2-<4-(4-fluorophenyl)piperazin-1-yl>ethanol | 90096-38-1

• 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>ethanol
• 英文别名: 2-(4-(4-fluorophenyl)piperazin-1-yl)ethanol；4-(4-fluorophenyl)-1-piperazineethanol；2-[4-(4-Fluorophenyl)piperazin-1-yl]ethan-1-ol；2-[4-(4-fluorophenyl)piperazin-1-yl]ethanol
• CAS: 90096-38-1
• 化学式: C₁₂H₁₇FN₂O
• mdl: MFCD11613829
• 分子量: 224.278
• InChiKey: ONKAXBAMDYNOFH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 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：
  26.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  1-(4-氟苯基)哌嗪 、 2-溴乙醇 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 生成 2-<4-(4-fluorophenyl)piperazin-1-yl>ethanol
  参考文献：
  名称：

  螺[吡咯烷-3,3'-羟吲哚]作为5-HT 7受体配体

  摘要：

  在这里，我们报告设计和合成的螺[吡咯烷-3,3'-oxindole]衍生物代表5-HT 7受体配体的新型支架。合成的类似物被验证为低纳摩尔配体，在一系列相关的5-羟色胺受体亚型（包括5-HT 1A R，5-HT 2A R和5-HT 6 R）中显示出选择性。

  DOI：

  10.1016/j.bmcl.2018.06.019

文献信息

• New 1,4-dihydropyridine derivatives with potent and long-lasting hypotensive effect.
  作者：KANJI MEGURO、MASAHIRO AIZAWA、TAKASHI SOHDA、YUTAKA KAWAMATSU、AKINOBU NAGAOKA

  DOI：10.1248/cpb.33.3787

  日期：——

  In a search for new 1, 4-dihydropyridine derivatives with a long-lasting effect on the cardiovascular system, a series of piperazinylalkyl esters (I) bearing a lipophilic substituent on the 4-nitrogen of the piperazine ring was synthesized and tested for hypotensive effect in spontaneously hypertensive rats (SHR). Compounds I, especially those having a diphenylmethyl moiety on the piperazine ring, showed extremely potent and long-lasting hypotensive properties. Analogues related to I were also prepared, and the structure-activity relationships are discussed.

  在寻找对心血管系统具有长效作用的新的1,4-二氢吡啶衍生物时，合成并测试了一系列在哌嗪环的4-氮上带有亲脂性取代基的吡哆酯类化合物I对自发性高血压大鼠(SHR)的降压效果。化合物I，尤其是那些在哌嗪环上有二苯甲基部分的化合物，显示出极其强大且长效的降压特性。还制备了与I相关的类似物，并讨论了结构-活性关系。
• Long-acting dihydropyridine calcium antagonists. 1. 2-Alkoxymethyl derivatives incorporating basic substituents
  作者：John E. Arrowsmith、Simon F. Campbell、Peter E. Cross、John K. Stubbs、Roger A. Burges、Donald G. Gardiner、Kenneth J. Blackburn

  DOI：10.1021/jm00159a022

  日期：1986.9

  A series of dihydropyridines substituted at the 2-position by basic side chains are described and their potencies as calcium antagonists listed. One compound, 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5- methoxycarbonyl-6-methyl-1,4-dihydropyridine (17, amlodipine) was found to be comparable in potency to nifedipine and to have an elimination half-life of 30 h in dogs. Oral bioavailability

  描述了一系列在2-位被碱性侧链取代的二氢吡啶，并列出了其作为钙拮抗剂的效力。发现一种化合物2-[（（2-氨基乙氧基）甲基] -4-（2-氯苯基）-3-乙氧基羰基-5-甲氧基羰基-6-甲基-1,4-二氢吡啶（17，氨氯地平）具有可比性。对硝苯地平有效，并具有30 h的消除半衰期。口服生物利用度接近100％，血液动力学反应起效缓慢，效果持久。已经制备了两种对映异构体，并且发现大部分活性与（-）异构体18有关。对17的相似类似物进行的X射线晶体学研究表明，两者之间存在弱氢键侧链氧和质子在环氮上。
• Syntheses, Calcium Channel Antagonist and Anticonvulsant Activities of Substituted 1,4-Dihydro-3,5-pyridinedicarboxylates Containing Various 3-Alkyl Ester Substituents
  作者：Sai-Hay Yiu、Edward E. Knaus

