Brown G R, Foubister A J
J Med Chem. 1984 Jan;27(1):79-81. doi: 10.1021/jm00367a016.
The blood glucose level lowering activity of [(acylamino)ethyl]benzoic acids, such as p-[2-(5-chloro-2-methoxy-benzamido)ethyl]benzoic acid (HB699, 2), is discussed in terms of binding at putative insulin-releasing receptor sites of pancreatic beta cells. The hypoglycemic potencies found for synthetic analogues of 2 indicate that high hypoglycemic activity is only found when a carboxyl group or a group that is readily oxidized to carboxyl in vivo, such as methyl, is attached to the aromatic ring of the phenethyl group. It is proposed that this carboxyl group is able to bind at the same receptor site as the SO2NHCONH group of the sulfonylurea drugs, such as tolbutamide (3). The role of the benzamide group in 2 was attributed to protein binding.
诸如对-[2-(5-氯-2-甲氧基-苯甲酰胺基)乙基]苯甲酸(HB699, 2)之类的[(酰基氨基)乙基]苯甲酸的降血糖活性，是根据其在胰腺β细胞假定的胰岛素释放受体位点处的结合情况来讨论的。所发现的2的合成类似物的降血糖效力表明，只有当羧基或在体内易于氧化成羧基的基团（如甲基）连接到苯乙基的芳环上时，才会出现高降血糖活性。有人提出，该羧基能够与磺脲类药物（如甲苯磺丁脲(3)）的SO2NHCONH基团结合在相同的受体位点上。2中苯甲酰胺基团的作用归因于蛋白质结合。
