In this study, we aimed to synthesize a novel blocker of transient receptor potential canonical 6 (TRPC6). The sp² carbon atoms of the aminoindane skeleton of the known inhibitor were replaced with sp³ carbon atoms to increase the molecular complexity, measured by fraction sp³ (Fsp³). The representative compound, a bicyclo[4.3.0]nonane derivative DS88790512, inhibited TRPC6 with an IC₅₀ value of 11 nM. Notably, DS88790512 exhibited excellent selectivity against hERG and hNa_V1.5 channels, and was identified as an orally bioavailable compound.

中文翻译：

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发现双环[4.3.0]壬烷衍生物DS88790512作为有效的，选择性的和口服生物利用型瞬态受体电位规范药物6（TRPC6）的阻滞剂

在这项研究中，我们旨在合成一种新型的瞬时受体电位规范6（TRPC6）阻断剂。已知抑制剂的氨基茚满骨架的sp ²碳原子被sp ³碳原子取代，从而增加了分子的复杂性，通过分数sp ³（Fsp ³）进行测量。代表性化合物双环[4.3.0]壬烷衍生物DS88790512抑制了TRPC6，IC ₅₀值为11 nM。值得注意的是，DS88790512对hERG和hNa _V 1.5通道表现出优异的选择性，并被确定为口服生物可利用的化合物。