2-(isocyanomethyl)thiophene | 99623-05-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 杂芳族化合物
• 英文名称: 2-(isocyanomethyl)thiophene
• CAS: 99623-05-9
• 化学式: C₆H₅NS
• 分子量: 123.178
• InChiKey: BIGWFEMYDVEWQP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  32.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(isocyanomethyl)thiophene 在 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 、 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.5h， 生成 5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)-N-(2-(4-(1-(1-(thiophen-2-ylmethyl)-1H-tetrazol-5-yl)propyl)piperazin-1-yl)benzothiazol-6-yl)pentanamide
  参考文献：
  名称：

  Small molecules enhance functional O-mannosylation of Alpha-dystroglycan

  摘要：

  Alpha-dystroglycan (alpha-DG), a highly glycosylated receptor for extracellular matrix proteins, plays a critical role in many biological processes. Hypoglycosylation of alpha-DG results in various types of muscular dystrophies and is also highly associated with progression of majority of cancers. Currently, there are no effective treatments for those devastating diseases. Enhancing functional O-mannosyl glycans (FOG) of alpha-DG on the cell surfaces is a potential approach to address this unmet challenge. Based on the hypothesis that the cells can up-regulate FOG of alpha-DG in response to certain chemical stimuli, we developed a cell-based high-throughput screening (HTS) platform for searching chemical enhancers of FOG of alpha-DG from a large chemical library with 364,168 compounds. Sequential validation of the hits from a primary screening campaign and chemical works led to identification of a cluster of compounds that positively modulate FOG of alpha-DG on various cell surfaces including patient-derived myoblasts. These compounds enhance FOG of alpha-DG by almost ten folds, which provide us powerful tools for O-mannosylation studies and potential starting points for the development of drug to treat dystroglycanopathy. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.11.011
• 作为产物：
  描述：

  N-(thiophen-2-ylmethyl)formamide 在 三光气 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.67h， 生成 2-(isocyanomethyl)thiophene
  参考文献：
  名称：

  Efficient Isocyanide-less Isocyanide-Based Multicomponent Reactions

  摘要：

  Isocyanides are the "Jekyll and Hyde" of organic chemistry allowing for extremely interesting transformations that are not only extremely odorous but also noxious. Therefore, an isocyanide-less isocyanide-based multicomponent reaction (IMCR) has been developed, and this protocol is expected to replace many of the old procedures in the future not only in IMCR but in other areas of organic chemistry as well.

  DOI：

  10.1021/acs.orglett.5b00759

文献信息

• Imidazodiazepines
  申请人：Hoffmann-La Roche Inc.

  公开号：US04775671A1

  公开（公告）日：1988-10-04

  There is presented compounds of the formula ##STR1## wherein A together with the two carbon atoms denoted by .alpha. and .beta. signifies one of the groups ##STR2## and the dotted line signifies the double bond present in cases (1), (2) and (4) and wherein R.sup.1 signifies a 5- or 6-membered aromatic heterocyclic group or the group --C(R.sup.6).dbd.NOR.sup.7 (B), R.sup.2 signifies hydrogen and R.sup.3 signifies hydrogen or lower alkyl or R.sup.2 and R.sup.3 together signify dimethylene, trimethylene or propenylene, R.sup.4 and R.sup.5 each signify hydrogen, halogen, trifluoromethyl, cyano, nitro, amino or lower alkyl, R.sup.6 signifies hydrogen or lower alkyl and R.sup.7 signifies lower alkyl, the compound of formula I having the (S) or (R,S) configuration with reference to the carbon atom denoted by .gamma. when R.sup.2 and R.sup.3 together signify dimethylene, trimethylene or propenylene, and pharmaceutically acceptable acid addition salts thereof have a pronounced affinity to the central benzodiazepine receptors and have anxiolytic, anticonvulsant, muscle relaxant and sedative-hypnotic properties.

  公式##STR1##中呈现了化合物，其中A与由α和β表示的两个碳原子一起表示##STR2##中的一组，虚线表示在情况(1)、(2)和(4)中存在的双键，其中R.sup.1表示5-或6-成员芳香杂环基团或基团--C(R.sup.6).dbd.NOR.sup.7 (B)，R.sup.2表示氢，R.sup.3表示氢或较低的烷基或R.sup.2和R.sup.3一起表示二甲亚甲基、三甲亚甲基或丙烯亚甲基，R.sup.4和R.sup.5各自表示氢、卤素、三氟甲基、氰基、硝基、氨基或较低的烷基，R.sup.6表示氢或较低的烷基，R.sup.7表示较低的烷基，具有参考碳原子γ时具有(S)或(R,S)构型的公式I的化合物，当R.sup.2和R.sup.3一起表示二甲亚甲基、三甲亚甲基或丙烯亚甲基时，以及其药学上可接受的酸盐具有明显的亲和力中枢苯二氮卓受体，并具有抗焦虑、抗惊厥、肌肉松弛和镇静催眠特性。
• Combining High‐Throughput Synthesis and High‐Throughput Protein Crystallography for Accelerated Hit Identification
  作者：Fandi Sutanto、Shabnam Shaabani、Rick Oerlemans、Deniz Eris、Pravin Patil、Mojgan Hadian、Meitian Wang、May Elizabeth Sharpe、Matthew R. Groves、Alexander Dömling

