- Design, synthesis and antiproliferative activity evaluation of a series of pyrrolo[2,1-f][1,2,4]triazine derivatives
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A series of 6-aminocarbonyl pyrrolo[2,1-f][1,2,4]triazine derivatives were designed by scaffold hopping strategy. The IC50 values of compound 14a against PI3Ks were measured, showing selective activity against p110α and p110δ with IC50s of 122 nM and 119 nM respectively. All the synthesized compounds were evaluated for their antiproliferative activity against human cancer cells by SRB assay. Compounds 14a, 14p and 14q exhibited potent antiproliferative activity against five types of human cancer cells and the PK property of 14q was also investigated here.
- Chen, Yan-Hong,Ding, Jian,Meng, Ling-Hua,Wang, Yi,Xiang, Hao-Yue,Yang, Chun-Hao,Zhang, Xi
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Read Online
- Preparation method and use of deuterated triazine compounds
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The present invention discloses a preparation method and a use of deuterated triazine compounds represented by formula (I), or pharmaceutically acceptable salts thereof. The deuterated triazine compounds of the present invention can be used for a PI3K/mTOR inhibitor.
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Paragraph 0040-0043
(2019/10/01)
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- Oxadiazolopyridine Derivates for Use as Ghrelin O-Acyl Transferase (GOAT) Inhibitors
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The present invention relates to compounds of general formula I, wherein the groups R1, R2 and n are defined as in claim 1, which have valuable pharmacological properties, in particular bind to ghrelin O-acyl transferase (GOAT) and modulate its activity. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular obesity.
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Paragraph 0302-0306; 0381-0383
(2018/03/01)
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- MECHANISTIC TARGET OF RAPAMYCIN SIGNALING PATHWAY INHIBITORS AND THERAPEUTIC APPLICATIONS THEREOF
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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.
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Paragraph 00209; 00210
(2018/04/11)
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- 4-(AZETIDIN-1-YL)PYRIMIDINE DERIVATIVES WITH ANTI-MITOTIC AND ANTI-PROLIFERATIVE ACTIVITY
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The invention relates to 4-(azetidin-1-yl)pyrimidyl compounds of formula (I), wherein X and Y are, independently of each other CH or N; U is O, CHOH, CHCH2OH, C(CH3)OH, CO, CHNH2; R1 and R2 are, independently of each other H, F or CH3; and R3 is H or CH3; and related compounds with anti-mitotic and anti-proliferative properties, and methods of making use of such compounds in therapy or diagnostics to attenuate undesired cell proliferation, growth, migration, metastasis tumor formation, and inflammatory conditions. Additionally, methods are disclosed of treating diseases associated with undesired angiogenesis and undesired proliferation, and methods of treating infectious and inflammatory diseases using such compounds.
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Paragraph 0161; 0162
(2017/11/04)
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- 2-MORPHOLIN-4,6-DISUBSTITUTED PYRIMIDINE DERIVATIVE, AND PREPARATION METHOD AND PHARMACEUTICAL USE THEREOF
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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.
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Paragraph 0091-0092
(2017/11/11)
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- And circular PI3K inhibitors (by machine translation)
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The invention belongs to the field of medical technology, in particular to general formula (I) and of the everted shown in the PI3K inhibitor, or a pharmaceutically acceptable salt, ester, stereo isomers, solvates, wherein R 1, R 2, R 3 as defined in the specification. The invention also relates to methods of preparing such compounds, pharmaceutical formulations containing these compounds and pharmaceutical compositions, use of these compounds in the preparation and treatment and/or prevention of proliferative diseases of application of the medicament. (by machine translation)
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Paragraph 0367; 0368; 0369
(2016/10/08)
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- PI3K kinase inhibitor, to pharmaceutical compositions comprising the same and application thereof
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The invention discloses a phosphoinositide 3-kinase (P13K) inhibitor, a pharmaceutical composition containing the P13K inhibitor, and application of the P13K inhibitor and the pharmaceutical composition. The P13K inhibitor comprises a pyrimidine compound and a stereoisomer/hydrate/pharmaceutically-acceptable salt thereof. The pyrimidine compound has a general formula I of which the structure is shown in the specification. The P13K inhibitor and the pharmaceutical composition containing the same can be used for inhibiting PI3 Ks and treating proliferative diseases on which the PI3 Ks act. According to the invention, high-effectiveness and high-selectivity inhibitors for treating proliferative diseases on which PI3Ks act can be provided.
