887309-87-7Relevant academic research and scientific papers
Development of anti-breast cancer PI3K inhibitors based on 7-azaindole derivatives through scaffold hopping: Design, synthesis and in vitro biological evaluation
Chen, Yi,Deng, Mingli,Jia, Yu,Ling, Yun,Liu, Xiaofeng,Lu, Mingzhu,Qiu, Tianze,Xiang, Ruiqing,Yang, Chengbin,Yang, Yongtai,Zhou, Yaming
supporting information, (2021/10/19)
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.
Benzoxazinone derivatives and application thereof
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Paragraph 0076-0077; 0090-0092, (2019/12/13)
The invention relates to benzoxazinone derivatives and an application thereof, and belongs to the technical field of antitumor drugs. The technical problem solved by the invention is to provide the novel benzoxazinone derivatives, and the compounds have a
Discovery of 4-phenyl-2H-benzo[b][1,4]oxazin-3(4H)-one derivatives as potent and orally active PI3K/mTOR dual inhibitors
Yan, Guoyi,Pu, Chunlan,Lan, Suke,Zhong, Xinxin,Zhou, Meng,Hou, Xueyan,Yang, Jie,Shan, Huifang,Zhao, Lifeng,Li, Rui
, p. 667 - 686 (2019/06/24)
PI3K/Akt/mTOR signaling pathway plays an important role in cancer cell growth and survival. In this study, a new class of molecules with skeleton of 4-phenyl-2H-benzo[b] [1,4]oxazin-3(4H)-one were designed and synthesized targeting this pathway. Bioassays showed that, among all the molecules, 8d-1 was a pan-class I PI3K/mTOR inhibitor with an IC50 of 0.63 nM against PI3Kα. In a wide panel of protein kinases assays, no off-target interactions of 8d-1 were identified. 8d-1 was orally available, and displayed favorable pharmacokinetic parameters in mice (oral bioavailability of 24.1%). In addition, 8d-1 demonstrated significant efficiency in Hela/A549 tumor xenograft models (TGI of 87.7% at dose of 50 mg/kg in Hela model) without causing significant weight loss and toxicity during 30 days treatment. Based on the bioassays, compound 8d-1 could be used as an anti-cancer drug candidate.
Micro-reactor tandem synthesis method of indole anticancer drug molecules
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Paragraph 0104-0106, (2019/12/08)
The invention relates to a micro-reactor tandem synthesis method of indole anticancer drug molecules. The method comprises the following steps: a reaction liquid 1 and a reaction liquid 2 are mixed, then are introduced into a first micro-reactor, and are reacted to obtain a first effluent, the first effluent and a reaction liquid 3 are mixed, then are introduced into a second micro-reactor, and are reacted to obtain a second effluent, the second effluent and a reaction liquid 4 are mixed, then are introduced into a third micro-reactor, and are reacted to obtain a final effluent, and the finaleffluent is concentrated and separated to obtain the indole anticancer drug molecules, wherein the reaction liquid 1 is a mixed solution containing 5-bromine-3-amino-2-substituted (R1)-pyridine, the reaction liquid 2 is substituted (R2)-benzenesulfonyl chloride, the reaction liquid 3 is a mixed solution containing bis(pinacolato)diboron, the reaction liquid 4 is a mixed solution containing a 5-bromo-7-azaindole derivative, and the indole anticancer drug molecules are benzenesulfonamidopyridylazaindole compounds. Compared with the prior art, the method of the invention has the advantages of high reaction efficiency, few side reactions and simple production process.
Discovery of new thienopyrimidine derivatives as potent and orally efficacious phosphoinositide 3-kinase inhibitors
Lin, Songwen,Wang, Chunyang,Ji, Ming,Wu, Deyu,Lv, Yuanhao,Sheng, Li,Han, Fangbin,Dong, Yi,Zhang, Kehui,Yang, Yakun,Li, Yan,Chen, Xiaoguang,Xu, Heng
supporting information, p. 637 - 646 (2018/01/05)
A series of new thienopyrimidine derivatives has been discovered as potent PI3K inhibitors. The systematic SAR studies for these analogues are described. Among them, 8a and 9a exhibit nanomolar enzymatic potencies and sub-micromolar cellular anti-prolifer
Discovery and Optimization of 2-Amino-4-methylquinazoline Derivatives as Highly Potent Phosphatidylinositol 3-Kinase Inhibitors for Cancer Treatment
Lin, Songwen,Wang, Chunyang,Ji, Ming,Wu, Deyu,Lv, Yuanhao,Zhang, Kehui,Dong, Yi,Jin, Jing,Chen, Jiajing,Zhang, Jingbo,Sheng, Li,Li, Yan,Chen, Xiaoguang,Xu, Heng
supporting information, p. 6087 - 6109 (2018/07/05)
Increased phosphatidylinositol 3-kinase (PI3K) signaling is among the most common alterations in cancer, spurring intensive efforts to develop new cancer therapeutics that target this pathway. In this work, we discovered a series of novel 2-amino-4-methylquinazoline derivatives through a hybridization and subsequent scaffold hopping approach that were highly potent class I PI3K inhibitors. Lead optimization resulted in several promising compounds (e.g., 19, 20, 37, and 43) with nanomolar PI3K potencies, prominent antiproliferative activities, favorable PK profiles, and robust in vivo antitumor efficacies. More interestingly, compared with 19 and 20, 37 and 43 demonstrated improved brain penetration and in vivo efficacy in an orthotopic glioblastoma xenograft model. Furthermore, preliminary safety assessments including hERG channel inhibition, AMES, CYP450 inhibition, and single-dose toxicity were performed to characterize their toxicological properties.
