CAS: 1001350-96-4; (S)-1-(4-((5-Cyclopropyl-1H-Pyrazol-3-yl)Amino)Pyrrolo[2,1-F][1,2,4]Triazin-2-yl)-N-(6-Fluoropyridin-3-yl)-2-Methylpyrrolidine-2-Carboxamide

该化合物是针对胰岛素型生长因子-1受体(IGF-1R)和胰岛素受体(IR)的一种强效和选择性的小分子抑制剂,具有很强的粘合性,抑制两种受体的自发性,在肿瘤研究中表现出潜力,特别是对于由IGF-1R/IR信号路径驱动的癌症.BMS-754807显示了有利的药理动能特性,包括临床前研究中的口服生物利用率和可控毒性特征.其双重抑制机制在针对肿瘤扩散和生存方面具有战略优势.该化合物因其在各种癌症模型中的功效而受到调查,使其成为研究IGF-1R/IR依赖的恶性病和治疗发育的宝贵工具.

结构式图片

合成工艺路线路线简述

    N-[2-(氨基羰基)-1H-吡咯-1-基]氨基甲酸乙酯置于四丁基氢氧化铵,Potassium Carbonate,N,N-二异丙基乙胺,N-[(Dimethylamino)-3-Oxo-1H-1,2,3-Triazolo[4,5-B]Pyridin-1-Yl-Methylene]-N-Methylmethanaminium Hexafluorophosphate,三氯氧磷体系中,用 N,N-二甲基甲酰胺,异丙醇,甲苯 用作溶剂,化学反应 119.0H,反应生成Bms 754807; (2S)-1-[4-[(5-环丙基-1H-吡唑-3-基)氨基]吡咯并[2,1-F][1,2,4]三嗪-2-基]-N-(6-氟-3-吡啶基)-2-甲基-2-吡咯烷甲酰胺
    参考文献:Pyrrolotriazine Kinase Inhibitors
    标题:Pyrrolotriazine Kinase Inhibitors
    摘要:本发明提供了公式i的化合物以及药用可接受的盐类.公式i的化合物通过抑制酪氨酸激酶活性,使其可作为抗癌剂以及用于治疗阿尔茨海默病.

    专利信息


    专利号:US-2012088848-A1
    优先权日:1998-03-19
    标 题 :Methods and compositions for controlled polypeptide synthesis
    发明人:DEMING TIMOTHY J; YU MIAOER; CURTIN SCOTT A; HWANG JUNGYEON; WYRSTA MICHAEL D; NOWAK ANDREW; SEIDEL SCOTT W
    权利人:DEMING TIMOTHY J; YU MIAOER; CURTIN SCOTT A; HWANG JUNGYEON; WYRSTA MICHAEL D; NOWAK ANDREW; SEIDEL SCOTT W
    摘要:Methods and compositions for the generation of polypeptides having varied material properties are disclosed herein. Methods include means for initiating the polymerization of aminoacid-N-carboxyanhydride (NCA) monomer by combining the monomer with an amido-containing metallacycle, for making self assembling amphiphilic block copolypeptides and related protocols for adding oligo(ethyleneglycol) functionalized aminoacid-N-carboxyanhydrides (NCAs) to polyaminoacid chains. Additional methods include means of adding an end group to the carboxy terminus of a polyaminoacid chain by reacting an alloc-protected amino acid amide with a transition metal-donor ligand complex to forming an amido-amidate metallacycle for use in further polymerization reactions. Novel compositions for use in peptide synthesis and design including five and six membered amido-containing metallacycles and block copolypeptides are also disclosed.

    专利号:WO-0068252-A1
    优先权日:1999-05-10
    标 题 :Methods and compositions for controlled polypeptide synthesis
    发明人:DEMING TIMOTHY J; YU MIAOER; CURTIN SCOTT A; HWANG JUNGYEON; WYRSTA MICHAEL D
    权利人:UNIV CALIFORNIA
    摘要:Methods and compositions for the generation of polypeptides having varied material properties are disclosed herein. Methods include means for making self assembling amphiphilic block copolypeptides and related protocols for adding oligo(ethyleneglycol) functionalized aminoacid-N-carboxyanhydrides (NCAs) to polyaminoacid chains. Additional methods include means of adding an end group to the carboxy terminus of a polyaminoacid chain by reacting an alloc-protected amino acid amide with a transition metal-donor ligand complex, thereby forming an amido-amidate metallacycle for use in further polymerization reactions. Novel compositions for use in peptide synthesis and design including five and six membered amido-containing metallacycles and block copolypeptides are also disclosed.

