CA2701766A1 - Amides useful as inhibitors of voltage-gated sodium channels - Google Patents
Amides useful as inhibitors of voltage-gated sodium channels Download PDFInfo
- Publication number
- CA2701766A1 CA2701766A1 CA2701766A CA2701766A CA2701766A1 CA 2701766 A1 CA2701766 A1 CA 2701766A1 CA 2701766 A CA2701766 A CA 2701766A CA 2701766 A CA2701766 A CA 2701766A CA 2701766 A1 CA2701766 A1 CA 2701766A1
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- CA
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- Prior art keywords
- pain
- ring
- aliphatic
- optionally substituted
- 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.)
- Abandoned
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- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
- 125000004941 pyridazin-5-yl group Chemical group N1=NC=CC(=C1)* 0.000 description 1
- 125000004942 pyridazin-6-yl group Chemical group N1=NC=CC=C1* 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
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- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
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- 150000003385 sodium Chemical class 0.000 description 1
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- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
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- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
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- MHXBHWLGRWOABW-UHFFFAOYSA-N tetradecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC MHXBHWLGRWOABW-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
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- PHCBRBWANGJMHS-UHFFFAOYSA-J tetrasodium;disulfate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O PHCBRBWANGJMHS-UHFFFAOYSA-J 0.000 description 1
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000010989 thermoception Effects 0.000 description 1
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 1
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 description 1
- 125000004300 thiazolidin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])SC1([H])* 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 229960001017 tolmetin Drugs 0.000 description 1
- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
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- 238000002646 transcutaneous electrical nerve stimulation Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000006168 tricyclic group Chemical group 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- FQCQGOZEWWPOKI-UHFFFAOYSA-K trisalicylate-choline Chemical compound [Mg+2].C[N+](C)(C)CCO.OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O FQCQGOZEWWPOKI-UHFFFAOYSA-K 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical class CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
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- FVECELJHCSPHKY-JLSHOZRYSA-N veratridine Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)O[C@@H]1[C@@]2(O)O[C@]34C[C@@]5(O)[C@H](CN6[C@@H](CC[C@H](C)C6)[C@@]6(C)O)[C@]6(O)[C@@H](O)C[C@@]5(O)[C@@H]4CC[C@H]2[C@]3(C)CC1 FVECELJHCSPHKY-JLSHOZRYSA-N 0.000 description 1
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- 238000003260 vortexing Methods 0.000 description 1
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- 239000002023 wood Substances 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
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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
