Linked Life Data

18251495

Source:http://linkedlifedata.com/resource/pubmed/id/18251495

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-2-21
pubmed:abstractText
Quinazolinones 8 and pyrido[3,4-d]pyrimidin-4-ones 9 as orally active and specific matrix metalloproteinase-13 inhibitors were discovered for the treatment of osteoarthritis. Starting from a high-through-put screening (HTS) hit thizolopyrimidin-dione 7, we obtained two chemotypes, 8 and 9, using computer-aided drug design (CADD) and methodical structure-activity relationship (SAR) studies. They occupy the unique S 1'-specificity pocket and do not bind to the Zn(2+) ion. Some pyrido[3,4-d]pyrimidin-4-ones, such as 10a, possess favorable absorption, distribution, metabolism, and elimination (ADME) and safety profiles. 10a effectively prevents cartilage damage in rabbit animal models of osteoarthritis without inducing musculoskeletal side effects when given at extremely high doses to rats.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
835-41
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Quinazolinones and pyrido[3,4-d]pyrimidin-4-ones as orally active and specific matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis.
pubmed:affiliation
Department of Chemistry, Michigan Laboratories, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, Michigan 48105, USA. jie.li1@bms.com
pubmed:publicationType
Journal Article