DK2468724T3 - Syntese af pyrrolidinforbindelser - Google Patents
Syntese af pyrrolidinforbindelser Download PDFInfo
- Publication number
- DK2468724T3 DK2468724T3 DK12159851.0T DK12159851T DK2468724T3 DK 2468724 T3 DK2468724 T3 DK 2468724T3 DK 12159851 T DK12159851 T DK 12159851T DK 2468724 T3 DK2468724 T3 DK 2468724T3
- Authority
- DK
- Denmark
- Prior art keywords
- compound
- formula
- water
- benzamidopyrrolidine
- optionally substituted
- Prior art date
Links
- 230000015572 biosynthetic process Effects 0.000 title claims description 26
- 238000003786 synthesis reaction Methods 0.000 title description 26
- 150000003235 pyrrolidines Chemical class 0.000 title description 4
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- AMUAXJVNXHQNBH-OXPNAJOUSA-N (2s,4r)-1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid;hydrate;hydrochloride Chemical compound O.Cl.C1[C@@H](C(O)=O)N(C(=O)CN)C[C@@H]1NC(=O)C1=CC=CC=C1 AMUAXJVNXHQNBH-OXPNAJOUSA-N 0.000 claims description 40
- 239000002904 solvent Substances 0.000 claims description 35
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- AHXPMNACLWKFRQ-DHXVBOOMSA-N (2s,4r)-1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid;hydrochloride Chemical compound Cl.C1[C@@H](C(O)=O)N(C(=O)CN)C[C@@H]1NC(=O)C1=CC=CC=C1 AHXPMNACLWKFRQ-DHXVBOOMSA-N 0.000 claims description 29
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
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- A—HUMAN NECESSITIES
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Claims (15)
1. Forbindelse, der er (2S, 4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidin-2-carboxylsyrehydrochlorid-monohydrat.
2. Forbindelse ifølge krav 1, som har en desolveringsbegyndelsestemperatur på 104 °C.
3. Forbindelse ifølge krav 1, som har to endoterme overgange med begyndelsestemperaturer på 104 °C og 168 °C.
4. Forbindelse ifølge et hvilket som helst af de foregående krav, som har røntgenpulverdiffraktionstoppunkter på 12,5 °2Θ og 19,0 °2Θ, som eventuelt yderligere har røntgenpulverdiffraktionstoppunkter på 17,1 °2Θ, 19,7°2Θ, 20,5 °2Θ, 21,8 °2Θ, 23,3 °2Θ og 23,4 °2Θ, som eventuelt yderligere har røntgenpulverdiffraktionstoppunkter på 5,4 °2Θ, 20,7 °2Θ, 21,2°2Θ, 23,1 °2Θ, 26,4 °2Θ og 27,4 °2Θ.
5. Farmaceutisk sammensætning omfattende en forbindelse ifølge et hvilket som helst af kravene 1 til 4 og en farmaceutisk acceptabel bærer.
6. Forbindelse ifølge et hvilket som helst af kravene 1 til 4 til anvendelse i terapi.
7. Forbindelse ifølge et hvilket som helst af kravene 1 til 4 til anvendelse i en fremgangsmåde til behandling af kardiovaskulær sygdom, osteoporose, inflammation i luftvejsepitelet, sygdomme i alveolært væv, blæreinkontinens, nedsat hørelse, endotelskader, type I- eller type ll-diabetes, diabetisk re-tinopati, diabetisk neuropati, aterosklerose, CNS-relaterede tilstande, krampeanfald, iskæmi, tandvævssygdomme, nyrelidelser, anæmi, leukopeni, trombocytopeni, pancytopeni, overfladiske sår, dybe sår som følge af traume, knoglefrakturer, erektil dysfunktion, urinblæreinkontinens, neuropatiske smerter, subkronisk og kronisk inflammation, cancer, knoglemarvsinsufficiens, stamcelletransplantation, tilstande, der opstår under transplantation af celler og væv, tilstande, der opstår under medicinske procedurer, tilstande forårsaget af et overskud af reaktive iltarter, frie radikaler eller nitrogenoxid, gravidi tetsrelaterede sygdomme eller lidelser, kvindelig infertilitet eller slagtilfælde, fortrinsvis til anvendelse i en fremgangsmåde til behandling af kardiovasku-lær sygdom eller i en fremgangsmåde til behandling af iskæmi.