- C07D213/60—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 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
- C07D213/72—Nitrogen atoms
- C07D213/76—Nitrogen atoms to which a second hetero atom is attached
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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
- C07D213/60—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 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
- C07D213/72—Nitrogen atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (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)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US97929207P | 2007-10-11 | 2007-10-11 | |
| US60/979,292 | 2007-10-11 | ||
| PCT/US2008/079544 WO2009049181A1 (en) | 2007-10-11 | 2008-10-10 | Amides useful as inhibitors of voltage-gated sodium channels |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2701766A1 true CA2701766A1 (en) | 2009-04-16 |
Family
ID=40373424
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2701766A Abandoned CA2701766A1 (en) | 2007-10-11 | 2008-10-10 | Amides useful as inhibitors of voltage-gated sodium channels |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US8389734B2 (enExample) |
| EP (1) | EP2212292B1 (enExample) |
| JP (1) | JP5436434B2 (enExample) |
| KR (1) | KR20100066583A (enExample) |
| CN (1) | CN101855210A (enExample) |
| AU (1) | AU2008310661A1 (enExample) |
| CA (1) | CA2701766A1 (enExample) |
| IL (1) | IL204977A0 (enExample) |
| MX (1) | MX2010003864A (enExample) |
| NZ (1) | NZ584474A (enExample) |
| RU (1) | RU2010118481A (enExample) |
| WO (1) | WO2009049181A1 (enExample) |
| ZA (1) | ZA201002471B (enExample) |
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| CN109112126B (zh) * | 2010-06-23 | 2024-06-14 | 库尔纳公司 | 通过抑制电压门控钠通道α亚基(SCNA)的天然反义转录物而治疗SCNA相关疾病 |
| WO2012004743A1 (en) | 2010-07-09 | 2012-01-12 | Pfizer Limited | Benzenesulfonamides useful as sodium channel inhibitors |
| CA2804351A1 (en) | 2010-07-12 | 2012-01-19 | Pfizer Limited | Chemical compounds |
| EP2593431B1 (en) | 2010-07-12 | 2014-11-19 | Pfizer Limited | N-sulfonylbenzamides as inhibitors of voltage-gated sodium channels |
| EP2593428B1 (en) | 2010-07-12 | 2014-11-19 | Pfizer Limited | N-sulfonylbenzamides as inhibitors of voltage-gated sodium channels |
| EP2593427B1 (en) | 2010-07-12 | 2014-12-24 | Pfizer Limited | Sulfonamide derivatives as nav1.7 inhibitors for the treatment of pain |
| JP2013532184A (ja) * | 2010-07-12 | 2013-08-15 | ファイザー・リミテッド | 電位開口型ナトリウムチャネル阻害剤として有用なｎ−スルホニルベンズアミド誘導体 |
| US9656959B2 (en) | 2010-12-22 | 2017-05-23 | Purdue Pharma L.P. | Substituted pyridines as sodium channel blockers |
| EP2567959B1 (en) | 2011-09-12 | 2014-04-16 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP2922847A1 (en) | 2012-11-20 | 2015-09-30 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of indoleamine 2,3-dioxygenase |
| BR112015018284B1 (pt) * | 2013-01-31 | 2023-03-07 | Vertex Pharmaceuticals Incorporated | Amidas como moduladores de canais de sódio, seus usos, e composição farmacêutica |
| KR102226587B1 (ko) | 2013-01-31 | 2021-03-11 | 버텍스 파마슈티칼스 인코포레이티드 | 나트륨 채널의 조절제로서의 퀴놀린 및 퀴나졸린 아미드 |
| CN105026373B (zh) * | 2013-01-31 | 2018-03-30 | 沃泰克斯药物股份有限公司 | 作为钠通道调节剂的吡啶酮酰胺 |
| JP6337109B2 (ja) | 2013-07-19 | 2018-06-06 | 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Ｖｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | ナトリウムチャネルの調節剤としてのスルホンアミド |
| SG11201604477SA (en) | 2013-12-13 | 2016-07-28 | Vertex Pharma | Prodrugs of pyridone amides useful as modulators of sodium channels |
