CA2772792A1 - Process for preparing azabicyclic compounds - Google Patents
Process for preparing azabicyclic compounds Download PDFInfo
- Publication number
- CA2772792A1 CA2772792A1 CA2772792A CA2772792A CA2772792A1 CA 2772792 A1 CA2772792 A1 CA 2772792A1 CA 2772792 A CA2772792 A CA 2772792A CA 2772792 A CA2772792 A CA 2772792A CA 2772792 A1 CA2772792 A1 CA 2772792A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- formula
- solvent
- mixture
- base
- 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
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 86
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 8
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 239000000203 mixture Substances 0.000 claims description 55
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 45
- 238000000034 method Methods 0.000 claims description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 29
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 26
- 239000002904 solvent Substances 0.000 claims description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- 230000008569 process Effects 0.000 claims description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 claims description 14
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 13
- 239000011541 reaction mixture Substances 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- IMLXLGZJLAOKJN-UHFFFAOYSA-N 4-aminocyclohexan-1-ol Chemical compound NC1CCC(O)CC1 IMLXLGZJLAOKJN-UHFFFAOYSA-N 0.000 claims description 8
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 6
- VUDZSIYXZUYWSC-DBRKOABJSA-N (4r)-1-[(2r,4r,5r)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one Chemical compound FC1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N[C@H](O)CC1 VUDZSIYXZUYWSC-DBRKOABJSA-N 0.000 claims description 4
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- 235000011181 potassium carbonates Nutrition 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- 235000017550 sodium carbonate Nutrition 0.000 claims description 4
- 238000011084 recovery Methods 0.000 claims description 3
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- 238000004821 distillation Methods 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- 150000003512 tertiary amines Chemical class 0.000 claims description 2
- 239000000543 intermediate Substances 0.000 abstract description 3
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- 239000007787 solid Substances 0.000 description 19
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical class CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 14
- 239000000725 suspension Substances 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 10
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 235000002639 sodium chloride Nutrition 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 5
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- DQARDWKWPIRJEH-UHFFFAOYSA-N tert-butyl n-(4-hydroxycyclohexyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(O)CC1 DQARDWKWPIRJEH-UHFFFAOYSA-N 0.000 description 5
- 239000001993 wax Substances 0.000 description 5
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
- JQHCKZLQJDVZPH-UHFFFAOYSA-N 7-azabicyclo[2.2.1]heptane;hydrochloride Chemical compound [Cl-].C1CC2CCC1[NH2+]2 JQHCKZLQJDVZPH-UHFFFAOYSA-N 0.000 description 4
- XSTRZZXVGQMKLM-LJGSYFOKSA-N N[C@H]1CC[C@H](CS(O)(=O)=O)CC1 Chemical compound N[C@H]1CC[C@H](CS(O)(=O)=O)CC1 XSTRZZXVGQMKLM-LJGSYFOKSA-N 0.000 description 4
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- 229920002472 Starch Polymers 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
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- 229940124597 therapeutic agent Drugs 0.000 description 4
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- 235000010443 alginic acid Nutrition 0.000 description 3
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- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B61/00—Other general methods
- C07B61/02—Generation of organic free radicals; Organic free radicals per se
