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4-Oxooctahydroquinoline-1(2H)-carboxamides as hepatitis B virus (HBV) capsid core protein assembly modulators.
Hwang, Nicky; Ban, Haiqun; Wu, Shuo; McGuire, Kelly; Hernandez, Ellen; Chen, Junjun; Zhao, Qiong; Suresh, Manasa; Blass, Benjamin; Viswanathan, Usha; Kulp, John; Chang, Jinhong; Clement, Jason; Menne, Stephan; Guo, Ju-Tao; Du, Yanming.
Afiliação
  • Hwang N; Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, USA.
  • Ban H; Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, USA; Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Pudong New District, Shanghai 200127, China.
  • Wu S; Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, USA.
  • McGuire K; Temple University, 1801 N Broad St, Philadelphia, PA 191222, USA.
  • Hernandez E; Delaware Valley University, 700 E Butler Ave, Doylestown, PA 18901, USA.
  • Chen J; Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, USA.
  • Zhao Q; Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, USA.
  • Suresh M; Georgetown University Medical Center, 3900 Reservoir Road, Washington, DC 20057, USA.
  • Blass B; Temple University School of Pharmacy, Department of Pharmaceutical Sciences 3307 North Broad Street, Philadelphia, PA 19140, USA.
  • Viswanathan U; Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, USA.
  • Kulp J; Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, USA.
  • Chang J; Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, USA.
  • Clement J; Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, USA.
  • Menne S; Georgetown University Medical Center, 3900 Reservoir Road, Washington, DC 20057, USA.
  • Guo JT; Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, USA. Electronic address: ju-tao.guo@bblumberg.org.
  • Du Y; Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, USA. Electronic address: yanming.du@bblumberg.org.
Bioorg Med Chem Lett ; 58: 128518, 2022 02 15.
Article em En | MEDLINE | ID: mdl-34979256
Hepatitis B virus (HBV) core protein, the building block of the HBV capsid, plays multiple roles in viral replication, and is an attractive target for development of antiviral agents with a new mechanism of action. In addition to the heteroaryldihydropyrimidines (HAPs), sulfamoylbenzamides (SBAs), dibenzothiazepine derivatives (DBTs), and sulfamoylpyrrolamides (SPAs) that inhibit HBV replication by modulation of viral capsid assembly and are currently under clinical trials for the treatment of chronic hepatitis B (CHB), other chemical structures with activity to modulate HBV capsid assembly have also been explored. Here we describe our continued optimization of a benzamide originating from our high throughput screening. A new bicyclic carboxamide lead featuring an electron deficient non-planar core structure was discovered. Evaluations of its ADMET (absorption, distribution, metabolism, excretion and toxicity) and pharmacokinetic (PK) profiles demonstrate improved metabolic stability and good bioavailability.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antivirais / Quinolinas / Vírus da Hepatite B Limite: Animals / Humans Idioma: En Revista: Bioorg Med Chem Lett Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antivirais / Quinolinas / Vírus da Hepatite B Limite: Animals / Humans Idioma: En Revista: Bioorg Med Chem Lett Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos