1- piperazine | 84359-49-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1- piperazine
• 英文别名: 1-[bis(4-methoxyphenyl)-methyl]piperazine；1-bis(4-methoxyphenyl)methylpiperazine；1-[bis(4-methoxyphenyl)methyl]piperazine
• CAS: 84359-49-9
• 化学式: C₁₉H₂₄N₂O₂
• 分子量: 312.412
• InChiKey: VDCGRZPITZRVEM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  33.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1- piperazine 在 碳酸氢钠 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 40.0h， 生成 6-[1-[1-[Bis(4-methoxyphenyl)methyl]piperazin-4-yl]-2-hydroxy-3-propanylthio]purine
  参考文献：
  名称：

  Synthesis and structure-activity relationship of 6-substituted purine derivatives as novel selective positive inotropes

  摘要：

  A series of purine derivatives was prepared and examined for selective inotropic activity in vitro and in vivo. Thioether-linked derivatives were superior to their oxygen and nitrogen isosteres. Substitution of electron-withdrawing groups on the benzhydryl moiety of these agents increased potency. The best compound of the study, 17 (carsatrin), was examined further and demonstrated selective oral activity as a positive inotrope. These compounds are presumed to act by affecting the kinetics of the cardiac sodium channel by analogy to the prototypic agent DPI 201106 (1). Their high selectivity for increasing contractile force and dP/dt without affecting blood pressure or heart rate is consistent with this mechanism. Carsatrin (17) was selected as a potential development candidate.

  DOI：

  10.1021/jm00102a001
• 作为产物：
  描述：

  二甲氧基苯甲醇 在 哌啶 、 氯化亚砜 作用下， 以 二氯甲烷 、 环己烷 为溶剂， 反应 20.0h， 生成 1- piperazine
  参考文献：
  名称：

  芳氧基乙酰胺衍生物作为神经保护剂的合成及生物学评价。

  摘要：

  设计并合成了一系列新的芳氧基乙酰胺衍生物10a-s和14a-m。在分化的大鼠嗜铬细胞瘤细胞（PC12细胞）中研究了它们对谷氨酸诱导的细胞死亡的保护活性。大多数化合物表现出神经保护作用，尤其是对10m，10r，14b和14c表现出神经保护作用，在三种剂量（0.1、1.0、10μM）下，PC12细胞都有潜在的保护作用。MTT分析，Hoechst 33342 / PI双重染色和高含量筛选（HCS）显示，用10m，10r，14b和14c预处理细胞以剂量依赖的方式显着降低了细胞凋亡的程度。蛋白质印迹分析的结果表明，这些化合物通过caspase-3途径抑制了谷氨酸诱导的PC12细胞凋亡。这些化合物可以是用于进一步发现用于治疗脑缺血性中风的神经保护剂的先导化合物。还介绍了基本的结构-活性关系。

  DOI：

  10.1016/j.bmcl.2016.03.094

文献信息

• Structure−Activity Relationship of Newly Synthesized Quinoline Derivatives for Reversal of Multidrug Resistance in Cancer
  作者：Tsuneji Suzuki、Nobuyuki Fukazawa、Kunio San-nohe、Wakao Sato、Osamu Yano、Takashi Tsuruo

  DOI：10.1021/jm960869l

  日期：1997.6.1

  interactions. Other major structural features which influence the MDR-reversing activities of these compounds are a quinoline nitrogen atom and a basic nitrogen atom in piperazine. Furthermore, in highly active compounds, the distance between the hydrophobic moiety and the basic nitrogen atom (an atom connected to 2-hydroxypropoxyquinoline) must be at least 5 A. Several compounds were found to reverse

