Linked Life Data

12061887

Source:http://linkedlifedata.com/resource/pubmed/id/12061887

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2002-6-13
pubmed:abstractText
A series of bicyclic trans-fused gamma-lactones and gamma-lactams have been previously described for the inhibition of human neutrophil elastase and as possible development candidates. During the discovery program, it had been assumed that their acylating power was due in part to the inherent strain energy in the bicyclic structure that was released upon ring opening. This is now shown not to be the case, and in fact, these compounds are no more reactive than simple but analogous gamma-lactams and gamma-lactones. The strain energy is not released in the transition state for alkaline hydrolysis or alcoholysis because the reaction proceeds with rate-limiting formation of the tetrahedral intermediate. A reactivity index of k(OH) is proposed as a simple guide to determine the usefulness of a potential inhibitor as an enzyme acylating agent.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2850-6
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Acylating agents as enzyme inhibitors and understanding their reactivity for drug design.
pubmed:affiliation
Department of Chemical and Biological Sciences, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, U.K.
pubmed:publicationType
Journal Article