Bioorganic & Medicinal Chemistry Letters 2004-03-22

Discovery of novel heteroaryl-substituted chalcones as inhibitors of TNF-alpha-induced VCAM-1 expression.

Charles Q Meng, X Sharon Zheng, Liming Ni, Zhihong Ye, Jacob E Simpson, Kimberly J Worsencroft, Martha R Hotema, M David Weingarten, Jason W Skudlarek, Joshua M Gilmore, Lee K Hoong, Russell R Hill, Elaine M Marino, Ki-Ling Suen, Charles Kunsch, Martin A Wasserman, James A Sikorski

Index: Bioorg. Med. Chem. Lett. 14(6) , 1513-7, (2004)

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Abstract

Novel chalcone derivatives have been discovered as potent inhibitors of TNF-alpha-induced VCAM-1 expression. Thienyl or benzothienyl substitution at the meta-position of ring B helps boost potency while large substitution at the para-position on ring B is detrimental. Various substitutions are tolerated on ring A. A lipophilicity-potency relationship has been observed in several sub-series of compounds.