  在体外检查了24种新合成的喹啉衍生物对肿瘤细胞多药耐药性（MDR）的影响。在低浓度下，这些化合物增强了[3H]长春新碱在K562 / ADM细胞中的积累，并逆转了肿瘤细胞MDR。结构-活性关系分析的结果表明，在高活性化合物中，疏水部分的两个芳基环偏离同一平面，因此它们能够与P-170糖蛋白（P-gp）的氢键供体相互作用pi-氢-pi相互作用。影响这些化合物的MDR-逆转活性的其他主要结构特征是哌嗪中的喹啉氮原子和碱性氮原子。此外，在高活性化合物中
• Sequential Selective C−H and C(sp ³ )− ⁺ P Bond Functionalizations: An Entry to Bioactive Arylated Scaffolds
  作者：K. Naresh Babu、Fedaa Massarwe、Israa Shioukhi、Ahmad Masarwa

  DOI：10.1002/anie.202111164

  日期：2021.12.6

  of the resulting phosphonium salt building blocks was demonstrated by the chemoselective post-functionalization of benzylic C(sp3 )-+ PPh3 groups to achieve aminations, thiolations, and arylations. In this way, benzhydrylamines, benzhydrylthioethers, and triarylmethanes, structural motifs that are present in many pharmaceuticals and agrochemicals, are readily accessed. These include the synthesis of

  含有 C(sp3 )-+ P 键的有机鏻盐是有机合成中用于构建 CC 双键的最常用试剂之一。然而，它们用作 C 选择性亲电基团的情况很少见。在这里，我们探索了一种有效且通用的无过渡金属方法，用于顺序化学和区域选择性 CH 和 C(sp3 )-+ P 键功能化。在本研究中，CH 烷基化导致二苯甲基三芳基鏻盐的合成是通过简单和市售起始材料的一锅四组分交叉偶联反应实现的。通过对苄基 C(sp3 )-+ PPh3 基团进行化学选择性后官能化以实现胺化、硫醇化和芳基化，证明了所得鏻盐结构单元的实用性。这样，二苯甲基胺、二苯甲基硫醚、和三芳基甲烷是许多药物和农用化学品中存在的结构基序，很容易获得。其中包括仅用两到三个步骤从简单材料合成两种抗癌剂。此外，还开发了使用二苯甲基鏻盐对生物活性药物进行后期功能化的协议。这种新方法应该为学术和药物研究中的应用提供新的转变。
• Amino acid derivative having anti-CCK activity
  申请人：Tobishi Pharmaceutical Co., Ltd.

  公开号：US05716958A1

  公开（公告）日：1998-02-10

  A compound represented by the formula (1): ##STR1## wherein, m is an integer of 1 to 3; n is an integer 0 or 1; A represents CH or N atom, and forms together with the N atom bonded to the carbonyl group a piperidine ring or a piperazine ring; R.sub.1 independently represents a straight or branched chain alkyl group having 1 to 4 carbon atoms; a cycloalkyl group having 3 to 8 carbon atoms; a phenyl group, unsubstituted or substituted with a halogen atom or with an alkoxy group having 1 to 4 carbon atoms; or a pyridyl group; or two R.sub.1, together with the group >CH-- to which they bind, form a dibenzo cycloheptenyl group or a fluorenyl group; R.sub.2 represents a phenyl group substituted with a carboxyl or substituted carboxyl group; a pyridyl group substituted with a carboxyl or substituted carboxyl group, a pyrazyl group substituted with a carboxyl or substituted carboxyl group, an oxazolyl substituted with a carboxyl or substituted carboxyl group, a triazolyl substituted with one or two carboxyl or substituted carboxyl groups, or a phosphonopyridyl group; and R.sub.3 represents an indolyl group unsubstituted or substituted with a substituent selected from the group consisting of a halogen atom, a hydroxy group, an alkoxy group having 1 to 4 carbon atoms and methoxycarbonyl ethyl group and the pharmaceutically acceptable salts thereof.

