. Author manuscript; available in PMC: 2021 May 14.

Published in final edited form as: J Med Chem. 2020 Apr 16;63(9):4929–4956. doi: 10.1021/acs.jmedchem.0c00311

Table 14.

Comparison of in vitro potency (3D7 parasites) and SCID mouse efficacy data for PfDHODH inhibitors.

Cmpd	3D7 EC₅₀ (μM)	Unbound 3D7 EC₅₀ (μM)^a	ED₉₀ (mg/kg/day)	Blood AUC_ED90 (μg.h/ml)	Unbound blood AUC (μg.h/ml)^b
37	0.016	0.0077	~50^* (QD)	~9	~1.1
1^#	0.0060	0.0010	8.1 (QD)	16.7	0.023
1^#	---	---	3.0 (BID)	10.8	0.015
DSM421^#	0.014	0.0070	2.6 (QD)	12.9	0.25

Data taken from^{21, 22, 26}.

QD=once daily dosing; BID=twice daily dosing. Studies compared use the standard Peters test with 4 days of consecutive dosing. Parasite levels one day after the final dose were used to determine the ED₉₀.

For 37 the ED₉₀ reflects the average from the two studies where 24 h after the last dose 85% reduction in parasitemia was observed in the GSK study and 97% reduction was observed in the Swiss TPH study, both at the 50 mg/kg dose.

obtained by multiplying the EC₅₀ by the fraction unbound in Albumax medium

approximated by multiplying the blood AUC_ED90 by the fraction unbound in blood (f_u(blood)) where f_u(blood) = f_u(plasma)/B:P