(S)-4-benzyl-3-(3-phenylbutanoyl)oxazolidin-2-one | 170450-77-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (S)-4-benzyl-3-(3-phenylbutanoyl)oxazolidin-2-one
• 英文别名: (S)-4-benzyl-3-(4-phenylbutanoyl)oxazolidin-2-one；4(S)-benzyl-3-(4-phenylbutanoyl)-2-oxazolidinone；4S-benzyl-3-(4-phenylbutanoyl)-oxazolidin-2-one；(4S)-4-benzyl-3-(4-phenylbutanoyl)-1,3-oxazolidin-2-one
• CAS: 170450-77-8
• 化学式: C₂₀H₂₁NO₃
• 分子量: 323.392
• InChiKey: YBRNOEDQAAWPSA-SFHVURJKSA-N

物化性质

• 沸点：
  511.2±29.0 °C(Predicted)
• 密度：
  1.195±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-4-benzyl-3-(3-phenylbutanoyl)oxazolidin-2-one 在 palladium on activated charcoal lithium hydroxide 、 氢气 、 双氧水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 、 lithium diisopropyl amide 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， -78.0~25.0 ℃ 、294.18 kPa 条件下， 反应 3.0h， 生成 (R)-N*4*-Hydroxy-N*1*-((S)-methylcarbamoyl-phenyl-methyl)-2-phenethyl-succinamide
  参考文献：
  名称：

  Inhibition of Membrane-Type 1 Matrix Metalloproteinase by Hydroxamate Inhibitors:  An Examination of the Subsite Pocket

  摘要：

  The membrane-type 1 matrix metalloproteinase (MT1-MMP) has been reported to mediate the activation of pro-gelatinase A (proMMP-2), which is associated with tumor proliferation and metastasis. MT1-MMP can also digest extracellular matrix (ECM) such as interstitial collagens, gelatin, and proteoglycan and thus may play an important role in pathophysiological digestion of ECM. We studied the inhibitory effect of various hydroxamate MMP inhibitors, including known inhibitors such as BB-94, BB-2516, GM6001, and Ro31-9790, on a deletion mutant of MT1-MMP lacking the transmembrane domain (Delta MT1) to further characterize the enzyme and develop a selective inhibitor for MT1-MMP. The evaluation of the inhibitory activities of various hydroxamates reveals general structural profiles affecting selectivities toward MMPs. In particular, a longer side chain at the P1' position is preferable for the binding to MMP-2, -3, and -9 and MT1-MMP. For the P2' position, an a-branched alkyl group is critical for the binding toward Delta MT1, while the introduction of a bulky group at the a-position of hydroxamic acid seems to diminish the activity against Delta MT1. Summation of the data on the sensitivity of Delta MT1 to various hydroxamate inhibitors indicates that (1) the volume of the S1' subsite of Delta MT1 is similar to that of MMP-2, -3, and -9, which is bigger than that of MMP-1, and (2) the S1 and S2' subsites are narrower than those in other MMPs. On the basis of these results, the hydroxamates with a P1' phenylpropyl and P2' alpha-branched alkyl group were synthesized and evaluated for inhibitory activity. These inhibitors (1h,i) showed strong activity against Delta MT1 over MMP-1, but no selectivity between Delta MT1 and MMP-9. These results are explained using molecular modeling studies conducted on MT1-MMP.

  DOI：

  10.1021/jm970404a
• 作为产物：
  描述：

  3-苯丙烯溴酸酯 在 palladium hydroxide - carbon 正丁基锂 、 草酰氯 、 氢气 作用下， 以 溶剂黄146 为溶剂， 生成 (S)-4-benzyl-3-(3-phenylbutanoyl)oxazolidin-2-one
  参考文献：
  名称：

  Orally active inhibitors of stromelysin-1 (MMP-3)

  摘要：

  Further development of N-carboxyalkyl dipeptide inhibitors of stromelysin-l (MMP-3) led to the discovery of C-carboxyalkyl dipeptide analogs with improved oral bioavailability. An in vivo assay of human MMP-3 mediated degradation of a macromolecular substrate in an extravascular space is described and inhibition studies are reported. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0960-894x(96)00109-6

文献信息

• The Mechanism of Caseinolytic Protease (ClpP) Inhibition
  作者：Malte Gersch、Felix Gut、Vadim S. Korotkov、Johannes Lehmann、Thomas Böttcher、Marion Rusch、Christian Hedberg、Herbert Waldmann、Gerhard Klebe、Stephan A. Sieber

  DOI：10.1002/anie.201204690

  日期：2013.3.4

  Catch me if you can: The ClpP protease mediates protein homeostasis and can be efficiently inhibited by β‐lactones. A combination of molecular docking, mutagenesis, activity‐based protein profiling, and kinetics studies now reveals the mechanism of ClpP inhibition. A hydrophobic pocket next to the active site allows binding of long aliphatic and aromatic residues. The preferred stereoisomer binds into

