Table 1.

Yields of synthesized benzamides and affinity towards human AT₂R in HEK-293 cells by displacement of either [¹²⁵I]CGP-42112A or [¹²⁵I]Sarile, and reference K_i values from displacement of [¹²⁵I]Ang II from the AT₂R in pig myometrial membrane.

Entry	Y	Z	Yield[a]	Yield[b]	Inhibition [%] of		Ki AT2R [μm]
			X=tBu	X=H	[125I]CGP binding		Human	Human	Pig
					1 μm	10 μm	[125I]CGP	[125I]Sarile	[125I]Ang II
1	H		78 % 9	21 % 37[e]	6	10
2	H		66 % 10	56 % 38[e]	3	11
3	H		70 % 11	75 % 39[e]	4	13
4	H		76 % 12	82 % 40[e]	–[c]	12
5	H		57 % 13	68 % 41[e]	5	6
6	H		24 % 14	73 % 42[e]	6	23	22.0	19.4
7	H		42 % 15	69 % 43[e]	2	4
8	H		75 % 16	65 % 44[e]	6	32	9.0	11.0
9	H		85 % 17	62 % 45[e]	6	7
10	H		55 % 18	95 % 46[e]	6	7
11	H		14 % 19	96 % 47[e]	13	43	7.5	9.6
12	H		43 % 20	64 % 48	14[d]	31[d]	11.0	3.1
13	H		70 % 21	89 % 49	–[c]	12
14	Me		85 % 22	47 % 50[e]	–[c]	7
15	Me		75 % 23	77 % 51[e]	7	13
16	Me		53 % 24	75 % 52[e]	4	7
17	Me		22 % 25	72 % 53[e]	28	62	2.4	2.6
18	Me		30 % 26	84 % 54[e]	1	18
19	Me		45 % 27	68 % 55[e]	16	34	7.6	11.2
20	Me		83 % 28	65 % 56[e]	1	7
21	Me		74 % 29	75 % 57[e]	1	4
22	Me		22 % 30	82 % 58[e]	18	62	2.5	2.3
23	Me		48 % 31	71 % 59	4[d]	54[d]	3.4	1.5
24	Me		75 % 32	76 % 60	–[c]	6
25	Et		48 % 33	58 % 61	6[d]	29[d]	10.0
26	Et		66 % 34	49 % 62	–[c]	26[d]	16.0
27	Et		50 % 35	52 % 63	11[d]	40[d]	8.3
28	Et		62 % 36	46 % 64	11[d]	50[d]	4.4
29		H	68 % 65	74 % 68	–[c]	–[c]	n.c.[f]
30		H	73 % 66	88 % 69	–[c]	7[d]	>100
31		H	16 % 67	57 % 70	–[c]	5[d]	35.0
	Compound
32	E						110.0	47.0	0.0166
33	F						63.0		0.0370
34	C						0.025		0.0005
35	B (Ang IV)						0.035		0.0077
36	A (Ang II)						0.044×10−3	0.0028	0.0003
37	D (C21/M024)						0.0098	0.0076	0.0004

^[a] Isolated yield after the aminocarbonylation reaction, >95 % purity.

^[b] Isolated yield after the deprotection, >95 % purity.

^[c] Not active.

^[d] Compound not included in the affinity screen, value taken from K_i determination.

^[e] Evaluated for AT₁R affinity, none of the compounds exhibited any binding.

^[f] Not calculable—less than 25 % displacement at highest concentration.