DK2820000T3 - Besylat- og tosylatsalte af et dihydroquinazolinderivat og deres anvendelse som antivirale midler - Google Patents
Besylat- og tosylatsalte af et dihydroquinazolinderivat og deres anvendelse som antivirale midler Download PDFInfo
- Publication number
- DK2820000T3 DK2820000T3 DK13709345.6T DK13709345T DK2820000T3 DK 2820000 T3 DK2820000 T3 DK 2820000T3 DK 13709345 T DK13709345 T DK 13709345T DK 2820000 T3 DK2820000 T3 DK 2820000T3
- Authority
- DK
- Denmark
- Prior art keywords
- salt
- methoxy
- phenyl
- fluoro
- trifluoromethyl
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/84—Nitrogen atoms
-
- 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
-
- 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
- A61P31/20—Antivirals for DNA viruses
-
- 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
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/01—Sulfonic acids
- C07C309/28—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/29—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton of non-condensed six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/01—Sulfonic acids
- C07C309/28—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/29—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton of non-condensed six-membered aromatic rings
- C07C309/30—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton of non-condensed six-membered aromatic rings of six-membered aromatic rings substituted by alkyl groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Claims (13)
1. Salt af {8-fluor-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluormethyl)phenyl]-3,4-dihydroquinazolin-4-yl}eddikesyre eller et solvat deraf, valgt fra gruppen bestående af krystallinske besylatsalte af {8-fluor-2-[4-i (3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluormethyl)phenyl]-3,4-dihydroquinazolin-4-yl}eddikesyre, krystallinske tosylatsalte af {8-fluor-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluormethyl)phenyl]-3,4-dihydroquinazolin-4-yl}eddikesyre og solvater deraf. ) 2. Saltet ifølge krav 1, der er monobesylatsaltet af {8-fluor-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluormethyl)phenyl]-3,4-dihydroquinazolin-4-yl}eddikesyre eller et solvat deraf.
3. Saltet ifølge krav 2, der er monobesylatsaltet af {8-fluor-2-[4-(3- i methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluormethyl)phenyl]-3,4-dihydroquinazolin-4-yl}eddikesyre.
4. Saltet ifølge krav 3, kendetegnet ved at det udviser karakteristiske toppe ved ca. 6,9, 10,1 og 22,2 grader 2theta i røntgenpulverdiffraktogrammet (XRD). )
5. Saltet ifølge krav 1, der er monotosylatsaltet af {8-fluor-2-[4-{3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluormethyl)phenyl]-3,4-dihydroquinazolin-4-yl}eddikesyre eller et solvat deraf.
6. Saltet ifølge krav 5, der er monotosylatsaltet af {8-fluor-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluormethyl)phenyl]-3,4-dihydroquinazolin-4-yl}eddikesyre.
7. Saltet ifølge krav 6, kendetegnet ved at det udviser karakteristiske toppe ved ) ca. 6,9 og 20,7 grader 2theta i røntgenpulverdiffraktogrammet (XRD).
8. Fremgangsmåde til fremstilling af et salt ifølge et hvilket som helst af kravene 1 til 7 under anvendelse af følgende trin: a.) Opløse {8-fluor-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluormethyl)phenyl]-3,4-dihydroquinazolin-4-yl}eddikesyre eller et solvat deraf i en blanding af vand og mindst én (C3-C6) alkanon, om nødvendigt under opvarmning. i b.) Tilsætte benzensulfonsyre eller toluensulfonsyre til opløsningen opnået i trin a.), c. ) Nedkøle opløsningen opnået i trin b.) med henblik på at initiere krystallisationen af saltet eller et solvat af et salt, d. ) Adskille det udskrystalliserede salt eller solvat deraf opnået i trin c.), og I e.) Tørre saltet eller solvatet opnået i trin d.).
9. Fremgangsmåde til oprensning af 18-fluor-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluormethyl)phenyl]-3,4-dihydroquinazolin-4-yl}eddikesyre under anvendelse af følgende trin: i 1.) Omsætte {8-fluor-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2- methoxy-5-(trifluormethyl)phenyl]-3,4-dihydroquinazolin-4-yl}eddikesyre i et opløsningsmiddel med benzensulfonsyre eller toluensulfonsyre for at opnå et krystallinsk salt ifølge krav 1, 2.) Isolere saltet opnået i trin 1.), I 3.) Behandle det isolerede salt opnået i trin 2.) med en bufferopløsning ved pH 5 til 7 for at frigive den zwitterionisk form af {8-fluor-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluormethyl]phenyl]- 3.4- dihydroquinazolin-4-yl}eddikesyre, and 4.) Isolere den zwitterioniske form af {8-fluor-2-[4-(3-i methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluormethyl)phenyl]- 3.4- dihydroquinazolin-4-yl}eddikesyre opnået i trin 3.).