  如果可以，请联系我：ClpP蛋白酶介导蛋白质稳态，并且可以被β-内酯有效地抑制。分子对接，诱变，基于活性的蛋白质谱分析和动力学研究相结合，现在揭示了ClpP抑制的机制。活性位点旁边的疏水口袋允许长的脂肪族和芳香族残基结合。优选的立体异构体结合到氧阴离子孔中。
• [EN] HYDROXY FORMAMIDE DERIVATIVES AND THEIR USE<br/>[FR] DÉRIVÉS D'HYDROXY FORMAMIDE ET LEUR UTILISATION
  申请人：GLAXOSMITHKLINE IP NO 2 LTD

  公开号：WO2015104684A1

  公开（公告）日：2015-07-16

  Disclosed are compounds having the formula (I): wherein R1, R2 and R3 are as defined herein, and methods of making and using the same, including use as inhibitors of BMP1, TLL1 and/or TLL2 and in treatment of diseases associated with BMP1, TLL1 and/or TLL2 activity.

  揭示了具有以下化学式（I）的化合物：其中R1、R2和R3如本文所定义，并且制备和使用这些化合物的方法，包括用作BMP1、TLL1和/或TLL2的抑制剂以及用于治疗与BMP1、TLL1和/或TLL2活性相关的疾病。
• HYDROXY FORMAMIDE DERIVATIVES AND THEIR USE
  申请人：GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED

  公开号：US20160340328A1

  公开（公告）日：2016-11-24

  Disclosed are compounds having the formula: wherein R1, R2 and R3 are as defined herein, and methods of making and using the same, including use as inhibitors of BMP1, TLL1 and/or TLL2 and in treatment of diseases associated with BMP1, TLL1 and/or TLL2 activity.

  揭示了具有以下公式的化合物：其中R1、R2和R3如本文所定义，并且制备和使用这些化合物的方法，包括用作BMP1、TLL1和/或TLL2的抑制剂以及用于治疗与BMP1、TLL1和/或TLL2活性相关的疾病。
• Total Synthesis of Stipiamide and Designed Polyenes as New Agents for the Reversal of Multidrug Resistance
  作者：Merritt B. Andrus、Salvatore D. Lepore、Timothy M. Turner

  DOI：10.1021/ja972603p

  日期：1997.12.17

  dihydroxylation of the terminal olefin of nonconjugated diene 7 using the Sharpless AD-mix reagent. The precursor to 16, (E,Z)-stannyl diene ester 13, was assembled with high selectivity in a single operation using a tandem syn-addition of tributyltin cuprate to acetylene followed by conjugate addition to ethyl propiolate. Structural variants 2 and 3 were assembled using palladium-catalyzed Sonogashira

  (-)-stipiamide (1) 的合成与设计的 enynes 2（6,7-dehydrostipiamide）和 3 一起被报道，它们现在被证明可以逆转人类乳腺癌细胞 (MCF-7adrR) 的多药耐药性 (MDR) . 使用 Stille 偶联与 (E)-乙烯基碘 17 和 (Z)-stannyl 酰胺 16 以 78% 的产率组装 Stipiamide。(E)-乙烯基碘化物 17 使用 Takai 反应和非共轭二烯 7 的末端烯烃的选择性二羟基化反应制备，使用 Sharpless AD-mix 试剂。使用三丁基铜酸锡与乙炔的串联顺式加成，然后与丙炔酸乙酯共轭加成，在单次操作中以高选择性组装 16, (E,Z)-甲锡二烯酯 13 的前体。结构变体 2 和 3 使用钯催化的 Sonogashira 偶联与乙烯基碘化物 17 和 35 以及乙炔 22 和 26 以接近 1:1 的化学计量比以高产率组装。发现化合物
• Condensation of Carboxylic Acids with Non-Nucleophilic <i>N</i>-Heterocycles and Anilides Using Boc₂O
  作者：Atsushi Umehara、Hirofumi Ueda、Hidetoshi Tokuyama

  DOI：10.1021/acs.joc.6b02097

  日期：2016.11.18

  A novel condensation reaction of carboxylic acids with various non-nucleophilic N-heterocycles and anilides was developed. The reaction proceeds in the presence of di-tert-butyl dicarbonate (Boc2O), catalytic 4-(dimethylamino)pyridine (DMAP), and 2,6-lutidine and is applicable to the acylation of a wide range of non-nucleophilic nitrogen compounds, including indoles, pyrroles, pyrazole, carbazole,

  开发了一种新型的羧酸与各种非亲核N-杂环和苯甲酸酯的缩合反应。在二-的存在下该反应进行叔丁基酯（BOC 2 O），催化4-（二甲氨基）吡啶（DMAP），和2,6-二甲基吡啶，并适用于范围广泛的非亲核的酰化具有高官能团相容性的氮化合物，包括吲哚，吡咯，吡唑，咔唑，内酰胺，恶唑烷酮和苯甲酸酯。还研究了吲哚，羧酸和苯胺的范围。