tert-butyl (S)-(1-cyclohexyl-2-(methylamino)-2-oxoethyl)carbamate | 862118-89-6

• 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: tert-butyl (S)-(1-cyclohexyl-2-(methylamino)-2-oxoethyl)carbamate
• 英文别名: ((s)-Cyclohexyl-methylcarbamoyl-methyl)-carbamic acid tert-butyl ester；tert-butyl N-[(1S)-1-cyclohexyl-2-(methylamino)-2-oxoethyl]carbamate
• CAS: 862118-89-6
• 化学式: C₁₄H₂₆N₂O₃
• 分子量: 270.372
• InChiKey: BLPKSXYXJXRXTO-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-(1-cyclohexyl-2-(methylamino)-2-oxoethyl)carbamate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.84h， 生成 L-isoleucyl-L-cyclohexylglycine methyl amide
  参考文献：
  名称：

  Squaric Acid-Based Peptidic Inhibitors of Matrix Metalloprotease-1

  摘要：

  A series of squaric acid-peptide conjugates were synthesized and evaluated as inhibitors of MMP-1. The cyclobut-3-enedione core was substituted at the 3-position with several functional groups, such as -N(alkyl)OH, -NHOH, and -OH, that are designed to bind to the zinc atom in the active site of the metalloprotease. The 4-position of the cyclobut-3-enedione was derivatized with mono- or dipeptides that are designed to bind in the S1' and S2' subsites of the enzyme, and position the metal chelating group appropriately in the active site for binding to zinc. Positional scanning revealed that -N(Me)OH provided the highest level of inhibition among the chelating groups that were tested, and Leu-Tle-NHMe was the preferred amino acid sequence. A combination of these groups yielded an inhibitor with an IC50 value of 95 mu M. For one inhibitor, conversion of one of the carbonyl groups on the cyclobut-3-enedione core to a thiocarbonyl group resulted in a 18-fold increase in potency, and yielded a compound with an IC50 value of 15 mu M.

  DOI：

  10.1021/jo0517848
• 作为产物：
  描述：

  Boc-L-环己基甘氨酸 在 盐酸甲胺 作用下， 以76%的产率得到tert-butyl (S)-(1-cyclohexyl-2-(methylamino)-2-oxoethyl)carbamate
  参考文献：
  名称：

  HCV NS-3 serine protease inhibitors

  摘要：

  HCV抑制剂，包含这些化合物作为活性成分的组合物，以及制备这些化合物的方法，其化学式为：其中A是

  公开号：

  EP1881002A1

文献信息

• Structure-Based Design and Synthesis of Potent and Selective Matrix Metalloproteinase 13 Inhibitors
  作者：Jun Yong Choi、Rita Fuerst、Anna M. Knapinska、Alexander B. Taylor、Lyndsay Smith、Xiaohang Cao、P. John Hart、Gregg B. Fields、William R. Roush

  DOI：10.1021/acs.jmedchem.7b00514

  日期：2017.7.13

  molecular design to develop potent and selective inhibitors (10d and (S)-17b) of matrix metalloproteinase 13 (MMP-13). We applied a three-step process, starting with a comparative analysis of the X-ray crystallographic structure of compound 5 in complex with MMP-13 with published structures of known MMP-13·inhibitor complexes followed by molecular design and synthesis of potent but nonselective zinc-chelating

  我们描述了使用比较结构分析和结构指导的分子设计来开发基质金属蛋白酶13（MMP-13）的有效和选择性抑制剂（10d和（S）-17b）。我们采用了三步过程，首先比较了化合物5与MMP-13的X射线晶体学结构，并比较了已知MMP-13·抑制剂配合物的结构，然后进行了分子设计和有效但非选择性的合成锌螯合MMP抑制剂（例如10a和10b）。在证明螯合抑制剂（S）-10a，（R）-图10a和10b结合在MMP-13活性位点内，Zn 2+螯合单元被桥接在Zn 2+结合位点上并到达溶剂可及区域的非螯合极性残基代替。经过两轮结构优化后，这些设计方法导致了小分子MMP-13抑制剂10d和（S）-17b，它们在MMP-13的底物结合位点内结合并包围具有催化活性的Zn 2+离子而不会与金属。这些化合物相对于其他MMP表现出至少500倍的选择性。
• [EN] SELECTIVE MATRIX METALLOPROTEINASE-13 INHIBITORS<br/>[FR] INHIBITEURS SÉLECTIFS DE MÉTALLOPROTÉINASES-13 MATRICIELLES
  申请人：FLORIDA ATLANTIC UNIV BOARD OF TRUSTEES

