ES2628465T3 - Derivados deuterados de ivacaftor - Google Patents
Derivados deuterados de ivacaftor Download PDFInfo
- Publication number
- ES2628465T3 ES2628465T3 ES12725197.3T ES12725197T ES2628465T3 ES 2628465 T3 ES2628465 T3 ES 2628465T3 ES 12725197 T ES12725197 T ES 12725197T ES 2628465 T3 ES2628465 T3 ES 2628465T3
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- Prior art keywords
- compound
- deuterium
- pharmaceutically acceptable
- acid
- formula
- 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.)
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- PURKAOJPTOLRMP-UHFFFAOYSA-N ivacaftor Chemical class C1=C(O)C(C(C)(C)C)=CC(C(C)(C)C)=C1NC(=O)C1=CNC2=CC=CC=C2C1=O PURKAOJPTOLRMP-UHFFFAOYSA-N 0.000 title description 19
- 150000001875 compounds Chemical class 0.000 claims abstract description 136
- 229910052805 deuterium Inorganic materials 0.000 claims abstract description 51
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims abstract description 46
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 230000000155 isotopic effect Effects 0.000 claims abstract description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 17
- 239000001257 hydrogen Substances 0.000 claims abstract description 17
- 125000004429 atom Chemical group 0.000 claims abstract description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 150000001975 deuterium Chemical group 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims description 77
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 16
- 229960004508 ivacaftor Drugs 0.000 description 15
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- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
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- DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical compound CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
- 229940049953 phenylacetate Drugs 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 229950009215 phenylbutanoic acid Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
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- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
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- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
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- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
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- 229940116351 sebacate Drugs 0.000 description 1
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- KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
- C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
-
- 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
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- 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
-
- 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
- A61P11/12—Mucolytics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/002—Heterocyclic compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Saccharide Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161487497P | 2011-05-18 | 2011-05-18 | |
| US201161487497P | 2011-05-18 | ||
| PCT/US2012/038297 WO2012158885A1 (en) | 2011-05-18 | 2012-05-17 | Deuterated derivatives of ivacaftor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2628465T3 true ES2628465T3 (es) | 2017-08-02 |
Family
ID=46201810
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES12725197.3T Active ES2628465T3 (es) | 2011-05-18 | 2012-05-17 | Derivados deuterados de ivacaftor |
| ES17160386T Active ES2758028T3 (es) | 2011-05-18 | 2012-05-17 | Derivados deuterados de ivacaftor |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES17160386T Active ES2758028T3 (es) | 2011-05-18 | 2012-05-17 | Derivados deuterados de ivacaftor |
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| EP (2) | EP2709986B1 (enExample) |
| JP (2) | JP6063455B2 (enExample) |
| AU (5) | AU2012255711B2 (enExample) |
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| CA (1) | CA2834574C (enExample) |
| CY (2) | CY1119090T1 (enExample) |
| DK (2) | DK2709986T3 (enExample) |
| EA (1) | EA028378B1 (enExample) |
| ES (2) | ES2628465T3 (enExample) |
| HR (2) | HRP20170754T1 (enExample) |
| HU (1) | HUE032771T2 (enExample) |
| LT (1) | LT2709986T (enExample) |
| ME (2) | ME02749B (enExample) |
| MX (1) | MX349159B (enExample) |
| PL (2) | PL3235812T3 (enExample) |
| PT (2) | PT3235812T (enExample) |
| RS (2) | RS59744B1 (enExample) |
