2-[4-(4-fluorophenyl)piperazin-1-yl]acetic acid | 938261-59-7

• 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-[4-(4-fluorophenyl)piperazin-1-yl]acetic acid
• 英文别名: 2-[4-(4-Fluorophenyl)piperazin-1-ium-1-yl]acetate
• CAS: 938261-59-7
• 化学式: C₁₂H₁₅FN₂O₂
• mdl: MFCD09712765
• 分子量: 238.262
• InChiKey: FYZQTJPHPXIWCX-UHFFFAOYSA-N

物化性质

• 沸点：
  405.9±45.0 °C(Predicted)
• 密度：
  1.259±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.416
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[4-(4-fluorophenyl)piperazin-1-yl]acetic acid 在 盐酸 、 4-二甲氨基吡啶 、 水 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 5.5h， 生成 2-[4-(4-fluorophenyl)piperazin-1-yl]-N-(5-hydroxypyridin-2-yl)acetamide
  参考文献：
  名称：

  [EN] INHIBITORS OF DIHYDROCERAMIDE DESATURASE FOR TREATING DISEASE
  [FR] INHIBITEURS DE DIHYDROCÉRAMIDE DÉSATURASE POUR LE TRAITEMENT DE MALADIES

  摘要：

  本文披露了二氢神经酰胺脱饱和酶1（Des1）抑制剂化合物和组合物，这些化合物在治疗疾病方面非常有用，如代谢性疾病、心血管疾病、纤维化疾病、自身免疫/慢性炎症性疾病、囊性纤维化、各种癌症、神经退行性疾病、脂质储存障碍和缺血/再灌注损伤，预期通过抑制Des1对患者具有治疗作用。还提供了在人类或动物受试者中抑制Des1活性的方法。

  公开号：

  WO2018112077A1
• 作为产物：
  描述：

  1-(4-氟苯基)哌嗪 在 碳酸氢钠 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 丙酮 为溶剂， 反应 28.0h， 生成 2-[4-(4-fluorophenyl)piperazin-1-yl]acetic acid
  参考文献：
  名称：

  以微管蛋白解聚为新抗癌剂的醋酸哌嗪鬼臼毒素酯衍生物的设计与合成

  摘要：

  本文合成和研究了一系列鬼臼毒素哌嗪乙酸酯衍生物，因为它们在不同的人类癌细胞系中具有抗增殖活性。在同类物中，C5对癌细胞表现出显着的细胞毒性，而不会通过抑制微管蛋白装配而对非癌细胞造成损害，并且对人类乳腺癌（MCF-7）细胞系具有较高的选择性损害作用（IC 50  = 2.78±0.15） （μM）。用C5处理MCF-7细胞导致细胞周期停滞在G2 / M期和微管网络破坏。此外，关于细胞周期相关蛋白CDK1的表达，有丝分裂起始所需的蛋白被上调。此外，Cyclin A，Cyclin B1和Cyclin D1蛋白也被下调。同时，似乎观察到C5对MCF-7细胞凋亡诱导的作用还不够明显。此外，对接分析表明同类物占据了微管蛋白的秋水仙碱结合口袋。

  DOI：

  10.1016/j.bmcl.2017.07.047

文献信息

• Novel heteroatom containing tetracyclic derivatives as selective estrogen receptor modulators
  申请人：——

  公开号：US20040259915A1

  公开（公告）日：2004-12-23

  The present invention is directed to novel heteroatom containing tetracyclic derivatives, pharmaceutical compositions containing them, their use in the treatment and/or prevention of disorders mediated by one or more estrogen receptors and processes for their preparation. The compounds of the invention are useful in the treatment and/or prevention of disorders associated with the depletion of estrogen such as hot flashes, vaginal dryness, osteopenia and osteoporosis; hormone sensitive cancers and hyperplasia of the breast, endometrium, cervix and prostate; endometriosis, uterine fibroids, osteoarthritis and as contraceptive agents, alone or in combination with a progestogen or progestogen antagonist.

  本发明涉及新颖的含杂原子四环衍生物、含有它们的药物组合物、它们在治疗和/或预防由一个或多个雌激素受体介导的疾病中的应用，以及它们的制备方法。本发明的化合物在治疗和/或预防与雌激素耗竭相关的疾病中具有用途，例如热潮红、阴道干燥、骨量减少和骨质疏松症；激素敏感性癌症以及乳腺、子宫内膜、宫颈和前列腺的增生；子宫内膜异位症、子宫肌瘤、骨关节炎，以及作为避孕剂，单独使用或与孕激素或孕激素拮抗剂联合使用。
• [EN] TETRACYCLIC HETEROCOMPOUNDS AS ESTROGEN RECEPTOR MODULATORS<br/>[FR] HETERO-COMPOSES TETRACYCLIQUES UTILISABLES COMME MODULATEURS DU RECEPTEUR DES OESTROGENES
  申请人：ORTHO MCNEIL PHARM INC

