High-throughput screening for the induction of a luciferase reporter gene in a thrombopoietin (TPO)-responsive cell line resulted in the identification of 4-diazo-3-hydroxy-1-naphthalenesulfonic acids as TPO mimics. Modification of the core structure and adjustment of unwanted functionality resulted in the development of (5-oxo-1,5-dihydropyrazol-4-ylidene)hydrazines which exhibited efficacies equivalent to those of TPO in several cell-based assays designed to measure thrombopoietic activity. Furthermore, these compounds elicited biochemical responses in TPO-receptor-expressing cells similar to those in TPO itself, including kinase activation and protein phosphorylation. Potencies for the best compounds were high for such low molecular weight compounds (MW < 500) with EC(50) values in the region of 1-20 nM.

l] M. R. Wasielewski in M. A. Fox and M. Chanon (Eds.): Photoinduced Elecfron Punsfir, Elsevier, Amsterdam and 1988, part A, p 161. 121 J. Breton and A. Vermeglio (Eds.): The Photosynthetic Bacterial Reaction Studies in the area of enediyne antibiotics" -31 recently reported from these laboratories include the total synthe-sisI4] of the oligosaccharide fragment of calicheamicin y: and the c o n s t r~c t i o n~~] of a number of dynemicin A models. Crucial to a successful total synthesis of calicheamicin $ is the stereoselective coupling of the oligosaccharide and agly-Stahl 0 yOMe OMe ? OMe CH~CH/ OMe OH Calicheamicin y,' H = = ? he OMe OH 0 OH Dynemicin A

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