75618-39-2Relevant academic research and scientific papers
Targeting the colchicine site in tubulin through cyclohexanedione derivatives
Canela, María-Dolores,Bueno, Oskía,Noppen, Sam,Sáez Calvo, Gonzalo,Estévez Gallego, Juan,Díaz,Camarasa, María-José,Liekens, Sandra,Pérez-Pérez, María-Jesús,Priego, Eva-María
, p. 19492 - 19506 (2016/03/01)
Cyclohexanedione derivatives represent a new family of colchicine-site binders that were identified through a ligand-based virtual screening approach. Structural modifications have now been performed at both distal sites of our identified hit [2-(1-((2-methoxyphenyl)amino)ethylidene)-5-phenylcyclohexane-1,3-dione (4)] in order to improve tubulin binding affinity, anti-proliferative activity and/or aqueous solubility. The results obtained indicate that the 2-methoxyphenyl ring, the fragment located closer to the αβ-tubulin interface according to docking studies, is the one that allows structural variation in order to improve the Ka value against tubulin (as in compound 20a with a Ka = 1.3 × 107 M-1, analogous to colchicine) or to improve aqueous solubility, as in compound 22c, being more than 10 times more soluble than the previous hit 4.
PROCESS FOR THE PRODUCTION OF OPTICALLY ACTIVE CYCLIC ENAMINONE DERIVATIVES
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, (2008/06/13)
A process for the production of optically active cyclic enaminone derivatives characterized by aminating one of the carbonyl groups of a cyclic 1,3-diketone derivative having a symmetry plane to obtain an optically isomeric mixture of chiral cyclic enamin
Synthesis and Antimalarial Properties of 1-Imino Derivatives of 7-Chloro-3-substituted-3,4-dihydro-1,9(2H,10H)-acridinediones and Related Structures
Kesten, Stephen J.,Degnan, Margaret J.,Hung, Jocelyn,McNamara, Dennis J.,Ortwine, Daniel F.,et al.
, p. 3429 - 3447 (2007/10/02)
To improve upon the activity and properties of the 3-aryl-7-chloro-3,4-dihydro-1,9(2H,10H)-acridinediones, a variety of 1-imino derivatives (3) were prepared and shown to be highly active antimalarial agents in both rodents and primates.Among structural modifications prepared, including N10-alkyl and C2-substituted analogs, removal of the C9 oxygen, and introduction of an imino side chain at C9, the imines of the N10-H acridinediones were the most active compounds obtained.The imino derivative of7-chloro-3-(2,4-dichlorophenyl)-3,4-dihydro-1,9(2H,10H)-acridinedione (9aa) proved to be highly active in advanced studies in primates.
