(1H-吡咯-3-基)甲胺 | 888473-50-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: (1H-吡咯-3-基)甲胺
• 英文名称: (1H-pyrrol-3-yl)methanamine
• 英文别名: 1H-pyrrol-3-ylmethanamine
• CAS: 888473-50-5
• 化学式: C₅H₈N₂
• mdl: MFCD12964602
• 分子量: 96.1319
• InChiKey: YECAHBRVIMAHCI-UHFFFAOYSA-N

物化性质

• 沸点：
  154 °C
• 密度：
  1.095±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  7
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  41.8
• 氢给体数：
  2
• 氢受体数：
  1

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  (1H-吡咯-3-基)甲胺 在 (1R,2R)-(-)-N,N'-二甲基-1,2-环己二胺 、 水 、 potassium carbonate 、 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 copper(I) bromide 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 51.25h， 生成 4-(3-(acrylamidomethyl)-1H-pyrrol-1-yl)benzoic acid
  参考文献：
  名称：

  An NMR-Guided Screening Method for Selective Fragment Docking and Synthesis of a Warhead Inhibitor

  摘要：

  针对布鲁氏菌梅利滕斯的谷胱甘肽还原酶同源物的选择性命中通过STD NMR确定，并通过trNOE和15N-HSQC滴定进行了验证。最有前途的命中物RK207被使用评分函数对接到目标分子上，以将模拟构象与实验数据进行比较。在阐明可能的构象后，该命中物通过与电亲性丙烯酰胺战斗头的扩展进一步优化为领先化合物。我们相信，在药物发现的早期阶段专注于选择性，将限制在优化领先化合物时可能与人类同源物发生的交叉反应性。动力学研究揭示，修饰有酯基的领先化合物5的反应性高于丙烯酰胺对照；然而，在修饰后，该化合物对细菌蛋白相较于人类同源物显示出很少的选择性。相比之下，将化合物5水解为酸性形式导致该化合物活性降低。这些结果表明，这种简单的化学框架需要更多的优化，并为发现针对谷胱甘肽还原酶蛋白的药物开辟了新途径——这之前未被开发的抗生素剂库。

  DOI：

  10.3390/molecules21070846
• 作为产物：
  描述：

  吡咯-3-甲醛 在 乙醇 、 盐酸羟胺 、 sodium 、 potassium carbonate 作用下， 以 水 为溶剂， 反应 0.5h， 生成 (1H-吡咯-3-基)甲胺
  参考文献：
  名称：

  Refinement of the Benzodiazepine Receptor Site Topology by Structure−Activity Relationships of New N-(Heteroarylmethyl)indol-3-ylglyoxylamides

  摘要：

  N-(Heteroaryiniethyl)indol-3-ylglyoxylamides (1-26) were synthesized and evaluated as ligands of the benzodiazepine receptor (BzR) to probe the hydrogen bonding properties of the so-called S, site of the BzR by means of suitable heterocyclic side chains. SARs were developed in light of our hypothesis of binding modes A and B. Pyrrole and furan derivatives adopting mode A (2, 8, 10, 20, 22) turned out to be more potent (K-i values < 35 nM) than their analogues lacking hydrogen bonding heterocyclic side chains. These data suggest that the most potent indoles interact with a hydrogen bond acceptor/donor (HBA/D) group located within the S, site of the BzR. Compounds 1, 2, 8, 19, 20, and 22, tested at recombinant rat (alpha(1)beta(2)gamma(2),, alpha(2)beta(2)gamma(2), and alpha(5)beta(3)gamma(2) BzRs, elicited selectivity for the alpha(1)beta(2)gamma(2) isoform. On the basis of published mutagenesis studies and the present SARs, we speculate that the S, HBA/D group might be identified as the hydroxyl of alpha(1)-Tyr209 or of other neighboring amino acids.

  DOI：

  10.1021/jm0511841

文献信息

• Ru-catalysed C–H silylation of unprotected gramines, tryptamines and their congeners
  作者：K. Devaraj、C. Sollert、C. Juds、P. J. Gates、L. T. Pilarski

  DOI：10.1039/c6cc00803h

  日期：——

  Selective Ru-catalysed C2-H silylation of heteroarenes is presented. The transformation works with or without directing group assistance and requires no protecting groups. Gramines and tryptamines may be converted efficiently whilst...

  提出了选择性Ru催化杂芳烃的C2-H甲硅烷基化。无论有没有直接的团体协助，这种转变都是有效的，并且不需要保护团体。谷氨酰胺和色胺可在...
• Rational Computational Design of Fourth-Generation EGFR Inhibitors to Combat Drug-Resistant Non-Small Cell Lung Cancer
  作者：Hwangseo Park、Hoi-Yun Jung、Kewon Kim、Myojeong Kim、Sungwoo Hong

  DOI：10.3390/ijms21239323

  日期：——

  third-generation EGFR inhibitors. Herein, we report the discovery of potent and highly selective inhibitors of EGFR exon 19 p.E746_A750del/EGFR exon 20 p.T790M/EGFR exon 20 p.C797S (d746-750/T790M/C797S) mutant, which were derived via two-track virtual screening and de novo design. This two-track approach was performed so as to maximize and minimize the inhibitory activity against the triple mutant and the

