(S)-2-((叔丁氧羰基)氨基)庚-6-烯酸 | 204711-97-7

• 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
• 中文名称: (S)-2-((叔丁氧羰基)氨基)庚-6-烯酸
• 英文名称: (S)-2-tert-butoxycarbonylamino-hept-6-enoic acid
• 英文别名: Boc-L-2-amino-6-heptenoic acid；(2S)-2-(Boc-amino)-6-heptenoic acid；(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]hept-6-enoic acid
• CAS: 204711-97-7
• 化学式: C₁₂H₂₁NO₄
• 分子量: 243.303
• InChiKey: WPKPUPUWFHDYRR-VIFPVBQESA-N

物化性质

• 沸点：
  391.3±35.0 °C(Predicted)
• 密度：
  1.062±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P330,P363,P501
• 危险性描述：
  H302,H312,H332
• 储存条件：
  2-8°C，惰性气体

反应信息

• 作为反应物：
  描述：

  (S)-2-((叔丁氧羰基)氨基)庚-6-烯酸 在 偶氮二异丁腈 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium thiomethoxide 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.83h， 生成 (R)-5-oxo-pyrrolidine-2-carboxylic acid ((S)-6-mercapto-1-phenylcarbamoyl-hexyl)-amide
  参考文献：
  名称：

  ST7612AA1, a Thioacetate-ω(γ-lactam carboxamide) Derivative Selected from a Novel Generation of Oral HDAC Inhibitors

  摘要：

  A systematic study of medicinal chemistry aimed at identifying a new generation of HDAC inhibitors, through the introduction of a thiol zinc-binding group (ZBG) and of an amide-lactam in the ?-position of the polyethylene chain of the vorinostat scaffold, allowed the selection of a new class of potent pan-HDAC inhibitors (pan-HDACis). Simple, highly versatile, and efficient synthetic approaches were used to synthesize a library of these new derivatives, which were then submitted to a screening for HDAC inhibition as well as to a preliminary in vitro assessment of their antiproliferative activity. Molecular docking into HDAC crystal structures suggested a binding mode for these thiol derivatives consistent with the stereoselectivity observed upon insertion of amide-lactam substituents in the ?-position. ST7612AA1 (117), selected as a drug candidate for further development, showed an in vitro activity in the nanomolar range associated with a remarkable in vivo antitumor activity, highly competitive with the most potent HDAC inhibitors, currently under clinical trials. A preliminary study of PK and metabolism is also illustrated.

  DOI：

  10.1021/jm5008209
• 作为产物：
  描述：

  6-庚烯酸 在 lithium hydroxide 、 双氧水 、 三甲基乙酰氯 、 双(三甲基硅烷基)氨基钾 、 三乙胺 、 tin(ll) chloride 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 22.75h， 生成 (S)-2-((叔丁氧羰基)氨基)庚-6-烯酸
  参考文献：
  名称：

  丙型肝炎病毒NS3蛋白酶的有效抑制剂：基于大环底物的β链模拟物的设计和合成

  摘要：

  病毒编码的NS3蛋白酶对丙型肝炎病毒（HCV）的生命周期至关重要，丙型肝炎病毒是导致慢性肝炎，肝硬化和肝细胞癌的重要人类病原体。将描述能够抑制HCV NS3蛋白酶与其多蛋白底物之间相互作用的15元环β链模拟物的设计和合成。通过NMR和分子动力学研究了大环配体与酶之间的结合相互作用，并建立了配体/酶复合物的模型。

  DOI：

  10.1021/jo049288r

文献信息

• [EN] HYDROXAMATE DERIVATIVES BEARING AMIDE-LACTAMS AS POTENT HDAC INHIBITORS AND THEIR USES AS MEDICAMENTS<br/>[FR] DÉRIVÉS D'HYDROXAMATE PORTANT DES AMIDE-LACTAMES À TITRE DE PUISSANTS INHIBITEURS D'HDAC ET LEURS UTILISATIONS À TITRE DE MÉDICAMENTS
  申请人：SIGMA TAU IND FARMACEUTI

  公开号：WO2014122222A1

  公开（公告）日：2014-08-14

  The present invention relates to novel amide compounds of Formula (I), and their use as anti-tumoral and pro-apoptotic agents. The invention includes the use of such compounds in medicine, in relation to cancer disease as well as other diseases where an inhibition of HDAC is responsive, and the pharmaceutical composition containing such compounds.

  本发明涉及式(I)的新酰胺化合物，及其用作抗肿瘤和促凋亡剂的应用。该发明包括将此类化合物用于医学领域，与癌症以及其他抑制HDAC有响应的疾病的治疗相关，以及包含此类化合物的药物组合物。
• Growth Hormone Secretagogue Receptor 1A Ligands
  申请人：Schambye Hans T.

