en) 2017-04-13 2020-02-19 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for the diagnosis and treatment of pancreatic ductal adenocarcinoma
CN108794480A (zh) * 2017-04-28 2018-11-13 天津药物研究院有限公司 吡咯并嘧啶类化合物、其制备方法和用途
JP2020520955A (ja) * 2017-05-23 2020-07-16 セラヴァンス バイオファーマ アール＆ディー アイピー， エルエルシー ヤヌスキナーゼ阻害剤のグルクロニドプロドラッグ
EP3609903A1 (en) 2017-05-23 2020-02-19 Theravance Biopharma R&D IP, LLC Thiocarbamate prodrugs of tofacitinib
US10596161B2 (en) 2017-12-08 2020-03-24 Incyte Corporation Low dose combination therapy for treatment of myeloproliferative neoplasms
JP7393348B2 (ja) 2018-01-30 2023-12-06 インサイト・コーポレイション （１－（３－フルオロ－２（トリフルオロメチル）イソニコチニル）ピぺリジン―４－オン）を作製するためのプロセス及び中間体
UA127519C2 (uk) 2018-02-16 2023-09-20 Інсайт Корпорейшн Інгібітори шляху jak1, призначені для лікування порушень, пов'язаних із цитокінами
JP7565798B2 (ja) 2018-03-30 2024-10-11 インサイト・コーポレイション 炎症性皮膚疾患のバイオマーカー
CN113768934A (zh) 2018-03-30 2021-12-10 因赛特公司 使用jak抑制剂治疗化脓性汗腺炎
MX2020010815A (es) 2018-04-13 2020-12-11 Incyte Corp Biomarcadores para enfermedad de injerto contra hospedero.
CA3224985C (en) 2018-07-31 2025-11-18 Loxo Oncology, Inc. SPRAY-DRIED DISPERSIONS, FORMULATIONS AND POLYMORPHIES OF (S)-5-AMINO-3-(4-((5-FLUORO-2-METHOXYBENZAMIDO)METHYL)PHENYL)(1,1,1-TRIFLUOROPROPANE-2-YL)-1H-PYRAZOLE-4-CARBOXAMIDE
EP3847158A1 (en) * 2018-09-06 2021-07-14 Arena Pharmaceuticals, Inc. Compounds useful in the treatment of autoimmune and inflammatory disorders
EA202191170A1 (ru) 2018-10-31 2021-07-27 Инсайт Корпорейшн Комбинированная терапия для лечения гематологических заболеваний
WO2020092015A1 (en) 2018-11-02 2020-05-07 University Of Rochester Therapeutic mitigation of epithelial infection
CN113474337A (zh) 2018-12-19 2021-10-01 奥瑞生物药品公司 作为fgfr抑制剂用于治疗癌症的7-((3，5-二甲氧基苯基)氨基)喹喔啉衍生物
EP3898626A1 (en) 2018-12-19 2021-10-27 Array Biopharma, Inc. Substituted pyrazolo[1,5-a]pyridine compounds as inhibitors of fgfr tyrosine kinases
JP2022549506A (ja) 2019-09-27 2022-11-25 ディスク・メディシン・インコーポレイテッド 骨髄線維症および関連状態を処置するための方法
CN110538183B (zh) * 2019-10-09 2021-05-04 吉林大学 一种预防和治疗小儿湿疹的组合物及其制备方法
US12360120B2 (en) 2019-10-10 2025-07-15 Incyte Corporation Biomarkers for graft-versus-host disease
EP4041204A1 (en) 2019-10-10 2022-08-17 Incyte Corporation Biomarkers for graft-versus-host disease
BR112022009710A2 (pt) 2019-11-22 2022-08-09 Incyte Corp Terapia de combinação compreendendo um inibidor de alk2 e um inibidor de jak2
KR20230012539A (ko) 2020-05-13 2023-01-26 디스크 메디슨, 인크. 골수섬유증을 치료하기 위한 항-헤모주벨린 (hjv) 항체
JP7802696B2 (ja) 2020-06-02 2026-01-20 インサイト・コーポレイション Ｊａｋ１阻害剤の調製プロセス
US11833155B2 (en) 2020-06-03 2023-12-05 Incyte Corporation Combination therapy for treatment of myeloproliferative neoplasms
WO2022040172A1 (en) 2020-08-18 2022-02-24 Incyte Corporation Process and intermediates for preparing a jak1 inhibitor
CR20230129A (es) 2020-08-18 2023-07-13 Incyte Corp Proceso e intermediarios para preparar un inhibidor de jak
JP2023552452A (ja) 2020-12-08 2023-12-15 インサイト・コーポレイション 白斑治療用のｊａｋ１経路阻害薬
EP4696710A3 (en) 2021-05-03 2026-05-06 Incyte Corporation Jak1 pathway inhibitors for the treatment of prurigo nodularis
CA3226714A1 (en) 2021-07-12 2023-01-19 Incyte Corporation Process and intermediates for preparing baricitinib