Compound containing L-prolinamide fragment, and preparation method and application thereof
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Paragraph 0046; 0047, (2017/07/12)
The invention discloses a compound containing an L-prolinamide fragment, and a preparation method and an application thereof and belongs to the technical field of antitumor drugs. The compound containing the L-prolinamide fragment comprises a 5-aryl pyrid
Discovery of a Novel Series of 7-Azaindole Scaffold Derivatives as PI3K Inhibitors with Potent Activity
Yang, Chengbin,Zhang, Xi,Wang, Yi,Yang, Yongtai,Liu, Xiaofeng,Deng, Mingli,Jia, Yu,Ling, Yun,Meng, Ling-Hua,Zhou, Yaming
supporting information, p. 875 - 880 (2017/08/16)
The phosphoinositide 3-kinase (PI3K) inhibitors potently inhibit the signaling pathway of PI3K/AKT/mTOR, which provides a promising new approach for the molecularly targeted cancer therapy. In this work, a novel series of 7-azaindole scaffold derivatives was discovered by the fragment-based growing strategy. The structure-activity relationship profiles identified that the 7-azaindole scaffold derivatives exhibit potent activity against PI3K at molecular and cellular levels as well as cell proliferation in a panel of human tumor cells.
Morphline and quinoline compound, preparation method thereof, and use thereof
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Paragraph 0202; 0203, (2016/10/07)
The invention discloses a morpholinoquinoline compound represented by a formula (I) which is shown in the description, wherein the R1 represents a C1-C6 alkyl group, an aryl group, an amino group, a C3-C10 cycloalkyl group, a heterocyclic radical, or a heteroaryl group; the R2 represents H, a halogen element, or -OR10; the R3 represents H, -NHR10, or -NHC(=O)R10; the R4 represents H, a C1-C6 alkyl group, -C(=O)R10, or -S(=O)2R10; the R5 and R6 individually represent H, a C1-C6 alkyl group, or a halogen element; the R7 and R8 individually represent H, a C1-C6 alkyl group, or a halogen element, or the R7 and R8 can be emerged as =O; the R9 represents H, a C1-C6 alkyl group, -OR10, or a halogen element; the R10 represents H, a C1-C6 alkyl group, a C3-C10 cycloalkyl group, an aryl group, or a heteroaryl group; the alkyl groups, alkoxyl groups, aryl groups, and heteroaryl groups mentioned above in R1 to R10 can be optionally replaced by one or more groups, and these groups can be alkyl group, alkenyl group, alkynyl group, halogen elements, alkoxyl group, aryl group, heteroaryl group, amino group, cyan group, nitro group, carboxyl group, ester group, carbamyl group, sulfonyl group, sulfamic group, or the like. The morpholinoquinoline compound can be used as a drug to treat diseases related with PI3K/mTOR.
As the PI3K/mTOR inhibitor compound, its preparation and use
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Paragraph 0197; 0198, (2017/05/20)
The invention discloses a compound used as a PI3K/mTOR inhibitor, which is a compound with a general formula of (IA) or (IB), wherein R1 is selected from hydrogen, halogen, alkyl, alkyloxy, and amido, or forms a fused ring with R2; R2 is selected from hydrogen, amido, sulfamine, sulfonylurea, alkyl, and alkyloxy, or forms a fused ring with R1; R3 is selected from hydrogen, and C1-C6 alkyl; R4 is selected from hydrogen, amido, acylamino, or sulfamine; R5 is selected from hydrogen, halogen, alkyl or alkyloxy. The invention also discloses a preparation method of the compound used as a PI3K/mTOR inhibitor, and an application of the compound as a drug in treating PI3K/mTOR related diseases, especially PI3K/mTOR related cancers.
