N¹-methyl lansoprazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: N¹-methyl lansoprazole
• 英文别名: N-methyl lansoprazole；1-methyl-2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl]benzimidazole
• 化学式: C₁₇H₁₆F₃N₃O₂S
• 分子量: 383.394
• InChiKey: OSFITLUTZVXDRB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  76.2
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  兰索拉唑 、 硫酸二甲酯 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 为溶剂， 生成 N¹-methyl lansoprazole
  参考文献：
  名称：

  质子泵抑制剂对胃 (H+, K+)-ATPase 的共价抑制化学

  摘要：

  质子泵抑制剂 (PPI) 是广泛用于治疗酸相关疾病的药物，是取代的吡啶基甲基亚磺酰基苯并咪唑或咪唑并吡啶衍生物。它们都是通过酸激活反应性亲硫体来抑制胃分泌酸 (H(+), K(+))-ATPase 的前药，这些亲硫体与一个或多个可从酶的外质表面接触的半胱氨酸形成二硫键。这种独特的酸催化机制归因于吡啶环的亲核性。然而，此处获得的数据表明，它们向反应性阳离子亲硫磺酸或次磺酰胺的转化主要不依赖于吡啶质子化，而是依赖于咪唑组分的第二次质子化，这增加了咪唑上 C-2 位的亲电性。这种质子化导致 C-2 与吡啶环的未质子化部分反应形成反应性衍生物。相关的 PPI pK(a) 由苯并咪唑或咪唑并吡啶亚磺酰基甲基部分在不同介质 pH 值下的紫外光谱测定。相对酸稳定的类似物 N(1)-甲基兰索拉唑 (6b) 的合成允许直接测定该完整 PPI 的两个 pK(a) 值，从而可以计算所有 PPI 的两个 pK(a)

  DOI：

  10.1021/ja049607w

文献信息

• [EN] INHIBITORS OF SARM1 NADase ACTIVITY AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACTIVITÉ SARM1 NADASE ET UTILISATIONS DE CEUX-CI
  申请人：UNIV WASHINGTON

  公开号：WO2018057989A1

  公开（公告）日：2018-03-29

  The present disclosure provides compounds useful as inhibitors of SARM1 NADase activity, compositions thereof, and methods of using the same. The present disclosure provides compounds useful for treating a neurodegenerative or neurological disease or disorder, compositions thereof, and methods of using the same.

  本公开提供了用作SARM1 NADase活性抑制剂的化合物，其组合物以及使用方法。本公开还提供了用于治疗神经退行性或神经疾病或失调的化合物，其组合物以及使用方法。
• Benzimidazole compounds, process for producing the same and use thereof
  申请人：——

  公开号：US20040039027A1

  公开（公告）日：2004-02-26

  A compound represented by the formula (I) 1 wherein each symbol is as defined in the specification, or a salt thereof (1) shows a superior anti-ulcer activity, a gastric acid secretion-suppressive action, a mucosa-protecting action, an anti- Helicobacter pylori action and the like in living organisms, (2) shows low toxicity, (3) is stable to acid (which obviates the need to formulate an enteric-coated preparation, thereby lowering the cost, and reduces the size of preparation to facilitate swallowing for patients having difficulty in swallowing), (4) shows faster absorption than enteric-coated preparations (rapid expression of gastric acid secretion-suppressive action), and (5) is sustainable. According to the present invention, a benzimidazole compound, which has superior stability to acid and which is converted to a proton pump inhibitor in living organisms to show an anti-ulcer activity and the like, can be provided.

  化合物式（I）所表示的化合物，其中每个符号如规范中所定义，或其盐（1）在生物体中表现出优越的抗溃疡活性，抑制胃酸分泌作用，保护粘膜作用，抗幽门螺杆菌作用等，（2）显示低毒性，（3）稳定耐酸（无需制备肠溶涂层制剂，从而降低成本，并减小制剂大小以便于吞咽难度较大的患者），（4）显示比肠溶涂层制剂更快的吸收（迅速表现出抑制胃酸分泌作用），（5）具有可持续性。根据本发明，可以提供一种苯并咪唑化合物，其对酸稳定性优越，并在生物体内转化为质子泵抑制剂以显示抗溃疡活性等。
• Methods of Preparing Sulfinamides and Sulfoxides
  申请人：Senanayake Hugh Chris

  公开号：US20070293682A1

  公开（公告）日：2007-12-20

  This invention encompasses novel methods of preparing sulfinamides and sulfoxides, particularly stereomerically pure sulfinamides and sulfoxides. The invention further encompasses novel compounds from which sulfinamides and sulfoxides can be prepared.

