(R)-3-甲基吡咯烷 | 69498-24-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: (R)-3-甲基吡咯烷
• 英文名称: (R)-3-methylpyrrolidine
• 英文别名: (3R)-3-methylpyrrolidine
• CAS: 69498-24-4
• 化学式: C₅H₁₁N
• 分子量: 85.149
• InChiKey: KYINPWAJIVTFBW-RXMQYKEDSA-N

物化性质

• 沸点：
  100 °C
• 密度：
  0.812

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  6
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  (R)-3-甲基吡咯烷 在 三乙基硼氢化锂 、 potassium iodide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Estrogen receptor ligands. Part 16: 2-Aryl indoles as highly subtype selective ligands for ERα

  摘要：

  A novel class of indole ligands for estrogen receptor alpha have been discovered which exhibit potent affinity and high selectivity. Substitution of the bazedoxifene skeleton to the linker present in the HTS lead 1a provided 22b which was found to be 130-fold alpha-selective and acted as an antagonist of estradiol activity in uterine tissue and MCF-7 cancer cells.

  DOI：

  10.1016/j.bmcl.2007.01.054
• 作为产物：
  描述：

  (3'R)-8-(3'-methylpyrrolidinyl)menthol 在 氢氧化钾 、 4 A molecular sieve 、 pyridinium chlorochromate 作用下， 生成 (R)-3-甲基吡咯烷
  参考文献：
  名称：

  Diastereoselective 5-exo-trig radical cyclisation on N-Acryloyl-tetrahydro-1,3-oxazines. A novel approach to enantiopure 3-substituted pyrrolidines

  摘要：

  N-Acryloyl-2-(phenylselenomethyl)-tetrahydro-1,3-oxazine 1 generates a carbon-centred radical in the presence of tri-n-butyltin hydride and AIBN. This radical underwent diastereoselective 5-exo-trig cyclisation leading to a mixture of five-membered lactams 2a and 2b (d.e. 68%). Chromatographic separation of the diastereomers and elimination of the chiral auxiliary provided enantiopure (R)-3-methylpyrrolidine in good chemical yield. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/s0040-4039(96)02091-6

文献信息

• [EN] 19-NOR NEUROACTIVE STEROIDS AND METHODS OF USE THEREOF<br/>[FR] 19-NOR-STÉROÏDES NEUROACTIFS ET PROCÉDÉS D'UTILISATION DE CEUX-CI
  申请人：SAGE THERAPEUTICS INC

  公开号：WO2014169836A1

  公开（公告）日：2014-10-23

  Provided herein are 3,3-disubstituted19-nor-steroidal compounds according to Formula(I): and pharmaceutical compositions thereof. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions,for example, treatment of sleep disorders, mood disorders,schizophrenia spectrum disorders, disorders of memory and/or cognition, movement disorders,personality disorders,autism spectrum disorders, pain,traumatic brain injury, vascular diseases,substance abuse disorders and/or withdrawal syndromes, tinnitus, status epilepticus.

  根据以下公式(I)，提供了3,3-二取代19-去甲类固醇化合物及其药物组合物。这些化合物被认为对预防和治疗各种与中枢神经系统相关的疾病有用，例如治疗睡眠障碍、情绪障碍、精神分裂症谱系障碍、记忆和/或认知障碍、运动障碍、人格障碍、自闭症谱系障碍、疼痛、创伤性脑损伤、血管疾病、物质滥用障碍和/或戒断综合征、耳鸣、癫痫持续状态。
• Optimization of Potent ATAD2 and CECR2 Bromodomain Inhibitors with an Atypical Binding Mode
  作者：Simon C. C. Lucas、Stephen J. Atkinson、Paul Bamborough、Heather Barnett、Chun-wa Chung、Laurie Gordon、Darren J. Mitchell、Alexander Phillipou、Rab K. Prinjha、Robert J. Sheppard、Nicholas C. O. Tomkinson、Robert J. Watson、Emmanuel H. Demont

  DOI：10.1021/acs.jmedchem.0c00021

  日期：2020.5.28

  Most bromodomain inhibitors mimic the interactions of the natural acetylated lysine (KAc) histone substrate through key interactions with conserved asparagine and tyrosine residues within the binding pocket. Herein we report the optimization of a series of phenyl sulfonamides that exhibit a novel mode of binding to non-bromodomain and extra terminal domain (non-BET) bromodomains through displacement

  大多数溴结构域抑制剂通过与结合口袋中保守的天冬酰胺和酪氨酸残基的关键相互作用来模拟天然乙酰化赖氨酸（KAc）组蛋白底物的相互作用。本文中，我们报告了一系列苯基磺酰胺的优化，这些苯基磺酰胺通过置换四个水分子的通常保守的网络，表现出与非溴结构域和额外末端结构域（非BET）溴结构域结合的新型模式。从最初的命中分子开始，我们报告了其对包含2个（ATAD2）和猫眼综合征染色体区域，候选2个（CECR2）域的ATPase家族AAA域的不同优化。这项工作结束于鉴定（R）-55（GSK232），这是一种具有优异理化特性的高选择性，细胞渗透性CECR2抑制剂。
• COMPOUNDS AND METHODS FOR TREATMENT OF CANCER
  申请人：Sudhakar Anantha

  公开号：US20110105497A1

  公开（公告）日：2011-05-05

  Compounds for treating, preventing or managing cancer are disclosed. Also provided are methods for using the compounds in treatment of various cancers. Also provided are methods of treatment using the compounds together with another chemotherapy, radiation therapy, hormonal therapy, biological therapy, or immunotherapy. Pharmaceutical compositions suitable for use in the methods are also disclosed.

  揭示了用于治疗、预防或管理癌症的化合物。还提供了使用这些化合物治疗各种癌症的方法。同时还提供了使用这些化合物与另一种化疗、放疗、激素疗法、生物疗法或免疫疗法结合的治疗方法。还公开了适用于这些方法的药物组合物。
• Structure-Based Design, Docking and Binding Free Energy Calculations of A366 Derivatives as Spindlin1 Inhibitors
  作者：Chiara Luise、Dina Robaa、Pierre Regenass、David Maurer、Dmytro Ostrovskyi、Ludwig Seifert、Johannes Bacher、Teresa Burgahn、Tobias Wagner、Johannes Seitz、Holger Greschik、Kwang-Su Park、Yan Xiong、Jian Jin、Roland Schüle、Bernhard Breit、Manfred Jung、Wolfgang Sippl

  DOI：10.3390/ijms22115910

  日期：——

  The chromatin reader protein Spindlin1 plays an important role in epigenetic regulation, through which it has been linked to several types of malignant tumors. In the current work, we report on the development of novel analogs of the previously published lead inhibitor A366. In an effort to improve the activity and explore the structure–activity relationship (SAR), a series of 21 derivatives was synthesized, tested in vitro, and investigated by means of molecular modeling tools. Docking studies and molecular dynamics (MD) simulations were performed to analyze and rationalize the structural differences responsible for the Spindlin1 activity. The analysis of MD simulations shed light on the important interactions. Our study highlighted the main structural features that are required for Spindlin1 inhibitory activity, which include a positively charged pyrrolidine moiety embedded into the aromatic cage connected via a propyloxy linker to the 2-aminoindole core. Of the latter, the amidine group anchor the compounds into the pocket through salt bridge interactions with Asp184. Different protocols were tested to identify a fast in silico method that could help to discriminate between active and inactive compounds within the A366 series. Rescoring the docking poses with MM-GBSA calculations was successful in this regard. Because A366 is known to be a G9a inhibitor, the most active developed Spindlin1 inhibitors were also tested over G9a and GLP to verify the selectivity profile of the A366 analogs. This resulted in the discovery of diverse selective compounds, among which 1s and 1t showed Spindlin1 activity in the nanomolar range and selectivity over G9a and GLP. Finally, future design hypotheses were suggested based on our findings.

  染色质阅读蛋白Spindlin1在表观遗传调控中扮演重要角色，已与多种恶性肿瘤相关。在当前工作中，我们报道了先前发表的主要抑制剂A366的新类似物的开发。为了提高活性并探索结构-活性关系（SAR），合成了一系列21个衍生物，在体内进行了测试，并通过分子建模工具进行了研究。进行了对接研究和分子动力学（MD）模拟，以分析和理解负责Spindlin1活性的结构差异。MD模拟的分析揭示了重要的相互作用。我们的研究突出显示了用于Spindlin1抑制活性所需的主要结构特征，其中包括嵌入芳香笼中的带正电的吡咯烷基，通过丙氧基连接到2-氨基吲哚核心。在后者中，酰胺基固定化合物到通过与Asp184的盐桥相互作用的口袋中。测试了不同的协议以识别一种快速的计算机辅助方法，可以帮助区分A366系列中的活性和非活性化合物。使用MM-GBSA计算重新评分对接姿势在这方面取得了成功。由于A366被认为是G9a的抑制剂，因此还测试了最活跃的开发的Spindlin1抑制剂对G9a和GLP的选择性配置文件进行验证A366类似物。这导致了多种选择性化合物的发现，其中1s和1t显示出纳摩尔级别的Spindlin1活性，并且对G9a和GLP具有选择性。最后，基于我们的发现提出了未来的设计假设。
• Design of SARS-CoV-2 PLpro Inhibitors for COVID-19 Antiviral Therapy Leveraging Binding Cooperativity
  作者：Zhengnan Shen、Kiira Ratia、Laura Cooper、Deyu Kong、Hyun Lee、Youngjin Kwon、Yangfeng Li、Saad Alqarni、Fei Huang、Oleksii Dubrovskyi、Lijun Rong、Gregory R. J. Thatcher、Rui Xiong

  DOI：10.1021/acs.jmedchem.1c01307

  日期：2022.2.24

  viral replication, also dysregulates host immune sensing by binding and deubiquitination of host protein substrates. PLpro is a promising therapeutic target, albeit challenging owing to featureless P1 and P2 sites recognizing glycine. To overcome this challenge, we leveraged the cooperativity of multiple shallow binding sites on the PLpro surface, yielding novel 2-phenylthiophenes with nanomolar inhibitory

  为了结束 COVID-19 大流行，迫切需要补充疫苗接种的抗病毒药物。SARS-CoV-2 木瓜蛋白酶样蛋白酶 (PLpro) 是调节病毒复制的仅有的两种必需半胱氨酸蛋白酶之一，也通过宿主蛋白底物的结合和去泛素化来失调宿主免疫感应。PLpro 是一个有前途的治疗靶点，尽管由于识别甘氨酸的 P1 和 P2 位点无特征而具有挑战性。为了克服这一挑战，我们利用 PLpro 表面上多个浅结合位点的协同作用，产生具有纳摩尔抑制效力的新型 2-苯基噻吩。新的共晶结构证实配体结合诱导与 PLpro 的新相互作用：通过关闭 PLpro 的 BL2 环形成新的“BL2 凹槽”，并模拟泛素与 PLpro 的 Glu167 的结合相互作用。总之，这种结合协同性转化为迄今为止报道的最有效的 PLpro 抑制剂，在 SARS-CoV-2 感染的人类细胞中具有缓慢的解离速率、改善的结合亲和力和低微摩尔抗病毒效力。