3-(4-嘧啶-2-哌嗪)-1-丙胺 | 57648-83-6

• 物质功能分类: 医药中间体 - 杂环化合物 - 嘧啶类化合物
• 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: 3-(4-嘧啶-2-哌嗪)-1-丙胺
• 中文别名: 3-（4-嘧啶-2-基哌嗪-1-基）丙-1-胺
• 英文名称: 4-(2-pyrimidinyl)-1-piperazinepropanamine
• 英文别名: 1-(pyrimidin-2-yl)-4-(3-aminopropyl)piperazine；3-[1-(2-pyrimidinyl)-4-piperazinyl]propylamine；3-[4-(2-pyrimidyl)-1-piperazinyl]propylamine；1-(3-aminopropyl)-4-(2-pyrimidinyl)piperazine；3-(4-Pyrimidin-2-ylpiperazin-1-yl)propan-1-amine
• CAS: 57648-83-6
• 化学式: C₁₁H₁₉N₅
• mdl: MFCD09041380
• 分子量: 221.305
• InChiKey: BCPGGRWLIFPTLE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.636
• 拓扑面积：
  58.3
• 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：

  3-(4-嘧啶-2-哌嗪)-1-丙胺 在 potassium carbonate 、 氯化铵 、 锌 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 0.01h， 生成 2-(4-fluorobenzyl)-2-phenyl-N-(3-(4-(pyrimidin-2-yl)piperazin-1-yl)propyl)hydrazine-1-carboxamide
  参考文献：
  名称：

  Benzyl Phenylsemicarbazides: A Chemistry-Driven Approach Leading to G Protein-Biased Dopamine D₄ Receptor Agonists with High Subtype Selectivity

  摘要：

  Many subtype-selective dopamine receptor ligands developed for the D-2-D-4 family incorporate a 1-arylpiperazine-derived primary recognition motif, which is connected to a lipophilic moiety occupying an extended binding pocket (EBP) of the receptor via an aliphatic linker of variable lengths. The evaluation of a novel group of dopamine receptor ligands now showed that highly subtype-selective ligands [up to K-i(D-4.4) = 0.25 nM, D-2L/D-4.4 = 320, D-3/D-4.4 = 710 for APH199 (17)] can be obtained by choosing a relatively large and conformationally flexible 1-benzyl-1-phenylsemicarbazide substructure to fill the EBP. The novel chemotype APH199 (17) was found to act as a full agonist at the D-4 receptor showing significant bias toward G protein activation over beta-arrestin recruitment in comparison to quinpirole.

  DOI：

  10.1021/acs.jmedchem.9b01085
• 作为产物：
  描述：

  [3-(4-Pyrimidin-2-yl-piperazin-1-yl)-propyl]-carbamic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以83%的产率得到3-(4-嘧啶-2-哌嗪)-1-丙胺
  参考文献：
  名称：

  5-(5,6-Dichloro-2-indolyl)-2-methoxy-2,4-pentadienamides:  Novel and Selective Inhibitors of the Vacuolar H⁺-ATPase of Osteoclasts with Bone Antiresorptive Activity

  摘要：

  The vacuolar H+-ATPase (V-ATPase) located on the ruffled border of the osteoclast, is a proton pump which is responsible for secreting the massive amounts of protons that are required for the bone resorption process. With the aim to identify new agents which are able to prevent the excessive bone resorption associated with osteoporosis, we have designed a novel class of potent and selective inhibitors of the osteoclast proton pump, starting from the structure of the specific V-ATPase inhibitor bafilomycin A(1). Compounds 3a-d potently inhibited the V-ATPase in chicken osteoclast membranes (IC50 = 60-180 nM) and were able to prevent bone resorption by human osteoclasts in vitro at low-nanomolar concentrations. Notably, the EC50 of compound 3c in this assay was 45-fold lower than the concentration required for half-maximal inhibition of the V-ATPase from human kidney cortex. These results support the validity of the osteoclast proton pump as a useful molecular target to produce novel inhibitors of bone resorption, potentially useful as antiosteporotic agents.

  DOI：

  10.1021/jm9800144

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。
• 2-pyrimidinyl-1-piperazine derivatives, processes for their preparation
  申请人：Troponwerke GmbH & Co., KG

  公开号：US04818756A1

  公开（公告）日：1989-04-04

  The invention relates to substituted 2-pyrimidinyl-1-piperazine derivatives defined herein by formula (I), processes for their manufacture, compositions containing said substituted 2-pyrimidinyl-1-piperazine derivatives as active materials and the use of said compounds and compositions as agents effecting the central nervous system. Also included in the invention are intermediates of formula (VIII) for making the active formula (I) compounds.

  这项发明涉及由以下公式（I）定义的取代2-嘧啶基-1-哌嗪衍生物，其制造方法，含有所述取代2-嘧啶基-1-哌嗪衍生物作为活性物质的组合物，以及将所述化合物和组合物用作影响中枢神经系统的药剂。该发明还包括用于制备活性公式（I）化合物的公式（VIII）的中间体。
• Use of aryl- and heteroaryl piperazinyl carboxamides in the treatment of
  申请人：American Home Products Corporation

  公开号：US05106849A1

  公开（公告）日：1992-04-21

  There are disclosed the use of the compounds of the formula (I) ##STR1## wherein R.sup.1 is 1-adamantyl, 3-methyl-1-adamantyl, 3-noradamantyl, unsubstituted or substituted-2-indolyl, 3-indolyl, 2-benzofuranyl or 3-benzofuranyl wherein the substituents are selected from lower alkyl, lower alkoxy and halo; R.sup.2 is unsubstituted or substituted phenyl, benzyl, or pyrimidinyl wherein the substituents are selected from lower alkyl, lower alkoxy, trifluoromethyl and halo; R.sup.3 is H or lower alkyl of 1 to 3 carbon atoms; n is the integer 0 or 1; and m is the integer from 2 to 5 and the pharmaceutically acceptable salts thereof.

