Fluorination Patterning: A Study of Structural Motifs That Impact Physicochemical Properties of Relevance to Drug Discovery
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- 作者：Quentin A. Huchet ; Bernd Kuhn ; Bj枚rn Wagner ; Nicole A. Kratochwil ; Holger Fischer ; Manfred Kansy ; Daniel Zimmerli ; Erick M. Carreira ; Klaus M眉ller
- 刊名：Journal of Medicinal Chemistry
- 出版年：2015
- 出版时间：November 25, 2015
- 年：2015
- 卷：58
- 期：22
- 页码：9041-9060
- 全文大小：814K
- ISSN：1520-4804
文摘
The synthesis of a collection of 3-substituted indole derivatives incorporating partially fluorinated n-propyl and n-butyl groups is described along with an in-depth study of the effects of various fluorination patterns on their properties, such as lipophilicity, aqueous solubility, and metabolic stability. The experimental observations confirm predictions of a marked lipophilicity decrease imparted by a vic-difluoro unit when compared to the gem-difluoro counterparts. The data involving the comparison of the two substitution patterns is expected to benefit molecular design in medicinal chemistry and, more broadly, in life as well as materials sciences.