10. Saltet ifølge et hvilket som helst af kravene 1 til 7 til anvendelse i en fremgangsmåde til behandling og/eller profylakse af sygdom, især af virusinfektioner, fortrinsvis HCMV-infektioner eller infektioner med en anden repræsentant af herpes viridae-gruppen.
11. Lægemiddel indeholdende et salt ifølge et hvilket som helst af kravene 1 til 7 i kombination med mindst én farmaceutisk acceptabel excipiens.
12. Lægemidlet ifølge krav 11 til anvendelse i en fremgangsmåde til behandling ) og/eller prophylaxis af virusinfektioner, fortrinsvis HCMV-infektioner eller infektioner med en anden repræsentant af herpes viridae-gruppen.
13. Anvendelsen af et salt ifølge et hvilket som helst af kravene 1 til 7 til fremstillingen af et medikament til behandlingen og/eller profylakse af i virusinfektioner, fortrinsvis HCMV-infektioner eller infektioner med et andet medlem af herpes viridae-gruppen.
14. Saltet ifølge et hvilket som helst af kravene 1 til 7 til anvendelse i en fremgangsmåde til bekæmpelse af virusinfektioner, fortrinsvis HCMV-infektioner ) eller infektioner med en anden repræsentant af herpes w'r/c/ae-gruppen, hos mennesker eller dyr ved administration af saltet eller lægemidlet ifølge kravene 11 eller 12 til et menneske eller et dyr der kræver en sådan behandling.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102012101673A DE102012101673A1 (de) | 2012-02-29 | 2012-02-29 | Salze eines Dihydrochinazolinderivats |
| PCT/EP2013/054109 WO2013127968A1 (de) | 2012-02-29 | 2013-02-28 | Besylat- und tosylatsalze eines dihydrochinazolinderivates und ihre verwendung als antivirale mittel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2820000T3 true DK2820000T3 (da) | 2016-07-25 |
Family
ID=47884256
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK13709345.6T DK2820000T3 (da) | 2012-02-29 | 2013-02-28 | Besylat- og tosylatsalte af et dihydroquinazolinderivat og deres anvendelse som antivirale midler |
Country Status (19)
| Country | Link |
|---|---|
| US (4) | US9512085B2 (da) |
| EP (1) | EP2820000B1 (da) |
| JP (1) | JP6235493B2 (da) |
| CN (1) | CN104144916B (da) |
| CA (1) | CA2865534C (da) |
| CY (1) | CY1118284T1 (da) |
| DE (1) | DE102012101673A1 (da) |
| DK (1) | DK2820000T3 (da) |
| ES (1) | ES2583360T3 (da) |
| HK (1) | HK1205511A1 (da) |
| HR (1) | HRP20160886T1 (da) |
| HU (1) | HUE027751T2 (da) |
| LT (1) | LT2820000T (da) |
| PL (1) | PL2820000T3 (da) |
| PT (1) | PT2820000T (da) |
| RS (1) | RS54989B1 (da) |
| SI (1) | SI2820000T1 (da) |
| SM (1) | SMT201600343B (da) |
| WO (1) | WO2013127968A1 (da) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10319612A1 (de) | 2003-05-02 | 2004-11-18 | Bayer Healthcare Ag | Substituierte Dihydrochinazoline |
| DE102012101659A1 (de) * | 2012-02-29 | 2013-08-29 | Aicuris Gmbh & Co. Kg | Salze eines Dihydrochinazolinderivats |
| DE102012101673A1 (de) | 2012-02-29 | 2013-08-29 | Aicuris Gmbh & Co. Kg | Salze eines Dihydrochinazolinderivats |
| CA2916143C (en) * | 2013-06-19 | 2019-01-29 | Aicuris Anti-Infective Cures Gmbh | Amorphous letermovir and solid pharmaceutical formulations thereof for oral administration |
| WO2015088931A1 (en) * | 2013-12-12 | 2015-06-18 | Merck Sharp & Dohme Corp. | Process for making substituted quinazoline compounds |
| WO2017091453A1 (en) * | 2015-11-24 | 2017-06-01 | Merck Sharp & Dohme Corp. | Novel processes for making substituted quinazoline compounds using hydrogen bonding catalysts |
| US11174270B2 (en) * | 2018-02-08 | 2021-11-16 | Phaeno Therapeutics Co., Ltd. | Crystal form of 3,4-dihydrothieno[3,2-d]pyrimidine compound and preparation method thereof |
