Linked Life Data

1588554

Source:http://linkedlifedata.com/resource/pubmed/id/1588554

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1992-6-23
pubmed:abstractText
A new series of renin inhibitors has been developed. The inhibitors feature a novel replacement for the P2/P3 dipeptide moiety normally associated with renin inhibitors. The dipeptide replacement was a (2S,4S)-3-aza(or oxa)-2,4-dialkylglutaric acid amide. Extensive structure-activity relationship studies determined that optimum potency was achieved when inhibitors employed a benzyl and butyl group at the C(4) and C(2) carbon position, respectively. In addition, maximum in vitro potency was obtained when the N-terminus was functionalized by incorporating a 4-(1,3-dioxabutyl)piperidine amide. SAR data suggested that the 1,3-dioxabutyl group (methoxymethyl ether) interacted by hydrogen bonding to groups in the S4 domain of renin. This hypothesis was strengthened when a 4-butylpiperidine amide was substituted and inhibitor potency decreased dramatically. Inhibitors employing this novel dipeptide mimic were prepared by coupling the glutaric acid amides with either the transition-state mimic (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6- methylheptane (18) or the hydroxyethylene dipeptide isostere. The glutaric acid amides were prepared by two general procedures. The first procedure involved the reductive amination of alpha-amino acid esters with alpha-keto esters. The second procedure involved the displacement reaction of alpha-bromo esters or acids with alpha-amino acid amides.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
N
pubmed:pagination
1722-34
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Nonpeptide renin inhibitors employing a novel 3-aza(or oxa)-2,4-dialkyl glutaric acid moiety as a P2/P3 amide bond replacement.
pubmed:affiliation
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064.
pubmed:publicationType
Journal Article