AI Article Synopsis
- The study presents a one-pot method for creating unsymmetrical 1,3,5-trisubstituted-1,2,4-triazoles through the coupling of amidines and carboxylic acids, followed by cyclization using hydrazines.
- The method achieved an 81% success rate in parallel synthesis and has the potential to generate over a billion unique chemical compounds.
- The created compound library includes over 10 million that meet lead-likeness criteria and 195 million sp-enriched compounds, making this method significant for advancements in medicinal chemistry.
Article Abstract
An implementation of the three-component one-pot approach to unsymmetrical 1,3,5-trisubstituted-1,2,4-triazoles into combinatorial chemistry is described. The procedure is based on the coupling of amidines with carboxylic acids and subsequent cyclization with hydrazines. After the preliminary assessment of the reagent scope, the method had 81% success rate in parallel synthesis. It was shown that over a billion-sized chemical space of readily accessible ("REAL") compounds may be generated based on the proposed methodology. Analysis of physicochemical parameters shows that the library contains significant fractions of both drug-like and "beyond-rule-of-five" members. More than 10 million of accessible compounds meet the strictest lead-likeness criteria. Additionally, 195 Mln of sp-enriched compounds can be produced. This makes the proposed approach a valuable tool in medicinal chemistry.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486894 | PMC |
| http://dx.doi.org/10.1007/s11030-021-10218-2 | DOI Listing |
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