R-3-[1-((1S)-4-benzyl-2-oxo-oxazolidin-3-yl)-methanoyl]-dadecanoic acid tert-butyl ester | 245652-05-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: R-3-[1-((1S)-4-benzyl-2-oxo-oxazolidin-3-yl)-methanoyl]-dadecanoic acid tert-butyl ester
• 英文别名: 4(S)-benzyl-3-[2-(R)-[(tert-butoxycarbonyl)methyl]undecanoyl]-2-oxazolidinone；tert-butyl (3R)-3-[(4S)-4-benzyl-2-oxo-1,3-oxazolidine-3-carbonyl]dodecanoate
• CAS: 245652-05-5
• 化学式: C₂₇H₄₁NO₅
• 分子量: 459.626
• InChiKey: XOFRZMJSKWDNIB-PKTZIBPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  33
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  R-3-[1-((1S)-4-benzyl-2-oxo-oxazolidin-3-yl)-methanoyl]-dadecanoic acid tert-butyl ester 在 lithium hydroxide 、 双氧水 、 sodium nitrite 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.5h， 生成 R-2-nonyl-succinic acid 4-t-butyl ester
  参考文献：
  名称：

  Novel mmp-2/mmp-9 inhibitors

  摘要：

  提供了新型MMP-2/MMP-9抑制剂及其使用方法。

  公开号：

  US20030225272A1
• 作为产物：
  描述：

  十一烷酰氯 在 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 生成 R-3-[1-((1S)-4-benzyl-2-oxo-oxazolidin-3-yl)-methanoyl]-dadecanoic acid tert-butyl ester
  参考文献：
  名称：

  Inhibition of Matrix Metalloproteinases: An examination of the S1′ pocket

  摘要：

  Peptidomimetic carboxylate- and hydroxamate-based inhibitors of matrix metalloproteinases containing extended P1' groups have been prepared. Potent inhibition and good selectivity for MMP-2 has been observed for the compounds produced. (C) 1997, Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(96)00602-6

文献信息

• Novel mmp-2/mmp-9 inhibitors
  申请人：——

  公开号：US20030225272A1

  公开（公告）日：2003-12-04

  Novel MMP-2/MMP-9 inhibitors and methods of using them are provided.

  提供了新型MMP-2/MMP-9抑制剂及其使用方法。
• Oxazolidinone to succinamide: a novel rearrangement reaction
  作者：Menyan Cheng、Biswanath De、Christopher T. Wahl、Neil G. Almstead、Michael G. Natchus、Stanislaw Pikul

  DOI：10.1016/s0040-4039(99)01168-5

  日期：1999.8

  disubstituted succinimide was obtained with a high degree of stereoselectivity as the major product. Subsequent investigative work confirmed the structure and further defined the scope of this rearrangement reaction.

  在将单取代的琥珀酸半酯束缚在手性恶唑烷酮上的研究过程中，获得了以高度立体选择性为主要产物的意想不到的二取代琥珀酰亚胺。随后的调查工作证实了该结构，并进一步确定了该重排反应的范围。
• Inhibition of Matrix Metalloproteinases: An examination of the S1′ pocket
  作者：Andrew Miller、Marion Askew、R.Paul Beckett、Claire L. Bellamy、Elisabeth A. Bone、Rachael E. Coates、Alan H. Davidson、Alan H. Drummond、Philip Huxley、Fionna M. Martin、Lydia Saroglou、Alison J. Thompson、Sonja E. van Dijk、Mark Whittaker

  DOI：10.1016/s0960-894x(96)00602-6

  日期：1997.1

  Peptidomimetic carboxylate- and hydroxamate-based inhibitors of matrix metalloproteinases containing extended P1' groups have been prepared. Potent inhibition and good selectivity for MMP-2 has been observed for the compounds produced. (C) 1997, Elsevier Science Ltd.
• [EN] METHODS OF TREATMENT USING DUAL MATRIX-METALLOPROTEINASE-2 AND MATRIX METALLOPROTEINASE-9 INHIBITORS<br/>[FR] PROCEDES DE TRAITEMENT AU MOYEN D'INHIBITEURS DOUBLES DE METALLOPROTEINASE-2 MATRICIELLE ET DE METALLOPROTEINASE-9 MATRICIELLE
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2001026671A1

  公开（公告）日：2001-04-19

  The invention relates to a method for treating a patient suffering from pain or stroke, said method comprising the step of administering to the patient a pain-treating effective amount of a dual inhibitor of human MMP-2 (SEQ ID NO:2) and MMP-9 (SEQ ID NO:4) in combination with a carrier.
• Inhibition of Membrane-Type 1 Matrix Metalloproteinase by Hydroxamate Inhibitors:  An Examination of the Subsite Pocket
  作者：Minoru Yamamoto、Hideki Tsujishita、Noriyuki Hori、Yuichi Ohishi、Shintaro Inoue、Shoji Ikeda、Yasunori Okada

  DOI：10.1021/jm970404a

  日期：1998.4.1

  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.