Pyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione derivatives: their cytoprotection effect from rotenone toxicity and preliminary DMPK properties.
Pyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione derivatives exhibited potent cytoprotective effect from rotenone toxicity. Lead optimization focused on the CC50/EC50 ratio and DMPK properties led to the overall improvement of the compound profile of this series with high CC50/EC50 ratio (92 for 1f), good metabolic stability in rat microsomes and medium to high aqueous solubility.
Zhou
Yuefen
Y
CytRx Corporation, 3030 Bunker Hill Street, Suite 101, San Diego, CA 92109, USA. yuefen.zhou@gmail.com
Liu
Gang
G
Chen
Jinhua
J
Reddy
P S Murali Mohan
PS
Yoon
Il Sang
IS
Zhang
Menghua
M
Zhang
Bin
B
Barber
Jack R
JR
Ng
Shi Chung
SC
D000818:Animals; D019610:Cytoprotection / Q000187:drug effects*; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy; D051381:Rats; D012402:Rotenone / Q000633:toxicity*; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics
D007306:Insecticides; D014227:Triazines; D012402:Rotenone