Synthesis, Biological Evaluation, and Structure–Activity Relationships of 2-[2-(Benzoylamino)benzoylamino]benzoic Acid Analogues as Inhibitors of Adenovirus Replication

Abstract

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.

2-[4,5-Difluoro-2-(2-Fluorobenzoylamino)-Benzoylamino]Benzoic Acid, an Antiviral Compound with Activity against Acyclovir-Resistant Isolates of Herpes Simplex Virus Types 1 and 2

“…All the previous results indicated that benzavir-1 and benzavir-2 were potent inhibitors of HSV replication and that they were active against acyclovir-resistant isolates of HSV. In addition, our previous structure-activity relationship analysis of benzavir-1 had indicated that benzavir-2 was a more potent inhibitor of HAdV replication than benzavir-1 (42). In the present study, on HSV replication, the results also indicated that benzavir-2 is a more potent antiviral agent than benzavir-1 ( Fig.…”

“…2B). Both benzavir-1 and benzavir-2 had similar activities against HSV, regardless of type, and the overall results indicate that benzavir-2 is more potent than benzavir-1, which is in line with the activity against HAdV (42).…”

“…Compounds. Benzavir-1 and benzavir-2 were synthesized as described previously (42). Acyclovir and cidofovir were purchased from Sigma-Aldrich (Schnelldorf, Germany) as a powder.…”

Isolation and Characterization of Anti-Adenoviral Secondary Metabolites from Marine Actinobacteria

“…We have previously developed a whole-cell based viral replication reporter gene assay utilizing a replication competent green fluorescent protein (GFP) expressing vector based on adenovirus type 11 (RCAd11GFP) [9,10]. This assay was used to screen novel synthetic small molecule inhibitors of viral replication [10] that have been further explored by chemical optimization and evaluation [11,12]. In this paper, we expand our screening-based approach and describe the screening of ethyl acetate (EtOAc) extracts derived from actinobacteria originating from Vestfjorden, Norway, and subsequent isolation and identification of anti-adenoviral butenolides 1 – 4 (Figure 1 and Figure 2) produced by a marine Streptomyces strain ( Streptomyces sp.…”

Photoinduced rotamerization and dissociation of o -fluorobenzoyl chloride in solid Ar

“…Benzoyl chloride derivatives have been used as a reagent for the syntheses of anticancer [1], antileukemic [2] and antiadenoviral [3] agents. Despite its practical use, the available properties on the structure and spectroscopy are relatively scarce.…”