| SI (2) | SI3235812T1 (enExample) |
| SM (2) | SMT201900679T1 (enExample) |
| WO (1) | WO2012158885A1 (enExample) |
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| CA2635581C (en) | 2005-12-28 | 2017-02-28 | Vertex Pharmaceuticals Incorporated | Solid forms of n-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide |
| US12458635B2 (en) | 2008-08-13 | 2025-11-04 | Vertex Pharmaceuticals Incorporated | Pharmaceutical composition and administrations thereof |
| SI3235812T1 (sl) * | 2011-05-18 | 2020-02-28 | Vertex Pharmaceuticals (Europe) Limited | Devterirani derivati ivakaftorja |
| HUE047354T2 (hu) | 2011-05-18 | 2020-04-28 | Vertex Pharmaceuticals Europe Ltd | Ivacaftor deuterizált származékai |
| HK1203840A1 (en) | 2012-02-27 | 2015-11-06 | 沃泰克斯药物股份有限公司 | Pharmaceutical composition and administration thereof |
| CA2869257A1 (en) | 2012-04-06 | 2013-10-10 | The Uab Research Foundation | Methods for increasing cftr activity |
| JP6146990B2 (ja) * | 2012-11-16 | 2017-06-14 | コンサート ファーマシューティカルズ インコーポレイテッド | 重水素化されたｃｆｔｒ増強物質 |
| WO2014078842A1 (en) * | 2012-11-19 | 2014-05-22 | Concert Pharmaceuticals, Inc. | Deuterated cftr potentiators |
| WO2016057572A1 (en) | 2014-10-06 | 2016-04-14 | Mark Thomas Miller | Modulators of cystic fibrosis transmembrane conductance regulator |
| JP6746569B2 (ja) | 2014-10-07 | 2020-08-26 | 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 | 嚢胞性線維症膜貫通コンダクタンス制御因子のモジュレーターの共結晶 |
| WO2016160945A1 (en) | 2015-03-31 | 2016-10-06 | Concert Pharmaceuticals, Inc. | Deuterated vx-661 |
| MA42488A (fr) | 2015-07-24 | 2018-05-30 | Proteostasis Therapeutics Inc | Composés, compositions et procédés pour augmenter l'activité du cftr |
| CA2998911C (en) * | 2015-09-21 | 2023-05-23 | Vertex Pharmaceuticals (Europe) Limited | Administration of deuterated cftr potentiators |
| HK1258473A1 (zh) | 2015-09-25 | 2019-11-15 | Vertex Pharmaceuticals (Europe) Limited | 氘代cftr增效剂 |
| AR108203A1 (es) * | 2016-04-07 | 2018-07-25 | Proteostasis Therapeutics Inc | Compuestos, composiciones y métodos para modular cftr (regulador de la conductancia transmembrana de la fibrosis quística) |
| WO2017223188A1 (en) | 2016-06-21 | 2017-12-28 | Proteostasis Therapeutics, Inc. | Compounds, compositions, and methods for increasing cftr activity |
| CN110267948B (zh) | 2016-12-09 | 2023-12-08 | 弗特克斯药品有限公司 | 囊性纤维化跨膜传导调控剂的调节剂、药物组合物、治疗方法和制备所述调节剂的方法 |
| JP2017105824A (ja) * | 2017-02-10 | 2017-06-15 | コンサート ファーマシューティカルズ インコーポレイテッド | 重水素化されたｃｆｔｒ増強物質 |
| CA3069226A1 (en) | 2017-07-17 | 2019-01-24 | Vertex Pharmaceuticals Incorporated | Methods of treatment for cystic fibrosis |
| KR102720000B1 (ko) | 2017-12-01 | 2024-10-21 | 버텍스 파마슈티칼스 인코포레이티드 | 낭포성 섬유증 막관통 조절 인자의 제조 방법 |
| KR102716244B1 (ko) | 2017-12-08 | 2024-10-14 | 버텍스 파마슈티칼스 인코포레이티드 | 낭포성 섬유증 막횡단 전도 조절자의 조정제의 제조 방법 |
| JP6654223B2 (ja) * | 2018-08-13 | 2020-02-26 | バーテックス ファーマシューティカルズ （ヨーロッパ） リミテッド | 重水素化されたｃｆｔｒ増強物質 |
| TWI848092B (zh) | 2019-04-03 | 2024-07-11 | 美商維泰克斯製藥公司 | 囊腫纖維化跨膜傳導調節蛋白調節劑 |
| WO2020214921A1 (en) | 2019-04-17 | 2020-10-22 | Vertex Pharmaceuticals Incorporated | Solid forms of modulators of cftr |
| HUE066896T2 (hu) | 2019-08-14 | 2024-09-28 | Vertex Pharma | Eljárás CFTR modulátorok elõállítására |
| MX2022001828A (es) | 2019-08-14 | 2022-06-08 | Vertex Pharma | Formas cristalinas de moduladores del regulador de conductancia transmembrana de la fibrosis quistica (cftr). |
| TWI867024B (zh) | 2019-08-14 | 2024-12-21 | 美商維泰克斯製藥公司 | 囊腫纖維化跨膜傳導調節蛋白之調節劑 |
| IL290408B2 (en) | 2019-08-14 | 2025-10-01 | Vertex Pharma | Cystic fibrosis transmembrane conductance regulator modulators |
| LV15575A (lv) | 2019-12-20 | 2021-06-20 | Latvijas Organiskās Sintēzes Institūts | Selenofēnhromēnu deiterēti analogi, to iegūšana un izmantošana |
| CR20230120A (es) | 2020-08-07 | 2023-09-01 | Vertex Pharma | Moduladores del regulador de la conductancia transmembrana de la fibrosis quística |
| WO2022036060A1 (en) | 2020-08-13 | 2022-02-17 | Vertex Pharmaceuticals Incorporated | Crystalline forms of cftr modulators |
| EP3970718A1 (en) | 2020-09-18 | 2022-03-23 | Charité - Universitätsmedizin Berlin | New medical use of cystic fibrosis transmembrane conductance regulator (cftr) modulators |
