title: 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.
authors.affiliation: Department of Chemistry, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Öberg
authors.forename: Mårten
authors.initials: M
authors.lastname: Strand
authors.forename: Emma K
authors.initials: EK
authors.lastname: Andersson
authors.forename: Karin
authors.initials: K
authors.lastname: Edlund
authors.forename: Nam Phuong Nguyen
authors.initials: NP
authors.lastname: Tran
authors.forename: Ya-Fang
authors.initials: YF
authors.lastname: Mei
authors.forename: Göran
authors.initials: G
authors.lastname: Wadell
authors.forename: Mikael
authors.initials: M
authors.lastname: Elofsson
mesh_terms: D000256:Adenoviridae / Q000187:drug effects* / Q000502:physiology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001565:Benzoates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: C574641:2-(4,5-difluoro-2-(2-fluorobenzoylamino)benzoylamino)benzoic acid; C574640:2-(5-chloro-2-(2-fluorobenzoylamino)benzoylamino)benzoic acid; D000998:Antiviral Agents; D001549:Benzamides; D001565:Benzoates