Table 2. Activation of Gq Pathway and Cellular Toxicity^a.

compd	R1	R2	R3	R4	BLT2 EC50 ± SEM (nM)	efficacy rel. to CAY10583% ± SEM	AT1 IC50 ± SEM (nM)	BLT1	live rate (%) after 3 days at 50 μM
1	Cyp		nBu	tetrazole	410 ± 34	69 ± 2	6 ± 0.6**	inactive	unaffected
8a	Cyp		nBu	COOH	1490 ± 168	95 ± 3	190 ± 6.6**	inactive	92
8b	Cyp		Ph	COOH	inactive		>10 μM	inactive	unaffected
8c	Cyp		Bn	COOH	6580 ± 956	88 ± 4	8650 ± 620	inactive	79
8d	Cyp		CH2CH2Ph	COOH	inactive	inactive	inactive	inactive	unaffected
8e	Cy		nBu	COOH	860 ± 88	64 ± 8	155 ± 2.2**	inactive	90
8f	CH3	iPr	nBu	tetrazole	67.6 ± 4	42 ± 4	15 ± 1.7**	inactive	unaffected
8g	CH3	Ph	nBu	tetrazole	550 ± 88	11 ± 4	25 ± 2.1**	inactive	56
13					24200 ± 3400	31 ± 1	7750 ± 660	inactive	unaffected
14					6390 ± 358	36 ± 4	390 ± 74**	inactive	77
15	CH3	CH3	nBu	tetrazole	8140 ± 815	36 ± 4	32 ± 8.9**	inactive	56
19a					inactive		1010 ± 34**	inactive	89
19b					7500 ± 1100	25 ± 2	∼10 μM	inactive	88

^aCompounds were tested for activation of BLT2 or BLT1 in the IP-One assay in agonist mode. For BLT2, efficacy was determined by comparison to reference agonist CAY10583 at 20 μM each. For BLT1, the reference agonist LTB₄ served as a positive control. Inhibition of the second off-target AT1 was tested in the IP-One assay in antagonist mode with [Val⁵-angiotensin II being present at a constant concentration of 10 nM. **Indicates that the respective compound is a full agonist with efficacy comparible to irbesartan (1). IP-One assays for the determination of EC₅₀ or IC₅₀ with SEM were conducted at least two times (n = 2). Cellular toxicity was tested on Hep-G2 cells treated for 3 days. ATP content as a measure for overall metabolic activity and cell survival was determined using the CellTiter-Glo assay. For 50 μM of compound, the live rate is reported as percent of DMSO control.