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/33—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C211/34—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of a saturated carbon skeleton
- C07C211/35—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of a saturated carbon skeleton containing only non-condensed rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
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| US24347709P | 2009-09-17 | 2009-09-17 | |
| US61/243,477 | 2009-09-17 | ||
| PCT/US2010/049306 WO2011035139A1 (en) | 2009-09-17 | 2010-09-17 | Process for preparing azabicyclic compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2772792A1 true CA2772792A1 (en) | 2011-03-24 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2772792A Abandoned CA2772792A1 (en) | 2009-09-17 | 2010-09-17 | Process for preparing azabicyclic compounds |
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| US (2) | US8404865B2 (enExample) |
| EP (1) | EP2477991B1 (enExample) |
| JP (1) | JP5793496B2 (enExample) |
| KR (1) | KR20120083416A (enExample) |
| CN (1) | CN102498112B (enExample) |
| AU (1) | AU2010295461B2 (enExample) |
| BR (1) | BR112012006031A2 (enExample) |
| CA (1) | CA2772792A1 (enExample) |
| ES (1) | ES2540810T3 (enExample) |
| IL (1) | IL218641A0 (enExample) |
| MX (1) | MX2012003343A (enExample) |
| NZ (1) | NZ598277A (enExample) |
| RU (1) | RU2543622C2 (enExample) |
| WO (1) | WO2011035139A1 (enExample) |
| ZA (1) | ZA201201252B (enExample) |
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| US7973169B2 (en) | 2003-09-06 | 2011-07-05 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-Binding Cassette transporters |
| CN101675928A (zh) * | 2003-11-14 | 2010-03-24 | 沃泰克斯药物股份有限公司 | 可用作atp-结合弹夹转运蛋白调控剂的噻唑和噁唑 |
| US7977322B2 (en) | 2004-08-20 | 2011-07-12 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-binding cassette transporters |
| CA2881078C (en) | 2004-06-24 | 2018-10-02 | Vertex Pharmaceuticals Incorporated | Modulators of atp-binding cassette transporters |
| RU2008109031A (ru) | 2005-08-11 | 2009-09-20 | Вертекс Фармасьютикалз Инкорпорейтед (Us) | Модуляторы муковисцидозного трансмембранного регулятора проводимости |
| PT2404919E (pt) | 2005-11-08 | 2013-10-22 | Vertex Pharma | Composto heterocíclico útil como um modulador de transportadores de cassete de ligação a atp |
| EP2016065B1 (en) | 2005-12-28 | 2012-09-19 | Vertex Pharmaceuticals Incorporated | 1-(benzo[d][1,3]dioxol-5-yl)-n-(phenyl)cyclopropane-carboxamide derivatives and related compounds as modulators of atp-binding cassette transporters for the treatment of cystic fibrosis |
| LT1993360T (lt) | 2005-12-28 | 2017-06-12 | Vertex Pharmaceuticals Incorporated | N-[2,4-bis(1,1-dimetiletil)-5-hidroksifenil]-1,4-dihidro-4-oksochinolin-3-karboksamido kieta forma |
| US7645789B2 (en) * | 2006-04-07 | 2010-01-12 | Vertex Pharmaceuticals Incorporated | Indole derivatives as CFTR modulators |
| USRE50453E1 (en) | 2006-04-07 | 2025-06-10 | Vertex Pharmaceuticals Incorporated | Indole derivatives as CFTR modulators |
| JP5420395B2 (ja) | 2006-04-07 | 2014-02-19 | 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 | Ａｔｐ結合カセット輸送体の調節剤 |
| US10022352B2 (en) | 2006-04-07 | 2018-07-17 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-binding cassette transporters |
| US8563573B2 (en) * | 2007-11-02 | 2013-10-22 | Vertex Pharmaceuticals Incorporated | Azaindole derivatives as CFTR modulators |
| EP2164840A2 (en) | 2007-05-09 | 2010-03-24 | Vertex Pharmaceuticals Incorporated | Modulators of cftr |
| CA2696298C (en) | 2007-08-24 | 2016-09-06 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| CN102743385B (zh) | 2007-11-16 | 2014-09-17 | 沃泰克斯药物股份有限公司 | Atp结合盒转运蛋白的异喹啉调节剂 |
| HUE049642T2 (hu) | 2007-12-07 | 2020-09-28 | Vertex Pharma | 3-(6-(1-(2,2-Difluorbenzo[d][1,3]dioxol-5-il)-ciklopropánkarboxamido)-3-metilpiridin-2-il)-benzoesav szilárd formái |
| CA2989620C (en) | 2007-12-07 | 2022-05-03 | Vertex Pharmaceuticals Incorporated | Processes for producing cycloalkylcarboxamido-pyridine benzoic acids |
