CAS: 915019-65-7; 2-Methyl-2-(4-(3-Methyl-2-Oxo-8-(Quinolin-3-yl)-2,3-Dihydro-1H-Imidazo[4,5-C]Quinolin-1-yl)Phenyl)Propanenitrile

该化合物是二磷酸丁基酚3-Kinase (PI3K)和哺乳动物的抑制性甲胺素(mtor)的双重目标,具有很强的抗肿瘤活动,它有选择地针对PI3K/AKT/mtor信号路径,这是细胞扩散和生存的重要调节器,是肿瘤研究的极佳候选体.Dactolisib 表现出对PI3K(α,β,γ,等形态)和Mtor(mTORC1/2)的高度抑制性能,与单一目标抑制性抑制剂有区别.它抑制途径的激活能力有效地减少了临床前型肿瘤的生长,特别是在PI3K路径调节的癌症中.该化合物被广泛用于生物化学和药理研究,以调查PI3K/Mtor驱动的恶性.

结构式图片

上下游产品

2-[4-(8-bromo-3-methyl-2-oxo-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-2-methyl-propionitrile quinolin-3-ylboronic acid 6-bromo-3-nitroquinolin-4-ol 6-bromo-4-chloro-3-nitroquinoline

合成工艺路线路线简述

  • 191162-39-7 + 2222382-41-2 + 115279-57-7 = 915019-65-7
    反应条件:1.1 Reagents: Hydrochloric Acid Solvents: 1,4-Dioxane,3-Pentanol; 20 Min,230 °C; 230 °C -> Rt1.2 Reagents: Tripotassium Phosphate Catalysts: Tetrakis(Triphenylphosphine)Palladium Solvents: Dimethylformamide,Water; 10 Min,150 °C; 150 °C -> Rt1.3 Reagents: Sodium Bicarbonate Solvents: Water; Rt
    标题:Acid-Promoted Cascade Reaction Of N-(4-Chloroquinolin-3-Yl)Carbamates With Amines: One-Pot Assembly Of Imidazo[4,5-C]Quinolin-2-Ones
    作者:Lu,Xiao; Kim,Myunghoon; Orr,Meghan J.; Li,Hao; Huang,Wenwei
    参考文献:European Journal Of Organic Chemistry 日期:2018 卷标:2018(13) 页码:1572-1580]

    191162-39-7 + 915019-50-0 = 915019-65-7
    反应条件:1.1 Reagents: Potassium Bicarbonate Catalysts: Triphenylphosphine,Dichlorobis(Triphenylphosphine)Palladium Solvents: Dimethylformamide,Water; 60 °C; 60 °C -> 100 °C; 95 - 100 °C; 1.5 H,> 95 °C; 2 - 6 H,> 95 °C1.2 Reagents: L-(+)-Cysteine Solvents: Water; 20 Min,> 95 °C; 0.5 - 1 H,> 95 °C; 9 H,95 °C -> 0 °C; 4 H,0 °C
    标题:Development Of A Robust Synthesis Of Dactolisib On A Commercial Manufacturing Scale
    作者:Baenziger,Markus; Pachinger,Werner; Stauffer,Frederic; Zaugg,Werner
    参考文献:Organic Process Research & Development 日期:2019 卷标:23(9) 页码:1908-1917]

    = 915019-65-7 [标题:Reaction Conditions
    标题:A Drug Targeting Only P110α Can Block Phosphoinositide 3-Kinase Signalling And Tumour Growth In Certain Cell Types
    作者:Jamieson,Stephen; Flanagan,Jack U.; Kolekar,Sharada; Buchanan,Christina; Kendall,Jackie D.; Et Al
    参考文献:Biochemical Journal 日期:2011 卷标:438(1) 页码:53-62
喹啉-3-硼酸,2-(4-(8-溴-3-甲基-2-氧代-2,3-二氢咪唑并[4,5-C]喹啉-1-基)苯基)-2-甲基丙腈置于喹啉-3-硼酸体系中,化学反应生成 苯乙氰,4-[2,3-二氢-3-甲基-2-氧代-8-(3-喹啉基)-1H-咪唑并[4,5-C]喹啉-1-基]-.Alpha.,.Alpha.-二甲基-
参考文献:Salts And Crystall Forms Of 2-Methyl-2-[4-(3-Methyl-2-Oxo-8-Quinolin-3-Yl-2,3-Dihydro-Imidazo[4,5-C]Quinolin-1-yl)-Phenyl]-Propionitrile
标题:Salts And Crystall Forms Of 2-Methyl-2-[4-(3-Methyl-2-Oxo-8-Quinolin-3-Yl-2,3-Dihydro-Imidazo[4,5-C]Quinolin-1-yl)-Phenyl]-Propionitrile
摘要:本发明涉及2-甲基-2-[4-(3-甲基-2-氧代-8-喹啉-3-基-2,3-二氢咪唑[4,5-C]喹啉-1-基)-苯基]-丙腈的特定晶体形式,其水合物和溶剂化合物,其盐及其盐的水合物和溶剂化合物,以及其制备的某些过程,含有这些晶体形式的制药组合物,并且它们在诊断方法中的使用或更好地用于治疗恒温动物,特别是人类,以及它们用作中间体或用于制备用于诊断方法或更好地用于治疗恒温动物,特别是人类的制药制剂.

