JPWO2019161078A5 - - Google Patents
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- JPWO2019161078A5 JPWO2019161078A5 JP2020543326A JP2020543326A JPWO2019161078A5 JP WO2019161078 A5 JPWO2019161078 A5 JP WO2019161078A5 JP 2020543326 A JP2020543326 A JP 2020543326A JP 2020543326 A JP2020543326 A JP 2020543326A JP WO2019161078 A5 JPWO2019161078 A5 JP WO2019161078A5
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- 229910052736 halogen Inorganic materials 0.000 claims description 277
- 150000002367 halogens Chemical class 0.000 claims description 277
- 125000000217 alkyl group Chemical group 0.000 claims description 246
- 150000001875 compounds Chemical class 0.000 claims description 236
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 204
- 150000003839 salts Chemical class 0.000 claims description 203
- 229910052739 hydrogen Inorganic materials 0.000 claims description 183
- 239000001257 hydrogen Substances 0.000 claims description 183
- 125000001188 haloalkyl group Chemical group 0.000 claims description 166
- 125000003545 alkoxy group Chemical group 0.000 claims description 161
- 125000005842 heteroatom Chemical group 0.000 claims description 116
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 115
- 150000002431 hydrogen Chemical class 0.000 claims description 101
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 95
- 125000000623 heterocyclic group Chemical group 0.000 claims description 77
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 68
- 125000004043 oxo group Chemical group O=* 0.000 claims description 63
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 51
- 229910052799 carbon Inorganic materials 0.000 claims description 51
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 41
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 40
- 125000001072 heteroaryl group Chemical group 0.000 claims description 38
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 36
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 31
- 125000004429 atom Chemical group 0.000 claims description 27
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 20
- 229910052805 deuterium Inorganic materials 0.000 claims description 20
- 125000004076 pyridyl group Chemical group 0.000 claims description 15
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims description 10
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims description 9
- 159000000007 calcium salts Chemical group 0.000 claims description 9
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 7
- 230000008878 coupling Effects 0.000 claims description 6
- 238000010168 coupling process Methods 0.000 claims description 6
- 238000005859 coupling reaction Methods 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical group [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 5
- 159000000000 sodium salts Chemical group 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 3
- -1 dehydrogen Chemical class 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 125000000262 haloalkenyl group Chemical group 0.000 claims 36
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims 29
- 125000005843 halogen group Chemical group 0.000 claims 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 14
- 230000006698 induction Effects 0.000 claims 1
- 125000004438 haloalkoxy group Chemical group 0.000 description 81
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 8
- 201000003883 Cystic fibrosis Diseases 0.000 description 7
- 125000006239 protecting group Chemical group 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 2
- 108010079245 Cystic Fibrosis Transmembrane Conductance Regulator Proteins 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical group O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 102000008371 intracellularly ATP-gated chloride channel activity proteins Human genes 0.000 description 1
- PURKAOJPTOLRMP-UHFFFAOYSA-N ivacaftor Chemical compound 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 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2022100979A JP2022126802A (ja) | 2018-02-15 | 2022-06-23 | 嚢胞性線維症膜コンダクタンス制御因子のモジュレーターとしての大環状分子、それらの医薬組成物、嚢胞性線維症の治療におけるそれらの使用、及びそれらの製造方法 |
| JP2024015975A JP2024050811A (ja) | 2018-02-15 | 2024-02-05 | 嚢胞性線維症膜コンダクタンス制御因子のモジュレーターとしての大環状分子、それらの医薬組成物、嚢胞性線維症の治療におけるそれらの使用、及びそれらの製造方法 |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862631453P | 2018-02-15 | 2018-02-15 | |
| US62/631,453 | 2018-02-15 | ||
