Analogs based on the 2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate scaffold showed high potency and selectivity as both group II mGlu receptors orthosteric agonists and antagonists. This scaffold was initially designed to mimic the fully extended glutamate backbone conformation that was hypothesized to be the active conformation for the group II mGlu receptors. With the availability of crystal structures of l-Glu-bound amino terminal domain proteins from multiple mGlu receptor subtypes spanning all three subgroups, a new steric hindrance hypothesis was proposed to account for the scaffold’s unique group II selectivity that explores the subtle distance differences between the α-carbon of l-Glu and the center of the tyrosine phenyl ring from the bottom lobe (e.g. Y216 of mGlu₂).

基于2-氨基双环[3.1.0]己烷-2,6-二羧酸酯骨架的类似物显示出高的效价和选择性，成为第II组mGlu受体正构激动剂和拮抗剂。该支架最初被设计为模拟完全延伸的谷氨酸骨架构象，该构象被认为是II族mGlu受体的活性构象。鉴于跨越所有三个亚组的多个mGlu受体亚型中与L -Glu结合的氨基末端结构域蛋白的晶体结构的可用性，提出了一种新的空间位阻假说，以解释支架独特的II组选择性，该选择性探讨了支架之间的细微距离差异。l -Glu的α碳和底部叶上酪氨酸苯环的中心（例如mGlu的Y216₂）。