tert-butyl 2-(hex-5-en-1-yl)hydrazinecarboxylate | 924289-35-0

• 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 2-(hex-5-en-1-yl)hydrazinecarboxylate
• 英文别名: N'-Hex-5-enyl-hydrazinecarboxylic acid tert-butyl ester；tert-butyl N-(hex-5-enylamino)carbamate
• CAS: 924289-35-0
• 化学式: C₁₁H₂₂N₂O₂
• 分子量: 214.308
• InChiKey: MRFRTKHBPAZCPE-UHFFFAOYSA-N

物化性质

• 密度：
  0.946±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  15
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  50.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-(hex-5-en-1-yl)hydrazinecarboxylate 在 正丁基锂 作用下， 以 四氢呋喃 、 异丙醇 、 乙腈 为溶剂， 反应 5.5h， 生成 8-methyl-2-oxooctahydropyrazolo[1,5-a]pyridin-8-ium-1-ide
  参考文献：
  名称：

  利用烯烃的协同胺化反应合成氨基酰亚胺：范围和机理信息

  摘要：

  氨基酰亚胺是合适的烯基-肼衍生物的热环加成中的关键中间体。底物修饰（β- N，N-二烷基）可分离这些反应性中间体，其立体化学分析为一致的（Cope型）加氢胺化和一致的[3 + 2]氨基羰基化反应途径提供了支持。这项工作还确立了这些方法以中等到极好的产率形成复杂的氨基酰亚胺的适用性。

  DOI：

  10.1021/acs.joc.9b01259
• 作为产物：
  描述：

  5-己烯醛 、 肼基甲酸叔丁酯 在 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 以37%的产率得到tert-butyl 2-(hex-5-en-1-yl)hydrazinecarboxylate
  参考文献：
  名称：

  使用氨基异氰酸酯的协同环加成反应进行分子内烯烃氨基羰基化

  摘要：

  氮杂环在生物活性分子中的普遍存在对合成化学家提出了挑战，要求他们开发各种用于构建它们的工具。在开展肼衍生物的无金属加氢胺化反应时，发现如果就地形成氮取代的异氰酸酯（N-异氰酸酯）作为反应性中间体，则氨基甲酸酯和氨基脲也可导致烯烃氨基羰基化产物。起初，该反应需要高温（150–200°C），问题包括竞争的胺化反应和N-异氰酸酯二聚途径。在此，据报道，改善了N-异氰酸酯分子内链烯氨基羰基化的条件。βN的使用氨基甲酸苄酯的前体可以有效地使N异氰酸酯的二聚作用最小化。减少的二聚作用可提高烯烃氨基羰基化产物的收率，在较低温度下具有反应性，并改善涉及烯烃氨基羰基化然后再进行1,2-苄基迁移的反应顺序。此外，对N-异氰酸酯前体上的封端（掩蔽）基团进行了微调，并且反应条件依赖于N的碱催化由较简单的前体形成的异氰酸酯可导致室温下的反应性，从而最大程度地减少了竞争性加氢途径。总的来说，这项工作强调了氨基异氰酸酯

  DOI：

  10.1002/chem.201600574

文献信息

• Macrocyclic Inhibitors of Hepatitis C Virus
  申请人：Wahling Horst

  公开号：US20090023758A1

  公开（公告）日：2009-01-22

  Compounds of the formula (I): and N-oxides, salts and stereoisomers thereof wherein A is OR 1 , NHS(═O) p R 2 , NHR 3 , NRaRb, C(═O)NHR 3 or C(═O)NRaRb wherein; R 1 is hydrogen, C 1 -C 6 alkyl, C 0 -C 3 alkylenecarbocyclyl, C 0 -C 3 alkyleneheterocyclyl; R 2 is C 1 -C 6 alkyl, C 0 -C 3 alkylenecarbocyclyl, C 0 -C 3 alkyleneheterocyclyl or NRaRb; R 3 is C 1 -C 6 alkyl, C 0 -C 3 alkylenecarbocyclyl, C 0 -C 3 alkyleneheterocyclyl, —OC 1 -C 6 alkyl, —OC 0 -C 3 alkylenecarbocyclyl, —OC 0 -C 3 alkyleneheterocyclyl; wherein any alkyl, carbocyclyl or heterocycylyl in R 1 , R 2 or R 3 are optionally substituted p is independently 1 or 2; n is 3, 4, 5 or 6; denotes an optional double bond; Rq is H or when L is CRz, Rq can also be C 1 -C 6 alkyl; Ry and Ry′ are independently C 1 -C 6 alkyl; L is N or CRz; Rz is H or forms a double bond with the asterisked carbon; W is —CH 2 —, —O—, —OC(═O)NH—, —OC(═O)—, —S—, —NH—, —NRa, —NHS(═O) 2 —, —NHC(=0)NH— or —NHC(═O)—, —NHC(═S)NH— or a bond; R 8 is an optionally substituted ring system containing 1 or 2 saturated, partially saturated or unsaturated carbo or heterocyclic rings have utility in the inhibition of NS-3 serine proteases, such as flavivirus infections.