8. Forbindelse til anvendelse ifølge et hvilket som helst af kravene 1 til 4 til anvendelse i en fremgangsmåde til forebyggelse eller behandling af iskæ-misk skade i et eller flere organer hos et pattedyr, hvor organet eventuelt er udvalgt blandt hjertet, centralnervesystemet, nyren, mave-tarm-kanalen, leveren, lungerne og ekstremiteterne.
9. Anvendelse af en forbindelse ifølge et hvilket som helst af kravene 1 til 4 til fremstilling af et medikament til behandling af kardiovaskulær sygdom, oste-oporose, inflammation i luftvejsepitelet, sygdomme i alveolært væv, blærein-kontinens, nedsat hørelse, endotelskader, type I- eller type ll-diabetes, diabetisk retinopati, diabetisk neuropati, aterosklerose, CNS-relaterede tilstande, krampeanfald, iskæmi, tandvævssygdomme, nyrelidelser, anæmi, leukopeni, trombocytopeni, pancytopeni, overfladiske sår, dybe sår som følge af traume, knoglefrakturer, erektil dysfunktion, urinblæreinkontinens, neuropatiske smerter, subkronisk og kronisk inflammation, cancer, knoglemarvsinsufficiens, stamcelletransplantation, tilstande, der opstår under transplantation af celler og væv, tilstande, der opstår under medicinske procedurer, tilstande forårsaget af et overskud af reaktive iltarter, frie radikaler eller nitrogenoxid, graviditetsrelaterede sygdomme eller lidelser, kvindelig infertilitet eller slagtilfælde, fortrinsvis til anvendelse i en fremgangsmåde til behandling af kardiovaskulær sygdom eller i en fremgangsmåde til behandling af iskæmi.
10. Anvendelse af en forbindelse ifølge et hvilket som helst af kravene 1 til 4 til fremstilling af et medikament til forebyggelse eller behandling af iskæmisk skade i et eller flere organer hos et pattedyr, hvor organet eventuelt er udvalgt blandt hjertet, centralnervesystemet, nyren, mave-tarm-kanalen, leveren, lungerne og ekstremiteterne.
11. Fremgangsmåde til fremstilling af en forbindelse defineret i et hvilket som helst af kravene 1 til 4, omfattende at tilvejebringe en opløsning af (2S, 4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidin-2-carboxylsyrehydrochlorid i et krystalliseringsmedium, hvor krystalliseringsmediet omfatter mindst et vand blandbart organisk opløsningsmiddel og vand, og at bevare opløsningen i et tidsrum og under betingelser, der er egnede til dannelse af (2S, 4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidin-2-carboxylsyrehydrochlorid-monohydrat.
12. Fremgangsmåde til fremstilling af en forbindelse defineret i et hvilket som helst af kravene 1 til 4 ifølge krav 11, hvor det mindst ene vandblandbare organiske opløsningsmiddel omfatter mindst et opløsningsmiddel udvalgt blandt vandblandbare alkoholer, vandblandbare ketoner og vandblandbare ethere, fortrinsvis udvalgt blandt vandblandbare CrCralkoholer, vandblandbare CrC6-ketoner og CrC6-vandblandbare ethere.
13. Fremgangsmåde til fremstilling af en forbindelse defineret i et hvilket som helst af kravene 1 til 4 ifølge krav 11, hvor det mindst ene vandblandbare organiske opløsningsmiddel omfatter en blanding af isopropanol, acetone og f-butylmethylether.
14. Fremgangsmåde til fremstilling af en forbindelse defineret i et hvilket som helst af kravene 1 til 4 ifølge krav 11, hvor betingelserne, der er egnede til dannelse af (2S, 4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidin-2-carboxylsyrehydrochlorid-monohydrat omfatter at holde opløsningen ved rumtemperatur.
15. Fremgangsmåde til fremstilling af en forbindelse defineret i et hvilket som helst af kravene 1 til 4 ifølge krav 11, hvor krystalliseringsmediet omfatter op til 5 volumen% vand.
