Linked Life Data

21417463

Source:http://linkedlifedata.com/resource/pubmed/id/21417463

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2011-4-21
pubmed:abstractText
A large series of derivatives and analogues of the uracil nucleotides UMP, UDP, and UTP with modifications in various positions of the uracil moiety and/or the phosphate groups were synthesized and evaluated at human P2Y(2), P2Y(4), and P2Y(6) receptors. 2-(Ar)alkylthio substitution of UMP and UDP was best tolerated by the P2Y(2) receptor. 2-Phenethylthio-UMP (13e) showed an EC(50) value of 1.3 ?M at P2Y(2) and >70-fold selectivity versus P2Y(4) and P2Y(6) receptors. Substitution of the 2-keto group in UMP by NH (13g, iso-CMP) resulted in the first potent and selective P2Y(4) agonist (EC(50) 4.98 ?M, >20-fold selective vs P2Y(2) and P2Y(6)). In contrast, replacement of the 2-keto function in UDP by NH yielded a potent P2Y(2) agonist (12g, iso-CDP, EC(50) = 0.604 ?M, >100-fold selective). In an attempt to obtain metabolically stable UTP analogues, ?,?-dichloro- and ?,?-difluoro-methylene-UTP derivatives were synthesized. The triphosphate modifications were much better tolerated by P2Y(2), and in some cases also by P2Y(6), than by P2Y(4) receptors. 4-Thio-?,?-difluoromethylene-UTP (14g) was a potent P2Y(2) agonist with an EC(50) value of 0.134 ?M and >50-fold selectivity. N3-Phenacyl-?,?-dichloromethylene-UTP (14b) proved to be a potent P2Y(6) receptor agonist (EC(50) 0.142 ?M) with high selectivity versus P2Y(4) (50-fold) and moderate selectivity versus P2Y(2) receptors (6-fold).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1520-4804
pubmed:author
pubmed:issnType
Electronic
pubmed:day
28
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2878-90
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Structural modifications of UMP, UDP, and UTP leading to subtype-selective agonists for P2Y2, P2Y4, and P2Y6 receptors.
pubmed:affiliation
PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, Bonn, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't