Solid phase synthesis of 1,3,4-oxadiazin-5(6R)-one and 1,3,4-oxadiazol-2-one scaffolds from resin-bound acyl hydrazides is described. We demonstrate here that the reactions of resin-bound aryl or hetero-aromatic acyl hydrazides with 2-substituted-2-bromoacetic acids and 4-nitrophenyl chloroformate and subsequent treatment with DIEA lead to intramolecular cyclization reactions to produce six-membered 1,3,4-oxadiazin-5(6R)-ones and five-membered 1,3,4-oxadiazol-2-ones, respectively. We also show that acyl hydrazide-derived 1,3,4-oxadiazol-2-ones may be useful serine hydrolase inhibitors. This journal is © The Royal Society of Chemistry 2015.

Sarma B.K.

Liu X.

Wu H.

Gao Y.

Kodadek T.

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Shiv Nadar University

Organic and Biomolecular Chemistry

A potent and selective inhibitor of platelet-activating factor acetylhydrolase 1B2 (PAFAH1B2) is described. The compound was derived by improvement of a modest affinity primary hit isolated from the screening of a bead-displayed peptoid–azapeptoid hybrid library tethered to an oxadiazolone ‘warhead’. The oxadiazolone moiety of the inhibitors was found to react covalently with the active site serine residue of PAFAH1B2. This screening strategy may be useful for the identification of many selective, covalent inhibitors of serine hydrolases. © 2016 Elsevier Ltd

Bioorganic and Medicinal Chemistry

Identification of selective covalent inhibitors of platelet activating factor acetylhydrolase 1B2 from the screening of an oxadiazolone-capped peptoid–azapeptoid hybrid library

Chem. Commun.

The use of a Mitsunobu reagent for the formation of heterocycles: a simple method for the preparation of 3-alkyl-5-aryl-1,3,4-oxadiazol-2(3H)-ones from carboxylic acids

Journal of Medicinal Chemistry

Chiral 1,3,4-Oxadiazol-2-ones as Highly Selective FAAH Inhibitors

Journal of the American Chemical Society

Screening Bicyclic Peptide Libraries for Protein–Protein Interaction Inhibitors: Discovery of a Tumor Necrosis Factor-α Antagonist

Chemistry & Biology

Synthesis and Screening of Stereochemically Diverse Combinatorial Libraries of Peptide Tertiary Amides

Organic & Biomolecular Chemistry

Synthesis of libraries of peptidomimetic compounds containing a 2-oxopiperazine unit in the main chain

Solid phase synthesis of 1,3,4-oxadiazin-5 (6R)-one and 1,3,4-oxadiazol-2-one scaffolds from acyl hydrazides