| CA2946378A1 (en) * | 2014-04-22 | 2015-10-29 | Q-State Biosciences, Inc. | Analysis of compounds for pain and sensory disorders |
| US10048275B2 (en) | 2015-03-13 | 2018-08-14 | Q-State Biosciences, Inc. | Cardiotoxicity screening methods |
| WO2016187543A1 (en) | 2015-05-21 | 2016-11-24 | Q-State Biosciences, Inc. | Optogenetics microscope |
| MX386261B (es) * | 2015-10-07 | 2025-03-18 | Univ Arizona | Inhibidores de sumoilacion de crmp2 y usos de los mismos |
| PL3481201T3 (pl) * | 2016-07-07 | 2021-03-22 | Corteva Agriscience Llc | Sposoby wytwarzania 4-alkoksy-3-(acylo lub alkilo)oksypikolinamidów |
| KR102714561B1 (ko) | 2017-05-16 | 2024-10-10 | 버텍스 파마슈티칼스 인코포레이티드 | 나트륨 채널의 조절제로서의 중수소화 피리돈 아미드 및 이의 프로드럭 |
| AU2018300150A1 (en) * | 2017-07-11 | 2020-01-30 | Vertex Pharmaceuticals Incorporated | Carboxamides as modulators of sodium channels |
| US20190343817A1 (en) | 2018-02-12 | 2019-11-14 | Vertex Pharmaceuticals Incorporated | Method of treating pain |
| SG11202100130QA (en) | 2018-07-09 | 2021-02-25 | Lieber Institute Inc | Pyridine carboxamide compounds for inhibiting nav1.8 |
| AU2019302534B2 (en) | 2018-07-09 | 2024-10-03 | Lieber Institute, Inc. | Pyridazine compounds for inhibiting NaV1.8 |
| CN110885328B (zh) * | 2018-09-10 | 2022-08-12 | 成都康弘药业集团股份有限公司 | 作为钠通道阻滞剂的磺酰胺类化合物及其用途 |
| WO2020092187A1 (en) * | 2018-11-02 | 2020-05-07 | Merck Sharp & Dohme Corp. | 2-amino-n-phenyl-nicotinamides as nav1.8 inhibitors |
| GEAP202315648A (en) | 2018-11-02 | 2023-07-25 | Merck Sharp & Dohme Llc | 2-amino-n-heteroaryl-nicotinamides as nav1.8 inhibitors |
| 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 |
| CN112390745B (zh) * | 2019-08-19 | 2022-10-21 | 江苏恒瑞医药股份有限公司 | 吡啶烟酰胺类衍生物、其制备方法及其在医药上的应用 |
| KR20220101606A (ko) * | 2019-09-12 | 2022-07-19 | 상하이 제민케어 파마슈티칼스 컴퍼니 리미티드 | 피리딘 산질화물 및 이의 제조 방법과 용도 |
| PH12022551379A1 (en) | 2019-12-06 | 2023-05-03 | Vertex Pharma | Substituted tetrahydrofurans as modulators of sodium channels |
| CN113045487B (zh) * | 2019-12-27 | 2025-01-17 | 明慧医药（上海）有限公司 | 一种选择性钠通道调节剂及其制备和应用 |
| KR20230026404A (ko) | 2020-06-17 | 2023-02-24 | 머크 샤프 앤드 돔 엘엘씨 | Nav1.8 억제제로서의 2-옥소-옥사졸리딘-5-카르복스아미드 |
| US11802122B2 (en) | 2020-06-17 | 2023-10-31 | Merck Sharp & Dohme Llc | 2-oxoimidazolidine-4-carboxamides as NAv1.8 inhibitors |
| EP4334293A1 (en) | 2021-05-07 | 2024-03-13 | Merck Sharp & Dohme LLC | Cycloalkyl 3-oxopiperazine carboxamides and cycloheteroalkyl 3-oxopiperazine carboxamides as nav1.8 inhibitors |
| WO2022256842A1 (en) | 2021-06-04 | 2022-12-08 | Vertex Pharmaceuticals Incorporated | Hydroxy and (halo)alkoxy substituted tetrahydrofurans as modulators of sodium channels |
| SI4347031T1 (sl) | 2021-06-04 | 2026-01-30 | Vertex Pharmaceuticals Incorporated | N-(hidroksialkil (hetero)aril) tetrahidrofuran karboksamidi kot modulatorji natrijevih kanalčkov |
| US11999699B2 (en) | 2021-06-15 | 2024-06-04 | Grünenthal GmbH | Substituted pyrazole amides |
| JP2025513455A (ja) | 2022-04-22 | 2025-04-24 | 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 | 疼痛の治療のためのヘテロアリール化合物 |
| CN117586180A (zh) * | 2022-08-12 | 2024-02-23 | 广州费米子科技有限责任公司 | 用作电压-门控钠通道抑制剂的化合物 |
| EP4385980A1 (en) | 2022-12-14 | 2024-06-19 | Grünenthal GmbH | Indazoles as inhibitors of nav1.8 |
| AR131345A1 (es) | 2022-12-14 | 2025-03-12 | Gruenenthal Gmbh | SULFOXIMINAS COMO INHIBIDORES DE NaV1.8 |
| EP4385979A1 (en) | 2022-12-14 | 2024-06-19 | Grünenthal GmbH | Multicyclic inhibitors of nav1.8 |
| EP4385984A1 (en) | 2022-12-14 | 2024-06-19 | Grünenthal GmbH | Pyridine-n-oxides as inhibitors of nav1.8 |
