5-chloro-1H-pyrrole-2-carboxylic acid | 27746-04-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 5-chloro-1H-pyrrole-2-carboxylic acid
• CAS: 27746-04-9
• 化学式: C₅H₄ClNO₂
• mdl: MFCD19230069
• 分子量: 145.545
• InChiKey: SWLUNFAAJVHVFI-UHFFFAOYSA-N

物化性质

• 沸点：
  361.9±22.0 °C(Predicted)
• 密度：
  1.577±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  53.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  对三氟甲氧基苯胺 、 5-chloro-1H-pyrrole-2-carboxylic acid 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium pyrosulfite 、 葫芦脲 水合物 、 copper(I) bromide 作用下， 以 neat (no solvent) 为溶剂， 反应 1.0h， 以81%的产率得到5-chloro-N-(4-(trifluoromethoxy)phenyl)thiophene-2-sulfonamide
  参考文献：
  名称：

  芳香族磺酰胺的机械化学合成

  摘要：

  开发了一种三组分 Pd 催化的 K 2 S 2 O 5和胺与芳基溴化物或芳族羧酸的氨基磺酰化反应。开发该策略是为了利用机械能并适应伯胺和仲脂肪族和芳族胺，为各种磺胺类药物提供新的捷径。对反应范围和局限性的研究表明，它可以容忍广泛的官能团和许多结构模式。反应放大到克级。

  DOI：

  10.1039/d1cc03224k
• 作为产物：
  描述：

  5-氯-1H-吡咯-2-甲酸甲酯 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 1.75h， 生成 5-chloro-1H-pyrrole-2-carboxylic acid
  参考文献：
  名称：

  2-Aminomethylphenylamine as a novel scaffold for factor Xa inhibitor

  摘要：

  We have been researching orally active factor Xa inhibitor for a long time. We explored the new diamine linker using effective ligands to obtain a new attractive original scaffold 2-aminomethylphenylamine derivative. Compound 1D showed very strong in vitro and in vivo factor Xa inhibitory activity, as well as favorable PK profiles in po administration to monkeys. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.01.035

文献信息

• Gatekeeping Ketosynthases Dictate Initiation of Assembly Line Biosynthesis of Pyrrolic Polyketides
  作者：Dongqi Yi、Atanu Acharya、James C. Gumbart、Will R. Gutekunst、Vinayak Agarwal

  DOI：10.1021/jacs.1c02371

  日期：2021.5.26

  Assembly line biosynthesis of polyketide natural products involves checkpoints where identities of thiotemplated intermediates are verified before polyketide extension reactions are allowed to proceed. Determining what these checkpoints are and how they operate is critical for reprogramming polyketide assembly lines. Here we demonstrate that ketosynthase (KS) domains can perform this gatekeeping role

  聚酮化合物天然产物的流水线生物合成涉及检查点，在允许进行聚酮化合物延伸反应之前验证硫模板化中间体的身份。确定这些检查点是什么以及它们如何运行对于重新编程聚酮化合物装配线至关重要。在这里，我们证明了酮合酶 (KS) 域可以执行此守门角色。通过比较扩展吡咯基和卤化吡咯基底物的聚酮合酶的底物特异性，我们发现需要区分这两种底物的 KS 域具有高选择性。我们还发现 KS 活性位点中的氨基酸残基促进了这种选择性，并且这些残基适合进行合理的工程改造。另一方面，不需要在其天然生理环境中做出选择性决定的 KS 域是底物混杂的。我们还提供证据表明，通过非天然载体蛋白将底物输送到聚酮合酶会伴随着生物合成效率的降低。
• Acetylene Derivatives
  申请人：Glatthar Ralf

  公开号：US20080214673A1

  公开（公告）日：2008-09-04

  The invention provides compounds of formula (I) wherein R 1 represents hydrogen or alkyl; R 2 represents an unsubstituted or substituted heterocycle or R 2 represents an unsubstituted or substituted aryl; R 3 represents alkyl or halogen; X represents a single bond or an alkandiyl-group, optionally interrupted by one or more oxygen atoms or carbonyl groups or carbonyloxy groups in free base or acid addition salt form, processes for their preparation and their use as pharmaceuticals.

