. 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 1.

Inhibition of NOS enzymes by synthesized compounds 5–37.^a

	K_i (μM)^a				Selectivity
compd	rnNOS	hnNOS	miNOS	heNOS	^rn/_mi	^hn/_he
1	0.066	0.440	28.4	11.8	431	27
2	0.058	0.295	27.7	7.41	478	25
3	0.033	0.031	6.7	5.63	203	181
4	0.025	0.030	4.83	5.76	193	192
5	0.105	0.122	21.7	23.3	207	191
6	0.246	-	-	-	-	-
7	0.045	0.088	16.3	18.7	362	212
8	0.090	0.149	-	-	-	-
9	0.140	-	27.5	-	197	-
10	0.119	0.151	2.86	41.9	24	277
11	0.935	-	-	-	-	-
12	0.055	0.060	24.2	52.6	440	877
13	0.107	-	-	-	-	-
14	1.03	-	-	-	-	-
15	0.285	-	-	-	-	-
16	0.254	-	-	-	-	-
17	0.159	-	-	-	-	-
18	0.180	-	-	-	-	-
19	0.108	-	-	-	-	-
20	0.235	-	-	-	-	-
21	1.42	-	-	-	-	-
22	0.390	-	-	-	-	-
23	0.106	-	-	-	-	-
24	0.058	0.111	24.2	18.2	418	164
25	0.072	0.058	23.9	12.9	333	223
26	0.071	0.066	25.5	20.2	360	307
27	0.062	0.072	9.66	5.65	156	78
28	0.049	0.096	10.4	22.8	212	238
29	0.039	0.046	32.8	21.0	841	457
30	0.083	-	-	-	-	-
31	0.055	0.114	13.5	8.31	246	73
32	0.052	0.076	45.7	23.7	879	312
33	0.044	0.045	8.18	7.73	186	172
34	0.056	0.106	-	-	-	-
35	0.043	0.031	4.32	6.20	100	200
36	0.043	0.063	16.4	27.3	382	433
37	0.053	0.046	21.0	20.0	397	435

The compounds were assayed for in vitro inhibition against four purified NOS isoforms: rat nNOS (rnNOS), human nNOS (hnNOS), murine iNOS (miNOS), and human eNOS (heNOS) using known literature methods (see Experimental Section for details), and K_i values are calculated directly from IC₅₀ values. 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 10%, and all correlation coefficients are good (r²> 0.87). Selectivity values are ratios of respective K_i values.