(rac)-trans-2-(4-phenylpiperazin-1-yl)cyclohexanol

• 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: (rac)-trans-2-(4-phenylpiperazin-1-yl)cyclohexanol
• 英文别名: (1R,2R)-2-(4-phenylpiperazin-1-yl)cyclohexan-1-ol
• 化学式: C₁₆H₂₄N₂O
• 分子量: 260.379
• InChiKey: BAAMFQVLPJYVQQ-HZPDHXFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  26.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (rac)-trans-2-(4-phenylpiperazin-1-yl)cyclohexanol 在 sodium dihydrogenphosphate 、 2,2,6,6-四甲基哌啶氧化物 、 sodium hypochlorite 、 sodium chlorite 作用下， 以 乙腈 、 水 为溶剂， 反应 0.08h， 以87%的产率得到rac-trans-1-(2-hydroxycyclohexyl)-4-phenylpiperazine-2,3-dione
  参考文献：
  名称：

  无过渡金属条件下哌嗪和吗啉的选择性，催化和双重C（sp 3）-H氧化

  摘要：

  通过使用廉价且无害的试剂（例如NaClO 2，NaOCl和催化量的TEMPO），将TEMPO C（sp 3）–H选择性和催化氧化哌嗪和吗啉氧化成2,3-二酮哌嗪的新环保协议（ 2,3-DKP）和3-吗啉酮（3-MP）已被开发出来。与传统的N-单酰化/分子内C–N环化方法相比，这种从哌嗪直接获得2,3-DKP的方法具有明显的优势。另外，通过调节TEMPO的量，可以从吗啉衍生物制备2-烷氧基氨基-3-吗啉酮，这将使吗啉骨架的C2位进一步官能化。

  DOI：

  10.1021/acs.joc.8b02564
• 作为产物：
  描述：

  N-苯基哌嗪 在 D-(+)-二对甲基苯甲酰酒石酸 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 22.0h， 生成 (rac)-trans-2-(4-phenylpiperazin-1-yl)cyclohexanol
  参考文献：
  名称：

  合成和评估aza-vesamicol同源系列作为改良的碘标记的sigma-1受体成像探针。

  摘要：

  用于确定表达水平的Sigma-1受体成像探针对于各种疾病的诊断以及针对sigma-1受体的治疗剂的伴随诊断是理想的。在这项研究中，我们旨在开发对sigma-1受体具有更高亲和力的探针。为此，我们合成并评估了化合物，即维他命醇衍生物，其中在哌嗪环和苯环之间引入了不同链长的烷基链。vesamicol衍生物对sigma-1受体的结合亲和力趋于增加，具体取决于苯环和哌嗪环之间的烷基链长度。2-（4-（3-苯基丙基）哌嗪-1-基）环己-1-醇（5）（Ki = 5.8 nM）的sigma-1受体具有最高的结合亲和力; 所以，我们在5中将放射性碘引入到苯环中。放射性碘标记的探针[125I] 2-（4-（3-（4-碘苯基）丙基）哌嗪-1-基）环己-1-醇（[125I] 10）显示在体外和体内表达sigma-1受体的DU-145细胞中都有高积累。[125I] 10与过量的sigma受体配体氟哌啶醇的共同注射

  DOI：

  10.1016/j.bmc.2019.03.054

文献信息

• In vitro activity of novel dual action MDR anthranilamide modulators with inhibitory activity on CYP-450 (Part 2)
  作者：Philippe Labrie、Shawn P. Maddaford、Jacques Lacroix、Concettina Catalano、David K.H. Lee、Suman Rakhit、René C. Gaudreault

  DOI：10.1016/j.bmc.2007.03.014

  日期：2007.6.1

  Synthesis and in vitro cytotoxicity assays of new anthranilamide MDR modulators have been performed to assess their inhibition potency on the P-glycoprotein (P-gp) transporter. Previous studies showed that the replacement of the aromatic spacer group between nitrogen atoms (N-1 and N-2) in the P-gp inhibitor XR9576 with ethyl or propyl chain is optimal for P-gp inhibition potency. To confirm that observation, the ethyl or the propyl linker arm was replaced with a pyrrolidine or an alicyclic group such as cyclohexyl. In addition, an arylpiperazinyl group and two methoxyl groups onto the anthranilic part were introduced to assess their effect on the anti P-gp activity. Five molecules were prepared and evaluated on CEM/VLB500. All new anthranilamides were more potent than verapamil, most of them exhibited a lower cytotoxicity than XR9576. Compound 5 was the most potent and its inhibition activity was similar to XR9576. Interestingly, in vitro biotransformation studies of compounds 4 and 5 using human CYP-450 isoforms revealed, that conversely to XR9576, compounds 4 and 5 inhibited CYP3A4, an enzyme that colocalizes with P-gp in the intestine and contributes to tumor cell chemoresistance by enhancing the biodisposition of numerous drugs, notably paclitaxel. In that context, 5 might be suitable for further drug development. (C) 2007 Published by Elsevier Ltd.
• Synthesis, in vitro acetylcholine-storage-blocking activities, and biological properties of derivatives and analogs of trans-2-(4-phenylpiperidino)cyclohexanol (vesamicol)
  作者：Gary A. Rogers、Stanley M. Parsons、D. C. Anderson、Lena M. Nilsson、Ben A. Bahr、Wayne D. Kornreich、Rose Kaufman、Robert S. Jacobs、Bernard Kirtman

