Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FI-00014, Finland; Department of Chemistry and NanoScience Center, University of Jyväskylä, P.O. Box 35, FI-40014, Jyväskylä, Finland.
Boehringer Ingelheim Pharma GmbH & Co. KG, Drug Discovery Sciences Germany, Birkendorfer Straße 65, 88397, Biberach an der Riß, Germany.
Eur J Med Chem. 2022 Jul 5;237:114374. doi: 10.1016/j.ejmech.2022.114374. Epub 2022 Apr 12.
Azulene is a bicyclic scaffold rarely applied in medicinal chemistry. Here we report physicochemical and in vitro parameters relevant for drug discovery for a series of diversely substituted azulenes. We synthesized and characterized several scaffold hopping series of analogously substituted azulenes, indoles and naphthalenes. This enabled a comparison of azulene with the more common scaffolds indole and naphthalene. Our data indicates that undesirably low photostability of azulenes is restricted to certain substitution patterns. Generally, we conclude that azulene is an underused lipophilic bicycle and should be considered as a valuable complement to the collection of medicinal chemistry scaffolds.
薁是一种在药物化学中很少应用的双环支架。在这里，我们报告了一系列不同取代薁的物理化学和体外参数，这些参数与药物发现相关。我们合成并表征了几类类似取代的薁、吲哚和萘的支架跃迁系列。这使我们能够将薁与更常见的吲哚和萘支架进行比较。我们的数据表明，薁的光不稳定性低是受到某些取代模式的限制。总的来说，我们得出结论，薁是一种未被充分利用的亲脂性双环化合物，应该被视为药物化学支架集合的有价值的补充。
