Conformationally Restricted Diamines in Medicinal Chemistry and Drug Discovery

One of the most popular approaches  in the synthesis of new molecular scaffolds for drug discovery is to generate platforms that allow for the arrangement of functional groups in a defined spatial manner [1]. In this respect,  considerable attention has been focused on the synthesis of so-called conformationally restricted scaffolds bearing two or more functional groups [2-3]. Indeed, a predefined spatial presentation of the ligand subunits covalently linked to such a scaffold should lead to a decrease in entropy of binding of the molecule with its biological target [4], as schematically shown in Figure 1.

Figure 1. Cartoon representation of a complex  formation between biological target  and  a drug molecule constructed around the conformationally rigid scaffold.

Conformationally restricted diamines (CRDAs) are especially attractive scaffolds because they offer the potential of the wide variability in the relative spatial arrangement of functional groups and exit vectors [3]. With  the chemistry of the amino group  being very well studied,  available methodology offers numerous routes for rational and selective chemical modification of the two nitrogen atoms in a CRDA. Therefore, it is not surprising that today there are quite a few commercially available drugs and many experimental drug candidates that contain fragments of N-substituted CRDAs [5]. Three examples of CRDA-based marketed drugs are given in Figure 2.

Figure 2. Examples of commercial drugs bearing fragments of substituted conformationally restricted diamines.

Several representative monoprotected conformationally restricted diamines (CRDAs) and related compounds available from Life Chemicals are listed below. The full list of titled compounds can be obtained upon request by emailing marketing@lifechemicals.com.

In addition to CRDAs already available in our stock, even more compounds can be synthesized to the customer’s order.

References

1. Maass, P.; Schulz-Gasch, T.; Stahl, M.; Rarey, M. J. Chem. Inf. Model. 2007, 47, 390.
2. Marson, C. M. Chem. Soc. Rev. 2011, 40, 5514.
3. Grygorenko, O. O.; Radchenko, D. S.; Volochnyuk, D. M.; Tolmachev, A. A.; Komarov, I. V. Chem. Rev. 2011, 111, 5506.
4. Patrick, G. L. An Introduction to Medicinal Chemistry; Oxford University Press: New York, 2005. pp 210–213
5. www.drugbank.ca