MX2016007258A - Profarmacos de amidas de piridona utiles como moduladores de canales de sodio. - Google Patents
Profarmacos de amidas de piridona utiles como moduladores de canales de sodio.Info
- Publication number
- MX2016007258A MX2016007258A MX2016007258A MX2016007258A MX2016007258A MX 2016007258 A MX2016007258 A MX 2016007258A MX 2016007258 A MX2016007258 A MX 2016007258A MX 2016007258 A MX2016007258 A MX 2016007258A MX 2016007258 A MX2016007258 A MX 2016007258A
- Authority
- MX
- Mexico
- Prior art keywords
- prodrugs
- modulators
- sodium channels
- amides useful
- compounds
- Prior art date
Links
- 229940002612 prodrug Drugs 0.000 title abstract 2
- 239000000651 prodrug Substances 0.000 title abstract 2
- 108010052164 Sodium Channels Proteins 0.000 title 1
- 102000018674 Sodium Channels Human genes 0.000 title 1
- -1 pyridone amides Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract 3
- 239000000203 mixture Substances 0.000 abstract 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 208000035475 disorder Diseases 0.000 abstract 1
Classifications
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- 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
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
- A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
-
- 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
- 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
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- 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
- A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
-
- 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
- A61P11/14—Antitussive agents
-
- 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
-
- 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
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- 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
-
- 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
-
- 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
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- 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
- 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
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic 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
- C07D213/02—Heterocyclic 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
- C07D213/04—Heterocyclic 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
- C07D213/06—Heterocyclic 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 containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
- C07D213/16—Heterocyclic 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 containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring
- C07D213/18—Salts thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/58—Pyridine rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/59—Hydrogenated pyridine rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Urology & Nephrology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pulmonology (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Thermistors And Varistors (AREA)
Abstract
La invención se refiere a compuestos profármacos de la fórmula I: (ver Fórmula) en donde R2, R3, R5, R7 y X son como se definen en el presente documento. La invención también proporciona composiciones farmacéuticamente aceptables que comprenden los compuestos de la invención y métodos para usar las composiciones en el tratamiento de diversos trastornos, incluyendo dolor. Los compuestos de la fórmula I poseen solubilidad y propiedades fisicoquímicas adecuadas.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361915937P | 2013-12-13 | 2013-12-13 | |
| PCT/US2014/069916 WO2015089361A1 (en) | 2013-12-13 | 2014-12-12 | Prodrugs of pyridone amides useful as modulators of sodium channels |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| MX2016007258A true MX2016007258A (es) | 2016-08-04 |
| MX379264B MX379264B (es) | 2025-03-11 |
Family
ID=52293220
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2016007258A MX379264B (es) | 2013-12-13 | 2014-12-12 | Profarmacos de amidas de piridona utiles como moduladores de canales de sodio. |
| MX2021000781A MX2021000781A (es) | 2013-12-13 | 2016-06-03 | Profarmacos de amidas de piridona utiles como moduladores de canales de sodio. |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2021000781A MX2021000781A (es) | 2013-12-13 | 2016-06-03 | Profarmacos de amidas de piridona utiles como moduladores de canales de sodio. |
Country Status (33)
| Country | Link |
|---|---|
| US (6) | US9163042B2 (es) |
| EP (2) | EP3080134B1 (es) |
| JP (3) | JP6463580B2 (es) |
| KR (1) | KR102435145B1 (es) |
| CN (2) | CN108395452B (es) |
| AP (1) | AP2016009287A0 (es) |
| AU (2) | AU2014362255B2 (es) |
| BR (1) | BR122020007729B1 (es) |
| CA (1) | CA2931550C (es) |
| CL (1) | CL2016001400A1 (es) |
| CY (1) | CY1121030T1 (es) |
| DK (1) | DK3080134T3 (es) |
| EC (1) | ECSP16025201A (es) |
| ES (2) | ES2986650T3 (es) |
| GE (2) | GEP20207082B (es) |
| HR (1) | HRP20181563T1 (es) |
| IL (1) | IL246061B (es) |
| LT (1) | LT3080134T (es) |
| MX (2) | MX379264B (es) |
| NZ (2) | NZ760006A (es) |
