1-(2-chloroethyl)-4-(4-fluorophenyl)-piperazine | 65274-89-7

• 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: 1-(2-chloroethyl)-4-(4-fluorophenyl)-piperazine
• 英文别名: 1-(2-Chloroethyl)-4-(4-fluorophenyl)piperazine
• CAS: 65274-89-7
• 化学式: C₁₂H₁₆ClFN₂
• 分子量: 242.724
• InChiKey: UWLHPACQOJQPAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.19
• 重原子数：
  16.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  6.48
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  1-(2-chloroethyl)-4-(4-fluorophenyl)-piperazine 在 sodium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 1-(2-Azidoethyl)-4-(4-fluorophenyl)piperazine
  参考文献：
  名称：

  Versatile Synthesis of Disubstituted Triazole Library for Dopamine and Serotonin Receptor Ligands

  摘要：

  DOI：

  10.5012/bkcs.2011.32.8.3101
• 作为产物：
  描述：

  2-<4-(4-fluorophenyl)piperazin-1-yl>ethanol 在 三乙胺 、 氯化亚砜 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.25h， 以60%的产率得到1-(2-chloroethyl)-4-(4-fluorophenyl)-piperazine
  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

文献信息

• Design, synthesis, and biological evaluation of arylpiperazine–benzylpiperidines with dual serotonin and norepinephrine reuptake inhibitory activities
  作者：Suresh Paudel、Srijan Acharya、Kyeong-Man Kim、Seung Hoon Cheon

  DOI：10.1016/j.bmc.2016.03.044

  日期：2016.5

  The limitations of established serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE) reuptake inhibitors necessitate the development of safer and more effective therapeutic agents. Based on the structures of 4-benzylpiperidine carboxamides and trazodone, arylpiperazine–benzylpiperidines with chemical scaffolds different from those of marketed drugs were designed, synthesized, and evaluated

  既定的5-羟色胺（5-羟色胺，5-HT）和去甲肾上腺素（NE）再摄取抑制剂的局限性需要开发更安全，更有效的治疗剂。根据4-苄基哌啶羧酰胺和曲唑酮的结构，设计，合成和评估化学支架与市售药物不同的芳基哌嗪-苄基哌啶，并评估其对神经递质再摄取的抑制活性。大多数合成化合物显示出比5-HT再摄取抑制更大的NE。其活性甚至大于标准药物盐酸文拉法辛。具有三碳连接基的衍生物表现出比具有二碳连接基的衍生物更好的活性。在新合成的化合物中，第2d表现出最强的神经递质再摄取抑制作用（ NE的IC 50 = 0.38μM，5-HT的IC 50 = 1.18μM）。生物学活性数据表明，芳基哌嗪-苄基哌啶具有开发作为治疗神经精神病和神经退行性疾病的新型治疗剂的潜力。
• Pyrroloazepine derivatives
  申请人：Suntory Limited

  公开号：US05962448A1

  公开（公告）日：1999-10-05

  A pyrroloazepine compound having the following formula (I): wherein the ring P represented by ##STR1## is a pyrrole ring having the following structure: ##STR2## wherein R.sub.1 represents C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.8 cycloalkyl-alkyl, C.sub.6 -C.sub.14 aryl or C.sub.7 -C.sub.22 aralkyl, which are optionally substituted; and R.sub.2 represents H or C.sub.1 -C.sub.8 alkyl, which is optionally substituted; the dashed line indicates the presence or absence of a bond; and, when the bond is present, Z.sub.2 is not present and Z.sub.1 represents H, but, when the bond is absent, Z.sub.1 and Z.sub.2 are both H; Z.sub.1 represents H and Z.sub.2 represents a group OR.sub.3, in which R.sub.3 represents H, C.sub.1 -C.sub.8 alkyl, or C.sub.7 -C.sub.22 aralkyl, which are optionally substituted; Z.sub.1 and Z.sub.2 both represent groups SR.sub.4, in which R.sub.4 represents C.sub.1 -C.sub.8 alkyl or C.sub.7 -C.sub.22 aralkyl, which are optionally substituted; or Z.sub.1 and Z.sub.2 are combined together to represent O, a group NOR.sub.5, in which R.sub.5 represents H, or C.sub.1 -C.sub.8 alkyl or C.sub.2 -C.sub.3 alkylenedithio, which are optionally substituted; A represents alkylene, alkenylene or alkynylene; and Y represents a group in which W is CH, C.dbd. or N, m is for 0 or 1, n is for 1, 2 or 3, G is O, S, C.dbd.O, sulfinyl, sulfonyl, alkylene, alkenylene or acetal; E.sub.1 and E.sub.2 is H or C.sub.1 -C.sub.8 alkyl; and D represents an aromatic hydrocarbon or an aromatic heterocyclic ring. The compound (I) has strong serotonin-2 receptor antagonistic action and low toxicity and less side effects, and is therapeutically useful in the treatment of circulatory diseases and/or conditions related thereto.

