(S)-tert-butyl (1-(1,3-dioxoisoindolin-2-yl)-3,3-dimethylbutan-2-yl)carbamate | 290815-00-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: (S)-tert-butyl (1-(1,3-dioxoisoindolin-2-yl)-3,3-dimethylbutan-2-yl)carbamate
• 英文别名: [(1S)-1-[(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)methyl]-2,2-dimethylpropyl]carbamic acid 1,1-dimethylethyl ester；Tert-butyl N-[(2S)-1-(1,3-dioxoisoindol-2-YL)-3,3-dimethylbutan-2-YL]carbamate
• CAS: 290815-00-8
• 化学式: C₁₉H₂₆N₂O₄
• 分子量: 346.426
• InChiKey: FFLNGFJKSGHOPH-CQSZACIVSA-N

物化性质

• 熔点：
  153-154 °C
• 沸点：
  471.7±28.0 °C(Predicted)
• 密度：
  1.149±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl (1-(1,3-dioxoisoindolin-2-yl)-3,3-dimethylbutan-2-yl)carbamate 在 甲胺 作用下， 以 水 为溶剂， 以88%的产率得到[(2S)-1-氨基-3,3-二甲基-2-丁烷基](2-甲基-2-丙基)氨基甲酸
  参考文献：
  名称：

  基于R 3延长的吡嗪酮支架的丙型肝炎病毒的Pan-NS3蛋白酶抑制剂

  摘要：

  在本文中，我们介绍了基于2（1 H）-吡嗪酮的HCV NS3蛋白酶抑制剂的设计和合成，并显示了延长的R 3尿素取代基与几种NS3蛋白变体的抑制能力增强相关。据信抑制剂依赖于模拟氢键的β-折叠，该氢键在不同的基因型和当前的抗药性变体上是相似的，并且对应于天然肽底物的β-折叠相互作用。例如，具有包括环状酰亚胺的尿素取代基的抑制剂36对基因型1a，野生型（K i  = 30 nM）和R155K（K i  = 2 nM）和基因型3a（Ki  = 5 nM）。

  DOI：

  10.1016/j.ejmech.2018.02.032
• 作为产物：
  描述：

  L-叔亮氨酸 在 lithium aluminium tetrahydride 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 (S)-tert-butyl (1-(1,3-dioxoisoindolin-2-yl)-3,3-dimethylbutan-2-yl)carbamate
  参考文献：
  名称：

  A convenient synthesis of (1S)-tert-butyl-1,2-ethylenediamine

  摘要：

  A practical four-step synthesis of (1S)-tert-butyl-1,2-ethylenediamine has been developed. The sequence proceeds in good overall yield via crystalline intermediates and provides the title compound in 99.3% ee. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(00)00145-2

文献信息

• 3,4-(cyclopentyl)-fused proline compounds as inhibitors of hepatitis C virus NS3 serine protease
  申请人：Njoroge George F.

  公开号：US20050197301A1

  公开（公告）日：2005-09-08

  The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.

  本发明公开了具有HCV蛋白酶抑制活性的新化合物，以及制备这种化合物的方法。在另一实施方式中，本发明公开了包含这种化合物的药物组合物，以及使用它们治疗与HCV蛋白酶相关的疾病的方法。
• [EN] NOVEL KETOAMIDES WITH CYCLIC P4'S AS INHIBITORS OF NS3 SERINE PROTEASE OF HEPATITIS C VIRUS<br/>[FR] NOUVEAUX CETOAMIDES A P4 CYCLIQUES EN TANT QU'INHIBITEURS DE LA NS3 SERINE PROTEASE DU VIRUS DE L'HEPATITE C
  申请人：SCHERING CORP

  公开号：WO2005085242A1

  公开（公告）日：2005-09-15

  The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.

