CN104136442B - 作为离子通道调节剂的吡喃‑螺环哌啶酰胺类 - Google Patents

作为离子通道调节剂的吡喃‑螺环哌啶酰胺类 Download PDF

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Publication number
CN104136442B
CN104136442B CN201380010104.4A CN201380010104A CN104136442B CN 104136442 B CN104136442 B CN 104136442B CN 201380010104 A CN201380010104 A CN 201380010104A CN 104136442 B CN104136442 B CN 104136442B
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och
pain
compound
mmol
isopropoxy
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Expired - Fee Related
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CN104136442A (zh
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S·S·阿迪达-鲁阿
V·阿鲁姆加姆
M·P·丹尼诺
B·A·弗里曼
E·A·卡莱勒
M·T·米勒
J·威
周竞兰
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Vertex Pharmaceuticals Inc
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Vertex Pharmaceuticals Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • 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
    • A61P1/12—Antidiarrhoeals
    • 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
    • A61P13/10—Drugs for disorders of the urinary system of the bladder
    • 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
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • 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
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • 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
    • A61P25/06—Antimigraine agents
    • 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
    • A61P25/08—Antiepileptics; Anticonvulsants
    • 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
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • 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
    • A61P25/22—Anxiolytics
    • 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
    • A61P25/24—Antidepressants
    • 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
    • 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
    • A61P9/06—Antiarrhythmics
    • 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
    • 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
    • A61P9/12—Antihypertensives

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Pain & Pain Management (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Psychiatry (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Immunology (AREA)
  • Rheumatology (AREA)
  • Vascular Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Plural Heterocyclic Compounds (AREA)
CN201380010104.4A 2012-01-16 2013-01-15 作为离子通道调节剂的吡喃‑螺环哌啶酰胺类 Expired - Fee Related CN104136442B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201261586875P 2012-01-16 2012-01-16
US61/586,875 2012-01-16
PCT/US2013/021535 WO2013109521A1 (en) 2012-01-16 2013-01-15 Pyran-spirocyclic piperidine amides as modulators of ion channels

Publications (2)

Publication Number Publication Date
CN104136442A CN104136442A (zh) 2014-11-05
CN104136442B true CN104136442B (zh) 2016-12-21

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Country Status (10)

Country Link
US (1) US9403839B2 (enExample)
EP (1) EP2804868B1 (enExample)
JP (1) JP6215230B2 (enExample)
CN (1) CN104136442B (enExample)
AU (1) AU2013209958B2 (enExample)
CA (1) CA2863343A1 (enExample)
ES (1) ES2631611T3 (enExample)
MX (1) MX2014008591A (enExample)
NZ (1) NZ627259A (enExample)
WO (1) WO2013109521A1 (enExample)