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Paragraph 0131-0134
(2016/11/24)
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- Pyrimidine compounds, PI3K inhibitors, include PI3K inhibitor drug composition and use thereof
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The invention discloses a pyrimidine compound of which the structure is shown in a general formula (I), and also discloses a PI3K inhibitor which is composed of at least one of the following substances: the pyrimidine compound shown in the general formula
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Paragraph 0093-0096
(2017/01/31)
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- Discovery of 2-(2-aminopyrimidin-5-yl)-4-morpholino-N-(pyridin-3-yl)quinazolin-7-amines as novel PI3K/mTOR inhibitors and anticancer agents
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In this study, a series of novel 7 or 8-substituted 4-morpholine-quinazoline derivatives was designed and synthesized. Their PI3Kα inhibitory activities, antiproliferative activities against seven cancer cell lines, namely, PC-3, DU145, MCF-7, BT474, SK-BR-3, U937 and A431, were evaluated in vitro. Compound 17f proved to be a potential drug candidate with high PI3Kα inhibition activity (IC50 = 4.2 nM) and good antiproliferative activity. Compound 17f was also tested for its inhibitory activities against other kinases, such as PI3Kβ, PI3Kγ, PI3Kδ and mTOR, its effects on p-Akt (S473) and cell cycle. These results suggested that compound 17f could significantly inhibit the PI3K/Akt/mTOR pathway as a potent PI3K inhibitor and anticancer agent.
- Peng, Wei,Tu, Zheng-Chao,Long, Zi-Jie,Liu, Quentin,Lu, Gui
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p. 644 - 654
(2015/12/31)
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- multi-links class PI3K inhibitors (by machine translation)
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The invention belongs to the field of medical technology, in particular of formula (I) shown in multi-links class of PI3K inhibitors, its stereoisomers or its pharmaceutically acceptable salt thereof, wherein the R 1, R 2, R 3, R 4 or R 5 as defined in the specification; the invention also relates to methods of preparing such compounds, pharmaceutical compositions of these compounds in the preparation and treatment and/or prevention of proliferative diseases of the use of the medicament. (by machine translation)
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Paragraph 0232; 0233; 0234
(2016/10/09)
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- PYRROLONE DERIVATIVES AS HERBICIDES
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The invention relates to pyrrolone compounds of the formula (I) wherein X, R1, R2, R3 and A are as defined in the specification. Furthermore, the present invention relates to processes and intermediates for making compounds of formula (I), to herbicidal compositions comprising these compounds and to methods of using these compounds to control plant growth.
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Page/Page column 67-68
(2015/02/25)
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- PYRAZOLYL PYRROLINONES AND THEIR USE AS HERBICIDES
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The invention relates to pyrrolone compounds of the formula (I) wherein X, R1, R2, R3 and A are as defined in the specification. Furthermore, the present invention relates to processes and intermediates for making compounds of formula (I), to herbicidal compositions comprising these compounds and to methods of using these compounds to control plant growth.
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Page/Page column 45
(2015/02/25)
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- PYRROLO[2,1-F][1,2,4]TRIAZINE COMPOUND, AND PREPARATION METHOD AND APPLICATION THEREOF
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The present invention relates to a pyrrolo[2,1-f][1,2,4]triazine compound, an isomer thereof or a pharmaceutically acceptable salt, ester or hydrate thereof, and a preparation method and application thereof. The pyrrolo[2,1-f][1,2,4]triazine compound has a structure expressed in general formula (I). The pyrrolo[2,1-f][1,2,4]triazine compound expressed in general formula (I) can inhibit a phosphatidylinositol-3 kinase (PI3K) signal pathway, thereby being used to prepare medicine for treating phosphatidylinositol-3 kinase related diseases such as cancer.
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Paragraph 0025
(2015/04/15)
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- PYRROLO[2,1-F][1,2,4]TRIAZINE COMPOUND, AND PREPARATION METHOD AND APPLICATION THEREOF
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The present invention relates to a pyrrolo[2,1-f][1,2,4]triazine compound, an isomer thereof or a pharmaceutically acceptable salt, ester or hydrate thereof, and a preparation method and application thereof. The pyrrolo[2,1-f][1,2,4]triazine compound has a structure expressed in general formula (I). The pyrrolo[2,1-f][1,2,4]triazine compound expressed in general formula (I) can inhibit a phosphatidylinositol-3 kinase (PI3K) signal pathway, thereby being used to prepare medicine for treating phosphatidylinositol-3 kinase related diseases such as cancer.
