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image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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Priprava enantiomera amlodipina rezolucijom lipazama

Preparations of pure amlodipine enantiomers by lipase resolution
Authors: Filipan, Mirela; Litvić, Mladen; Cepanec, Ivica; Kos, Karmen; Vinković, Vladimir;

Priprava enantiomera amlodipina rezolucijom lipazama

Abstract

Amlodipin pripada skupini 1, 4-dihidropiridinskih biološko aktivnih spojeva, a veoma je uspješan lijek protiv koronarnih bolesti koji se već niz godina nalazi među desetak lijekova s najvećom upotrebom i zaradom na svjetskom tržištu. Za S-enantiomer amlodipina je poznato da je kao antihipertenziv neusporedivo aktivniji od odgovarajućeg R-enantiomera, međutim, na tržištu se taj lijek još uvijek nalazi isključivo kao racemat. Jedan od razloga za to je nedostatak kvalitetnih metoda njegove priprave. Lipazama katalizirano aciliranje se često koristi za resoluciju primarnih amina, ali te reakcije su zbog velike nukleofilnosti amina mnogo osjetljivije nego kada se radi s alkoholima. Iz tog razloga nije do sada u literaturi zabilježen nijedan pokušaj direktne enzimske resolucije enantiomera amlodipina. Ispitan je set od 25 različitih enzima u resoluciji racemičnog amlodipina putem amonolize acetatnih estera. Nakon iscrpnih ispitivanja utvrđeno je da su dvije lipaze, Pseudomonas cepacia i Candida antarctica "B", pogodne za visoko enantioselektivnu resoluciju racemičnog amlodipina s acetatnim esterima. Usporedbom dobivenih produkata sa standardom poznate apsolutne konfiguracije, utvrđeno je da P. cepacia konvertira S-enantiomer amlodipina, a zaostaje neizreagirani R-amlodipin. Suprotno, uz Candida antarctica lipazu "B" nastaje R-acetamidni derivat amlodipina, uz neizreagirani S-amlodipin. Ove reakcije predstavljaju prvu poznatu metodu priprave oba enantiomera amlodipina visoke enantiomerne čistoće upotrebom lipaza.

Country
Croatia
Keywords

amlodipin; enantiomeri; lipaze

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
0
Average
Average
Average
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