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. 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 2.

Carboxylic Acid Sidechain SAR.

graphic file with name nihms-1036286-t0013.jpg
Compd Z G SRE.L IC50 (nM)a, b MLM T1/2 (min)d
8j (CH2)2 CO2H 4 (2c) >60
6 (CH2)2 CO2Et 2.6 -
9 (CH2)2 CONHCH3 >100,000 -
8p CH2 CO2H >100,000 -
8q (CH2)3 CO2H 1.8 (0.84c) >60
8r (CH2)4 CO2H 43 -
a

Inhibition of Gα12-stimulated SRE.L (mean of n = 3, SEM < 10%) in PC3 cells.

b

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

c

SRE.L assay performed in HEK293T cells (mean of n = 3, SEM < 10%).

d

Half-life in mouse liver microsomes.