- Design, Synthesis, and Biological Evaluation of Dimorpholine Substituted Thienopyrimidines as Potential Class I PI3K/mTOR Dual Inhibitors
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Dysfunctional signaling of the PI3K/AKT/mTOR pathway in cancer and its crucial role in cell growth and survival have made it a much desired target for cancer therapeutics. A series of dimorpholine substituted thienopyrimidine derivatives had been prepared and evaluated in vitro and in vivo. Among them, compound 14o was identified as a dual Class I PI3K and mTOR kinase inhibitor, which had an approximately 8-fold improvement in mTOR inhibition relative to the class I PI3K inhibitor 1 (pictilisib, GDC-0941). Western blot analysis confirmed the 14o mechanistic modulation of the cellular PI3K/AKT/mTOR pathway through inhibiting phosphorylation of both AKT and S6 in human cancer cell lines. In addition, 14o demonstrated significant efficacy in SKOV-3 and U87MG tumor xenograft models without causing significant weight loss and toxicity.
- Zhan, Miao,Deng, Yufang,Zhao, Lifeng,Yan, Guoyi,Wang, Fangying,Tian, Ye,Zhang, Lanxi,Jiang, Hongxia,Chen, Yuanwei
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- Heterocyclic Compounds For Preventing And Treating Disorders Associated With Excessive Bone Loss
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This invention relates to pyrimidine compounds of formula (I), formula (I′), and formula (I″): and pharmaceutically acceptable salts, solvates, clathrates, and prodrugs thereof, wherein R1, R2, R3, R4, R5/
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Page/Page column 54
(2010/11/30)
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- Novel compounds
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This invention features a compound of formula (I): R1 is aryl or heteroaryl; each of R2 and R4, independently, is H, halogen, CN, alkyl, ORa, or NRaRb; R3 is H, halogen, CN, alky
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- Solution-phase synthesis of 2,6,9-trisubstituted purines
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A simple three-step method for the solution-phase combinatorial synthesis of 2,6,9-trisubstituted purines from 2,6-dichloropurine is described. The synthesis exploits the use of resin capture to remove excess reagent used in the final step.
- Fiorini, Maria T.,Abell, Chris
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p. 1827 - 1830
(2007/10/03)
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