. Author manuscript; available in PMC: 2022 Feb 12.

Published in final edited form as: J Med Chem. 2021 Jul 16;64(15):11045–11062. doi: 10.1021/acs.jmedchem.1c00439

Table 2.

AR Binding and Antagonistic Activity of Propanamide Derivatives (26a–h) with Biaryl or Diaryl B-Ring Modifications


Compound (W)	B-ring	Binding (K_i) / Transactivation (IC₅₀) (μM)		SARD Activity (% degradation)
		K_i (DHT=lnM)^a	IC₅₀^a	Full Length^a (LNCaP) at 1 μM	Splice Variant^a (22RV1) at 10 μM
11 (C)^b		0.078	0.048^c	70,100^d	71–100
12 (C)^c		0.267	0.085	65–83	60–100
26a (C)		0.322	0.178 Partial	0, 40^d	0
26b (C)		0.259	0.226	100	60
26c (C)		0.612	0.969	60	0
26d (C)		N.A.^e	No effect	N.A.	N.A.
26e (C)		0.275	0.172	42	16
26f (C)		>10	0.383	84	74
26g (N)		1.486	0.217	12	0
26h (C)		0.703	0.317	73	N.A.
3 (bicalutamide)^c		0.509	0.248	-	-
5 (enzalutamide)^c		3.641	0.216	-	-

AR binding, transactivation, and degradation assays were performed, and values are reported, as described in Table 1.

The compound was reported in the literature in the same assay as described here.⁴⁰

The result was reported in the literature in the same assay as described here.^38,40

The two values indicate SARD assays run with 1 and 10 μM of antagonist.

N.A. means data not available.