CA2938103C - Crystalline forms of dolutegravir sodium - Google Patents
Crystalline forms of dolutegravir sodium Download PDFInfo
- Publication number
- CA2938103C CA2938103C CA2938103A CA2938103A CA2938103C CA 2938103 C CA2938103 C CA 2938103C CA 2938103 A CA2938103 A CA 2938103A CA 2938103 A CA2938103 A CA 2938103A CA 2938103 C CA2938103 C CA 2938103C
- Authority
- CA
- Canada
- Prior art keywords
- dolutegravir sodium
- sodium form
- crystalline
- dolutegravir
- crystalline dolutegravir
- 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.)
- Active
Links
- UGWJRRXTMKRYNK-VSLILLSYSA-M dolutegravir sodium Chemical compound [Na+].C([C@@H]1OCC[C@H](N1C(=O)C1=C([O-])C2=O)C)N1C=C2C(=O)NCC1=CC=C(F)C=C1F UGWJRRXTMKRYNK-VSLILLSYSA-M 0.000 title claims abstract description 101
- 229960001976 dolutegravir sodium Drugs 0.000 title claims abstract description 98
- 238000002360 preparation method Methods 0.000 claims abstract description 26
- 238000000034 method Methods 0.000 claims abstract description 14
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 60
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 46
- 229960002542 dolutegravir Drugs 0.000 claims description 14
- RHWKPHLQXYSBKR-BMIGLBTASA-N dolutegravir Chemical compound C([C@@H]1OCC[C@H](N1C(=O)C1=C(O)C2=O)C)N1C=C2C(=O)NCC1=CC=C(F)C=C1F RHWKPHLQXYSBKR-BMIGLBTASA-N 0.000 claims description 13
- 238000001035 drying Methods 0.000 claims description 11
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 11
- 239000003960 organic solvent Substances 0.000 claims description 8
- 230000001476 alcoholic effect Effects 0.000 claims description 6
- 239000007787 solid Substances 0.000 description 22
- 235000011121 sodium hydroxide Nutrition 0.000 description 15
- 238000001144 powder X-ray diffraction data Methods 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 7
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 239000003586 protic polar solvent Substances 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 229940124525 integrase strand transfer inhibitor Drugs 0.000 description 2
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 125000006507 2,4-difluorobenzyl group Chemical group [H]C1=C(F)C([H])=C(F)C(=C1[H])C([H])([H])* 0.000 description 1
- -1 2-prapanol Substances 0.000 description 1
- XPOQHMRABVBWPR-UHFFFAOYSA-N Efavirenz Natural products O1C(=O)NC2=CC=C(Cl)C=C2C1(C(F)(F)F)C#CC1CC1 XPOQHMRABVBWPR-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 108700020129 Human immunodeficiency virus 1 p31 integrase Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241000721701 Lynx Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 1
- SUJUHGSWHZTSEU-UHFFFAOYSA-N Tipranavir Natural products C1C(O)=C(C(CC)C=2C=C(NS(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)C(=O)OC1(CCC)CCC1=CC=CC=C1 SUJUHGSWHZTSEU-UHFFFAOYSA-N 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 description 1
- 229960003804 efavirenz Drugs 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- MLBVMOWEQCZNCC-OEMFJLHTSA-N fosamprenavir Chemical compound C([C@@H]([C@H](OP(O)(O)=O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 MLBVMOWEQCZNCC-OEMFJLHTSA-N 0.000 description 1
- 229960003142 fosamprenavir Drugs 0.000 description 1
- 239000005414 inactive ingredient Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 229940124524 integrase inhibitor Drugs 0.000 description 1
- 239000002850 integrase inhibitor Substances 0.000 description 1
- 229940035429 isobutyl alcohol Drugs 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 1
- 229960001225 rifampicin Drugs 0.000 description 1
- 229960000311 ritonavir Drugs 0.000 description 1
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- JYGQNQHGQBEFJQ-UHFFFAOYSA-M sodium;propan-2-ol;hydroxide Chemical compound [OH-].[Na+].CC(C)O JYGQNQHGQBEFJQ-UHFFFAOYSA-M 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229960000838 tipranavir Drugs 0.000 description 1
