2-[2-(4-phenylpiperazin-1-yl)acetylamino]benzothiazole | 191598-86-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-[2-(4-phenylpiperazin-1-yl)acetylamino]benzothiazole
• 英文别名: N-(1,3-benzothiazol-2-yl)-2-(4-phenylpiperazin-1-yl)acetamide
• CAS: 191598-86-4
• 化学式: C₁₉H₂₀N₄OS
• mdl: MFCD05144681
• 分子量: 352.46
• InChiKey: HWTOESXSHJRETQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  76.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氨基苯并噻唑 在 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 4.33h， 生成 2-[2-(4-phenylpiperazin-1-yl)acetylamino]benzothiazole
  参考文献：
  名称：

  N-（苯并[ d ]噻唑-2-基）-2-（哌嗪-1-基）乙酰胺类似物作为COX-2抑制剂的合成，药理学评价和对接研究

  摘要：

  现有的具有多种毒性的NSAID强调了发现新的无毒抗炎剂的需要。在这封信中，我们介绍了简单的两步化学合成，体内药理学筛选和对接研究，研究了几种N-（苯并[ d ]噻唑-2-基）-2-（哌嗪-1-基）乙酰胺类似物。将不同的氨基苯并噻唑进行氯乙酰化，并在碱的存在下与取代的哌嗪进一步反应，得到N-（苯并[ d ]噻唑-2-基）-2-（哌嗪-1-基）乙酰胺类似物（A1 - C4）。通过角叉菜胶诱导的爪水肿方法评价了这些化合物的抗炎活性。通过评估致溃疡的可能性来筛选有前景的化合物的毒性。使用Sybyl软件的Surflex-Dock GeomX程序在Dell T-1500工作站上针对COX-2酶进行了分子对接实验，以确认系列中活性化合物的作用机理。在计算机研究中，N-（苯并[ d ]噻唑-2-基）-2-（哌嗪-1-基）乙酰胺类似物与COX-2蛋白的结合相互作用与体内抗炎活性一致。

  DOI：

  10.1016/j.bmcl.2011.12.062

文献信息

• 2-piperazinoalkylaminobenzoazole derivatives: dopamine receptor subtype specific ligands
  申请人：Neurogen Corporation

  公开号：US20020058666A1

  公开（公告）日：2002-05-16

  Disclosed are compounds of the formula: 1 or pharmaceutically acceptable salts thereof, wherein: A is (un)substituted alkylene; R 1 and R 2 are the same or different and represent hydrogen, halogen, alkyl, alkoxy, alkylthio, hydroxy, (un)substitutedamino, cyano, nitro, sulfonamide, trifluoromethyl or trifluoromethoxy; R 3 , R 4 , R 5 , R 6 , and R 8 are independently hydrogen or alkyl; and X is sulfur, oxygen or NR 7 where R 8 is defined herein; m is an integer chosen from 0, 1 or 2; and Ar is an aryl or heteroaryl group as further defined herein, which compounds are useful for the treatment and/or prevention of neuropsychological disorders including, but not limited to, schizophrenia, mania, dementia, depression, anxiety, compulsive behavior, substance abuse, Parkinson-like motor disorders and motion disorders related to the use of neuroleptic agents.

  本发明公开了以下式子的化合物 1 或其药学上可接受的盐，其中 A 是（未）取代的亚烷基； R 1 和 R 2 相同或不同，代表氢、卤素、烷基、烷氧基、烷硫基、羟基、（未）取代氨基、氰基、硝基、磺酰胺、三氟甲基或三氟甲氧基； R 3 , R 4 , R 5 , R 6 和 R 8 独立地为氢或烷基；以及 X 是硫、氧或 NR 7 其中 R 8 在此定义； m 是选自 0、1 或 2 的整数；以及 Ar 是本文进一步定义的芳基或杂芳基、 这些化合物可用于治疗和/或预防神经心理障碍，包括但不限于精神分裂症、躁狂症、痴呆症、抑郁症、焦虑症、强迫行为、药物滥用、帕金森样运动障碍以及与使用神经安定剂有关的运动障碍。
• Targeting EGFR tyrosine kinase: Synthesis, in vitro antitumor evaluation, and molecular modeling studies of benzothiazole-based derivatives
  作者：Amal M. Mokhtar、Shahenda M. El-Messery、Mariam A. Ghaly、Ghada S. Hassan

