[3-(tert-butyldimethylsilanyloxy)-(1S)-(N-methoxy-N-methylcarbamoyl)propyl]carbamic acid tert-butyl ester | 915194-01-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [3-(tert-butyldimethylsilanyloxy)-(1S)-(N-methoxy-N-methylcarbamoyl)propyl]carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-{(S)-4-[(tert-butyldimethylsilyl)oxy]-1-[methoxy(methyl)amino]-1-oxobutan-2-yl}carbamate；(2S)-tert-butyl (3,9,9,10,10-pentamethyl-4-oxo-2,8-dioxa-3-aza-9-silaundecan-5-yl)carbamate
• CAS: 915194-01-3
• 化学式: C₁₇H₃₆N₂O₅Si
• 分子量: 376.569
• InChiKey: ICYTXANNYRZSEF-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.31
• 重原子数：
  25.0
• 可旋转键数：
  7.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  77.1
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  [3-(tert-butyldimethylsilanyloxy)-(1S)-(N-methoxy-N-methylcarbamoyl)propyl]carbamic acid tert-butyl ester 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 [(1S)-(2-hydroxyethyl)-2-oxohex-5-enyl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  Inhibition of P-glycoprotein-mediated multidrug efflux by aminomethylene and ketomethylene analogs of reversins

  摘要：

  Several aminomethylene analogs and a ketomethylene analog of reversins were synthesized in order to evaluate their ability to inhibit P-glycoprotein-mediated drug efflux in K562/R7 human leukemic cells overexpressing P-glycoprotein. These analogs retained good activity compared to cyclosporin A and the original reversins. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.07.059
• 作为产物：
  描述：

  (S)-2-氨基-4-((叔丁基二甲基甲硅烷基)氧基)丁酸 在 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 36.0h， 生成 [3-(tert-butyldimethylsilanyloxy)-(1S)-(N-methoxy-N-methylcarbamoyl)propyl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  Inhibition of P-glycoprotein-mediated multidrug efflux by aminomethylene and ketomethylene analogs of reversins

  摘要：

  Several aminomethylene analogs and a ketomethylene analog of reversins were synthesized in order to evaluate their ability to inhibit P-glycoprotein-mediated drug efflux in K562/R7 human leukemic cells overexpressing P-glycoprotein. These analogs retained good activity compared to cyclosporin A and the original reversins. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.07.059

文献信息

• Macrocyclic BACE1 inhibitors with hydrophobic cross-linked structures: Optimization of ring size and ring structure
  作者：Takuya Otani、Yasunao Hattori、Kenichi Akaji、Kazuya Kobayashi

  DOI：10.1016/j.bmc.2021.116517

  日期：2021.12

  Based on the X-ray crystallography of recombinant BACE1 and a hydroxyethylamine-type peptidic inhibitor, we introduced a cross-linked structure between the P1 and P3 side chains of the inhibitor to enhance its inhibitory activity. The P1 and P3 fragments bearing terminal alkenes were synthesized, and a ring-closing metathesis of these alkenes was used to construct the cross-linked structure. Evaluation

  基于重组 BACE1 和羟乙胺型肽抑制剂的 X 射线晶体学，我们在抑制剂的 P1 和 P3 侧链之间引入了交联结构，以增强其抑制活性。合成了带有末端烯烃的P1和P3片段，并使用这些烯烃的闭环复分解来构建交联结构。使用具有不同侧链长度的 P1 和 P3 片段评估环大小表明，13 元环是最佳的，尽管它们的活性与母体化合物相比有所降低。此外，发现最佳环结构是在 P3 β 位具有二甲基支链取代基的大环，其活性比未取代的大环高约 100 倍。此外，
• Synthesis of Ureidomuraymycidine Derivatives for Structure– Activity Relationship Studies of Muraymycins
  作者：Bilal A. Aleiwi、Christopher M. Schneider、Michio Kurosu

  DOI：10.1021/jo300205b

  日期：2012.4.20

  One of the key constituents of the muraymycins is the 6-membered cyclic guanidine, (2S,3S)-muraymycidine (or epi-capreomycidine). In order to diversify the structure of the oligopeptide moiety of the muraymycins for thorough structure activity relationship studies, we have developed a highly stereoselective synthesis of ureidomuraymycidine derivatives with the lactone 4a.
• Potent and Fully Noncompetitive Peptidomimetic Inhibitor of Multidrug Resistance P-Glycoprotein
  作者：Ophélie Arnaud、Ali Koubeissi、Laurent Ettouati、Raphaël Terreux、Ghina Alamé、Catherine Grenot、Charles Dumontet、Attilio Di Pietro、Joëlle Paris、Pierre Falson

  DOI：10.1021/jm100839w

  日期：2010.9.23

  N-alpha-Boc-L-Asp(OBn)-L-Lys(Z)-OtBu (reversin 121, I), an inhibitor of the P-gp ABC transporter, was used to conceive compounds inhibiting the drug efflux occurring through the Hoechst 33342 and daunorubicin transport sites of P-gp, respectively H and R sites. Replacement of the aspartyl residue by trans-4-hydroxy-L-proline (4(R)Hyp) gave compounds 11 and 15 characterized by half-maximal inhibitory concentrations (1050) of 0.6 and 0.2 mu M, which are 2- and 7-fold lower than that of the parent molecule. The difference in IC50 between 11 and 15 rests on the carbonyl group of the peptidyl bond, reduced in 15. Those compounds are rather specific of P-gp, having no or limited activity on MRP1 and BCRP. 15 displayed no marked cytotoxicity up to 10-fold its IC50. Importantly, 15 equally inhibited the Hoechst 33342 and daunorubicin effluxes through a typical noncompetitive inhibition mechanism, suggesting its binding to a site different from the and R drug-transport sites.