Table 1. Chemical Structures, Binding Data, Distribution Coefficients, Plasma Protein Binding Properties, and Phospholipid Interaction Capabilities of Benzamides 6 and 8.

Ligand	R1	R2	R3	R4	R5	IC50 (μM)a	Ki (μM)a	elog D7.4b	PPB (%)c	CHIIAMd
2						13 ± 2.7	3.3 ± 1.4	0.5	51	–4.0
3						19 ± 1.5	6.4 ± 0.8	–0.4	12	–2.6
6a	H	H	H	H	H	127 ± 40	63 ± 21	–0.3	10	6.3
6b	F	F	F	F	H	65 ± 26	30 ± 14	0.9	17	16.7
8a	H	NH2	H	H	H	107 ± 45	53 ± 24	–1.2	4	–1.1
8b	F	NH2	H	H	H	93 ± 19	45 ± 9.9	–1.2	4	0.7
8c	H	H	NH2	H	H	86 ± 21	41 ± 11	–2.0	3	–1.1
8d	F	H	NH2	H	H	63 ± 16	29 ± 8.2	–0.7	5	5.2
8e	H	H	H	H	NH2	74 ± 14	35 ± 7.0	–0.5	9	6.2
8f	F	H	H	H	NH2	114 ± 60	56 ± 31	–0.1	12	8.1

^aAffinity values determined in a competitive MST assay as described in the methods sections. For comparison, pomalidomide (2) and lenalidomide (3) were included, for which data is from ref (30).

^bDistribution coefficients at pH 7.4 were estimated by an HPLC-based method.

^cPlasma protein binding; experimentally determined percentage of compound bound to human serum albumin.

^dChromatographic hydrophobicity index values referring to IAM chromatography (CHI_IAM values), an estimate for drug–membrane interactions and permeability.