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BR112016000825B1 (pt) 2013-07-19 2023-04-25 Vertex Pharmaceuticals Incorporated Compostos moduladores de sulfonamidas dos canais de sódio, composição farmacêutica, e uso dos mesmos
US9163042B2 (en) 2013-12-13 2015-10-20 Vertex Pharmaceuticals Incorporated Prodrugs of pyridone amides useful as modulators of sodium channels
AU2018271110A1 (en) 2017-05-16 2019-12-05 Vertex Pharmaceuticals Incorporated Deuterated pyridone amides and prodrugs thereof as modulators of sodium channels
CN111065383A (zh) 2017-07-11 2020-04-24 沃泰克斯药物股份有限公司 用作钠通道调节剂的羧酰胺
MX2020004400A (es) * 2017-11-01 2020-08-06 Bristol Myers Squibb Co Compuestos espirociclicos como moduladores del receptor farnesoide x.
CN108276307A (zh) * 2018-01-17 2018-07-13 常熟浸大科技有限公司 3-氰基-4-烃氧基苯甲酸酯的合成方法
US11529337B2 (en) 2018-02-12 2022-12-20 Vertex Pharmaceuticals Incorporated Method of treating pain
MY196582A (en) 2018-02-13 2023-04-19 Gilead Sciences Inc PD-1/PD-L1 Inhibitors
CN110156674A (zh) * 2018-02-13 2019-08-23 中国科学院上海有机化学研究所 一种作为吲哚胺-2,3-双加氧酶抑制剂的螺环化合物
WO2019204609A1 (en) 2018-04-19 2019-10-24 Gilead Sciences, Inc. Pd-1/pd-l1 inhibitors
SG11202100137TA (en) * 2018-07-09 2021-02-25 Lieber Institute Inc PYRIDAZINE COMPOUNDS FOR INHIBITING Nav1.8
US12234221B2 (en) 2018-07-09 2025-02-25 Lieber Institute, Inc. Pyridine carboxamide compounds for inhibiting NAV1.8
PT3820572T (pt) 2018-07-13 2023-11-10 Gilead Sciences Inc Inibidores pd-1/pd-l1
EP3870566A1 (en) 2018-10-24 2021-09-01 Gilead Sciences, Inc. Pd-1/pd-l1 inhibitors
US12440481B2 (en) 2019-01-10 2025-10-14 Vertex Pharmaceuticals Incorporated Esters and carbamates as modulators of sodium channels
WO2020146682A1 (en) 2019-01-10 2020-07-16 Vertex Pharmaceuticals Incorporated Carboxamides as modulators of sodium channels
WO2020176763A1 (en) 2019-02-27 2020-09-03 Vertex Pharmaceuticals Incorporated Dosage form comprising prodrug of na 1.8 sodium channel inhibitor
WO2020219867A1 (en) 2019-04-25 2020-10-29 Vertex Pharmaceuticals Incorporated Pyridone amide co-crystal compositions for the treatment of pain
LT4069691T (lt) 2019-12-06 2024-12-10 Vertex Pharmaceuticals Incorporated Pakeistieji tetrahidrofuranai kaip natrio kanalų moduliatoriai
DK4347031T3 (da) 2021-06-04 2025-12-01 Vertex Pharma N-(hydroxyalkyl-(hetero)aryl)-tetrahydrofuran-carboxamider som modulatorer af natriumkanaler
CN117794919A (zh) 2021-06-04 2024-03-29 沃泰克斯药物股份有限公司 N-(羟烷基(杂)芳基)四氢呋喃甲酰胺类似物作为钠通道调节剂
EP4347032A1 (en) 2021-06-04 2024-04-10 Vertex Pharmaceuticals Incorporated Substituted tetrahydrofuran-2-carboxamides as modulators of sodium channels
CA3221938A1 (en) 2021-06-04 2022-12-08 Vertex Pharmaceuticals Incorporated Substituted tetrahydrofuran analogs as modulators of sodium channels
CN117858875A (zh) 2021-06-04 2024-04-09 沃泰克斯药物股份有限公司 羟基和(卤代)烷氧基取代的四氢呋喃作为钠通道调节剂
EP4346818B1 (en) 2021-06-04 2025-12-03 Vertex Pharmaceuticals Incorporated Solid dosage forms and dosing regimens comprising (2r,3s,4s,5r)-4-[[3-(3,4-difluoro-2-methoxy-phenyl)-4,5-dimethyl-5-(trifluoromethyl) tetrahydrofuran-2-carbonyl]amino]pyridine-2-carboxamide
CN119487003A (zh) 2022-04-22 2025-02-18 沃泰克斯药物股份有限公司 用于治疗疼痛的杂芳基化合物
WO2023205468A1 (en) 2022-04-22 2023-10-26 Vertex Pharmaceuticals Incorporated Heteroaryl compounds for the treatment of pain
CR20240513A (es) 2022-04-22 2025-04-30 Vertex Pharma Compuestos de heteroarilo para el tratamiento del dolor
WO2023205778A1 (en) 2022-04-22 2023-10-26 Vertex Pharmaceuticals Incorporated Heteroaryl compounds for the treatment of pain
CN120603815A (zh) 2022-12-06 2025-09-05 沃泰克斯药物股份有限公司 钠通道的取代四氢呋喃调节剂的合成方法
TW202523313A (zh) 2023-10-23 2025-06-16 美商維泰克斯製藥公司 用於治療疼痛之雜芳基化合物
WO2025090516A1 (en) 2023-10-23 2025-05-01 Vertex Pharmaceuticals Incorporated Methods of preparing compounds for treating pain and solid forms thereof
TW202535867A (zh) 2023-10-23 2025-09-16 美商維泰克斯製藥公司 用於治療疼痛之鈉通道調節劑及其固體形式的製備方法
WO2025090480A1 (en) 2023-10-23 2025-05-01 Vertex Pharmaceuticals Incorporated Heteroaryl compounds for the treatment of pain
US20250186419A1 (en) 2023-12-07 2025-06-12 Vertex Pharmaceuticals Incorporated Dosing regimens for treating pain