  尽管单突变表皮生长因子受体（EGFR）激酶的抑制剂可有效治疗非小细胞肺癌（NSCLC），但由于各种具有耐药性的双重和三重EGFR突变体的出现，其临床疗效受到了限制。因此，鉴定对第一，第二和第三代EGFR抑制剂具有抗性的三重突变EGFR的有效和选择性抑制剂已变得迫在眉睫。在此，我们报告了发现了有效且高度选择性的EGFR外显子19 p.E746_A750del / EGFR外显子20 p.T790M / EGFR外显子20 p.C797S（d746-750 / T790M / C797S）突变体的抑制剂，这些突变体是通过两个跟踪虚拟筛选和从头设计。进行这种两轨方法以便最大化和最小化分别对三重突变体和野生型的抑制活性。最初命中化合物的广泛化学修饰导致鉴定了d746-750 / T790M / C797S突变体的几种低纳摩尔抑制剂。其中，与野生型相比，两种化合物在抑制EGFRd746-750 / T790M
• Dual FLT3/haspin kinase inhibitor based on 3<i>H</i>-pyrazolo[4,3-<i>f</i>]quinoline scaffold with activities against acute myeloid leukemia
  作者：Allison L. Kempen、Nickolas R. Brauer、Herman O. Sintim

  DOI：10.1039/d3md00192j

  日期：——

  in cells. While multi-component reactions (MCRs) have been used to make many bioactive molecules, there are very few examples of using MCRs to make compounds that target protein kinases, which have emerged as one of the top drug candidates (especially in oncology). This work highlights our recent efforts to make ultrapotent protein kinase inhibitors using multi-component reactions (especially the Doebner–Povarov

  3 H-吡唑并[4,3- f ]喹啉核心是一种来自喹啉和吲唑的特殊融合部分，可在一烧瓶多组分Doebner-Povarov反应中轻松合成，是一种新描述的激酶铰链结合物。先前的工作已经证明，3 H-吡唑并[4,3- f ]喹啉部分可以通过明智的取代模式进行调整，以选择性抑制癌症相关激酶，例如FLT3和haspin。第一代基于3 H-吡唑并[4,3- f ]喹啉的haspin抑制剂HSD972和FLT3抑制剂HSD1169先前被公开为多种癌细胞系的抑制剂。鉴于最近发现 haspin 过度表达并在许多癌症中发挥关键的增殖作用，并且许多小组现在正在积极开发具有针对 FLT3 和其他重要激酶双重活性的化合物，我们对优化 3 H -吡唑并[ 4,3- f ]喹啉基化合物可提高针对 FLT3 和 haspin 的活性。在此，我们报告了基于 3 H-吡唑并[4,3- f ]喹啉的新型双 FLT3/haspin
• Generation and structure-activity relationships of novel imidazo-thienopyridine based TLR7 agonists: application as payloads for immunostimulatory antibody drug-conjugates
  作者：Michael G. Brant、Graham A.E. Garnett、Joy Guedia、Manuel Lasalle、Samuel Lawn、Mark E. Petersen、Renee Duan、José Mendez-Campos、Truman Hirkala-Schaefer、Geoffrey C. Winters、Stuart D. Barnscher

  DOI：10.1016/j.bmcl.2023.129348

  日期：2023.7
• Refinement of the Benzodiazepine Receptor Site Topology by Structure−Activity Relationships of New <i>N</i>-(Heteroarylmethyl)indol-3-ylglyoxylamides
  作者：Giampaolo Primofiore、Federico Da Settimo、Anna Maria Marini、Sabrina Taliani、Concettina La Motta、Francesca Simorini、Ettore Novellino、Giovanni Greco、Barbara Cosimelli、Marina Ehlardo、Annalisa Sala、François Besnard、Marina Montali、Claudia Martini

  DOI：10.1021/jm0511841

  日期：2006.4.1

  N-(Heteroaryiniethyl)indol-3-ylglyoxylamides (1-26) were synthesized and evaluated as ligands of the benzodiazepine receptor (BzR) to probe the hydrogen bonding properties of the so-called S, site of the BzR by means of suitable heterocyclic side chains. SARs were developed in light of our hypothesis of binding modes A and B. Pyrrole and furan derivatives adopting mode A (2, 8, 10, 20, 22) turned out to be more potent (K-i values < 35 nM) than their analogues lacking hydrogen bonding heterocyclic side chains. These data suggest that the most potent indoles interact with a hydrogen bond acceptor/donor (HBA/D) group located within the S, site of the BzR. Compounds 1, 2, 8, 19, 20, and 22, tested at recombinant rat (alpha(1)beta(2)gamma(2),, alpha(2)beta(2)gamma(2), and alpha(5)beta(3)gamma(2) BzRs, elicited selectivity for the alpha(1)beta(2)gamma(2) isoform. On the basis of published mutagenesis studies and the present SARs, we speculate that the S, HBA/D group might be identified as the hydroxyl of alpha(1)-Tyr209 or of other neighboring amino acids.