期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 55, 期 1, 页码 342-356出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm201229j
关键词
-
资金
- Basic Science Research [2008-314-E00304]
- National Core Research Center [2011-0006244]
- World Class University [R31-2008-000-10010-0]
- National Leading Research Lab [2011-0028885]
- Brain Research Center of the 21st Century Frontier Research from National Research Foundation (NRF), Korea [2011K000289]
- NIDDK, NIH, Bethesda, MD, U.S.
Truncated N-6-substituted-4'-oxo- and 4'-thioadenosine derivatives with C2 or C8 substitution were studied as dual acting A(2A) and A(3) adenosine receptor (AR) ligands. The lithiation-mediated stannyl transfer and palladium-catalyzed cross-coupling reactions were utilized for functionalization of the C2 position of 6-chloropurine nucleosides. An unsubstituted 6-amino group and a hydrophobic C2 substituent were required for high affinity at the hA(2A)AR, but hydrophobic C8 substitution abolished binding at the hA(2A)AR. However, most of synthesized compounds displayed medium to high binding affinity at the hA(3)AR, regardless of C2 or C8 substitution, and low efficacy in a functional cAMP assay. Several compounds tended to be full hA(2A)AR agonists. C2 substitution probed geometrically through hA(2A)ARdocking was important for binding in order of hexynyl > hexenyl > hexanyl. Compound 4g was the most potent ligand acting dually as hA(2A)AR agonist and hA(3)AR antagonist, which might be useful for treatment of asthma or other inflammatory diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据