  公开号：WO2003053977A1

  公开（公告）日：2003-07-03

  The present invention is directed to novel heteroatom containing tetracyclic derivatives, pharmaceutical compositions containing them, their use in the treatment and / or prevention of disorders mediated by one or more estrogen receptors and processes for their preparation. The compounds of the invention are useful in the treatment and / or prevention of disorders associated with the depletion of estrogen such as hot flashes, vaginal dryness, osteopenia and osteoporosis; hormone sensitive cancers and hyperplasia of the breast, endometrium, cervix and prostate; endometriosis, uterine fibroids, osteoarthritis and as contraceptive agents, alone or in combination with a progestogen or progestogen antagonist.

  本发明涉及新型含杂原子的四环衍生物、含有它们的药物组合物、它们在治疗和/或预防由一个或多个雌激素受体介导的疾病中的使用以及它们的制备过程。该发明的化合物在治疗和/或预防与雌激素缺乏有关的疾病方面具有用处，例如潮热、阴道干燥、骨质疏松症和骨质疏松症；激素敏感性癌症和乳腺、子宫内膜、子宫颈和前列腺的增生；子宫内膜异位症、子宫肌瘤、骨关节炎以及作为避孕药物，单独使用或与孕激素或孕激素拮抗剂组合使用。
• Inhibitors of dihydroceramide desaturase for treating disease
  申请人：Centaurus Therapeutics

  公开号：US11135207B2

  公开（公告）日：2021-10-05

  Disclosed herein are dihydroceramide desaturase 1 (Des1) inhibitor compounds and compositions, which are useful in the treatment of diseases, such as metabolic, cardiovascular, fibrotic, autoimmune/chronic inflammatory diseases, cystic fibrosis, various cancers, neurodegenerative diseases, lipid storage disorders, and ischemia/reperfusion injury, where inhibition of Des1 is expected to be therapeutic to a patient. Methods of inhibition of Des1 activity in a human or animal subject are also provided.

  本公开涉及二氢神经酰胺脱饱和酶1（Des1）抑制剂化合物和组合物，这些化合物和组合物在治疗某些疾病（例如代谢性疾病、心血管疾病、纤维化疾病、自身免疫性疾病/慢性炎症性疾病、囊性纤维化、多种癌症、神经退行性疾病、脂质沉积障碍及缺血/再灌注损伤）时是有用的，且预期对于患者而言Des1的抑制具有治疗作用。本发明还提供了抑制人类或动物受试者Des1活性的方法。
• Arylpiperazines as fatty acid transport protein 1 (FATP1) inhibitors with improved potency and pharmacokinetic properties
  作者：Tetsuyoshi Matsufuji、Mika Ikeda、Asuka Naito、Masakazu Hirouchi、Shoichi Kanda、Masanori Izumi、Jun Harada、Tsuyoshi Shinozuka

  DOI：10.1016/j.bmcl.2013.02.116

  日期：2013.5

  The discovery and optimization of a novel series of FATP1 inhibitors are described. Through the derivatization process, arylpiperazine derivatives 5k and 12a were identified as possessing potent in vitro activity against human and mouse FATP1s as well as excellent pharmacokinetic properties. In vivo evaluation of triglyceride accumulation in the liver, white gastrocnemius muscle and soleus is also described. (C) 2013 Elsevier Ltd. All rights reserved.
• Synthesis, crystal structures, molecular docking, and urease inhibitory activity of transition metal complexes with 2-[4-(4-fluorophenyl)piperazin-1-yl]acetic acid
  作者：Zhi-Jian Chen、Chun-Na Xu、Jin-Long Zhu、Dan-Dan Yang、Shan-Shan Zhao、Ya-Nan Chen、Shao-Song Qian

  DOI：10.17344/acsi.2015.2109

  日期：2016.3.15

  Two novel mononuclear complexes, [Cu(L)(2)(H2O)] center dot 2H(2)O (1) and [Ni(L)(2)(H2O)(2)] (2) (HL = 2-[4-(4-fluorophenyl)piperazin-1-yl]acetic acid) were synthesized and structurally determined by single-crystal X-ray diffraction. Their inhibitory activities were tested in vitro against jack bean urease. Molecular docking was investigated to determine the probable binding mode. The experimental values and docking simulation exhibited that complex 1 had better inhibitory activity than the positive reference acetohydroxamic acid (AHA), showing IC50 value of 0.15 +/- 0.08 mu M, while 2 showed no inhibitory activity.