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| EP2074087A2 (en) | 2006-12-21 | 2009-07-01 | Wyeth | Synthesis of pyrrolidine compounds |
| CN101863817A (zh) * | 2009-06-09 | 2010-10-20 | 大连凯飞精细化工有限公司 | (2s,4r)-4-氨基吡咯啉-1,2-二羧酸-1-叔丁酯-2-甲酯盐酸盐的制法 |
| CN103333094B (zh) * | 2013-06-19 | 2015-05-13 | 广东肇庆星湖生物科技股份有限公司 | 一种脯氨酸结晶精制的工艺方法 |
| CN110709096B (zh) | 2017-05-05 | 2023-10-31 | 泽兰德制药公司 | 细胞间隙连接通讯调节剂及其在糖尿病性眼病治疗中的应用 |
| CN112142823B (zh) * | 2019-06-28 | 2022-08-05 | 深圳翰宇药业股份有限公司 | 一种zp-1609的合成方法 |
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| JP2025500123A (ja) | 2021-12-22 | 2025-01-09 | ブルイエ・セラピューティクス・アー・ペー・エス | ギャップ結合モジュレーターおよび加齢黄斑変性の処置のためのその使用 |
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| SI21507A (sl) * | 2003-05-16 | 2004-12-31 | LEK farmacevtska dru�ba d.d. | Postopek za pripravo spojin z ace inhibitornim delovanjem |
| WO2005037214A2 (en) | 2003-10-14 | 2005-04-28 | Intermune, Inc. | Macrocyclic carboxylic acids and acylsulfonamides as inhibitors of hcv replication |
| CN1528745A (zh) | 2003-10-21 | 2004-09-15 | 山东大学 | 吡咯烷类基质金属蛋白酶抑制剂及其制备方法 |
| EP1742914A1 (en) | 2004-02-27 | 2007-01-17 | Schering Corporation | Cyclobutenedione groups-containing compounds as inhibitors of hepatitis c virus ns3 serine protease |
| AU2005224091B2 (en) * | 2004-03-15 | 2012-02-02 | Janssen Pharmaceutica, N.V. | Novel compounds as opioid receptor modulators |
| AP2006003763A0 (en) | 2004-03-30 | 2006-10-31 | Intermune Inc | Macrocyclic compounds as inhibitors of viral replication |
| EP1604977A1 (en) | 2004-06-02 | 2005-12-14 | Faust Pharmaceuticals | CIS pyrrolidinyl derivatives and their uses |
| RS51974B (sr) | 2004-07-16 | 2012-02-29 | Gilead Sciences Inc. | Antivirusna jedinjenja |
| US7820699B2 (en) | 2005-04-27 | 2010-10-26 | Hoffmann-La Roche Inc. | Cyclic amines |
| UA96283C2 (uk) * | 2005-12-23 | 2011-10-25 | Зіланд Фарма А/С | Модифіковані міметики лізину |
| EP2074087A2 (en) | 2006-12-21 | 2009-07-01 | Wyeth | Synthesis of pyrrolidine compounds |
-
2007
- 2007-12-20 EP EP07867854A patent/EP2074087A2/en not_active Withdrawn
- 2007-12-20 PL PL12159851T patent/PL2468724T3/pl unknown
- 2007-12-20 EP EP12159851.0A patent/EP2468724B1/en active Active
- 2007-12-20 ES ES12159851.0T patent/ES2558856T3/es active Active
- 2007-12-20 US US12/005,118 patent/US20080188545A1/en not_active Abandoned
- 2007-12-20 AR ARP070105792A patent/AR064626A1/es unknown
- 2007-12-20 WO PCT/US2007/026002 patent/WO2008079266A2/en not_active Ceased
- 2007-12-20 DK DK12159851.0T patent/DK2468724T3/da active
- 2007-12-21 TW TW096149203A patent/TW200833660A/zh unknown
-
2008
- 2008-01-02 PE PE2008000034A patent/PE20081400A1/es not_active Application Discontinuation
-
2010
- 2010-01-19 US US12/690,043 patent/US20100249207A1/en not_active Abandoned
-
2012
- 2012-08-23 US US13/593,110 patent/US8927590B2/en active Active
-
2014
- 2014-12-16 US US14/572,262 patent/US9469609B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| EP2468724A1 (en) | 2012-06-27 |
| US9469609B2 (en) | 2016-10-18 |
| ES2558856T3 (es) | 2016-02-09 |
| PE20081400A1 (es) | 2008-10-24 |
| TW200833660A (en) | 2008-08-16 |
| PL2468724T3 (pl) | 2016-05-31 |
| EP2074087A2 (en) | 2009-07-01 |
| US20130053344A1 (en) | 2013-02-28 |
| WO2008079266A2 (en) | 2008-07-03 |
| US20150322007A1 (en) | 2015-11-12 |
| US20100249207A1 (en) | 2010-09-30 |
| EP2468724B1 (en) | 2015-11-18 |
| US8927590B2 (en) | 2015-01-06 |
| US20080188545A1 (en) | 2008-08-07 |
| WO2008079266A3 (en) | 2008-11-06 |
| AR064626A1 (es) | 2009-04-15 |
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