Linked Life Data

7783143

Source:http://linkedlifedata.com/resource/pubmed/id/7783143

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1995-7-14
pubmed:abstractText
Hydroxamic acids 6a-h, derived from malonyl amino acids, and 25a-d, derived from succinyl amino acids, were synthesized as inhibitors of human bronchiolar smooth muscle endothelin-converting enzyme (HBSM ECE). Several unexpected side reactions were discovered, particularly in the synthesis of hydroxamates derived from succinates. In vitro evaluation against human bronchiolar ECE revealed that in all cases hydroxamates derived from malonate were more potent than hydroxamates derived from succinate. Isopropyl and isobutyl P1' side chains were suitable; omission of the P1' side chain seriously diminished potency. In the P2' position, several amino acids gave potent malonate-derived hydroxamate inhibitors (6b, d-h, IC50 = 0.2-6.8 nM), and beta-Ala provided an extremely potent inhibitor (6c, IC50 = 0.01 nM). C-terminus carboxylates are much more potent ECE inhibitors than the corresponding amides. Most of the hydroxamates were also potent inhibitors of thermolysin and neutral endopeptidase (NEP); however, the P2' beta-Ala derivative 6c uniquely inhibited HBSM ECE much more potently than NEP.
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
9
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2119-29
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Hydroxamic acids as potent inhibitors of endothelin-converting enzyme from human bronchiolar smooth muscle.
pubmed:affiliation
Berlex Laboratories, Inc., Cedar Knolls, New Jersey 07927, USA.
pubmed:publicationType
Journal Article