    专利号:US-7968519-B2
    优先权日:1998-03-19
    标 题 :Methods and compositions for controlled polypeptide synthesis
    发明人:DEMING TIMOTHY J; YU MIAOER; CURTIN SCOTT A; HWANG JUNGYEON; WYRSTA MICHAEL D; NOWAK ANDREW; SEIDEL SCOTT W
    权利人:UNIV CALIFORNIA
    摘要:Methods and compositions for the generation of polypeptides having varied material properties are disclosed herein. Methods include means for initiating the polymerization of aminoacid-N-carboxyanhydride (NCA) monomer by combining the monomer with an amido-containing metallacycle, for making self assembling amphiphilic block copolypeptides and related protocols for adding oligo(ethyleneglycol) functionalized aminoacid-N-carboxyanhydrides (NCAs) to polyaminoacid chains. Additional methods include means of adding an end group to the carboxy terminus of a polyaminoacid chain by reacting an alloc-protected amino acid amide with a transition metal-donor ligand complex to forming an amido-amidate metallacycle for use in further polymerization reactions. Novel compositions for use in peptide synthesis and design including five and six membered amido-containing metallacycles and block copolypeptides are also disclosed.

    专利号:US-6013626-A
    优先权日:1993-12-21
    标题 :Cryptophycins from synthesis
    发明人:MOORE RICHARD E; TIUS MARCUS A; BARROW RUSSELL A; LIANG JIAN; CORBETT THOMAS H; VALERIOTE FREDERICK A; GOLAKOTI TRIMURTULU; HEMSCHEIDT THOMAS K
    权利人:UNIV HAWAII; UNIV WAYNE STATE
    摘要:A cryptophycin compound is provided having the structure: ##STR1## Further provided are methods of producing cryptophycins by total synthesis and methods of using cryptophycins in pharmaceuticals. It is a further object of this invention to use cryptophycins to inhibit the proliferation of mammalian cells. Moreover, methods of using cryptophycins to treat neoplasia is also provided.

    专利号:US-6632922-B1
    优先权日:1998-03-19
    标题 :Methods and compositions for controlled polypeptide synthesis
    发明人:DEMING TIMOTHY J; CURTIN SCOTT A
    权利人:UNIV CALIFORNIA
    摘要:Methods and compositions for the generation of polypeptides having varied material properties are disclosed herein. Methods include means for making self assembling amphiphilic block copolypeptides and related protocols adding oligo(ethyleneglycol) functionalized aninoacid-N-carboxyanhydrides (NCAs) to polyaminoacid chains. Additional methods include means of adding an end group to the carboxy terminus of a polyaminoacid chain by reacting an alloc-protected amino acid amide with a transition metal-donor ligand complex, thereby forming an amido-amidate metallacycle for use in further polymerization reactions. Novel compositions for use in peptide synthesis and design including five and six membered amido-containing metallacycles and block copolypeptides are also disclosed.

    专利号:WO-2011018796-A1
    优先权日:2009-08-13
    标 题 :An improved process for the synthesis of alkyl/aralkyl (2s)-2-(tert-butoxycarbonyl)-amino-2-[-8-azabicyclo[3.2.1]oct-3-yl]-exo-acetate and analogs thereof: key intermediates for the preparation of dppiv inhibitors
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    CAS号:1001350-96-4
    中文名:BMS-754807
    英文名:BMS-754807
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    主要参考文献


    1: Hebron KE, Wan X, Roth JS, Liewehr DJ, Sealover NE, Frye WJE, Kim A, Stauffer S, Perkins OL, Sun W, Isanogle KA, Robinson CM, James A, Awasthi P, Shankarappa P, Luo X, Lei H, Butcher D, Smith R, Edmondson EF, Chen JQ, Kedei N, Peer CJ, Shern JF, Figg WD, Chen L, Hall MD, Difilippantonio S, Barr FG, Kortum RL, Robey RW, Vaseva AV, Khan J, Yohe ME. The Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models. Clin Cancer Res. 2023 Jan 17;29(2):472-487. doi: 10.1158/1078-0432.CCR-22-1646.
    2: Cyra M, Schulte M, Berthold R, Heinst L, Jansen EP, Grünewald I, Elges S, Larsson O, Schliemann C, Steinestel K, Hafner S, Simmet T, Wardelmann E, Kailayangiri S, Rossig C, Isfort I, Trautmann M, Hartmann W. SS18-SSX drives CREB activation in synovial sarcoma. Cell Oncol (Dordr). 2022 Jun;45(3):399-413. doi: 10.1007/s13402-022-00673-w. Epub 2022 May 12.
    3: Eke I, Aryankalayil MJ, Bylicky MA, Makinde AY, Liotta L, Calvert V, Petricoin EF, Graves EE, Coleman CN. Radiotherapy alters expression of molecular targets in prostate cancer in a fractionation- and time-dependent manner. Sci Rep. 2022 Mar 3;12(1):3500. doi: 10.1038/s41598-022-07394-y.

    合成参考文献


    参考文献:10.1158/1541-7786.mcr-19-1098
    摘要:Sia KCS, Zhong L, Mayoh C, Norris MD, Haber M, Marshall GM, Raftery MJ, Lock RB. Targeting TSLP-Induced Tyrosine Kinase Signaling Pathways in CRLF2-Rearranged Ph-like ALL. Mol Cancer Res. 2020 Dec;18(12):1767–76. doi: 10.1158/1541-7786.mcr-19-1098.
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