Design and synthesis of substituted nicotinamides as inhibitors of soluble epoxide hydrolase

…, NA Farrow, I Muegge, A Kukulka, AK Kabcenell…

Index: Taylor, Steven J.; Soleymanzadeh, Fariba; Eldrup, Anne B.; Farrow, Neil A.; Muegge, Ingo; Kukulka, Alison; Kabcenell, Alisa K.; Lombaert, Stephane De Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 20 p. 5864 - 5868

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Citation Number: 15

Abstract

A series of potent nicotinamide inhibitors of soluble epoxides hydrolase (sEH) is disclosed. This series was designed using structure-based deconstruction and a combination of two HTS hit series, resulting in hybrid analogs that retained the optimal potency from one series, and acceptable in vitro metabolic stability from the other. Structure-guided optimization of these analogs gave rise to nanomolar inhibitors of human sEH that had acceptable ...