Bioorganic and Medicinal Chemistry Letters p. 5630 - 5633 (2007)
Update date:2022-08-04
Topics:
Bursavich, Matthew G.
Gilbert, Adam M.
Lombardi, Sabrina
Georgiadis, Katy E.
Reifenberg, Erica
Flannery, Carl R.
Morris, Elisabeth A.
5′-Phenyl-3′H-spiro[indoline-3,2′-[1,3,4]thiadiazol]-2-one inhibitors of ADAMTS-5 (Aggrecanase-2) have been prepared via commercially available starting materials. Selected compounds 23, 33-35 show sub-micromolar ADAMTS-5 potency and strong SAR trends with selectivity over the related metalloproteases ADAMTS-4 (Aggrecanase-1), MMP12, and MMP13. This series of compounds represents progress toward a selective ADAMTS-5 inhibitor as a disease modifying osteoarthritis drug.
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