title: Identification of novel 7-amino-5-methyl-1,6-naphthyridin-2(1H)-one derivatives as potent PI3K/mTOR dual inhibitors.
abstract: Inhibition of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway is one of the most intensively studied approaches to cancer therapy. Rational design led to the identification of novel 7-amino-5-methyl-1,6-naphthyridin-2(1H)-one derivatives as potent PI3K/mTOR dual inhibitors. Design, synthesis and structure activity relationship are reported.
authors.affiliation: PKUCare Pharmaceutical R&D Center, A106-109, Biotech Innovation Works, No. 29 Life Science Park Road, Changping District, Beijing 102206, PR China.
authors.forename: Songwen
authors.initials: S
authors.lastname: Lin
authors.affiliation: PKUCare Pharmaceutical R&D Center, A106-109, Biotech Innovation Works, No. 29 Life Science Park Road, Changping District, Beijing 102206, PR China.
authors.forename: Fangbin
authors.initials: F
authors.lastname: Han
authors.affiliation: PKUCare Pharmaceutical R&D Center, A106-109, Biotech Innovation Works, No. 29 Life Science Park Road, Changping District, Beijing 102206, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: PKUCare Pharmaceutical R&D Center, A106-109, Biotech Innovation Works, No. 29 Life Science Park Road, Changping District, Beijing 102206, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tao
authors.affiliation: PKUCare Pharmaceutical R&D Center, A106-109, Biotech Innovation Works, No. 29 Life Science Park Road, Changping District, Beijing 102206, PR China.
authors.forename: Xuechao
authors.initials: X
authors.lastname: Zhong
authors.affiliation: PKUCare Pharmaceutical R&D Center, A106-109, Biotech Innovation Works, No. 29 Life Science Park Road, Changping District, Beijing 102206, PR China.
authors.forename: Xiujie
authors.initials: X
authors.lastname: Liu
authors.affiliation: PKUCare Pharmaceutical R&D Center, A106-109, Biotech Innovation Works, No. 29 Life Science Park Road, Changping District, Beijing 102206, PR China. Electronic address: yichongqin@founder.com.
authors.forename: Chongqin
authors.initials: C
authors.lastname: Yi
authors.affiliation: PKUCare Pharmaceutical R&D Center, A106-109, Biotech Innovation Works, No. 29 Life Science Park Road, Changping District, Beijing 102206, PR China. Electronic address: xuheng@pkucare-pharm.com.
authors.forename: Heng
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D001665:Binding Sites; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D009287:Naphthyridines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D009287:Naphthyridines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D058570:TOR Serine-Threonine Kinases
keywords: Anti-tumor activity; Dual inhibitor; Mammalian target of rapamycin; Phosphoinositide 3-kinase