托品醇 | 135-97-7

• 物质功能分类: 天然产物 - 生物碱
• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 中文名称: 托品醇
• 中文别名: 莨菪醇；endo-8-甲基-8-氮杂双环[3.2.1]辛-3-醇；8-甲基-8-氮杂双环[3.2.1]-3-辛烷醇；3-羟基莨菪烷；托品；品托碱；α-托品醇
• 英文名称: exo-8-methyl-8-azabicyclo[3.2.1]octan-3-ol
• 英文别名: (1S,5R)-8-methyl-8-azabicyclo[3.2.1]octan-3-ol
• CAS: 135-97-7；120-29-6
• 化学式: C₈H₁₅NO
• 分子量: 141.213
• InChiKey: CYHOMWAPJJPNMW-DHBOJHSNSA-N

物化性质

• 熔点：
  50-60 °C(lit.)
• 沸点：
  233 °C(lit.)
• 密度：
  1.045 g/mL at 25 °C(lit.)
• 闪点：
  232-234°C
• 溶解度：
  H2O：0.1 g/mL，澄清
• LogP：
  -0.100 (est)
• 物理描述：
  Hygroscopic solid; [Merck Index] White or cream-colored crystalline powder; Hygroscopic; [Alfa Aesar MSDS]
• 蒸汽压力：
  0.01 [mmHg]
• 解离常数：
  10.06
• 保留指数：
  1167

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• TSCA：
  Yes
• 危险等级：
  6.1(b)

制备方法与用途

概述

托品醇，即α-托品醇，是合成阿托品的重要中间体。阿托品是一种副交感神经抑制剂，在眼科中主要用于扩瞳和作为泻药。

生物活性

Tropine（伪托品醇、3α-托品醇）是一种天然存在的莨菪烷生物碱，也是多种具有生物活性的生物碱合成过程中的中间体。这些生物碱大多具备显著的神经学作用。

用途

托品醇用作医药中间体。

反应信息

• 作为反应物：
  描述：

  托品醇 在 2-双环己基膦-2',6'-二甲氧基联苯 、 双(乙腈)氯化钯(II) 、 sodium hydride 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 、 三乙胺 、 mineral oil 为溶剂， 反应 3.0h， 生成 N-(cyclopropyl(phenyl)methyl)-3-(4-(((exo)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl)oxy)phenyl)-1H-indazole-5-carboxamide
  参考文献：
  名称：

  The Discovery of Orally Bioavailable Tyrosine Threonine Kinase (TTK) Inhibitors: 3-(4-(heterocyclyl)phenyl)-1H-indazole-5-carboxamides as Anticancer Agents

  摘要：

  The acetamido and carboxamido substituted 3-(1H-indazol-3-yl)benzenesulfonamides are potent TTK inhibitors. However, they display modest ability to attenuate cancer cell growth; their physicochemical properties, and attendant pharmacokinetic parameters, are not drug-like. By eliminating the polar 3-sulfonamide group and grafting a heterocycle at the 4 position of the phenyl ring, potent inhibitors with oral exposure were obtained. An X-ray cocrystal structure and a refined binding model allowed for a structure guided approach. Systematic optimization resulted in novel TTK inhibitors, namely 3-(4-(heterocyclyl)phenyl)-1H-indazole-5-carboxamides. Compounds incorporating the 3-hydroxy-8-azabicyclo[3.2.1]octan-8-yl bicyclic system were potent (TTK IC50 < 10 nM, HCT116 GI(50) < 0.1 mu M), displayed low off-target activity (>500X), and microsomal stability (T-1/2 > 30 min). A subset was tested in rodent PK and mouse xenograft models of human cancer. Compound 75 (CFI-401870) recapitulated the phenotype of TTK RNAi, demonstrated in vivo tumor growth inhibition upon oral dosing, and was selected for preclinical evaluation.

  DOI：

  10.1021/jm501740a
• 作为产物：
  描述：

  tropinone 在 tris(triphenylphosphine)ruthenium(II) chloride 、 2-(diphenylphosphaneyl)-N,N-dimethyl-1H-pyrrol-1-amine 、 potassium hydroxide 作用下， 以 异丙醇 为溶剂， 反应 3.0h， 以90%的产率得到托品醇
  参考文献：
  名称：

  [N，P]-吡咯-膦配体：Ru催化的转移加氢微波辅助反应的高效且坚固的配体

  摘要：

  评价含吡咯基的[NP]-配体（L1）和[Ru]作为酮转移氢化反应中的催化体系。微波辐射与常规加热条件之间的比较表明，MW可以成功用作能源，缩短了反应时间。的L1 /钌（II）被证明是一种活性的，高效且健壮的催化体系。使用包括实现65-95％的转化率的吸电子基团和电子给体基团在内的多种底物评估了该催化体系的范围。而且，该催化体系即使具有高度空间位阻的酮也显示出良好的活性。

  DOI：

  10.1016/j.catcom.2018.07.009

文献信息

• Npy antagonists, preparation and uses
  申请人：Botez Iuliana

  公开号：US20090233910A1

  公开（公告）日：2009-09-17

  The present invention concerns novel compounds, their preparation and their uses, therapeutic uses in particular. More specifically it concerns derivative compounds having at least two aromatic cycles, their preparation and their uses, in particular in the area of human or animal health. These compounds have an affinity for the biological receptors of neuropeptide Y, NPY, present in the central and peripheral nervous systems. The compounds of the invention are preferably NPY antagonists, and more particularly antagonists of sub-type NPY Y1, and can therefore be used for the therapeutic or prophylactic treatment of any disorder involving NPY. The present invention also concerns pharmaceutical compositions containing said compounds, their preparation and their uses, as well as treatment methods using said compounds.

