| Literature DB >> 31091098 |
Yossi Zafrani1, Gali Sod-Moriah1, Dina Yeffet1, Anat Berliner1, Dafna Amir1, Daniele Marciano1, Shlomi Elias1, Shahaf Katalan1, Nissan Ashkenazi1, Moran Madmon1, Eytan Gershonov1, Sigal Saphier1.
Abstract
The effects of the CF2H moiety on H-bond (HB) acidity and lipophilicity of various compounds, when attached directly to an aromatic ring or to other functions like alkyls, ethers/thioethers, or electron-withdrawing groups, are discussed. It was found that the CF2H group acts as a HB donor with a strong dependence on the attached functional group ( A = 0.035-0.165). Regarding lipophilicity, the CF2H group may act as a more lipophilic bioisostere of OH but as a similar or less lipophilic bioisostere of SH and CH3, respectively, when attached to Ar or alkyl. In addition, the lipophilicity of ethers, sulfoxides, and sulfones is dramatically increased upon CH3/CF2H exchange at the α position. Interestingly, this exchange significantly affects not only the polarity and the volume of the solutes but also their HB-accepting ability, the main factors influencing log Poct. Accordingly, this study may be helpful in the rational design of drugs containing this moiety.Entities:
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Year: 2019 PMID： 31091098 DOI： 10.1021/acs.jmedchem.9b00604
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446