Show simple item record

dc.contributorWichita State University. Department of Chemistryen_US
dc.contributor.authorKuang, Rongzeen_US
dc.contributor.authorEpp, Jeffrey B.en_US
dc.contributor.authorRuan, Sumeien_US
dc.contributor.authorChong, Lee S.en_US
dc.contributor.authorVenkataraman, Radhikaen_US
dc.contributor.authorTu, Juanen_US
dc.contributor.authorHe, Shuen_US
dc.contributor.authorTruong, Tien M.en_US
dc.contributor.authorGroutas, William C.en_US
dc.identifierHL 57788en_US
dc.identifier.citationBioorganic & medicinal chemistry. 2000 May; 8(5): 1005-16.en_US
dc.descriptionFull text of this article is not available in SOAR.en_US
dc.description.abstractA series of carboxylate derivatives based on the 1,2,5-thiadiazolidin-3-one 1,1 dioxide and isothiazolidin-3-one 1,1 dioxide scaffolds has been synthesized and the inhibitory profile of these compounds toward human leukocyte elastase (HLE), cathepsin G (Cat G) and proteinase 3 (PR 3) was then determined. Most of the compounds were found to be potent, time-dependent inhibitors of elastase, with some of the compounds exhibiting k(inact)/K1 values as high as 4,928,300 M(-1) s(-1). The inhibitory potency of carboxylate derivatives based on the 1,2,5-thiadiazolidin-3-one 1,1 dioxide platform was found to be influenced by both the pKa and the inherent structure of the leaving group. Proper selection of the primary specificity group (R(I)) was found to lead to selective inhibition of HLE over Cat G, however, those compounds that inhibited HLE also inhibited PR 3, albeit less efficiently. The predictable mode of binding of these compounds suggests that, among closely-related serine proteases, highly selective inhibitors of a particular serine protease can be fashioned by exploiting subtle differences in their S' subsites. This study has also demonstrated that the degradative action of elastase on elastin can be abrogated in the presence of inhibitor 17.en_US
dc.description.sponsorshipNHLBI NIH HHSen_US
dc.relation.ispartofseriesBioorganic & medicinal chemistryen_US
dc.relation.ispartofseriesBioorg. Med. Chem.en_US
dc.subjectResearch Support, Non-U.S. Gov'ten_US
dc.subjectResearch Support, U.S. Gov't, P.H.S.en_US
dc.subject.meshCyclic S-Oxides/chemistryen_US
dc.subject.meshDrug Designen_US
dc.subject.meshMagnetic Resonance Spectroscopyen_US
dc.subject.meshModels, Molecularen_US
dc.subject.meshSerine Proteinase Inhibitors/chemistryen_US
dc.subject.meshStructure-Activity Relationshipen_US
dc.subject.meshSerine Proteinase Inhibitors/metabolismen_US
dc.subject.meshSerine Proteinase Inhibitors/pharmacologyen_US
dc.titleUtilization of the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold in the design of potent inhibitors of serine proteases: SAR studies using carboxylatesen_US
dc.description.versionpeer revieweden_US
dc.rights.holderCopyright © 2000, Elsevieren_US

Files in this item


There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record