  本发明涉及新颖化合物，它们的制备和用途，特别是在治疗方面的用途。更具体地说，它涉及至少具有两个芳香环的衍生化合物，它们的制备和用途，特别是在人类或动物健康领域。这些化合物对存在于中枢和外周神经系统中的神经肽Y（NPY）的生物受体具有亲和力。本发明的化合物优选为NPY拮抗剂，更具体地说是NPY Y1亚型的拮抗剂，因此可用于治疗或预防涉及NPY的任何疾病。本发明还涉及含有所述化合物的药物组合物，其制备和用途，以及使用所述化合物的治疗方法。
• [EN] ALKALOID AMINOESTER DERIVATIVES AND MEDICINAL COMPOSITION THEREOF<br/>[FR] DÉRIVÉS AMINOESTÉRIFIÉS D'ALCALOÏDES ET COMPOSITION MÉDICINALE LES INCLUANT
  申请人：CHIESI FARMA SPA

  公开号：WO2010072338A1

  公开（公告）日：2010-07-01

  The present invention relates to alkaloid aminoester derivatives acting as muscarinic receptor antagonists, to methods of preparing such derivatives, to compositions comprising them and therapeutic use thereof.

  本发明涉及作为毒蕈碱受体拮抗剂的生物碱氨基酸酯衍生物，制备此类衍生物的方法，包含它们的组合物以及它们的治疗用途。
• Novel sulfonyldiazomethanes, photoacid generators, resist compositions, and patterning process
  申请人：——

  公开号：US20040167322A1

  公开（公告）日：2004-08-26

  A chemical amplification type resist composition comprising a specific benzenesulfonyldiazomethane containing a long-chain alkoxyl group at the 2-position on benzene ring has many advantages including improved resolution, improved focus latitude, minimized line width variation or shape degradation even on long-term PED, minimized debris left after coating, development and peeling, and improved pattern profile after development and is thus suited for microfabrication.

  一种化学放大型抗蚀组合物，包括在苯环上的2-位含有长链烷氧基基团的特定苯磺酰二氮甲烷，具有许多优点，包括提高分辨率，改善焦点宽度，即使在长期PED上也减少线宽变化或形状退化，涂层、显影和剥离后减少残留物，并在显影后改善图案轮廓，因此适用于微加工。
• Amino-substituted tricyclic derivatives and methods of use
  申请人：Schrimpf R. Michael

  公开号：US20050234031A1

  公开（公告）日：2005-10-20

  Compounds of formula (I) wherein A and B are amine-substituted sidechains, Y 1 and Y 2 form various tricyclic cores, X a and X b are C, CH, or N, as defined herein, and R x is an optional substituent. Compounds and compositions of formula (I) are contemplated as well as methods for treating conditions or disorders prevented by or ameliorated by α7nAChR ligands that encompass compounds of formula (I) and other tricyclic derivatives. Methods of using amino-substituted tricyclic derivatives also are described herein.

  式（I）的化合物 其中A和B是胺基取代的侧链，Y 1 和Y 2 形成各种三环核，X a 和X b 为C、CH或N，如本文所定义，R x 是可选的取代基。考虑到式（I）的化合物和组合物，以及用于治疗由α7nAChR配体预防或改善的疾病或疾病的方法，这些方法涵盖了式（I）的化合物和其他三环衍生物。本文还描述了使用氨基取代的三环衍生物的方法。
• COMPOUND, RESIN, MATERIAL FOR FORMING UNDERLAYER FILM FOR LITHOGRAPHY, UNDERLAYER FILM FOR LITHOGRAPHY, PATTERN FORMING METHOD, AND METHOD FOR PURIFYING THE COMPOUND OR RESIN
  申请人：Mitsubishi Gas Chemical Company, Inc.

  公开号：US20170073288A1

  公开（公告）日：2017-03-16

  The compound according to the present invention is represented by a specific formula. The compound according to the present invention has a structure according to the specific formula, and therefore can be applied to a wet process and is excellent in heat resistance and etching resistance. In addition, the compound according to the present invention has such a specific structure, and therefore has a high heat resistance, a relatively high carbon concentration, a relatively low oxygen concentration and also a high solvent solubility. Therefore, the compound according to the present invention can be used to form an underlayer film whose degradation is suppressed at high-temperature baking and which is also excellent in etching resistance to oxygen plasma etching or the like. Furthermore, the compound is also excellent in adhesiveness with a resist layer and therefore can form an excellent resist pattern.

  根据本发明，该化合物由特定的公式表示。根据本发明，该化合物具有特定公式的结构，因此可应用于湿法工艺，具有优异的耐热性和耐蚀性。此外，根据本发明，该化合物具有特定结构，因此具有高耐热性、相对较高的碳浓度、相对较低的氧浓度以及高溶剂溶解性。因此，根据本发明的化合物可用于形成在高温烘烤时降解受抑制且在氧等离子体蚀刻中具有优异耐蚀性的底层膜。此外，该化合物在与光阻层的粘附性方面也表现出色，因此可形成优异的光阻图案。