Modifications of C-2 on the pyrroloquinoline template aimed at the development of potent herpesvirus antivirals with improved aqueous solubility.
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.
Nieman
James A
JA
Global Research and Development, Pfizer, Inc., Kalamazoo, MI 49007, USA. jnieman@naeja.com
Nair
Sajiv K
SK
Heasley
Steven E
SE
Schultz
Brenda L
BL
Zerth
Herbert M
HM
Nugent
Richard A
RA
Chen
Ke
K
Stephanski
Kevin J
KJ
Hopkins
Todd A
TA
Knechtel
Mary L
ML
Oien
Nancee L
NL
Wieber
Janet L
JL
Wathen
Michael W
MW
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D003587:Cytomegalovirus / Q000187:drug effects; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D006564:Herpesviridae / Q000201:enzymology*; D018259:Herpesvirus 1, Human / Q000187:drug effects; D014645:Herpesvirus 3, Human / Q000187:drug effects; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012995:Solubility; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D019384:Nucleic Acid Synthesis Inhibitors; D011758:Pyrroles; D011804:Quinolines; C410406:pyrroloquinoline; D004259:DNA-Directed DNA Polymerase