Identification of a pharmacophore for thrombopoietic activity of small, non-peptidyl molecules. 1. Discovery and optimization of salicylaldehyde thiosemicarbazone thrombopoietin mimics.
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.
Duffy
Kevin J
KJ
Shaw
Anthony N
AN
Delorme
Evelyne
E
Dillon
Susan B
SB
Erickson-Miller
Connie
C
Giampa
Leslie
L
Huang
Yifang
Y
Keenan
Richard M
RM
Lamb
Peter
P
Liu
Nannan
N
Miller
Stephen G
SG
Price
Alan T
AT
Rosen
Jon
J
Smith
Heather
H
Wiggall
Kenneth J
KJ
Zhang
Lihua
L
Luengo
Juan I
JI
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
D000447:Aldehydes; D011994:Recombinant Proteins; D013882:Thiosemicarbazones; C062542:salicylaldehyde thiosemicarbazone; D013926:Thrombopoietin