title: A modular lead-oriented synthesis of diverse piperazine, 1,4-diazepane and 1,5-diazocane scaffolds.
abstract: Piperazines are found widely in commercially-available compounds and bioactive molecules (including many drugs). However, in the vast majority of these molecules, the piperazine ring is isolated (i.e. not fused to another ring) and is not substituted on any of its carbon atoms. A modular synthetic approach is described in which combinations of cyclic sulfamidate and hydroxy sulfonamide building blocks may be converted into piperazines and related 1,4-diazepine and 1,5-diazocane scaffolds. By variation of the combinations of building blocks used, it was possible to vary the ring size, substitution and configuration of the resulting heterocyclic scaffolds. The approach was exemplified in the synthesis of a range of heterocyclic scaffolds that, on decoration, would target lead-like chemical space. It was demonstrated that lead-like small molecules based on these scaffolds would likely complement those found in large compound collections.
authors.affiliation: School of Chemistry, University of Leeds, Leeds, LS2 9JT, UK. a.s.nelson@leeds.ac.uk.
authors.forename: Thomas
authors.initials: T
authors.lastname: James
authors.forename: Paul
authors.initials: P
authors.lastname: Maclellan
authors.forename: George M
authors.initials: GM
authors.lastname: Burslem
authors.forename: Iain
authors.initials: I
authors.lastname: Simpson
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Grant
authors.forename: Stuart
authors.initials: S
authors.lastname: Warriner
authors.forename: Visuvanathar
authors.initials: V
authors.lastname: Sridharan
authors.forename: Adam
authors.initials: A
authors.lastname: Nelson
mesh_terms: D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C545228:1,4-diazepane; D001381:Azepines; D006573:Heterocyclic Compounds, 1-Ring; D010879:Piperazines; D000077489:Piperazine