RU2650118C2 - Способ лечения острого, хронического и подострого кашля и непреодолимого желания откашляться - Google Patents
Способ лечения острого, хронического и подострого кашля и непреодолимого желания откашляться Download PDFInfo
- Publication number
- RU2650118C2 RU2650118C2 RU2016105581A RU2016105581A RU2650118C2 RU 2650118 C2 RU2650118 C2 RU 2650118C2 RU 2016105581 A RU2016105581 A RU 2016105581A RU 2016105581 A RU2016105581 A RU 2016105581A RU 2650118 C2 RU2650118 C2 RU 2650118C2
- Authority
- RU
- Russia
- Prior art keywords
- alkyl
- cough
- compound
- formula
- haloc
- Prior art date
Links
- 206010011224 Cough Diseases 0.000 title claims abstract description 266
- 238000000034 method Methods 0.000 title claims abstract description 86
- 238000011282 treatment Methods 0.000 title claims abstract description 70
- 230000001684 chronic effect Effects 0.000 title abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 186
- 208000013116 chronic cough Diseases 0.000 claims abstract description 91
- -1 phenylaminocarbonylamino, carbonylamino Chemical group 0.000 claims abstract description 84
- 208000023504 respiratory system disease Diseases 0.000 claims abstract description 54
- 239000001257 hydrogen Substances 0.000 claims abstract description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 41
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims abstract description 32
- 150000003839 salts Chemical class 0.000 claims abstract description 32
- 239000003814 drug Substances 0.000 claims abstract description 31
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 26
- 150000002367 halogens Chemical class 0.000 claims abstract description 26
- 238000002360 preparation method Methods 0.000 claims abstract description 26
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 24
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 24
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 23
- 206010020751 Hypersensitivity Diseases 0.000 claims abstract description 18
- 208000026935 allergic disease Diseases 0.000 claims abstract description 18
- 230000009610 hypersensitivity Effects 0.000 claims abstract description 18
- 210000002569 neuron Anatomy 0.000 claims abstract description 16
- 239000004480 active ingredient Substances 0.000 claims abstract description 13
- 230000001154 acute effect Effects 0.000 claims abstract description 13
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 claims abstract description 11
- 230000002085 persistent effect Effects 0.000 claims abstract description 9
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract 13
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims abstract 12
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims abstract 11
- 125000004750 (C1-C6) alkylaminosulfonyl group Chemical group 0.000 claims abstract 10
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract 10
- 150000001408 amides Chemical class 0.000 claims abstract 10
- 125000006598 aminocarbonylamino group Chemical group 0.000 claims abstract 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 33
- 230000000241 respiratory effect Effects 0.000 claims description 21
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 230000002829 reductive effect Effects 0.000 claims description 8
- 101710189968 P2X purinoceptor 2 Proteins 0.000 abstract description 26
- 102100040479 P2X purinoceptor 2 Human genes 0.000 abstract description 26
- 239000000126 substance Substances 0.000 abstract description 12
- 230000000694 effects Effects 0.000 abstract description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 2
- 229940126202 P2X3 receptor antagonist Drugs 0.000 abstract 1
- 230000001537 neural effect Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 99
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- 125000001188 haloalkyl group Chemical group 0.000 description 24
- 239000011734 sodium Substances 0.000 description 24
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- 230000001404 mediated effect Effects 0.000 description 23
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 21
- 125000004181 carboxyalkyl group Chemical group 0.000 description 21
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 229940126142 compound 16 Drugs 0.000 description 18
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- 125000003545 alkoxy group Chemical group 0.000 description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 15
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
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- 125000000304 alkynyl group Chemical group 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 14
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- 125000004391 aryl sulfonyl group Chemical group 0.000 description 13
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 13
- 125000005113 hydroxyalkoxy group Chemical group 0.000 description 13