海关参考信息

专利信息


专利号:US-12391691-B2
优先权日:2018-11-16
标题:Synthesis of key intermediate of KRAS G12C inhibitor compound
发明人:PARSONS ANDREW THOMAS; COCHRAN BRIAN MCNEIL; POWAZINIK IV WILLIAM; CAPORINI MARC ANTHONY
权利人:AMGEN INC
摘要:The present invention relates to an improved, efficient, scalable process to prepare intermediate compounds, such as compound 5M, having the structure n nuseful for the synthesis of compounds that target KRAS G12C mutations, such as

专利号:US-2025206736-A1
优先权日:2019-11-14
标题 :Synthesis of kras g12c inhibitor compound
发明人:CORBETT MICHAEL THOMAS; CAILLE SEBASTIEN
权利人:AMGEN INC
摘要:The present disclosure relates to an improved, efficient, scalable process to prepare intermediate compounds, such as 2-isopropyl-4-methylpyridin-3-amine, useful for the synthesis of compounds, such as Compound 9, for the treatment of KRAS G12C mutated cancers.

专利号:US-2017283878-A1
优先权日:2015-12-11
标题:Modulation of globoseries glycosphingolipid synthesis and cancer biomarkers
发明人:WONG CHI-HUEY; WU CHUNG-YI; CHEUNG SARAH K C; CHUANG PO-KAI; HSU TSUI-LING
权利人:ACADEMIA SINICA
摘要:The present disclosure relates to methods and compositions which can modulate the globoseries glycosphingolipid synthesis. Particularly, the present disclosure is directed to glycoenzyme inhibitor compound and compositions and methods of use thereof that can modulate the synthesis of globoseries glycosphingolipid SSEA-3/SSEA-4/GloboH in the biosynthetic pathway; particularly, the glycoenzyme inhibitors target the alpha-4GalT; beta-4GalNAcT-I; or beta-3GalT-V enzymes in the globoseries synthetic pathway. Additionally, the present disclosure is also directed to vaccines, antibodies, and/or immunogenic conjugate compositions targeting the SSEA-3/SSEA-4/GLOBO H associated epitopes (natural and modified) which elicit antibodies and/or binding fragment production useful for modulating the globoseries glycosphingolipid synthesis. Moreover, the present disclosure is also directed to the method of using the compositions described herein for the treatment or detection of hyperproliferative diseases and/or conditions. Furthermore, the instant disclosure also relates to cancer stem cell biomarkers for diagnostic and therapeutic uses.

专利号:US-2025206743-A1
优先权日:2022-03-25
标 题:Tyk2 inhibitor synthesis and intermediates thereof
发明人:MASSE CRAIG E; PHADKE AVINASH S; LAWSON JON P; LEVY STUART; YANG XIAOWEI; WU GUISHENG; FAN SHUFENG
权利人:TAKEDA PHARMACEUTICALS CO
摘要:Described herein are methods of synthesis of a tyrosine-protein kinase 2 (TYK2) inhibitor and to intermediate compounds of the synthesis and methods of making the intermediates. Also provided are pharmaceutically acceptable compositions including compounds prepared by the synthetic method and methods of treating disorders using the same.

专利号:WO-2025128098-A1
优先权日:2023-12-13
标 题 :Solid oral dosage forms, kits, and methods of using the same
发明人:LI YING; LANGER ROBERT; TRAVERSO CARLO
权利人:MASSACHUSETTS INST TECHNOLOGY; BRIGHAM & WOMENS HOSPITAL INC
摘要:Provided herein are solid oral dosage forms, methods, and kits useful, e.g, for the extension of the residence time of active pharmaceutical agents in vivo by the synthesis of a polymer in situ in a subject. In particular, the solid oral dosage forms, methods, and kits disclosed herein are particularly useful for drugs that require more than once daily administration (e.g, drugs that have short half-lives).

