5-氟-2-(1-哌嗪基)-嘧啶 | 87789-49-9

• 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: 5-氟-2-(1-哌嗪基)-嘧啶
• 英文名称: 5-fluoro-2-(piperazin-1-yl)-pyrimidine
• 英文别名: 5-Fluoro-2-(piperazin-1-YL)pyrimidine；5-fluoro-2-piperazin-1-ylpyrimidine
• CAS: 87789-49-9
• 化学式: C₈H₁₁FN₄
• mdl: MFCD00792681
• 分子量: 182.201
• InChiKey: GXXFECFLKWGTNP-UHFFFAOYSA-N

物化性质

• 熔点：
  38.5-40 °C
• 沸点：
  332.3±52.0 °C(Predicted)
• 密度：
  1.227±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  41
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  5-氟-2-(1-哌嗪基)-嘧啶 在 potassium carbonate 、 三氟乙酸 、 potassium iodide 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 72.0h， 生成 1-<4,4-bis(4-fluorophenyl)-3-butenyl>-4-(5-fluoro-2-pyrimidinyl)piperazine
  参考文献：
  名称：

  Synthesis and biological characterization of .alpha.-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazinebutanol and analogs as potential atypical antipsychotic agents

  摘要：

  A series of 1-(pyrimidin-2-yl)piperazine derivatives were prepared and evaluated in receptor binding assays and in in vivo behavioral paradigms as potential atypical antipsychotic agents. Compound 16 (BMS 181100 (formerly BMY 14802)) emerged as the lead compound from within the series on the basis of its good activity and duration of action in the inhibition of both conditioned avoidance responding and apomorphine-induced stereotopy in the rat. Compound 16 not only failed to induce catalepsy in the rat but was quite effective in reversing the cataleptic effect of neuroleptic agents, thus indicating a low propensity for causing extrapyramidal side effects. In comparison to reference antipsychotic agents, 16 appeared to be less sedating and was relatively weaker in causing muscle incoordination. The compound was essentially inactive in binding to dopamine D2 receptors and its chronic administration to rats did not result in dopamine receptor supersensitivity. It exhibited modest to weak affinity for 5-HT1A and alpha1 receptors but was found to be a fairly potent ligand for sigma binding sites (IC50 vs (+)-[H-3]-3-PPP = 112 nM). Although the resolved enantiomers of racemic 16 did not show dramatic differences from racemate or from each other in most tests, the R(+) enantiomer was up to 11-fold more potent than its antipode in binding to sigma sites. Several studies have indicated that 16 may be a limbic-selective agent which may modulate dopaminergic activity by an indirect mechanism. The compound has been selected for clinical evaluation in the treatment of psychosis.

  DOI：

  10.1021/jm00102a002
• 作为产物：
  描述：

  4-(5-氟嘧啶-2-基)哌嗪-1-羧酸乙酯 以quant的产率得到5-氟-2-(1-哌嗪基)-嘧啶
  参考文献：
  名称：

  Antipsychotic 1-fluorophenylbutyl-4-(2-pyrimidinyl)piperazine derivatives

  摘要：

  本文介绍了二取代N，N-哌嗪基衍生物，其中一个取代基为嘧啶-2-基环，另一个取代基为4个碳链，连接到末端碳上的对氟苯基环。此丁二烯链的末端碳也与氧原子结合，作为羰基，碳醇或缩醛的一部分。这些化合物具有精神药理学特性，特别是良好持续的非典型抗精神病活性。通过临床前药理学测试，这些化合物似乎有用作潜在抗精神病药物，其缺乏标准抗精神病药物的典型运动障碍副作用。

  公开号：

  US04605655A1
• 作为试剂：
  描述：

  5-氟-2-(1-哌嗪基)-嘧啶 、 4-chloro-1-(4-(18F)fluoranylphenyl)butan-1-one 在 5-氟-2-(1-哌嗪基)-嘧啶 作用下， 生成 1-(4-氟苯基)-4-[4-(5-氟嘧啶-2-基)哌嗪-1-基]丁烷-1-酮
  参考文献：
  名称：

  J. Nucl. Med. 1993, 34, 246

  摘要：

  DOI：

文献信息

• Synthesis and Anxiolytic Activity of N-Substituted Cyclic Imides(1R*,2S*,3R*,4S*)-N-(4-(4-(2-Pyrimidinyl)-1-piperazinyl)butyl)-2,3-bicyclo(2.2.1)heptanedicarboximide(Tandospirone) and Related Compounds.
  作者：Kikuo ISHIZUMI、Atsuyuki KOJIMA、Fujio ANTOKU

  DOI：10.1248/cpb.39.2288

  日期：——

  The in vitro binding affinities of these compounds were also examined for 5-HT1A receptor sites. Structure-activity relationships within these series are discussed. One of these compounds, (1R*,2S*,-3R*,4S*)-N-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-2,3- bicyclo[2.2.1]heptanedicarboximide (1: tandospirone), was found to be equipotent with buspirone in its anxiolytic activity and more anxio-selective

