(+/-)-methyl 2-(tert-butoxycarbonylamino)-5-phenylpent-4-ynoate | 291534-50-4

• 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: (+/-)-methyl 2-(tert-butoxycarbonylamino)-5-phenylpent-4-ynoate
• 英文别名: methyl 2-[(tert-butoxycarbonyl)amino]-5-phenyl-4-pentynoate；Methyl 2-N-boc-amino-5-phenylpent-4-ynoate；Methyl 2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-phenylpent-4-ynoate
• CAS: 291534-50-4
• 化学式: C₁₇H₂₁NO₄
• 分子量: 303.358
• InChiKey: SESIIDQHODUSLV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+/-)-methyl 2-(tert-butoxycarbonylamino)-5-phenylpent-4-ynoate 在 盐酸 、 gold(III) chloride 作用下， 以 乙酸乙酯 、 乙腈 为溶剂， 生成 甲基5-苯基-3,4-二氢-2H-吡咯-2-甲酸基酯
  参考文献：
  名称：

  含炔氨基酸的金催化环异构化：CN 与 CO 反应性的可控调节

  摘要：

  菲尔：梅德兰，诺埃莉亚·索莱达。Consejo Nacional de Investigaciones Cientificas y Tecnicas。Centro Cientifico Tecnologico Conicet - 罗萨里奥。Instituto de Quimica Rosario。罗萨里奥国立大学。Facultad de Ciencias Bioquimicas y Farmaceuticas。Instituto de Quimica Rosario；阿根廷

  DOI：

  10.1002/ejoc.201600429
• 作为产物：
  描述：

  methyl 2-aminopent-4-ynoate 在 copper(l) iodide 、 四(三苯基膦)钯 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 (+/-)-methyl 2-(tert-butoxycarbonylamino)-5-phenylpent-4-ynoate
  参考文献：
  名称：

  Development of New Carboxylic Acid-Based MMP Inhibitors Derived from Functionalized Propargylglycines

  摘要：

  A series of carboxylic acids were prepared from a propargylglycine scaffold and tested for efficacy as matrix metalloproteinase (MMP) inhibitors. Detailed SAR for the series is reported for four enzymes within the MMP family. The inhibitors were typically potent against collagenase-3 (MMP-13) and gelatinase A (MMP-2), while they spared collagenase-1 (MMP-1) and only moderately inhibited stromelysin (MMP-3). Compound 40 represents a typical inhibition profile of a compound with reasonable potency. Introduction of polar groups was required in order to generate inhibitors with acceptable water solubility, and this often resulted in a loss of potency as in compound 63. High serum protein binding proved to be a difficult hurdle with many compounds such as 48 showing > 99% binding. Some compounds such as 64 displayed similar to 90% binding, but no reliable method was discovered for designing molecules with low protein binding. Finally, selected data regarding the pharmacokinetic behavior of these compounds is presented.

  DOI：

  10.1021/jm000477l

文献信息

• Alkenyl- and alkynl-containing metalloprotease inhibitors
  申请人：The Procter & Gamble Co.

  公开号：US06197770B1

  公开（公告）日：2001-03-06

  Disclosed are compounds which are inhibitors of metalloproteases and which are effective in treating conditions characterized by excess activity of these enzymes. In particular, the compounds have a structure according to the following Formula (I): where X, W, Z, A, G, R1, R2, R3, R4, R5, R5′ and k have the meanings described in the specification. This invention also includes optical isomers, diastereomers and enantiomers of the formula above, and pharmaceutically-acceptable salts, biohydrolyzable amides, esters, and imides thereof Also described are pharmaceutical compositions comprising these compounds, and methods of treating or preventing metalloprotease-related maladies using the compounds or the pharmaceutical compositions.