| PE (1) | PE20161131A1 (es) |
| PH (1) | PH12016501028A1 (es) |
| PL (1) | PL3080134T3 (es) |
| PT (1) | PT3080134T (es) |
| RS (1) | RS57700B1 (es) |
| RU (1) | RU2692766C1 (es) |
| SG (2) | SG10201913313QA (es) |
| SI (1) | SI3080134T1 (es) |
| SM (1) | SMT201800521T1 (es) |
| TW (3) | TWI668226B (es) |
| UA (1) | UA121379C2 (es) |
| WO (1) | WO2015089361A1 (es) |
| ZA (1) | ZA201603546B (es) |
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|---|---|---|---|---|
| BR112014027983B1 (pt) | 2012-05-08 | 2022-05-24 | Aeromics, Inc | Uso de inibidores de aquaporina seletivos |
| AU2014212509B2 (en) | 2013-01-31 | 2018-05-10 | Vertex Pharmaceuticals Incorporated | Pyridone amides as modulators of sodium channels |
| EP2951168B1 (en) | 2013-01-31 | 2017-01-04 | Vertex Pharmaceuticals Incorporated | Quinoline and quinoxaline amides as modulators of sodium channels |
| ES2654393T3 (es) | 2013-07-19 | 2018-02-13 | Vertex Pharmaceuticals Incorporated | Sulfonamidas como moduladores de los canales de sodio |
| RU2691951C2 (ru) | 2013-11-06 | 2019-06-19 | Аэромикс, Инк. | Новые составы |
| US9163042B2 (en) | 2013-12-13 | 2015-10-20 | Vertex Pharmaceuticals Incorporated | Prodrugs of pyridone amides useful as modulators of sodium channels |
| US11221329B2 (en) | 2015-10-30 | 2022-01-11 | Lieber Institute, Inc. | Treatment of neurological and neurodevelopmental diseases and disorders associated with aberrant ion channel expression and activity |
| US20170239183A1 (en) * | 2016-02-23 | 2017-08-24 | PixarBio Corporation | COMPOSITIONS COMPRISING NAv1.7 SELECTIVE INHIBITORS FOR TREATING ACUTE, POST-OPERATIVE, OR CHRONIC PAIN AND METHODS OF USING THE SAME |
| AU2017261828B2 (en) | 2016-05-13 | 2023-04-13 | Aeromics, Inc. | Crystals |
| KR102714561B1 (ko) * | 2017-05-16 | 2024-10-10 | 버텍스 파마슈티칼스 인코포레이티드 | 나트륨 채널의 조절제로서의 중수소화 피리돈 아미드 및 이의 프로드럭 |
| TW201920081A (zh) | 2017-07-11 | 2019-06-01 | 美商維泰克斯製藥公司 | 作為鈉通道調節劑的羧醯胺 |
| US10495175B2 (en) * | 2017-08-08 | 2019-12-03 | Ford Global Technologies, Llc | Composite materials having embedded metal ropes for increased damping capacity and methods of manufacturing same |
| AU2019218387A1 (en) * | 2018-02-12 | 2020-08-27 | Vertex Pharmaceuticals Incorporated | A method of treating pain |
| US11993581B2 (en) | 2018-07-09 | 2024-05-28 | Lieber Institue, Inc | Pyridazine compounds for inhibiting Nav1.8 |
| AU2019301628C1 (en) | 2018-07-09 | 2025-02-06 | Lieber Institute, Inc. | Pyridine carboxamide compounds for inhibiting NaV1.8 |
| GEP20237568B (en) | 2018-11-02 | 2023-11-27 | Merck Sharp & Dohme Llc | 2-amino-n-heteroaryl-nicotinamides as nav1.8 inhibitors |
| US12344595B2 (en) | 2018-11-02 | 2025-07-01 | Merck Sharp & Dohme Llc | 2-amino-n-phenyl-nicotinamides as NAV1.8 inhibitors |
| US12441703B2 (en) | 2019-01-10 | 2025-10-14 | Vertex Pharmaceuticals Incorporated | Carboxamides as modulators of sodium channels |
| WO2020146612A1 (en) | 2019-01-10 | 2020-07-16 | Vertex Pharmaceuticals Incorporated | Esters and carbamates as modulators of sodium channels |
| TW202043200A (zh) * | 2019-01-25 | 2020-12-01 | 大陸商江蘇恆瑞醫藥股份有限公司 | 2-側氧基-1,2-二氫吡啶類衍生物、其製備方法及其在醫藥上的應用 |
| JP2022521483A (ja) * | 2019-02-20 | 2022-04-08 | ジエンス ヘンルイ メデイシンカンパニー リミテッド | 6-オキソ-1,6-ジヒドロピリダジンプロドラッグ誘導体、その調製方法、およびその医薬への応用6-オキソ-1,6-ジヒドロピリダジンプロドラッグ誘導体物、その調製方法、およびその医薬への応用 |
| WO2020176763A1 (en) | 2019-02-27 | 2020-09-03 | Vertex Pharmaceuticals Incorporated | Dosage form comprising prodrug of na 1.8 sodium channel inhibitor |
| WO2020206119A1 (en) | 2019-04-02 | 2020-10-08 | Vertex Pharmaceuticals Incorporated | Process for making pyridone amides and prodrugs thereof useful as modulators of sodium channels |
| WO2020219867A1 (en) | 2019-04-25 | 2020-10-29 | Vertex Pharmaceuticals Incorporated | Pyridone amide co-crystal compositions for the treatment of pain |
| WO2021018165A1 (zh) * | 2019-07-30 | 2021-02-04 | 江苏恒瑞医药股份有限公司 | 吡啶苯甲酰胺类衍生物、其制备方法及其在医药上的应用 |
| WO2021032074A1 (zh) * | 2019-08-19 | 2021-02-25 | 江苏恒瑞医药股份有限公司 | 苯甲酰胺稠芳环类衍生物、其制备方法及其在医药上的应用 |
| CA3150400A1 (en) * | 2019-09-12 | 2021-03-18 | Shanghai Jemincare Pharmaceuticals Co., Ltd | Pyridine oxynitride, preparation method therefor and use thereof |
| UY38979A (es) | 2019-12-06 | 2021-07-30 | Vertex Pharma | Tetrahidrofuranos sustituidos como moduladores de canales de sodio |
| 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 |
| KR20230026404A (ko) | 2020-06-17 | 2023-02-24 | 머크 샤프 앤드 돔 엘엘씨 | Nav1.8 억제제로서의 2-옥소-옥사졸리딘-5-카르복스아미드 |
| WO2021257490A1 (en) | 2020-06-17 | 2021-12-23 | Merck Sharp & Dohme Corp. | 2-oxoimidazolidine-4-carboxamides as nav1.8 inhibitors |
| 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 |
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| 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 |
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| WO2022179624A1 (zh) * | 2021-02-26 | 2022-09-01 | 江苏恒瑞医药股份有限公司 | 一种选择性NaV抑制剂的可药用盐、结晶形式及其制备方法 |
| BR112023023239A2 (pt) | 2021-05-07 | 2024-01-23 | Merck Sharp & Dohme Llc | Carboxamidas de cicloalquil 3-oxopiperazina e carboxamidas de cicloheteroalquil 3-oxopiperazina como inibidores de nav1.8 |
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