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.
CytRx Corporation, 3030 Bunker Hill Street, Suite 101, San Diego, CA 92109, USA. yuefen.zhou@gmail.com
Yuefen
Y
Zhou
Gang
G
Liu
Jinhua
J
Chen
P S Murali Mohan
PS
Reddy
Il Sang
IS
Yoon
Menghua
M
Zhang
Bin
B
Zhang
Jack R
JR
Barber
Shi Chung
SC
Ng
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