(+)-cyclazocine | 7313-86-2

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 6,7-苯并吗啡烷
• 英文名称: (+)-cyclazocine
• 英文别名: (-)-cis-Cyclazocine；(1R,9R,13R)-10-(cyclopropylmethyl)-1,13-dimethyl-10-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-4-ol
• CAS: 7313-86-2
• 化学式: C₁₈H₂₅NO
• 分子量: 271.403
• InChiKey: YQYVFVRQLZMJKJ-JBBXEZCESA-N

物化性质

• 熔点：
  188-190°C
• 沸点：
  399.2±42.0 °C(Predicted)
• 密度：
  1.123±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿、乙醇、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (+)-cyclazocine 在 吡啶 、 1,1'-双(二苯基膦)二茂铁 、 tris(dibenzylideneacetone)dipalladium (0) 、 盐酸羟胺 、 sodium acetate 、 sodium t-butanolate 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 生成 8-amino-3-(cyclopropylmethyl)-1,2,3,4,5,6-hexahydro-cis-6,11-dimethyl-2,6-methano-3-benzazocine
  参考文献：
  名称：

  Syntheses and Opioid Receptor Binding Affinities of 8-Amino-2,6-methano-3-benzazocines

  摘要：

  8-Amino-2,6-methano-3-benzazocine derivatives have been made using Pd-catalyzed amination procedures, and their affinities for opioid receptors were assessed. The 8-amino group was hypothesized to be a replacement for the prototypic 8-OH substituent for 2,6-methano-3-benzazocines and related opiates. This OH group is generally required for binding yet is implicated in unfavorable pharmacokinetic characteristics such as low oral bioavailability and rapid clearance via O-glucuronidation. The core structures in which the 8-OH group was replaced were cyclazocine and its enantiomers, ethylketocyclazocine and its enantiomers, ketocyclazocine, and Mr2034. Many new analogues had high affinity for opioid receptors with several in the subnanomolar range. Highest affinity was seen in analogues with secondary 8-(hetero)arylamino appendages. Binding to opioid receptors was enantioselective with the (2R,6R,11R)-configuration preferred and high selectivity for mu and kappa over delta opioid receptors was observed within the series. Several derivatives were shown to have intrinsic opioid-receptor-mediated activity in [S-35]GTPgammaS assays.

  DOI：

  10.1021/jm020429w
• 作为产物：
  描述：

  6-乙氧基-2,2,4-三甲基-1,2-二氢喹啉 、 溴甲基环丙烷 以 乙腈 为溶剂， 反应 20.0h， 生成 (+)-cyclazocine
  参考文献：
  名称：

  [EN] BENZOMORPHAN COMPOUNDS
  [FR] COMPOSÉS À BASE DE BENZOMORPHANE

  摘要：

  本发明涉及公式（I）的苯并吗啡化合物：其中X，R1，R2，R3，R4和R5如本文所定义。这些化合物可用于治疗便秘，特别是由μ-阿片受体激动剂治疗引起的便秘。

  公开号：

  WO2009068989A1

文献信息

• Improved Resolution of (±)-<i>cis</i>-2′-Hydroxy-5,9-dimethyl-6, 7-benzomorphan and Preparation of Racemic, (+)-, and (-)-<i>cis</i>-2-Methylcyclopropyl-2′-hydroxy-5,9-dimethyl-6,7-benzomorphan (Cyclazocine)
  作者：William A. Boulanger

  DOI：10.1080/00397919908086216

  日期：1999.6

  Abstract We report novel procedures for the efficient resolution of (±)-cis-2 -hydroxy-5, 9-dimethyl-6, 7-benzomorphan via the (-)-N-acetyl-L-glutamate and (+)-α-bromocamphor-φ-sulfonate salts, the direct N-substitution of the (+)-α-bromocamphor-φ-sulfonate salts, and the use of these methods for the synthesis of racemic, (+)-, and (-)-cyclazocine.

