- Development of anti-breast cancer PI3K inhibitors based on 7-azaindole derivatives through scaffold hopping: Design, synthesis and in vitro biological evaluation
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Breast cancer is the cancer with the highest incidence all over the world. Phosphatidylinositol 3-kinase is an important regulator of intracellular signaling pathways, which is frequently mutated and overexpressed in majority of human breast cancers, and the inhibition of PI3K has been considered as a promising approach for the treatment of the cancer. Here, we report our design and synthesis of new 7-azaindole derivatives as PI3K inhibitors through the scaffold hopping strategy. By varying the groups at the 3-position of 7-azaindole, we identified a series of potent PI3K inhibitors, whose antiproliferative activities against two human breast cancer MCF-7 and MDA-MB-231 cell lines were evaluated. Representative derivatives FD2054 and FD2078 showed better activity than BKM120 in antiproliferation, reduced the levels of phospho-AKT and induced cell apoptosis. All these results suggested that FD2054 and FD2078 are potent PI3K inhibitors that could be considered as potential candidates for the development of anticancer agents.
- Chen, Yi,Deng, Mingli,Jia, Yu,Ling, Yun,Liu, Xiaofeng,Lu, Mingzhu,Qiu, Tianze,Xiang, Ruiqing,Yang, Chengbin,Yang, Yongtai,Zhou, Yaming
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supporting information
(2021/10/19)
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- AZAINDOLE DERIVATIVE AND USE THEREOF AS FGFR AND C-MET INHIBITOR
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A series of pyrazolopymidine derivatives, and use thereof in the preparation of a medicament for treating disease associated with FGFR and c-Met. The pyrazolopymidine derivative is a compound represented by formula (I), a tautomer, or a pharmaceutically acceptable salt thereof.
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Paragraph 0117; 0121
(2021/05/29)
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- A Monophosphine Ligand Derived from Anthracene Photodimer: Synthetic Applications for Palladium-Catalyzed Coupling Reactions
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Herein, we present an air-stable dianthracenyl monophosphine ligand (diAnthPhos) which can be prepared in two steps from commercially available anthracene derivatives. The ligand exhibits excellent efficiency for palladium-catalyzed coupling reactions. In particular, Miyaura borylation of heterocycle-containing electrophiles can be facilitated employing the diAnthPhos ligand with a broad substrate scope and low catalyst loading. The valuable synthetic utility of the new ligand is further demonstrated by a one-pot Miyaura borylation/Suzuki coupling protocol for heteroaryl-containing substrates.
- Wang, Xin,Liu, Wei-Gang,Tung, Chen-Ho,Wu, Li-Zhu,Cong, Huan
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supporting information
p. 8158 - 8163
(2019/09/07)
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- PYRROLO [2, 3-B] PYRIDINES OR PYRROLO [2, 3-B] PYRAZINES AS HPK1 INHIBITOR AND THE USE THEREOF
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Disclosed herein is a compound of Formula (AIII) or (III), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and pharmaceutical compositions comprising thereof. Also disclosed is a method of treating HPK1 related disorders or diseases by using the compound disclosed herein.
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Paragraph 0401; 0458; 0463-0464; 0677-0679
(2020/01/08)
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- Heterocyclic boronic acid compound synthesis process
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The invention relates to a synthetic process of a heterocyclic boric acid compound. The process comprises the following steps: carrying out reaction on 5-chloro-7-azaindole and tert-butyldimethylsilyl chloride in the presence of triethylamine to carry out posttreatment to obtain a yellow solid; carrying out reaction on yellow solid and trimethyl borate in the presence of sodium carbonate to carry out post-treatment to obtain a yellow oily object; carrying out reaction on the yellow oily object and pinacol and concentrating to obtain a colorless oily object; and carrying out posttreatment on the colorless oily object to obtain a white solid to obtain 7-azaindole-pinacol boronate. Not only is the synthetic method provided by the invention yield and high in purity, but also the toxicity of the used chemical reagent is less, so that the damage on the operator is reduced, thereby facilitating industrial scaled production. The synthetic method is also suitable for synthesizing other heterocyclic boric acid compounds such as 7-azaindole-4-pinacol boronate, 7-azaindole-3-pinacol boronate and has an important application value.
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Paragraph 0016; 0017; 0018; 0019; 0020; 0021-0036
(2017/08/25)
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- Alkynyl compound and its method and use thereof
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The invention provides a novel substituted alkynyl compound and its pharmaceutically acceptable salt and medicinal preparation, and a use of the novel substituted alkynyl compound and its pharmaceutically acceptable salt and medicinal preparation in adjustment of protein kinase activity and intercellular or intracellular signal response. The invention also relates to a pharmaceutical composition containing the novel substituted alkynyl compound and a method for treating high-proliferative diseases of mammals especially such as human by the pharmaceutical composition.
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Paragraph 0527; 0529; 0530
(2018/11/03)
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- Method for synthesizing Venetoclax key intermediates
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The invention discloses a method for synthesizing Venetoclax key intermediates. The method includes steps of (1), carrying out coupling reaction on 5-bromine-7-azaindole and bisdiboron in solvents under the effects of organic palladium catalysts and alkali, and carrying out after-treatment after the reaction is completely carried out so as to obtain 7-azaindole-5-pinacol borate; (2), carrying out hydrolysis reaction on the 7-azaindole-5-pinacol borate obtained at the step (1) under the effect of sodium perborate, and carrying out after-treatment after the reaction is completely carried out so as to obtain the Venetoclax key intermediates. The method has the advantages that the method is easy to implement, highly toxic reagents can be omitted, and the HPLC (high-performance liquid chromatography) purity of the Venetoclax key intermediates which are products obtained by the aid of the method is higher than 99%.
