Boost your Research with our Original Cyclopropanes

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 orders@lifechemicals.com.

References:

1. (a) Lamberth, C. Tetrahedron 2019, 75, 4365-4383. (b) Salaün, J. Top. Curr. Chem. 2000, 207, 1-67.
2. Marson, C. M. Chem. Soc. Rev. 2011, 40, 5514.
3. Reichelt, A.; Martin, S. F. Acc. Chem. Res. 2006, 39, 433.
4. Kazuta, Y. et al. J. Med. Chem. 2003, 46, 1980.
5. Guay, D. et al. Bioorg. Med. Chem. Lett. 2009, 19, 5392.
6. Shiozaki, M. et al. Bioorg. Med. Chem. Lett. 2009, 19, 6213.