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. 2018 Dec 3;10(1):86–91. doi: 10.1021/acsmedchemlett.8b00462

Table 2. Exploration of Imidazole Headgroup and Biphenyl Substitution.

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compound R3 R4 R5 R6 n AT1 pKi NEP pIC50 % inhibition of ang-II pressor response (3 mg/kg, iv) urinary cGMP fold increase over vehicle (3 mg/kg, iv)
losartan           8.3 <5 67  
omapatrilat           <5 9.7   5.3
7 Cl n-Bu H H 1 7.8 7.2 11 2.2
21 Cl n-Bu H H 0 7.2 9    
22 Me n-Bu H H 1 7.3 7.1    
23 Me n-Bu H H 0 6.7 9.2    
24 Et n-Bu H H 1 8.3 6.9 68 2.6
25 Et n-Bu H H 0 7.4 8.5 18 3.2
26 Cyclopropyl n-Bu H H 1 8.2 6.9 55 1.8
27 Cyclopropyl n-Bu H H 0 7.5 9.0 5 4
28 i-Bu n-Bu H H 1 8.1 6.9    
29 i-Bu n-Bu H H 0 7.5 7.7 32 1.9
30 Et PrO H H 1 8.6 7.3 65 1.9
31 Et PrO H H 0 7.7 9 23 3.8
32 Et EtO H H 1 8.9 7.5 67 2.9
33 Et EtO H H 0 8.2 9 57 3.6
34 Et EtO F H 1 9.1 7.8 85 1.8
35 Et EtO F H 0 8.9 9.2 76 3.5
36 Et EtO H F 1 8.9 7.1    
37 Et EtO H F 0 8.3 8.5 57 3.3
38 Et EtO F F 0 8.3 7.8