Translations:Discovery and development of angiotensin receptor blockers/23/en

Using nuclear magnetic resonance studies on the spatial structure of Ang II, scientists at DuPont discovered that the Takeda structures had to be enlarged at a particular position to resemble more closely the much larger peptide Ang II. Computer modeling was used to compare S-8308 and S-8307 with Ang II and it was seen that Ang II contains two acidic residues near the NH₂ terminus. These groups were not mimicked by the Takeda leads and therefore it was hypothesized that acidic functional groups would have to be added to the compounds.
The 4-carboxy-derivative EXP-6155 had a binding activity which was ten-fold greater than that of S-8308 which further strengthened this hypothesis.