tert-butyl N-[(4S)-3-hydroxy-2,6-dimethylhept-1-en-4-yl]carbamate | 1609959-45-6

• 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 N-[(4S)-3-hydroxy-2,6-dimethylhept-1-en-4-yl]carbamate
• 英文别名: N-[(1S)-2-Hydroxy-3-methyl-1-(2-methylpropyl)-3-buten-1-yl]-carbamic Acid 1,1-Dimethylethyl Ester
• CAS: 1609959-45-6
• 化学式: C₁₄H₂₇NO₃
• 分子量: 257.373
• InChiKey: RZYBVTBIWWSVJN-PXYINDEMSA-N

物化性质

• 沸点：
  363.7±35.0 °C(Predicted)
• 密度：
  0.969±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(4S)-3-hydroxy-2,6-dimethylhept-1-en-4-yl]carbamate 在 1-羟基苯并三唑 、 戴斯-马丁氧化剂 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 间氯过氧苯甲酸 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 8.5h， 生成 3-amino-N-((S)-4-methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-yl)-3-phenylpropanamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel tripeptidyl epoxyketone derivatives constructed from β-amino acid as proteasome inhibitors

  摘要：

  A series of novel tripeptidyl epoxyketone derivatives constructed from beta-amino acid were designed, synthesized and evaluated as proteasome inhibitors. All target compounds were tested for their proteasome inhibitory activities and selected compounds were tested for their anti-proliferation activities against two multiple myeloma (MM) cell lines RPMI 8226 and NCI-H929. Among them, eleven compounds exhibited proteasome inhibitory rates of more than 50% at the concentration of 1 mu g/mL and nine compounds showed anti-proliferation activities with IC50 values at low micromolar level. Compound 20h displayed the most potent proteasome inhibitory activities (IC50: 0.11 +/- 0.01 mu M) and anti-proliferation activities with IC50 values at 0.23 +/- 0.01 and 0.17 +/- 0.02 mu M against two tested cell lines. Additionally, the poly-ubiquitin accumulation in the western blot analysis supported that proteasome inhibition in a cellular system was induced by compound 20h. All these experimental results confirmed that b-amino acid can be introduced as a building block for the development of proteasome inhibitors. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.04.011
• 作为产物：
  描述：

  N-(叔丁氧基羰基)-L-亮氨酸-N′-甲氧基-N′-甲酰胺 在 甲醇 、 sodium tetrahydroborate 、 cerium(III) chloride heptahydrate 、 碘 、 magnesium 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 tert-butyl N-[(4S)-3-hydroxy-2,6-dimethylhept-1-en-4-yl]carbamate
  参考文献：
  名称：

  一种卡非佐米中间体的制备方法

  摘要：

  本发明涉及一种卡非佐米中间体F的制备方法，属于药物化学领域。所述制备方法可以通过以叔丁氧羰基‑L‑亮氨酸为起始物料，经过缩合、格式、还原、环氧化、氧化、成盐反应，得到卡非佐米关键中间体F；该方法反应条件温和，收率高，选择性好，产生的三废少，适合工业放大生产。

  公开号：

  CN113200943A

文献信息

• 결정형 펩티드 에폭시 케톤 프로테아제 저해제 및 아미노산 케토-에폭시드의 합성
  申请人：ONYX THERAPEUTICS, INC. 오닉스 세라퓨틱스, 인크.(520100211870)

  公开号：KR20150131405A

  公开（公告）日：2015-11-24

  본 발명은 결정 펩티드 케토 에폭시드 화합물, 이 화합물의 제법 및 관련 약학 조성물에 관한 것이다. 본 발명은 또한 아미노산 케토-에폭시드 제법에 관한 것이기도 하다. 특히, 아릴 케톤은 입체선택적으로 원하는 케토 에폭시드로 전환된다.

  本发明涉及晶体肽酮环氧化合物，以及该化合物的制备和相关的药学组合物。本发明还涉及氨基酸酮环氧化合物的制备方法。特别地，芳基酮可以立体选择性地转化为所需的酮环氧化合物。
• [EN] AN IMPROVED PROCESSES FOR THE PREPARATION OF CARFILZOMIB OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF<br/>[FR] PROCÉDÉ PERFECTIONNÉ DE PRÉPARATION DE CARFILZOMIB OU DE SELS PHARMACEUTIQUEMENT ACCEPTABLES DE CELUI-CI
  申请人：LAURUS LABS PRIVATE LTD

  公开号：WO2016185450A1

  公开（公告）日：2016-11-24

  The present invention relates to an improved process for the preparation of carfilzomib or a pharmaceutically acceptable salt thereof. The present invention also relates to a process for the preparation of amorphous form of carfilzomib.

  本发明涉及一种改进的制备卡菲唑胺或其药学上可接受的盐的工艺。本发明还涉及一种制备卡菲唑胺非晶态形式的工艺。
• PROCESSES FOR THE PREPARATION OF CARFILZOMIB OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
  申请人：LAURUS LABS LIMITED

  公开号：US20190284231A1

  公开（公告）日：2019-09-19

  The present invention relates to an improved process for the preparation of carfilzomib or a pharmaceutically acceptable salt thereof. The present invention also relates to a process for the preparation of amorphous form of carfilzomib.

  本发明涉及一种改进的制备卡非索米或其药学上可接受的盐的方法。本发明还涉及一种制备卡非索米非晶态的方法。
• Processes for the preparation of carfilzomib or pharmaceutically acceptable salts thereof
  申请人：LAURUS LABS PRIVATE LIMITED

  公开号：US10364269B2

  公开（公告）日：2019-07-30

  The present invention relates to an improved process for the preparation of carfilzomib or a pharmaceutically acceptable salt thereof. The present invention also relates to a process for the preparation of amorphous form of carfilzomib.

  本发明涉及一种制备卡非佐米或其药学上可接受的盐的改进工艺。本发明还涉及一种制备无定形卡非佐米的工艺。
• Covalent docking modelling-based discovery of tripeptidyl epoxyketone proteasome inhibitors composed of aliphatic-heterocycles
  作者：Xiao-Wu Dong、Jian-Kang Zhang、Lei Xu、Jin-Xin Che、Gang Cheng、Xiao-Bei Hu、Li Sheng、An-Hui Gao、Jia Li、Tao Liu、Yong-Zhou Hu、Yu-Bo Zhou

  DOI：10.1016/j.ejmech.2018.12.064

  日期：2019.2

  The potential of specific proteasome inhibitors to act as anti-cancer agents has attracted intensive investigations. The proteasome can be covalently inhibited by epoxyketone derivatives via a two-step reaction. Several computational approaches have been developed to mimic the covalent binding event. Compound 1 composed of a six-membered heterocyclic ring was designed by using covalent docking. With a possible different binding mode from the clinical compound Carfilzomib, it occupied the 55 pocket of 20S proteasome and showed favorable inhibitory activity. Subsequently optimization and evaluation were taken place. Among these compounds, 11h demonstrated extraordinary in vitro inhibitory activity and selectivity, and good in vivo proteasome inhibitory activity, a favorable pharmacokinetic profile and xenograft tumor inhibition. The possible binding pattern of compound 11h against proteasome was further fully explored via calculations, providing a theoretical basis for finding potent proteasome inhibitors. (C) 2018 Elsevier Masson SAS. All rights reserved.