SGT1416 | 7643-96-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: SGT1416
• 英文别名: 4-Amino-1-(4-fluoro-phenyl)-butan-1-one；4-amino-1-(4-fluorophenyl)butan-1-one
• CAS: 7643-96-1
• 化学式: C₁₀H₁₂FNO
• 分子量: 181.21
• InChiKey: WIUNBQSCYJOJFI-UHFFFAOYSA-N

物化性质

• 沸点：
  300.6±22.0 °C(Predicted)
• 密度：
  1.119±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  43.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  SGT1416 在 sodium methylate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 12.08h， 生成 N-(4-(4-fluorophenyl)-4-oxobutyl)-4-methoxy-N-methylbenzenesulfonamide
  参考文献：
  名称：

  COMPOUNDS TO INHIBIT CALCIUM/CALMODULIN DEPENDENT PROTEIN KINASE II AND APPLICATIONS THEREOF

  摘要：

  提供了一些新型苯磺酰胺化合物，可以抑制钙/钙调蛋白激酶II（CaMKII）的活性，以及含有这些苯磺酰胺化合物的药物组合物。此外，还提供了使用这些苯磺酰胺化合物治疗与CaMKII活性有关的疾病或病症（如黄病毒感染）的方法。

  公开号：

  US20190300475A1
• 作为产物：
  描述：

  N-[4-(4-fluoro-phenyl)-4-oxo-butyl]-phthalimide 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以72%的产率得到SGT1416
  参考文献：
  名称：

  Antagonism of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane stimulus with a newly identified 5-HT2- versus 5-HT1C-selective antagonist

  摘要：

  DOM [i.e., 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane] is a 5-HT1C/2 serotonin agonist that exerts stimulus control of behavior in animals. In order to determine if the discriminative stimulus effect of DOM is 5-HT1C- or 5-HT2-mediated, it would be informative to conduct tests of stimulus antagonism with a 5-HT1C- or 5-HT2-selective antagonist. To date, no such agents exist. Although the neuroleptic agent spiperone binds at D2 dopamine receptors and 5-HT1A serotonin receptors, (a) it displays about a 1000-fold selectivity for 5-HT2 versus 5-HT1C sites and (b) it has been used as a ''5-HT2-selective'' antagonist. Because spiperone is a behaviorally disruptive agent, it is not suitable for use in drug-discrimination studies. Using the spiperone molecule as a starting point, a limited structure-affinity investigation was conducted in order to identify a suitable antagonist with high affinity and selectivity for 5-HT2 receptors, and yet an antagonist that might lack the disruptive actions of spiperone. Various modifications of the spiperone molecule were examined, but most resulted in decreased 5-HT2 affinity or in loss of selectivity. One compound, 8-[3-(4-fluorophenoxy)propyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one(26), was shown to bind at 5-HT2 sites with high affinity (K(i) = 2 nM) and >2,000-fold selectivity versus 5-HT1C sites. In tests of stimulus antagonism using rats trained to discriminate 1 mg/kg of DOM from saline vehicle, 26 behaved as a potent antagonist (ED50 = 0.003 mg/kg) and lacked the disruptive effects associated with spiperone. As such, (a) it would appear that the DOM stimulus is primarily a 5-HT2-mediated, and not 5-HT1C-mediated, phenomenon, and (b) compound 26 may find application in other pharmacologic investigations where spiperone may not be a suitable antagonist.

  DOI：

  10.1021/jm00069a010

文献信息

• Structure-based design of haloperidol analogues as inhibitors of acetyltransferase Eis from <i>Mycobacterium tuberculosis</i> to overcome kanamycin resistance
  作者：Ankita Punetha、Keith D. Green、Atefeh Garzan、Nishad Thamban Chandrika、Melisa J. Willby、Allan H. Pang、Caixia Hou、Selina Y. L. Holbrook、Kyle Krieger、James E. Posey、Tanya Parish、Oleg V. Tsodikov、Sylvie Garneau-Tsodikova

  DOI：10.1039/d1md00239b

  日期：——

  structure of the Eis-haloperidol (1) complex, which guided synthesis of 34 analogues. The structure–activity relationship study showed that in addition to haloperidol (1), eight analogues, some of which were smaller than 1, potently inhibited Eis (IC50 ≤ 1 μM). Crystal structures of Eis in complexes with three potent analogues and droperidol (DPD), an antiemetic and antipsychotic, were determined. Three

