. 2021 Jan 13;6(3):2284–2311. doi: 10.1021/acsomega.0c05589

Table 3. In Vitro Evaluation of Spirocycle Analogues.

graphic file with name ao0c05589_0010.jpg

	R₂	R₃	MIC^a (μM)	clog D_pH7.4	hERG^a IC₅₀ (μM)	HepG2^a IC₅₀ (μM)	mouse Cli^a (mL/min/g)
11	phenyl	OMe	0.12	2.5	2.1^a	23	>50
12	phenyl	CyPr	0.10	3.0	2.2^a	22	>50
13	phenyl	CHF₂	0.20	3.1	3.6^a	15	>50
14	phenyl	CF₃	0.09	3.1	4.7^a	30	>50
15	4-(hydroxymethyl) phenyl	Me	1.5	2.0	5.0^a	>50	8.5
16	4-methylphenyl	Me	0.08	2.6	2.5^a	11	>50
17	4-(trifluoromethoxy) phenyl	Me	0.36	3.4	1.9^a	8.6	7
18	6-methoxy pyridin-3-yl	Me	0.37	2.0	3.5^a	>50	44
19	6-(difluoromethoxy)-pyridin-3-yl	Me	0.21	2.5	0.52^a	18	25
20	6-(trifluoromethyl) pyridin-3-yl	Me	0.51	2.6	2.7^a	42	10
21	2-benzoic acid	Me	>20	0.6	>30^a	>50	<0.5
22	3-benzoic acid	Me	3.7	0.5	10.2^a	>50	1.6
23	4-benzoic acid	Me	4.8	0.6	>30^a	>50	0.5
24	4-benzoic acid	Et	0.77	0.9	>30^a	>50	1.1
25	4-benzoic acid	iPr	3.8	1.4	>30^a	>50	1.2
26	4-benzoic acid	tBu	5.5	1.3	>30^a	>50	1.1
27	4-benzoic acid	CHF₂	1.4	1.3	>30^a	>50	0.7
28	4-benzoic acid	CF₃	0.65	1.5	>30^a	>50	1
29	4-benzoic acid	CyPr	0.66	1.2	>30^a	>50	1.1
30	4-benzoic acid	CyBu	1.8	1.5	>30^a	>50	1.6
31	4-benzoic acid	OMe	1.9	0.6	>30^a	>50	1.3
32	4-benzoic acid	OEt	0.53	0.9	>30^a	>50	3.8
33	4-benzoic acid	N-pyrrolidino-	13	1.3		>50	1.5
34	4-benzoic acid	N-morpholino-	>20	1.3		>50	<0.5

See Table 1 for explanation.