16075-42-6Relevant articles and documents
MECHANISTIC TARGET OF RAPAMYCIN SIGNALING PATHWAY INHIBITORS AND THERAPEUTIC APPLICATIONS THEREOF
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Paragraph 00218; 00219, (2018/04/11)
Selective mTOR inhibitors of formulas (I)-(III), processes for their preparation, pharmaceutical compositions containing them, and their use in the treatment of diseases and disorders, arising from abnormal cell growth, functions, or behaviors mediated by an mTOR kinase and/or one or more PI3K enzyme, are provided. Such diseases and disorder include cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine function disorders and neurological disorders.
Identification of NVP-BKM120 as a potent, selective, orally bioavailable class i PI3 kinase inhibitor for treating cancer
Burger, Matthew T.,Pecchi, Sabina,Wagman, Allan,Ni, Zhi-Jie,Knapp, Mark,Hendrickson, Thomas,Atallah, Gordana,Pfister, Keith,Zhang, Yanchen,Bartulis, Sarah,Frazier, Kelly,Ng, Simon,Smith, Aaron,Verhagen, Joelle,Haznedar, Joshua,Huh, Kay,Iwanowicz, Ed,Xin, Xiaohua,Menezes, Daniel,Merritt, Hanne,Lee, Isabelle,Wiesmann, Marion,Kaufman, Susan,Crawford, Kenneth,Chin, Michael,Bussiere, Dirksen,Shoemaker, Kevin,Zaror, Isabel,Maira, Sauveur-Michel,Voliva, Charles F.
supporting information; experimental part, p. 774 - 779 (2011/12/03)
Phosphoinositide-3-kinases (PI3Ks) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein we describe the structure guided optimization of a series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines where the pharmacokinetic properties were improved by modulating the electronics of the 6-position heterocycle, and the overall druglike properties were fine-tuned further by modification of the 4-position substituent. The resulting 2,4-bismorpholino 6-heterocyclic pyrimidines are potent class I PI3K inhibitors showing mechanism modulation in PI3K dependent cell lines and in vivo efficacy in tumor xenograft models with PI3K pathway deregulation (A2780 ovarian and U87MG glioma). These efforts culminated in the discovery of 15 (NVP-BKM120), currently in Phase II clinical trials for the treatment of cancer.
PYRIMIDINE DERIVATIVES USED AS PI-3 KINASE INHIBITORS
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Page/Page column 95, (2010/11/28)
Phosphatidylinositol (PI) 3-kinase inhibitor compounds (I), their pharmaceutically acceptable salts, and prodrugs thereof ; compositions of the new compounds, either alone or in combination with at least one additional therapeutic agent, with a pharmaceutically acceptable carrier; and uses of the new compounds, either alone or in combination with at least one additional therapeutic agent, in the prophylaxis or treatment of proliferative diseases characterized by the abnormal activity of growth factors, protein serine/threonine kinases, and phospholipid kinases.