TWI659945B - 作爲鈉通道調節劑之醯胺 - Google Patents

作爲鈉通道調節劑之醯胺 Download PDF

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Publication number
TWI659945B
TWI659945B TW103103690A TW103103690A TWI659945B TW I659945 B TWI659945 B TW I659945B TW 103103690 A TW103103690 A TW 103103690A TW 103103690 A TW103103690 A TW 103103690A TW I659945 B TWI659945 B TW I659945B
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another embodiment
alkyl
pain
benzylidene
halogen
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TW103103690A
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Chinese (zh)
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TW201443005A (zh
Inventor
儒雅 莎拉 賽賓娜 哈迪達
寇里 安德森
維札亞拉克斯米 阿魯穆格
尤莉安娜 露希 亞斯甘
布萊恩 李察 貝爾
安德亞斯P 特明
詹姆斯 菲利浦 強森
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維泰克斯製藥公司
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    • 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/192Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary 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
    • 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
    • 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/06Antiarrhythmics
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/42Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/44Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
    • C07C235/58Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho-position to carbon atoms of the same non-condensed six-membered aromatic ring
    • C07C235/64Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho-position to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/78Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79Acids; Esters

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (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)
  • Neurology (AREA)
  • Pain & Pain Management (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Rheumatology (AREA)
  • Urology & Nephrology (AREA)
  • Cardiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Hydrogenated Pyridines (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyridine Compounds (AREA)
TW103103690A 2013-01-31 2014-01-29 作爲鈉通道調節劑之醯胺 TWI659945B (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201361759062P 2013-01-31 2013-01-31
US61/759,062 2013-01-31

Publications (2)

Publication Number Publication Date
TW201443005A TW201443005A (zh) 2014-11-16
TWI659945B true TWI659945B (zh) 2019-05-21

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TW103103690A TWI659945B (zh) 2013-01-31 2014-01-29 作爲鈉通道調節劑之醯胺

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US (2) US9108903B2 (enExample)
EP (1) EP2951155B1 (enExample)
JP (1) JP6346622B2 (enExample)
KR (1) KR102226588B1 (enExample)
CN (1) CN104968647B (enExample)
AR (1) AR094668A1 (enExample)
AU (1) AU2014212431B2 (enExample)
BR (1) BR112015018284B1 (enExample)
CA (1) CA2898653C (enExample)
IL (1) IL240196B (enExample)
MX (1) MX359882B (enExample)
RU (1) RU2658920C2 (enExample)
SG (1) SG11201505954RA (enExample)
TW (1) TWI659945B (enExample)
WO (1) WO2014120820A1 (enExample)

