benzyl 2-methylene-4-phenylbutanoate | 118786-28-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: benzyl 2-methylene-4-phenylbutanoate
• 英文别名: Benzyl 2-methylene-4-phenyl-butanoate；benzyl 2-methylidene-4-phenylbutanoate
• CAS: 118786-28-0
• 化学式: C₁₈H₁₈O₂
• 分子量: 266.34
• InChiKey: CMGTVKCTPMIWAO-UHFFFAOYSA-N

物化性质

• 沸点：
  387.8±21.0 °C(Predicted)
• 密度：
  1.076±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  benzyl 2-methylene-4-phenylbutanoate 在 palladium on activated charcoal sodium hydroxide 、 N,O-双三甲硅基乙酰胺 、 氢气 、 N,N-二异丙基乙胺 、 N,N'-羰基二咪唑 、 四甲基胍 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 为溶剂， 生成 [4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-butyl]-[(S)-2-((S)-3-methyl-1-phenylcarbamoyl-butylcarbamoyl)-4-phenyl-butyl]-phosphinic acid
  参考文献：
  名称：

  Phosphinic acid inhibitors of matrix metalloproteinases

  摘要：

  The matrix metalloproteinase stromelysin-1 (MMP-3) is inhibited more strongly by peptidyl phosphinic acid 7 than by its corresponding phosphonamidate and phosphonate analogs. Extending a benzyl group at P-1' to a phenylethyl group in 8 further increases the potency (K-i = 1.4 nM). Enhanced potency with an extended substituent into the P-3 region was observed.

  DOI：

  10.1016/0960-894x(96)00023-6
• 作为产物：
  描述：

  2-phenylethylmalonic acid 在 potassium carbonate 、 三乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 benzyl 2-methylene-4-phenylbutanoate
  参考文献：
  名称：

  Design and Pharmacological Activity of Phosphinic Acid Based NAALADase Inhibitors

  摘要：

  A novel series of phosphinic acid based inhibitors of the neuropeptidase NAALADase are described in this work. This series of compounds is the most potent series of inhibitors of the enzyme described to date. In addition, we have shown that these compounds are protective in animal models of neurodegeneration. Compound 34 significantly prevented neurodegeneration in a middle cerebral artery occlusion model of cerebral ischemia. In addition, in the chronic constrictive mc del of neuropathic pain, compound 34 significantly attenuated the hypersensitivity observed with saline-treated animals. These data suggest that NAALADase inhibition may provide a new approach for the treatment of both neurodegenerative disorders and peripheral neuropathies.

  DOI：

  10.1021/jm0001774

文献信息

• Visible-Light-Mediated Manganese-Catalyzed Allylation Reactions of Unactivated Alkyl Iodides
  作者：Xiaochen Wang、Jianyang Dong、Yongqiang Li、Yuxiu Liu、Qingmin Wang

  DOI：10.1021/acs.joc.0c00861

  日期：2020.6.5

  report a protocol for visible-light-mediated allylation reactions between unactivated alkyl iodides and allyl sulfones under mild conditions with catalysis by inexpensive and readily available Mn2(CO)10. This protocol is compatible with a wide array of sensitive functional groups and has a broad substrate scope with regard to both alkyl iodides and allyl sulfones.

  在这里，我们报告协议的可见光介导的烯化反应未活化的烷基碘和烯丙基砜之间的温和条件下由廉价和容易获得的Mn 2（CO）10催化。该协议与各种敏感的官能团兼容，并且对于烷基碘和烯丙基砜均具有广泛的底物范围。
• Substituted phosphinic acid-containing peptidyl derivatives as
  申请人：Merck & Co., Inc.

  公开号：US05679700A1

  公开（公告）日：1997-10-21

  Novel phosphinic acid-containing peptidyl compounds of formula I are found to be useful inhibitors of matrix metalloendoproteinase-mediated diseases including osteoarthritis, rheumatoid arthritis, septic arthritis, tumor invasion in certain cancers, periodontal disease, corneal ulceration, proteinuria, dystrophobic epidermolysis bullosa, and coronary thrombosis associated with atherosclerotic plaque rupture. These inhibitors may also be useful in preventing the pathological sequelae following a traumatic injury that could lead to permanent disability. These compounds may also have utility as a means for birth control by preventing ovulation or implantation. ##STR1##

