atropine | 83454-31-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: atropine
• 英文别名: Tropasaeure-tropan-3-ylester；atropin；L-Hyoscyamine；(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 3-hydroxy-2-phenylpropanoate
• CAS: 83454-31-3；784090-27-3；791013-25-7
• 化学式: C₁₇H₂₃NO₃
• 分子量: 289.375
• InChiKey: RKUNBYITZUJHSG-UHFFFAOYSA-N

物化性质

• 颜色/状态：
  Long, orthorhombic prisms from acetone
• 熔点：
  113.5 °C
• 溶解度：
  In water, 2,200 mg/l @ 25 °C
• 稳定性/保质期：

  Atropine sulfate should be stored below 40 °C, preferably at room temp. Freezing should be avoided. Minimum hydrolysis occurs at pH 3.5. Atropine sulfate 1 mg/ml was found to retain potency for 3 months at room temp when 0.5 or 1 ml of soln was packaged in Tubex. /Atropine sulfate/

• 旋光度：
  SPECIFIC OPTICAL ROTATION (ALCOHOL): -21.0 DEG AT 20 °C/D
• 分解：
  When heated to decomposition it emits toxic fumes of /nitrogen oxides/.
• 解离常数：
  K= 1.9X10-12 AT 19 °C
• 保留指数：
  2145;2169;2183;2169;2147;2200;2175;2194;2184;2199;2147;2169;2169;2175;2147;2145;2199;2202;2202

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

ADMET

毒理性

• 肝毒性

尽管在过去几十年里被广泛使用，但氢溴酸东莨菪碱并未与肝酶升高或临床上明显的肝脏损伤病例有关联。其安全性较高的一个主要原因是每日剂量较低且使用时限较短。 关于抗胆碱能药物的安全性和潜在肝毒性的参考资料，在抗胆碱能药物概述部分之后会一起给出。 药物类别：胃肠用药；抗胆碱能药物

Despite widespread use over many decades, hyoscyamine has not been linked to episodes of liver enzyme elevations or clinically apparent liver injury. A major reason for its safety may relate to the low daily dose and limited duration of use. References on the safety and potential hepatotoxicity of anticholinergics are given together after the Overview section on Anticholinergic Agents. Drug Class: Gastrointestinal Agents; Anticholinergic Agents

来源:LiverTox

反应信息

• 作为反应物：
  描述：

  atropine 以95%的产率得到
  参考文献：
  名称：

  SANTAMARIA, J.;OUCHABANE, R.;RIGAUDY, J., TETRAHEDRON LETT., 30,(1989) N2, C. 2927-2928

  摘要：

  DOI：
• 作为产物：
  描述：

  DL-托品酸 在 盐酸 、 氯化亚砜 作用下， 反应 30.5h， 生成 atropine
  参考文献：
  名称：

  Differential analgesic activity of the enantiomers of atropine derivatives does not correlate with their muscarinic subtype selectivity

  摘要：

  The enantiomers of several tropic and p-substituted tropic acid esters related to atropine obtained by esterification under non-racemizing conditions after resolution of the corresponding racemic acids [(+)- and (-)-18, (+)- and (-)-19] are reported. They were tested in vitro on muscarinic subtype receptors and in vivo for their analgesic activity on mice. As in the case of the lead compound, R-(+)-hyoscyamine, these substances show enantioselectivity in analgesic tests, the eutomers being the R-(+) or R-(+)-p-substituted tropic acid derivatives. However, this property, which is a consequence of increased central release of ACh, seems unrelated to muscarinic subtype selectivity insofar as the compounds are unable to discriminate muscarinic subtype receptors. A possible explanation of these results which does not involve subtype selectivity is proposed, based on the recently developed concept of inverse agonism.

  DOI：

  10.1016/s0223-5234(97)83285-0

文献信息

• [EN] QUINUCLIDINE COMPOUNDS AS ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS<br/>[FR] COMPOSÉS QUINUCLIDINE EN TANT QUE LIGANDS DU RÉCEPTEUR NICOTINIQUE ALPHA-7 DE L'ACÉTYLCHOLINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2016073407A1

  公开（公告）日：2016-05-12

  There are disclosed a series of quinuclidines having the Formula (I). which bind to the nicotinic α7 receptor and may be useful for the treatment of disorders of the central nervous system.

