AR105091A1 - Procedimiento para la síntesis de derivados de rapamicina - Google Patents
Procedimiento para la síntesis de derivados de rapamicinaInfo
- Publication number
- AR105091A1 AR105091A1 ARP160101863A ARP160101863A AR105091A1 AR 105091 A1 AR105091 A1 AR 105091A1 AR P160101863 A ARP160101863 A AR P160101863A AR P160101863 A ARP160101863 A AR P160101863A AR 105091 A1 AR105091 A1 AR 105091A1
- Authority
- AR
- Argentina
- Prior art keywords
- formula
- triflate
- trisubstituted
- rapamycin
- rapamycin derivative
- Prior art date
Links
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical class C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 title abstract 9
- 238000000034 method Methods 0.000 title abstract 4
- 230000015572 biosynthetic process Effects 0.000 title 1
- 238000003786 synthesis reaction Methods 0.000 title 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 abstract 4
- 238000006243 chemical reaction Methods 0.000 abstract 3
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 abstract 2
- 238000004519 manufacturing process Methods 0.000 abstract 2
- 150000007530 organic bases Chemical class 0.000 abstract 2
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 abstract 2
- BABPEPRNSRIYFA-UHFFFAOYSA-N silyl trifluoromethanesulfonate Chemical class FC(F)(F)S(=O)(=O)O[SiH3] BABPEPRNSRIYFA-UHFFFAOYSA-N 0.000 abstract 2
- 229960002930 sirolimus Drugs 0.000 abstract 2
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 238000010511 deprotection reaction Methods 0.000 abstract 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 abstract 1
Classifications
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07D498/16—Peri-condensed systems
-
- 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
- C07D498/18—Bridged systems
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)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
La presente se refiere a un procedimiento para la producción de un derivado de rapamicina de fórmula (1), comprendiendo el procedimiento la preparación de un triflato de 2-(sililo trisustituido)oxietilo mediante la reacción de óxido de etileno y un triflato de sililo trisustituido, la reacción del triflato de 2-(sililo trisustituido)oxietilo resultante con rapamicina en presencia de un exceso molar de base orgánica, y la desprotección para obtener el derivado de rapamicina del compuesto de fórmula (1). Reivindicación 1: Procedimiento para la producción de un derivado de rapamicina de fórmula (1), caracterizado porque comprende: (a) preparar un triflato de 2-(sililo trisustituido)oxietilo de fórmula (3) mediante la reacción de óxido de etileno y un triflato de sililo trisustituido de fórmula (2) en el que R¹, R², y R³ se seleccionaron en forma independiente del grupo que consiste de alquilo C₁₋₁₂ y arilo C₁₋₁₂; (b) hacer reaccionar el triflato de 2-(sililo trisustituido)oxietilo de fórmula (3) obtenido en el paso (a) con rapamicina en presencia de un exceso molar de base orgánica para obtener un derivado de rapamicina protegido de fórmula (4); y (c) desproteger el derivado de rapamicina protegido de fórmula (4) para obtener el derivado de rapamicina si es la fórmula (1).
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP15173283.1A EP3109250A1 (en) | 2015-06-23 | 2015-06-23 | Method for the synthesis of rapamycin derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR105091A1 true AR105091A1 (es) | 2017-09-06 |
Family
ID=53488213
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP160101863A AR105091A1 (es) | 2015-06-23 | 2016-06-22 | Procedimiento para la síntesis de derivados de rapamicina |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US10308665B2 (es) |
| EP (2) | EP3109250A1 (es) |
| JP (1) | JP6745823B2 (es) |
| KR (1) | KR102621941B1 (es) |
| CN (1) | CN107735398B (es) |
| AR (1) | AR105091A1 (es) |
| AU (1) | AU2016282816A1 (es) |
| ES (1) | ES2741013T3 (es) |
| HU (1) | HUE045651T2 (es) |
| MX (1) | MX2017017022A (es) |
| PL (1) | PL3313853T3 (es) |
| RU (1) | RU2718058C2 (es) |
| SI (1) | SI3313853T1 (es) |
| TW (1) | TWI646100B (es) |
| UY (1) | UY36746A (es) |