Families Citing this family (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI714967B (zh) 2013-01-31 2021-01-01 美商維泰克斯製藥公司 作為鈉通道調節劑之吡啶酮醯胺
RU2683788C2 (ru) 2013-01-31 2019-04-02 Вертекс Фармасьютикалз Инкорпорейтед Амиды хинолина и хиназолина, полезные в качестве модуляторов натриевых каналов
UA119147C2 (uk) 2013-07-19 2019-05-10 Вертекс Фармасьютікалз Інкорпорейтед Сульфонаміди як модулятори натрієвих каналів
HRP20181563T1 (hr) 2013-12-13 2018-11-30 Vertex Pharmaceuticals Incorporated Predlijekovi piridonskih amida korisni kao modulatori natrijevih kanala
KR102714561B1 (ko) 2017-05-16 2024-10-10 버텍스 파마슈티칼스 인코포레이티드 나트륨 채널의 조절제로서의 중수소화 피리돈 아미드 및 이의 프로드럭
SG11202000230VA (en) * 2017-07-11 2020-02-27 Vertex Pharma Carboxamides as modulators of sodium channels
EP3752152A1 (en) 2018-02-12 2020-12-23 Vertex Pharmaceuticals Incorporated A method of treating pain
EP3873468A4 (en) 2018-11-02 2022-10-26 Merck Sharp & Dohme LLC 2-AMINO-N-PHENYL-NICOTINAMIDES AS NAV1.8 INHIBITORS
SG11202104326TA (en) * 2018-11-02 2021-05-28 Merck Sharp & Dohme 2-amino-n-heteroaryl-nicotinamides as nav1.8 inhibitors
AU2020205139A1 (en) * 2019-01-04 2021-08-19 Jiangsu Hengrui Medicine Co., Ltd. 6-oxo-1,6-dihydropyridazine derivative, preparation method therefor and medical use thereof
WO2020146612A1 (en) 2019-01-10 2020-07-16 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
BR112021014178A2 (pt) * 2019-02-20 2021-09-21 Jiangsu Hengrui Medicine Co., Ltd. Derivado de pró-fármaco de 6-oxo-1,6-diidropiridazina, método de preparação para o mesmo e aplicação do mesmo na medicina
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
CA3150400A1 (en) * 2019-09-12 2021-03-18 Shanghai Jemincare Pharmaceuticals Co., Ltd Pyridine oxynitride, preparation method therefor and use thereof
DK4069691T3 (da) 2019-12-06 2024-10-28 Vertex Pharma Substituerede tetrahydrofuraner som modulatorer af natriumkanaler
CN114437062B (zh) * 2020-04-30 2024-05-17 成都海博为药业有限公司 一种可作为钠通道调节剂的化合物及其用途
CR20220642A (es) 2020-06-17 2023-02-15 Merck Sharp & Dohme Llc 2-oxoimidazolidin-4-carboxamidas como inhibidores de nav1.8
CN113880771B (zh) * 2020-07-03 2023-09-19 福建盛迪医药有限公司 一种选择性Nav抑制剂的结晶形式及其制备方法
CN114031518B (zh) * 2020-12-08 2023-08-18 成都海博为药业有限公司 一种苄胺或苄醇衍生物及其用途
CN112225695B (zh) * 2020-12-15 2021-03-02 上海济煜医药科技有限公司 一种氮氧化合物及其制备方法和用途
TW202300147A (zh) * 2021-03-11 2023-01-01 大陸商上海濟煜醫藥科技有限公司 吡啶氮氧化合物晶型及其應用
GEAP202416407A (en) 2021-05-07 2024-03-25 Merck Sharp & Dohme Llc Cycloalkyl 3-oxopiperazine carboxamides and cycloheteroalkyl 3-oxopiperazine carboxamides as nav1.8 inhibitors
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
AU2022283934A1 (en) 2021-06-04 2023-11-30 Vertex Pharmaceuticals Incorporated Substituted tetrahydrofuran-2-carboxamides as modulators of sodium channels
US20250213555A1 (en) 2021-06-04 2025-07-03 Vertex Pharmaceuticals Incorporated Substituted tetrahydrofuran analogs as modulators of sodium channels
US11827627B2 (en) 2021-06-04 2023-11-28 Vertex Pharmaceuticals Incorporated N-(hydroxyalkyl (hetero)aryl) tetrahydrofuran carboxamides as modulators of sodium channels
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
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
WO2023205463A1 (en) 2022-04-22 2023-10-26 Vertex Pharmaceuticals Incorporated Heteroaryl compounds for the treatment of pain
EP4511117A1 (en) 2022-04-22 2025-02-26 Vertex Pharmaceuticals Incorporated Heteroaryl compounds for the treatment of pain
PE20250931A1 (es) 2022-04-22 2025-04-02 Vertex Pharma Compuestos de heteroarilo para el tratamiento del dolor
US20250388543A1 (en) 2022-04-22 2025-12-25 Vertex Pharmaceuticals Incorporated Heteroaryl compounds for the treatment of pain
PE20251183A1 (es) 2022-04-25 2025-04-23 Siteone Therapeutics Inc Inhibidores de amida heterociclica biciclica de sodio activado por voltaje 1.8 (nav 1.8) para el tratamiento del dolor
AU2023391870A1 (en) 2022-12-06 2025-06-05 Vertex Pharmaceuticals Incorporated Process for the synthesis of substituted tetrahydrofuran modulators of sodium channels
TW202434235A (zh) * 2023-01-18 2024-09-01 芬蘭商奧利安公司 3-(4,5-二氯-2-(4-(三氟甲氧基)苯氧基)苯甲醯胺基)吡啶1-氧化物的製備方法
WO2025090480A1 (en) 2023-10-23 2025-05-01 Vertex Pharmaceuticals Incorporated Heteroaryl compounds for the treatment of pain
WO2025090516A1 (en) 2023-10-23 2025-05-01 Vertex Pharmaceuticals Incorporated Methods of preparing compounds for treating pain and solid forms thereof
WO2025090465A1 (en) 2023-10-23 2025-05-01 Vertex Pharmaceuticals Incorporated Heteroaryl compounds for the treatment of pain
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
WO2025122953A1 (en) 2023-12-07 2025-06-12 Vertex Pharmaceuticals Incorporated Dosing regimens and formulations of suzetrigine for use in the treatment of acute and chronic pain
WO2025160286A1 (en) 2024-01-24 2025-07-31 Siteone Therapeutics, Inc. 2-aryl cycloalkyl and heterocycloalkyl inhibitors of nav1.8 for the treatment of pain
WO2026006674A1 (en) 2024-06-28 2026-01-02 Vertex Pharmaceuticals Incorporated Heteroaryl compounds for the treatment of pain

