1-二苯环庚基哌嗪 | 69159-50-8

• 物质功能分类: 医药中间体 - 哌嗪类化合物
• 分子结构分类: 有机化合物 - 苯类化合物 - 二苯并环庚烯
• 中文名称: 1-二苯环庚基哌嗪
• 中文别名: 1-(二苯基环庚基)-哌嗪
• 英文名称: 1-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)piperazine
• 英文别名: 1-(10,11-dihydro-5H-dibenzocycloheptene-5-yl)piperazine；N-(10,11-dihydro-5H-dibenzocycloheptan-5-yl)piperazine；1-(10,11-dihydro-5H-dibenzocyclohepten-5-yl)piperazine；1-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-yl)piperazine；5-PIPERAZINYL 10,11-DIHYDRO-5H-DIBENZO[a,d]CYCLOHEPTENE；5-Piperazino-dibenzocycloheptadien；N-(dibenzosuberan-5-yl)piperazine；1-(dibenzosuberyl)piperazine；5-(Suberan-5-yl)piperazine；N-(dibenzosuberane-5-yl)piperazine；1-(2-tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,11,13-hexaenyl)piperazine
• CAS: 69159-50-8
• 化学式: C₁₉H₂₂N₂
• mdl: MFCD01703212
• 分子量: 278.397
• InChiKey: MDBCLUYDTRHKCA-UHFFFAOYSA-N

物化性质

• 熔点：
  105-107°C
• 沸点：
  402.9±40.0 °C(Predicted)
• 密度：
  1.109±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.368
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险品标志：
  Xi
• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  1-二苯环庚基哌嗪 在 sodium hydroxide 、 氨 、 氢气 、 镍 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 25.0~100.0 ℃ 、607.95 kPa 条件下， 生成 2-[4-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)-piperazin-1-yl]-ethylamine
  参考文献：
  名称：

  New triazine derivatives as potent modulators of multidrug resistance

  摘要：

  A series of 70 triazine derivatives have been synthesized and tested for their capacity to modulate multidrug resistance (MDR) in DC-3F/AD and KB-A1 tumor cells in vitro, in comparison with verapamil (VRP), a calcium channel antagonist currently used in therapy as an antihypertensive drug, which also shows MDR modulating activity. Among the 12 selected compounds, 16 (S9788) showed high MDR reversing properties in vitro (300- and 6-fold VRP at 5-mu-M in DC-3F/AD and KB-A1 cells, respectively) and induced a strong accumulation of adriamycin. The relationship between the increase of ADR accumulation and the fold reversal induced by these compounds and their lack of effects on the sensitive DC-3F cells suggest that they act mainly by inhibiting the P-glycoprotein (Pgp) catalyzed efflux of cytotoxic agents, as already described for a majority of MDR modulators. In vivo, in association with the antitumor drug vincristine (0.25 mg/kg), 16 (100 mg/kg) increased the TIC by 39% in mice bearing the resistant tumor cell line P388/VCR. According to these interesting properties, 16 was selected for a clinical development because it was more bioavailable than 34, even though it was less active.

  DOI：

  10.1021/jm00091a017
• 作为产物：
  描述：

  10,11-二氢二苯并[a,b]环庚烯-5-酮 在 盐酸 、 sodium tetrahydroborate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 水 、 异丙醇 为溶剂， 反应 13.5h， 生成 1-二苯环庚基哌嗪
  参考文献：
  名称：

  二芳基哌嗪类化合物及其医药用途

  摘要：

  本发明涉及通式I所表示的二芳基哌嗪类化合物，其溶剂合物、立体异构体或其可药用盐，含有它们的药用组合物，以及所述化合物用于制备预防或治疗手术后疼痛、偏头痛、内脏痛、神经性疼痛等各种疼痛以及由阿片类等镇痛药物引起的成瘾性和耐受性等病症的用途。

  公开号：

  CN103130745B

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
• Compounds enhancing antitumor activity of other cytotoxic agents
  申请人：Pfizer Inc

  公开号：US06130217A1

  公开（公告）日：2000-10-10

  This invention relates to certain heterocyclic compounds and their pharmaceutically acceptable salts, which are useful for sensitizing multidrug-resistant tumor cells to anticancer agents and multidrug resistant forms of malaria, tuberculosis, leishmania and amoebic dysentery to chemotherapeutants. The compounds and their pharmaceutically acceptable salts are also inhibitors of the active drug transport capability of P-glycoprotein which is encoded by the human MDR1 gene, as well as of certain other related ATP-binding-cassette transporters from eukaryotic and prokaryotic organisms (e.g., pfmdr from Plasmodium falciprum, and murine mdr1 and mdr3 gene products).

