Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10593379 | Bioorganic & Medicinal Chemistry Letters | 2013 | 6 Pages |
Abstract
Cinnamoylanthranilates including tranilast have been identified as promising antifibrotics that can reduce fibrosis occurring in the kidney during diabetes, thereby delaying and/or preventing kidney dysfunction. Structure-activity relationships aimed at improving potency and metabolic stability have led to the discovery of FT061. This compound, which bears a bis-difluoromethoxy catechol, attenuates TGF-β-stimulated production of collagen in cultured renal mesangial cells (approx 50% at 3 μM). When dosed orally at 20 mg/kg to male Sprague Dawley rats, FT061 exhibited a high bioavailability (73%), Cmax of 200 μM and Tmax of 150 min, and a half-life of 5.4 h. FT061 reduced albuminuria when orally dosed in rats at 200 mg kg/day in a late intervention study of a rat model of progressive diabetic nephropathy.
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Authors
Spencer J. Williams, Steven C. Zammit, Alison J. Cox, David M. Shackleford, Julia Morizzi, Yuan Zhang, Andrew K. Powell, Richard E. Gilbert, Henry Krum, Darren J. Kelly,