Synthesis, molecular modeling and biological activity of methyl and thiomethyl substituted pyrimidines as corticotropin releasing hormone type 1 antagonists

Title: Synthesis, molecular modeling and biological activity of methyl and thiomethyl substituted pyrimidines as corticotropin releasing hormone type 1 antagonists
Creator: McCluskey, Adam; Keller, Paul A.; Morgan, Jody; Garner, James
Relation: Organic and Biomolecular Chemistry Vol. 1, Issue 19, p. 3353-3361
Publisher Link: http://dx.doi.org/10.1039/b305458f
Publisher: Royal Society of Chemistry
Resource Type: journal article
Date: 2003
Description: Four small, targeted libraries of differentially substituted amino pyrimidines were synthesized in moderate to good yields. Excellent regiochemistry was observed for substitution at C2/C4 with selectivity >50 : 1 noted. All analogues were screened for their ability to interact with CRH₁ and CRH₂ receptors. In all instances only poor agonistic and/or antagonistic behaviour was noted at CRH₂. However, several compounds were potent and selective CRH₁ antagonists, most notably 13a Ki = 39nM. Additionally we have utilized these data and that recently reported by others to refine our original CRH₁ pharmacophore.
Subject: synthesis; amino pyrimidines; molecular modeling; corticotropin releasing hormone type 1 antagonists
Identifier: uon:1663
Identifier: http://hdl.handle.net/1959.13/27430
Identifier: ISSN:1477-0520
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