BR112021009122A2 - produto de composto ativo de {4,6-diamino-2-[5-flúor-1-(2-fluorbenzil)-1h-pirazolo[3,4-b] piridin-3-il]pirimidin-5-il}carbamato de metila tendo propriedades, produção e formulação melhoradas do mesmo - Google Patents
produto de composto ativo de {4,6-diamino-2-[5-flúor-1-(2-fluorbenzil)-1h-pirazolo[3,4-b] piridin-3-il]pirimidin-5-il}carbamato de metila tendo propriedades, produção e formulação melhoradas do mesmo Download PDFInfo
- Publication number
- BR112021009122A2 BR112021009122A2 BR112021009122-0A BR112021009122A BR112021009122A2 BR 112021009122 A2 BR112021009122 A2 BR 112021009122A2 BR 112021009122 A BR112021009122 A BR 112021009122A BR 112021009122 A2 BR112021009122 A2 BR 112021009122A2
- Authority
- BR
- Brazil
- Prior art keywords
- active compound
- wetting agent
- formula
- water
- methyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 356
- 239000000203 mixture Substances 0.000 title abstract description 45
- 238000004519 manufacturing process Methods 0.000 title abstract description 41
- 238000009472 formulation Methods 0.000 title abstract description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 title description 8
- OWSMCPGVQOVOGQ-UHFFFAOYSA-N [4,6-diamino-2-[5-fluoro-1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl]carbamic acid Chemical compound NC1=C(NC(O)=O)C(N)=NC(C=2C3=CC(F)=CN=C3N(CC=3C(=CC=CC=3)F)N=2)=N1 OWSMCPGVQOVOGQ-UHFFFAOYSA-N 0.000 title description 3
- 238000000034 method Methods 0.000 claims abstract description 133
- 230000008569 process Effects 0.000 claims abstract description 108
- 238000001035 drying Methods 0.000 claims abstract description 36
- 238000007873 sieving Methods 0.000 claims abstract description 32
- 238000002955 isolation Methods 0.000 claims abstract description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 141
- 239000000080 wetting agent Substances 0.000 claims description 100
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 96
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 95
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 48
- 230000004048 modification Effects 0.000 claims description 46
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- 239000007787 solid Substances 0.000 claims description 32
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- 239000002904 solvent Substances 0.000 claims description 29
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 16
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- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 8
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- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
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- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 8
- ZNOVTXRBGFNYRX-UHFFFAOYSA-N 2-[[4-[(2-amino-5-methyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 ZNOVTXRBGFNYRX-UHFFFAOYSA-N 0.000 claims description 7
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- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 7
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 6
- FFOPEPMHKILNIT-UHFFFAOYSA-N Isopropyl butyrate Chemical compound CCCC(=O)OC(C)C FFOPEPMHKILNIT-UHFFFAOYSA-N 0.000 claims description 6
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- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 6
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- 239000013078 crystal Substances 0.000 claims description 6
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP18213115 | 2018-12-17 | ||
| EP18213115.1 | 2018-12-17 | ||
| PCT/EP2019/085255 WO2020126983A1 (en) | 2018-12-17 | 2019-12-16 | Methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate active compound product having improved properties, production and formulation thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BR112021009122A2 true BR112021009122A2 (pt) | 2021-08-10 |
Family
ID=64744472
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR112021009122-0A BR112021009122A2 (pt) | 2018-12-17 | 2019-12-16 | produto de composto ativo de {4,6-diamino-2-[5-flúor-1-(2-fluorbenzil)-1h-pirazolo[3,4-b] piridin-3-il]pirimidin-5-il}carbamato de metila tendo propriedades, produção e formulação melhoradas do mesmo |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US12172996B2 (https=) |
| EP (1) | EP3898624A1 (https=) |
| JP (1) | JP7529667B2 (https=) |
| KR (1) | KR102872983B1 (https=) |
| CN (1) | CN113207290B (https=) |
| AR (1) | AR116912A1 (https=) |
| AU (1) | AU2019409269B2 (https=) |
| BR (1) | BR112021009122A2 (https=) |
| CA (1) | CA3123360A1 (https=) |
| CL (1) | CL2021001580A1 (https=) |
