Table 2.

Structures and Pharmacological Activities of Pyridoxal and Pyridoxine Derivatives (phosphates and phosphonates) at P2 Receptors

compd	positions					recombinant IC50 (μM)			PLC assay IC50 (μM)
	2′	3′	4′	5′	X	P2X1a or % inhib	P2X2a	P2X3a	P2Y1c
1	SO3H	H	SO3H	H	CH2O	0.099 ± 0.006	1.6 ± 0.1	0.240 ± 0.038	16.6 ± 2.5
(PPADS)
2	SO3H	H	H	SO3H	CH2O	0.043 ± 0.018	0.398 ± 0.125	0.084 ± 0.004	21.4 ± 9.0
(IsoPPADS)
4 d,f	H	H	COOH	H	CH2O	0.0094 ± 0.0017	11.9 ± 1.4	0.140 ± 0.011	~100
5	H	H	COOH	H	CH2	0.0081 ± 0.0021	0.150 ± 0.020	0.128 ± 0.019
6 d	H	H	COOH	H	CH2CH2	0.020 ± 0.003	2.4 ± 0.3	0.145 ± 0.057	~100
7	COOH	H	H	COOH	CH2	0.037 ± 0.008	0.486 ± 0.023	0.330 ± 0.014
8 d	H	H	H	H	CH2O	0.042 ± 0.006	1.2 ± 0.2	0.480 ± 0.090	54 ± 3
9 f	H	CH2P(O)(OH)2	H	CH2P(O)(OH)2	CH2	0.011 ± 0.005	0.280 ± 0.030	0.025 ± 0.007	14.5 ± 2.1
10 d,f	SO3H	H	H	SO3H	CH2	0.012 ± 0.003	1.1 ± 0.2	0.340 ± 0.040	46 ± 21
11 f	H	H	P(O)(OH)2	H	CH2	0.012 ± 0.008	0.948 ± 0.019	0.036 ± 0.010	27 ± 3
12 e						5.9 ± 1.8 (EC50)g	inactive	inactive	inactive
3 e	SO3H	H	H	SO3H	H	10.2 ± 2.6	inactive	58.3 ± 0.1	inactive
13	Cl	H	H	SO3H	H	43 ± 4%b
14	H	H	COOH	H	H	39 ± 10%b
15	SO3H	H	H	SO3H	CH3CO	inactive
16	H	H	H	H	H	inactive			inactive
17						inactive			inactive
18	SO3H	H	H	SO3H		27 ± 7%b			~100
19	Cl	H	H	SO3H		78 ± 7%b		30 ± 10%b	~100
20	H	H	H	H		50 ± 4%b			>100

^aInhibition of ion current (mean ± SEM, n = 4), unless noted, induced by ATP (at the EC₇₀ values in μM for respective subtypes: P2X₁ 1, P2X₂ 10, and P2X₃ 3) at recombinant P2X receptors expressed in Xenopus oocytes

^b(% inhibition at 10 μM).

^cInhibition of 10 nM 2-MeSADP-stimulated phospholipase C in turkey erythrocyte membranes (mean ± SEM, n = 3), labeled using [³H]inositol.

^dCompounds reported by Kim et al.²⁵

^eCompounds and values reported by Jacobson et al.¹⁴

^fCompound 4, MRS 2159; compound 5, MRS 2284; compound 9, MRS 2257; compound 10, MRS 2191; compound 11, MRS 2273.

^gCompound 12 potentiates the effect of ATP at P2X receptors.¹⁴