  摘要 我们报告了通过 (-)-N-乙酰基-L-谷氨酸和 (+)-α 有效拆分 (±)-cis-2 -hydroxy-5, 9-dimethyl-6, 7-benzomorphan 的新程序-溴樟脑-φ-磺酸盐，(+)-α-溴樟脑-φ-磺酸盐的直接N-取代，以及使用这些方法合成外消旋、(+)-和(-)-环佐辛。
• Novel nonnarcotic analgesics with an improved therapeutic ratio. Structure-activity relationships of 8-(methylthio)- and 8-(acylthio)-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines
  作者：Mikio Hori、Masatoshi Ban、Eiji Imai、Noriyuki Iwata、Yoshinari Suzuki、Yutaka Baba、Tokiko Morita、Hajime Fujimura、Masakatsu Nozaki、Masayuki Niwa

  DOI：10.1021/jm00149a020

  日期：1985.11

  synthesis of 3. As the most effective route, Newman-Kwart rearrangement of benzazocines was selected and closely investigated. 8-(N,N-Dimethylthiocarbamoyl)oxy derivatives (6a-e) rearranged to 8-(N,N-dimethylcarbamoyl)thio derivatives (7a-e) in good yields. Reductive cleavage of 7a-e and subsequent methylation or acylations gave the title compounds (3, 8-24). Although analgesic activities of sulfur-containing

  通过三种不同的途径将8-酚的1,2,3,4,5,6-六氢-2,6-甲氧基-3-苯并偶氮恶唑转化为相应的8-硫酚类似物。8-氨基-2,6-甲基-3-苯甲唑啉重氮化（2），然后与CH3SNa反应，得到8-（甲硫基）-1,2,3,4,5,6-六氢-2,6-甲基-3-苯甲唑啉（3）。还研究了使用Grewe环化的另一条路线来合成3。作为最有效的路线，选择并仔细研究了苯佐唑啉的Newman-Kwart重排。8-（N，N-二甲基硫代氨基甲酰基）氧基衍生物（6a-e）以高收率重排为8-（N，N-二甲基氨基甲酰基）硫基衍生物（7a-e）。7a-e的还原裂解以及随后的甲基化或酰化得到标题化合物（3，8-24）。
• [EN] BENZOMORPHAN COMPOUNDS<br/>[FR] COMPOSÉS À BASE DE BENZOMORPHANE
  申请人：PURDUE PHARMA LP

  公开号：WO2009068989A1

  公开（公告）日：2009-06-04

  The invention relates to Benzomorphan Compounds of Formula (I): wherein X, R1, R2, R3, R4, and R5 are as defined herein. These compounds are useful for treating constipation preferably constipation caused by mu-opioid agonist therapy.

  本发明涉及公式（I）的苯并吗啡化合物：其中X，R1，R2，R3，R4和R5如本文所定义。这些化合物可用于治疗便秘，特别是由μ-阿片受体激动剂治疗引起的便秘。
• Methods for Treating Depressive Symptoms
  申请人：Alkermes Pharma Ireland Limited

  公开号：US20150072971A1

  公开（公告）日：2015-03-12

  The present application relates methods for treating a depressive symptom comprising administering an effective amount of a μ opioid receptor agonist or a pharmaceutically acceptable salt thereof to a subject in need thereof. Non-limiting examples of such agonist include the compounds of Formulas I, II, III, and IV, as well as the compounds of Table A.

  本申请涉及治疗抑郁症状的方法，包括向需要治疗的对象施用有效量的μ阿片受体激动剂或其药学上可接受的盐。此类激动剂的非限定性示例包括公式I、II、III和IV的化合物，以及表A中的化合物。
• Methods for treating depressive symptoms
  申请人：Alkermes Pharma Ireland Limited

  公开号：US10231963B2

  公开（公告）日：2019-03-19

  The present application relates methods for treating a depressive symptom comprising administering an effective amount of a μ opioid receptor agonist or a pharmaceutically acceptable salt thereof to a subject in need thereof. Non-limiting examples of such agonist include the compounds of Formulas I, II, III, and IV, as well as the compounds of Table A.

  本申请涉及治疗抑郁症状的方法，包括向有需要的受试者施用有效量的μ阿片受体激动剂或其药学上可接受的盐。此类激动剂的非限制性实例包括式I、II、III和IV化合物以及表A化合物。