Pyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione derivatives: their cytoprotection effect from rotenone toxicity and preliminary DMPK properties

Yuefen Zhou; Gang Liu; Jinhua Chen; P S Murali Mohan Reddy; Il Sang Yoon; Menghua Zhang; Bin Zhang; Jack R Barber; Shi Chung Ng

doi:10.1016/j.bmcl.2009.09.021

Pyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione derivatives: their cytoprotection effect from rotenone toxicity and preliminary DMPK properties

Bioorg Med Chem Lett. 2009 Nov 1;19(21):6114-8. doi: 10.1016/j.bmcl.2009.09.021. Epub 2009 Sep 10.

Authors

Yuefen Zhou¹, Gang Liu, Jinhua Chen, P S Murali Mohan Reddy, Il Sang Yoon, Menghua Zhang, Bin Zhang, Jack R Barber, Shi Chung Ng

Affiliation

¹ CytRx Corporation, 3030 Bunker Hill Street, Suite 101, San Diego, CA 92109, USA. yuefen.zhou@gmail.com

PMID: 19786349
DOI: 10.1016/j.bmcl.2009.09.021

Abstract

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.

MeSH terms

Animals
Cytoprotection / drug effects*
Insecticides / toxicity*
Male
Microsomes, Liver / metabolism
Parkinson Disease / drug therapy
Rats
Rotenone / toxicity*
Structure-Activity Relationship
Triazines / chemical synthesis
Triazines / chemistry*
Triazines / pharmacokinetics

Substances

Insecticides
Triazines
Rotenone