Small, lipophilic, and conformationally-constrained substituted cyclopropane rings are finding increasingly sophisticated use in pharmaceuticals.1 Unlike the monosubstituted ring, di- and tri-substituted cyclopropane rings can give rise to crucial stereochemical features.2 For instance, introducing a cyclopropane ring as a conformational constraint into a flexible peptide ligand can provide a preorganized pseudo peptide having significantly higher activity.3
Combining a substituted cyclopropane fragment with other privileged substructures (mainly heterocycles) has been successfully adopted in drug design. Presently, a number of both approved drugs and experimental drug candidates contain the cyclopropane as a scaffold to link the functional substructures with other privileged ligands in a spatially well-defined fashion. For instance, antiplatelet agent Ticarelor 1, shown in Figure 1, has the trans-disubstituted cyclopropane bridging pharmacologically active difluorophenyl and heterocyclic fragments.
Recently discovered highly selective histamine H3 receptor agonist 2 (Fig. 1) contains a cis-disubstituted cyclopropane ring that connects privileged imidazole moiety and 2-aminoethyl group.4 Compounds 35 and 46 are examples of potent and specific enzyme inhibitors in which the functional substructures are connected through tri- and tetrasubstituted cyclopropane rings, respectively.
Figure 1. Some biologically active molecules containing the cyclopropane moiety.
A representative set of cyclopropane derivatives available from Life Chemicals is provided below. To explore the full data set, please, send your request to firstname.lastname@example.org.
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- Shiozaki, M. et al. Bioorg. Med. Chem. Lett. 2009, 19, 6213.