944401-58-5Relevant articles and documents
One-Step Synthesis of 3,4-Disubstituted 2-Oxazolidinones by Base-Catalyzed CO2 Fixation and Aza-Michael Addition
Mannisto, Jere K.,Sahari, Aleksi,Lagerblom, Kalle,Niemi, Teemu,Nieger, Martin,Sztanó, Gábor,Repo, Timo
supporting information, p. 10284 - 10289 (2019/08/01)
2-Oxazolidinones are saturated heterocyclic compounds, which are highly attractive targets in modern drug design. Herein, we describe a new, single-step approach to 3,4-disubstituted 2-oxazolidinones by aza-Michael addition using CO2 as a carbonyl source and 1,1,3,3-tetramethylguanidine (TMG) as a catalyst. The modular reaction, which occurs between a γ-brominated Michael acceptor, CO2 and an arylamine, aliphatic amine or phenylhydrazine, is performed under mild conditions. The regiospecific reaction displays good yields (av. 75 %) and excellent functional-group compatibility. In addition, late-stage functionalization of drug and drug-like molecules is demonstrated. The experimental results suggest a mechanism consisting of several elementary steps: TMG-assisted carboxylation of aniline; generation of an O-alkyl carbamate; and the final ring-forming step through an intramolecular aza-Michael addition.
2-MORPHOLIN-4,6-DISUBSTITUTED PYRIMIDINE DERIVATIVE, AND PREPARATION METHOD AND PHARMACEUTICAL USE THEREOF
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Paragraph 0093; 0096, (2017/11/11)
Disclosed is a 2-morpholin-4,6-disubstituted pyrimidine derivative as shown in formula (I) below, and a pharmaceutically acceptable salt, solvate, stereoisomer or prodrug thereof, and a pharmaceutical composition thereof and a use thereof, wherein the definition of each group is as shown in the description. The compound has a PI3K kinase inhibition activity, and has a relatively high inhibitive ability and a low cytotoxicity against PIK3CA mutant breast cancer cell strains T47D and MCF-7.
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.
Oxazolidin-2-one-Pyrimidine Derivatives
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, (2014/05/20)
The present invention relates to oxazolidin-2-one substituted pyrimidine compounds that act as PI3K (phosphatidylinositol-3-kinase) inhibitors, as well as pharmaceutical compositions thereof, methods for their manufacture and uses for the treatment of conditions, diseases and disorders dependent on PI3K.
OXAZOLIDIN-2-ONE COMPOUNDS AND USES THEREOF
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, (2013/09/12)
The present invention relates to oxazolidin-2-one substituted pyrimidine compounds that act as PI3K (phosphatidylinositol-3-kinase) inhibitors, as well as pharmaceutical compositions thereof, methods for their manufacture and uses for the treatment of conditions, diseases and disorders dependent on PI3K.
METHOD OF INHIBITING HAMARTOMA TUMOR CELLS
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Page/Page column 21, (2012/08/28)
Dimorpholinopyrimidines are useful for inhibiting growth or proliferation of hamartoma tumor cells. Because the Dimorpholinopyrimidines inhibit the growth and proliferation of hamartoma tumor cells they are also useful in treating PTEN hamartoma tumor syndromes. The therapeutic and prophylactic treatments provided by this invention are practiced by administering to a patient in need thereof an amount of a compound of dimorpholinopyrimidine derivative that is effective to inhibit growth or proliferation of the hamartoma tumor cells.
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.
PI 3-KINASE INHIBITORS AND METHODS OF THEIR USE
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Page/Page column 63-64, (2008/12/08)
Phosphatidylinositol (PI) 3-kinase inhibitor compounds, 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 diseases characterized by the abnormal activity of growth factors, protein serine/threonine kinases, and phospholipid kinases, including proliferative diseases, inflammatory and obstructive airways diseases, allergic conditions, auutoimmune and cardiovascular diseases.
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.
