Novel diphenylmethyl-Derived Amide Protecting Group for Efficient Liquid-Phase Peptide Synthesis: AJIPHASE

An efficient method for the synthesis of peptides bearing an amide at the C-terminal is described. This method involves the attachment of a C-terminal protecting group bearing long aliphatic chains, followed by the repetition of simple reaction and precipitation steps with the combined advantages of liquid-phase peptide synthesis (LPPS) and solid-phase peptide synthesis (SPPS). Using this method, a hydrophobic peptide was successfully synthesized in good yield and high purity, which cannot be obtained satisfactorily by SPPS

Discovery of DS-1558: A Potent and Orally Bioavailable GPR40 Agonist

GPR40 is a G protein-coupled receptor that is predominantly expressed in pancreatic β-cells. GPR40 agonists stimulate insulin secretion in the presence of high glucose concentration. On the basis of this mechanism, GPR40 agonists are possible novel insulin secretagogues with reduced or no risk of hypoglycemia. The improvement of <i>in vitro</i> activity and metabolic stability of compound <b>1</b> led to the discovery of <b>13</b>, (3<i>S</i>)-3-ethoxy-3-(4-{[(1<i>R</i>)-4-(trifluoromethyl)-2,3-dihydro-1<i>H</i>-inden-1-yl]­oxy}­phenyl)­propanoic acid, as a potent and orally available GPR40 agonist. Compound <b>13</b> (DS-1558) was found to have potent glucose lowering effects during an oral glucose tolerance test in ZDF rats