  结核病 (TB) 由结核分枝杆菌( Mtb ) 引起，是一种致命的细菌性疾病。Mtb的耐药菌株使根除结核病成为一项艰巨的任务。Mtb过度表达增强的细胞内存活 (Eis) 蛋白赋予了对二线抗生素卡那霉素 (KAN) 的抗性。Eis 是一种乙酰转移酶，可将 KAN 乙酰​​化，使其抗菌功能失活。开发 Eis 抑制剂作为 KAN 辅助治疗剂是预防和克服 KAN 耐药性的一条有吸引力的途径。我们发现抗精神病药物氟哌啶醇 (HPD, 1 ) 是一种有效的 Eis 抑制剂，IC 50= 0.39 ± 0.08 μM。我们确定了 Eis-氟哌啶醇 ( 1 ) 复合物的晶体结构，该复合物指导了 34 种类似物的合成。构效关系研究表明，除氟哌啶醇 ( 1 ) 外，还有 8 种类似物，其中一些小于1，可有效抑制 Eis (IC 50 ≤ 1 μM)。确定了 Eis 与三种强效类似物和氟哌利多 (DPD)（一种
• Sigma receptor ligands and methods of modulating cellular protein homeostasis using same
  申请人：DREXEL UNIVERSITY

  公开号：US10314795B2

  公开（公告）日：2019-06-11

  The present invention includes compounds useful in preventing, treating or ameliorating Sigma-related disorders or diseases. The compounds of the invention may modulate cellular protein homeostasis, which includes: translation initiation, folding, processing, transport, and degradation (including ubiquitin selective autophagy) of proteins. The present invention also includes methods of preventing, treating or ameliorating a Sigma-related disorder or disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a Sigma-modulating compound. The present invention also includes methods of preventing, treating or ameliorating a Sigma-related disorder or disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a Sigma-modulating compound, further comprising administering an effective amount of a compound that inhibits the ubiquitin proteasome system (UPS) and/or autophagic survival pathways.

  本发明包括可用于预防、治疗或改善西格玛相关紊乱或疾病的化合物。本发明的化合物可调节细胞蛋白质的平衡，其中包括：蛋白质的翻译起始、折叠、加工、运输和降解（包括泛素选择性自噬）。本发明还包括预防、治疗或改善有需要的受试者与 Sigma 相关的失调或疾病的方法，该方法包括向受试者施用有效量的 Sigma 调节化合物。本发明还包括预防、治疗或改善有需要的受试者的西格玛相关紊乱或疾病的方法，该方法包括向受试者施用有效量的西格玛调节化合物，进一步包括施用有效量的抑制泛素蛋白酶体系统（UPS）和/或自噬存活途径的化合物。
• DE2817494
  申请人：——

  公开号：——

  公开（公告）日：——
• Benzenesulfonamide Derivatives as Calcium/Calmodulin-Dependent Protein Kinase Inhibitors and Antiviral Agents against Dengue and Zika Virus Infections
  作者：Wei-Chia Chen、Yogy Simanjuntak、Li-Wei Chu、Yueh-Hsin Ping、Yi-Ling Lee、Yi-Ling Lin、Wen-Shan Li

  DOI：10.1021/acs.jmedchem.9b01779

  日期：2020.2.13

  Emerging and resurging mosquito-borne flaviviruses are an important public health challenge. The increased prevalence of dengue virus (DENY) infection has had a significant socioeconomic impact on epidemic countries. The recent outbreak of Zika virus (ZIKV) has created an international public health emergency because ZIKV infection has been linked to congenital defects and Guillain-Barre syndrome. To develop potentially prophylactic antiviral drugs for combating these acute infectious diseases, we have targeted the host calcium/calmodulin-dependent kinase II (CaMKII) for inhibition. By using CaMKII structure-guided inhibitor design, we generated four families of benzenesulfonamide (BSA) derivatives for SAR analysis. Among these substances, N-(4-cyclohepty1-4-oxobuty1)-4-methoxy-N-phenylbenzenesulfonamide (9) showed superior properties as a lead CaMKII inhibitor and antiviral agent. BSA 9 inhibited CaMKII activity with an IC50 value of 0.79 mu M and displayed EC50 values of 1.52 mu M and 1.91 mu M against DENY and ZIKV infections of human neuronal BE(2)C cells, respectively. Notably, 9 significantly reduced the viremia level and increased animal survival time in mouse-challenge models.
• METHODS OF IDENTIFYING AND TREATING TUMORS WITH SIGMA1 INHIBITORS
  申请人：DREXEL UNIVERSITY

  公开号：US20200087730A1

  公开（公告）日：2020-03-19

  Methods and uses of using Sigma1 inhibitors are provide herein, including diagnostic methods for predicting or identifying quantitatively whether a human tumor is responsive or non-responsive to treatment with Sigma1 inhibition are also provided.