| AU2008335439A1 (en) * | 2007-12-07 | 2009-06-18 | Vertex Pharmaceuticals Incorporated | Formulations of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid |
| US20100036130A1 (en) | 2007-12-07 | 2010-02-11 | Vertex Pharmaceuticals Incorporated | Processes for producing cycloalkylcarboxamido-pyridine benzoic acids |
| CA2716109C (en) | 2008-02-28 | 2016-07-19 | Vertex Pharmaceuticals Incorporated | Heteroaryl derivatives as cftr modulators |
| NZ616097A (en) | 2008-03-31 | 2015-04-24 | Vertex Pharma | Pyridyl derivatives as cftr modulators |
| US20100074949A1 (en) | 2008-08-13 | 2010-03-25 | William Rowe | Pharmaceutical composition and administration thereof |
| US12458635B2 (en) | 2008-08-13 | 2025-11-04 | Vertex Pharmaceuticals Incorporated | Pharmaceutical composition and administrations thereof |
| WO2010037066A2 (en) * | 2008-09-29 | 2010-04-01 | Vertex Pharmaceuticals Incorporated | Dosage units of 3-(6-(1-(2,2-difluorobenzo [d] [1,3] dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid |
| MX2011004375A (es) | 2008-10-23 | 2013-03-07 | Vertex Pharma | Moduladores del regulador de conductancia transmembrana de fibrosis quistica. |
| SI3330255T1 (sl) | 2009-03-20 | 2021-03-31 | Vertex Pharmaceuticals Incorporated | Postopek izdelave regulatorja transmembranske prevodnosti pri cistični fibrozi |
| WO2011035139A1 (en) * | 2009-09-17 | 2011-03-24 | Vertex Pharmaceuticals Incorporated | Process for preparing azabicyclic compounds |
| US8802868B2 (en) | 2010-03-25 | 2014-08-12 | Vertex Pharmaceuticals Incorporated | Solid forms of (R)-1(2,2-difluorobenzo[D][1,3]dioxo1-5-yl)-N-(1-(2,3-dihydroxypropyl-6-fluoro-2-(1-hydroxy-2-methylpropan2-yl)-1H-Indol-5-yl)-Cyclopropanecarboxamide |
| ES2900353T3 (es) | 2010-04-07 | 2022-03-16 | Vertex Pharma | Composiciones farmacéuticas de ácido 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-il)ciclopropanocarboxamido)-3-metilpiriidin-2-il)benzoico y administración de las mismas |
| TWI549950B (zh) | 2010-04-07 | 2016-09-21 | 維泰克斯製藥公司 | ３－（６－（１－（２，２－二氟苯并［ｄ］［１，３］二氧雜環戊烯－５－基）環丙烷甲醯胺基）－３－甲基吡啶－２－基）苯甲酸之固體形式 |
| RU2569678C2 (ru) | 2010-04-22 | 2015-11-27 | Вертекс Фармасьютикалз Инкорпорейтед | Способ получения циклоалкилкарбоксамидо-индольных соединений |
| NZ603042A (en) | 2010-04-22 | 2015-02-27 | Vertex Pharma | Pharmaceutical compositions comprising cftr modulators and administrations thereof |
| WO2011133953A1 (en) | 2010-04-22 | 2011-10-27 | Vertex Pharmaceuticals Incorporated | Pharmaceutical compositions and administrations thereof |
| US8563593B2 (en) | 2010-06-08 | 2013-10-22 | Vertex Pharmaceuticals Incorporated | Formulations of (R)-1-(2,2-difluorobenzo[D] [1,3] dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide |
| CA2852991C (en) | 2011-11-08 | 2019-12-31 | Vertex Pharmaceuticals Incorporated | Modulators of atp-binding cassette transporters |
| NZ727015A (en) | 2012-01-25 | 2017-12-22 | Vertex Pharma | Formulations of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid |
| EP2819670B1 (en) | 2012-02-27 | 2026-05-20 | Vertex Pharmaceuticals Incorporated | Pharmaceutical Composition and Their Administration |
| CN102633804B (zh) * | 2012-04-19 | 2014-09-24 | 中南大学 | 一种制备7-氮杂双环[2.2.1]庚烷的方法 |
| US8674108B2 (en) | 2012-04-20 | 2014-03-18 | Vertex Pharmaceuticals Incorporated | Solid forms of N-[2,4-bis(1,1-dimethylethy)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide |
| AU2013290444B2 (en) | 2012-07-16 | 2018-04-26 | Vertex Pharmaceuticals Incorporated | Pharmaceutical compositions of (R)-1-(2,2-diflurorbenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl) cyclopropanecarboxamide and administration thereof |
| CA2930199C (en) | 2013-11-12 | 2022-10-25 | Vertex Pharmaceuticals Incorporated | Process of preparing pharmaceutical compositions for the treatment of cftr mediated diseases |
| PL3925607T5 (pl) | 2014-04-15 | 2026-06-01 | Vertex Pharmaceuticals Incorporated | Kompozycje farmaceutyczne do leczenia chorób, w których pośredniczy mukowiscydozowy przezbłonowy regulator przewodnictwa |
| CA2963945C (en) | 2014-10-07 | 2023-01-10 | Vertex Pharmaceuticals Incorporated | Co-crystals of modulators of cystic fibrosis transmembrane conductance regulator |
