4,6‐Disubstituted 2,2‐dimethylchromans are reported as pharmacologically active compounds that mainly target the ATP‐sensitive potassium channels. The present study is an attempt to characterize the impact of the nature of substituents introduced at the 4‐ and 6‐positions of 2,2‐dimethylchromans on their capacities to inhibit insulin release from pancreatic β‐cells or to relax vascular smooth muscle cells, both biological responses that are supposed to reflect interaction with specific ion channels. From the core structure 4‐amino‐2,2‐dimethylchroman, a progressive increase in the steric hindrance of the chemical functionalities introduced at the 4‐position (amino, formamido, acetamido, arylureido/thioureido) and at the 6‐position (amino, formamido, acetamido, alkoxycarbonylamino) led to a progressive magnification of the inhibitory effect on the insulin release process and, to a lesser extent, of the vasorelaxant activity. Moreover, the dextrorotatory enantiomer of 2,2‐dimethylchroman compound 29 was more potent than its levorotatory counterpart for inhibiting the insulin secretory process. Additional pharmacological investigations suggested, however, that the myorelaxant activity of 11 and 15 resulted from a direct Ca²⁺ entry blockade.

中文翻译：

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一系列2,2-二甲基苯并二氢吡喃类化合物的结构-活性关系的解密，这些抑制剂可作为胰岛素释放和平滑肌松弛剂的抑制剂

据报道4,6-二取代的2,2-二甲基苯并二氢吡喃是主要针对ATP敏感钾通道的药理活性化合物。本研究旨在描述在2,2-二甲基苯并吡喃的4和6位上引入的取代基的性质对其抑制胰岛β细胞释放胰岛素或舒张血管平滑肌细胞的能力的影响，这两种生物反应都应该反映与特定离子通道的相互作用。从4-氨基-2,2-二甲基苯并吡喃的核心结构中，在4-位（氨基，甲酰胺基，乙酰胺基，芳基脲基/硫脲基）和6-位（氨基，甲酰胺，乙酰胺，烷氧基羰基氨基）导致对胰岛素释放过程的抑制作用逐步扩大，并且在较小程度上导致血管舒张活性降低。此外，2,2-二甲基苯并二氢吡喃化合物的右旋对映异构体29比左旋对应物对抑制胰岛素分泌过程更有效。然而，另外的药理研究表明，11和15的肌肉松弛药活性是由直接的Ca ²⁺进入封锁引起的。