载堇碱盐酸盐 | 632-47-3

• 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 - 阿朴菲
• 中文名称: 载堇碱盐酸盐
• 中文别名: 紫堇碱盐酸盐
• 英文名称: Bulbocapnine hydrochloride
• 英文别名: (12S)-17-methoxy-11-methyl-3,5-dioxa-11-azapentacyclo[10.7.1.02,6.08,20.014,19]icosa-1(20),2(6),7,14(19),15,17-hexaen-18-ol;hydrochloride
• CAS: 632-47-3
• 化学式: C19H20ClNO4
• mdl: MFCD00069363
• 分子量: 361.8
• InChiKey: SRGIVPUDHITDMK-YDALLXLXSA-N

物化性质

• 熔点：
  209-210°C
• 溶解度：
  DMSO（微溶）、甲醇（微溶、超声处理）
• 稳定性/保质期：
  远离氧化物。

计算性质

• 辛醇/水分配系数(LogP)：
  2.86
• 重原子数：
  25
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.368
• 拓扑面积：
  52.4
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S36
• 危险类别码：
  R22
• WGK Germany：
  3

文献信息

• Apomorphine inhibitors of amyloid-beta (Abeta) fibril formation and their use in amyloidosis based disease
  申请人：——

  公开号：US20030187011A1

  公开（公告）日：2003-10-02

  Described is a new class of small molecule inhibitors of amyloid &bgr; protein (A&bgr;) aggregation, based on apomorphine. These molecules target the nucleation phase of A&bgr; self-assembly and interfere effectively with aggregation of A&bgr; 1-40 into amyloid fibrils in vitro as determined by transmission electron microscopy, Thioflavin T (ThT) fluorescence, and velocity sedimentation. Structure-activity studies using apomorphine analogues demonstrate that 10,11-dihydroxy substitutions of the D ring are preferred for the inhibitory effectiveness of these aporphines, and that methylation of these hydroxyl groups reduces their inhibitory potency. The ability of these small molecules to inhibit A&bgr; amyloid fibril formation appears to be linked to their ability to undergo auto-oxidation in solution, implicating an auto-oxidation product as the active A&bgr; inhibitor. Sedimentation velocity and electron microscopy studies demonstrate that apomorphine and analogues facilitate oligomerization of A&bgr; into short nonfibrillar soluble assemblies, but inhibit A&bgr; fibrillization.

  描述的是一类基于阿朴吗啡的新型淀粉样&bgr;蛋白（A&bgr;）聚集小分子抑制剂。这些分子以 A&bgr; 自组装的成核阶段为目标，通过透射电子显微镜、硫黄素 T（ThT）荧光和速度沉降法测定，可有效干扰 A&bgr; 1-40 在体外聚集成淀粉样纤维。使用阿朴吗啡类似物进行的结构-活性研究表明，D环的10,11-二羟基取代是这些阿朴吗啡类药物发挥抑制作用的首选，而这些羟基的甲基化会降低它们的抑制效力。这些小分子抑制 A&bgr; 淀粉样纤维形成的能力似乎与它们在溶液中发生自身氧化的能力有关，这意味着一种自身氧化产物是活性 A&bgr; 抑制剂。沉降速度和电子显微镜研究表明，阿朴吗啡和类似物可促进 A&bgr; 的低聚作用，使其变成短的非纤维状可溶集合体，但会抑制 A&bgr; 的纤维化。
• APOMORPHINE INHIBITORS OF AMYLOID-BETA (ABETA) FIBRIL FORMATION AND THEIR USE IN AMYLOIDOSIS BASED DISEASE
  申请人：Lashuel A. Hilal

  公开号：US20080096909A1

  公开（公告）日：2008-04-24

  Described is a new class of small molecule inhibitors of amyloid β protein (Aβ) aggregation, based on apomorphine. These molecules target the nucleation phase of Aβ self-assembly and interfere effectively with aggregation of Aβ 1-40 into amyloid fibrils in vitro as determined by transmission electron microscopy, Thioflavin T (ThT) fluorescence, and velocity sedimentation. Structure-activity studies using apomorphine analogues demonstrate that 10,11-dihydroxy substitutions of the D ring are preferred for the inhibitory effectiveness of these aporphines, and that methylation of these hydroxyl groups reduces their inhibitory potency. The ability of these small molecules to inhibit Aβ amyloid fibril formation appears to be linked to their ability to undergo auto-oxidation in solution, implicating an auto-oxidation product as the active Aβ inhibitor. Sedimentation velocity and electron microscopy studies demonstrate that apomorphine and analogues facilitate oligomerization of Aβ into short nonfibrillar soluble assemblies, but inhibit Aβ fibrillization.
• [EN] APOMORPHINE INHIBITORS OF AMYLOID-beta (Abeta) FIBRIL FORMATION AND THEIR USE IN AMYLOIDOSIS BASED DISEASE<br/>[FR] INHIBITEURS APOMORPHINES DE LA FORMATION DES FIBRILLES DE L'AMYLOIDE- DOLLAR G(B) A DOLLAR G(B) ET LEUR UTILISATION DANS LES MALADIES DERIVEES DE L'AMYLOIDOSE
  申请人：PICOWER INST MED RES

  公开号：WO2003053356A2

  公开（公告）日：2003-07-03

  Described is a new class of small molecule inhibitors of amyloid β protein (Aβ) aggregation, based on apomorphine. These molecules target the nucleation phase of Aβ self-assembly and interfere effectively with aggregation of Aβ 1-40 into amyloid fibrils invitro as determined by transmission electron microscopy, Thioflavin T (ThT) fluorescence, and velocity sedimentation. Structure-activity studies using apomorphine analogues demonstrate that 10, 11-dihydroxy substitutions of the D ring are preferred for the inhibitory effectiveness of these aporphines, and that methylation of these hydroxyl groups reduces their inhibitory potency. The ability of these small molecules to inhibit Aβ amyloid fibril formation appears to be linked to their ability to undergo auto-oxidation in solution, implicating an auto-oxidation product as the active A&beta, inhibitor. Sedimentation velocity and electron microscopy studies demonstrate that apomorphine and analogues facilitate oligomerization of Aβ into short nonfibrillar soluble assemblies, but inhibit Aβ fibrilization.