Table 7.

AT1 receptor antagonist and in vivo activities of carboxylic acid 33 and a series of related isosteres.^[39]

Compd	X	pKa estimated	IC50[a] [μm]	Dose[b] [mgkg−1]
				iv	po
33	COOH	5	0.23	3	11[c]
34	CONHOH	10.5	4.1	3	>30[d]
35	CONHOCH3	10.9	2.9	10	inactive[e]
36	CONHSO2Ph	8.4	0.14	>3[d]	30
37	NHSO2CF3	4.5	0.083	10	100
38		5–6	0.019	0.80[c]	0.59[c]

^[a]Inhibition of specific binding of [³H]angiotensin II (2 nm) to rat adrenal cortical microsomes.

^[b]Intravenous (iv) and oral (po) dose at which statistically significant drops in blood pressure were observed (>15 mmHg) in renal hypertensive rats.

^[c]Value given is the effective dose that lowers the blood pressure by 30 mmHg (ED₃₀).

^[d]At this dose, no statistically significant drop in blood pressure was observed.

^[e]Compound failed to cause a significant drop in blood pressure even at 100 mgkg⁻¹.