一种作为共价修饰剂用于提高水溶性的不带电荷的氧杂环丁烷亚砜
An uncharged oxetanyl sulfoxide as a covalent modifier for improving aqueous solubility.
作者信息
Skoda Erin M, Sacher Joshua R, Kazancioglu Mustafa Z, Saha Jaideep, Wipf Peter
机构信息
Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
出版信息
ACS Med Chem Lett. 2014 Jun 27;5(8):900-4. doi: 10.1021/ml5001504. eCollection 2014 Aug 14.
Abstract
Low aqueous solubility is a common challenge in drug discovery and development and can lead to inconclusive biological assay results. Attaching small, polar groups that do not interfere with the bioactivity of the pharmacophore often improves solubility, but there is a dearth of viable neutral moieties available for this purpose. We have modified several poorly soluble drugs or drug candidates with the oxetanyl sulfoxide moiety of the DMSO analog MMS-350 and noted in most cases a moderate to large improvement of aqueous solubility. Furthermore, the membrane permeability of a test sample was enhanced compared to the parent compound.
摘要
低水溶性是药物研发过程中常见的挑战，可能导致生物学测定结果不明确。连接不干扰药效团生物活性的小极性基团通常可提高溶解度，但目前缺乏适用于此目的的可行中性部分。我们用二甲基亚砜类似物MMS-350的氧杂环丁烷亚砜部分修饰了几种难溶性药物或候选药物，发现在大多数情况下，水溶性有中度到大幅的提高。此外，与母体化合物相比，测试样品的膜通透性增强。
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