  该发明提供了公式(I)的化合物，其中R1代表氢或烷基；R2代表未取代或取代的杂环或未取代或取代的芳基；R3代表烷基或卤素；X代表单键或烷基基团，可选地被一个或多个氧原子或羰基或羰氧基所中断，以自由碱基或酸加成盐形式存在，以及它们的制备方法和作为药物的用途。
• ACETYLENE DERIVATIVES
  申请人：GLATTHAR Ralf

  公开号：US20100099682A1

  公开（公告）日：2010-04-22

  The invention provides compounds of formula (I) wherein R 1 represents hydrogen or alkyl; R 2 represents an unsubstituted or substituted heterocycle or R 2 represents an unsubstituted or substituted aryl; R 3 represents alkyl or halogen; X represents a single bond or an alkandiyl-group, optionally interrupted by one or more oxygen atoms or carbonyl groups or carbonyloxy groups in free base or acid addition salt form, processes for their preparation and their use as pharmaceuticals.

  本发明提供了式（I）的化合物，其中R1代表氢或烷基；R2代表未取代或取代的杂环或R2代表未取代或取代的芳基；R3代表烷基或卤素；X代表单键或者是烷基基团，可以被一个或多个氧原子或羰基或羰氧基所中断，以自由碱或酸加成盐形式存在，以及制备它们的方法和作为药物的用途。
• Novel endothelin receptor antagonists isolated from microbispora
  申请人：MERCK & CO. INC.

  公开号：EP0496452A1

  公开（公告）日：1992-07-29

  Novel cyclic depsipeptides derived from a culture of Microbispora are receptor antagonists of endothelin, a potent vasoconstrictor, and are thus useful in treating cardiovascular disorders. Endothelin has also other physiological effects, and the endothelin receptor antagonists of the present invention thus have also other therapeutic uses. The compounds are cyclic depsipeptides of N-(pyrrol-2-carboxy) - L-Phe, D-allo-Thr, D-Phe, D-Ala, D- or L-dihydroxyphenyl-Gly, and D-dihydroxyphenyl-Gly.

  从微囊藻培养物中提取的新型环去肽是一种强效血管收缩剂--内皮素的受体拮抗剂，因此可用于治疗心血管疾病。内皮素还具有其他生理作用，因此本发明的内皮素受体拮抗剂还具有其他治疗用途。这些化合物是 N-（吡咯-2-羧基）-L-Phe、D-allo-Thr、D-Phe、D-Ala、D-或 L-二羟基苯基-Gly 和 D-二羟基苯基-Gly 的环状去肽。
• Improved Stability of Proline-Derived Direct Thrombin Inhibitors through Hydroxyl to Heterocycle Replacement
  作者：Harry R. Chobanian、Barbara Pio、Yan Guo、Hong Shen、Mark A. Huffman、Maria Madeira、Gino Salituro、Jenna L. Terebetski、James Ormes、Nina Jochnowitz、Lizbeth Hoos、Yuchen Zhou、Dale Lewis、Brian Hawes、Lyndon Mitnaul、Kim O’Neill、Kenneth Ellsworth、Liangsu Wang、Tesfaye Biftu、Joseph L. Duffy

  DOI：10.1021/acsmedchemlett.5b00047

  日期：2015.5.14

  Modification of the previously disclosed (S)-N-(2-aminmethyl-5-chlorobenzyl)-1-((R)-2-hydroxy-3,3-dimethylbutanoyl)pyrrolidine-2-carboxamide 2 by optimization of the P3 group afforded novel, low molecular weight thrombin inhibitors. Heterocycle replacement of the hydroxyl functional group helped maintain thrombin in vitro potency while improving the chemical stability and pharmacokinetic profile. These modifications led to the identification of compound 10, which showed excellent selectivity over related serine proteases as well as in vivo efficacy in the rat arteriovenous shunt. Compound 10 exhibited significantly improved chemical stability and pharmacokinetic properties over 2 and may be utilized as a structurally differentiated preclinical tool comparator to dabigatran etexilate (Pro-1) to interrogate the on- and off-target effects of oral direct thrombin inhibitors.