Saccharin Aza BioisosteresSynthesis and Preclinical Property Comparisons

Saccharin Aza BioisosteresSynthesis and Preclinical Property Comparisons

Saccharin is a well-known scaffold in drug discovery. Herein, we report the synthesis and preclinical property comparisons of three bioisosteres of saccharin: aza-pseudosaccharins (cluster B), and two new types of aza-saccharins (clusters C and D). We demonstrate a convenient protocol to selectively...

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Veröffentlicht in:ACS medicinal chemistry letters 2017-06, Vol.8 (6), p.672-677
Hauptverfasser: Chen, Yantao, Aurell, Carl-Johan, Pettersen, Anna, Lewis, Richard J, Hayes, Martin A, Lepistö, Matti, Jonson, Anna C, Leek, Hanna, Thunberg, Linda
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container_end_page 677
container_issue 6
container_start_page 672
container_title ACS medicinal chemistry letters
container_volume 8
creator Chen, Yantao
Aurell, Carl-Johan
Pettersen, Anna
Lewis, Richard J
Hayes, Martin A
Lepistö, Matti
Jonson, Anna C
Leek, Hanna
Thunberg, Linda
description Saccharin is a well-known scaffold in drug discovery. Herein, we report the synthesis and preclinical property comparisons of three bioisosteres of saccharin: aza-pseudosaccharins (cluster B), and two new types of aza-saccharins (clusters C and D). We demonstrate a convenient protocol to selectively synthesize products in cluster C or D when primary amines are used. Preclinical characterization of selected matched-pair products is reported. Through comparison of two diastereomers, we highlight how stereochemistry affects the preclinical properties. Given that saccharin-based derivatives are widely used in many chemistry fields, we foresee that structures exemplified by clusters C and D offer new opportunities for novel drug design, creating a chiral center on the sulfur atom and the option of substitution at two different nitrogens.
doi_str_mv 10.1021/acsmedchemlett.7b00137
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title Saccharin Aza BioisosteresSynthesis and Preclinical Property Comparisons
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