Modification and Functionalization of the Guanidine Group by Tailor-made Precursors

Citations Over Time

Abstract

The guanidine group is one of the most important pharmacophoric groups in medicinal chemistry. The only amino acid carrying a guanidine group is arginine. In this article, an easy method for the modification of the guanidine group in peptidic ligands is provided, with an example of RGD-binding integrin ligands. It was recently demonstrated that the distinct modification of the guanidine group in these ligands allows for the selective modulation of the subtype (e.g., between the subtypes αv and α5). Moreover, a formerly unknown strategy for the functionalization via the guanidine group was demonstrated, and the synthetic approach is reviewed in this document. The modifications described here involve terminally (Nω) alkylated and acetylated guanidine groups. For the synthesis, tailor-made precursor molecules are synthesized, which are then subjected to a reaction with an orthogonally deprotected amine to transfer the pre-modified guanidine group. For the synthesis of alkylated guanidines, precursors based on N,N'-Di-Boc-1H-pyrazole-1-carboxamidine are used to synthesize acylated compounds, the precursor of choice being a correspondingly acylated derivative of N-Boc-S-methylisothiourea, which can be obtained in one- and two-step reactions.

Related Papers

• → Amidine‒ and guanidine‒based synthetic methods for CO2 capture and utilization(2023)22 cited
• → Poly(amidine)s and poly(guanidine)s ? synthesis and some properties(1979)5 cited
• [Relationships between structure and the noradrenaline depleting effects of guanidine and amidine derivatives (author's transl)].(1975)
• → Amidines and Guanidines in Natural Products and Medicines(2009)27 cited
• → ChemInform Abstract: Guanidine Synthesis: Use of Amidines as Guanylating Agents.(2016)