  DOI：10.1016/j.bioorg.2020.104259

  日期：2020.11

  New benzothiazole-based derivatives were synthesized in the present work with the aim of evaluating their antitumor activity. They were in vitro tested against hepatocellular carcinoma (HepG2), colorectal carcinoma (HCT-116), mammary gland cancer (MCF-7), prostate cancer (PC-3), and epithelioid carcinoma (HeLa). The results of the in vitro antitumor evaluation revealed that the most active compounds were 39, 40, 51, 56, and 61 exhibiting IC50 values comparable to the reference drug lapatinib. The most active compounds were further subjected to EGFR inhibitory activity assay to rationalize their potency mode. Notably, the most active antitumor compounds 39 and 40 represented the most potent inhibitors to EGFR with IC50 values of 24.58 and 30.42 nM respectively in comparison with 17.38 nM for lapatinib as a standard drug. Molecular modeling studies were also conducted for the synthesized compounds, including docking into EGFR active site and surface mapping. Results proved the superior binding of the hydrazone derivatives 39 and 40 with EGFR suggesting them as good candidates for targeted antitumor therapy through EGFR kinase inhibition.
• Effect of benzothiazole/piperazine derivatives on intracerebroventricular streptozotocin-induced cognitive deficits
  作者：Ümide Demir Özkay、Özgür Devrim Can、Yusuf Özkay、Yusuf Öztürk

  DOI：10.1016/s1734-1140(12)70878-2

  日期：2012.7

  Background: In this study, benzothiazole-piperazine compounds were synthesized by condensing the functional groups of donepezil (DNP), FK-960, and sabeluzole, which are known to have therapeutic potential against Alzheimer's disease, with the aim of obtaining new and potent anti-Alzheimer agents. Methods: Initially, acetylcholinesterase/butyrylcholinesterase enzyme inhibition activities of the synthesized test compounds were investigated by Ellman's method. Effects of the compounds on a streptozotocin (STZ) model of Alzheimer's disease (SMAD) were investigated in rats. SMAD was established by intracerebroventricular (icv) injection of STZ (3 mg/kg), bilaterally. The elevated plus maze, Morris water maze, and active avoidance tests were used to examine the effects of test compounds (1, 5, and 10 mg/kg) on learning and memory parameters of icv STZ-injected rats. Effects of the test compounds on spontaneous locomotor activities of rats were examined with the activity cage test. Results: The compounds B2-B5 and DNP exhibited significant selective inhibitory potencies against acetylcholinesterase. Compounds B2 and B3 at 10 mg/kg doses and compounds B4 and B5 at 5 and 10 mg/kg doses, as well as the reference drug DNP (1 and 3 mg/kg), significantly improved the learning and memory parameters of animals in all cognition tests. None of the test compounds changed spontaneous locomotor activities. Conclusion: Results of the present study revealed that compounds B2-B5 repaired the parameters related to the learning and memory deficits of icv STZ-injected rats. Potencies of these test compounds were comparable to the activity of DNP.
• Synthesis and biological evaluation of new thiazolyl/benzothiazolyl-amides, derivatives of 4-phenyl-piperazine
  作者：Christina Papadopoulou、Athina Geronikaki、Dimitra Hadjipavlou-Litina

  DOI：10.1016/j.farmac.2005.06.014

  日期：2005.11

  A series of thiazolyl-N-phenyl piperazines has been synthesised and tested for anti-inflammatory activity. Their R(M) values were determined as an expression of their lipophilicity. Theoretical calculation of their lipophilicity, as clog P and logPsk also performed. The effect of the synthesised compounds on inflammation, using the carrageenin induced mouse paw oedema model was studied. In general, the studied compounds were found to be potent anti-inflammatory agents (44-74.1%). Anti-inflammatory activity was influenced by some structural characteristics of the synthesised compounds. An attempt was made to correlate their biological activity with some physicochemical parameters using a quantitative structure-activity relationship approach (QSAR).
• US6284759B1
  申请人：——

  公开号：US6284759B1

  公开（公告）日：2001-09-04