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Rational Design, Synthesis, and Evaluation of Nanomolar Type II Dehydroquinase Inhibitors

✍ Scribed by Richard J. Payne; Fabienne Peyrot; Olivier Kerbarh; Andrew D. Abell; Chris Abell

Publisher
John Wiley and Sons
Year
2007
Tongue
English
Weight
641 KB
Volume
2
Category
Article
ISSN
1860-7179

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✦ Synopsis

Abstract

The in silico design, synthesis, and biological evaluation of ten potent type II dehydroquinase inhibitors are described. These compounds contain an anhydroquinate core, incorporated as a mimic of the enolate reaction intermediate. This substructure is attached by a variety of linking units to a terminal phenyl group that binds in an adjacent pocket. Inhibitors were synthesised from (−)‐quinic acid using palladium‐catalysed Stille and carboamidation chemistry. Several inhibitors exhibited nanomolar inhibition constants against type II dehydroquinases from Streptomyces coelicolor and Mycobacterium tuberculosis. These are among the most potent inhibitors of these enzymes reported to date.

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✍ Cristina Sánchez-Sixto; Verónica F. V. Prazeres; Luis Castedo; Se Won Suh; Heath 📂 Article 📅 2008 🏛 John Wiley and Sons 🌐 English ⚖ 746 KB

## Abstract Several 3‐heteroaryl analogs of the known dehydroquinase inhibitor (1R,4R,5R)‐1,4,5‐trihydroxy‐2‐cyclohexene‐1‐carboxylic acid (**4**) were synthesized and tested as inhibitors of Helicobacter pylori type II dehydroquinase, the third enzyme of the shikimic acid pathway. All of these com