Family Cites Families (73)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3036390A1 (de) 1980-09-26 1982-05-13 Troponwerke GmbH & Co KG, 5000 Köln Neue pyrrolo-pyrimidine, verfahren zu ihrer herstellung und ihre verwendung bei der herstellung von biologischen wirkstoffen
US5521184A (en) 1992-04-03 1996-05-28 Ciba-Geigy Corporation Pyrimidine derivatives and processes for the preparation thereof
DE69618959T2 (de) 1995-07-05 2002-08-29 E.I. Du Pont De Nemours And Co., Wilmington Pyrimidone und ihre verwendug als fungizide
EP0836605B1 (en) 1995-07-06 2002-02-06 Novartis AG Pyrrolopyrimidines and processes for the preparation thereof
US6232320B1 (en) 1998-06-04 2001-05-15 Abbott Laboratories Cell adhesion-inhibiting antiinflammatory compounds
KR20010052570A (ko) 1998-06-04 2001-06-25 스티븐 에프. 웨인스톡 세포 유착을 억제하는 소염성 화합물
PL198640B1 (pl) 1998-06-19 2008-07-31 Pfizer Prod Inc Związki pirolo[2,3-d]pirymidynowe, środek farmaceutyczny i zastosowanie tych związków
PA8474101A1 (es) 1998-06-19 2000-09-29 Pfizer Prod Inc Compuestos de pirrolo [2,3-d] pirimidina
EP1107964B8 (en) 1998-08-11 2010-04-07 Novartis AG Isoquinoline derivatives with angiogenesis inhibiting activity
US6133031A (en) 1999-08-19 2000-10-17 Isis Pharmaceuticals Inc. Antisense inhibition of focal adhesion kinase expression
GB9905075D0 (en) 1999-03-06 1999-04-28 Zeneca Ltd Chemical compounds
EA006227B1 (ru) * 1999-12-10 2005-10-27 Пфайзер Продактс Инк. СОЕДИНЕНИЯ ПИРРОЛО[2,3-d]ПИРИМИДИНА
EP1990343B1 (en) 1999-12-24 2012-04-04 Aventis Pharma Limited Azaindoles
GB0004890D0 (en) 2000-03-01 2000-04-19 Astrazeneca Uk Ltd Chemical compounds
US6335342B1 (en) 2000-06-19 2002-01-01 Pharmacia & Upjohn S.P.A. Azaindole derivatives, process for their preparation, and their use as antitumor agents
CA2413313C (en) 2000-06-23 2011-06-14 Mitsubishi Pharma Corporation Antitumor effect potentiators
EA006153B1 (ru) 2000-06-26 2005-10-27 Пфайзер Продактс Инк. СОЕДИНЕНИЯ ПИРРОЛО[2,3-d]ПИРИМИДИНА В КАЧЕСТВЕ ИММУНОДЕПРЕССАНТОВ
KR100786927B1 (ko) 2000-06-28 2007-12-17 스미스클라인비이참피이엘시이 습식 분쇄방법
GB0100622D0 (en) 2001-01-10 2001-02-21 Vernalis Res Ltd Chemical compounds V111
EP1363702A4 (en) 2001-01-30 2007-08-22 Cytopia Pty Ltd PROCESS FOR INHIBITING KINASES
US7301023B2 (en) 2001-05-31 2007-11-27 Pfizer Inc. Chiral salt resolution
AU2002355732B2 (en) 2001-08-01 2006-11-09 Merck Sharp & Dohme Corp. Benzimidazo[4,5-f]isoquinolinone derivatives
AU2002337142B2 (en) 2001-09-19 2007-10-11 Aventis Pharma S.A. Indolizines as kinase protein inhibitors
IL161156A0 (en) 2001-10-30 2004-08-31 Novartis Ag Staurosporine derivatives as inhibitors of flt3 receptor tyrosine kinase activity
PY0228255A (es) 2001-12-06 2004-06-01 Pfizer Prod Inc Compuestos cristalinos novedosos
TW200403058A (en) 2002-04-19 2004-03-01 Bristol Myers Squibb Co Heterocyclo inhibitors of potassium channel function
TW200406374A (en) 2002-05-29 2004-05-01 Novartis Ag Diaryl urea derivatives useful for the treatment of protein kinase dependent diseases
