CAS: 1088965-37-0; 3-Chloro-N-((S)-1-(2-(Dimethylamino)Acetamido)-3-(4-(8-((S)-1-Hydroxyethyl)Imidazo[1,2-A]Pyridin-2-yl)Phenyl)Propan-2-yl)-4-Isopropoxybenzamide
该化合物是一个小分子,主要因其在治疗各种疾病,特别是在肿瘤学领域的潜在治疗应用而得到调查,它作为某些蛋白质动脉的选择性抑制器,在细胞发育,分化和存活的细胞信号路径中发挥着关键作用.该化合物的行动机制通常涉及调整与癌症细胞扩散和生存有关的具体途径,使其成为定向癌症治疗的候选对象.就其物理和化学特性而言,其分子结构的特点是,它包括有助于其生物活动和溶解性的具体功能组.和许多调查化合物一样,对它的药理,毒性和功效进行详细研究对于了解其作为治疗剂的潜力至关重要.为了充分阐明其在临床环境中的特点和应用,必须进行进一步的研究.
- 英文名称3-Chloro-N-((S)-1-(2-(Dimethylamino)Acetamido)-3-(4-(8-((S)-1-Hydroxyethyl)Imidazo[1,2-A]Pyridin-2-yl)Phenyl)Propan-2-yl)-4-Isopropoxybenzamide
- 中文名称3-氯-n-((s)-1-(2-(二甲基氨基)乙酰氨基)-3-(4-(8-((s)-1-羟基乙基)咪唑并[1,2-a]吡啶-2-基)苯基)丙烷-2-基)-4-异丙氧基苯甲酰胺
- IUPAC名称3-chloro-N-((S)-1-(2-(dimethylamino)acetamido)-3-(4-(8-((S)-1-hydroxyethyl)imidazo[1,2-a]pyridin-2-yl)phenyl)propan-2-yl)-4-isopropoxybenzamide
- CAS编号1088965-37-0
- MFCD编号:MFCD16038931
- FDA UNII编号:072702W9QD
- 分子式:C32H38ClN5O4分子量:592.14
- 产品CID: 124986
- 产品分类医药中间体 → 吡啶类化合物
物理性质
- 熔点197-198°C
- 沸点197-198°C
- 密度1.25
- pKa:13.12±0.20(预测)
- PSA:108.2
- LogP:5.2959
- 溶解性Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly, Sonicated)
- 外观形态淡黄色至淡黄色固体
- 储存条件-20°C 冰箱, 在惰性气其中
- 产品应用该化合物是三百三十条癌症细胞线(平均值为 GI50 = 253 NM; 中位 GI 50 = 32 NM) 的强效,选择性和止动抑制剂, 与 MEK/ERK 路径抑制剂结合, 效果会提高. 在维沃, 它在多颗固态肿瘤-色素模型中, 包括COLO205, 尤因的沙眼, ROHABIDOMOTOMA和RHABDOMIOSARCOMA 中, 有剂量依赖抗暴动作用, 导致细胞细胞细胞体细胞细胞237的细胞板块(平均为 GIM = 230 NM ; 中等GI50= 32 NM) 体内的抗扰动剂. 在第一阶段临床调查中, 它作为治疗剂, 尤其是皮肤癌.
上下游产品
1,1-dimethylethyl [(1S)-2-(4-bromophenyl)-1-(hydroxymethyl)ethyl]carbamate 1,1-dimethylethyl {(1S)-2-[4-(bromoacetyl)phenyl]-1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]ethyl}carbamate 2-amino-3-[(1S)-1-hydroxyethyl]pyridine合成工艺路线路线简述
📜1,1-Dimethylethyl [(1S)-2-(4-Bromophenyl)-1-(Hydroxymethyl)Ethyl]Carbamate置于盐酸,Bis-Triphenylphosphine-Palladium(II) Chloride,Dipotassium Hydrogenphosphate,N-溴代丁二酰亚胺(Nbs),偶氮二甲酸二异丙酯,碳酸氢钠,一水合肼,N,N-二异丙基乙胺,三苯基膦体系中,用 四氢呋喃,2-甲基四氢呋喃,1,4-二氧六环,乙醇,二氯甲烷,甲基叔丁基醚,水,乙腈 用作溶剂,化学反应 30.0H,反应生成3-氯-N-((S)-1-(2-(二甲基氨基)乙酰氨基)-3-(4-(8-((S)-1-羟基乙基)咪唑并[1,2-A]吡啶-2-基)苯基)丙烷-2-基)-4-异丙氧基苯甲酰胺
参考文献:发现和开发新型cenp-E抑制剂gsk923295A的高效,可扩展且鲁棒的路线
标题:发现和开发新型cenp-E抑制剂gsk923295A的高效,可扩展且鲁棒的路线
摘要:Cenp-E抑制剂3-Chloro-N-{(1 S)-2-[(n,N-二甲基甘氨酰)氨基]-1-[(4-{8-[描述了(1S)-1-羟乙基]咪唑并[1,2-A ]吡啶-2-基}苯基)甲基]乙基}-4-[[1-甲基乙基)氧基]苯甲酰胺(gsk923295A).通往gsk923295A的现有途径昂贵,不稳固,使用过的非理想试剂,并且始终难以提供临床研究所需的api.新的综合从容易获得的l开始-苯丙氨醇,使用关键的friedel-Crafts酰化反应以及选择性的酰化化学反应平稳地转化为gsk923295A.Gsk923295A的下游化学反应产量高且稳定,并且首先在千克规模上证明了所产生的过程,随后在成功制备了55千克的中试工厂中进行了证明.生成的过程简单,使用较便宜的原料,更绿色,因为它避免了使用铝,锡和溴化化学试剂,并且无需进行色谱纯化.还讨论了路线衍生的杂质,如何明确地准备它
Doi:10.1021/op100186C
专利信息
专利号:US-11285169-B2
优先权日:2013-03-13
标题 :Methods for modulating chemotherapeutic cytotoxicity
发明人：ROBERTS DAVID D; SOTO PANTOJA DAVID R
权利人:US HEALTH