| US20230374038A1 (en) | 2020-10-07 | 2023-11-23 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| US20230416275A1 (en) | 2020-10-07 | 2023-12-28 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| EP4225762A1 (en) | 2020-10-07 | 2023-08-16 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| WO2022076627A1 (en) | 2020-10-07 | 2022-04-14 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| EP4225750A1 (en) | 2020-10-07 | 2023-08-16 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| JP2023545762A (ja) | 2020-10-07 | 2023-10-31 | 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 | 嚢胞性線維症膜貫通コンダクタンス制御因子の調節因子 |
| PE20231185A1 (es) | 2020-10-07 | 2023-08-11 | Vertex Pharma | Moduladores del regulador de la conductancia transmembrana de la fibrosis quistica |
| WO2022076621A1 (en) | 2020-10-07 | 2022-04-14 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| MX2023004072A (es) | 2020-10-07 | 2023-07-05 | Vertex Pharma | Moduladores del regulador de la conductancia transmembrana de la fibrosis quistica. |
| EP4225737A1 (en) | 2020-10-07 | 2023-08-16 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| US12324802B2 (en) | 2020-11-18 | 2025-06-10 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| MX2023006770A (es) | 2020-12-10 | 2023-08-14 | Vertex Pharma | Metodos de tratamiento para fibrosis quistica. |
| US20250320226A1 (en) | 2022-02-03 | 2025-10-16 | Vertex Pharmaceuticals Incorporated | Methods of preparing and crystalline forms of (6a,12a)-17-amino-12-methyl-6,15-bis(trifluoromethyl)-13,19-dioxa-3,4,18-triazatricyclo[12.3.1.12,5]nonadeca-1(18),2,4,14,16-pentaen-6-ol |
| TW202333699A (zh) | 2022-02-03 | 2023-09-01 | 美商維泰克斯製藥公司 | 囊腫纖維化之治療方法 |
| JP2025505643A (ja) | 2022-02-08 | 2025-02-28 | 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 | 嚢胞性線維症膜コンダクタンス制御因子の調節因子 |
| CN119343355A (zh) | 2022-04-06 | 2025-01-21 | 弗特克斯药品有限公司 | 囊性纤维化跨膜传导调控因子的调节剂 |
| CA3253026A1 (en) | 2022-05-16 | 2023-11-23 | Vertex Pharmaceuticals Incorporated | TREATMENT METHODS FOR CYSTIC FIBROSIS |
| AU2023272562A1 (en) | 2022-05-16 | 2024-11-07 | Vertex Pharmaceuticals Incorporated | Solid forms of a macrocyclic compounds as cftr modulators and their preparation |
| WO2025076235A1 (en) | 2023-10-04 | 2025-04-10 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| WO2025076240A1 (en) | 2023-10-04 | 2025-04-10 | Vertex Pharmaceuticals Incorporated | Solid forms of modulators of cystic fibrosis transmembrane conductance regulator |
| WO2025166342A1 (en) | 2024-02-04 | 2025-08-07 | Vertex Pharmaceuticals Incorporated | Combination of vanzacaftor, tezacaftor, deutivacaftor for use in treating cystic fibrosis |
| WO2025171098A1 (en) | 2024-02-07 | 2025-08-14 | Vertex Pharmaceuticals Incorporated | Compositions for the treatment of cftr-mediated diseases |
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| BR9507200A (pt) * | 1994-03-25 | 1997-09-16 | Isotechnika Inc | Melhora da eficácia de drogas por deuteração |
| GB9925962D0 (en) | 1999-11-02 | 1999-12-29 | Novartis Ag | Organic compounds |
| MXPA03009971A (es) | 2001-05-03 | 2004-02-12 | Hoffmann La Roche | FORMA DE DOSIFICACIoN FARMACEUTICA DE MESILATO DE NELFINAVIR AMORFO. |
| EP1392262A1 (en) | 2001-05-24 | 2004-03-03 | Alexza Molecular Delivery Corporation | Delivery of drug esters through an inhalation route |
| ME02799B (me) * | 2004-06-24 | 2018-01-20 | Vertex Pharma | Modulatori ATP-vezujućih kasetnih transportera |
| CN101076319A (zh) | 2004-09-29 | 2007-11-21 | 科迪斯公司 | 稳定的非晶形雷帕霉素样化合物的药物剂型 |
| AU2006331565A1 (en) | 2005-12-27 | 2007-07-05 | Vertex Pharmaceuticals Incorporated | Compounds useful in CFTR assays and methods therewith |
| CA2635581C (en) | 2005-12-28 | 2017-02-28 | Vertex Pharmaceuticals Incorporated | Solid forms of n-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide |
| CN101478964B (zh) | 2006-05-12 | 2012-02-29 | 沃泰克斯药物股份有限公司 | N-[2,4-双(1,1-二甲基乙基)-5-羟苯基]-1,4-二氢-4-氧代喹啉-3-羧酰胺的组合物 |
| WO2009035652A1 (en) * | 2007-09-13 | 2009-03-19 | Concert Pharmaceuticals, Inc. | Synthesis of deuterated catechols and benzo[d][1,3] dioxoles and derivatives thereof |
| US20100074949A1 (en) | 2008-08-13 | 2010-03-25 | William Rowe | Pharmaceutical composition and administration thereof |
| MX366161B (es) | 2008-08-13 | 2019-07-01 | Vertex Pharmaceutical Incorporated | Composicion farmaceutica y su administracion. |
| EA021227B1 (ru) * | 2008-09-03 | 2015-05-29 | Тева Фармасьютикал Индастриз Лтд. | 2-оксо-1,2-дигидрохинолиновые модуляторы иммунной функции |
| SI3235812T1 (sl) * | 2011-05-18 | 2020-02-28 | Vertex Pharmaceuticals (Europe) Limited | Devterirani derivati ivakaftorja |
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