Lead optimization of methionine aminopeptidase-2 (MetAP2) inhibitors containing sulfonamides of 5, 6-disubstituted anthranilic acids

…, Q Zhang, P Lou, LA Garcia, J Bouska, M Yates…

Index: Wang, Gary T.; Mantei, Robert A.; Kawai, Megumi; Tedrow, Jason S.; Barnes, David M.; Wang, Jieyi; Zhang, Qian; Lou, Pingping; Garcia, Lora A.; Bouska, Jennifer; Yates, Melinda; Park, Chang; Judge, Russell A.; Lesniewski, Richard; Sheppard, George S.; Bell, Randy L. Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 10 p. 2817 - 2822

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Citation Number: 20

Abstract

A series of aryl sulfonamides of 5, 6-disubstituted anthranilic acids were identified as potent inhibitors of methionine aminopeptidase-2 (MetAP2). Small alkyl groups and 3-furyl were tolerated at the 5-position of anthranilic acid, while–OCH3, CH3, and Cl were found optimal for the 6-position. Placement of 2-aminoethoxy group at the 6-position enabled interaction with the second Mn2+ but did not result in enhancement in potency. Introduction of a ...