GB0215676D0 (en) 2002-07-05 2002-08-14 Novartis Ag Organic compounds
US7259161B2 (en) 2002-11-04 2007-08-21 Vertex Pharmaceuticals Incorporated Compositions useful as inhibitors of JAK and other protein kinases
AR042052A1 (es) 2002-11-15 2005-06-08 Vertex Pharma Diaminotriazoles utiles como inhibidores de proteinquinasas
AU2003276591A1 (en) 2002-11-26 2004-06-18 Pfizer Products Inc. Method of treatment of transplant rejection
UA80767C2 (en) 2002-12-20 2007-10-25 Pfizer Prod Inc Pyrimidine derivatives for the treatment of abnormal cell growth
AU2004212421B2 (en) 2003-02-07 2009-08-20 Vertex Pharmaceuticals Incorporated Heteroaryl substituted pyrolls useful as inhibitors of protein kinases
GB0305929D0 (en) 2003-03-14 2003-04-23 Novartis Ag Organic compounds
SE0301372D0 (sv) 2003-05-09 2003-05-09 Astrazeneca Ab Novel compounds
SE0301373D0 (sv) 2003-05-09 2003-05-09 Astrazeneca Ab Novel compounds
US20050043346A1 (en) 2003-08-08 2005-02-24 Pharmacia Italia S.P.A. Pyridylpyrrole derivatives active as kinase inhibitors
AR045944A1 (es) 2003-09-24 2005-11-16 Novartis Ag Derivados de isoquinolina 1.4-disustituidas
CA2545192A1 (en) 2003-11-25 2005-06-09 Pfizer Products Inc. Method of treatment of atherosclerosis
CA2549485A1 (en) 2003-12-17 2005-07-07 Pfizer Products Inc. Pyrrolo [2,3-d] pyrimidine compounds for treating transplant rejection
US20050187389A1 (en) 2004-01-13 2005-08-25 Ambit Biosciences Corporation Pyrrolopyrimidine derivatives and analogs and their use in the treatment and prevention of diseases
US7507826B2 (en) 2004-03-30 2009-03-24 Vertex Pharmaceuticals Incorporated Azaindoles useful as inhibitors of JAK and other protein kinases
WO2005105988A2 (en) 2004-04-28 2005-11-10 Vertex Pharmaceuticals Incorporated Crystal structure of human jak3 kinase domain complex and binding pockets thereof
WO2005105814A1 (en) 2004-04-28 2005-11-10 Incyte Corporation Tetracyclic inhibitors of janus kinases
MXPA06012663A (es) 2004-05-03 2007-01-16 Novartis Ag Combinaciones que comprenden un agonista del receptor s1p y un inhibidor de quinasa jak3.
JP2007537296A (ja) 2004-05-14 2007-12-20 アボット・ラボラトリーズ 治療薬としてのキナーゼ阻害薬
PE20060426A1 (es) 2004-06-02 2006-06-28 Schering Corp DERIVADOS DE ACIDO TARTARICO COMO INHIBIDORES DE MMPs, ADAMs, TACE Y TNF-alfa
WO2006013114A1 (en) 2004-08-06 2006-02-09 Develogen Aktiengesellschaft Use of a timp-2 secreted protein product for preventing and treating pancreatic diseases and/or obesity and/or metabolic syndrome
UY29177A1 (es) 2004-10-25 2006-05-31 Astex Therapeutics Ltd Derivados sustituidos de purina, purinona y deazapurina, composiciones que los contienen métodos para su preparación y sus usos
MY179032A (en) 2004-10-25 2020-10-26 Cancer Research Tech Ltd Ortho-condensed pyridine and pyrimidine derivatives (e.g.purines) as protein kinase inhibitors
KR20070085433A (ko) 2004-11-24 2007-08-27 노파르티스 아게 Ｊａｋ 저해제들과 ｂｃｒ-ａｂｌ, ｆｌｔ-3, ｆａｋ 또는ｒａｆ 키나제 저해제들 중 하나 이상의 조합물
