title: Identification of a pharmacophore for thrombopoietic activity of small, non-peptidyl molecules. 1. Discovery and optimization of salicylaldehyde thiosemicarbazone thrombopoietin mimics.
abstract: High-throughput screening has resulted in the discovery of thiosemicarbazone thrombopoietin mimics. A shared pharmacophore hypothesis between this series and a previously identified class, the pyrazol-4-ylidenehydrazines, led to the rapid optimization of both potency and efficacy of the thiosemicarbazones. The application of high-throughput chemistry and purification techniques allowed for the rapid elucidation of structure-activity relationships.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Duffy
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Shaw
authors.forename: Evelyne
authors.initials: E
authors.lastname: Delorme
authors.forename: Susan B
authors.initials: SB
authors.lastname: Dillon
authors.forename: Connie
authors.initials: C
authors.lastname: Erickson-Miller
authors.forename: Leslie
authors.initials: L
authors.lastname: Giampa
authors.forename: Yifang
authors.initials: Y
authors.lastname: Huang
authors.forename: Richard M
authors.initials: RM
authors.lastname: Keenan
authors.forename: Peter
authors.initials: P
authors.lastname: Lamb
authors.forename: Nannan
authors.initials: N
authors.lastname: Liu
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Miller
authors.forename: Alan T
authors.initials: AT
authors.lastname: Price
authors.forename: Jon
authors.initials: J
authors.lastname: Rosen
authors.forename: Heather
authors.initials: H
authors.lastname: Smith
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Wiggall
authors.forename: Lihua
authors.initials: L
authors.lastname: Zhang
authors.forename: Juan I
authors.initials: JI
authors.lastname: Luengo
mesh_terms: D000447:Aldehydes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D008958:Models, Molecular; D018716:Molecular Mimicry; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013926:Thrombopoietin / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000447:Aldehydes; D011994:Recombinant Proteins; D013882:Thiosemicarbazones; C062542:salicylaldehyde thiosemicarbazone; D013926:Thrombopoietin