专利号:US-2025289827-A1
优先权日:2022-12-02
标 题:Morphic forms of a mutant braf degrader and methods of manufacture thereof
发明人:YU ROBERT T; HE MINSHENG; SCHNADERBECK MATTHEW J; KREGER BRIDGET; POLLOCK ROY MACFARLANE; JIANG SIYI; LI MEIQI; CHEN BOLU; LU JIANNAN
权利人:C4 THERAPEUTICS INC
摘要:Advantageous isolated morphic forms of (3R)-3-[6-[2-cyano-3-[[ethyl(methyl)sulfamoyl]amino]-6-fluorophenoxy]-4-oxoquinazolin-3-yl]-8-[2-[1-[3-(2,4-dioxo-1,3-diazinan-1-yl)-5-fluoro-1-methylindazol-6-yl]-4-hydroxypiperidin-4-yl]acetyl]-1-oxa-8-azaspiro[4.5]decane (Compound 1), which is a mutant BRAF degrader, and methods to prepare Compound 1 morphic forms for therapeutic applications are provided in the invention. The invention also provides improved methods for the synthesis of Compound 1, new pharmaceutical compositions comprising Compound 1, and new uses of Compound 1.
上海泽涵生物医药科技有限公司
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南京江恒医药化工有限公司
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主要参考文献


1: Witteck L, Jaster R. Trametinib and dactolisib but not regorafenib exert antiproliferative effects on rat pancreatic stellate cells. Hepatobiliary Pancreat Dis Int. 2015 Dec;14(6):642-50. doi: 10.1186/s12885-016-2712-4.
3: Choudhary GS, Al-Harbi S, Mazumder S, Hill BT, Smith MR, Bodo J, Hsi ED, Almasan A. MCL-1 and BCL-xL-dependent resistance to the BCL-2 inhibitor ABT-199 can be overcome by preventing PI3K/AKT/mTOR activation in lymphoid malignancies. Cell Death Dis. 2015 Jan 15;6:e1593. doi: 10.1038/cddis.2014.525.
4: Bellozi PM, Lima IV, Dória JG, Vieira ÉL, Campos AC, Candelario-Jalil E, Reis HJ, Teixeira AL, Ribeiro FM, de Oliveira AC. Neuroprotective effects of the anticancer drug NVP-BEZ235 (dactolisib) on amyloid-β 1-42 induced neurotoxicity and memory impairment. Sci Rep. 2016 May 4;6:25226. doi: 10.1038/srep25226.

合成参考文献


参考文献:10.1186/bcr2883
摘要:Zhang Y, Moerkens M, Ramaiahgari S, de Bont H, Price L, Meerman J, van de Water B. Elevated insulin-like growth factor 1 receptor signaling induces antiestrogen resistance through the MAPK/ERK and PI3K/Akt signaling routes. Breast Cancer Res. 2011 May 19;13(3):R52.
参考文献:10.2119/molmed.2011.00115
摘要:Mimeault M, Batra SK. Frequent Gene Products and Molecular Pathways Altered in Prostate Cancer- and Metastasis-Initiating Cells and Their Progenies and Novel Promising Multitargeted Therapies. Molecular Medicine. 2011 May 20;17(9-10):949–64. doi: 10.2119/molmed.2011.00115.
参考文献:10.1158/0008-5472.can-12-1365
摘要:Rahmani M, Aust MM, Attkisson E, Williams DC, Ferreira-Gonzalez A, Grant S. Dual inhibition of Bcl-2 and Bcl-xL strikingly enhances PI3K inhibition-induced apoptosis in human myeloid leukemia cells through a GSK3- and Bim-dependent mechanism. Cancer Res. 2013 Feb 15;73(4):1340–51.
参考文献:10.1038/onc.2012.572
摘要:Montero JC, Esparís-Ogando A, Re-Louhau MF, Seoane S, Abad M, Calero R, Ocaña A, Pandiella A. Active kinase profiling, genetic and pharmacological data define mTOR as an important common target in triple-negative breast cancer. Oncogene. 2014 Jan 09;33(2):148–56. doi: 10.1038/onc.2012.572.
参考文献:10.1158/2159-8290.cd-12-0262
摘要:Jia S, Gao X, Lee SH, Maira SM, Wu X, Stack EC, Signoretti S, Loda M, Zhao JJ, Roberts TM. Opposing effects of androgen deprivation and targeted therapy on prostate cancer prevention. Cancer Discov. 2013 Jan;3(1):44–51.
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