CAS: 1269440-17-6; (S)-Methyl (1-((4-(3-(5-Chloro-2-Fluoro-3-(Methylsulfonamido)Phenyl)-1-Isopropyl-1H-Pyrazol-4-yl)Pyrimidin-2-yl)Amino)Propan-2-yl)Carbamate

该化合物是一个小分子,主要作为某些动脉的选择性抑制剂,特别是涉及癌症细胞扩散和生存的动脉;旨在针对BRAF基因中与包括黑素瘤在内的各种癌症通常相关的特定突变,该基因具有很高的威力和选择性,使其成为有目标癌症治疗的有希望对象;LGX818的典型特征是其分子结构,包括有助于其生物活动的具体功能组;就溶解性而言,它往往为临床环境中的最佳吸收和生物利用率而设计;LGX818的药理学系涉及其新陈代谢和排出路径,对于确定治疗应用中的剂量疗法至关重要;与许多调查药物一样,正在进行的研究侧重于了解其功效,安全特征和病人的潜在副作用.

结构式图片

欧盟法规

C&L通报

上下游产品

(S)-methyl 1-(4-(3-(3-amino-2-chloro-5-fluorophenyl)-1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate methanesulfonyl chloride 2-bromo-4-chloro-1-fluorobenzene 3-bromo-5-chloro-2-fluorobenzoic acid

合成工艺路线路线简述

  • 合成目标产物 Encorafenib (Lgx818) 主要起始原料 2-Bromo-4-Chloro-1-Fluorobenzene
  • (文献来源)合成步骤主要原料 2-Bromo-4-Chloro-1-Fluorobenzene
2-氯-4-[3-碘-1-(异丙基)-1H-吡唑-4-基]嘧啶置于四(三苯基膦)钯 吡啶,Sodium Carbonate,三乙胺体系中,用 1,4-二氧六环,乙醇,二氯甲烷,水,异丙醇,甲苯 用作溶剂,化学反应 80.0H,反应生成康奈非尼
参考文献: Compounds And Compositions As Protein Kinase Inhibitors[fr] Composés Et Compositions En Tant Qu'Inhibiteurs De Protéine Kinase
标题: Compounds And Compositions As Protein Kinase Inhibitors[fr] Composés Et Compositions En Tant Qu'Inhibiteurs De Protéine Kinase
摘要:这项发明提供了一类新型的化合物,其化学式为1,包括这些化合物的药物组合物以及使用这些化合物来治疗或预防与异常或失调的激酶活性相关的疾病或障碍的方法,特别是涉及b-Raf异常激活的疾病或障碍.

海关参考信息

专利信息


专利号:US-11612610-B2
优先权日:2018-12-14
标题:Mito-magnolol compounds and methods of synthesis and use thereof
发明人:KALYANARAMAN BALARAMAN; ZIELONKA JACEK MICHAL; CHENG GANG; HARDY MICAEL JOËL; OUARI OLIVIER
权利人:MEDICAL COLLEGE WISCONSIN INC; AIX MARSEILLE UNIV; MEDICAL COLLEGE OF WISCONSIN INC
摘要:The present invention provides mito-magnolol compounds, pharmaceutical compositions thereof, and methods of using the mito-magnolol compounds in the treatment of cancer, especially anti-cancer therapy or kinase resistant cancers.

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.

专利号:US-2025313551-A1
优先权日:2022-12-15
标题 :Process for the preparation of a quinazolinone derivative
发明人:DOTT PASCAL JEAN CLAUDE; FANTASIA SERENA MARIA; GUILLEMOT-PLASS MAUD; KALDRE DAINIS; LARI GIACOMO MARCO; MODOLO-CHELLAT ISABELLE GEORGETTE HUGUETTE; SEDELMEIER JOERG MATHIAS; TROKOWSKI SEBASTIAN
权利人:HOFFMANN LA ROCHE
摘要:The present invention relates to a new process for the preparation of (3R)—N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1-sulfonamide, as well as to a novel intermediate useful for the synthesis of said compound at large scale.