| WO (1) | WO2016207205A1 (es) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102641816B1 (ko) | 2016-07-19 | 2024-02-29 | 삼성디스플레이 주식회사 | 디스플레이 장치 |
| CN109206441B (zh) * | 2017-06-30 | 2022-05-20 | 正大天晴药业集团股份有限公司 | 一种依维莫司的纯化方法 |
| UY37900A (es) | 2017-09-26 | 2019-04-30 | Novartis Ag | Nuevos derivados de rapamicina |
| LT3898637T (lt) | 2018-12-18 | 2025-03-10 | Novartis Ag | Rapamicino dariniai |
| CN109776571B (zh) * | 2019-01-31 | 2021-06-11 | 哈药慈航制药股份有限公司 | 一种雷帕霉素类似物及其制备方法和应用 |
| RU2716714C1 (ru) * | 2019-08-26 | 2020-03-16 | Закрытое Акционерное Общество "Биокад" | Новый способ получения эверолимуса |
| CN113735880B (zh) * | 2020-05-29 | 2023-12-22 | 鲁南制药集团股份有限公司 | 一种依维莫司的制备方法及其中间体 |
| CN114671891A (zh) * | 2020-12-24 | 2022-06-28 | 鲁南制药集团股份有限公司 | 一种依维莫司乙基化杂质的制备方法 |
| CN115028658A (zh) * | 2022-07-06 | 2022-09-09 | 国药集团川抗制药有限公司 | 雷帕霉素硅醇酯及其制备方法和应用 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9221220D0 (en) | 1992-10-09 | 1992-11-25 | Sandoz Ag | Organic componds |
| GB0601406D0 (en) * | 2006-01-24 | 2006-03-08 | Novartis Ag | Organic Compounds |
| GB0609962D0 (en) * | 2006-05-19 | 2006-06-28 | Biotica Tech Ltd | Novel compounds |
| CN102127092B (zh) * | 2010-01-18 | 2013-04-17 | 东南大学 | 依维莫斯的制备 |
| WO2012066502A1 (en) | 2010-11-19 | 2012-05-24 | Biocon Limited | Processes for preparation of everolimus and intermediates thereof |
| EP4230631A3 (en) | 2011-02-04 | 2024-03-27 | Synthon B.V. | Process for making trisubstituted silyloxyethyl triflates |
| CN102268015B (zh) * | 2011-08-30 | 2013-08-28 | 成都摩尔生物医药有限公司 | 一种依维莫司的合成方法 |
| CN102786534A (zh) * | 2012-05-25 | 2012-11-21 | 上海现代制药股份有限公司 | 一种依维莫司的制备方法 |
| AU2012395673A1 (en) * | 2012-11-30 | 2014-08-14 | Hangzhou Zylox Pharma Co., Ltd. | Rapamycin analogs and methods for making same |
| RU2691728C2 (ru) | 2013-06-20 | 2019-06-18 | Новартис Аг | Алкилирование сульфонатом алкилфторалкила |
| CN103848849B (zh) * | 2014-03-24 | 2016-02-24 | 上海医药工业研究院 | 依维莫司的制备工艺 |
| CN104478898A (zh) * | 2014-11-18 | 2015-04-01 | 连云港恒运医药科技有限公司 | 依维莫司及其中间体的制备方法 |
-
2015
- 2015-06-23 EP EP15173283.1A patent/EP3109250A1/en not_active Withdrawn
-
2016
- 2016-06-22 EP EP16731862.5A patent/EP3313853B1/en active Active
- 2016-06-22 WO PCT/EP2016/064389 patent/WO2016207205A1/en not_active Ceased
- 2016-06-22 CN CN201680036479.1A patent/CN107735398B/zh active Active
- 2016-06-22 JP JP2017566621A patent/JP6745823B2/ja active Active
- 2016-06-22 MX MX2017017022A patent/MX2017017022A/es unknown
- 2016-06-22 HU HUE16731862A patent/HUE045651T2/hu unknown
- 2016-06-22 KR KR1020187001488A patent/KR102621941B1/ko active Active
- 2016-06-22 PL PL16731862T patent/PL3313853T3/pl unknown
- 2016-06-22 UY UY0001036746A patent/UY36746A/es not_active Application Discontinuation
- 2016-06-22 ES ES16731862T patent/ES2741013T3/es active Active
- 2016-06-22 SI SI201630337T patent/SI3313853T1/sl unknown
- 2016-06-22 AR ARP160101863A patent/AR105091A1/es unknown
- 2016-06-22 AU AU2016282816A patent/AU2016282816A1/en not_active Abandoned
- 2016-06-22 TW TW105119625A patent/TWI646100B/zh active
- 2016-06-22 US US15/737,861 patent/US10308665B2/en active Active
- 2016-06-22 RU RU2017144050A patent/RU2718058C2/ru active
Also Published As
| Publication number | Publication date |
|---|---|
| CN107735398A (zh) | 2018-02-23 |
| HUE045651T2 (hu) | 2020-01-28 |
| RU2718058C2 (ru) | 2020-03-30 |
| US10308665B2 (en) | 2019-06-04 |
| EP3109250A1 (en) | 2016-12-28 |
| EP3313853A1 (en) | 2018-05-02 |
| TW201713669A (zh) | 2017-04-16 |
| JP6745823B2 (ja) | 2020-08-26 |
| US20190010168A1 (en) | 2019-01-10 |
| SI3313853T1 (sl) | 2019-10-30 |
| AU2016282816A1 (en) | 2018-01-04 |
| WO2016207205A1 (en) | 2016-12-29 |
| TWI646100B (zh) | 2019-01-01 |
| UY36746A (es) | 2016-12-30 |
| KR20180015257A (ko) | 2018-02-12 |
| RU2017144050A3 (es) | 2019-11-11 |
| PL3313853T3 (pl) | 2020-01-31 |
| JP2018518504A (ja) | 2018-07-12 |
| KR102621941B1 (ko) | 2024-01-05 |
| ES2741013T3 (es) | 2020-02-07 |
| EP3313853B1 (en) | 2019-05-08 |
| MX2017017022A (es) | 2018-08-15 |
| RU2017144050A (ru) | 2019-07-23 |
| CN107735398B (zh) | 2020-07-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FB | Suspension of granting procedure |