Pasquier, Benoit; El-Ahmad, Youssef; Filoche-Romme, Bruno; Dureuil, Christine; Fassy, Florence; Abecassis, Pierre-Yves; Mathieu, Magali; Bertrand, Thomas; Benard, Tsiala; Barriere, Cedric; El Batti, Samira; Letallec, Jean-Philippe; Sonnefraud, Veronique; Brollo, Maurice; Delbarre, Laurence; Loyau, Veronique; Pilorge, Fabienne; Bertin, Luc; Richepin, Patrick; Arigon, Jerome; Labrosse, Jean-Robert; Clement, Jacques; Durand, Florence; Combet, Romain; Perraut, Pierre; Leroy, Vincent; Gay, Frederic; Lefrancois, Dominique; Bretin, Francois; Marquette, Jean-Pierre; Michot, Nadine; Caron, Anne; Castell, Christelle; Schio, Laurent; McCort, Gary; Goulaouic, Helene; Garcia-Echeverria, Carlos; Ronan, Baptiste published the artcile< Discovery of (2S)-8-[(3R)-3-Methylmorpholin-4-yl]-1-(3-methyl-2-oxobutyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido[1,2-a]pyrimidin-6-one: A Novel Potent and Selective Inhibitor of Vps34 for the Treatment of Solid Tumors>, Category: esters-buliding-blocks, the main research area is dihydropyrimidopyrimidinone preparation phosphoinositide kinase inhibitor antitumor neoplasm.
Vps34 (the human class III phosphoinositide 3-kinase) is a lipid kinase involved in vesicle trafficking and autophagy and therefore constitutes an interesting target for cancer treatment. Because of the lack of specific Vps34 kinase inhibitors, the authors aimed to identify such compounds to further validate the role of this lipid kinase in cancer maintenance and progression. Herein, the authors report the discovery of a series of tetrahydropyrimidopyrimidinone derivatives Starting with hit compound I, medicinal chem. optimization led to compound 31. This mol. displays potent activity, an exquisite selectivity for Vps34 with excellent properties. The x-ray crystal structure of compound II in human Vps34 illustrates how the unique mol. features of the morpholine synthon bestows selectivity against class I PI3Ks. This mol. exhibits suitable in vivo mouse PK parameters and induces a sustained inhibition of Vps34 upon acute administration. Compound II constitutes an optimized Vps34 inhibitor that could be used to investigate human cancer biol.
Journal of Medicinal Chemistry published new progress about Antitumor agents. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Category: esters-buliding-blocks.
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