title: Synthesis and structure-activity relationships of PI3K/mTOR dual inhibitors from a series of 2-amino-4-methylpyrido[2,3-d]pyrimidine derivatives.
abstract: Inhibition of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway by PI3K/mTOR dual inhibitors provides a promising new approach to the treatment of cancers. In this Letter, we identified structurally novel and potent PI3K/mTOR dual inhibitors from a series of 2-amino-4-methylpyrido[2,3-d]pyrimidine derivatives. Their synthesis and structure-activity relationships 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: 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: 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: 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: 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: D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D058570:TOR Serine-Threonine Kinases; C000596676:2-amino-4-methylpyrido(2,3-d)pyrimidine
keywords: Anti-tumor activity; Dual inhibitor; Mammalian target of rapamycin; Phosphoinositide 3-kinase