4-(((tert-butyldimethylsilyl)oxy)methyl)-1H-imidazole | 127056-45-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(((tert-butyldimethylsilyl)oxy)methyl)-1H-imidazole
• 英文别名: tert-butyl(dimethyl)silyl 1H-imidazol-4-ylmethyl ether；tert-butyl-(1H-imidazol-5-ylmethoxy)-dimethylsilane
• CAS: 127056-45-5
• 化学式: C₁₀H₂₀N₂OSi
• 分子量: 212.367
• InChiKey: JNYVFHASMHPMFL-UHFFFAOYSA-N

物化性质

• 沸点：
  307.9±17.0 °C(Predicted)
• 密度：
  0.971±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.93
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  37.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(((tert-butyldimethylsilyl)oxy)methyl)-1H-imidazole 在 manganese(IV) oxide 、 sodium hydride 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正庚烷 、 二氯甲烷 、 乙基苯 为溶剂， 反应 1.5h， 生成 [4-[[Tert-butyl(dimethyl)silyl]oxymethyl]-1-(2-trimethylsilylethoxymethyl)imidazol-2-yl]-[1-[(4-chlorophenyl)methyl]indol-3-yl]methanone
  参考文献：
  名称：

  Conjugated indole-imidazole derivatives displaying cytotoxicity against multidrug resistant cancer cell lines

  摘要：

  We report herein the SAR studies of a series of indole-imidazole compounds. that demonstrate substantial in vitro anti-proliferative activities against cancer cell lines, including multidrug resistance (MDR) phenotypes. The in vitro cytotoxic effects have been demonstrated across a wide array of tumor types, including hematologic and solid tumor cell lines of various origins (e.g., leukemia, breast, colon, and uterine). (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.07.020
• 作为产物：
  描述：

  4-羟甲基咪唑盐酸盐 、 叔丁基二甲基氯硅烷 在 咪唑 、 4-二甲氨基吡啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以97.6%的产率得到4-(((tert-butyldimethylsilyl)oxy)methyl)-1H-imidazole
  参考文献：
  名称：

  Synthesis of 1,5-disubstituted imidazoles including an imidazole analogue of prostaglandin from 4(5)-hydroxymethylimidazole.

  摘要：

  1-(6-羧基己基)-5-[(E)-3-羟基-1-辛烯基]咪唑，一种前列腺素的咪唑类似物，由4(5)-羟甲基咪唑盐酸盐合成。关键步骤包括对4(5)-叔丁基二甲基硅氧甲基咪唑进行位点选择性烷基化，以得到主要1,5-二取代的咪唑。

  DOI：

  10.1248/cpb.37.1481

文献信息

• Investigations into the Potential Role of Metabolites on the Anti-Leukemic Activity of Imatinib, Nilotinib and Midostaurin
  作者：Paul W. Manley

  DOI：10.2533/chimia.2019.561

  日期：——

  The efficacy and side-effects of drugs do not just reflect the biochemical and pharmacodynamic properties of the parent compound, but often comprise of cooperative effects between the properties of the parent and active metabolites. Metabolites of imatinib, nilotinib and midostaurin have been synthesised and evaluated in assays to compare their properties as protein kinase inhibitors with the parent drugs. The N-desmethyl-metabolite of imatinib is substantially less active than imatinib as a BCR-ABL1 kinase inhibitor, thus providing an explanation as to why patients producing high levels of this metabolite show a relatively low response rate in chronic myeloid leukaemia (CML) treatment. The hydroxymethylphenyl and N-oxide metabolites of imatinib and nilotinib are only weakly active as BCR-ABL1 inhibitors and are unlikely to play a role in the efficacy of either drug in CML. The 3-(R)-HO-metabolite of midostaurin shows appreciable accumulation following chronic drug administration and, in addition to mutant forms of FLT3, potently inhibits the PDPK1 and VEGFR2 kinases (IC50 values

  药物的功效和副作用不仅仅反映了母化合物的生化和药效特性，而且通常包括母化合物和活性代谢物之间的协同效应。已经合成和评估了伊马替尼、尼洛替尼和米多斯他林的代谢物，以比较它们作为蛋白激酶抑制剂的特性与母药的区别。伊马替尼的N-去甲基代谢物作为BCR-ABL1激酶抑制剂的活性明显低于伊马替尼，这解释了为什么产生高水平该代谢物的患者在慢性髓细胞白血病（CML）治疗中显示相对较低的反应率。伊马替尼和尼洛替尼的羟甲基苯和N-氧代谢物作为BCR-ABL1抑制剂的活性很弱，不太可能在CML中发挥作用。米多斯他林的3-(R)-HO-代谢物在长期用药后显示出明显的积累，并且除了FLT3的突变形式外，还强力抑制PDPK1和VEGFR2激酶（IC50值

