. Author manuscript; available in PMC: 2021 May 14.

Published in final edited form as: J Med Chem. 2020 Apr 17;63(9):4528–4554. doi: 10.1021/acs.jmedchem.9b01573

Table 3.

Inhibition data for wild-type and mutant NOS enzymes by selected compounds (7, 10, 12, 29, 32, and 36)^a

	K_i (μM)				Selectivity
Compd	WT-rnNOS	heNOS	D597N rnNOS	M336V/D597N rnNOS	^WT/_SM	^WT/_DM
7	0.045	18.7	0.273	0.215	6	5
10	0.119	41.9	2.11	1.57	18	13
12	0.055	52.6	0.416	1.60	8	29
29	0.039	21.0	0.246	0.189	6	5
32	0.052	23.7	0.384	0.159	7	3
36	0.043	27.3	0.575	0.114	13	3

The compounds were assayed for in vitro inhibition against purified NOS isoforms: rat nNOS (rnNOS, and human eNOS (heNOS), as well as single mutant (SM) (D597N) and double mutant (DM) (M336V/D597N) of rat nNOS using known literature methods, and K_i values were calculated directly from IC₅₀ values using the Cheng–Prusoff equation. IC₅₀ values are the average of at least two replicates from 6–9 data points; all experimental standard error values (for the LogIC₅₀) are less than ± 0.10. Selectivity values are ratios of respective K_i values.