DK1279665T3 - Fremgangsmåde til fremstilling af perindopril, analoge forbindelser og salte heraf ved anvendelse af 2,5-dioxo-oxazolidin-mellemforbindelser - Google Patents
Fremgangsmåde til fremstilling af perindopril, analoge forbindelser og salte heraf ved anvendelse af 2,5-dioxo-oxazolidin-mellemforbindelserInfo
- Publication number
- DK1279665T3 DK1279665T3 DK02016262T DK02016262T DK1279665T3 DK 1279665 T3 DK1279665 T3 DK 1279665T3 DK 02016262 T DK02016262 T DK 02016262T DK 02016262 T DK02016262 T DK 02016262T DK 1279665 T3 DK1279665 T3 DK 1279665T3
- Authority
- DK
- Denmark
- Prior art keywords
- perindopril
- dioxo
- salts
- preparation
- analogous compounds
- Prior art date
Links
- ARAFEULRMHFMDE-UHFFFAOYSA-N 1,3-oxazolidine-2,5-dione Chemical compound O=C1CNC(=O)O1 ARAFEULRMHFMDE-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 title 1
- 239000000543 intermediate Substances 0.000 title 1
- IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 title 1
- 229960002582 perindopril Drugs 0.000 title 1
- 150000003839 salts Chemical class 0.000 title 1
Classifications
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three 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
- C07D263/44—Two oxygen atoms
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Heart & Thoracic Surgery (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Cephalosporin Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01500197 | 2001-07-24 | ||
| EP02016262A EP1279665B1 (en) | 2001-07-24 | 2002-07-23 | A process for the preparation of perindopril, its analogous compounds and salts thereof using 2,5-dioxo-oxazolidine intermediate compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK1279665T3 true DK1279665T3 (da) | 2008-06-23 |
Family
ID=8183486
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK02016262T DK1279665T3 (da) | 2001-07-24 | 2002-07-23 | Fremgangsmåde til fremstilling af perindopril, analoge forbindelser og salte heraf ved anvendelse af 2,5-dioxo-oxazolidin-mellemforbindelser |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US20040248814A1 (da) |
| EP (1) | EP1279665B1 (da) |
| JP (1) | JP4083118B2 (da) |
| KR (1) | KR100694528B1 (da) |
| CN (1) | CN100503568C (da) |
| AR (1) | AR036187A1 (da) |
| AT (1) | ATE386717T1 (da) |
| AU (1) | AU2002328954B2 (da) |
| BR (1) | BR0211422A (da) |
| CY (1) | CY1107403T1 (da) |
| DE (1) | DE60225092T2 (da) |
| DK (1) | DK1279665T3 (da) |
| EA (1) | EA007000B1 (da) |
| ES (1) | ES2300402T3 (da) |
| HU (1) | HUP0202414A3 (da) |
| MX (1) | MXPA04000649A (da) |
| NO (1) | NO20040278L (da) |
| NZ (1) | NZ530578A (da) |
| PL (1) | PL355161A1 (da) |
| PT (1) | PT1279665E (da) |
| SI (1) | SI1279665T1 (da) |
| WO (1) | WO2003010142A2 (da) |
| ZA (1) | ZA200400323B (da) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1333026B1 (en) * | 2002-01-30 | 2007-06-27 | Les Laboratoires Servier | Process for the preparation of high purity perindopril and intermediates useful in the synthesis |
| CA2517205C (en) | 2003-02-28 | 2010-08-24 | Lupin Limited | Process for preparation of perindopril and salts thereof |
| JP4733023B2 (ja) | 2003-04-16 | 2011-07-27 | ブリストル−マイヤーズ スクイブ カンパニー | Ｃ型肝炎ウイルスの大環状イソキノリンペプチド阻害剤 |
| SI21506A (sl) * | 2003-05-08 | 2004-12-31 | LEK farmacevtska dru�ba d.d. | Postopek za pripravo perindoprila |
| SI21507A (sl) * | 2003-05-16 | 2004-12-31 | LEK farmacevtska dru�ba d.d. | Postopek za pripravo spojin z ace inhibitornim delovanjem |
