Table 2. Potency and Properties of Selected Analogues^a.

				EC50 (nM)b			CLintc
compd	R1	R2	A	induced hTGR5	uninduced hTGR5	uninduced dTGR5	HLM	DLM	eLog D
1				166	5540	4960	<8.0		1.85d
2				24	316	445	>320		3.90
3				154	3220	2060	249		5.10
4				47	1420	584	>320	630	2.90
12	EtNH	H	CH	257	8320	N.T.	79		1.40
13	EtNH	CH3	CH	78	3780	5800	168		2.00e
14	EtNH	CH2CH3	CH	9.2	215	828	238		2.40
5	EtNH	CH(CH3)2	CH	3.6	158	213	>317	139	3.40
15	EtNH	OCH3	CH	137	2430	4280	96	27	1.05
16	EtNH	OCF3	CH	2.3	75	135	184	115	3.00
17	EtNH	SCF3	CH	1.6	48	112	>298		3.50
18	EtNH	CH2CF3	CH	4.7	154	233	141	68	2.60
19	EtNH	CF2CH3	CH	2.7	146	382	211		2.20
20	EtNH	CF2CH3	N	43	2990	3200	18	18	1.40
21	Et	OCF3	CH	2.0	83	220	174		2.90
22	EtO	OCF3	CH	3.3	112	303	115		2.90
23	cPr	OCF3	CH	2.8	43	407	217		3.30

^aNT, not tested.

^bMost values are reflective of n ≥ 3 experiments. Please see the Supporting Information for the number of experiments and associated error. All values are for full agonists relative to a standard.

^cIntrinsic clearance μL/min/mg.

^dMeasured Log D by shake-flask method.

^eCalculated Log D using a model based on Cubist modeling methodology [Rulequest Research, www.rulequest.com]. The training set for the model was based on >45000 measured eLog D values.²⁴