  一种具有以下式（I）的吡咯环辛烷化合物：其中由##STR1##表示的环P是具有以下结构的吡咯环：##STR2##其中R.sub.1表示C.sub.1 -C.sub.8烷基，C.sub.3 -C.sub.8环烷基，C.sub.4 -C.sub.8环烷基-烷基，C.sub.6 -C.sub.14芳基或C.sub.7 -C.sub.22芳基烷基，可以选择性地取代；而R.sub.2表示H或C.sub.1 -C.sub.8烷基，可以选择性地取代；虚线表示键的存在或不存在；当键存在时，Z.sub.2不存在，Z.sub.1表示H，但当键不存在时，Z.sub.1和Z.sub.2都是H；Z.sub.1表示H，Z.sub.2表示OR.sub.3基团，其中R.sub.3表示H，C.sub.1 -C.sub.8烷基或C.sub.7 -C.sub.22芳基烷基，可以选择性地取代；Z.sub.1和Z.sub.2都表示SR.sub.4基团，其中R.sub.4表示C.sub.1 -C.sub.8烷基或C.sub.7 -C.sub.22芳基烷基，可以选择性地取代；或Z.sub.1和Z.sub.2结合在一起表示O，NOR.sub.5基团，其中R.sub.5表示H，或C.sub.1 -C.sub.8烷基或C.sub.2 -C.sub.3烷基二硫，可以选择性地取代；A表示烷基，烯烃基或炔烃基；Y表示一个基团，其中W为CH，C.dbd.或N，m为0或1，n为1，2或3，G为O，S，C.dbd.O，亚砜，砜基，烷基，烯烃基或缩醛基；E.sub.1和E.sub.2为H或C.sub.1 -C.sub.8烷基；D表示芳香烃或芳香杂环。化合物（I）具有强烈的5-羟色胺2受体拮抗作用，毒性低，副作用少，在治疗循环系统疾病和/或相关疾病方面具有治疗用途。
• Synthesis and Serotonin 2 (5-HT2) Receptor Antagonist Activity of 5-Aminoalkyl-Substituted Pyrrolo[3,2-c]azepines and Related Compounds.
  作者：Akira MIZUNO、Atsto OGATA、Tomoe KAMEI、Makoto SHIBATA、Tetsuo SHIMAMOTO、Yasuhiro HAYASHI、Kyoko NAKANISHI、Chikako TAKIGUCHI、Naomi OKA、Norio INOMATA

  DOI：10.1248/cpb.48.623

  日期：——

  2-c]azepine derivatives was synthesized and their serotonin 2 (5-HT2) receptor antagonist and antiplatelet aggregation activities were evaluated. 5-HT2 receptor antagonist activity was largely determined by the nature of the substituent at the 8-position as well as the aminoalkyl group at the 5-position of the pyrrolo[3,2-c]azepine ring. Compound 18a, 5-[3-[4-(4-fluorophenyl)piperazin-1-yl]propyl]-8-hydroxy-1-methyl-