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Paragraph 0016; 0031; 0034; 0037; 0040
(2017/09/05)
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- ORGANIC LIGHT-EMITTING COMPOUND AND ORGANIC ELECTROLUMINESCENT DEVICE USING SAME
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The present invention relates to a novel indole-based compound having excellent hole injection and transport capabilities, light-emission, and other properties, and to an organic electroluminescent device the luminous efficiency, driving voltage, service
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Page/Page column
(2015/08/04)
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- Organic light emitting compd. and organic electroluminescence element using the same
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The present invention relates to a novel indole-based compound having excellent hole injection and transport capabilities, light-emission, and other properties, and to an organic electroluminescent device the luminous efficiency, driving voltage, service life, and other characteristics of which are improved due to containing the compound in one or more organic material layers.
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Paragraph 0045-0046; 0090
(2016/10/24)
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- ALKYNYL COMPOUNDS AND METHODS OF USE
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The present invention provides novel substituted alkynyl compounds, pharmaceutical acceptable salts and formulations thereof useful in modulating the protein tyrosine kinase activity, and in modulating cellular activities such as proliferation, differentiation, apoptosis, migration and invasion. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.
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Page/Page column 67-68
(2014/06/24)
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- SUBSTITUTED 5-(PYRAZIN-2-YL)-1H-PYRAZOLO [3,4-B] PYRIDINE AND PYRAZOLO [3,4-B] PYRIDINE DERIVATIVES AS PROTEIN KINASE INHIBITORS
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Substituted 5-(pyrazin-2-yl)-1H-pyrazolo [3,4-b] pyridine, 5-(pyrazin-2-yl)-1H-pyrrolo[2,3-b]pyridine and pyrazolo [3,4-b] pyridine derivatives according to formula I, II and VII, and methods for making same, which are inhibitors of constitutively activated Tyrosine Kinase-Like (TKL), CMGC protein kinases family members and can be useful in the treatment of Parkinson?s disease, Alzheimer?s disease, Down?s Syndrome, Huntington?s disease, other neurodegenerative and central nervous system disorders, cancer, metabolic disorders and inflammatory diseases. Also disclosed are pharmaceutical compositions including the compounds and methods of inhibiting wild type and/or mutated protein kinase activities of these families and the treatment of disorders associated there with using compounds and pharmaceutical compositions including the compounds.
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Page/Page column 75
(2012/10/18)
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- BIARYL SUBSTITUTED DIAZABICYCLOALKANE DERIVATIVES
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The invention relates biaryl substituted diazabicycloalkanes of foraula (I), and more particularly bicycloheteroaryl substituted fused diazabicycloalkane derivatives, compositions comprising such compounds, and such compounds for use for treating or preve
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Page/Page column 51
(2009/06/27)
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- SPIROCYCLIC AZAADAMANTANE DERIVATIVES AND METHODS OF USE
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The invention relates to compounds that are spirocyclic azaadamantane derivatives derivatives, particularly spirocyclic azaadamantanyl ether or amine derivatives, compositions comprising such compounds, methods of using such compounds and compositions, processes for preparing such compounds, and intermediates obtained during such processes.
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Page/Page column 24
(2008/12/06)
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- SUBSTITUTED IMIDAZOPYRIDAZINES AND PYRROLOPYRIMIDINES AS LIPID KINASE INHIBITORS
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The present invention relates to compounds are of the formula I, processes for the preparation thereof, more generally these compounds for use in the treatment of the human or animal body, in the treatment of an inflammatory or obstructive airway disease, disorders commonly occurring in connection with transplantation, or a proliferative disease, which disease responds to an inhibition of kinases of the PI3-kinase-related protein kinase family.
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Page/Page column 201
(2009/01/20)
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- FUSED BICYCLOHETEROCYCLE SUBSTITUTED AZABICYCLIC ALKANE DERIVATIVES
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The invention relates to fused bicycloheterocycle substituted azabicyclic alkane derivatives, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions.
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Page/Page column 27
(2008/06/13)
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- INDOLE DERIVATIVES
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The invention concerns indole derivatives of Formula (I) or pharmaceutically-acceptable salts thereof, wherein each of Ring A, m, R1, R2, n, R3 and G1 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in therapy, for example in the treatment of disease mediated by a PI3K enzyme and/or a mTOR kinase.
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- 1H-PYRROLO[2,3-B]PYRIDINES
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Derivatives of pyrrolo[2,3-b]pyridine which are useful as SGK-1 kinase inhibitors are described herein. The invention described herein also describes pharmaceutical compositions containing derivatives of pyrrolo[2,3-b]pyridine and methods of using pyrrolo[2,3-b]pyridine derivatives and pharmaceutical compositions thereof in the treatment of diseases mediated by SGK-1.
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Page/Page column 67-68
(2008/06/13)
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- SYNTHESIS
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The present invention provides a novel substituted azaindoline intermediate of formula (I) and a method for its synthesis. The novel substitued azaindoline intermediate (I) is provided for use in the manufacture of 5-substituted 7-azaindolines and 5-substituted 7-azaindoles.
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