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Saccharin Aza Bioisosteres-Synthesis and Preclinical Property Comparisons.

ABSTRACT: 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.

SUBMITTER: Chen Y

PROVIDER: S-EPMC5467200 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Saccharin Aza Bioisosteres-Synthesis and Preclinical Property Comparisons.

Chen Yantao Y Aurell Carl-Johan CJ Pettersen Anna A Lewis Richard J RJ Hayes Martin A MA Lepistö Matti M Jonson Anna C AC Leek Hanna H Thunberg Linda L

ACS medicinal chemistry letters 20170501 6

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 o ...[more]

PMID: 28626531

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