CAS: 905579-51-3; ((1S,2S,4R)-4-(4-(((S)-2,3-Dihydro-1H-Inden-1-yl)Amino)-7H-Pyrrolo[2,3-D]Pyrimidin-7-yl)-2-Hydroxycyclopentyl)Methyl Sulfamate

该化合物是一个小分子抑制剂,主要针对NEDD8活性酶,在无处不在的蛋白质系统中起着关键作用,这种抑制干扰了电磁过程,导致通常降解的蛋白质累积,从而影响各种细胞路径,包括细胞循环调节和吸附病.Pevonedistat在治疗各种癌症,特别是血癌方面显示出潜力,目前正在临床试验中进行调查.该化合物的特点是能够诱发细胞细胞死亡,提高其他治疗剂的功效.其化学结构包括有助于其生物活动的功能组的独特组合.作为研究化合物,Pevonedistat对肿瘤学有着重大兴趣,特别是其克服现有疗法抗药性的潜力.然而,与许多调查药物一样,其安全和功效简介仍在临床环境中评估.

结构式图片

物理性质

MSDS等安全信息

上下游产品

is°Cyanate de chlorosulfonyle (1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-(hydroxymethyl)-cyclopentanol 6-(tert-butyldiphenylsilanyloxymethyl)-2,2-dimethyltetrahydr°Cyclopenta[1,3]dioxol-4-one 6-(tert-butyldiphenylsilanyloxymethyl)-2,2-dimethyltetrahydr°Cyclopenta[1,3]dioxol-4-ol

合成工艺路线路线简述

  • 1281922-83-5 = 905579-51-3
    反应条件:1.1 Reagents: Trifluoroacetic Acid Solvents: Water; 2 H,Rt
    标题:Stereoselective Synthesis Of Mln4924,An Inhibitor Of Nedd8-Activating Enzyme
    作者:Lee,Hyuk Woo; Nam,Soo Kyung; Choi,Won Jun; Kim,Hea Ok; Jeong,Lak Shin
    参考文献:Journal Of Organic Chemistry 日期:2011 卷标:76(9) 页码:3557-3561]

    905580-90-7 = 905579-51-3
    反应条件:1.1 Reagents: Triethylamine,N′-(Chlorosulfonyl)-N,N-Diphenylurea Solvents: Tetrahydrofuran; Rt -> 0 °C; 15 Min,0 °C; 2 H,0 °C1.2 Reagents: Hydrochloric Acid Solvents: Water; 0 °C; 0 °C -> Rt; 1 H,Rt1.3 Reagents: Sodium Bicarbonate Solvents: Water; Ph 8
    标题:An Inhibitor Of Nedd8-Activating Enzyme As A New Approach To Treat Cancer
    作者:Soucy,Teresa A.; Smith,Peter G.; Milhollen,Michael A.; Berger,Allison J.; Gavin,James M.; Et Al
    参考文献:Nature (London 日期:2009 卷标:458(7239) 页码:732-736]

    905580-90-7 + 1375958-75-0 = 905579-51-3
    反应条件:1.1 Solvents: Acetonitrile; Rt -> 53 °C; 5 H,53 °C; 53 °C -> 15 °C1.2 Reagents: Hydrochloric Acid Solvents: Acetonitrile,Water; 5 °C; 5 °C -> 20 °C1.3 Reagents: Sodium Bicarbonate Solvents: Water; Ph 7
    标题:Process Development And Gmp Production Of A Potent Nae Inhibitor Pevonedistat
    作者:Armitage,Ian; Elliott,Eric L.; Hicks,Frederick; Langston,Marianne; Mccarron,Ashley; Et Al
    参考文献:Organic Process Research & Development 日期:2015 卷标:19(9) 页码:1299-1307]

