化学
亲脂性
氢键
部分
胺气处理
药物化学
生物甾体
苯胺
硫酚
债券定单
立体化学
有机化学
分子
化学合成
粘结长度
生物化学
体外
作者
Yossi Zafrani,Dina Yeffet,Gali Sod‐Moriah,Anat Berliner,Dafna Amir,Daniele Marciano,Eytan Gershonov,Sigal Saphier
标识
DOI:10.1021/acs.jmedchem.6b01691
摘要
There is a growing interest in organic compounds containing the difluoromethyl group, as it is considered a lipophilic hydrogen bond donor that may act as a bioisostere of hydroxyl, thiol, or amine groups. A series of difluoromethyl anisoles and thioanisoles was prepared and their druglike properties, hydrogen bonding, and lipophilicity were studied. The hydrogen bond acidity parameters A (0.085–0.126) were determined using Abraham's solute 1H NMR analysis. It was found that the difluoromethyl group acts as a hydrogen bond donor on a scale similar to that of thiophenol, aniline, and amine groups but not as that of hydroxyl. Although difluoromethyl is considered a lipophilicity enhancing group, the range of the experimental Δlog P(water–octanol) values (log P(XCF2H) – log P(XCH3)) spanned from −0.1 to +0.4. For both parameters, a linear correlation was found between the measured values and Hammett σ constants. These results may aid in the rational design of drugs containing the difluoromethyl moiety.
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