专利号:US-2018371021-A1
优先权日:2017-05-11
标 题 :Peptidomimetic macrocycles and uses thereof
发明人:AIVADO MANUEL; GUERLAVAIS VINCENT; OLSON KAREN
权利人:AILERON THERAPEUTICS INC
摘要:The present disclosure describes the synthesis of peptidomimetic macrocycles and methods of using peptidomimetic macrocycles to treat a condition. The present disclosure also describes methods of using peptidomimetic macrocycles in combination with at least one additional pharmaceutically-active agent for the treatment of a condition, for example, cancer.

专利号:US-2022259212-A1
优先权日:2019-07-11
标题:Inhibitors of indoleamine 2,3-dioxygenase and/or tryptophan 2,3-dioxygenase
发明人:BOSS CHRISTOPH; CREN SYLVAINE; KIMMERLIN THIERRY; LOTZ-JENNE CARINA; POTHIER JULIEN; TIDTEN-LUKSCH NAOMI
权利人:IDORSIA PHARMACEUTICALS LTD
摘要:The present invention relates to compounds of Formula (I) inhibiting indoleamine 2,3-dioxygenase (IDO) and/or tryptophan 2,3-dioxygenase (TDO) enzymes. Further, their synthesis and their use as medicaments in the treatment of inter alia cancer is disclosed.

专利号:US-12390420-B1
优先权日:2024-10-22
标题 :Compositions for targeted delivery of therapeutic agents and methods for the synthesis and use thereof
发明人:EGUCHI MASAKATSU
权利人:BRYET US INC
摘要:The present disclosure provides compositions and methods for delivering therapeutic agents to particular tissues or cells in a subject. The composition disclosed herein combines unique properties of porous micro- or nano-particles with host-guest chemistry provided by functionalized silicon particle, offering a versatile approach to addressing the challenges associated with delivering therapeutic agents to target tissues or sites within the body. The present disclosure also provides a method for synthesizing a composition capable of delivering therapeutic agents to particular tissues or cells in a subject.
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主要参考文献


1: Yonesaka K. Updated result from the phase 2 PHAROS study: has the sustained efficacy and tolerability of encorafenib plus binimetinib been demonstrated in patients with BRAF V600E-mutant metastatic non-small-cell lung cancer? J Thorac Dis. 2025 Dec 31;17(12):10605-10608. doi: 10.21037/jtd-2025-1908. Epub 2025 Dec 24.
2: Rose AAN, Maxwell J, Rousselle E, Mukonoweshuro CL, Elkholi IE, Riaud M, Biondini M, Cianfarano E, Soria-Bretones I, Tobin C, McGuire M, Law RWY, Elia AJ, Wang BX, King I, Zhang T, Pugh TJ, Kamil ZS, Butler M, Shepherd FA, Leighl NB, Razak AA, Hansen A, Saibil SD, Bedard PL, Siegel PM, Siu LL, Cescon DW, Spreafico A. Binimetinib and encorafenib for the treatment of advanced solid tumors with non-V600E BRAF mutations: results from the Phase II BEAVER trial. Nat Commun. 2026 Jan 3. doi: 10.1038/s41467-025-68076-7. Epub ahead of print. 50(1):102746. doi: 10.1016/j.clinre.2025.102746. Epub 2025 Dec 16. encorafenib for colorectal cancer, daratumumab for multiple myeloma, repotrectinib for NTRK-fusion positive solid tumors, and venetoclax for leukemia. Int J Clin Oncol. 2025 Dec 15. doi: 10.1007/s10147-025-02939-3. Epub ahead of print. 117(3):104529. English, Spanish. doi: 10.1016/j.ad.2025.104529. Epub ahead of print. 17(1):87. doi: 10.1007/s12672-025-04265-6.
7: Onaga R, Enokida T, Tomioka T, Sakashita S, Sato M, Tanaka N, Hoshi Y, Kishida T, Kuboki R, Fujisawa T, Okano S, Matsuura K, Tahara M. Intracranial antitumor efficacy of combination treatment with encorafenib plus binimetinib in BRAF V600E-mutated anaplastic thyroid carcinoma. Auris Nasus Larynx. 2025 Dec 4;53(1):7-12. doi: 10.1016/j.anl.2025.11.007. Epub ahead of print. 44(1):103-108. doi: 10.1080/07357907.2025.2595301. Epub 2025 Dec 4. 153(1):103446. doi: 10.1016/j.annder.2025.103446. Epub ahead of print. 21(28):3585-3588. doi: 10.1080/14796694.2025.2579882. Epub 2025 Nov 13.
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