    905580-90-7 = 905579-51-3
    反应条件:1.1 Reagents: 2633004-37-0 Solvents: Acetonitrile; 3 H,Rt1.2 Reagents: Hydrochloric Acid Solvents: Water; Rt; 8 H,Rt
    标题:Preparation Of Sulfamates And Sulfamides Using A Selective Sulfamoylation Agent
    作者:Wang,Hai-Ming; Xiong,Chao-Dong; Chen,Xiao-Qu; Hu,Chun; Wang,Dong-Yu
    参考文献:Organic Letters 日期:2021 卷标:23(7) 页码:2595-2599
📜(1S,4R)-4-甲基环戊-2-烯甲酸甲酯盐酸盐置于叔丁基过氧化氢,硼烷四氢呋喃络合物,L-(+)-酒石酸二乙酯,Palladium On Activated Charcoal,1,4-Diazabicyclo[2.2.2]octan-1-Ium Chloride,氢气,二异丁基氢化铝,1,8-二氮杂双环[5.4.0]十一碳-7-烯,三乙胺,N,N-二异丙基乙胺体系中,用 甲醇,二氯甲烷,异丙醇,甲苯,乙腈,仲丁醇 作为反应溶剂,5.0~130.0 °C,600.01 Kpa 条件下,反应生成 氨基磺酸 [(1S,2S,4R)-4-[4-[[(1S)-2,3-二氢-1H-茚-1-基]氨基]-7H-吡咯并[2,3-D]嘧啶-7-基]-2-羟基环戊基]甲基酯
参考文献:Process Development And Gmp Production Of A Potent Nae Inhibitor Pevonedistat
标题:Process Development And Gmp Production Of A Potent Nae Inhibitor Pevonedistat
摘要:A Practical Synthesis Of A Novel Nedd8-Activating Enzyme (Nae) Inhibitor Pevonedistat (Mln4924) Is Described. Key Steps Include An Enantioselective Synthesis Of An Amino-Diol Cyclopentane Intermediate Containing Three Chiral Centers And A Novel,Regioselective Sulfamoylation Using N-(Tert-Butoxycarbonyl)-N-[(Triethylenediammonium)Sulfonyl]Azanide. The Linear Process,Involving Six Solid Isolations,Has Been Carried Out In Multiple Cgmp Productions On 15-30 Kg Scale To Produce Pevonedistat In 98% (A/a) Chemical Purity And 25% Overall Yield.
DOI:10.1021/acs.Oprd.5B00209

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主要参考文献


1: Foster JH, Reid JM, Minard C, Woodfield S, Denic KZ, Isikwei E, Voss SD, Nelson M, Liu X, Berg SL, Fox E, Weigel BJ. Phase 1 study of NEDD8 activating enzyme inhibitor pevonedistat in combination with chemotherapy in pediatric patients with recurrent or refractory solid tumors (ADVL1615). Eur J Cancer. 2024 Aug 2;209:114241. doi: 10.1016/j.ejca.2024.114241. Epub ahead of print. 14(7):738. doi: 10.3390/biom14070738.
3: Jiang Z, Li Z, Chen Y, Nie N, Liu X, Liu J, Shen Y. MLN4924 alleviates autoimmune myocarditis by promoting Act1 degradation and blocking Act1-mediated mRNA stability. Int Immunopharmacol. 2024 Sep 30;139:112716. doi: 10.1016/j.intimp.2024.112716. Epub 2024 Jul 21. 5(7):101653. doi: 10.1016/j.xcrm.2024.101653.
5: Zhou Q, Yu H, Chen Y, Ren J, Lu Y, Sun Y. The CRL3KCTD10 ubiquitin ligase-USP18 axis coordinately regulates cystine uptake and ferroptosis by modulating SLC7A11. Proc Natl Acad Sci U S A. 2024 Jul 9;121(28):e2320655121. doi: 10.1073/pnas.2320655121. Epub 2024 Jul 3.

合成参考文献


参考文献:10.1016/j.ejmech.2022.114227
摘要:Hua D, Wu X. Small-molecule inhibitors targeting small ubiquitin-like modifier pathway for the treatment of cancers and other diseases. European Journal of Medicinal Chemistry. 2022 Apr;233():114227. doi: 10.1016/j.ejmech.2022.114227.
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