Linked Life Data

16651001

Source:http://linkedlifedata.com/resource/pubmed/id/16651001

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2006-7-10
pubmed:abstractText
Calpain-mediated proteolysis has been implicated as a major process in neuronal cell death including retinal neurological degeneration. The previously reported calpain inhibitor SJA6017 (1) showed oral efficacy in a retinal pharmacological model, but its oral bioavailability was low due to the metabolic lability and low water-solubility. The purpose of present study was to identify good orally bioavailable calpain inhibitors. A series of water-soluble dipeptidyl alpha-ketoamides containing a pyridine moiety at P3 were designed, synthesized, and evaluated for their oral bioavailability and retinal penetration. Introduction of a pyridineethanol moiety provided the potent alpha-ketoamide inhibitor 8 with good oral bioavailability. Compound 8 showed about 12-fold higher retinal AUC than 1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0968-0896
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5691-8
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Exploration of orally available calpain inhibitors. Part 3: Dipeptidyl alpha-ketoamide derivatives containing pyridine moiety.
pubmed:affiliation
Research Laboratory of Ocular Science, Senju Pharmaceutical Co. Ltd, Nishi-ku, Kobe, Hyogo, Japan. shirasaki@senju.co.jp
pubmed:publicationType
Journal Article