  化合物的化学式为(1): ##STR1## 其中，m为1到3的整数；n为0或1的整数；A表示CH或N原子，并与与羰基团结合的N原子一起形成哌啶环或哌嗪环；R.sub.1独立表示直链或支链烷基，其具有1到4个碳原子；环状烷基，其具有3到8个碳原子；苯基，未取代或取代有1到4个碳原子的卤素基或烷氧基；或吡啶基；或两个R.sub.1与它们结合的>CH--基团一起形成二苯并环庚烯基团或芴基团；R.sub.2表示取代有羧基或取代羧基的苯基，取代有羧基或取代羧基的吡啶基，取代有羧基或取代羧基的吡唑基，取代有羧基或取代羧基的噁唑基，取代有一或两个羧基或取代羧基的三唑基，或取代有磷酸甲基吡啶基；R.sub.3表示未取代或取代有卤素原子、羟基、具有1到4个碳原子的烷氧基和甲氧羰基乙基基团的吲哚基团或其药学上可接受的盐。
• Substituted imidazolyl-alkyl-piperazine and -diazepine derivatives
  申请人：SYNTEX PHARMACEUTICALS LTD.

  公开号：EP0289227A1

  公开（公告）日：1988-11-02

  Substituted imidazolyl-alkyl-piperazine and diazepine derivatives of Formula A: wherein:     R¹ is aryl;     R² is aryl, C₁₋₄ alkyl, or hydrogen;     R³ is C₁₋₄ alkyl, hydroxy, or hydrogen;     R⁴ is aryl;     R⁵ is aryl;     m is two or three;     n is zero, one or two, provided that when R³ is hydroxy, n is one or two; and     q is zero, one, two, or three; and the pharmaceutically acceptable salts thereof, are useful for treating mammals having a variety of disease states, such as stroke, epilepsy or epileptic psychotic symptoms, hypertension, angina, migraine, arrhythmia, thrombosis, embolism, acute cardiac failure, irritable bowel syndrome, neurodegenerative diseases such as Alzheimer's or Huntington's chorea, diuresis, ischemia such as focal and global ischemia or cerebrovascular ischemia induced by cocaine abuse, and also for treatment of spinal injuries.

  式 A 的取代咪唑烷基哌嗪和二氮杂卓衍生物： 其中 R¹ 是芳基； R² 是芳基、C₁₋₄ 烷基或氢； R³ 是 C₁₋₄ 烷基、羟基或氢； R⁴ 是芳基； R⁵ 是芳基； m 是两个或三个； n 为 0、1 或 2、 当 R³ 为羟基时，n 为一或二；以及 q 为零、一、二或三； 及其药学上可接受的盐类，可用于治疗哺乳动物的多种疾病，如中风、癫痫或癫痫性精神症状、高血压、心绞痛、偏头痛、心律失常、血栓形成、栓塞、急性心力衰竭、肠易激综合征、神经性肠病、心绞痛、偏头痛、心律失常、血栓形成、栓塞、急性心力衰竭、肠易激综合征、神经退行性疾病（如阿尔茨海默氏症或亨廷顿舞蹈症）、利尿、缺血（如局灶性和全身性缺血或滥用可卡因引起的脑血管缺血），以及用于治疗脊柱损伤。
• Structure–activity relationships of diphenylpiperazine N-type calcium channel inhibitors
  作者：Hassan Pajouhesh、Zhong-Ping Feng、Yanbing Ding、Lingyun Zhang、Hossein Pajouhesh、Jerrie-Lynn Morrison、Francesco Belardetti、Elizabeth Tringham、Eric Simonson、Todd W. Vanderah、Frank Porreca、Gerald W. Zamponi、Lester A. Mitscher、Terrance P. Snutch

  DOI：10.1016/j.bmcl.2010.01.008

  日期：2010.2

  A novel series of compounds derived from the previously reported N-type calcium channel blocker NP118809 (1-(4-benzhydrylpiperazin-1-yl)-3,3-diphenylpropan-1-one) is described. Extensive SAR studies resulted in compounds with IC50 values in the range of 10-150 nM and selectivity over the L-type channels up to nearly 1200-fold. Orally administered compounds 5 and 21 exhibited both anti-allodynic and anti-hyperalgesic activity in the spinal nerve ligation model of neuropathic pain. (C) 2010 Elsevier Ltd. All rights reserved.