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Barraza SJ, Denmark SE. Synthesis, Reactivity, Functionalization, and ADMET Properties of Silicon-Containing Nitrogen Heterocycles. J Am Chem Soc. 2018;140(21):6668-6684doi: 10.1021/jacs.8b03187.
Barraza, S. J., & Denmark, S. E. (2018). Synthesis, Reactivity, Functionalization, and ADMET Properties of Silicon-Containing Nitrogen Heterocycles. Journal of the American Chemical Society, 140(21), 6668-6684. https://doi.org/10.1021/jacs.8b03187
Barraza, Scott J, and Denmark, Scott E. "Synthesis, Reactivity, Functionalization, and ADMET Properties of Silicon-Containing Nitrogen Heterocycles." Journal of the American Chemical Society vol. 140,21 (2018): 6668-6684. doi: https://doi.org/10.1021/jacs.8b03187
Barraza SJ, Denmark SE. Synthesis, Reactivity, Functionalization, and ADMET Properties of Silicon-Containing Nitrogen Heterocycles. J Am Chem Soc. 2018 May 30;140(21):6668-6684. doi: 10.1021/jacs.8b03187. Epub 2018 May 15. PMID: 29763323; PMCID: PMC6011798.
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J Am Chem Soc. 2018 May 30;140(21):6668-6684. doi: 10.1021/jacs.8b03187. Epub 2018 May 15.

Synthesis, Reactivity, Functionalization, and ADMET Properties of Silicon-Containing Nitrogen Heterocycles.

Journal of the American Chemical Society

Scott J Barraza, Scott E Denmark

Affiliations

  1. Roger Adams Laboratory, Department of Chemistry , University of Illinois , Urbana , Illinois 61801 , United States.

PMID: 29763323 PMCID: PMC6011798 DOI: 10.1021/jacs.8b03187

Abstract

Silicon-containing compounds have been largely ignored in drug design and development, despite their potential to improve not only the potency but also the physicochemical and ADMET ( absorption, distribution, metabolism, excretion, toxicity) properties of drug-like candidates because of the unique characteristics of silicon. This deficiency is in large part attributable to a lack of general methods for synthesizing diverse organosilicon structures. Accordingly, a new building block strategy has been developed that diverges from traditional approaches to incorporation of silicon into drug candidates. Flexible, multi-gram-scale syntheses of silicon-containing tetrahydroquinoline and tetrahydroisoquinoline building blocks are described, along with methods by which diversely functionalized silicon-containing nitrogen heterocycles can be rapidly built using common reactions optimized to accommodate the properties of silicon. Furthermore, to better clarify the liabilities and advantages of silicon incorporation, select compounds and their carbon analogues were challenged in ADMET-focused biological studies.

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