摘要:Methods of reducing cytotoxicity of a chemotherapeutic agent to non-cancer cells by administering to a subject with cancer an effective amount of an agent that inhibits CD47 signaling and a DNA damaging agent, such as an anthracycline, topoisomerase inhibitor, or nucleotide synthesis inhibitor, are provided. Example disclosed methods reduce cardiotoxicity. In one example, the methods include administering to a subject with cancer an effective amount of a CD47 antisense morpholino oligonucleotide and an anthracycline such as doxorubicin. Methods of increasing cytotoxicity of a chemotherapeutic agent in cancer cells by administering to a subject with a tumor an effective amount of an agent that inhibits CD47 signaling and a DNA damaging agent such as an anthracycline, topoisomerase inhibitor, or nucleotide synthesis inhibitor, are also provided. In some embodiments, the inhibitor of CD47 signaling is administered to the subject before, during, or after the administration of the DNA damaging agent.
供应商参考报价(招募中)
品牌试剂参考报价(招募中)
📌 第三方产品分析报告
主要参考文献
1: Mayes PA, Degenhardt YY, Wood A, Toporovskya Y, Diskin SJ, Haglund E, Moy C, Wooster R, Maris JM. Mitogen-activated protein kinase (MEK/ERK) inhibition sensitizes cancer cells to centromere-associated protein E inhibition. Int J Cancer. 2013 Feb 1;132(3):E149-57. doi: 10.1002/ijc.27781. Epub 2012 Sep 28. doi: 10.1007/s00280-011-1756-z. Epub 2011 Oct 22. doi: 10.1002/pbc.23176. Epub 2011 May 16.
4: Balamuth NJ, Wood A, Wang Q, Jagannathan J, Mayes P, Zhang Z, Chen Z, Rappaport E, Courtright J, Pawel B, Weber B, Wooster R, Sekyere EO, Marshall GM, Maris JM. Serial transcriptome analysis and cross-species integration identifies centromere-associated protein E as a novel neuroblastoma target. Cancer Res. 2010 Apr 1;70(7):2749-58. doi: 10.1158/0008-5472.CAN-09-3844. Epub 2010 Mar 16.
5: Wood KW, Lad L, Luo L, Qian X, Knight SD, Nevins N, Brejc K, Sutton D, Gilmartin AG, Chua PR, Desai R, Schauer SP, McNulty DE, Annan RS, Belmont LD, Garcia C, Lee Y, Diamond MA, Faucette LF, Giardiniere M, Zhang S, Sun CM, Vidal JD, Lichtsteiner S, Cornwell WD, Greshock JD, Wooster RF, Finer JT, Copeland RA, Huang PS, Morgans DJ Jr, Dhanak D, Bergnes G, Sakowicz R, Jackson JR. Antitumor activity of an allosteric inhibitor of centromere-associated protein-E. Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):5839-44. doi: 10.1073/pnas.0915068107. Epub 2010 Feb 18.
合成参考文献
参考文献:10.1002/pbc.23176
摘要:Lock RB, Carol H, Morton CL, Keir ST, Reynolds CP, Kang MH, Maris JM, Wozniak AW, Gorlick R, Kolb EA, Houghton PJ, Smith MA. Initial testing of the CENP-E inhibitor GSK923295A by the pediatric preclinical testing program. Pediatr Blood Cancer. 2012 Jun;58(6):916–23.
📝 需求与反馈
尽可能描述清楚需求与问题信息
