Table 1. Profiles of potent analogs 5–11 with EC₅₀ less than 300 nM in the RXFP1 transfected HEK293 cAMP assay.

EC₅₀s of compounds are given in micromolar units for the HEK293 cells stably transfected with RXFP1 (HEK-RXFP1), for THP1 cells which endogenously express RXFP1, for HEK293 cells stably transfected with RXFP2 (HEK-RXFP2), as well as the vasopressin receptor (HEK-V1b), and for cytotoxicity at 72 h using the HEK293 cells stably transfected with RXFP1 (HEK-RXFP1). Replicate compound concentration-response data is also provided (Supplementary Fig. S1). The series has good selectivity against RXFP2 and AVPR1B receptors stably transfected into HEK293 cells. Phosphate buffered saline (PBS) solubility analysis was performed by Analiza Inc. and based upon quantitative nitrogen detection as described (www.analiza.com). Mouse liver microsomal (MLM) stability analyses were performed by Pharmaron and are based upon duplicate incubations of test reagent in pooled male mouse liver microsomes (www.pharmaron.com). Analysis in the absence and presence of glutamate synthase (NADPH) was performed to assess NADPH free degradation. Half-lifes (T_1/2) were calcuated only in NADPH (+) degradation (Supplementary Table S2)

ID	HEK-RXFP1 EC50 (µM)	THP1 EC50 (µM)	HEK-RXFP2 EC50 (µM)	HEK-V1b EC50 (µM)	ATP Tox. EC50 (µM)	PBS Solubility (µM)	MLM Stability (T1/2 in min.)
5	0.297	0.523	3.34	inactive	3.74	2.9	N/A
6	0.188	0.358	inactive	inactive	29.7	6.3	N/A
7	0.188	0.362	7.47	inactive	18.8	< 1.1	1732
8	0.094	0.200	inactive	inactive	9.4	7.0	122
9	0.067	0.107	inactive	inactive	29.7	3.3	100
10	0.052	0.105	inactive	inactive	9.4	17.0	133
11	0.047	0.124	inactive	inactive	59.3	5.3	178