  合成了一系列的5-氨基烷基吡咯并[3,2-c]氮杂环庚烷衍生物，并评估了它们的5-羟色胺2（5-HT2）受​​体拮抗剂和抗血小板聚集活性。5-HT 2受体拮抗剂的活性在很大程度上取决于吡咯并[3，2-c] a庚环的8位上的取代基以及5位上的氨基烷基。化合物18a，5- [3- [4-（4-氟苯基）哌嗪-1-基]丙基] -8-羟基-1-甲基-1,4,5,6,7,8-六氢吡咯并[3,2 -c] azepin-4-one被认为具有强大的5-HT2受体拮抗活性，但具有弱的α1肾上腺素受体阻断活性，且无明显的D2受体结合亲和力，而相应的异构体吡咯并[3,4-c] azepine衍生物（22 ）仅显示弱的5-HT2受体拮抗剂活性。外消旋体18a通过非对映异构体盐的形成直接拆分后，可以精确评估每种对映体。发现18a的5-HT2受体拮抗剂活性主要存在于（-）-18a中（在分离的豚鼠动脉中，其效力比（+）-
• Substituted pyrido[3,2-b]oxazin-3(4H)-ones: synthesis and evaluation of antinociceptive activity
  作者：L. Savelon、J.G. Bizot-Espiard、D.H. Caignard、B. Pfeiffer、P. Renard、M.C. Viaud、G. Guillaumet

  DOI：10.1016/s0968-0896(97)10005-0

  日期：1998.2

  and compared with acetyl salicylic acid. The compound with the maximal combination of safety and analgesic efficacy was 4-¿3-[4-(4-fluorophenyl-1-piperazinyl)propyl]¿-2H-pyrido[3,2-b]-1, 4-oxazin-3(4H)-one (6c) with ED50 values of 12.5 mg/kg po (mouse: phenylquinone writhing test) and 27.8 mg/kg po (rat: acetic acid writhing test), respectively. Compound 6c proved to be more active than aspirin with

  合成了一系列新的N-取代的吡啶并[3,2-b]恶嗪酮，进行了药理学评估，并与乙酰水杨酸进行了比较。具有最大安全性和止痛效果的化合物为4-?? 3- [4-（4-氟苯基-1-哌嗪基）丙基] ??-2H-吡啶基[3,2-b] -1，4-恶嗪- 3（4H）-一（6c），ED50值分别为12.5 mg / kg po（小鼠：苯醌扭曲试验）和27.8 mg / kg po（大鼠：乙酸扭曲试验）。事实证明，化合物6c比阿司匹林更具活性，安全指数为5.1。
• Studies on Antihypertensive Agents with Antithrombotic Activity. 2. Syntheses and Pharmacological Evaluation of Pyrrolo[2,3-c]azepine Derivatives.
  作者：Akira MIZUNO、Mikiko MIYA、Tomoe KAMEI、Makoto SHIBATA、Toshio TATSUOKA、Kyoko NAKANISHI、Chikako TAKIGUCHI、Toshinori HIDAKA、Akira YAMAKI、Norio INOMATA

  DOI：10.1248/cpb.48.1129

  日期：——

  finding a novel potent antihypertensive agent with both activities. Among the compounds obtained in this study, (E)-1-ethyl-7-[3-[4-(4-fluorophenyl)piperazin-1-yl]propyl]-4-hy droxyimino-1,4,5,6,7,8-hexahydropyrrolo[2,3-c]azepin-8-on e (16d) displayed potent alpha1-adrenoceptor blocking activity (pA2=7.83+/-0.20) and 5-HT2-receptor blocking activity (pA2=9.47+/-0.17) in isolated guinea pig arteries. At

  作为我们先前研究的扩展，合成了一系列7-氨基烷基吡咯并[2,3-c]氮杂环庚烷衍生物，并将其评估为α1-肾上腺素和血清素2（5-HT2）受​​体拮抗剂，目的是寻找一种具有两种活性的新型高效降压药。在这项研究中获得的化合物中，（E）-1-乙基-7- [3- [4-（4-氟苯基）哌嗪-1-基]丙基] -4-hy羟亚氨基-1,4,5,6 ，7,8-hexahydropyrrolo [2,3-c] azepin-8-on e（16d）显示出有效的α1-肾上腺素受体阻断活性（pA2 = 7.83 +/- 0.20）和5-HT2受体阻断活性（pA2 = 9.47） +/- 0.17）在孤立的豚鼠动脉中。在3 mg / kg口服给药时，化合物16d在醋酸脱氧皮质酮盐酸盐（DOCA）盐高血压犬中显示出比多沙唑嗪更有效的降压活性。此外，