  公开号：US20080300180A1

  公开（公告）日：2008-12-04

  The present invention relates to new growth hormone secretagogue receptor 1A (GHS-R 1A) ligands, and pharmaceutical compositions comprising any of the new GHS-R1 A ligands. The ligands are suitable for a wide range of applications, and thus the present invention also relates to use of the GHS-R1 A ligands according to the present invention in the manufacture of a medicament for the treatment of an individual in need thereof. In another aspect, the present invention relates to a method of treatment of an individual in need thereof, comprising administering to said individual one or more of the GHS-R1A ligands disclosed herein, such as e.g. for treatment of cancer cachexia.

  本发明涉及新型生长激素促分泌素受体1A（GHS-R 1A）配体，以及包含任何此类新型GHS-R1A配体的药物组合物。这些配体适用于广泛的应用范围，因此本发明还涉及根据本发明的GHS-R1A配体在制造用于治疗有此需要的个体的药物中的用途。在另一方面，本发明涉及一种治疗有此需要的个体的方法，包括向该个体施用本文披露的一种或多种GHS-R1A配体，例如用于治疗癌症恶病质。
• Insight into Transannular Cyclization Reactions To Synthesize Azabicyclo[<i>X</i>.<i>Y</i>.<i>Z</i>]alkanone Amino Acid Derivatives from 8-, 9-, and 10-Membered Macrocyclic Dipeptide Lactams
  作者：N. D. Prasad Atmuri、William D. Lubell

  DOI：10.1021/acs.joc.5b00237

  日期：2015.5.15

  An efficient method for synthesizing different functionalized azabicyclo[X.Y.0]alkanone amino acid derivatives has been developed employing electrophilic transannular cyclizations of 8-, 9-, and 10-membered unsaturated macrocycles to form 5,5-, 6,5-, 7,5-, and 6,6-fused bicylic amino acids, respectively. Macrocycles were obtained by a sequence featuring peptide coupling of vinyl-, allyl-, homoallyl-

  一种合成不同功能化氮杂双环[ X的有效方法。ÿ.0]烷酮氨基酸衍生物是利用8、9和10元不饱和大环的亲电跨环环化反应形成5、5、6、5、7、5和6，6稠合的双环氨基酸。通过以乙烯基-，烯丙基-，高烯丙基-和高同烯丙基甘氨酸结构单元的肽偶联为特征，然后闭环易位的序列获得大环。对8元，9元和10元大环内酰胺起始原料以及某些双环氨基酸产物的X射线晶体学分析提供了对它们的构象偏爱以及非对映选择性形成特定氮杂双环烷酮氨基酸的机理的见解。环戊内酰胺化反应的方式。
• Aliphatic chain-containing macrocycles as diazonamide A analogs
  作者：Viktorija Vitkovska、Rimants Zogota、Toms Kalnins、Diana Zelencova、Edgars Suna

  DOI：10.1007/s10593-020-02704-6

  日期：2020.5

  Aliphatic alkyl chain-containing 12–14-membered macrocycles have been designed as structural analogs of antimitotic natural product diazonamide A. Macrocycles were synthesized from 5-bromooxazole in 7 to 9 linear steps using Ru-catalyzed ring-closing metathesis as the key transformation. Heat effect of binding to α,β-tubulin tetramer (T4-RB3 complex) has been measured for the synthesized macrocycles

  设计了含脂肪族烷基链的12-14元大环化合物作为抗有丝分裂天然产物重氮酰胺A的结构类似物。大环化合物是由5-溴恶唑以7到9个线性步骤合成的，使用Ru催化的闭环复分解为关键转化。通过等温滴定热法测定了合成的大环与α，β-微管蛋白四聚体（T4-RB3配合物）结合的热效应。
• [EN] MACROCYCLIC LACTAMS AND PHARMACEUTICAL USE THEREOF<br/>[FR] LACTAMES MACROCYCLIQUES ET LEUR UTILISATION PHARMACEUTIQUE
  申请人：NOVARTIS AG

  公开号：WO2005049585A1

  公开（公告）日：2005-06-02

  The present invention relates to novel macrocyclic compounds of the formula (I) wherein R1, R2, R3, U, V, W, X, Y, Z and n are as defined in the specification, the number of ring atoms included in the macrocyclic ring being 14, 15, 16 or 17, in free base form or in acid addition salt form, to their preparation, to their use as pharmaceuticals and to pharma­ceutical compositions comprising them.

  本发明涉及以下式（I）的新型大环化合物，其中R1、R2、R3、U、V、W、X、Y、Z和n如规范中所定义，大环环中包含的环原子数为14、15、16或17，以自由碱形式或酸盐形式存在，以及它们的制备方法，用作药物的用途，以及包含它们的药物组合物。