| AU2003263584A1 (en) * | 2003-08-21 | 2005-03-10 | Hetero Drugs Limited | Process for pure perindopril tert-butylamine salt |
| DK1675827T3 (da) * | 2003-10-21 | 2010-04-19 | Servier Lab | Ny fremgangsmåde til fremstilling af krystallint perindopril erbumin |
| SI21703A (en) | 2004-01-14 | 2005-08-31 | Lek Farmacevtska Druzba Dd | Inclusion complexes of perindopril, procedure of their preparation, pharmaceutical compositions containing these complexes and their application in treatment of hypertensia |
| SI21881A (sl) | 2004-10-15 | 2006-04-30 | Diagen, Smartno Pri Ljubljani, D.O.O. | Nove kristalne oblike perindopril erbumin hidratov, postopek za njihovo pripravo in farmacevtske oblike, ki vsebujejo te spojine |
| ES2255872B1 (es) * | 2004-12-31 | 2007-08-16 | Quimica Sintetica, S.A. | Procedimiento para la preparacion de perindopril erbumina. |
| US7291745B2 (en) | 2005-03-21 | 2007-11-06 | Glenmark Pharmaceuticals Limited | Process for the preparation of perindopril |
| JP2006290825A (ja) * | 2005-04-13 | 2006-10-26 | Shiono Chemical Co Ltd | アルファ型ペリンドプリルエルブミンの製造法 |
| WO2006137082A1 (en) * | 2005-06-23 | 2006-12-28 | Ramesh Babu Potluri | Process for industrially viable preparation of perindopril erbumine |
| FR2894825B1 (fr) * | 2005-12-21 | 2010-12-03 | Servier Lab | Nouvelle association d'un inhibiteur du courant if sinusal et d'un inhibiteur de l'enzyme de conversion et les compositions pharmaceutiques qui la contiennent |
| UA98767C2 (uk) * | 2006-05-12 | 2012-06-25 | Егіш Дьйодьсердьяр Нільваношан Мюкьодо Ресвеньтаршашаг | Фармацевтичні проміжні сполуки в синтезі інгібіторів ацетилхолінестерази (асе) |
| 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 |
| EP2150538B1 (en) | 2007-06-06 | 2012-03-28 | DSM Sinochem Pharmaceuticals Netherlands B.V. | Novel 5-substituted hydantoins |
| FR2985512B1 (fr) | 2012-01-05 | 2014-06-20 | Servier Lab | Procede de preparation du sel de l-arginine du perindopril |
| PH12018502155B1 (en) | 2016-04-20 | 2024-03-27 | Servier Lab | Pharmaceutical composition comprising a beta blocker, a converting enzyme inhibitor and an antihypertensive or an nsaid |
| 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 (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2487829A2 (fr) * | 1979-12-07 | 1982-02-05 | Science Union & Cie | Nouveaux imino acides substitues, leurs procedes de preparation et leur emploi comme inhibiteur d'enzyme |
| US4508729A (en) * | 1979-12-07 | 1985-04-02 | Adir | Substituted iminodiacids, their preparation and pharmaceutical compositions containing them |
| US4350704A (en) * | 1980-10-06 | 1982-09-21 | Warner-Lambert Company | Substituted acyl derivatives of octahydro-1H-indole-2-carboxylic acids |
| ZA817261B (en) * | 1980-10-23 | 1982-09-29 | Schering Corp | Carboxyalkyl dipeptides,processes for their production and pharmaceutical compositions containing them |
| ATE20469T1 (de) * | 1980-10-23 | 1986-07-15 | Schering Corp | Carboxyalkyl-dipeptide, verfahren zu ihrer herstellung und diese enthaltende arzneimittel. |
| US4558038A (en) * | 1981-03-30 | 1985-12-10 | Usv Pharmaceutical Corp. | N-Substituted-amindo-amino acids |
| US4496542A (en) * | 1981-03-30 | 1985-01-29 | Usv Pharmaceutical Corporation | N-substituted-amido-amino acids |
| US4686295A (en) * | 1982-03-10 | 1987-08-11 | Usv Pharmaceutical Corporation | N-carboxy anhydride intermediates |
