Agonists and antagonists for P2 receptors.
Agonists and antagonists for P2 receptors.
复制标题
P2 受体的激动剂和拮抗剂。
DOI：
10.1002/9780470032244.ch6
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发表时间：
2006
影响因子：
--
通讯作者：
Mamedova,Liaman
中科院分区：
文献类型：
--
作者：
Jacobson,KennethA;Costanzi,Stefano;Joshi,BhalchandraV;Besada,Pedro;Shin,DaeHong;Ko,Hyojin;Ivanov,AndreiA;Mamedova,Liaman
Recent work has identified nucleotide agonists selective for P2Y1, P2Y2and P2Y6receptors and nucleotide antagonists selective for P2Y1, P2Y12and P2X1receptors. Selective non‐nucleotide antagonists have been reported for P2Y1, P2Y2, P2Y6, P2Y12, P2Y13, P2X2/3/P2X3and P2X7receptors. For example, the dinucleotide INS 37217 (Up4dC) potently activates the P2Y2receptor, and the non‐nucleotide antagonist A‐317491 is selective for P2X2/3/P2X3receptors. Nucleotide analogues in which the ribose moiety is substituted by a variety of novel ring systems, including conformationally locked moieties, have been synthesized as ligands for P2Y receptors. The focus on conformational factors of the ribose‐like moiety allows the inclusion of general modifications that lead to enhanced potency and selectivity. At P2Y1,2,4,11receptors, there is a preference for the North conformation as indicated with (N)‐methanocarba analogues. The P2Y1antagonist MRS2500 inhibited ADP‐induced human platelet aggregation with an IC50of 0.95 nM. MRS2365, an (N)‐methanocarba analogue of 2‐MeSADP, displayed potency (EC50) of 0.4 nM at the P2Y1receptor, with >10 000‐fold selectivity in comparison to P2Y12and P2Y13receptors. At P2Y6receptors there is a dramatic preference for the South conformation. Three‐dimensional structures of P2Y receptors have been deduced from structure activity relationships (SAR), mutagenesis and modelling studies. Detailed three‐dimensional structures of P2X receptors have not yet been proposed.