  本发明涉及一类金属蛋白酶抑制剂化合物，用于治疗由这些酶活性过度引起的疾病。具体来说，这些化合物具有以下式（I）的结构，其中X、W、Z、A、G、R1、R2、R3、R4、R5、R5'和k的含义如规范中所述。本发明还包括上述式的光学异构体、顺反异构体和对映体，以及这些化合物的药用盐、生物水解酰胺、酯和亚酰胺。还描述了包含这些化合物的药物组合物，以及使用这些化合物或药物组合物来治疗或预防与金属蛋白酶相关的疾病的方法。
• Transition Metal-Catalyzed Synthesis of Novel Biologically Relevant Tryptophan Analogues
  作者：Bart C. J. van Esseveldt、Floris L. van Delft、Jan M. M. Smits、René de Gelder、Hans E. Schoemaker、Floris P. J. T. Rutjes

  DOI：10.1002/adsc.200404012

  日期：2004.6

  synthetic approach to the synthesis of novel tryptophan derivatives and benzofuran-containing amino acids is detailed. The sequence starts from enzymatically resolved enantiopure acetylene-containing amino acids, of which the acetylene function can be efficiently transformed into the targeted 2-substited indole and benzofuran moieties via Sonogashira-type coupling and metal-catalyzed cyclization.

  详细介绍了合成新型色氨酸衍生物和含苯并呋喃氨基酸的合成方法。该序列从酶促拆分的对映体纯的含乙炔的氨基酸开始，其乙炔功能可通过Sonogashira型偶联和金属催化的环化反应有效地转化为目标2取代的吲哚和苯并呋喃部分。
• Palladium-Catalyzed Synthesis of Novel Optically Active Tryptophan Analogues
  作者：Bart C. J. van Esseveldt、Floris L. van Delft、René de Gelder、Floris P. J. T. Rutjes

  DOI：10.1021/ol034360d

  日期：2003.5.1

  [reaction: see text] Both unsaturated proline derivatives and optically active tryptophan analogues have been obtained via Pd-catalyzed cyclization of aniline-containing acetylenic amino acids. The side chain length of the cyclization precursor determines which one of the two possible products will be formed.

  [反应：见正文]不饱和脯氨酸衍生物和旋光性色氨酸类似物都是通过Pd催化含苯胺基乙炔氨基酸的环化反应而获得的。环化前体的侧链长度决定了将形成两种可能产物中的哪一种。
• Gold-Catalyzed Cycloisomerization of Alkyne-Containing Amino Acids: Controlled Tuning of C-N vs. C-O Reactivity
  作者：Noelia S. Medran、Matías Villalba、Ernesto G. Mata、Sebastián A. Testero

  DOI：10.1002/ejoc.201600429

  日期：2016.8

  Medran, Noelia Soledad. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Rosario. Instituto de Quimica Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquimicas y Farmaceuticas. Instituto de Quimica Rosario; Argentina

  菲尔：梅德兰，诺埃莉亚·索莱达。Consejo Nacional de Investigaciones Cientificas y Tecnicas。Centro Cientifico Tecnologico Conicet - 罗萨里奥。Instituto de Quimica Rosario。罗萨里奥国立大学。Facultad de Ciencias Bioquimicas y Farmaceuticas。Instituto de Quimica Rosario；阿根廷
• Development of New Carboxylic Acid-Based MMP Inhibitors Derived from Functionalized Propargylglycines
  作者：Michael G. Natchus、Roger G. Bookland、Matthew J. Laufersweiler、Staszek Pikul、Neil G. Almstead、Biswanath De、Michael J. Janusz、Lily C. Hsieh、Fei Gu、Matthew E. Pokross、Vikram S. Patel、Susan M. Garver、Sean X. Peng、Todd M. Branch、Selane L. King、Timothy R. Baker、David J. Foltz、Glen E. Mieling

  DOI：10.1021/jm000477l

  日期：2001.3.1

  A series of carboxylic acids were prepared from a propargylglycine scaffold and tested for efficacy as matrix metalloproteinase (MMP) inhibitors. Detailed SAR for the series is reported for four enzymes within the MMP family. The inhibitors were typically potent against collagenase-3 (MMP-13) and gelatinase A (MMP-2), while they spared collagenase-1 (MMP-1) and only moderately inhibited stromelysin (MMP-3). Compound 40 represents a typical inhibition profile of a compound with reasonable potency. Introduction of polar groups was required in order to generate inhibitors with acceptable water solubility, and this often resulted in a loss of potency as in compound 63. High serum protein binding proved to be a difficult hurdle with many compounds such as 48 showing > 99% binding. Some compounds such as 64 displayed similar to 90% binding, but no reliable method was discovered for designing molecules with low protein binding. Finally, selected data regarding the pharmacokinetic behavior of these compounds is presented.