  公开号：WO2018226837A1

  公开（公告）日：2018-12-13

  We describe the use of comparative structural analysis and structure-guided molecular design to develop potent and selective inhibitors (10d and (S)-17b) of matrix metalloproteinase 13 (MMP-13). We applied a three-step process, starting with a comparative analysis of the X-ray crystallographic structure of compound 5 in complex with MMP-13 with published structures of known MMP-13inhibitor complexes followed by molecular design and synthesis of potent, but non-selective zinc-chelating MMP inhibitors (e.g., 10a and 10b). After demonstrating that the pharmacophores of the chelating inhibitors (S)-10a, (R)-10a, and 10b were binding within the MMP-13 active site, the Zn2+ chelating unit was replaced with non-chelating polar residues that bridged over the Zn2+ binding site and reach into a solvent accessible area. After two rounds of structural optimization, these design approaches led to small molecule MMP-13 inhibitors 10d and (S)-17b which bind within the substrate-binding site of MMP-13 and surround the catalytically active Zn2+ ion without chelating to the metal. These compounds exhibit at least 500-fold selectivity versus other MMPs.

  我们描述了比较结构分析和结构引导的分子设计的使用，以开发针对基质金属蛋白酶13（MMP-13）的有效且选择性抑制剂（10d和（S）-17b）。我们应用了一个三步过程，首先是对化合物5与MMP-13复合物的X射线晶体结构进行比较分析，然后与已知的MMP-13抑制剂复合物的已发表结构进行比较，接着进行分子设计和合成有效但非选择性的锌螯合MMP抑制剂（例如10a和10b）。在证明了螯合抑制剂（S）-10a、（R）-10a和10b的药效团结合在MMP-13活性位点内后，Zn2+螯合单元被替换为桥接到Zn2+结合位点并伸入溶剂可接触区域的非螯合极性残基。经过两轮结构优化，这些设计方法导致小分子MMP-13抑制剂10d和（S）-17b，它们结合在MMP-13的底物结合位点，并围绕着催化活性的Zn2+离子，而不与金属螯合。这些化合物与其他MMP至少具有500倍的选择性。
• HCV NS-3 Serine Protease Inhibitors
  申请人：Rosenquist Asa

  公开号：US20100003216A1

  公开（公告）日：2010-01-07

  Compounds of the formula where the variables are as defined in the specification inhibit the NS3 protease of flavivirus sych as hepatitis C virus (HCV). The compounds comprise a novel linkage between a heterocyclic P2 unit and those portions of the inhibitor more distal to the nominal cleavage site of the native substrate, which linkage reverses the orientation of peptidic bonds on the distal side relative to those proximal to the cleavage site.

  式中的变量如规范中所定义，可以抑制黄热病病毒(NS3蛋白酶)等黄病毒的蛋白酶，如丙型肝炎病毒(HCV)。这些化合物包括一个新的链接，连接一个杂环P2单位和那些离原生底物的名义剪切位点更远的抑制剂部位，该链接将离剪切位点远侧的肽键的方向与靠近剪切位点的肽键的方向相反。
• Hcv ns-3 serine protease inhibitors
  申请人：Rosenquist Asa

  公开号：US20070161574A1

  公开（公告）日：2007-07-12

  Compounds of the formula where the variables are as defined in the specification inhibit the NS3 protease of flavivirus such as hepatitis C virus (HCV). The compounds comprise a novel linkage between a heterocyclic P2 unit and those portions of the inhibitor more distal to the nominal cleavage site of the native substrate, which linkage reverses the orientation of peptidic bonds on the distal side relative to those proximal to the cleavage site.

  式子中的变量如规范所定义，能够抑制类黄病毒的NS3蛋白酶，例如丙型肝炎病毒（HCV）。这些化合物包括一种新颖的连接方式，连接了一个杂环P2单元和抑制剂更远离天然底物裂解位点的部分，该连接方式反转了远离裂解位点的肽键方向相对于靠近裂解位点的肽键方向。
• Hcv Ns-3 Serine Protease Inhibitors
  申请人：Rosenquist Asa

  公开号：US20070203072A1

  公开（公告）日：2007-08-30

  Peptidomimetic compounds are described which inhibit the NS3 protease of the hepatitis C virus (HCV). The compounds have the formula where the variable definitions are as provided in the specification. The compounds comprise a carbocyclic P2 unit in conjunction with a novel linkage to those portions of the inhibitor more distal to the nominal cleavage site of the native substrate, which linkage reverses the orientation of peptidic bonds on the distal side relative to those proximal to the cleavage site.

  本文描述了一种抑制丙型肝炎病毒（HCV）的NS3蛋白酶的肽类类似物化合物。该化合物的化学式中，变量定义如规范中所提供。该化合物包括一个碳环P2单元，与抑制剂更远离天然底物的名义剪切位点的那些部分的新型连接结合，该连接将远侧的肽键方向相对于靠近剪切位点的肽键反转。