Novel benzthiodiazepinones as antiherpetic agents: SAR improvement of therapeutic index by alterations of the seven-membered ring.
A series of novel benzthiodiazepinones was studied as antiherpetic agents. Significant improvements in potency and therapeutic index in a viral replication assay were realized over the starting molecule. The role of stereospecific substitution on the diazepine ring and optimal nitrogen substitution were investigated.
Hamilton
Harriet W
HW
Department of Chemistry, Pfizer Global R&D, Ann Arbor, MI 48118, USA. harriet.hamilton@pfizer.com
Nishiguchi
Gisele
G
Hagen
Susan E
SE
Domagala
John D
JD
Weber
Peter C
PC
Gracheck
Stephen
S
Boulware
Stefanie L
SL
Nordby
Eric C
EC
Cho
Hidetsura
H
Nakamura
Takeshi
T
Ikeda
Satoru
S
Watanabe
Wataru
W
D000478:Alkylation; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001381:Azepines / Q000138:chemical synthesis* / Q000494:pharmacology*; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000235:genetics; D007202:Indicators and Reagents; D007763:Lac Operon / Q000187:drug effects; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D001381:Azepines; D007202:Indicators and Reagents; C435483:PD 146626; D013876:Thiophenes