Bicyclo[1.1.1]pentane (BCP) as an sp3 Carbon-rich Bioisostere for para-Phenyl and tert-Butyl Groups
To conclude, bicyclo[1.1.1]pentane (BCP) is unique as a non-classical p-phenyl isostere as well as a t-butyl isostere. In comparison to CUB and BCO, it is the shortest in terms of diagonal distance and the smallest in size. Since it has the least number of carbons vs. BCO and CUB, BCP is the least lipophilic. BCP is an especially useful isostere for phenyl fragment when it serves largely as a spacer rather than engaging π-stacking interactions with the target protein. While maintaining the biological activities as the p-phenyl analogue, BCP isosteres provide superior biopharmaceutical properties such as solubility, permeability, and in vitro stability. BCP’s utility in medicinal chemistry is expected to grow in the future.
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