|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
10
|
|
pubmed:dateCreated |
2011-5-2
|
|
pubmed:abstractText |
Seeking compounds preferentially potent and selective for MMP-13, we reported in the preceding Letter on a series of hydroxamic acids with a flexible benzamide tail groups.(1a) Here, we replace the amide moiety with non-hydrolyzable heterocycles in an effort to improve half-life. We identify a hydroxamate tetrazole 4e that spares MMP-1 and -14, shows >400-fold selectivity versus MMP-8 and >600-fold selectivity versus MMP-2, and has a 4.8 h half-life in rats. X-ray data (1.9 Å) for tetrazole 4c is presented.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
May
|
|
pubmed:issn |
1464-3405
|
|
pubmed:author |
pubmed-author:BartaThomas ETE,
pubmed-author:BeckerDaniel PDP,
pubmed-author:BedellLouis JLJ,
pubmed-author:EastonAlan MAM,
pubmed-author:HockermanSusan LSL,
pubmed-author:KieferJamesJ,
pubmed-author:LiMadeleine HMH,
pubmed-author:MathisKarl JKJ,
pubmed-author:MunieGrace EGE,
pubmed-author:RicoJoseph GJG,
pubmed-author:VillamilClara ICI,
pubmed-author:WilliamsJennifer MJM
|
|
pubmed:copyrightInfo |
Copyright © 2011 Elsevier Ltd. All rights reserved.
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
15
|
|
pubmed:volume |
21
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
2820-2
|
|
pubmed:meshHeading |
pubmed-meshheading:21507637-Amides,
pubmed-meshheading:21507637-Animals,
pubmed-meshheading:21507637-Crystallography, X-Ray,
pubmed-meshheading:21507637-Enzyme Inhibitors,
pubmed-meshheading:21507637-Heterocyclic Compounds,
pubmed-meshheading:21507637-Hydroxamic Acids,
pubmed-meshheading:21507637-Matrix Metalloproteinase 13,
pubmed-meshheading:21507637-Models, Molecular,
pubmed-meshheading:21507637-Rats,
pubmed-meshheading:21507637-Structure-Activity Relationship,
pubmed-meshheading:21507637-Substrate Specificity,
pubmed-meshheading:21507637-Sulfones
|
|
pubmed:year |
2011
|
|
pubmed:articleTitle |
MMP-13 selective ?-sulfone hydroxamates: a survey of P1' heterocyclic amide isosteres.
|
|
pubmed:affiliation |
Department of Medicinal Chemistry, Pfizer Research & Development, 4901 Searle Parkway, Skokie, IL 60077, USA. thomas_e_barta@yahoo.com
|
|
pubmed:publicationType |
Journal Article
|