| CO (1) | CO2021007668A2 (https=) |
| IL (1) | IL283976B2 (https=) |
| JO (1) | JOP20210155B1 (https=) |
| MX (1) | MX2021007090A (https=) |
| PE (1) | PE20211593A1 (https=) |
| SG (1) | SG11202104953VA (https=) |
| TW (1) | TWI830835B (https=) |
| UA (1) | UA129677C2 (https=) |
| WO (1) | WO2020126983A1 (https=) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI830835B (zh) | 2018-12-17 | 2024-02-01 | 德商亞德維瑞醫藥有限公司 | 具改善性質之{4,6-二胺基-2-[5-氟-1-(2-氟芐基)-1H-吡唑並[3,4-b]吡啶-3-基]嘧啶-5-基}胺基甲酸甲酯活性化合物產物、其製造及調配物 |
| EP4099987B1 (en) | 2020-02-03 | 2025-03-12 | Adverio Pharma GmbH | Nanoformulations of methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate |
| EP3925953A1 (en) | 2020-06-16 | 2021-12-22 | Adverio Pharma GmbH | Process for preparing methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate |
| WO2025114276A1 (en) | 2023-12-01 | 2025-06-05 | Krka, D.D., Novo Mesto | Solid oral composition comprising vericiguat |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
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| FR2745813B1 (fr) | 1996-03-07 | 1998-05-07 | Rhone Poulenc Chimie | Agglomerats spheriques d'acide 10-phenothiazinylpropanoique et leur procede de preparation |
| DE19834044A1 (de) | 1998-07-29 | 2000-02-03 | Bayer Ag | Neue substituierte Pyrazolderivate |
| UY33041A (es) | 2009-11-27 | 2011-06-30 | Bayer Schering Pharma Aktienegesellschaft | Procedimiento para la preparaciòn de {4,6-diamino-2-[1-(2-fluorobencil)-1h-pirazolo[3,4-b]piridin-3-il]pirimidin-5-il}carbamato de metilo y su purificaciòn para el uso como principio activo farmacèutico |
| PL2604608T3 (pl) | 2009-11-27 | 2016-02-29 | Adverio Pharma Gmbh | Sposób wytwarzania {4,6-diamino-2-[1-(2-fluorobenzylo)-1H-pirazolo[3,4-b]pirydyn-3-ylo]pirymidyn-5-ylo}metylokarbaminianu metylu |
| DE102010021637A1 (de) | 2010-05-26 | 2011-12-01 | Bayer Schering Pharma Aktiengesellschaft | Substituierte 5-Fluor-1H-Pyrazolopyridine und ihre Verwendung |
| ES2603028T3 (es) * | 2011-11-25 | 2017-02-23 | Adverio Pharma Gmbh | Procedimiento para la preparación de (Z)-alfa-fluoro-beta-amino-acrilaldehídos sustituidos |
| MX2015010725A (es) * | 2013-02-21 | 2016-05-31 | Adverio Pharma Gmbh | Formas de metil {4,6-diamino-2-[1-(2-fluorobencil)-1h-pirazolo [3,4-b] piridino-3-il] pirimidino-5-il} metil carbamato. |
| PL2792682T3 (pl) | 2013-04-19 | 2017-04-28 | Zach System | Sposób wytwarzania stałej postaci octanu abirateronu |
| WO2016113415A1 (en) * | 2015-01-16 | 2016-07-21 | Sandoz Ag | Process for the preparation of riociguat essentially free from genotoxic impurities |
| WO2017025981A1 (en) * | 2015-08-13 | 2017-02-16 | Msn Laboratories Private Limited | Process for the preparation of methyl 4,6-diamino-2-[l-(2-fhiorobenzvr)-lh-pyrazolo i3,4-blpvridin-3-vn-5-pyrimidinyl(methvl)carbamate and its polymorphs thereof |
| TWI830835B (zh) | 2018-12-17 | 2024-02-01 | 德商亞德維瑞醫藥有限公司 | 具改善性質之{4,6-二胺基-2-[5-氟-1-(2-氟芐基)-1H-吡唑並[3,4-b]吡啶-3-基]嘧啶-5-基}胺基甲酸甲酯活性化合物產物、其製造及調配物 |
| CN113272286B (zh) | 2019-01-22 | 2024-04-16 | 阿德弗里奥药品有限责任公司 | 制备4-(2,2,3,3-四氟丙基)吗啉的方法 |
| EP4099987B1 (en) * | 2020-02-03 | 2025-03-12 | Adverio Pharma GmbH | Nanoformulations of methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate |
| EP3925953A1 (en) * | 2020-06-16 | 2021-12-22 | Adverio Pharma GmbH | Process for preparing methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate |
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2019
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- 2019-12-16 WO PCT/EP2019/085255 patent/WO2020126983A1/en not_active Ceased
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| PE20211593A1 (es) | 2021-08-18 |
| CL2021001580A1 (es) | 2021-12-03 |
| SG11202104953VA (en) | 2021-06-29 |
| JOP20210155B1 (ar) | 2025-10-01 |
| AU2019409269A1 (en) | 2021-06-03 |
| JP7529667B2 (ja) | 2024-08-06 |
| IL283976B1 (en) | 2024-12-01 |
| TW202039488A (zh) | 2020-11-01 |
| IL283976B2 (en) | 2025-04-01 |
| CN113207290A (zh) | 2021-08-03 |
| JOP20210155A1 (ar) | 2023-01-30 |
| EP3898624A1 (en) | 2021-10-27 |
| KR102872983B1 (ko) | 2025-10-17 |
| US20220048907A1 (en) | 2022-02-17 |
| UA129677C2 (uk) | 2025-07-02 |
| WO2020126983A1 (en) | 2020-06-25 |
| IL283976A (en) | 2021-07-29 |
| CA3123360A1 (en) | 2020-06-25 |
| JP2022515376A (ja) | 2022-02-18 |
| AR116912A1 (es) | 2021-06-23 |
| AU2019409269B2 (en) | 2025-04-03 |
| TWI830835B (zh) | 2024-02-01 |
| CO2021007668A2 (es) | 2021-07-19 |
| CN113207290B (zh) | 2024-04-09 |
| KR20210104703A (ko) | 2021-08-25 |
| US12172996B2 (en) | 2024-12-24 |
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