29123-25-9Relevant articles and documents
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Amos et al.
, p. 236 (1958)
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Kochetkov et al.
, (1966)
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Human P2Y14 receptor agonists: Truncation of the hexose moiety of uridine-5′-diphosphoglucose and its replacement with alkyl and aryl groups
Das, Arijit,Ko, Hyojin,Burianek, Lauren E.,Barrett, Matthew O.,Harden, T. Kendall,Jacobson, Kenneth A.
scheme or table, p. 471 - 480 (2010/05/02)
Uridine-5′-diphosphoglucose (UDPG) activates the P2Y14 receptor, a neuroimmune system GPCR. P2Y14 receptor tolerates glucose substitution with small alkyl or aryl groups or its truncation to uridine 5′-diphosphate (UDP), a full agonist at the human P2Y14 receptor expressed in HEK-293 cells. 2-Thiouracil derivatives displayed selectivity for activation of the human P2Y14 vs the P2Y6 receptor, such as 2-thio-UDP 4 (EC50=1.92 nMat P2Y14, 224-fold selectivity vs P2Y6) and its β-propyloxy ester 18. EC50 values of the β-methyl ester of UDP and its 2-thio analogue were 2730 and 56 nM, respectively. β-tert-Butyl ester of 4 was 11-fold more potent than UDPG, but β-aryloxy or larger, branched β-alkyl esters, such as cyclohexyl, were less potent. Ribose replacement of UDP with a rigid North or South methanocarba (bicyclo[3.1.0]hexane) group abolished P2Y14 receptor agonist activity. α,β-Methylene and difluoromethylene groups were well tolerated at the P2Y14 receptor and are expected to provide enhanced stability in biological systems. α,β-Methylene-2-thio-UDP 11 (EC50 = 0.92 nM) was 2160-fold selective versus P2Y6. Thus, these nucleotides and their congeners may serve as important pharmacological probes for the detection and characterization of the P2Y14 receptor.
Synthesis and structure-activity relationships of uracil nucleotide derivatives and analogues as agonists at human P2Y2, P2Y4, and P2Y6 receptors
El-Tayeb, Ali,Qi, Aidong,Müller, Christa E.
, p. 7076 - 7087 (2007/10/03)
A series of UTP, UDP, and UMP derivatives and analogues were synthesized and evaluated at the human pyrimidinergic P2Y receptor subtypes P2Y2, P2Y4, and P2Y6 stably expressed in 1321N1 astrocytoma cells. Substituents at N3
