Table 1.

Summary of β-aminophenylketones 3a–k data: Yield, inhibition (IC₅₀) of the interaction between coregulatory peptide SRC2-2 and TRα/TRβ, viability (LD₅₀) of U2OS and ARO cells in the presence of compound, solubility in PBS buffer containing 5% DMSO, and permeability across an artificial membrane (PAMPA).

					In vitro Potency			Cytotoxicity		Pharmacological Properties
Entry	R1	R2	Compound	Yielda (%)	TRαb IC50 (μM)	TRβb IC50 (μM)	TRα: TRβ ratio	AROc LD50 (μM)	U2OSc LD50 (μM)	Solubilityc (μM)	Permeabilityc (10−6 cm/s)
1	2-phenylethyl	methyl	3a	84	3.6	1.5	2.4	2.5	18.4	15	57
2	2-hydroxyethyl	methyl	3b	87	3.0	1.6	1.9	13.2	13.2	97	965
3	isopropyl	isopropyl	3c	81	4.1	2.0	2.1	15.4	20.7	55	747
4	pyrroline		3d	85	4.3	2.7	1.6	19.0	38.4	341	2144
5	morpholine		3e	90	4.1	2.7	1.5	7.2	20.8	110	1210
6	methyl carboxylate	piperidine-4-	3f	86	6.3	3.9	1.6	8.2	19.7	27	145
7	n-butyl	n-butyl	3g	90	6.9	4.2	1.6	5.4	25.5	152	1957
8	methyl	methyl	3h	94	10.6	4.3	2.5	11.0	34.9	321	2323
9	furan-2-ylmethyl	methyl	3i	92	22.6	12.1	1.9	15.5	18.6	47	681
10	cyclohexyl	cyclohexyl	3j	78	16.5	12.7	1.3	25.6	27.3	32	104
11	n-propyl	hydrogen	3k	93	25.8	15.2	1.7	102	160	354	254

^aIsolated yield;

^bvalues are means of two independent experiments done in quadruplicate; the general error limits are 10%;

^cvalues are means of two independent experiments done in triplicate; the general error limits are 10–15%. Actual error values for each measurement are omitted for clarity but are included in tables in the supplemental materials.