Synthesis, biological evaluation, and structure-activity relationships of 2-[2-(benzoylamino)benzoylamino]benzoic acid analogues as inhibitors of adenovirus replication.

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Öberg CT, Strand M, Andersson EK, Edlund K, Tran NPN, Mei Y, Wadell G, Elofsson M

J. Med. Chem. 55 (7) 3170-3181 [2012-04-12; online 2012-03-01]

2-[2-Benzoylamino)benzoylamino]benzoic acid (1) was previously identified as a potent and nontoxic antiadenoviral compound (Antimicrob. Agents Chemother. 2010, 54, 3871). Here, the potency of 1 was improved over three generations of compounds. We found that the ortho, ortho substituent pattern and the presence of the carboxylic acid of 1 are favorable for this class of compounds and that the direction of the amide bonds (as in 1) is obligatory. Some variability in the N-terminal moiety was tolerated, but benzamides appear to be preferred. The substituents on the middle and C-terminal rings were varied, resulting in two potent inhibitors, 35g and 35j, with EC(50) = 0.6 μM and low cell toxicity.

Chemical Biology Consortium Sweden (CBCS) [Collaborative]

PubMed 22369233

DOI 10.1021/jm201636v

Crossref 10.1021/jm201636v

Laboratories for Chemical Biology Umeå (LCBU)