Modifications of C-2 on the pyrroloquinoline template aimed at the development of potent herpesvirus antivirals with improved aqueous solubility

• Published in: Bioorganic & medicinal chemistry letters 2010-05, Vol.20 (10), p.3039-3042
• Main Authors: Nieman, James A., Nair, Sajiv K., Heasley, Steven E., Schultz, Brenda L., Zerth, Herbert M., Nugent, Richard A., Chen, Ke, Stephanski, Kevin J., Hopkins, Todd A., Knechtel, Mary L., Oien, Nancee L., Wieber, Janet L., Wathen, Michael W.
• Format: Article
• Language: English
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral activity; Antiviral agents; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Biological and medical sciences; Cytomegalovirus; Cytomegalovirus - drug effects; DNA-Directed DNA Polymerase - metabolism; HCMV; Herpes simplex virus 1; Herpesviridae - enzymology; Herpesvirus; Herpesvirus 1, Human - drug effects; Herpesvirus 3, Human - drug effects; Humans; Medical sciences; Nucleic Acid Synthesis Inhibitors; Pharmacology. Drug treatments; Pyrroles - chemical synthesis; Pyrroles - chemistry; Pyrroles - pharmacology; Pyrroloquinoline; Quinolines - chemical synthesis; Quinolines - chemistry; Quinolines - pharmacology; Solubility; Structure-Activity Relationship; Varicella-zoster
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2010.03.115

The synthesis of pyrroloquinoline analogs at C-2 with broad-spectrum anti-herpetic activity and improved solubility are reported. A series of C-2 pyrroloquinoline analogs designed to improve aqueous solubility were examined for herpesvirus polymerase and antiviral activity. Several analogs were identified that maintained the antiviral activity of the previous development candidate against HCMV, HSV-1 and VZV, but with significantly improved aqueous solubility.