New 4-Acyl-1-phenylaminocarbonyl-2-phenylpiperazine Derivatives as Potential Inhibitors of Adenovirus Infection. Synthesis, Biological Evaluation, and Structure-activity Relationships

被引：30

作者：

Sanchez-Cespedes, Javier ^{[1
]}

Martinez-Aguado, Pablo ^{[1
]}

Vega-Holm, Margarita ^{[2
]}

Serna-Gallego, Ana ^{[1
]}

Ignacio Candela, Jose ^{[2
]}

Antonio Marrugal-Lorenzo, Jose ^{[1
]}

Pachon, Jeronimo ^{[1
,3
]}

Iglesias-Guerra, Fernando ^{[2
]}

Manuel Vega-Perez, Jose ^{[2
]}

机构：

[1] Univ Seville, Unit Infect Dis Microbiol & Prevent Med, Inst Biomed Seville IBiS, Univ Hosp Virgen Rocio,CSIC, E-41013 Seville, Spain

[2] Univ Seville, Dept Organ & Med Chem, Fac Pharm, Prof Garcia Gonzalez 2, E-41071 Seville, Spain

[3] Univ Seville, Dept Med, E-41009 Seville, Spain

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 59卷 / 11期

关键词：

ORGAN TRANSPLANT RECIPIENTS; ENTRY INHIBITORS; IN-VITRO; VIRAL-INFECTIONS; VIRUS-INFECTION; REPLICATION; ANALOGS; FUSION; CELLS; CYTOMEGALOVIRUS;

D O I：

10.1021/acs.jmedchem.6b00300

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The search for human adenovirus (HAdV)-specific antiviral drugs for the treatment of HAdV infections in immunocompromised patients continues to be a challenging goal for medicinal chemistry. Here, we report the synthesis, biological evaluation, and structure activity relationships of a small molecules library. We have identified six phenylpiperazine derivatives that significantly inhibited HAdV infection. These six compounds showed the capacity to block HAdV and, in addition, human cytomegalovirus (HCMV) replications at low micromolar concentration, with little or no cytotoxicity. On the basis of our biological studies, these molecules block HAdV and HCMV infections in different phases of their life cycle, providing potential candidates for the development of a new family of antiviral drugs for the treatment of infections by DNA viruses.

引用

页码：5432 / 5448

页数：17

共 51 条

[1] Small-Molecule Screening Using a Whole-Cell Viral Replication Reporter Gene Assay Identifies 2-{[2-(Benzoylamino)Benzoyl]Amino}-Benzoic Acid as a Novel Antiadenoviral Compound [J].