• [EN] ANTICANCER BENZOPYRAZINES VIA THE INHIBITION OF FGFR KINASES<br/>[FR] BENZOPYRAZINES ANTICANCÉREUSES PAR LE BIAIS DE L'INHIBITION DE FGFR KINASES
  申请人：ASTEX THERAPEUTICS LTD

  公开号：WO2013061081A1

  公开（公告）日：2013-05-02

  The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

  这项发明涉及新的喹啉衍生物化合物，包括含有该化合物的药物组合物，用于制备该化合物的方法以及该化合物在治疗疾病（例如癌症）中的用途。
• Synthesis and antibacterial activity of novel 4-pyrrolidinylthio carbapenems. Part III:
  作者：Hidenori Azami、David Barrett、Keiji Matsuda、Hideo Tsutsumi、Kenichi Washizuka、Minoru Sakurai、Satoru Kuroda、Fumiyuki Shirai、Toshiyuki Chiba、Toshiaki Kamimura、Masayoshi Murata

  DOI：10.1016/s0968-0896(99)00085-1

  日期：1999.8

  The synthesis and biological activity of a novel series of 2-alkyl-4-pyrrolidinylthio-beta-methylcarbapenems containing a variety of cationic heteroaromatic substituents is described. As a result of these studies, we uncovered a relationship between in vitro antibacterial activity and the length of the alkyl spacer part, and discovered FR20950 (1c), containing a two methylene spacer moiety and an imidazolio

  描述了含有各种阳离子杂芳族取代基的一系列新的2-烷基-4-吡咯烷基硫基-β-甲基卡巴南的合成和生物活性。这些研究的结果是，我们发现了体外抗菌活性与烷基间隔部分长度之间的关系，并发现了含有两个亚甲基间隔部分和一个咪唑基团的FR20950（1c），该基团具有均衡的抗菌谱活性，包括铜绿假单胞菌和耐甲氧西林的金黄色葡萄球菌（MRSA）。此外，FR20950表现出出色的尿液恢复能力，并且与比阿培南相比具有相对于肾脏脱氢肽酶-I（DHP-1）相当的稳定性。通过在咪唑环上引入取代基可以改善DHP-1的稳定性。
• [EN] (AZA)INDAZOLYL-ARYL SULFONAMIDE AND RELATED COMPOUNDS AND THEIR USE IN TREATING MEDICAL CONDITIONS<br/>[FR] (AZA) INDAZOLYL-ARYLE SULFONAMIDE ET COMPOSÉS APPARENTÉS ET LEUR UTILISATION DANS LE TRAITEMENT D'ÉTATS MÉDICAUX
  申请人：HIBERCELL INC

  公开号：WO2020210828A1

  公开（公告）日：2020-10-15

  The invention provides (aza)indazolyl-aryl sulfonamide and related compounds, pharmaceutical compositions, and their use in the treatment of medical conditions, such as cancer, and in inhibiting GCN2 activity.

  这项发明提供了(aza)吲哚基芳基磺酰胺及相关化合物、药物组合物，以及它们在治疗医疗状况（如癌症）和抑制GCN2活性中的用途。
• N-coating heterocyclic compounds
  申请人：——

  公开号：US20030176454A1

  公开（公告）日：2003-09-18

  A compound of the formula (I): wherein A is a hydrogen atom, an optionally substituted, unsaturated, N-containing heterocyclic group or a group of the formula (a): wherein R is an optionally substituted aryl group or an optionally substituted heterocyclic group; M is —(CH 2 )n-, —(CH 2 )n-O—(CH 2 )m-or —(CH 2 )n-NH—(CH 2 )m-, wherein n and m are independently 0, 1 or 2; Q is an optionally substituted cycloalkylene group, an optionally substituted arylene group or an optionally substituted divalent heterocyclic group; and the moiety of the formula (b): is an optionally substituted, unsaturated, mono-, di-, tri- or tetra-cyclic, N-containing heterocyclic group which may contain additional hetero atom(s) selected from the group consisting of nitrogen, oxygen and sulfur atoms as the ring member(s), its prodrug or a pharmaceutically acceptable salt thereof.

  公式(I)的化合物：其中A是氢原子，一个可选地取代的、不饱和的、含氮的杂环基团，或者公式(a)的基团：其中R是一个可选地取代的芳香族基团或者一个可选地取代的杂环基团；M是—(CH2)n-, —(CH2)n-O—(CH2)m-或—(CH2)n-NH—(CH2)m-，其中n和m各自为0、1或2；Q是一个可选地取代的环烷基烯基团、一个可选地取代的芳香族基团或者一个可选地取代的二价杂环基团；以及公式(b)的部分：是一个可选地取代的、不饱和的、单环、双环、三环或四环的、含氮的杂环基团，它可以包含作为环成员的额外杂原子，选自由氮、氧和硫原子组成的组，其前药或药用盐。