Table 1. In vitro.

pharmacological data for various nucleotide 5′-phosphonate derivatives analogues and the corresponding native ribosides (X = OCH₂) in the stimulation of PLC at recombinant human P2Y receptors expressed in 1321N1 astrocytoma cells.

No	Name	R	n	B	X	Receptor	EC50, μMa	Reference comp. (X = OCH2) EC50, μM7–11
1	adenosine 5′-(diphospho)-phosphonate	HO	2	A	CH2	P2Y2	1.4 ± 0.6	0.085 ± 0.012
						P2Y4	<50% at 10 μM	Antagonist12
2	uridine 5′-(diphospho)-phosphonate	HO	2	U	CH2	P2Y2	8.6 ± 3.1	0.049 ± 0.012
						P2Y4	NE	0.073 ± 0.02
						P2Y6	NE	>1010
3	uridine 5′-(diphospho)- vinylphosphonate	HO	2	U	trans -CH=CH	P2Y2	1.0 ± 0.4	0.049 ± 0.012
						P2Y4	<50% at 10 μM	0.09 ± 0.0121
						P2Y6	NE	NE
4	uridine 5′-phospho- phosphonate	HO	1	U	CH2	P2Y2	3.4 ± 1.1 (partial ag)	NE
						P2Y4	NE	NE
						P2Y6	1.9 ± 0.7	0.046 ± 0.020
5	di-(uridine- phosphonate)		1	U	CH2	P2Y2	<50% at 10 μM	NE8
						P2Y4	NE	NE8
						P2Y6	NE	1.26 ± 0.17b
6	uridine 5′-(glucose[1′]phos- pho)phosphonate		1	U	CH2	P2Y14	NE	0.301 ± 0.07
7	uridine 5 ′-methylene-phosphonate	HO	0	U	CH2	P2Y2	1.6 ± 0.4 (partial ag)	NE
						P2Y4	NE	NE
						P2Y6	NE	NE

^aAgonist potencies were calculated using a four-parameter logistic equation and the GraphPad software package (GraphPad, San Diego, CA). EC₅₀ values (mean ± standard error) represent the concentration at which 50% of the maximal effect was achieved. A maximal effect (100% apparent efficacy) equivalent to that of the cognate agonist for the tested receptor was observed unless where indicated for two compounds (1 and 3) that exhibited <50% of maximal effect at the highest 10 μM concentration tested at the P2Y₄ receptor and for two compounds (4 and 7) that produced apparently saturable activation that was much less than that observed with UTP at the P2Y₂ receptor. The data for 4 and 7 are denoted as consistent with partial agonist (partial ag.) activity. N = 4 – 6 conc.-effect curves for each analogue.

^bUp₂U. NE - no effect at 10 μM.