- SUJUHGSWHZTSEU-FYBSXPHGSA-N tipranavir Chemical compound C([C@@]1(CCC)OC(=O)C([C@H](CC)C=2C=C(NS(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)=C(O)C1)CC1=CC=CC=C1 SUJUHGSWHZTSEU-FYBSXPHGSA-N 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 229940014075 tivicay Drugs 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/14—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Virology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Communicable Diseases (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Saccharide Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN455/MUM/2014 | 2014-02-07 | ||
| IN455MU2014 IN2014MU00455A (en:Method) | 2014-02-07 | 2015-02-04 | |
| PCT/IB2015/050841 WO2015118460A1 (en) | 2014-02-07 | 2015-02-04 | Crystalline forms of dolutegravir sodium |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2938103A1 CA2938103A1 (en) | 2015-08-13 |
| CA2938103C true CA2938103C (en) | 2021-08-10 |
Family
ID=53777379
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2938103A Active CA2938103C (en) | 2014-02-07 | 2015-02-04 | Crystalline forms of dolutegravir sodium |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US10087193B2 (en:Method) |
| EP (1) | EP3102582A1 (en:Method) |
| AU (1) | AU2015215630B2 (en:Method) |
| BR (1) | BR112016018056A2 (en:Method) |
| CA (1) | CA2938103C (en:Method) |
| IN (1) | IN2014MU00455A (en:Method) |
| WO (1) | WO2015118460A1 (en:Method) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10189860B2 (en) * | 2014-07-29 | 2019-01-29 | Lek Pharmaceuticals D.D. | Hydrates of dolutegravir sodium |
| EP3337479B1 (en) | 2015-08-19 | 2023-12-13 | Laurus Labs Limited | Novel polymorphs of dolutegravir and salts thereof |
| WO2017046131A1 (en) * | 2015-09-15 | 2017-03-23 | Ratiopharm Gmbh | Processes for preparing solid state forms of dolutegravir sodium |
| WO2017208105A1 (en) | 2016-05-30 | 2017-12-07 | Lupin Limited | Novel crystalline form of dolutegravir sodium |
| CN110958883A (zh) * | 2017-06-30 | 2020-04-03 | Viiv保健公司 | 组合及其用途和疗法 |
| US20210040116A1 (en) | 2017-09-07 | 2021-02-11 | Cipla Limited | New Polymorphs of Dolutegravir Sodium |
| US12227518B2 (en) * | 2019-02-05 | 2025-02-18 | Msn Laboratories Private Limited, R&D Center | Crystalline polymorphs of sodium (4R,12AS)-9-{[(2,4-difluorophenyl) methyl]carbamoyl}-4-methyl-6,8-dioxo-3,4,6,8,12,12A-hexahydro-2H-pyrido [1′,2′:4,5]pyrazino[2,1-b][1,3]oxazin-7-olate and process for preparation thereof |
| CN114213432B (zh) * | 2021-12-31 | 2023-02-17 | 瑞孚信江苏药业股份有限公司 | 度鲁特韦的制备方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2744019C (en) | 2008-12-11 | 2017-03-14 | Shionogi & Co., Ltd. | Synthesis of carbamoylpyridone hiv integrase inhibitors and intermediates |
| WO2013038407A1 (en) | 2011-09-14 | 2013-03-21 | Mapi Pharma Ltd. | Amorphous form of dolutegravir |
| EP3022209B1 (en) | 2013-07-17 | 2018-03-07 | ratiopharm GmbH | Dolutegravir potassium salt |
| WO2015019310A1 (en) * | 2013-08-07 | 2015-02-12 | Mylan Laboratories Ltd | Process for the preparation of dolute-gravir and intermediates thereof |
-
2015
- 2015-02-04 WO PCT/IB2015/050841 patent/WO2015118460A1/en active Application Filing
- 2015-02-04 BR BR112016018056A patent/BR112016018056A2/pt not_active Application Discontinuation
- 2015-02-04 IN IN455MU2014 patent/IN2014MU00455A/en unknown
- 2015-02-04 CA CA2938103A patent/CA2938103C/en active Active
- 2015-02-04 EP EP15710893.7A patent/EP3102582A1/en not_active Withdrawn
- 2015-02-04 AU AU2015215630A patent/AU2015215630B2/en not_active Ceased
- 2015-02-04 US US15/114,991 patent/US10087193B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| US10087193B2 (en) | 2018-10-02 |
| CA2938103A1 (en) | 2015-08-13 |
| US20160347766A1 (en) | 2016-12-01 |
| AU2015215630B2 (en) | 2018-08-16 |
| IN2014MU00455A (en:Method) | 2015-09-25 |
| WO2015118460A1 (en) | 2015-08-13 |
| AU2015215630A1 (en) | 2016-09-22 |
| BR112016018056A2 (pt) | 2017-08-08 |
| EP3102582A1 (en) | 2016-12-14 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20200204 |