  这项发明涉及某些杂环化合物及其药用可接受的盐，这些化合物对于使多药耐药肿瘤细胞对抗癌药物和多药耐药形式的疟疾、结核病、利什曼病和阿米巴痢疾对化疗药物具有敏感性是有用的。这些化合物及其药用可接受的盐还是人类MDR1基因编码的P-糖蛋白的活性药物转运能力的抑制剂，以及来自真核和原核生物（例如，来自疟原虫的pfmdr，以及小鼠mdr1和mdr3基因产物）的某些其他相关的ATP结合盒转运蛋白的抑制剂。
• Reversed isoniazids: Design, synthesis and evaluation against Mycobacterium tuberculosis
  作者：Malkeet Kumar、Kawaljit Singh、Andile H. Ngwane、Fahreta Hamzabegovic、Getahun Abate、Bienyameen Baker、Ian Wiid、Daniel F. Hoft、Peter Ruminski、Kelly Chibale

  DOI：10.1016/j.bmc.2017.12.047

  日期：2018.2

  Novel reversed isoniazid (RINH) agents were synthesized by covalently linking isoniazid with various efflux pump inhibitor (EPI) cores and their structural motifs. These RINH agents were then evaluated for anti-mycobacterial activity against sensitive, isoniazid mono-resistant and MDR clinical isolates of M. tuberculosis and a selected number of compounds were also tested ex vivo for intracellular

  通过将异烟肼与各种外排泵抑制剂（EPI）核及其结构基序共价连接，合成了新型反向异烟肼（RINH）剂。这些RINH剂然后针对敏感，异烟肼单抗性和MDR临床分离株的抗分枝杆菌活性的评估结核分枝杆菌和所选择的一些化合物还测试了离体细胞内的活性以及在溴化乙锭（EB）测定外排泵抑制功效。针对的各种菌株一些化合物的效力的结核分枝杆菌（4A - ç，7和8 ;分枝杆菌H37Rv-MIC 99 ≤1.25μM，R5401-MIC 99≤2.5微米，X_61-MIC 99 ≤5微米）证明的逆转抗结核剂战略走向新的抗分枝杆菌剂的发展，解决耐药性的迅速增长的问题的可能性。此外，对于> 90％的通过抑制巨噬细胞活性1A - Ç和图3b（MIC 90 ≤13.42μM）和EB的抑制流出证明这些化合物是令人鼓舞的。
• Bis-benzo or benzopyrido cyclohepta piperidene, piperidylidene and
  申请人：Schering Corporation

  公开号：US05422351A1

  公开（公告）日：1995-06-06

  Bis-benzo or benzopyrido piperidene, piperidylidene and piperazine compounds of the formula: ##STR1## and pharmaceutically acceptable salts thereof are disclosed, wherein Z represents --(C(R.sup.a).sub.2).sub.m --Y--(C(R.sup.a).sub.2).sub.n -- or ##STR2## The compounds of Formula I possess anti-allergic and anti-inflammatory activity. Methods for preparing and using the compounds are also described.

  本发明揭示了一种具有以下结构的双苯或苯并吡啶哌啶烯，哌啶基亚甲基和哌嗪类化合物的药用盐：其中Z代表--(C(R^a)_2)_m--Y--(C(R^a)_2)_n--或##STR2##。式I的化合物具有抗过敏和抗炎活性。还描述了制备和使用这些化合物的方法。
• Piperazinyl-substituted pyridylalkane, alkene and alkine carboxamides
  申请人：Biedermann Elfi

  公开号：US06903118B1

  公开（公告）日：2005-06-07

  The invention relates to new piperazinyl-substituted pyridylalkane, alkene, and alkine acid amides substituted with saturated or one or several-fold unsaturated hydrocarbon residue in the carboxylic acid group according to the general formula (I) as well as methods for the production of these compounds, medicaments containing these and their production as well as their therapeutic use, especially as cytostatic agents and immunosuppressive agents, for example in the treatment or prevention of various types of tumors and control of immune reactions such as autoimmune diseases.

  该发明涉及一种新的哌嗪基取代的吡啶烷、烯烃和炔烃酸酰胺，其在羧酸基团中取代有饱和或一种或多种不饱和的碳氢残基，其通式为(I)，以及制备这些化合物的方法，含有这些化合物的药物及其制备，以及它们的治疗用途，特别是作为细胞毒药物和免疫抑制剂，例如在治疗或预防各种类型的肿瘤和控制免疫反应如自身免疫疾病中的应用。