(S)-2-((S)-4-methyl-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)pentanamido)-3-phenyipropanoic acid(2S)-2-amino-4-methyl-1-[(2R)-2-methyloxiran-2-yl]pentan-1-onedichloromethane(S)-2-amino-4-methyl-1-((R)-2-methyloxiran-2-yl)pentan-1-one trifluoroacetic acid salt
合成工艺路线路线简述
3235-69-6 + 254888-42-1 = 868540-17-4 反应条件:1.1 Reagents: Trifluoroacetic Acid Solvents: Dimethylformamide; 25 H,Rt1.2 Reagents: Diisopropylethylamine,1-[bis(Dimethylamino)Methylene]-1H-Benzotriazolium Hexafluorophosphate(1-) 3-Oxi... Solvents: Dichloromethane; 2 H,Rt 标题:Nature Of Pharmacophore Influences Active Site Specificity Of Proteasome Inhibitors 作者:Screen,Michael; Et Al 参考文献:Journal Of Biological Chemistry 日期:2010 卷标:285(51) 页码:40125-40134]
1396006-45-3 + 869804-84-2 = 868540-17-4 反应条件:1.1 Reagents: 1-Hydroxybenzotriazole,Diisopropylethylamine,Pybop Solvents: Acetonitrile; 5 °C; 10 - 15 H,25 - 30 °C 标题:Process For The Preparation Of Carfilzomib 作者:Anonymous 参考文献:Ip.Com Journal 日期:2014 卷标:14 页码:1-19]
= 868540-17-4 反应条件:1.1 Reagents: Potassium Iodide Solvents: Tetrahydrofuran; 12 H,Rt 标题:Allenone-Mediated Racemization/epimerization-Free Peptide Bond Formation And Its Application In Peptide Synthesis 作者:Wang,Zhengning; Et Al 参考文献:Journal Of The American Chemical Society 日期:2021 卷标:143(27) 页码:10374-10381]
专利号:WO-2024220674-A1 优先权日:2023-04-18 标题:Timescale-guided microfluidic synthesis of polyphenol-iron iii network nanocapsules of hydrophobic drugs 发明人:YEO YOON; HAN BUMSOO; SHEN YINGNAN 权利人:PURDUE RESEARCH FOUNDATION 摘要:A scalable method of continuous microfluidic synthesis of tannic acid-iron III (TA-FeIII) network (TFN) nanocapsules of a hydrophobic drug; a scalable method of continuous microfluidic synthesis of epigallocatechin-3-gallate iron III (EGCG-FeIII) network, (EFN) nanocapsules; hydrophobic drug nanocapsules synthesized in accordance with the method; and a method of administering a hydrophobic drug to a patient in need thereof by administering to the patient the hydrophobic drug nanocapsules.
专利号:US-12351573-B2 优先权日:2019-05-09 标 题:Compounds for use in synthesis of peptidomimetics 发明人:AL-ABED YOUSEF; CHENG KAI FAN 权利人:FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH 摘要:Synthesis of O-benzotriazole and O-imidazole synthons are described. Uses of synthons in synthesis of azapeptides and other peptidomimetics, azapeptides and other peptidomimetics synthesized from the synthons and uses of azapeptides and other peptidomimetics are also described.
专利号:US-2023159450-A1 优先权日:2020-05-08 标 题 :Dimers for use in synthesis of peptidomimetics 发明人:AL-ABED YOUSEF; ALTITI AHMAD 权利人:FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH 摘要:Dimers for use in synthesis of peptidomimetics are described. Uses of dimers as synthons in synthesis of azapeptides and other peptidomimetics, azapeptides and other peptidomimetics synthesized from the dimers and uses of azapeptides and other peptidomimetics are also described.
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-11708341-B2 优先权日:2016-08-05 标题:Synthesis of (S)-2-amino-4-methyl-((R)-2-methyloxirane-2-yl)-pentan-1-one and pharmaceutically acceptable salts thereof 发明人:Beaver Matthew; CUI SHENG; SHI XIANGQING 权利人:AMGEN INC 摘要:The present invention provides new methods for preparing compound 5, and pharmaceutically acceptable salts thereof, of structure n nCompound 5, or a pharmaceutically acceptable salt thereof, is an important intermediate in the synthesis of carfilzomib. The invention further provides methods of making a useful manganese catalyst that may be used in the epoxidation step of the present invention.
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.
1: Moreau P, Dimopoulos MA, Mikhael J, Yong K, Capra M, Facon T, Hajek R, Špička I, Baker R, Kim K, Martinez G, Min CK, Pour L, Leleu X, Oriol A, Koh Y, Suzuki K, Risse ML, Asset G, Macé S, Martin T; IKEMA study group. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. Lancet. 2021 Jun 19;397(10292):2361-2371. doi: 10.1016/S0140-6736(21)00592-4. Epub 2021 Jun 4. 396(10245):186-197. doi: 10.1016/S0140-6736(20)30734-0. Erratum in: Lancet. 2020 Aug 15;396(10249):466. ASPIRE Investigators. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015 Jan 8;372(2):142-52. doi: 10.1056/NEJMoa1411321. Epub 2014 Dec 6. 22(12):1705-1720. doi: 10.1016/S1470-2045(21)00535-0. Epub 2021 Nov 11. ENDEAVOR Investigators. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016 Jan;17(1):27-38. doi: 10.1016/S1470-2045(15)00464-7. Epub 2015 Dec 5. 14(1):e14502. doi: 10.15252/emmm.202114502. Epub 2021 Dec 13. 7: Chari A, Martinez-Lopez J, Mateos MV, Bladé J, Benboubker L, Oriol A, Arnulf B, Rodriguez-Otero P, Pineiro L, Jakubowiak A, de Boer C, Wang J, Clemens PL, Ukropec J, Schecter J, Lonial S, Moreau P. Daratumumab plus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Blood. 2019 Aug 1;134(5):421-431. doi: 10.1182/blood.2019000722. Epub 2019 May 21. 8: Kortuem KM, Stewart AK. Carfilzomib. Blood. 2013 Feb 7;121(6):893-7. doi: 10.1182/blood-2012-10-459883. 126(5):718-725. doi: 10.1038/s41416-021-01608-2. Epub 2021 Nov 20.
合成参考文献
参考文献:10.1158/1535-7163.mct-10-1108 摘要:Dasmahapatra G, Lembersky D, Son MP, Attkisson E, Dent P, Fisher RI, Friedberg JW, Grant S. Carfilzomib Interacts Synergistically with Histone Deacetylase Inhibitors in Mantle Cell Lymphoma Cells In Vitro and In Vivo. 2011 Sep 01;10(9):1686–97. doi: 10.1158/1535-7163.mct-10-1108. 参考文献:10.1124/dmd.111.039164 摘要:Yang J, Wang Z, Fang Y, Jiang J, Zhao F, Wong H, Bennett MK, Molineaux CJ, Kirk CJ. Pharmacokinetics, pharmacodynamics, metabolism, distribution, and excretion of carfilzomib in rats. Drug Metab Dispos. 2011 Oct;39(10):1873–82. doi: 10.1124/dmd.111.039164. 参考文献:10.1155/2011/514261 摘要:Miller CP, Singh MM, Rivera-Del Valle N, Manton CA, Chandra J. Therapeutic strategies to enhance the anticancer efficacy of histone deacetylase inhibitors. J Biomed Biotechnol. 2011;2011():514261.