Franchini S, Sorbi C, Linciano P, Brasili L, Tait A
Pharmazie. 2019 Mar 1;74(3):131-135. doi: 10.1691/ph.2019.8878.
Propranolol is a popular β adrenergic antagonists that, together with pindolol, binds also to serotoninergic receptors, namely 5-HT. In this work the rigidification of the propranolol structure by locking its hydroxyl group within a 1,3-dioxolane ring was investigated. Constrained derivatives of propranolol were synthesized, fully characterized and tested for their affinity at β-adrenoreceptors and 5-HT receptors using radioligand binding assay. The constrained derivatives were inactive, as expected, at β adrenergic receptors. Although less expected, these derivatives failed to bind also to 5-HT receptors. The rigidification of propranolol is detrimental for 5-HTR activity.
普萘洛尔是一种常见的β肾上腺素能拮抗剂，它与吲哚洛尔一起，也能与血清素能受体即5-羟色胺（5-HT）结合。在这项研究中，我们通过将普萘洛尔的羟基锁定在1,3 -二氧戊环中来研究其结构的刚性化。合成了普萘洛尔的受限衍生物，对其进行了全面表征，并使用放射性配体结合试验检测了它们对β -肾上腺素能受体和5-羟色胺受体的亲和力。不出所料，这些受限衍生物在β肾上腺素能受体上无活性。尽管不太出人意料，但这些衍生物也未能与5-羟色胺受体结合。普萘洛尔的刚性化对5-羟色胺受体活性有害。
