ArticleACS medicinal chemistry letters2026
Synthesis and LCMS Characterization of a 1275-Member Library of 24-Atom Triazine Macrocycles Derived from Quantitative Dimerization Occurring with >99.9% Fidelity.
Article in ACS medicinal chemistry letters, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Efficient routes to libraries of nonpeptidic macrocycles facilitate drug discovery. Monomers presenting hydrazine and acetal groups separated by a triazine ring and glycine linker dimerize efficiently to yield homodimers (when one monomer is employed) or a mixture of two homodimers and a heterodimer (when two monomers are used). Descriptively, dimerization proceeds quantitatively. The solvent and byproducts are volatile, eliminating the need for additional purification. To evaluate the functional group tolerances of this chemistry, a library of 1275 compounds was created from 50 monomers. Liquid chromatography-mass spectrometry validates the integrity of the library. All reactions yield macrocycles, but under the reaction conditions employed, partial hydrolysis is observed with three ester-containing monomers. Cleavage of a naphthylethyl group is observed for another. Monomers containing a BOC-protected amine, a
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