N-Benzoyl amino acids as ICAM/LFA-1 inhibitors. Part 2: Structure–activity relationship of the benzoyl moiety

…, I Aliagas-Martin, M Stanley, M Beresini, K Clark…

Index: Burdick, Daniel J.; Marsters Jr., James C.; Aliagas-Martin, Ignacio; Stanley, Mark; Beresini, Maureen; Clark, Kevin; McDowell, Robert S.; Gadek, Thomas R. Bioorganic and Medicinal Chemistry Letters, 2004 , vol. 14, # 9 p. 2055 - 2059

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Citation Number: 17

Abstract

o-Bromobenzoyl l-tryptophan 1 inhibits the association of LFA-1 with ICAM-1 with an IC50 of 1.7 μM. Evaluation of the structure–activity relationship of the benzoyl moiety shows that 2, 6- di-substitutions greatly enhance potency of this class of inhibitors. Electronegative substitutions that favor a 90° angle between the benzoyl ring and the amide bond yield the most potent compounds. There is a strong correlation between the potency of the ...