| IT202000017617A1 (it) | 2020-07-21 | 2022-01-21 | Olon Spa | Procedimento per la preparazione di un intermedio utilizzato nella sintesi del letermovir |
| US20230312485A1 (en) | 2020-08-17 | 2023-10-05 | Lupin Limited | A precipitation process for amorphous letermovir |
| CN113880776B (zh) * | 2021-11-16 | 2023-06-16 | 山东诚创蓝海医药科技有限公司 | 一种莱特莫韦中间体的制备方法 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10319612A1 (de) | 2003-05-02 | 2004-11-18 | Bayer Healthcare Ag | Substituierte Dihydrochinazoline |
| DE10352499A1 (de) * | 2003-11-11 | 2005-06-09 | Bayer Healthcare Ag | Substituierte Dihydrochinazoline II |
| DE102005027517A1 (de) * | 2005-06-15 | 2006-12-21 | Bayer Healthcare Ag | Verfahren zur Herstellung von Dihydrochinazolinen |
| DE102011101446A1 (de) | 2011-05-10 | 2012-11-15 | Aicuris Gmbh & Co. Kg | Herstellung von "Dense Bodies" (DB) |
| DE102012101659A1 (de) * | 2012-02-29 | 2013-08-29 | Aicuris Gmbh & Co. Kg | Salze eines Dihydrochinazolinderivats |
| DE102012101673A1 (de) | 2012-02-29 | 2013-08-29 | Aicuris Gmbh & Co. Kg | Salze eines Dihydrochinazolinderivats |
| CA2916143C (en) | 2013-06-19 | 2019-01-29 | Aicuris Anti-Infective Cures Gmbh | Amorphous letermovir and solid pharmaceutical formulations thereof for oral administration |
-
2012
- 2012-02-29 DE DE102012101673A patent/DE102012101673A1/de not_active Ceased
-
2013
- 2013-02-28 CA CA2865534A patent/CA2865534C/en active Active
- 2013-02-28 PL PL13709345T patent/PL2820000T3/pl unknown
- 2013-02-28 JP JP2014559231A patent/JP6235493B2/ja active Active
- 2013-02-28 US US14/381,625 patent/US9512085B2/en active Active
- 2013-02-28 LT LTEP13709345.6T patent/LT2820000T/lt unknown
- 2013-02-28 HU HUE13709345A patent/HUE027751T2/en unknown
- 2013-02-28 SI SI201330242A patent/SI2820000T1/sl unknown
- 2013-02-28 WO PCT/EP2013/054109 patent/WO2013127968A1/de active Application Filing
- 2013-02-28 DK DK13709345.6T patent/DK2820000T3/da active
- 2013-02-28 CN CN201380011791.1A patent/CN104144916B/zh active Active
- 2013-02-28 EP EP13709345.6A patent/EP2820000B1/de active Active
- 2013-02-28 PT PT137093456T patent/PT2820000T/pt unknown
- 2013-02-28 RS RS20160574A patent/RS54989B1/sr unknown
- 2013-02-28 ES ES13709345.6T patent/ES2583360T3/es active Active
-
2015
- 2015-06-25 HK HK15106079.4A patent/HK1205511A1/zh unknown
-
2016
- 2016-07-15 HR HRP20160886TT patent/HRP20160886T1/hr unknown
- 2016-07-18 CY CY20161100699T patent/CY1118284T1/el unknown
- 2016-09-30 SM SM201600343T patent/SMT201600343B/it unknown
- 2016-10-31 US US15/338,984 patent/US10287254B2/en not_active Ceased
-
2017
- 2017-07-03 US US15/640,661 patent/US20170362186A1/en not_active Abandoned
-
2021
- 2021-05-14 US US17/320,587 patent/USRE49897E1/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| EP2820000B1 (de) | 2016-04-20 |
| USRE49897E1 (en) | 2024-04-02 |
| US9512085B2 (en) | 2016-12-06 |
| US20170362186A1 (en) | 2017-12-21 |
| CA2865534A1 (en) | 2013-09-06 |
| SI2820000T1 (sl) | 2016-08-31 |
| HRP20160886T1 (hr) | 2016-09-23 |
| SMT201600343B (da) | 2016-11-10 |
| LT2820000T (lt) | 2016-11-10 |
| CN104144916B (zh) | 2016-08-24 |
| CA2865534C (en) | 2019-04-02 |
| US10287254B2 (en) | 2019-05-14 |
| US20150045371A1 (en) | 2015-02-12 |
| HUE027751T2 (en) | 2016-10-28 |
| HK1205511A1 (zh) | 2015-12-18 |
| PT2820000T (pt) | 2016-07-20 |
| JP6235493B2 (ja) | 2017-11-22 |
| PL2820000T3 (pl) | 2017-07-31 |
| US20170114026A1 (en) | 2017-04-27 |
| JP2015508800A (ja) | 2015-03-23 |
| RS54989B1 (sr) | 2016-11-30 |
| CN104144916A (zh) | 2014-11-12 |
| CY1118284T1 (el) | 2017-06-28 |
| DE102012101673A1 (de) | 2013-08-29 |
| WO2013127968A1 (de) | 2013-09-06 |
| ES2583360T3 (es) | 2016-09-20 |
| EP2820000A1 (de) | 2015-01-07 |
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