| HUE055423T2 (hu) | 2014-11-18 | 2021-11-29 | Vertex Pharma | Eljárás nagy áteresztõképességû tesztelõ nagy teljesítményû folyadék-kromatográfia elvégzésére |
| CR20230120A (es) | 2020-08-07 | 2023-09-01 | Vertex Pharma | Moduladores del regulador de la conductancia transmembrana de la fibrosis quística |
| US12324802B2 (en) | 2020-11-18 | 2025-06-10 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| US12655863B2 (en) | 2023-06-16 | 2026-06-16 | Frank V. Patterson | Hollow wall mounting device |
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| US6060473A (en) | 1993-04-01 | 2000-05-09 | Ucb S.A. - Dtb | 7-azabicyclo[2.2.1]-heptane and -heptene derivatives as cholinergic receptor ligands |
| JPH06312989A (ja) * | 1993-04-30 | 1994-11-08 | Nippon Chemiphar Co Ltd | （１ｒｓ，２ｒｓ，４ｓｒ）−２−（６−クロロ−３−ピリジル）−７−アザビシクロ［２．２．１］ヘプタンの製造方法 |
| US6117889A (en) | 1994-04-01 | 2000-09-12 | University Of Virginia | 7-Azabicyclo-[2.2.1]-heptane and -heptene derivatives as analgesics and anti-inflammatory agents |
| TW200407127A (en) * | 2002-08-21 | 2004-05-16 | Astrazeneca Ab | Chemical compounds |
| EP1730155A1 (en) * | 2004-02-20 | 2006-12-13 | AstraZeneca AB | Thienopyrroles as antagonists of gnrh |
| CA2881078C (en) * | 2004-06-24 | 2018-10-02 | Vertex Pharmaceuticals Incorporated | Modulators of atp-binding cassette transporters |
| US20080194635A1 (en) * | 2005-01-21 | 2008-08-14 | Pfizer Inc. | Crystalline Forms of Cis-5-Fluoro-N-[4-(2-Hydroxy-4-Methylbenzamido) Cyclohexyl]-2-(Tetrahydrothiopyran-4-Yloxy) Nicotinamide |
| WO2008117871A1 (ja) * | 2007-03-28 | 2008-10-02 | Nagasaki University | 含窒素レドックス触媒 |
| MX2011004375A (es) * | 2008-10-23 | 2013-03-07 | Vertex Pharma | Moduladores del regulador de conductancia transmembrana de fibrosis quistica. |
| NZ592504A (en) * | 2008-10-23 | 2013-04-26 | Vertex Pharma | Solid forms of n-(4-(7-azabicyclo[2.2.1]heptan-7-yl)-2-(trifluoromethyl)phenyl)-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxamide |
| WO2011035139A1 (en) * | 2009-09-17 | 2011-03-24 | Vertex Pharmaceuticals Incorporated | Process for preparing azabicyclic compounds |
| CN102666546B (zh) * | 2009-10-23 | 2015-09-09 | 沃泰克斯药物股份有限公司 | N-(4-(7-氮杂双环[2.2.1]庚-7-基)-2-(三氟甲基)苯基)-4-氧代-5-(三氟甲基)-1,4-二氢喹啉-3-甲酰胺的固体形式 |
| NZ600172A (en) * | 2009-10-23 | 2014-07-25 | Vertex Pharma | Process for preparing modulators of cystic fibrosis transmembrane conductance regulator |
| TW201202250A (en) * | 2010-05-20 | 2012-01-16 | Vertex Pharma | Processes for producing modulators of cystic fibrosis transmembrane conductance regulator |
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- 2010-09-17 EP EP10757544.1A patent/EP2477991B1/en not_active Not-in-force
- 2010-09-17 NZ NZ598277A patent/NZ598277A/en not_active IP Right Cessation
- 2010-09-17 JP JP2012529933A patent/JP5793496B2/ja not_active Expired - Fee Related
- 2010-09-17 BR BR112012006031A patent/BR112012006031A2/pt not_active IP Right Cessation
- 2010-09-17 AU AU2010295461A patent/AU2010295461B2/en not_active Expired - Fee Related
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- 2010-09-17 MX MX2012003343A patent/MX2012003343A/es active IP Right Grant
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| MX2012003343A (es) | 2012-08-17 |
| RU2543622C2 (ru) | 2015-03-10 |
| AU2010295461A1 (en) | 2012-03-08 |
| EP2477991A1 (en) | 2012-07-25 |
| JP5793496B2 (ja) | 2015-10-14 |
| US8461352B2 (en) | 2013-06-11 |
| US20110065928A1 (en) | 2011-03-17 |
| ZA201201252B (en) | 2013-05-29 |
| JP2013505259A (ja) | 2013-02-14 |
| US20120259129A1 (en) | 2012-10-11 |
| US8404865B2 (en) | 2013-03-26 |
| RU2012115111A (ru) | 2013-10-27 |
| BR112012006031A2 (pt) | 2019-09-24 |
| WO2011035139A1 (en) | 2011-03-24 |
| CN102498112B (zh) | 2015-05-20 |
| ES2540810T3 (es) | 2015-07-13 |
| IL218641A0 (en) | 2012-05-31 |
| NZ598277A (en) | 2014-03-28 |
| CN102498112A (zh) | 2012-06-13 |
| KR20120083416A (ko) | 2012-07-25 |
| HK1169106A1 (en) | 2013-01-18 |
| AU2010295461B2 (en) | 2016-03-03 |
| EP2477991B1 (en) | 2015-04-15 |
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