1-(2-氯乙基)-4-(4-硝基苯基)哌嗪 | 710272-54-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 1-(2-氯乙基)-4-(4-硝基苯基)哌嗪
• 英文名称: 1-(2-chloroethyl)-4-(4-nitrophenyl)piperazine
• 英文别名: 1-(2-Chlorethyl)-4-(4-nitro-phenyl)-piperazin
• CAS: 710272-54-1
• 化学式: C₁₂H₁₆ClN₃O₂
• 分子量: 269.731
• InChiKey: NULZRBUCTPOMMW-UHFFFAOYSA-N

物化性质

• 沸点：
  429.0±45.0 °C(Predicted)
• 密度：
  1.263±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2-氯乙基)-4-(4-硝基苯基)哌嗪 在 sodium azide 、 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 生成 1-(2-azidoethyl)-4-(4-nitrophenyl)piperazine
  参考文献：
  名称：

  [EN] 2-AMINOPYRIMIDINE AND 2-AMINOPYRIDINE-4-CARBAMATES FOR USE IN THE TREATMENT OF AUTOIMMUNE DISEASES
  [FR] 2-AMINOPYRIMIDINE ET 2-AMINOPYRIDINE-4-CARBAMATES DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DE MALADIES AUTO-IMMUNES

  摘要：

  本发明涉及具有通用式（1）的嘧啶或吡啶羰酸酯化合物及其药用可接受的盐或衍生物。还包括治疗各种疾病和症状的方法，包括炎症、抑制T细胞激活和增殖、关节炎、器官移植、缺血或再灌注损伤、心肌梗死、中风、多发性硬化、炎症性肠病、克罗恩病、狼疮、过敏、1型糖尿病、牛皮癣、皮炎、桥本氏甲状腺炎、干燥综合征、自身免疫性甲状腺功能亢进症、艾迪生病、自身免疫疾病、肾小球肾炎、过敏性疾病、哮喘、花粉症、湿疹、癌症、结肠癌、胸腺瘤等，在哺乳动物中的方法，包括给予通用式I的化合物的治疗有效量，或如上所述的盐或衍生物形式。

  公开号：

  WO2005009978A1
• 作为产物：
  描述：

  1-(4-硝基苯基)哌嗪 在 三乙胺 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.25h， 生成 1-(2-氯乙基)-4-(4-硝基苯基)哌嗪
  参考文献：
  名称：

  Novel aryl piperazines for alleviation of ‘andropause’ associated prostatic disorders and depression

  摘要：

  A series of seventeen piperazine derivatives have been synthesized and biologically evaluated for the management of andropause-associated prostatic disorders and depression. Five compounds 16,19, 20, 21 and 22 significantly inhibited proliferation of androgen-sensitive LNCaP prostatic cell line with EC50 values of 12.4 mu M, 15.6 11.8 mu M, 10.4 mu M, 12.2 mu M respectively and decreased Ca2+ entry through adrenergic-receptor alpha(1A) blocking activity. Anti-androgenic behaviour of compound 19 and 22 was evident by decreased luciferase activity. The high EC50 value in AR-negative cells PC3 and DU145 suggested that the cytotoxicity of compounds was due to AR down regulation. Compound 19 reduced the prostate weight of rats by 53.8%. Further, forced-swimming and tail-suspension tests revealed antidepressant-like activity of compound 19, lacking effects on neuromuscular co-ordination. In silico ADMET predictions revealed that the compound 19 had good oral absorption, aqueous solubility, non-hepatotoxic and good affinity for plasma protein binding. Pharmacokinetic and tissue uptake of 19 at 10 mg/kg demonstrated an oral bioavailability of 35.4%. In silico docking studies predicted similar binding pattern of compound 19 on androgen receptor as hydroxyflutamide. Compound 19 appears to be a unique scaffold with promising activities against androgen associated prostatic disorders in males like prostate cancer and BPH and associated depression. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.03.036
• 作为试剂：
  描述：

  2-[4-(4-硝基苯基)哌嗪]-1-乙醇 、 盐酸 、 在 氯化亚砜 、 二氯甲烷 、 1-(2-氯乙基)-4-(4-硝基苯基)哌嗪 作用下， 以 二氯甲烷 、 乙醚 为溶剂， 反应 6.5h， 生成 1-(2-氯乙基)-4-(4-硝基苯基)哌嗪
  参考文献：
  名称：

  Substituted heterocyclic compounds and methods of use

  摘要：

  本发明涉及具有一般式I的嘧啶或吡啶氨基甲酸酯化合物及其药学上可接受的盐或衍生物。还包括治疗各种疾病和病症的方法，包括炎症，抑制T细胞激活和增殖，关节炎，器官移植，缺血或再灌注损伤，心肌梗塞，中风，多发性硬化症，炎症性肠病，克罗恩病，狼疮，过敏，1型糖尿病，银屑病，皮炎，桥本甲状腺炎，Sjogren综合征，自身免疫性甲状腺功能亢进症，Addison病，自身免疫性疾病，肾小球肾炎，过敏性疾病，哮喘，花粉症，湿疹，癌症，结肠癌，胸腺瘤等，在哺乳动物中的方法，包括给予一种化合物I的治疗有效量，或上述化合物的盐或衍生物形式。