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WO2010002483A1 (en) * 2008-07-03 2010-01-07 Cv Therapeutics, Inc. Optionally condensed dihydro pyridine, dihydropyrimidine and dihydro pyrane derivatives acting as late sodium channel blockers
CN101910166A (zh) * 2007-11-13 2010-12-08 沃泰克斯药物股份有限公司 用作钠离子通道调节剂的杂环衍生物
CN102036985A (zh) * 2007-11-13 2011-04-27 沃泰克斯药物股份有限公司 用于治疗疼痛的作为离子通道调节剂的4(-3-(-2-(苯基)吗啉代)-2-氧代吡咯烷-1-基)-n-(噻唑-2-基)苯磺酰胺衍生物和相关化合物
CN102099356A (zh) * 2008-07-01 2011-06-15 沃泰克斯药物股份有限公司 用作离子通道调节剂的杂环衍生物
WO2012125613A1 (en) * 2011-03-14 2012-09-20 Vertex Pharmaceuticals Incorporated Morpholine-spirocyclic piperidine amides as modulators of ion channels

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Patent Citations (6)

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US20060052597A1 (en) * 2002-10-22 2006-03-09 Best Desmond J Aryloxyalkylamine derivatives as h3 receptor ligands
CN101910166A (zh) * 2007-11-13 2010-12-08 沃泰克斯药物股份有限公司 用作钠离子通道调节剂的杂环衍生物
CN102036985A (zh) * 2007-11-13 2011-04-27 沃泰克斯药物股份有限公司 用于治疗疼痛的作为离子通道调节剂的4(-3-(-2-(苯基)吗啉代)-2-氧代吡咯烷-1-基)-n-(噻唑-2-基)苯磺酰胺衍生物和相关化合物
CN102099356A (zh) * 2008-07-01 2011-06-15 沃泰克斯药物股份有限公司 用作离子通道调节剂的杂环衍生物
WO2010002483A1 (en) * 2008-07-03 2010-01-07 Cv Therapeutics, Inc. Optionally condensed dihydro pyridine, dihydropyrimidine and dihydro pyrane derivatives acting as late sodium channel blockers
WO2012125613A1 (en) * 2011-03-14 2012-09-20 Vertex Pharmaceuticals Incorporated Morpholine-spirocyclic piperidine amides as modulators of ion channels

Also Published As

Publication number Publication date
US9403839B2 (en) 2016-08-02
JP2015505321A (ja) 2015-02-19
CA2863343A1 (en) 2013-07-25
AU2013209958B2 (en) 2017-09-07
US20150005304A1 (en) 2015-01-01
HK1203074A1 (zh) 2015-10-16
WO2013109521A1 (en) 2013-07-25
AU2013209958A1 (en) 2014-08-07
CN104136442A (zh) 2014-11-05
EP2804868A1 (en) 2014-11-26
ES2631611T3 (es) 2017-09-01
NZ627259A (en) 2016-12-23
JP6215230B2 (ja) 2017-10-18
EP2804868B1 (en) 2017-04-12
MX2014008591A (es) 2014-08-22

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