  本发明涵盖了制备磺酰胺和磺醇的新方法，特别是立体异构纯的磺酰胺和磺醇。该发明还涵盖了可以制备磺酰胺和磺醇的新化合物。
• BENZIMIDAZOLE COMPOUNDS, PROCESS FOR PRODUCING THE SAME AND USE THEREOF
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1334971A1

  公开（公告）日：2003-08-13

  A compound represented by the formula (I) wherein each symbol is as defined in the specification, or a salt thereof (1) shows a superior anti-ulcer activity, a gastric acid secretion-suppressive action, a mucosa-protecting action, an anti-Helicobacter pylori action and the like in living organisms, (2) shows low toxicity, (3) is stable to acid (which obviates the need to formulate an enteric-coated preparation, thereby lowering the cost, and reduces the size of preparation to facilitate swallowing for patients having difficulty in swallowing), (4) shows faster absorption than enteric-coated preparations (rapid expression of gastric acid secretion-suppressive action), and (5) is sustainable. According to the present invention, a benzimidazole compound, which has superior stability to acid and which is converted to a proton pump inhibitor in living organisms to show an anti-ulcer activity and the like, can be provided.

  由式(I)代表的化合物 其中各符号如说明书中所定义，或其盐 (1) 在生物体内显示出卓越的抗溃疡活性、胃酸分泌抑制作用、粘膜保护作用、抗幽门螺杆菌作用等；(2) 毒性低；(3) 对酸稳定（无需配制肠溶制剂、(4) 比肠溶制剂吸收更快（快速发挥抑制胃酸分泌的作用），以及 (5) 具有可持续性。 根据本发明，可以提供一种苯并咪唑化合物，该化合物对酸具有超强的稳定性，在生物体内可转化为质子泵抑制剂，从而显示出抗溃疡等活性。
• Evaluation of [¹¹C]<i>N</i>-Methyl Lansoprazole as a Radiopharmaceutical for PET Imaging of Tau Neurofibrillary Tangles
  作者：Xia Shao、Garrett M. Carpenter、Timothy J. Desmond、Phillip Sherman、Carole A. Quesada、Maria Fawaz、Allen F. Brooks、Michael R. Kilbourn、Roger L. Albin、Kirk A. Frey、Peter J. H. Scott

  DOI：10.1021/ml300216t

  日期：2012.11.8

  [C-11]N-Methyl lansoprazole ([C-11]NML, 3) was synthesized and evaluated as a radiopharmaceutical for quantifying tau neurofibrillary tangle (NFT) burden using positron emission tomography (PET) imaging. [C-11]NML was synthesized from commercially available lansoprazole in 4.6% radiochemical yield (noncorrected RCY, based upon [C-11]MeI), 99% radiochemical purity, and 16095 Ci/mmol specific activity (n = 5). Log P was determined to be 2.18. A lack of brain uptake in rodent inicroPET imaging revealed [C-11]NML to be a,substrate for the rodent permeability-glycoprotein 1 (PGP) transporter, but this could be overcome by, pretreating with cyclosporin A to block the PGP. Contrastingly, [C-11]NML was not found to be a substrate for the primate PGP, and microPET imaging in rhesus revealed [C-11]NML uptake in the healthy primate brain of similar to 1600 nCi/cc maximum at 3 min followed by rapid egress to 500 nCi/cc. Comparative autoradiography between wild type rats and transgenic rats expressing human tau (hTau +/+) revealed 12% higher uptake of [C-11]NML in the cortex of brains expressing human tau. Further autoradiography with tau positive brain samples from progressive supranuclear palsy (PSP) patients revealed colocalization of [C-11]NML with tau NFTs identified using modified Bielschowsky staining. Finally, saturation binding experiments with heparin-induced tau confirmed K-d and Bmax values of [C-11]NML as 700 pM and 0.214 fmol/mu g, respectively.