AR054416A1 (es) 2004-12-22 2007-06-27 Incyte Corp Pirrolo [2,3-b]piridin-4-il-aminas y pirrolo [2,3-b]pirimidin-4-il-aminas como inhibidores de las quinasas janus. composiciones farmaceuticas.
JP2008528627A (ja) * 2005-01-31 2008-07-31 マイラン ラボラトリーズ インク． グルクロン酸化されたネビボロール代謝産物
EP1844050B1 (en) 2005-02-03 2009-01-14 Vertex Pharmaceuticals, Inc. Pyrrolopyrimidines useful as inhibitors of protein kinase
US7019626B1 (en) * 2005-03-03 2006-03-28 Omnitek Engineering, Inc. Multi-fuel engine conversion system and method
KR20080016659A (ko) 2005-05-20 2008-02-21 버텍스 파마슈티칼스 인코포레이티드 단백질 키나제의 억제제로서 유용한 피롤로피리딘
US20070049591A1 (en) 2005-08-25 2007-03-01 Kalypsys, Inc. Inhibitors of MAPK/Erk Kinase
EP2270014A1 (en) 2005-09-22 2011-01-05 Incyte Corporation Azepine inhibitors of janus kinases
JP2009513571A (ja) 2005-09-30 2009-04-02 バーテックス ファーマシューティカルズ インコーポレイテッド ヤヌスキナーゼ阻害剤として有用なデアザプリン
CN103214484B (zh) * 2005-12-13 2016-07-06 因塞特控股公司 作为两面神激酶抑制剂的杂芳基取代的吡咯并[2,3-b]吡啶和吡咯并[2,3-b]嘧啶
EP1968568A4 (en) 2005-12-22 2011-04-13 Glaxosmithkline Llc HEMMER OF NUTS ACTIVITY
TW201412738A (zh) 2006-01-17 2014-04-01 Vertex Pharma 適合作為傑納斯激酶（ｊａｎｕｓ ｋｉｎａｓｅ）抑制劑之氮雜吲哚
CA2648250A1 (en) * 2006-04-05 2007-10-18 Vertex Pharmaceuticals Incorporated Deazapurines useful as inhibitors of janus kinases
ES2415863T3 (es) 2006-12-22 2013-07-29 Incyte Corporation Heterociclos sustituidos como inhibidores de Janus Quinasas
HUE029236T2 (en) 2007-06-13 2017-02-28 Incyte Holdings Corp (R) -3- (4- (7H-Pyrrolo [2,3-d] pyrimidin-4-yl) -1H-pyrazol-1-yl) -3-cyclopentylpropanenitrile Crystalline salts of Janus kinase inhibitor
CL2008001709A1 (es) * 2007-06-13 2008-11-03 Incyte Corp Compuestos derivados de pirrolo [2,3-b]pirimidina, moduladores de quinasas jak; composicion farmaceutica; y uso en el tratamiento de enfermedades tales como cancer, psoriasis, artritis reumatoide, entre otras.
TWI444382B (zh) * 2008-03-11 2014-07-11 Incyte Corp 作為ｊａｋ抑制劑之氮雜環丁烷及環丁烷衍生物
CL2009001884A1 (es) * 2008-10-02 2010-05-14 Incyte Holdings Corp Uso de 3-ciclopentil-3-[4-(7h-pirrolo[2,3-d]pirimidin-4-il)-1h-pirazol-1-il)propanonitrilo, inhibidor de janus quinasa, y uso de una composición que lo comprende para el tratamiento del ojo seco.
PE20211639A1 (es) * 2009-01-15 2021-08-24 Incyte Holdings Corp Procesos para preparar inhibidores de jak y compuestos intermediarios relacionado
MY156727A (en) * 2009-05-22 2016-03-15 Incyte Corp N-(hetero)aryl-pyrrolidine derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines and pyrrol-3-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors
TW201113285A (en) * 2009-09-01 2011-04-16 Incyte Corp Heterocyclic derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors
MX2012004180A (es) * 2009-10-09 2012-07-17 Incyte Corp Derivados de hidroxil, ceto y glucuronido de 3-(4-7h-pirrolo[2,3-d ]pirimidin-a-il)-1h-pirazol-1-il)-3-ciclopentilpropanonitrilo.
CA2790070C (en) * 2010-02-18 2018-03-06 Incyte Corporation Cyclobutane and methylcyclobutane derivatives as janus kinase inhibitors