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Paragraph 0066
(2015/05/26)
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- Design, synthesis, and biological evaluation of novel imidazo[1,2-a]pyridine derivatives as potent c-met inhibitors
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A series of imidazo[1,2-a]pyridine derivatives against c-Met was designed by means of bioisosteric replacement. In this study, a selective, potent c-Met inhibitor, 22e was identified, with IC50 values of 3.9 nM against c-Met kinase and 45.0 nM
- Li, Chunpu,Ai, Jing,Zhang, Dengyou,Peng, Xia,Chen, Xi,Gao, Zhiwei,Su, Yi,Zhu, Wei,Ji, Yinchun,Chen, Xiaoyan,Geng, Meiyu,Liu, Hong
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supporting information
p. 507 - 512
(2015/05/27)
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- NOVEL MANUFACTURING PROCESS FOR TRIAZINE, PYRIMIDINE AND PYRIDINE DERIVATIVES
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The invention relates to a method of manufacturing triazine, pyrimidine and pyridine derivatives of formula (I), wherein U, V, W and Z are nitrogen or carbon atoms, whereby at least one of U, V and W is nitrogen, and the other substituents are defined as in the specification, by condensing a corresponding halo-triazine, pyrimidine or pyridine in a type of Suzuki coupling with a pyridyl- or pyrimidinyl-borane, wherein the amino function is protected as a formamidine. The invention further relates to suitable intermediates and methods of manufacturing of such intermediates. Furthermore the invention relates to pure 5-(4,6-dimorpholino-1,3,5- triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine in solid form.
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Page/Page column 21; 22; 23
(2015/11/16)
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- ANDROGEN RECEPTOR ANTAGONISTS
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Disclosed herein are compositions and methods for modulating the androgen receptor.
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Paragraph 0326
(2016/04/26)
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- QUINAZOLINES AND AZAQUINAZOLINES AS DUAL INHIBITORS OF RAS/RAF/MEK/ERK AND PI3K/AKT/PTEN/MTOR PATHWAYS
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The present application provides novel quinazolines and azaquinazolines and pharmaceutically acceptable salts thereof. Also provided are methods for preparing these compounds. These compounds are useful in for co-regulating RAS/RAF/MEK/ERK and PI3K/AKT/PTEN/mTOR pathways by administering a therapeutically effective amount of one or more of the compounds of formula (I), wherein X, Y, T and R4, and R6 to R8' are defined herein, to a patient. By doing so, these compounds are effective in treating conditions associated with the dysregulation of the RAS/RAF/MEK/ERK and PI3K/AKT/PTEN/mTOR pathways. A variety of conditions can be treated using these compounds and include diseases which are characterized by abnormal cellular proliferation. In one embodiment/ the disease is cancer.
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Page/Page column 56
(2014/10/29)
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- NOVEL TRIAZINE COMPOUNDS
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The present invention relates to novel triazine compounds of formula (1). The present invention also discloses compounds of formula I along with other pharmaceutical ac-ceptable excipients and use of the compounds to modulate the PI3K/ mTOR pathway
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Page/Page column 116
(2014/02/16)
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- METHOD OF INHIBITING HAMARTOMA TUMOR CELLS
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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.
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Page/Page column 19
(2012/08/28)
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- MANUFACTURING PROCESS FOR PYRIMIDINE DERIVATIVES
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The invention relates to processes for manufacturing a compound of formula (5) or a stereoisomer, tautomer or a salt thereof, wherein the substituents are as defined in the specification. The invention further relates to new manufacturing processes for specific solid forms of Compound A and its salts, to such solid forms and to use of said solid forms for the therapeutic treatment of warm-blooded animals.
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Page/Page column 65-66
(2012/04/17)
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- Identification of NVP-BKM120 as a potent, selective, orally bioavailable class i PI3 kinase inhibitor for treating cancer
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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.
- 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.
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supporting information; experimental part
p. 774 - 779
(2011/12/03)
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- PI 3-KINASE INHIBITORS AND METHODS OF THEIR USE
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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.
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Page/Page column 61-62
(2008/12/08)
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- PYRIMIDINE DERIVATIVES USED AS PI-3 KINASE INHIBITORS
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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.
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Page/Page column 93
(2010/11/28)
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