1,2,4-Oxadiazoles

Research output: Chapter in Book/Report/Conference proceedingChapter

26 Citations (Scopus)

Abstract

The uses of 1,2,4-oxadiazoles include those as agonists at muscarinic receptors, 5-hydroxytryptamine (5-HT) receptor antagonists, benzodiazepine receptor agonists, potent antagonists of the (serotonin) 5-HT1B/D receptors, muscarinic receptor ‘superagonists’, selective inhibitors of human neutrophil elastase, and as active and selective A2B adenosine receptor antagonists. Much interest stems from the use of the fully conjugated 1,2,4-oxadiazole as a hydrolysis resistant ester or amide bioisostere and peptidomimetic. Amongst the non- fully conjugated systems, the soluble guanylyl cyclase inhibitor ODQ is a potent and selective inhibitor of nitric oxide-sensitive guanylyl cyclase and (S)-quisqualic acid is a neuroexcitatory naturally occurring amino acid. Synthetic approaches to the fully conjugated system are dominated by the conversion of a carboxylic acid into an activated derivative, followed by O-acylation of an amidoxime fragment and ring closure. A second popular route is 1,3-dipolar cycloaddition of a nitrile oxide to a nitrile. The reaction of an amidoxime with a carbonyl or the 1,3-dipolar cycloaddition of a nitrile oxide to an imine, or of a nitrone to a nitrile, provides the major routes to the nonconjugated dihydro-1,2,4-oxadiazoles. The reactions of fully conjugated 1,2,4-oxadiazoles and their nonconjugated analogues are detailed together with an in-depth analysis of their structural, theoretical, and thermodynamic properties.
LanguageEnglish
Title of host publicationComprehensive Heterocyclic Chemistry III
EditorsAlan R. Katritzky, Christopher A. Ramsden, Richard J.K. Taylor
PublisherElsevier Ltd
Chapter5.04
Pages243-314
Number of pages72
Volume5
ISBN (Print)9780080449920
DOIs
Publication statusPublished - 1 Dec 2008

Fingerprint

Oxadiazoles
Nitriles
Cycloaddition
Serotonin 5-HT1 Receptor Antagonists
Acylation
Oxides
Guanylate Cyclase
Nitric oxide
Cycloaddition Reaction
Muscarinic Receptors
Carboxylic acids
Amides
Amino acids
Structural properties
Hydrolysis
Esters
Thermodynamic properties
Adenosine A2 Receptor Antagonists
Secretory Proteinase Inhibitory Proteins
Quisqualic Acid

Cite this

Hemming, K. (2008). 1,2,4-Oxadiazoles. In A. R. Katritzky, C. A. Ramsden, & R. J. K. Taylor (Eds.), Comprehensive Heterocyclic Chemistry III (Vol. 5, pp. 243-314). Elsevier Ltd. https://doi.org/10.1016/B978-008044992-0.00504-6
Hemming, K. / 1,2,4-Oxadiazoles. Comprehensive Heterocyclic Chemistry III. editor / Alan R. Katritzky ; Christopher A. Ramsden ; Richard J.K. Taylor. Vol. 5 Elsevier Ltd, 2008. pp. 243-314
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Hemming, K 2008, 1,2,4-Oxadiazoles. in AR Katritzky, CA Ramsden & RJK Taylor (eds), Comprehensive Heterocyclic Chemistry III. vol. 5, Elsevier Ltd, pp. 243-314. https://doi.org/10.1016/B978-008044992-0.00504-6

1,2,4-Oxadiazoles. / Hemming, K.

Comprehensive Heterocyclic Chemistry III. ed. / Alan R. Katritzky; Christopher A. Ramsden; Richard J.K. Taylor. Vol. 5 Elsevier Ltd, 2008. p. 243-314.

Research output: Chapter in Book/Report/Conference proceedingChapter

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N2 - The uses of 1,2,4-oxadiazoles include those as agonists at muscarinic receptors, 5-hydroxytryptamine (5-HT) receptor antagonists, benzodiazepine receptor agonists, potent antagonists of the (serotonin) 5-HT1B/D receptors, muscarinic receptor ‘superagonists’, selective inhibitors of human neutrophil elastase, and as active and selective A2B adenosine receptor antagonists. Much interest stems from the use of the fully conjugated 1,2,4-oxadiazole as a hydrolysis resistant ester or amide bioisostere and peptidomimetic. Amongst the non- fully conjugated systems, the soluble guanylyl cyclase inhibitor ODQ is a potent and selective inhibitor of nitric oxide-sensitive guanylyl cyclase and (S)-quisqualic acid is a neuroexcitatory naturally occurring amino acid. Synthetic approaches to the fully conjugated system are dominated by the conversion of a carboxylic acid into an activated derivative, followed by O-acylation of an amidoxime fragment and ring closure. A second popular route is 1,3-dipolar cycloaddition of a nitrile oxide to a nitrile. The reaction of an amidoxime with a carbonyl or the 1,3-dipolar cycloaddition of a nitrile oxide to an imine, or of a nitrone to a nitrile, provides the major routes to the nonconjugated dihydro-1,2,4-oxadiazoles. The reactions of fully conjugated 1,2,4-oxadiazoles and their nonconjugated analogues are detailed together with an in-depth analysis of their structural, theoretical, and thermodynamic properties.

AB - The uses of 1,2,4-oxadiazoles include those as agonists at muscarinic receptors, 5-hydroxytryptamine (5-HT) receptor antagonists, benzodiazepine receptor agonists, potent antagonists of the (serotonin) 5-HT1B/D receptors, muscarinic receptor ‘superagonists’, selective inhibitors of human neutrophil elastase, and as active and selective A2B adenosine receptor antagonists. Much interest stems from the use of the fully conjugated 1,2,4-oxadiazole as a hydrolysis resistant ester or amide bioisostere and peptidomimetic. Amongst the non- fully conjugated systems, the soluble guanylyl cyclase inhibitor ODQ is a potent and selective inhibitor of nitric oxide-sensitive guanylyl cyclase and (S)-quisqualic acid is a neuroexcitatory naturally occurring amino acid. Synthetic approaches to the fully conjugated system are dominated by the conversion of a carboxylic acid into an activated derivative, followed by O-acylation of an amidoxime fragment and ring closure. A second popular route is 1,3-dipolar cycloaddition of a nitrile oxide to a nitrile. The reaction of an amidoxime with a carbonyl or the 1,3-dipolar cycloaddition of a nitrile oxide to an imine, or of a nitrone to a nitrile, provides the major routes to the nonconjugated dihydro-1,2,4-oxadiazoles. The reactions of fully conjugated 1,2,4-oxadiazoles and their nonconjugated analogues are detailed together with an in-depth analysis of their structural, theoretical, and thermodynamic properties.

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Hemming K. 1,2,4-Oxadiazoles. In Katritzky AR, Ramsden CA, Taylor RJK, editors, Comprehensive Heterocyclic Chemistry III. Vol. 5. Elsevier Ltd. 2008. p. 243-314 https://doi.org/10.1016/B978-008044992-0.00504-6