  式(I)的化合物：及其N-氧化物、盐和立体异构体，其中A为OR1、NHS(═O)pR2、NHR3、NRaRb、C(═O)NHR3或C(═O)NRaRb，其中；R1为氢、C1-C6烷基、C0-C3烷基环戊基、C0-C3烷基杂环戊基；R2为C1-C6烷基、C0-C3烷基环戊基、C0-C3烷基杂环戊基或NRaRb；R3为C1-C6烷基、C0-C3烷基环戊基、C0-C3烷基杂环戊基、—OC1-C6烷基、—OC0-C3烷基环戊基、—OC0-C3烷基杂环戊基；其中R1、R2或R3中的任何烷基、环戊基或杂环戊基可选择性地被取代；p独立地为1或2；n为3、4、5或6；表示可选的双键；Rq为H或当L为CRz时，Rq也可以是C1-C6烷基；Ry和Ry′独立地为C1-C6烷基；L为N或CRz；Rz为H或与带星号的碳形成双键；W为—CH2—、—O—、—OC(═O)NH—、—OC(═O)—、—S—、—NH—、—NRa、—NHS(═O)2—、—NHC(=0)NH—或—NHC(═O)—、—NHC(═S)NH—或键；R8为含有1或2个饱和、部分饱和或不饱和碳或杂环环的可选择性取代的环系统，在NS-3丝氨酸蛋白酶的抑制中具有用途，例如黄病毒感染。
• AZA-PEPTIDE MACROCYCLIC HEPATITIS C SERINE PROTEASE INHIBITORS
  申请人：Or Yat Sun

  公开号：US20080274080A1

  公开（公告）日：2008-11-06

  The present invention relates to compounds of Formula I, or a pharmaceutically acceptable salt, ester, or prodrug, thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

  本发明涉及公式I的化合物，或其药用可接受的盐、酯或前药，它们抑制丝氨酸蛋白酶活性，特别是乙型肝炎病毒（HCV）NS3-NS4A蛋白酶的活性。因此，本发明的化合物干扰了乙型肝炎病毒的生命周期，并且也可作为抗病毒药物使用。本发明进一步涉及包括上述化合物的药物组合物，用于治疗患有HCV感染的受试者。该发明还涉及通过给受试者投予包含本发明化合物的药物组合物来治疗受试者的HCV感染的方法。
• CARBOCYCLIC OXIME HEPATITIS C VIRUS SERINE PROTEASE INHIBITORS
  申请人：Liu Dong

  公开号：US20090149491A1

  公开（公告）日：2009-06-11

  The present invention discloses compounds of formula I, II, or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. More specifically, the invention relates to oxime compounds containing a carbocyclic P2 unit. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

  本发明揭示了化合物I、II的结构，或其药用可接受的盐、酯或前药：这些化合物抑制丝氨酸蛋白酶活性，特别是乙型肝炎病毒（HCV）NS3-NS4A蛋白酶的活性。因此，本发明的化合物干扰了乙型肝炎病毒的生命周期，并且还可用作抗病毒剂。更具体地，本发明涉及含有环戊二烯基P2单元的肟化合物。本发明还涉及包括上述化合物的药物组合物，用于给患有HCV感染的受试者。该发明还涉及通过给予含有本发明化合物的药物组合物来治疗受试者的HCV感染的方法。
• 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。
• Novel potent macrocyclic inhibitors of the hepatitis C virus NS3 protease: Use of cyclopentane and cyclopentene P2-motifs
  作者：Marcus Bäck、Per-Ola Johansson、Fredrik Wångsell、Fredrik Thorstensson、Ingemar Kvarnström、Susana Ayesa、Horst Wähling、Mikael Pelcman、Katarina Jansson、Stefan Lindström、Hans Wallberg、Björn Classon、Christina Rydergård、Lotta Vrang、Elizabeth Hamelink、Anders Hallberg、Åsa Rosenquist、Bertil Samuelsson

  DOI：10.1016/j.bmc.2007.07.027

  日期：2007.11

  Several highly potent novel HCV NS3 protease inhibitors have been developed from two inhibitor series containing either a P2 trisubstituted macrocyclic cyclopentane- or a P2 cyclopentene dicarboxylic acid moiety as surrogates for the widely used N-acyl-(4R)-hydroxyproline in the P2 position. These inhibitors were optimized for anti HCV activities through examination of different ring sizes in the macrocyclic systems and further by exploring the effect of P4 substituent removal on potency. The target molecules were synthesized from readily available starting materials, furnishing the inhibitor compounds in good overall yields. It was found that the 14-membered ring system was the most potent in these two series and that the corresponding 13-, 15-, and 16-membered macrocyclic rings delivered less potent inhibitors. Moreover, the corresponding PI acylsulfonamides had superior potencies over the corresponding PI carboxylic acids. It is noteworthy that it has been possible to develop highly potent HCV protease inhibitors that altogether lack the P4 substituent. Thus the most potent inhibitor described in this work, inhibitor 20, displays a K-i value of 0.41 nM and an EC50 value of 9 nM in the subgenomic HCV replicon cell model on genotype lb. To the best of our knowledge this is the first example described in the literature of a HCV protease inhibitor displaying high potency in the replicon assav and lacking the P4 substituent, a finding which Should facilitate the development of orally active small molecule inhibitors against the HCV protease. (C) 2007 Elsevier Ltd. All rights reserved.