JP2008500263A - ペリンドプリル及びその薬学的に許容し得る塩の新規合成方法 - Google Patents
ペリンドプリル及びその薬学的に許容し得る塩の新規合成方法 Download PDFInfo
- Publication number
- JP2008500263A JP2008500263A JP2006515296A JP2006515296A JP2008500263A JP 2008500263 A JP2008500263 A JP 2008500263A JP 2006515296 A JP2006515296 A JP 2006515296A JP 2006515296 A JP2006515296 A JP 2006515296A JP 2008500263 A JP2008500263 A JP 2008500263A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- perindopril
- compound
- pharmaceutically acceptable
- group
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/022—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2
- C07K5/0222—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2 with the first amino acid being heterocyclic, e.g. Pro, Trp
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Cardiology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
0℃で、N−[(S)−エトキシカルボニル−1−ブチル]−(S)−アラニン200g、トルエン1.5リットル、次いで1,1’−カルボニルジイミダゾール184gを反応器に導入し、その後反応混合物の温度を20℃にした。20℃で1時間攪拌後、混合物を再び0℃に冷却し、得られた沈殿物を濾別し、次いで濾液を蒸発させ、表題化合物を90%の収率で得た。
(2S)−2,3,4,5,6,7−ヘキサヒドロ−1H−インドール−2−カルボン酸200g及びジクロロメタン1.5リットルを反応器に導入し、次いでトリエチルアミン180mlを導入した。続いて、上記工程で得られた化合物290gのジクロロメタン500ml溶液をゆっくりと加え、次いで周囲温度でさらに1時間攪拌した。水を加えた後、反応混合物を15℃に冷却し、2N塩酸溶液の添加により、pHを4.2に調整した。抽出に続き、有機層を洗浄し、次いで蒸発させて、所望の化合物を得た。
上記工程で得られた化合物200gの酢酸溶液、次いで10%Pt/C 5gを水素化容器に導入した。周囲温度で5barの圧力下、理論量の水素が吸収されるまで水素化した。濾過により触媒を除き、次いで0〜5℃に冷却し、濾過により得られた固体を回収した。ケークを洗浄し、それを一定重量になるまで乾燥した。
上記工程で得られた化合物(200g)を酢酸エチル2.8リットルに溶解し、次いでtert−ブチルアミン40g及び酢酸エチル0.4リットルを加えた。次いで得られた懸濁液を、完全に溶解するまで還流し、その後得られた溶液を加熱状態で濾過し、攪拌しながら15〜20℃の温度まで冷却した。続いて得られた沈殿物を濾別し、酢酸エチルで再びペースト状とし、乾燥させ、次いで粉砕し、95%の収率で所望の化合物を得た。
Claims (5)
- 式(I):
のペリンドプリル及びその薬学的に許容し得る塩の合成方法であって、式(II):
の化合物を、式(III):
(式中、X1及びX2は、同一又は異なっていてもよく、各々脱離基を表す)
の化合物と反応させ、式(IV):
の化合物を得て、それを式(V):
(式中、Rは、水素原子、あるいはベンジル又は直鎖状若しくは分岐鎖状の(C1−C6)アルキル基を表す)
の化合物又はその無機酸若しくは有機酸との付加塩と反応させ、単離の後、式(VI):
(式中、Rは、上記と同義である)
の化合物を得て、それを1〜30barの水素圧下、触媒の存在下に水素化し、酸官能基で必要であれば脱保護の後、式(I)のペリンドプリルを得て、所望の場合、それを薬学的に許容し得る塩に変換することを特徴とする、合成方法。 - 水素化反応における水素圧が、1〜10barであることを特徴とする、請求項1記載の合成方法。
- 触媒が、パラジウム、白金、ロジウム及びニッケルから選択される、請求項1記載の合成方法。
- X1及びX2が、各々塩素原子又はイミダゾリル若しくはトリクロロメトキシ基である、請求項1〜3のいずれか1項記載の合成方法。
- tert−ブチルアミン塩の形態のペリンドプリルの合成のための、請求項1〜4のいずれか1項記載の方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP03291600A EP1362864B1 (fr) | 2003-06-30 | 2003-06-30 | Nouveau procédé de synthèse du perindopril et de ses sels pharmaceutiquement acceptables |
PCT/FR2004/001638 WO2005005461A2 (fr) | 2003-06-30 | 2004-06-28 | Nouveau procede de synthese du perindopril et de ses sels pharmaceutiquement acceptables |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2008500263A true JP2008500263A (ja) | 2008-01-10 |
JP4347342B2 JP4347342B2 (ja) | 2009-10-21 |
Family
ID=29266055
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2006515296A Expired - Fee Related JP4347342B2 (ja) | 2003-06-30 | 2004-06-28 | ペリンドプリル及びその薬学的に許容し得る塩の新規合成方法 |
Country Status (20)
Country | Link |
---|---|
US (1) | US7220776B2 (ja) |
EP (1) | EP1362864B1 (ja) |
JP (1) | JP4347342B2 (ja) |
CN (1) | CN100383159C (ja) |
AR (1) | AR044943A1 (ja) |
AT (1) | ATE360638T1 (ja) |
AU (1) | AU2004255899B2 (ja) |
CY (1) | CY1106471T1 (ja) |
DE (1) | DE60313391T2 (ja) |
DK (1) | DK1362864T3 (ja) |
EA (1) | EA009458B1 (ja) |
ES (1) | ES2286393T3 (ja) |
