Linked Life Data

21082722

Source:http://linkedlifedata.com/resource/pubmed/id/21082722

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-12-28
pubmed:abstractText
A series of 52 cis-configured 1-alkyl-3-phenylaziridine-2-carboxylates were synthesized as new pseudo-irreversible inhibitors of Candida albicans secreted aspartic acid protease?1 (SAP1), SAP2, SAP3, and SAP8. Some of the compounds, which were obtained as diastereomers with S,S- and R,R-configured aziridine rings by Cromwell synthesis of racemic (2R,3S+2S,3R)-dibromophenylpropionic acid ester with amines, followed by ester hydrolysis and coupling to hydrophobic amino acid esters, were separated by preparative HPLC. The absolute configuration of the aziridine ring was assigned by a combination of experimental circular dichroism (CD) investigations and quantum chemical CD calculations. In agreement with previous docking studies, the diastereomers all exhibit similar activity. The compounds were found to be more active against the related mammalian enzyme cathepsin?D, presumably due to productive interactions of the N-alkyl substituent with the highly lipophilic S2 pocket. The most active inhibitors (5, 9, 10, 21, and 28), characterized by benzyl, cyclohexylmethyl, tert-butyl, or 1,4-dimethylpentyl moieties at the aziridine nitrogen atom, exhibit k(2nd) values between 500 and 900×10³?M?¹?min?¹ and K(i) values near or below 1??M for cathepsin?D.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1860-7187
pubmed:author
pubmed:issnType
Electronic
pubmed:day
3
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
141-52
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
New cis-configured aziridine-2-carboxylates as aspartic acid protease inhibitors.
pubmed:affiliation
Institute of Pharmacy and Food Chemistry, University of Würzburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't