  本发明公开了具有HCV蛋白酶抑制活性的新化合物，以及制备这种化合物的方法。在另一实施方式中，该发明公开了包含这种化合物的药物组合物，以及使用它们治疗与HCV蛋白酶相关的疾病的方法。
• Development of Diphenylamine-Linked Bis(imidazoline) Ligands and Their Application in Asymmetric Friedel-Crafts Alkylation of Indole Derivatives with Nitroalkenes
  作者：Han Liu、Da-Ming Du

  DOI：10.1002/adsc.201000111

  日期：——

  diphenylamine‐linked bis(imidazoline) ligands were prepared through Kelly‐You’s imidazoline formation procedure mediated by Hendrickson’s reagent in good yields. The novel ligands were tested in the asymmetric Friedel–Crafts alkylation of indole derivatives with nitroalkenes. In most cases, good yields (up to 97%) and excellent enantioselectivities (up to 98%) can be achieved. The optimized bis(imidazoline) ligand

  通过由Hendrickson试剂介导的Kelly-You的咪唑啉形成步骤制备了新的由二苯胺连接的双（咪唑啉）配体，收率很高。在吲哚衍生物与硝基烯烃的不对称Friedel-Crafts烷基化反应中测试了新型配体。在大多数情况下，可以获得良好的收率（高达97％）和出色的对映选择性（高达98％）。经过优化的咪唑啉环上具有反式二苯取代基的双咪唑啉配体比相应的双恶唑啉配体具有更好的对映选择性。
• NOVEL NICOTINAMIDE DERIVATIVE OR SALT THEREOF
  申请人：FUJIWARA Hideyasu

  公开号：US20130116430A1

  公开（公告）日：2013-05-09

  An object of the present invention is to provide to a compound and a pharmaceutical composition, which have excellent Syk-inhibitory activity. The present invention provides a nicotinamide derivative represented by the following formula (I) (wherein R 1 represents a halogen atom; R 2 represents a C 1-12 alkyl group, a C 2-12 alkenyl group, a C 2-12 alkynyl group, a C 3-8 cycloalkyl group, an aryl group, an ar-C 1-6 alkyl group or a heterocyclic group, each optionally having at least one substituent; R 3 represents an aryl group or a heterocyclic group each optionally having at least one substituent; and R 4 and R 5 each independently represent a hydrogen atom; and R 2 and R 4 may form a cyclic amino group optionally having at least one substituent together with the nitrogen atom to which they bind) or a salt thereof, and a pharmaceutical composition for use in the treatment of a Syk-related disease which comprises the nicotinamide derivative or a salt thereof.

  本发明的目的是提供一种具有优异的Syk抑制活性的化合物和制药组合物。本发明提供了一种由以下式(I)表示的烟酰胺衍生物（其中R1表示卤素原子；R2表示C1-12烷基、C2-12烯基、C2-12炔基、C3-8环烷基、芳基、芳基-C1-6烷基或杂环基，每种均可选地具有至少一个取代基；R3表示芳基或杂环基，每种均可选地具有至少一个取代基；R4和R5各自独立地表示氢原子；且R2和R4可以与它们结合的氮原子一起形成具有至少一个取代基的环状氨基团）或其盐，并且用于治疗Syk相关疾病的制药组合物包括该烟酰胺衍生物或其盐。
• Novel potent inhibitors of hepatitis C virus (HCV) NS3 protease with cyclic sulfonyl P3 cappings
  作者：Kevin X. Chen、Bancha Vibulbhan、Weiying Yang、Latha G. Nair、Xiao Tong、Kuo-Chi Cheng、F. George Njoroge

  DOI：10.1016/j.bmcl.2008.12.111

  日期：2009.2

  Extensive SAR studies of the P3 capping group led to the discovery of a series of potent inhibitors with sultam and cyclic sulfonyl urea moieties as the P3 capping. The bicyclic thiophene-sultam or phenyl- sultam cappings were selected for further SAR development. Modi. cation at the P3 side chain determined that the tert-butyl group was the best choice at that position. Optimization of P1 residue significantly improved potency and selectivity. The combination of optimal moieties at all positions led to the discovery of compound 33. This compound had the best overall pro. le in potency and PK profile: excellent K-i* of 5.3 nM and activity in replicon (EC90) of 80 nM, extremely high selectivity of 6100, and a good rat PO AUC of 1.43 mu Mh. (C) 2009 Elsevier Ltd. All rights reserved.