  DOI：10.1002/ardp.19973300109

  日期：——

  5‐pyridinedicarboxylates 10–20 containing an amine, quaternary ammonium, aryl(heteroaryl)alkenyl, 4 ‐ (4‐fluorophenyl)‐piperazin‐1‐yl or methoxy moiety in the C‐3 alkyl ester R‐substituent in combination with a C‐4 phenyl ring bearing a 2,3‐Cl2, 3‐NO2, 3‐NMe2, 4‐NMe2 or 3,4,5‐(OMe)3 X‐substituent were prepared using the Hantzsch 1,4‐dihydropyridine reaction. In vitro calcium channel antagonist activity (CCA)

  一组 3-烷基 5-异丙基 4-芳基-1,4-二氢-2,6-二甲基-3,5-吡啶二羧酸酯 10-20 含有胺、季铵、芳基（杂芳基）烯基、4-（4 -氟苯基) -哌嗪 - C-3烷基酯R-取代基中的1-基或甲氧基部分与带有2,3-Cl2、3-NO2、3-NMe2、4-NMe2的C-4苯环组合或 3,4,5- (OMe) 3 X- 取代基使用 Hantzsch 1,4-二氢吡啶反应制备。使用豚鼠回肠纵向平滑肌测定法测定体外钙通道拮抗剂活性(CCA)。在C-4 3-硝基苯基系列化合物中，C-3酯R-取代基是CCA活性的决定因素，其中相对效力顺序为-CH2CH2CH=C-(2-甲基苯基)2±-CH2CH2NMe2.HCl>- CH2CH2CH = C-(3-甲基-2-噻吩基) 2> -CH2CH2 + NMe3 I-。C-4苯基X-取代基的位置和性质也是CCA活性的决定因素，其中相对活性顺序为3-NMe2>4-NMe2>3
• Substituted heterocyclylalkyl esters of
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04892875A1

  公开（公告）日：1990-01-09

  Dihydropyridine derivatives and acid addition salts thereof which are of use as prophylactic or/and therapeutic drugs for cardiovascular diseases, said dihydropyridine derivatives having the formula ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 are the same or different and each is alkyl, cycloalkyl, cycloalkylalkyl or alkoxyalkyl; R.sup.4 and R.sup.5 are the same or different and each is hydrogen, halogen, nitro, trifluoromethyl, alkyl, cycloalkyl, alkoxy, cyano, alkoxycarbonyl or alkylthio; R.sup.6 is hydrogen, alkyl, cycloalkyl, aralkyl, aryl or a pyridyl; X is oxygen, sulfur, vinylene, azomethine or a group of the formula ##STR2## A is alkylene; Ar is aryl or a pyridyl; m is an integer of 1 to 3; n is an integer of 0 to 2.

  二氢吡啶衍生物及其酸加成盐，可用于心血管疾病的预防和/或治疗药物，所述二氢吡啶衍生物具有以下式子：##STR1## 其中R.sup.1，R.sup.2和R.sup.3相同或不同，每个都是烷基，环烷基，环烷基烷基或烷氧基烷基; R.sup.4和R.sup.5相同或不同，每个都是氢，卤素，硝基，三氟甲基，烷基，环烷基，烷氧基，氰基，烷氧羰基或烷基硫基; R.sup.6是氢，烷基，环烷基，芳基烷基，芳基或吡啶基; X是氧，硫，乙烯基，偶氮基或式子##STR2## 的基团; A是烷基; Ar是芳基或吡啶基; m是1到3的整数; n是0到2的整数。
• Calvi; Picciola; Carenini, Farmaco, Edizione Scientifica, 1985, vol. 40, # 5, p. 334 - 346
  作者：Calvi、Picciola、Carenini、Gentili

  DOI：——

  日期：——