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101855210A (zh) * 2007-10-11 2010-10-06 沃泰克斯药物股份有限公司 用作电压-门控钠通道抑制剂的酰胺类

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2511231A (en) * 1949-03-26 1950-06-13 Eastman Kodak Co 1-cyanophenyl-3-acylamino-5-pyrazolone couplers for color photography
KR20080109918A (ko) 2006-04-11 2008-12-17 버텍스 파마슈티칼스 인코포레이티드 전압 개폐 나트륨 채널의 억제제로서 유용한 조성물
US8519137B2 (en) 2007-10-11 2013-08-27 Vertex Pharmaceuticals Incorporated Heteroaryl amides useful as inhibitors of voltage-gated sodium channels
KR20100075631A (ko) 2007-10-11 2010-07-02 버텍스 파마슈티칼스 인코포레이티드 전압­개폐 나트륨 채널의 억제제로서 유용한 아릴 아미드
MX2011012712A (es) * 2009-05-29 2012-01-30 Raqualia Pharma Inc Derivados de carboxamida sustituidos con arilo como bloqueadores del canal de calcio o sodio.

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101855210A (zh) * 2007-10-11 2010-10-06 沃泰克斯药物股份有限公司 用作电压-门控钠通道抑制剂的酰胺类

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Publication number Publication date
IL240196A0 (en) 2015-09-24
US9108903B2 (en) 2015-08-18
US9421196B2 (en) 2016-08-23
RU2015136779A (ru) 2017-03-07
BR112015018284A2 (pt) 2017-07-18
CA2898653C (en) 2021-09-28
CN104968647B (zh) 2018-01-26
RU2658920C2 (ru) 2018-06-26
US20140221435A1 (en) 2014-08-07
HK1217692A1 (en) 2017-01-20
SG11201505954RA (en) 2015-08-28
IL240196B (en) 2019-08-29
EP2951155B1 (en) 2019-06-19
MX2015009591A (es) 2016-04-15
AU2014212431A1 (en) 2015-08-06
CA2898653A1 (en) 2014-08-07
MX359882B (es) 2018-10-15
WO2014120820A1 (en) 2014-08-07
BR112015018284B1 (pt) 2023-03-07
AU2014212431B2 (en) 2018-04-05
WO2014120820A9 (en) 2015-07-02
EP2951155A1 (en) 2015-12-09
JP2016508500A (ja) 2016-03-22
NZ710293A (en) 2020-09-25
US20150328196A1 (en) 2015-11-19
KR20150118964A (ko) 2015-10-23
TW201443005A (zh) 2014-11-16
CN104968647A (zh) 2015-10-07
JP6346622B2 (ja) 2018-06-20
AR094668A1 (es) 2015-08-19
KR102226588B1 (ko) 2021-03-11

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