  公开了使用式(I)的化合物，其中R.sup.1为1-金刚烷基、3-甲基-1-金刚烷基、3-去金刚烷基、未取代或取代的2-吲哚基、3-吲哚基、2-苯并呋喃基或3-苯并呋喃基，其中取代基选自较低的烷基、较低的烷氧基和卤素；R.sup.2为未取代或取代的苯基、苄基或嘧啶基，其中取代基选自较低的烷基、较低的烷氧基、三氟甲基和卤素；R.sup.3为H或1至3个碳原子的较低烷基；n为整数0或1；m为2至5的整数及其药用盐。
• Polycyclic-carbamic acid piperazinoalkyl esters and amides
  申请人：American Home Products Corporation

  公开号：US04882432A1

  公开（公告）日：1989-11-21

  The compounds of the formula: ##STR1## wherein Ad is 1-adamantyl, 2-adamantyl or 3-noradamantyl; X is --O-- or ##STR2## n is 1,2,3 or 4; R.sup.1 and R.sup.2 are, independently, hydrogen, alkyl, phenyl, benzyl, or substituted phenyl or benzyl in which the substituent is alkyl, alkoxy, halo, cyano, nitro or trifluoromethyl; and R.sup.3 is phenyl, benzyl or substituted phenyl or benzyl in which the substituent is alkyl, alkoxy, halo, nitro, cyano or perhalomethyl, 2-, 3-, or 4-pyridinyl, 2-, 4-or 5-pyrimidiny; or 2- or 3-pyrazinyl; R.sup.4 and R.sup.5 are independently, hydrogen, methyl, phenyl or benzyl; or a pharmaceutically acceptable salt thereof, are useful anxiolytic/antidepressant agents, with elements of antipsychotic activity.

  该公式化合物为：##STR1## 其中Ad是1-金刚烷基、2-金刚烷基或3-去金刚烷基；X为--O--或##STR2## n为1、2、3或4；R.sup.1和R.sup.2分别为氢、烷基、苯基、苄基或取代苯基或苄基，其中取代基为烷基、烷氧基、卤素、氰基、硝基或三氟甲基；R.sup.3为苯基、苄基或取代苯基或苄基，其中取代基为烷基、烷氧基、卤素、硝基、氰基或全氟甲基，2-、3-或4-吡啶基、2-、4-或5-吡咯啉基；或2-或3-吡嗪基；R.sup.4和R.sup.5分别为氢、甲基、苯基或苄基；或其药学上可接受的盐，可用作抗焦虑/抗抑郁药物，具有抗精神病活性成分。
• Characteristics of metabolic stability and the cell permeability of 2‐pyrimidinyl‐piperazinyl‐alkyl derivatives of 1H‐imidazo[2,1 <i>‐f</i> ]purine‐2,4(3 <i>H</i> ,8 <i>H</i> )‐dione with antidepressant‐ and anxiolytic‐like activities
  作者：Agnieszka Zagórska、Anna Partyka、Adam Bucki、Marcin Kołaczkowski、Magdalena Jastrzębska‐Więsek、Anna Czopek、Agata Siwek、Monika Głuch‐Lutwin、Marek Bednarski、Marek Bajda、Jakub Jończyk、Kamil Piska、Paulina Koczurkiewicz、Anna Wesołowska、Maciej Pawłowski

  DOI：10.1111/cbdd.13442

  日期：2019.4

  antagonist of 5-HT1A . Molecular modeling studies revealed differences in binding mode between compound 4b and buspirone, which might reflect variation of the ligands' affinity and potency in the 5-HT1A receptor. Compound 4b in silico models demonstrated drug-likeness properties and, contrary to buspirone, showed a metabolic stability in mouse liver microsomes system. Experimentally obtained value

  为了发现一类新型的精神药物，已经合成了一系列的1H-咪唑并[2,1-f]嘌呤-2,4（3H，8H）-二酮的2-嘧啶基-哌嗪基-烷基衍生物。评价化合物对5-羟色胺5-HT1A，5-HT7和磷酸二酯酶PDE4和PDE10的体外亲和力。最有效的化合物2-嘧啶基-1-哌嗪基丁基-咪唑并[2,1-f]嘌呤-2,4-二酮（4b）是5-HT1A的强效选择性拮抗剂。分子模型研究表明，化合物4b与丁螺环酮之间的结合方式不同，这可能反映了5HT1A受体中配体亲和力和效力的变化。在计算机模拟模型中，化合物4b表现出药物相似性，并且与丁螺环酮相反，在小鼠肝微粒体系统中表现出代谢稳定性。在平行人工渗透率测定中，实验获得的4b的表观渗透率系数Papp值表明与血浆蛋白弱结合和高肠道吸收率的可能性。评估4b的抗抑郁药和抗焦虑药活性表明，在相同剂量的1.25 mg / kg时，两种活性均具有特异性。4b的抗抑郁和/或抗焦虑特性可能与其首过效应有关。