Discovery and SAR of thiazolidine-2,4-dione analogues as insulin-like growth factor-1 receptor (IGF-1R) inhibitors via hierarchical virtual screening.

Insulin-like growth factor-1 receptor (IGF-1R) is a growth factor receptor tyrosine kinase acting as a critical mediator of cell proliferation and survival. Novel 5-benzylidenethiazolidine-2,4-dione (5) and 5-(furan-2-ylmethylene)thiazolidine-2,4-dione (6) compounds were identified as potent and selective IGF-1R inhibitors via hierarchical virtual screening. Initial SAR and biological activity of the analogues of 5 and 6 with thiazolidine-2,4-dione template are presented, and several inhibitors with low nanomolar potency are reported.

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