Agonists of the Follicle Stimulating Hormone Receptor from an Encoded Thiazolidinone Library

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Abstract
The design, synthesis, characterization, and screening of a large, encoded thiazolidinone library are described. Three sets of 35 building blocks were combined by encoded split−pool synthesis to give a library containing more than 42 000 members. Building block selection was based in part on a novel small molecule follicle stimulating hormone receptor agonist hit and in part for diversity. HPLC/MS techniques were applied at the single-bead level to build confidence in the reliability of library construction. Application of two distinct screening strategies resulted in the identification of compounds with significantly improved potency over the initial hit. This work demonstrates the versatility of encoded libraries for preparing a large number of analogues of a given hit while simultaneously generating a large collection of compounds for screening against other targets.

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