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

James A Nieman; Sajiv K Nair; Steven E Heasley; Brenda L Schultz; Herbert M Zerth; Richard A Nugent; Ke Chen; Kevin J Stephanski; Todd A Hopkins; Mary L Knechtel; Nancee L Oien; Janet L Wieber; Michael W Wathen

doi:10.1016/j.bmcl.2010.03.115

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

Bioorg Med Chem Lett. 2010 May 15;20(10):3039-42. doi: 10.1016/j.bmcl.2010.03.115. Epub 2010 Apr 3.

Authors

James A Nieman¹, Sajiv K Nair, Steven E Heasley, Brenda L Schultz, Herbert M Zerth, Richard A Nugent, Ke Chen, Kevin J Stephanski, Todd A Hopkins, Mary L Knechtel, Nancee L Oien, Janet L Wieber, Michael W Wathen

Affiliation

¹ Global Research and Development, Pfizer, Inc., Kalamazoo, MI 49007, USA. jnieman@naeja.com

PMID: 20403696
DOI: 10.1016/j.bmcl.2010.03.115

Abstract

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.

MeSH terms

Antiviral Agents / chemical synthesis
Antiviral Agents / chemistry*
Antiviral Agents / pharmacology
Cytomegalovirus / drug effects
DNA-Directed DNA Polymerase / metabolism
Herpesviridae / enzymology*
Herpesvirus 1, Human / drug effects
Herpesvirus 3, Human / drug effects
Humans
Nucleic Acid Synthesis Inhibitors*
Pyrroles / chemical synthesis
Pyrroles / chemistry*
Pyrroles / pharmacology
Quinolines / chemical synthesis
Quinolines / chemistry*
Quinolines / pharmacology
Solubility
Structure-Activity Relationship

Substances

Antiviral Agents
Nucleic Acid Synthesis Inhibitors
Pyrroles
Quinolines
pyrroloquinoline
DNA-Directed DNA Polymerase