2-(4-fluoronaphthalen-1-yl)acetyl chloride | 2927-80-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-(4-fluoronaphthalen-1-yl)acetyl chloride
• 英文别名: 4-Fluoro-1-naphthaleneacetyl chloride
• CAS: 2927-80-2
• 化学式: C₁₂H₈ClFO
• 分子量: 222.646
• InChiKey: KPUIVSUPMBTSRT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(4-fluoronaphthalen-1-yl)acetyl chloride 在 三氯化铝 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 5-氟苊-1-酮
  参考文献：
  名称：

  BENZIMIDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF

  摘要：

  公开号：

  EP2128154B1
• 作为产物：
  描述：

  2-(4-氟萘-1-基)丙酸 在 N,N-二甲基甲酰胺 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 2-(4-fluoronaphthalen-1-yl)acetyl chloride
  参考文献：
  名称：

  BENZIMIDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF

  摘要：

  公开号：

  EP2128154B1

文献信息

• Hit discovery of Mycobacterium tuberculosis inosine 5′-monophosphate dehydrogenase, GuaB2, inhibitors
  作者：Niteshkumar U. Sahu、Vinayak Singh、Davide M. Ferraris、Menico Rizzi、Prashant S. Kharkar

  DOI：10.1016/j.bmcl.2018.04.045

  日期：2018.6

  physicochemical properties, for growth inhibitory activity against drug-sensitive MtbH37Rv. The eight hits and mycophenolic acid, a prototype IMPDH inhibitor, were further evaluated for activity on purified Mtb-GuaB2 enzyme, target selectivity using a conditional knockdown mutant of guaB2 in Mtb, followed by cross-resistance to IMPDH inhibitor-resistant SRMV2.6 strain of Mtb, and activity on human IMPDH2 isoform

  结核病仍然是全球关注的问题。由于抗药性结核分枝杆菌（Mtb）的发展，迫切需要更新的抗结核药物。鸟嘌呤核苷酸生物合成所需的Mtb的肌苷5'-单磷酸脱氢酶（IMPDH）guaB2是药物开发的有吸引力的靶标。在这项研究中，我们筛选了一个集中的库，该库包含73种具有期望的计算/预测的理化性质的药物样分子，用于针对药物敏感性MtbH37Rv的生长抑制活性。进一步评估了八种命中物和一种原型IMPDH抑制剂麦考酚酸对纯化的Mtb-GuaB2酶的活性，使用条件敲低guaB2突变体在Mtb中对靶标的选择性进行了评估，然后对抗IMPDH抑制剂的SRMV2.6菌株进行交叉耐药和对人IMPDH2亚型的活性。命中之一13是5-氨基邻苯二甲酰胺衍生物，已显示出对Mtb-GuaB2酶具有抑制生长的潜力和靶标特异性。13号命中分子是有前途的分子，有可能作为抗结核药进一步发展。
• Design, synthesis and biological evaluation of Helicobacter pylori inosine 5′-monophosphate dehydrogenase (HpIMPDH) inhibitors. Further optimization of selectivity towards HpIMPDH over human IMPDH2
  作者：Chetan P. Shah、Gayathri Purushothaman、Vijay Thiruvenkatam、Sivapriya Kirubakaran、Kapil Juvale、Prashant S. Kharkar

  DOI：10.1016/j.bioorg.2019.04.001

  日期：2019.6

  Inosine 5'-monophosphate dehydrogenase (IMPDH, EC 1.1.1.205) catalyzes a crucial step in guanine nucleotide biosynthesis, thereby governing cell proliferation. In contrast to mammalian IMPDH5, microbial IMPDH5 are relatively less explored as potential targets for antimicrobial drug discovery. In continuation with our previous work, here we report the discovery of moderately potent and highly selective Helicobacter pylori IMPDH (HpIMPDH) inhibitors. The present study is mainly focused around our previously identified, modestly potent and relatively nonselective (for HpIMPDH over human IMPDH2) hit molecule IX (16i). In an attempt to optimize the selectivity for the bacterial enzyme, we screened a set of 48 redesigned new chemical entities (NCEs) belonging to 5-aminoisobenzofuran-1(3H)-one series for their in vitro HpIMPDH and human IMPDH2 inhibition. A total of 12 compounds (hits) demonstrated >= 70% HpIMPDH inhibition at 10 mu M concentration; none of the hits were active against hIMPDH2. Compound 24 was found to be the most potent and selective molecule (HpIMPDH IC50 = 2.21 mu M) in the series. The study reaffirmed the utility of 5-aminoisobenzofiffan-1(3H)-one as a promising scaffold with great potential for further development of potent and selective HpIMPDH inhibitors.