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- OMPGYSFGCUXAEG-UHFFFAOYSA-N 5-(5-amino-4-methoxy-2-propan-2-ylphenoxy)pyrimidine-2,4-diamine Chemical compound C1=C(N)C(OC)=CC(C(C)C)=C1OC1=CN=C(N)N=C1N OMPGYSFGCUXAEG-UHFFFAOYSA-N 0.000 description 11
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- 125000004432 carbon atom Chemical group C* 0.000 description 10
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- 230000004913 activation Effects 0.000 description 9
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- 210000004027 cell Anatomy 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
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- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 8
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| PCT/US2014/052389 WO2015027212A1 (en) | 2013-08-23 | 2014-08-22 | Diaminopyrimidine p2x3 and p2x 2/3 receptor modulators for treatment of acute, sub-acute or chronic cough |
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| AU2014308606B2 (en) * | 2013-08-23 | 2017-08-03 | Afferent Pharmaceuticals Inc. | Diaminopyrimidine P2X3 and P2X 2/3 receptor modulators for treatment of acute, sub-acute or chronic cough |
| ES2792682T3 (es) | 2014-02-10 | 2020-11-11 | Respivant Sciences Gmbh | Métodos para el tratamiento de enfermedades pulmonares con estabilizadores de mastocitos |
| PL3104853T3 (pl) | 2014-02-10 | 2020-05-18 | Respivant Sciences Gmbh | Leczenie stabilizatorami komórek tucznych zaburzeń ogólnoustrojowych |
| WO2017011729A1 (en) | 2015-07-16 | 2017-01-19 | Patara Pharma, LLC | Combination therapies for the treatment of lung diseases |
| WO2017027402A1 (en) | 2015-08-07 | 2017-02-16 | Patara Pharma, LLC | Methods for the treatment of systemic disorders treatable with mast cell stabilizers, including mast cell related disorders |
| US10238625B2 (en) | 2015-08-07 | 2019-03-26 | Respivant Sciences Gmbh | Methods for the treatment of mast cell related disorders with mast cell stabilizers |
| DK3355889T3 (da) * | 2015-09-29 | 2023-05-15 | Afferent Pharmaceuticals Inc | Diaminopyrimidin-p2x3- og p2x2/3-receptormodulatorer til anvendelse i behandling af hoste |
| US9907795B2 (en) * | 2016-01-08 | 2018-03-06 | Nerre Therapeutics Limited | Method of treatment of chronic cough administering orvepitant in combination with other therapeutic agents |
| AU2017237929B2 (en) | 2016-03-25 | 2021-04-15 | Afferent Pharmaceuticals Inc. | Pyrimidines and variants thereof, and uses therefor |
| WO2018044942A1 (en) | 2016-08-31 | 2018-03-08 | Patara Pharma, LLC | Cromolyn compositions for treatment of chronic cough due to idiopathic pulmonary fibrosis |
| EP3522983A4 (en) | 2016-10-07 | 2020-06-03 | Respivant Sciences GmbH | CROMOLYN COMPOSITION FOR TREATING LUNG FIBROSIS |
| WO2018111738A1 (en) * | 2016-12-15 | 2018-06-21 | Afferent Pharmaceuticals, Inc. | Substituted pyrazole-pyrimidines, variants thereof, and uses therefore |
| CN110087654A (zh) * | 2016-12-20 | 2019-08-02 | 传入制药公司 | P2x3拮抗剂的结晶盐和多晶型物 |
| US10111883B1 (en) * | 2017-09-18 | 2018-10-30 | Bellus Health Cough Inc. | Selective P2X3 modulators |
| CN108904507A (zh) * | 2018-02-11 | 2018-11-30 | 赖英杰 | P2x3受体调节剂苯并咪唑化合物在制备抗呼吸疾病药物中的应用 |
| EP3765072B1 (en) | 2018-03-15 | 2024-07-31 | Danmir Therapeutics, LLC | 3",5"-dialkoxybenzoyl-3'-amino-3'-deoxyadenosine-5'-triphosphates and pharmaceutical uses thereof |
| EP3784242A4 (en) * | 2018-04-23 | 2021-12-22 | Merck Sharp & Dohme Corp. | NEW PROCESS FOR PREPARING A PHENOXYDIAMINOPYRIMIDINE COMPOUND |
| EP3793553A1 (en) | 2018-05-15 | 2021-03-24 | Bayer Aktiengesellschaft | 1,3-thiazol-2-yl substituted benzamides for the treatment of diseases associated with nerve fiber sensitization |
| EA202092678A1 (ru) | 2018-05-15 | 2021-04-12 | Байер Акциенгезельшафт | 1,3-тиазол-2-ил-замещенные бензамиды для лечения заболеваний, ассоциированных с сенситизацией нервных волокон |
| IL318587A (en) * | 2018-07-23 | 2025-03-01 | Trevi Therapeutics Inc | Treatment of chronic cough, shortness of breath and wheezing |
| ES2963702T3 (es) | 2018-10-05 | 2024-04-01 | Shionogi & Co | Medicina para tratar la tos crónica |
| JP7578602B2 (ja) | 2019-02-25 | 2024-11-06 | グラクソスミスクライン、インテレクチュアル、プロパティー、（ナンバー３）、リミテッド | Ｐ２ｘ３修飾薬での治療 |
| ES3056709T3 (en) * | 2019-04-30 | 2026-02-24 | Beijing Tide Pharmaceutical Co Ltd | Salt of diaminopyrimidine compounds, and solid form thereof, preparation method therefor and use thereof |
| BR112021021600A2 (pt) * | 2019-04-30 | 2022-01-04 | Beijing Tide Pharmaceutical Co Ltd | Método para tratamento de tosse usando composto de diaminopirimidina |
| TWI889708B (zh) | 2019-09-19 | 2025-07-11 | 日商塩野義製藥股份有限公司 | 1，3，5-三衍生物或其溶劑合物之結晶及其製造方法 |
| IL294601A (en) | 2020-01-10 | 2022-09-01 | Trevi Therapeutics Inc | Methods of administration of nalbuphine |
| CN111635368B (zh) * | 2020-06-12 | 2021-06-29 | 东莞市东阳光仿制药研发有限公司 | 一种胺化合物的制备方法 |
| WO2024080126A1 (ja) | 2022-10-12 | 2024-04-18 | ソフトバンクグループ株式会社 | 情報処理システム、情報処理装置、制御装置及びプログラム |
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