Skip to main content
. 2020 Jul 28;63(17):9300–9315. doi: 10.1021/acs.jmedchem.0c00451

Table 1. Physicochemical Properties and Activity Data of TCMDC-135051 Ring A Analogues.

graphic file with name jm0c00451_0010.jpg

        PfCLK3
 3D7
    
analogue R1 R2 R3 IC50 (nM)a pIC50 EC50 (nM)b pEC50 log D7.4c clint (mL/min/g liver)d
1 NEt2 OMe H 40 7.4 (±0.221) 180 6.7 (±0.126) 0.93 1.12
8a NMe2 OMe H 29 7.5 (±0.224) 457 6.3 (±0.129) 0.85 2.53
8b N-pyrrolidinyl OMe H 38 7.4 (±0.113) 382 6.4 (±0.081) 2.43 1.94
8c N-morpholinyl OMe H 9 8.0 (±0.191) 1339 5.9 (±0.118) 1.20 1.60
12 NH2 OMe H 76 7.1 (±0.142) 2801 5.6 (±0.104) 0.61 2.92
15 H OMe H 79 7.1 (±0.132) 1456 5.8 (±0.152) 2.45 2.54
19 NEt2 OH H 22 7.7 (±0.115) 3529 5.5 (±0.133) 0.59 1.94
23 NEt2 H H 25 7.6 (±0.089) 309 6.5 (±0.114) 0.80 0.85
27 NEt2 H OMe 17 7.7 (±0.116) 3167 5.6 (±0.109) 0.74 1.65
a

IC50 (the concentration of an inhibitor where the response is reduced by half).

b

EC50 (the concentration of a drug that gives half-maximal response). IC50 and EC50 values are means ± SEM of three independent experiments run in triplicates (n = 3).

c

log D7.4 (distribution co-efficient) was estimated using HPLC chromatography.

d

In vitro intrinsic clearance in mouse liver microsomes.