Quinolone-based IMPDH inhibitors: introduction of basic residues on ring D and SAR of the corresponding mono, di and benzofused analogues.
The synthesis and the structure-activity relationships (SAR) of analogues derived from the introduction of basic residues on ring D of quinolone-based inhibitors of IMPDH are described. This led to the identification of compound 27 as a potent inhibitor of IMPDH with significantly improved aqueous solubility over the lead compound 1.
Dhar
T G Murali
TG
Bristol-Myers Squibb PRI, Princeton, NJ 08543-4000, USA. dharm@bms.com
Watterson
Scott H
SH
Chen
Ping
P
Shen
Zhongqi
Z
Gu
Henry H
HH
Norris
Derek
D
Carlsen
Marianne
M
Haslow
Kristin D
KD
Pitts
William J
WJ
Guo
Junqing
J
Chorba
John
J
Fleener
Catherine A
CA
Rouleau
Katherine A
KA
Townsend
Robert
R
Hollenbaugh
Diane
D
Iwanowicz
Edwin J
EJ
D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors*; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D015363:Quinolones; D007168:IMP Dehydrogenase