  揭示了一系列具有化学式（I）的喹诺啉类化合物，它们与尼古丁型α7受体结合，可能对中枢神经系统疾病的治疗有用。
• [EN] NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS<br/>[FR] NOUVEAUX COMPOSÉS ET COMPOSITIONS PHARMACEUTIQUES LES COMPRENANT POUR LE TRAITEMENT DE TROUBLES INFLAMMATOIRES
  申请人：GALAPAGOS NV

  公开号：WO2017012647A1

  公开（公告）日：2017-01-26

  The present invention discloses compounds according to Formula (I), wherein R1, R3, R4, R5, L1, and Cy are as defined herein. The present invention also provides compounds, methods for the production of said compounds of the invention, pharmaceutical compositions comprising the same and their use in allergic or inflammatory conditions, autoimmune diseases, proliferative diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6 and/or interferons. The present invention also methods for the prevention and/or treatment of the aforementioned diseases by administering a compound of the invention.

  本发明公开了根据式（I）的化合物，其中R1、R3、R4、R5、L1和Cy如本文所定义。本发明还提供了该发明的化合物、制备该化合物的方法、包括相同化合物的药物组合物以及它们在过敏或炎症症状、自身免疫疾病、增殖性疾病、移植排斥、涉及软骨周转障碍的疾病、先天软骨畸形和/或与IL6和/或干扰素过度分泌相关的疾病中的使用。本发明还提供了通过给予该发明的化合物来预防和/或治疗上述疾病的方法。
• [EN] 3,5-DIAMINO-6-CHLORO-N-(N-(4-PHENYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2- CARBOXAMIDE COMPOUNDS<br/>[FR] COMPOSÉS 3,5-DIAMINO -6-CHLORO-N-(N- (4-PHÉNYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2-CARBOXAMIDE
  申请人：PARION SCIENCES INC

  公开号：WO2014099673A1

  公开（公告）日：2014-06-26

  The present invention relates compounds of the formula: or pharmaceutically acceptable salts thereof, useful as sodium channel blockers, as well as compositions containing the same, processes for the preparation of the same, and therapeutic methods of use therefore in promoting hydration of mucosal surfaces and the treatment of diseases including cystic fibrosis, chronic obstructive pulmonary disease, asthma, bronchiectasis, acute and chronic bronchitis, emphysema, and pneumonia.

  本发明涉及以下化合物的公式：或其药学上可接受的盐，用作钠通道阻滞剂，以及含有这些化合物的组合物，制备这些化合物的方法，以及在促进粘膜表面水合和治疗包括囊性纤维化、慢性阻塞性肺病、哮喘、支气管扩张、急性和慢性支气管炎、肺气肿和肺炎等疾病的治疗方法。
• CHLORO-PYRAZINE CARBOXAMIDE DERIVATIVES WITH EPITHELIAL SODIUM CHANNEL BLOCKING ACTIVITY
  申请人：Parion Sciences, Inc.

  公开号：US20140171447A1

  公开（公告）日：2014-06-19

  This invention provides compounds of the formula I: and their pharmaceutically acceptable salts, useful as sodium channel blockers, compositions containing the same, therapeutic methods and uses for the same and processes for preparing the same.

  这项发明提供了式I的化合物及其药用盐，可用作钠通道阻滞剂，包含这些化合物的组合物，以及用于这些化合物的治疗方法和用途，以及制备这些化合物的方法。
• Dual Pharmacophores - PDE4-Muscarinic Antagonistics
  申请人：Callahan James Francis

  公开号：US20090203657A1

  公开（公告）日：2009-08-13

  The present invention is directed to novel compounds of Formula (I) and pharmaceutically acceptable salts thereof, pharmaceutical compositions and their use as dual chromaphores having inhibitory activity against PDE4 and muscarinic acetylcholine receptors (mAChRs), and thus being useful for treating respiratory diseases.

  本发明涉及具有式（I）的新化合物及其药用盐，药物组合物及其用作对PDE4和肌胆碱受体（mAChRs）具有抑制活性的双色素，因此可用于治疗呼吸道疾病。

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