  公开号：

  US07442698B2

文献信息

• [EN] SUBSTITUTED HETEROCYCLIC COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSES HETEROCYCLIQUES SUBSTITUES ET LEURS PROCEDES D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2005042518A3

  公开（公告）日：2005-06-09
• Mahesh; Venkatesha Perumal; Pandi, Pharmazie, 2005, vol. 60, # 6, p. 411 - 414
  作者：Mahesh、Venkatesha Perumal、Pandi

  DOI：——

  日期：——
• US7442698B2
  申请人：——

  公开号：US7442698B2

  公开（公告）日：2008-10-28
• [EN] 2-AMINOPYRIMIDINE AND 2-AMINOPYRIDINE-4-CARBAMATES FOR USE IN THE TREATMENT OF AUTOIMMUNE DISEASES<br/>[FR] 2-AMINOPYRIMIDINE ET 2-AMINOPYRIDINE-4-CARBAMATES DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DE MALADIES AUTO-IMMUNES
  申请人：AMGEN INC

  公开号：WO2005009978A1

  公开（公告）日：2005-02-03

  The present invention relates to pyrimidine or pyridine carbamate compounds having the general Formula (1) and pharmaceutically acceptable salts or derivatives thereof. Also included are methods of treatment of various diseases and conditions, including inflammation, inhibition of T cell activation and proliferation, arthritis, organ transplant, ischemic or reperfusion injury, myocardial infarction, stroke, multiple sclerosis, inflammatory bowel disease, Crohn's disease, lupus, hypersensitivity, type 1 diabetes, psoriasis, dermatitis, Hashimoto's thyroiditis, Sjogren's syndrome, autoimmune hyperthyroidism, Addison's disease, autoimmune diseases, glomerulonephritis, allergic diseases, asthma, hayfever, eczema, cancer, colon carcinoma, thymoma, just to name a few, in a mammal, the methods comprising administering a therapeutically-effective amount a compound of Formula I, or a salt or derivative form thereof, as described above.

  本发明涉及具有通用式（1）的嘧啶或吡啶羰酸酯化合物及其药用可接受的盐或衍生物。还包括治疗各种疾病和症状的方法，包括炎症、抑制T细胞激活和增殖、关节炎、器官移植、缺血或再灌注损伤、心肌梗死、中风、多发性硬化、炎症性肠病、克罗恩病、狼疮、过敏、1型糖尿病、牛皮癣、皮炎、桥本氏甲状腺炎、干燥综合征、自身免疫性甲状腺功能亢进症、艾迪生病、自身免疫疾病、肾小球肾炎、过敏性疾病、哮喘、花粉症、湿疹、癌症、结肠癌、胸腺瘤等，在哺乳动物中的方法，包括给予通用式I的化合物的治疗有效量，或如上所述的盐或衍生物形式。
• Novel aryl piperazines for alleviation of ‘andropause’ associated prostatic disorders and depression
  作者：Sonal Gupta、Deepti Pandey、Dhanaraju Mandalapu、Vikas Sharma、Mahendra Shukla、Seema Singh、Nidhi Singh、Santosh Kumar Yadav、Dilip Kumar Tanpula、Surabhi Singh、Jagdamba P. Maikhuri、Shubha Shukla、Jawahar Lal、Mohammad I. Siddiqi、Gopal Gupta、Vishnu L. Sharma

  DOI：10.1016/j.ejmech.2017.03.036

  日期：2017.5

  A series of seventeen piperazine derivatives have been synthesized and biologically evaluated for the management of andropause-associated prostatic disorders and depression. Five compounds 16,19, 20, 21 and 22 significantly inhibited proliferation of androgen-sensitive LNCaP prostatic cell line with EC50 values of 12.4 mu M, 15.6 11.8 mu M, 10.4 mu M, 12.2 mu M respectively and decreased Ca2+ entry through adrenergic-receptor alpha(1A) blocking activity. Anti-androgenic behaviour of compound 19 and 22 was evident by decreased luciferase activity. The high EC50 value in AR-negative cells PC3 and DU145 suggested that the cytotoxicity of compounds was due to AR down regulation. Compound 19 reduced the prostate weight of rats by 53.8%. Further, forced-swimming and tail-suspension tests revealed antidepressant-like activity of compound 19, lacking effects on neuromuscular co-ordination. In silico ADMET predictions revealed that the compound 19 had good oral absorption, aqueous solubility, non-hepatotoxic and good affinity for plasma protein binding. Pharmacokinetic and tissue uptake of 19 at 10 mg/kg demonstrated an oral bioavailability of 35.4%. In silico docking studies predicted similar binding pattern of compound 19 on androgen receptor as hydroxyflutamide. Compound 19 appears to be a unique scaffold with promising activities against androgen associated prostatic disorders in males like prostate cancer and BPH and associated depression. (C) 2017 Elsevier Masson SAS. All rights reserved.