| PCT/US2019/018042 WO2019161078A1 (en) | 2018-02-15 | 2019-02-14 | Macrocycles as modulators of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions thereof, their use in the treatment of cycstic fibrosis, and process for making them |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022100979A Division JP2022126802A (ja) | 2018-02-15 | 2022-06-23 | 嚢胞性線維症膜コンダクタンス制御因子のモジュレーターとしての大環状分子、それらの医薬組成物、嚢胞性線維症の治療におけるそれらの使用、及びそれらの製造方法 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| JP2021513967A JP2021513967A (ja) | 2021-06-03 |
| JP2021513967A5 JP2021513967A5 (https=) | 2022-02-21 |
| JPWO2019161078A5 true JPWO2019161078A5 (https=) | 2022-02-21 |
| JP7214743B2 JP7214743B2 (ja) | 2023-01-30 |
Family
ID=65529899
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020543326A Active JP7214743B2 (ja) | 2018-02-15 | 2019-02-14 | 嚢胞性線維症膜コンダクタンス制御因子のモジュレーターとしての大環状分子、それらの医薬組成物、嚢胞性線維症の治療におけるそれらの使用、及びそれらの製造方法 |
| JP2022100979A Withdrawn JP2022126802A (ja) | 2018-02-15 | 2022-06-23 | 嚢胞性線維症膜コンダクタンス制御因子のモジュレーターとしての大環状分子、それらの医薬組成物、嚢胞性線維症の治療におけるそれらの使用、及びそれらの製造方法 |
| JP2024015975A Withdrawn JP2024050811A (ja) | 2018-02-15 | 2024-02-05 | 嚢胞性線維症膜コンダクタンス制御因子のモジュレーターとしての大環状分子、それらの医薬組成物、嚢胞性線維症の治療におけるそれらの使用、及びそれらの製造方法 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022100979A Withdrawn JP2022126802A (ja) | 2018-02-15 | 2022-06-23 | 嚢胞性線維症膜コンダクタンス制御因子のモジュレーターとしての大環状分子、それらの医薬組成物、嚢胞性線維症の治療におけるそれらの使用、及びそれらの製造方法 |
| JP2024015975A Withdrawn JP2024050811A (ja) | 2018-02-15 | 2024-02-05 | 嚢胞性線維症膜コンダクタンス制御因子のモジュレーターとしての大環状分子、それらの医薬組成物、嚢胞性線維症の治療におけるそれらの使用、及びそれらの製造方法 |
Country Status (42)
Families Citing this family (41)
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| JP7214743B2 (ja) * | 2018-02-15 | 2023-01-30 | 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モジュレーターとしての大環状分子、それらの医薬組成物、嚢胞性線維症の治療におけるそれらの使用、及びそれらの製造方法 |
| EA202191361A1 (ru) * | 2018-11-14 | 2021-08-11 | Вертекс Фармасьютикалз Инкорпорейтед | Способы лечения муковисцидоза |
| CA3119656A1 (en) * | 2018-12-21 | 2020-06-25 | Novartis Ag | Macrocyclic compounds and their use in the treatment of disease |
| UY38630A (es) | 2019-04-03 | 2020-10-30 | Vertex Pharma | Agentes moduladores del regulador de la conductancia transmembrana de la fibrosis quística |
| WO2021030552A1 (en) * | 2019-08-14 | 2021-02-18 | Vertex Pharmaceuticals Incorporated | Crystalline forms of cftr modulators |
| US20220313698A1 (en) * | 2019-08-14 | 2022-10-06 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| 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 |
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| CN110551077B (zh) * | 2019-09-24 | 2023-01-31 | 新乡市润宇新材料科技有限公司 | 一种光催化分子氧氧化制备n-叔丁基-2-苯并噻唑亚磺酰胺的方法 |
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| WO2022194399A1 (en) | 2020-07-13 | 2022-09-22 | Idorsia Pharmaceuticals Ltd | Macrocycles as cftr modulators |
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| IL300413A (en) | 2020-08-13 | 2023-04-01 | Vertex Pharma | Crystal forms of CFTR modulators |
| WO2022076626A1 (en) * | 2020-10-07 | 2022-04-14 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| EP4225761A1 (en) * | 2020-10-07 | 2023-08-16 | 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 |
| KR20230104618A (ko) * | 2020-10-07 | 2023-07-10 | 버텍스 파마슈티칼스 인코포레이티드 | 낭성 섬유증 막관통 전도도 조절자의 조절제 |
| AU2021356651A1 (en) * | 2020-10-07 | 2023-05-18 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| WO2022076622A2 (en) * | 2020-10-07 | 2022-04-14 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| EP4225446A1 (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 |
| CA3201793A1 (en) * | 2020-11-18 | 2022-05-27 | Vertex Pharmaceuticals Incorporated | Macrocycles containing a 1,3,4-oxadiazole ring for use as modulators of cystic fibrosis transmembrane conductance regulator |
| KR20230118123A (ko) | 2020-12-10 | 2023-08-10 | 버텍스 파마슈티칼스 인코포레이티드 | 낭성 섬유증 치료 방법 |
| CA3249865A1 (en) | 2022-02-03 | 2023-08-10 | Vertex Pharmaceuticals Incorporated | PROCESSES FOR PREPARATION 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 |
| JP2025506382A (ja) | 2022-02-03 | 2025-03-11 | 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 | 嚢胞性線維症の治療方法 |
| 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 |
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| JP2025517323A (ja) | 2022-05-16 | 2025-06-05 | 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 | Ｃｆｔｒモジュレーターとしての大環状化合物の固体形態及びその調製 |
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| CN119998297A (zh) | 2022-09-15 | 2025-05-13 | 爱杜西亚药品有限公司 | (3S,7S,10R,13R)-13-苄基-20-氟-7-异丁基-N-(2-(3-甲氧基-1,2,4-噁二唑-5-基)乙基)-6,9-二甲基-1,5,8,11-四氧代-10-(2,2,2-三氟乙基)-1,2,3,4,5,6,7,8,9,10,11,12,13,14-十四氢-[1]氧杂[4,7,10,14]四氮杂环十七烷并[16,17-f]喹啉-3-甲酰胺的晶型 |
| CN115536493A (zh) * | 2022-10-20 | 2022-12-30 | 海门瑞一医药科技有限公司 | 一种制取3,3,3-三氟甲基-2,2-二甲基丙烷醇的简单方法 |
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