| US4885293A (en) * | 1984-09-24 | 1989-12-05 | Schering Corporation | Antiglaucoma agents |
| JPS6248696A (ja) * | 1985-08-27 | 1987-03-03 | Kanegafuchi Chem Ind Co Ltd | Ｎ−〔１（ｓ）−エトキシカルボニル−３−フエニルプロピル〕−ｌ−アラニル−ｌ−プロリンの製造法 |
| ES2004804A6 (es) * | 1987-08-13 | 1989-02-01 | Pharma Investi S A | Un procedimiento para preparar derivados de carboxialquildipeptidos |
| FR2620703B1 (fr) * | 1987-09-17 | 1991-10-04 | Adir | Procede de synthese industrielle de l'acide perhydroindole carboxylique - 2(2s, 3as, 7as). application a la synthese de carboxyalkyl dipeptides |
| FR2620699B1 (fr) * | 1987-09-17 | 1990-06-01 | Adir | Procede de synthese d'alpha amino acides n alkyles et de leurs esters. application a la synthese de carboxyalkyl dipeptides |
| FR2620700B1 (fr) * | 1987-09-17 | 1990-06-01 | Adir | Procede de synthese d'alpha amino acides n alkyles et leurs esters. application a la synthese de carboxyalkyl dipeptides |
| FR2620709B1 (fr) * | 1987-09-17 | 1990-09-07 | Adir | Procede de synthese industrielle du perindopril et de ses principaux intermediaires de synthese |
| US5258525A (en) * | 1991-03-27 | 1993-11-02 | Mcneilab, Inc. | Processes for preparing [2S-(2α,3aβ,7aβ)]octahydro-1H-indole-2-carboxylic acid and esters |
| SI9200213A (en) * | 1992-09-16 | 1994-03-31 | Krka | Process for preparing alkyl-l-alanil-l-proline derivates |
| IN184759B (da) | 1997-07-22 | 2000-09-23 | Kaneka Corp | |
| SE0000382D0 (sv) * | 2000-02-07 | 2000-02-07 | Astrazeneca Ab | New process |
-
2002
- 2002-07-22 AR ARP020102743A patent/AR036187A1/es not_active Application Discontinuation
- 2002-07-23 EP EP02016262A patent/EP1279665B1/en not_active Revoked
- 2002-07-23 DK DK02016262T patent/DK1279665T3/da active
- 2002-07-23 KR KR1020047001019A patent/KR100694528B1/ko not_active Expired - Fee Related
- 2002-07-23 US US10/484,672 patent/US20040248814A1/en not_active Abandoned
- 2002-07-23 JP JP2003515501A patent/JP4083118B2/ja not_active Expired - Fee Related
- 2002-07-23 PT PT02016262T patent/PT1279665E/pt unknown
- 2002-07-23 EA EA200400129A patent/EA007000B1/ru not_active IP Right Cessation
- 2002-07-23 SI SI200230668T patent/SI1279665T1/sl unknown
- 2002-07-23 CN CNB028143221A patent/CN100503568C/zh not_active Expired - Fee Related
- 2002-07-23 PL PL02355161A patent/PL355161A1/xx not_active Application Discontinuation
- 2002-07-23 WO PCT/EP2002/008223 patent/WO2003010142A2/en not_active Ceased
- 2002-07-23 MX MXPA04000649A patent/MXPA04000649A/es active IP Right Grant
- 2002-07-23 BR BR0211422-4A patent/BR0211422A/pt not_active IP Right Cessation
- 2002-07-23 ES ES02016262T patent/ES2300402T3/es not_active Expired - Lifetime
- 2002-07-23 DE DE60225092T patent/DE60225092T2/de not_active Revoked
- 2002-07-23 HU HU0202414A patent/HUP0202414A3/hu unknown
- 2002-07-23 AU AU2002328954A patent/AU2002328954B2/en not_active Ceased
- 2002-07-23 AT AT02016262T patent/ATE386717T1/de active
- 2002-07-23 NZ NZ530578A patent/NZ530578A/en not_active IP Right Cessation
-
2004
- 2004-01-15 ZA ZA2004/00323A patent/ZA200400323B/en unknown
- 2004-01-21 NO NO20040278A patent/NO20040278L/no not_active Application Discontinuation
-
2008
- 2008-04-21 CY CY20081100440T patent/CY1107403T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BR0211422A (pt) | 2004-08-17 |
| EA200400129A1 (ru) | 2004-08-26 |
| HUP0202414A2 (hu) | 2003-02-28 |
| DE60225092T2 (de) | 2009-02-19 |
| CN100503568C (zh) | 2009-06-24 |
| DE60225092D1 (de) | 2008-04-03 |
