Skip to main content
. Author manuscript; available in PMC: 2019 Jun 24.
Published in final edited form as: J Med Chem. 2019 Apr 18;62(9):4350–4369. doi: 10.1021/acs.jmedchem.8b01772

Table 3.

SRE.L Activity of 5-Aryl-1,3,4-Oxadiazole-2-thiobutanoic Acids.

graphic file with name nihms-1036286-t0014.jpg
Cmpd R1 R2 R3 R4 SRE.L IC50 (nM)a, b MLM T1/2 (min)b
8q Cl H Cl H 0.84 >60
8s Cl H Me H 0.1c 28
8t Cl H MeO H 2 -
19a Cl H Et H 0.0007 -
19b Cl H Pr H <0.0001 -
19c Cl H i-Pr H 0.0007 -
8u H H CF3 H 46 -
8v CF3 H H H 10,000 -
8w Cl H CF3 H 0.06 >60
19d Cl H CF(CH3)2 H 0.5 -
8x Cl H Br H 0.07 -
8y Cl H Ph H 25 -
19e Cl cPr H H 0.019 -
19f Cl H c-Pr H 0.001 (0.0012c) 47
19g Cl H H cPr 20 -
19h Cl H O-cyclopropyl H 1.3 >60
19i Cl H O-oxetanyl H 370 -
a

Inhibition of Gα12-stimulated SRE.L activity (mean of n = 3, SEM < 10%) in HEK cells.

b

Cell viability and proliferation assay with WST-1 < 5% inhibition up to 100 μM inhibitor (mean of n = 3, SEM < 10%).

c

SRE.L data generated with transfected PC-3 cells (mean of n = 3, SEM < 10%).

d

Half-life in mouse liver microsomes.