Novel guanidine-based inhibitors of inosine monophosphate dehydrogenase.
A series of novel guanidine-based small molecule inhibitors of inosine monophosphate dehydrogenase (IMPDH) was explored. IMPDH catalyzes the rate determining step in guanine nucleotide biosynthesis and is a target for anticancer, immunosuppressive and antiviral therapy. The synthesis and the structure-activity relationships (SARs), derived from in vitro studies, for this new series of inhibitors is given.
Iwanowicz
Edwin J
EJ
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA. iwanowie@bms.com
Watterson
Scott H
SH
Liu
Chunjian
C
Gu
Henry H
HH
Mitt
Toomas
T
Leftheris
Katerina
K
Barrish
Joel C
JC
Fleener
Catherine A
CA
Rouleau
Katherine
K
Sherbina
N Z
NZ
Hollenbaugh
Diane L
DL
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D019791:Guanidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors*; D007202:Indicators and Reagents; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D007168:IMP Dehydrogenase; D019791:Guanidine