. Author manuscript; available in PMC: 2022 Oct 18.

Published in final edited form as: J Med Chem. 2020 Sep 17;63(19):11054–11084. doi: 10.1021/acs.jmedchem.0c00996

Table 5.

ADME Profile Obtained for Advanced Analogue (±)-44

	microsomal CL_int (μL/(min mg))^b				liver microsomal stability (% remaining at 30 min)^c							%PPB^e
solubility (μM)^a	H	R	M	cyno	HLM	RLM	MLM	cyno LM	CYP inhibition (% inhibition at 10, μM) 2C9, 2C19, 2D6, 3A4	hERG^d (IC₅₀) (μM)	PPARγ (IC₅₀) (μM)	H	R	M
187.4	<0.0231				105	93	95	103	2C9—0%	>30	>100	99.8	96	96
									2C19—(−)8%
									2D6—18.1%
									3A4—(−)2.2%

Kinetic solubility measured in PBR (pH = 7.4).

Microsomal intrinsic clearance (CL_int); H = human; R = rat; M = mouse; cyno = cynomolgus monkey.

Liver microsomal metabolic stability, % of parent drug remaining after a 30 min incubation in the presence of the microsomes; HLM = human liver microsomes; RLM = rat liver microsomes; MLM = mouse liver microsomes; cyno LM = cynomolgus monkey liver microsomes.

CiPA hERG QPatch assay; compounds were tested (n = 2) in a five-point concentration–response study.

%PPB = plasma protein binding; H = human, R = rat, M = mouse.