Cpds R4 R5 R6 R7 hlIC50, µMa rlIC50, µMa
2.8 H H Cl H 0.25 2
3.1 H Cl H H 0.6 20
3.2 H H F H 1 2
3.3 H F H H 0.8 2
3.4 H Br H H 2.7 20
3.5 H H Br H 0.7 2
3.6 HO H H H 2.5 20
3.7 Me H H H 1.75 20
3.8 H F F H 0.45 2
3.9 H Cl Cl H 2.2 2
3.10 H Cl F H 0.95 2
3.11 H F NH2 Br 1.2 5
3.12 H F F F 1.55 10
3.13 F F F H 0.5 6
3.14 Me Me Cl Br 0.4 2.5
3.15 Br Cl Me Me 0.75 2.7
3.16 Me Me Me Me 0.25 2.25
aHLF, human liver FBPase; RLF, rat liver FBPase; glucose lowering was measured after iv dosing of 10 mg/kg compounds. bND, not determined
Table 3: Benzimidazole SAR of compound 2.3 Analogsa.