HK (1) | HK1089187A1 (ja) |
MY (1) | MY136938A (ja) |
NZ (1) | NZ544004A (ja) |
PL (1) | PL211491B1 (ja) |
PT (1) | PT1362864E (ja) |
SI (1) | SI1362864T1 (ja) |
WO (1) | WO2005005461A2 (ja) |
ZA (1) | ZA200510324B (ja) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ZA200605383B (en) | 2003-12-29 | 2008-06-25 | Sepracor Inc | Pyrrole and pyrazole daao inhibitors |
ATE409036T1 (de) | 2005-01-06 | 2008-10-15 | Ipca Lab Ltd | Verfahren zur synthese von (2s,3as,7as)-1-(s)- alanyl-octahydro-1h-2-carbonsäurederivaten und verwendung in der synthese von perindopril |
WO2007006003A2 (en) | 2005-07-06 | 2007-01-11 | Sepracor Inc. | Combinations of eszopiclone and trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-napthalenamine or trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine, and methods of treatment of menopause and mood, anxiety, and cognitive disorders |
WO2007081542A2 (en) | 2006-01-06 | 2007-07-19 | Sepracor Inc. | Tetralone-based monoamine reuptake inhibitors |
RU2430913C2 (ru) | 2006-01-06 | 2011-10-10 | Сепракор Инк. | Циклоалкиламины в качестве ингибиторов повторного поглощения моноамина |
DK2013835T3 (en) | 2006-03-31 | 2015-12-14 | Sunovion Pharmaceuticals Inc | Preparation of chiral amides and AMINES |
US7884124B2 (en) | 2006-06-30 | 2011-02-08 | Sepracor Inc. | Fluoro-substituted inhibitors of D-amino acid oxidase |
JP2008019214A (ja) * | 2006-07-13 | 2008-01-31 | Shiono Chemical Co Ltd | ペリンドプリルまたはその誘導体の製造方法 |
US7902252B2 (en) | 2007-01-18 | 2011-03-08 | Sepracor, Inc. | Inhibitors of D-amino acid oxidase |
BRPI0811639A2 (pt) | 2007-05-31 | 2014-09-30 | Sepracor Inc | Cicloaquilaminas fenil substituídas como inibidores da recaptação de monoamina |
FR3050380B1 (fr) | 2016-04-20 | 2020-07-10 | Les Laboratoires Servier | Composition pharmaceutique comprenant un betabloquant, un inhibiteur de l'enzyme de conversion et un antihypertenseur ou un ains. |
CN111116709B (zh) * | 2019-12-31 | 2022-06-24 | 北京鑫开元医药科技有限公司 | 一种培哚普利制备方法 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2620709B1 (fr) * | 1987-09-17 | 1990-09-07 | Adir | Procede de synthese industrielle du perindopril et de ses principaux intermediaires de synthese |
EP1321471B1 (fr) * | 2003-03-12 | 2005-05-04 | Les Laboratoires Servier | Nouveau procédé de synthèse du perindopril et de ses sels pharmaceutiquement acceptables |
SI1367061T1 (sl) * | 2003-06-30 | 2006-04-30 | Servier Lab | Nov postopek za sintezo perindoprila in njegovih farmacevtsko sprejemljivih soli |
-
2003
- 2003-06-30 AT AT03291600T patent/ATE360638T1/de active
- 2003-06-30 PT PT03291600T patent/PT1362864E/pt unknown
- 2003-06-30 DK DK03291600T patent/DK1362864T3/da active
- 2003-06-30 EP EP03291600A patent/EP1362864B1/fr not_active Expired - Lifetime
- 2003-06-30 ES ES03291600T patent/ES2286393T3/es not_active Expired - Lifetime
- 2003-06-30 SI SI200330844T patent/SI1362864T1/sl unknown
- 2003-06-30 DE DE60313391T patent/DE60313391T2/de not_active Expired - Lifetime
-
2004
- 2004-06-28 ZA ZA200510324A patent/ZA200510324B/xx unknown
- 2004-06-28 NZ NZ544004A patent/NZ544004A/xx not_active IP Right Cessation
- 2004-06-28 US US10/562,950 patent/US7220776B2/en not_active Expired - Fee Related
- 2004-06-28 AU AU2004255899A patent/AU2004255899B2/en not_active Ceased