  DOI：10.1002/anie.202105584

  日期：2021.8.9

  mmol scale synthesis on 96-well format and on a high-throughput nanoscale format in a highly automated fashion. High-throughput PX of our libraries efficiently yielded potent covalent inhibitors of the main protease of the COVID-19 causing agent, SARS-CoV-2. Our results demonstrate, that the marriage of in situ HT synthesis of (covalent) libraires and HT PX has the potential to accelerate hit finding

  蛋白质晶体学 (PX) 广泛用于推动药物优化的高级阶段或通过片段浸泡发现药物化学起点。然而，PX 的最新进展可能会使其在早期药物发现中发挥更综合的作用。在这里，我们首次展示了高通量合成和高通量 PX 的相互作用。我们描述了一种实用的多组分反应方法，适用于以高度自动化的方式在 96 孔格式和高通量纳米级格式上进行毫摩尔级合成的不同结构单元的丙烯酰胺和丙烯酰胺和酯。我们文库的高通量 PX 有效地产生了 COVID-19 致病因子 SARS-CoV-2 的主要蛋白酶的有效共价抑制剂。我们的结果表明，（共价）库的原位 HT 合成和 HT PX 的结合有可能加速命中发现并为药物化学项目提供有意义的策略。
• Automated and accelerated synthesis of indole derivatives on a nano-scale
  作者：Shabnam Shaabani、Ruixue Xu、Maryam Ahmadianmoghaddam、Li Gao、Martin Stahorsky、Joe Olechno、Richard Ellson、Michael Kossenjans、Victoria Helan、Alexander Dömling

  DOI：10.1039/c8gc03039a

  日期：——

  miniaturized and accelerated synthesis for efficient property optimization is a formidable challenge for chemistry in the 21st century as it helps to reduce resources and waste and can deliver products in shorter time frames. Here, we used for the first-time acoustic droplet ejection (ADE) technology and fast quality control to screen efficiency of synthetic reactions on a nanomole scale in an automated

  实现高效性能优化的自动化、小型化和加速合成是 21 世纪化学面临的巨大挑战，因为它有助于减少资源和浪费，并可以在更短的时间内交付产品。在这里，我们首次使用声学液滴喷射（ADE）技术和快速质量控制，以自动化和小型化的方式筛选纳摩尔级合成反应的效率。中断的费歇尔吲哚与 Ugi 型反应相结合，产生了几种有吸引力的药物样支架。在 384 孔板中，产生了一组不同的间断 Fischer 吲哚中间体，并通过两步序列与三环乙内酰脲骨架反应。同样，预制的 Fischer 吲哚中间体用于生产多种 Ugi 产品，并将效率与原位方法进行了比较。在制备毫摩尔规模上重新合成了多个反应，显示出从纳米到毫克的可扩展性，从而显示出合成实用性。前所未有的大量建筑被用于快速范围和限制研究（68 种异氰化物，72 种羧酸）。生成的大合成数据的小型化和分析使得能够更深入地探索化学空间，并获得以前不切实际或不可能的知识，例如反应、结构单元和官能团兼容性的快速调查。
• Sustainability by design: automated nanoscale 2,3,4-trisubstituted quinazoline diversity
  作者：Mojgan Hadian、Shabnam Shaabani、Pravin Patil、Svitlana V. Shishkina、Harry Böltz、Alexander Dömling

  DOI：10.1039/d0gc00363h

  日期：——

  up to 10-gram resynthesis of quinazolines enabled by the simultaneous variation of four classes of building blocks. Benefits of our approach include a simple to perform, one-step procedure, mild reaction conditions and access to a very large chemical space through accessing many available building blocks. More than thousand derivatives were produced in an automated fashion on a nanoscale using positive

  小分子合成对于材料和药物同样重要。但是，在药物研发中执行的传统方法（包括维护数百万个文库以及以毫摩尔或更大的规模优化数百乃至数千种化学物质的合成）缺乏可持续性。在这里，我们举例说明了新设计的喹喔啉反应的合成实施，以实现化学上的转化可持续性。这包括纳米级合成，深化学空间探索，通过同时改变四类构建基团而实现的从毫克到10克重合成喹唑啉的6个数量级的可扩展性。我们的方法的好处包括执行简单，只需一步，温和的反应条件，以及通过使用许多可用的构建基块来访问很大的化学空间。使用正压促进分配以纳米级的自动化方式生产了数千种衍生物。伴随着这些优势，合成工作量，试剂，溶剂，玻璃和塑料消耗品以及功耗的可观减少大大减少了合成化学的足迹。
• Small-compound enhancers for functional O-mannosylation of alpha-dystroglycan, and uses thereof
  申请人：Wu Xiaohua

  公开号：US10221168B1

  公开（公告）日：2019-03-05

  The present invention provides compounds that can enhance functional O-mannosylation of proteins including alpha-dystroglycan. Also provided are methods of preparation of the compounds defined by the formula I. Also provided are the methods of using the compounds or the pharmaceutical acceptable salts or prodrugs thereof in treating and preventing subjects suffering from the diseases including muscular dystrophies and cancers.

  本发明提供了一种可以增强蛋白质的O-甘露糖基化功能，包括α-骨骼肌糖蛋白的化合物。还提供了一种按照式I定义的化合物的制备方法。同时提供了使用这些化合物或其药用可接受的盐或前药来治疗和预防患有包括肌肉萎缩症和癌症在内的疾病的方法。