| HK1067129A1 (en) | 2005-04-01 |
| EP1279665A3 (en) | 2003-03-12 |
| HU0202414D0 (da) | 2002-09-28 |
| NZ530578A (en) | 2007-02-23 |
| WO2003010142A2 (en) | 2003-02-06 |
| EA007000B1 (ru) | 2006-06-30 |
| ZA200400323B (en) | 2005-03-30 |
| PL355161A1 (en) | 2003-01-13 |
| CN1529694A (zh) | 2004-09-15 |
| ATE386717T1 (de) | 2008-03-15 |
| HUP0202414A3 (en) | 2003-05-28 |
| MXPA04000649A (es) | 2004-10-27 |
| KR20040029378A (ko) | 2004-04-06 |
| PT1279665E (pt) | 2008-03-28 |
| EP1279665A2 (en) | 2003-01-29 |
| ES2300402T3 (es) | 2008-06-16 |
| SI1279665T1 (sl) | 2008-06-30 |
| AR036187A1 (es) | 2004-08-18 |
| EP1279665B1 (en) | 2008-02-20 |
| KR100694528B1 (ko) | 2007-03-13 |
| NO20040278L (no) | 2004-01-21 |
| WO2003010142A3 (en) | 2003-08-28 |
| CY1107403T1 (el) | 2012-12-19 |
| AU2002328954B2 (en) | 2007-10-04 |
| US20040248814A1 (en) | 2004-12-09 |
| JP4083118B2 (ja) | 2008-04-30 |
| JP2005501829A (ja) | 2005-01-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DK1279665T3 (da) | Fremgangsmåde til fremstilling af perindopril, analoge forbindelser og salte heraf ved anvendelse af 2,5-dioxo-oxazolidin-mellemforbindelser | |
| DK1312406T3 (da) | Fremgangsmåde til rensning af syntesegas | |
| DK1163207T3 (da) | Forbedret fremgangsmåde til fremstillingen af ikke-hygroskopiske salte af L(-)-carnitin | |
| DK1268424T3 (da) | Fremgangsmåde til syntese af perindopril og dets farmaceutisk acceptable salte | |
| DK1296935T3 (da) | Fremgangsmåde til fremstilling af substituerede octanoylamider | |
| IS7755A (is) | Aðferð við framleiðslu á (S,S)-cis-2-benshýdríl-3-bensýlamínókínuklídín | |
| DK1380121T3 (da) | Fremgangsmåde til fremstilling af oxazolidinoner | |
| DK1383733T3 (da) | Fremgangsmåde til fremstilling af 1,3-substituerede indener og aryl-sammenföjede azapolycykliske forbindelser | |
| DK1546122T3 (da) | Fremgangsmåde til fremstilling af valsartan | |
| DK1385826T3 (da) | Fremgangsmåde til fremstilling af (S)-(+)- og (R)-(-)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azapin-5-carboxamid | |
| DK1392318T3 (da) | 15-keto-prostaglandiner til behandling af lægemiddelinduceret forstoppelse | |
| DK1407037T3 (da) | Fremgangsmåde til fremstilling af tagatose | |
| NO20033433D0 (no) | Fremgangsmåte for fremstilling av 2-(2-pyridylmetyl)sulfinyl- 1H-benzimidasol | |
| DK1110922T3 (da) | Fremgangsmåde til termisk behandling af melformede råmaterialer | |
| DK1958938T3 (da) | Fremgangsmåde til fremstilling af 10,11-dihydro-10-oxo-5H-dibenz[b,f]azepin-5-carboxamid | |
| NO331195B1 (no) | Fremgangsmate for fremstilling av halogen-substituerte monosulfider og deres hydroksymonosulfid-evkivalenter som mellomprodukter. | |
| DK1456229T3 (da) | Fremgangsmåe til fremstilling af echinocandin-derivater | |
| DK1373232T3 (da) | Fremgangsmåde til fremstilling af N-substituerede 2,6-dialkylmorpholiner | |
| DK1075473T3 (da) | Fremgangsmåde til fremstilling af 1,3-disubstituerede-4-oxocykliske urinstoffer | |
| DK1395587T3 (da) | Fremgangsmåde til fremstilling af imipenem | |
| DK1511724T3 (da) | Fremgangsmåde til fremstilling af thioalkylaminderivater | |
| DK1503995T3 (da) | Fremgangsmåde til fremstilling af substituerede phenylsulfonylurinstoffer | |
| DK1519936T3 (da) | Fremgangsmåde til fremstilling af nevirapin | |
| EP1565448A4 (en) | PROCESS FOR THE PREPARATION OF 10H-DIBENZOçB, F] ç1,4] THIAZEPIN-11-ON | |
| DK0981950T3 (da) | Fremgangsm,åde til formering af phyllocactus |