Table 3.

In vitro inhibitory potencies for NEP and APN and antinociceptive properties in the hot plate test in mice for the optically pure aminophosphinic-inhibitors                

Compounds	R1	R2	R3	Ki (nM)*		Antinociceptive properties§ ED50, μg (95% confidence limits)
				NEP†	APN‡
7(B)	CH2Ph	CH2Ph(p-Ph)	CH3	2.2 ± 0.3	5.3 ± 0.7	11 (6.84–17.7) 19.1 nmol
8(B)	Ph	CH2Ph(p-Ph)	CH3	2.0 ± 0.5	4.8 ± 0.7	10.5 (5.83–18.9) 18.7 nmol
9(B)	CH3	CH2Ph(p-Ph)	CH3	1.2 ± 0.2	2.9 ± 0.3	6 (3.66–9.84) 12 nmol

^*Values are the mean ± SEM from three independent experiments performed in triplicate of five inhibitor concentrations. 

^†NEP activity was measured by using DGNPA as substrate. 

^‡APN activity was measured by using Ala-p.NA as substrate. 

^§Inhibitors were administered ICV 15 min before the plate test.