  发现具有化学式I的新型含膦酸的肽类化合物可用作基质金属蛋白酶介导疾病的有效抑制剂，包括骨关节炎、类风湿关节炎、脓性关节炎、某些癌症中的肿瘤侵袭、牙周病、角膜溃疡、蛋白尿、皮肤萎缩性表皮松解症和与动脉粥样硬化斑块破裂相关的冠状动脉血栓形成。这些抑制剂还可能在预防创伤后可能导致永久残疾的病理后遗症方面发挥作用。这些化合物还可能作为一种避孕手段，通过阻止排卵或着床来实现。
• Synthesis and Structural/Functional Characterization of Selective M14 Metallocarboxypeptidase Inhibitors Based on Phosphinic Pseudopeptide Scaffold: Implications on the Design of Specific Optical Probes
  作者：Giovanni Covaleda、Pablo Gallego、Josep Vendrell、Dimitris Georgiadis、Julia Lorenzo、Vincent Dive、Francesc Xavier Aviles、David Reverter、Laurent Devel

  DOI：10.1021/acs.jmedchem.8b01465

  日期：2019.2.28

  we describe the synthesis and functional/structural characterization of a series of reversible tight-binding phosphinic pseudopeptide inhibitors that show high specificity and potency toward these proteases. Characterization of their inhibitory potential against a large variety of MCPs, combined with high-resolution crystal structures of three selected candidates in complex with human carboxypeptidase

  M14家族的金属羧肽酶（MCP）是Zn2 +依赖性外切蛋白酶，几乎存在于哺乳动物的每个组织或体液中。这些酶执行多种生理功能，并涉及多种病理，例如胰腺疾病，炎症，纤维蛋白溶解和癌症。在这里，我们描述了一系列可逆的紧密结合的次膦膦假肽抑制剂的合成和功能/结构表征，这些抑制剂对这些蛋白酶显示出高特异性和强效性。表征其对多种MCP的抑制潜能，并结合与人羧肽酶A（CPA）1结合的三个选定候选物的高分辨率晶体结构，可以解释决定M14A MCP对A型选择性的结构决定因素家庭。进一步，利用次膦假肽构架产生选择性靶向人CPA的光学探针。本文介绍的次膦酸酯假肽构成了化学探针的第一个实例，可用于选择性报告复杂培养基中的A型MCP活性。
• Phosphinic acid-based MMP-13 inhibitors that spare MMP-1 and MMP-3
  作者：Lawrence A. Reiter、Peter G. Mitchell、Gary J. Martinelli、Lori L. Lopresti-Morrow、Sue A. Yocum、James D. Eskra

  DOI：10.1016/s0960-894x(03)00413-x

  日期：2003.7

  Phosphinic acid-based inhibitors of MMP-13 have been investigated with the aim of identifying potent inhibitors with high selectivity versus MMP-1. Independent variation of the substituents on a P-1' phenethyl group and a P-2 benzyl group improved potencies in both cases around 3-fold over the unsubstituted parent. Combining improved P-1' and P-2 groups into a single molecule gave an inhibitor with a 4.5 nM IC50 against MMP-13 and which is 270-fold selective over MMP-1. (C) 2003 Elsevier Science Ltd. All rights reserved.
• Inhibition of MMP-1 and MMP-13 with phosphinic acids that exploit binding in the S2 pocket
  作者：Lawrence A. Reiter、James P. Rizzi、Jayvardan Pandit、Michael J. Lasut、Shunda M. McGahee、Vinod D. Parikh、James F. Blake、Dennis E. Danley、Ellen R. Laird、Arturo Lopez-Anaya、Lori L. Lopresti-Morrow、Mahmoud N. Mansour、Gary J. Martinelli、Peter G. Mitchell、Brian S. Owens、Thomas A. Pauly、Lisa M. Reeves、Gayle K. Schulte、Sue A. Yocum

  DOI：10.1016/s0960-894x(98)00729-x

  日期：1999.1

  Through the use of empirical and computational methods, phosphinate-based inhibitors of MMP-1 and MMP-13 that bind into the S-2 pocket of these enzymes were designed. The synthesis and testing of 2 suggested that binding was occurring as hypothesized. Structure determination of a co-crystal of 2 bound to the catalytic domain of MMP-1 confirmed the binding mode. Substituents binding into S-2, S-1', S-2' and S-3', were optimized yielding compounds with low double-digit nM IC50's against these enzymes. (C) 1999 Elsevier Science Ltd. All rights reserved.