  合成了一系列带有ω-（4-芳基和4-杂芳基-1-哌嗪基）烷基的环状酰亚胺，并在体内测试其抗焦虑活性。还检查了这些化合物的体外结合亲和力的5-HT1A受体位点。讨论了这些系列中的构效关系。这些化合物之一，（1R *，2S *，-3R *，4S *）-N- [4- [4-（4-嘧啶基）-1-哌嗪基]丁基] -2,3-双环[2.2.1已发现]庚烷二甲酰亚胺（1：tandospirone）与丁螺环酮具有相同的抗焦虑活性，并且比丁螺环酮和地西epa具有更高的选择性。Tandospirone（1）目前正在作为一种选择性抗焦虑药进行临床评估。
• [EN] VASOPRESSIN RECEPTOR ANTAGONISTS AND PRODUCTS AND METHODS RELATED THERETO<br/>[FR] ANTAGONISTES DU RÉCEPTEUR DE LA VASOPRESSINE, PRODUITS ET PROCÉDÉS ASSOCIÉS
  申请人：BLACKTHORN THERAPEUTICS INC

  公开号：WO2019050988A1

  公开（公告）日：2019-03-14

  Compounds are provided that antagonize vasopressin receptors, particularly the V1a receptor products containing such compounds, as well as to methods of their use and synthesis. Such compounds have the structure of Formula (I), or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof: (I) wherein Q1, Q2, Q3, R2a, R2b, R3 and X are as defined herein.

  提供了拮抗加压素受体的化合物，特别是含有这些化合物的V1a受体产品，以及它们的使用和合成方法。这些化合物具有以下结构的结构（I），或其药学上可接受的异构体、消旋体、水合物、溶剂合物、同位素或盐：（I）其中Q1、Q2、Q3、R2a、R2b、R3和X如本文所定义。
• Agents for treatment of brain ischemia
  申请人：Bristol-Myers Squibb Co.

  公开号：US04994460A1

  公开（公告）日：1991-02-19

  A series of 5-halopyrimidin-2-ylpiperazinylalkyl derivatives having useful anti-ischemic properties for treatment and prevention of dirorders resulting from brain and/or spinal cord anoxia.

  一系列具有有用的抗缺血特性的5-卤代嘧啶-2-基哌嗪基烷基衍生物，用于治疗和预防由脑部和/或脊髓缺氧引起的疾病。
• [EN] ANTIBIOTIC RESISTANCE BREAKERS<br/>[FR] AGENTS DE RUPTURE DE RÉSISTANCE AUX ANTIBIOTIQUES
  申请人：KING S COLLEGE LONDON

  公开号：WO2018220365A1

  公开（公告）日：2018-12-06

  The invention relates to antibiotic compounds of formula (A1) and pharmaceutically acceptable salts, solvates, tautomers and combinations thereof, wherein X and L are optional linkers and one of RA or R1 comprises Ar1, wherein Ar1 is an antibiotic resistance breaker moiety which comprises an optionally substituted C6-10 aryl, C7-13 aralkyl, C5-10 heteroaryl, C6-13 heteroaralkyl, C5-10 heterocyclyl, C6-13 heterocyclalkyl, C3-10 carbocyclyl, C4-13 carbocyclalkyl, -C(=NR')-NR'R'' or –CH2- CH=CH2 group; wherein after administration of the compound to a bacterial infection this moiety reduces or prevents efflux. The invention also discloses pharmaceutical compositions comprising compounds of formula (A1) and the use of such compounds as medicaments, in particular, to treat bacterial infections, such as drug-resistant bacterial infections.

  该发明涉及公式（A1）的抗生素化合物及其药学上可接受的盐、溶剂化合物、互变异构体和它们的组合，其中X和L是可选的连接物，RA或R1中的一个包括Ar1，其中Ar1是一种抗生素耐药性破坏基团，包括可选择取代的C6-10芳基，C7-13芳基烷基，C5-10杂芳基，C6-13杂芳基烷基，C5-10杂环烷基，C6-13杂环烷基，C3-10碳环烷基，C4-13碳环烷基，-C(=NR')-NR'R''或–CH2- CH=CH2基团；在将该化合物用于细菌感染后，该基团减少或预防外流。该发明还公开了包括公式（A1）化合物的药物组合物以及将这些化合物用作药物的用途，特别是用于治疗细菌感染，如耐药性细菌感染。
• Methods for preparation of 2-(4-(4-(4,5-dichloro-2-methylimidazol-1-yl)butyl)-1-piperazinyl)-5-fluoropyrimidine and salts thereof
  申请人：Laboratories del Dr. Esteve S.A.

  公开号：US06346620B1

  公开（公告）日：2002-02-12

  Methods for preparing 2-(4-(4-(4,5-dichloro-2-methylimidazol-1yl)butyl)-1-piperazinyl)-5-fluoropyrimidine and its physiologically acceptable salts are disclosed.

  公开了制备2-(4-(4-(4,5-二氯-2-甲基咪唑-1-基)丁基)-1-哌嗪基)-5-氟吡咯嘧啶及其生理上可接受的盐的方法。