title: Rapid synthesis and zebrafish evaluation of a phenanthridine-based small molecule library.
abstract: A Heck cyclisation approach is described for the rapid synthesis of a library of natural product-like small molecules, based on the phenanthridine core. The synthesis of a range of substituted benzylamine building blocks and their incorporation into the library is reported, together with a highly selective cis-dihydroxylation protocol that enables access to the target compounds in an efficient manner. Biological evaluation of the library using zebrafish phenotyping has led to the discovery of compound 20c, a novel inhibitor of early-stage zebrafish embryo development.
authors.affiliation: School of Chemistry, The University of Edinburgh, West Mains Road, Edinburgh, UK EH9 3JJ.
authors.forename: Lauren R
authors.initials: LR
authors.lastname: Donaldson
authors.forename: Stephen
authors.initials: S
authors.lastname: Wallace
authors.forename: David
authors.initials: D
authors.lastname: Haigh
authors.forename: E Elizabeth
authors.initials: EE
authors.lastname: Patton
authors.forename: Alison N
authors.initials: AN
authors.lastname: Hulme
mesh_terms: D000818:Animals; D003500:Cyclization; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015394:Molecular Structure; D010617:Phenanthridines / Q000138:chemical synthesis* / Q000494:pharmacology; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000494:pharmacology; D013997:Time Factors; D015027:Zebrafish / Q000196:embryology
chemical_list: D010617:Phenanthridines; D054852:Small Molecule Libraries