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. 2010 Nov 2;2(1):58–62. doi: 10.1021/ml100215b

Table 2. Optimization of Benzimidazole Fragment: In Vitro hmGluR5 Antagonism.

graphic file with name ml-2010-00215b_0005.jpg

compd R1 4-W 5-W 6-W 7-W IC50 [μM]a HLMb RLMb
15b Pr H H H H 0.10 83 158
15c Et H H H H 0.11 120 118
15d Bu H H H H 0.36 347 279
15e iBu H H H H 0.11 55 826
15f Pr Cl H H H 0.20 74 69
15g Pr H Cl H H >0.5 400 34
15h Pr H H Cl H 0.13 56 33
15i Pr H H H Cl 0.024 83 112
a

hmGluR5 Ca2+ flux7 using glutamate as agonist; data are geometric means of n ≥ 2.

b

HLM: human liver microsomes. RLM: rat liver microsomes. CLint (intrinsic clearance) reported in μL/min/mg protein.