Fluorination Patterning: A Study of Structural Motifs That Impact Physicochemical Properties of Relevance to Drug Discovery

被引：187

作者：

Huchet, Quentin A. ^{[1
]}

Kuhn, Bernd ^{[2
]}

Wagner, Bjorn ^{[2
]}

Kratochwil, Nicole A. ^{[2
]}

Fischer, Holger ^{[2
]}

Kansy, Manfred ^{[2
]}

Zimmerli, Daniel ^{[2
]}

Carreira, Erick M. ^{[1
]}

Muller, Klaus ^{[2
]}

机构：

[1] ETH, Organ Chem Lab, CH-8093 Zurich, Switzerland

[2] F Hoffinann La Roche AG, Roche Innovat Ctr Basel, Roche Pharma Res & Early Dev, CH-4070 Basel, Switzerland

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 58卷 / 22期

关键词：

MEDICINAL CHEMISTRY; OPTIMIZATION; ALCOHOLS; PERMEABILITY; CONFORMATION; ALLYLATION; SOLUBILITY; POLARITY; DESIGN; ACCESS;

D O I：

10.1021/acs.jmedchem.5b01455

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：9041 / 9060

页数：20

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