  DOI：10.1021/jm00126a013

  日期：1989.6

  Eighty-four analogues and derivatives of the acetylcholine-storage-blocking drug trans-2-(4-phenylpiperidino)-cyclohexanol (vesamicol) were synthesized, and their potencies were evaluated with the acetylcholine active-transport assay utilizing purified synaptic vesicles from Torpedo electric organ. The parent drug exhibits enantioselectivity, with (-)-vesamicol being 25-fold more potent than (+)-vesamicol. The atomic structure and absolute configuration of (+)-vesamicol were determined by X-ray crystallography. The absolute configuration of (-)-vesamicol is 1R,2R. Structure-activity evidence indicates that (-)-vesamicol does not act as an acetylcholine analogue. Alterations to all three rings can have large effects on potency. Unexpectedly, analogues locking the alcohol and ammonium groups trans-diequatorial or trans-diaxial both exhibit good potency. A potent benzovesamicol family has been discovered that is suitable for facile elaboration of the sort useful in affinity labeling and affinity chromatography applications. A good correlation was found between potencies as assessed by the acetylcholine transport assay and LD50 values in mouse.
• Aminocyclohexyl Esters
  作者：Seymour L. Shapiro、Harold Soloway、Harris J. Shapiro、Louis Freedman

  DOI：10.1021/ja01524a043

  日期：1959.8
• New systematically modified vesamicol analogs and their affinity and selectivity for the vesicular acetylcholine transporter – A critical examination of the lead structure
  作者：Claudia Barthel、Dietlind Sorger、Winnie Deuther-Conrad、Matthias Scheunemann、Stephanie Schweiger、Petra Jäckel、Ali Roghani、Jörg Steinbach、Gerrit Schüürmann、Osama Sabri、Peter Brust、Barbara Wenzel

  DOI：10.1016/j.ejmech.2015.05.033

  日期：2015.7

  To verify vesamicol as lead structure in the development of radioligands for imaging of VAChT in the brain by PET, we systematically modified this molecule and investigated four different groups of derivatives. Structural changes were conducted in all three ring systems A, B, and C resulting in a library of different vesamicol analogs. Based on their in vitro binding affinity toward VAChT as well as sigma(1) and sigma(2) receptors, we performed a structure-affinity relationship (SAR) study regarding both affinity and selectivity. The compounds possessed VAChT affinities in the range of 132 nM (benzovesamicol) to >10 mu M and selectivity factors from 0.1 to 73 regarding sigma(1) and sigma(2) receptors, respectively. We could confirm the exceptional position of benzovesamicols as most affine VAChT ligands. However, we also observed that most of the compounds with high VAChT affinity demonstrated considerable affinity in particular to the sigma(1) receptor. Finally, none of the various vesamicol analogs in all four groups showed an in vitro binding profile suitable for specific VAChT imaging in the brain. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Selective, Catalytic, and Dual C(sp³)–H Oxidation of Piperazines and Morpholines under Transition-Metal-Free Conditions
  作者：Delfino Chamorro-Arenas、Urbano Osorio-Nieto、Leticia Quintero、Luís Hernández-García、Fernando Sartillo-Piscil

  DOI：10.1021/acs.joc.8b02564

  日期：2018.12.21

  innocuous reagents, such as NaClO2, NaOCl, and catalytic amounts of TEMPO, a new environmentally friendly protocol for the selective and catalytic TEMPO C(sp3)–H oxidation of piperazines and morpholines to 2,3-diketopiperazines (2,3-DKP) and 3-morpholinones (3-MPs), respectively, has been developed. This novel direct access to 2,3-DKP from piperazines provides significant advantages over the traditional

  通过使用廉价且无害的试剂（例如NaClO 2，NaOCl和催化量的TEMPO），将TEMPO C（sp 3）–H选择性和催化氧化哌嗪和吗啉氧化成2,3-二酮哌嗪的新环保协议（ 2,3-DKP）和3-吗啉酮（3-MP）已被开发出来。与传统的N-单酰化/分子内C–N环化方法相比，这种从哌嗪直接获得2,3-DKP的方法具有明显的优势。另外，通过调节TEMPO的量，可以从吗啉衍生物制备2-烷氧基氨基-3-吗啉酮，这将使吗啉骨架的C2位进一步官能化。