In the early 1980s it was noted that a series of imidazole-5-acetic acidderivatives diminished blood pressure responses to Ang II in rats. Two compounds, S-8307 and S-8308, were later found to be highly specific and promising non-peptide Ang II receptor antagonists but using molecular modeling it was seen that their structures would have to mimic more closely the pharmacophore of Ang II. Structural modifications were made and the orally active, potent and selective nonpeptide AT1 receptor blocker losartan was developed. In 1995 losartan was approved for clinical use in the United States and since then six additional ARBs have been approved. These drugs are known for their excellent side-effects profiles, which clinical trials have shown to be similar to those of placebos.