Also Published As

Publication number Publication date
EA201200565A1 (ru) 2012-09-28
EP2486041A1 (en) 2012-08-15
CN102596960A (zh) 2012-07-18
KR101921850B1 (ko) 2018-11-23
PL2486041T3 (pl) 2014-01-31
JP2013507390A (ja) 2013-03-04
JP2017226695A (ja) 2017-12-28
ES2435491T3 (es) 2013-12-19
CN105541847B (zh) 2019-08-16
JP5946768B2 (ja) 2016-07-06
CN105541847A (zh) 2016-05-04
KR101805936B1 (ko) 2017-12-07
US20130345157A1 (en) 2013-12-26
EA021478B1 (ru) 2015-06-30
US20140378400A1 (en) 2014-12-25
JP6251232B2 (ja) 2017-12-20
US9512161B2 (en) 2016-12-06
HK1174899A1 (en) 2013-06-21
CN102596960B (zh) 2016-01-20
JP2016056183A (ja) 2016-04-21
EP2486041B1 (en) 2013-08-14
KR20170098334A (ko) 2017-08-29
KR20120102604A (ko) 2012-09-18
CA2777114A1 (en) 2011-04-14
US20110086810A1 (en) 2011-04-14
PT2486041E (pt) 2013-11-14
AU2010303245A1 (en) 2012-05-10
US8486902B2 (en) 2013-07-16
MX2012004180A (es) 2012-07-17
US8748401B2 (en) 2014-06-10
BR112012008267A2 (enExample) 2021-11-03
WO2011044481A1 (en) 2011-04-14
BR112012008267B1 (pt) 2022-10-04
KR20180126619A (ko) 2018-11-27

Similar Documents

Publication Publication Date Title
MX2012004180A (es) Derivados de hidroxil, ceto y glucuronido de 3-(4-7h-pirrolo[2,3-d ]pirimidin-a-il)-1h-pirazol-1-il)-3-ciclopentilpropanonitrilo.
MX2010004576A (es) Derivados de pirimidina novedosos.
PH12012501346A1 (en) Heteroaryl compounds and uses thereof
WO2010077740A3 (en) Novel antiviral compounds, compositions, and methods of use
MX2009009773A (es) Sintesis de gamma-carbolinas fusionadas con heterociclo substituido.
WO2011031896A3 (en) Pi3 kinase inhibitors and uses thereof
SI2432472T1 (sl) 3-(4-(7H-pirolo(2,3-d)pirimidin-4-il)-1H-pirazol-1-il)oktan- ali heptan-nitril kot inhibitorji JAK
AU2009276339A8 (en) Pyrimidine compounds, compositions and methods of use
WO2008100805A3 (en) Anti-robo4 antibodies and uses therefor
ZA200807274B (en) Novel pyridine derivatives
WO2008144223A3 (en) Triazolyl aminopyrimidine compounds
AU2007329728A1 (en) 3-(dihydro-1H-pyrazolo (4,3-d) pyrimidin-5-yl)-4-propoxybenzenesulfonamide derivatives and methods of use
TN2009000446A1 (en) P70 s6 kinase inhibitors
WO2009042114A3 (en) Phenazine derivatives and uses thereof
WO2009015037A3 (en) 5-pyridinone substituted indazoles
JO2822B1 (en) Inhibitors of the enzyme kinase P70 S6 and AKT
WO2010054107A3 (en) Kinase knockdown via electrophilically enhanced inhibitors
TW200942530A (en) Pyridine compounds
WO2008027600A3 (en) Imatinib compositions
WO2009115084A3 (de) Pyrrolopyrimidin-derivate und deren verwendungen
MY185134A (en) 6-substituted phenoxychroman carboxylic acis derivatives
WO2011117870A3 (en) Compositions for topical administration
AU2009235634A8 (en) Substituted sulfonamide derivatives
WO2008144222A3 (en) Triazolyl aminopyrimidine compounds
HK1134493A (en) 3-(dihydro-1h-pyrazolo ü4,3-d¨pyrimidin-5-yl)-4-propoxybenzenesulfonamide derivatives and methods of use

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20151002

MPN Maintenance fee for patent paid

Free format text: FEE DESCRIPTION TEXT: MF (PATENT, 15TH ANNIV.) - STANDARD

Year of fee payment: 15

U00 Fee paid

Free format text: ST27 STATUS EVENT CODE: A-4-4-U10-U00-U101 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE REQUEST RECEIVED

Effective date: 20250916

U11 Full renewal or maintenance fee paid

Free format text: ST27 STATUS EVENT CODE: A-4-4-U10-U11-U102 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE FEE PAYMENT PAID IN FULL

Effective date: 20250916