- 2004-06-28 JP JP2006515296A patent/JP4347342B2/ja not_active Expired - Fee Related
- 2004-06-28 EA EA200501900A patent/EA009458B1/ru not_active IP Right Cessation
- 2004-06-28 WO PCT/FR2004/001638 patent/WO2005005461A2/fr active Application Filing
- 2004-06-28 MY MYPI20042539A patent/MY136938A/en unknown
- 2004-06-28 CN CNB2004800163249A patent/CN100383159C/zh not_active Expired - Fee Related
- 2004-06-28 PL PL379630A patent/PL211491B1/pl unknown
- 2004-06-29 AR ARP040102276A patent/AR044943A1/es not_active Application Discontinuation
-
2006
- 2006-08-30 HK HK06109648A patent/HK1089187A1/xx not_active IP Right Cessation
-
2007
- 2007-05-16 CY CY20071100663T patent/CY1106471T1/el unknown
Also Published As
Publication number | Publication date |
---|---|
EA009458B1 (ru) | 2007-12-28 |
WO2005005461A2 (fr) | 2005-01-20 |
EP1362864A1 (fr) | 2003-11-19 |
WO2005005461A3 (fr) | 2005-03-31 |
HK1089187A1 (en) | 2006-11-24 |
AU2004255899B2 (en) | 2008-03-13 |
SI1362864T1 (sl) | 2007-08-31 |
NZ544004A (en) | 2009-03-31 |
EP1362864B1 (fr) | 2007-04-25 |
DK1362864T3 (da) | 2007-09-17 |
AR044943A1 (es) | 2005-10-12 |
MY136938A (en) | 2008-11-28 |
PL379630A1 (pl) | 2006-10-30 |
AU2004255899A1 (en) | 2005-01-20 |
ZA200510324B (en) | 2007-03-28 |
DE60313391T2 (de) | 2008-01-17 |
US20060148884A1 (en) | 2006-07-06 |
ES2286393T3 (es) | 2007-12-01 |
DE60313391D1 (de) | 2007-06-06 |
CY1106471T1 (el) | 2012-01-25 |
CN100383159C (zh) | 2008-04-23 |
CN1805972A (zh) | 2006-07-19 |
EA200501900A1 (ru) | 2006-06-30 |
PT1362864E (pt) | 2007-07-23 |
PL211491B1 (pl) | 2012-05-31 |
ATE360638T1 (de) | 2007-05-15 |
US7220776B2 (en) | 2007-05-22 |
JP4347342B2 (ja) | 2009-10-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6835843B2 (en) | Method for synthesis of perindopril and its pharmaceutically acceptable salts | |
JP4347342B2 (ja) | ペリンドプリル及びその薬学的に許容し得る塩の新規合成方法 | |
JP4347341B2 (ja) | ペリンドプリル及びその薬学的に許容し得る塩の新規合成方法 | |
JP4331207B2 (ja) | ペリンドプリルおよびその薬学的に許容され得る塩の、新規な合成方法 | |
JP4331205B2 (ja) | ペリンドプリルおよびその薬学的に許容され得るその塩の、新規な合成方法 | |
EP1321471B1 (fr) | Nouveau procédé de synthèse du perindopril et de ses sels pharmaceutiquement acceptables | |
JP4331206B2 (ja) | ペリンドプリルおよびその薬学的に許容され得る塩の、新規な合成方法 | |
EP1420029B9 (fr) | Procédé de synthèse du perindopril et ses sels pharmaceutiquement acceptables | |
JP4563372B2 (ja) | ペリンドプリルおよびその薬理上許容される塩を合成する新規な方法 | |
JP4263744B2 (ja) | ペリンドプリル及びその薬学的に許容し得る塩の新規な合成方法 | |
JP4263743B2 (ja) | ペリンドプリル及びその薬学的に許容し得る塩の新規な合成方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20081224 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20090324 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20090331 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20090424 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20090507 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090525 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20090707 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20090715 |
|
R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120724 Year of fee payment: 3 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130724 Year of fee payment: 4 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
LAPS | Cancellation because of no payment of annual fees |