| WO2024217344A1 (zh) * | 2023-04-19 | 2024-10-24 | 中国科学院上海药物研究所 | Nav1.8抑制剂及其制备方法和用途 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL105345C (enExample) * | 1957-05-29 | |||
| CA1135705A (en) | 1978-07-20 | 1982-11-16 | Jens-Uwe Bliesener | N-arylsulfonylpyrroles, their preparation, and therapeutic agents containing these compounds |
| US4228449A (en) * | 1978-12-26 | 1980-10-14 | Hughes Aircraft Company | Semiconductor diode array liquid crystal device |
| US6620849B2 (en) * | 2000-07-26 | 2003-09-16 | Icafen, Inc. | Potassium channel inhibitors |
| US6995162B2 (en) | 2001-01-12 | 2006-02-07 | Amgen Inc. | Substituted alkylamine derivatives and methods of use |
| US7105682B2 (en) | 2001-01-12 | 2006-09-12 | Amgen Inc. | Substituted amine derivatives and methods of use |
| AU2002363250A1 (en) | 2001-11-01 | 2003-05-12 | Icagen, Inc. | Pyrazole-amides and-sulfonamides |
| SE0203752D0 (sv) | 2002-12-17 | 2002-12-17 | Astrazeneca Ab | New compounds |
| WO2004106324A1 (en) | 2003-05-27 | 2004-12-09 | E.I. Dupont De Nemours And Company | Azolecarboxamide herbicides |
| AU2004247559B2 (en) * | 2003-06-12 | 2009-08-27 | Astellas Pharma Inc. | Benzamide derivative or salt thereof |
| GB0317482D0 (en) * | 2003-07-25 | 2003-08-27 | Pfizer Ltd | Nicotinamide derivatives useful as pde4 inhibitors |
| KR20060073930A (ko) * | 2003-08-08 | 2006-06-29 | 버텍스 파마슈티칼스 인코포레이티드 | 통증 치료시 나트륨 또는 칼슘 채널 차단제로서 유용한헤테로아릴아미노설포닐페닐 유도체 |
| JP2008519850A (ja) | 2004-11-10 | 2008-06-12 | シンタ ファーマシューティカルズ コーポレーション | Ｉｌ−１２調節化合物 |
| DOP2006000210A (es) | 2005-10-04 | 2007-06-15 | Aventis Pharma Inc | Compuestos de pirimidina amida como inhibidores de pgds |
| MX2008013194A (es) * | 2006-04-11 | 2008-12-01 | Vertex Pharma | Composiciones utiles como inhibidores de canales de sodio regulados por voltaje. |
| US8383734B2 (en) * | 2006-07-17 | 2013-02-26 | Syracuse University | Multi-solution bone cements and methods of making the same |
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2008
- 2008-10-10 MX MX2010003864A patent/MX2010003864A/es not_active Application Discontinuation
- 2008-10-10 RU RU2010118481/04A patent/RU2010118481A/ru not_active Application Discontinuation
- 2008-10-10 EP EP08837614A patent/EP2212292B1/en active Active
- 2008-10-10 AU AU2008310661A patent/AU2008310661A1/en not_active Abandoned
- 2008-10-10 JP JP2010529092A patent/JP5436434B2/ja not_active Expired - Fee Related
- 2008-10-10 WO PCT/US2008/079544 patent/WO2009049181A1/en not_active Ceased
- 2008-10-10 US US12/249,251 patent/US8389734B2/en active Active
- 2008-10-10 CN CN200880115687A patent/CN101855210A/zh active Pending
- 2008-10-10 KR KR1020107010372A patent/KR20100066583A/ko not_active Withdrawn
- 2008-10-10 CA CA2701766A patent/CA2701766A1/en not_active Abandoned
- 2008-10-10 NZ NZ584474A patent/NZ584474A/en not_active IP Right Cessation
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| JP2011500599A (ja) | 2011-01-06 |
| KR20100066583A (ko) | 2010-06-17 |
| WO2009049181A1 (en) | 2009-04-16 |
| MX2010003864A (es) | 2010-06-01 |
| EP2212292B1 (en) | 2012-12-05 |
| US8865771B2 (en) | 2014-10-21 |
| EP2212292A1 (en) | 2010-08-04 |
| JP5436434B2 (ja) | 2014-03-05 |
| IL204977A0 (en) | 2010-11-30 |
| CN101855210A (zh) | 2010-10-06 |
| NZ584474A (en) | 2012-06-29 |
| RU2010118481A (ru) | 2011-11-20 |
| US8389734B2 (en) | 2013-03-05 |
| ZA201002471B (en) | 2011-06-29 |
| AU2008310661A1 (en) | 2009-04-16 |
| US20130231370A1 (en) | 2013-09-05 |
| US20090118333A1 (en) | 2009-05-07 |
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