10-O-(3-benzoyloxycarbamoylpropionyl)ryanodine | 146036-45-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 10-O-(3-benzoyloxycarbamoylpropionyl)ryanodine
• 英文别名: O^10eq-Cbz-β-alanylryanodine；[(1R,2R,3S,6S,7S,9S,10R,11S,12R,13S,14R)-6,9,11,13,14-pentahydroxy-3,7,10-trimethyl-2-[3-(phenylmethoxycarbonylamino)propanoyloxy]-11-propan-2-yl-15-oxapentacyclo[7.5.1.01,6.07,13.010,14]pentadecan-12-yl] 1H-pyrrole-2-carboxylate
• CAS: 146036-45-5
• 化学式: C₃₆H₄₆N₂O₁₂
• 分子量: 698.767
• InChiKey: YNAMTGCWRIKJBG-UQDKULHGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  50
• 可旋转键数：
  12
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  217
• 氢给体数：
  7
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  10-O-(3-benzoyloxycarbamoylpropionyl)ryanodine 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 乙醇 为溶剂， 生成 O^10eq-β-alanylryanodine
  参考文献：
  名称：

  C10-Oe-N-(4-azido-5-125iodo salicyloyl)-β-alanyl-β alanyl ryanodine (Az-βAR), a novel photo-affinity ligand for the ryanodine binding site

  摘要：

  我们合成了一种与肌质网钙释放通道的雷诺丁结合位点具有高亲和力、可光激活的放射性碘化配体--C10-Oeq-N-（4-叠氮-5-125 碘水杨酰）-β-丙氨酰-β-丙氨酰雷诺丁（Az-βAR），其比活度为 1400mCi/mmol。Az-βAR 是由多功能合成物 N-（4-叠氮-5125 碘水杨酰）-β-丙氨酸与 C10-Oeq-β-丙氨酰雷诺丁缩合而成，与 [3H] 雷诺丁一样，Az-βAR 不显示饱和结合动力学。127Az-βAR 对分离自家兔骨骼肌的肌质网囊泡的雷诺丁受体/钙释放通道的 IC50 为 27.2 ± 2 × 10-9 M（平均值 ± SD），而雷诺丁的 IC50 为 6.2 ± 0.4 × 10-9 M。

  DOI：

  10.1002/jlcr.2580340106
• 作为产物：
  描述：

  N-CBZ-beta-丙氨酸 、 ryanodine 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 7.0h， 生成 10-O-(3-benzoyloxycarbamoylpropionyl)ryanodine
  参考文献：
  名称：

  C10-Oe-N-(4-azido-5-125iodo salicyloyl)-β-alanyl-β alanyl ryanodine (Az-βAR), a novel photo-affinity ligand for the ryanodine binding site

  摘要：

  我们合成了一种与肌质网钙释放通道的雷诺丁结合位点具有高亲和力、可光激活的放射性碘化配体--C10-Oeq-N-（4-叠氮-5-125 碘水杨酰）-β-丙氨酰-β-丙氨酰雷诺丁（Az-βAR），其比活度为 1400mCi/mmol。Az-βAR 是由多功能合成物 N-（4-叠氮-5125 碘水杨酰）-β-丙氨酸与 C10-Oeq-β-丙氨酰雷诺丁缩合而成，与 [3H] 雷诺丁一样，Az-βAR 不显示饱和结合动力学。127Az-βAR 对分离自家兔骨骼肌的肌质网囊泡的雷诺丁受体/钙释放通道的 IC50 为 27.2 ± 2 × 10-9 M（平均值 ± SD），而雷诺丁的 IC50 为 6.2 ± 0.4 × 10-9 M。

  DOI：

  10.1002/jlcr.2580340106

文献信息

• Amino- and guanidinoacylryanodines: basic ryanodine esters with enhanced affinity for the sarcoplasmic reticulum calcium (2+)-release channel
  作者：Koert Gerzon、Rod A. Humerickhouse、Henry R. Besch、Keshore R. Bidasee、Jeffrey T. Emmick、Roger W. Roeske、Zhenping Tian、Luc Ruest、John L. Sutko

  DOI：10.1021/jm00062a003

  日期：1993.5

  Amino- and guanidinoacyl esters of ryanodine were prepared to evaluate the effect of basicity on the binding affinity of these derivatives for the sarcoplasmic reticulum Ca2+-release channel (SR CRC). In the presence of DCC and DMAP Cbz-beta-alanine reacts with ryanodine in CH2Cl2 to give O10eq-Cbz-beta-alanylryanodine (3a), which on hydrogenolysis yields the beta-alanyl ester (4a). N,N'-bis-Cbz-S-methylthiourea reacts with 4a to yield beta-N,N'-bis-Cbz-guanidinopropionylryanodine (5a). O10eq-beta-guanidinopropionylryanodine (6a) is obtained on hydrogenolytic deprotection of 5a. The binding affinity of beta-alanine ester (4a) and its glycyl congener (4b) is 2-3-fold greater, and that of the beta-guanidinopropionyl ester (6a) and its acetyl congener (6b) 3-6-fold greater, than that of ryanodine. The effect of ryanodine on SR Ca2+ flux is of a biphasic nature: nanomolar levels open (activate) the channel, while micromolar levels close (deactivate) it. The base-substituted esters 4a and 6a both display a unidirectional effect: they only open the channel. An understanding of ryanodine's mode of action and the design of effective SR CRC activating and deactivating ryanoids for possible therapeutic application are major research objectives.
• Characterisation of antibody models of the ryanodine receptor for use in high-throughput screening†
  作者：Andrew J. Dinsmore、William Rees-Blanchard、Philip Bentley、Terence Lewis、Steven D. Kahl、Peter S. McPherson、Michael J. Mullinnix、Kevin P. Campbell、John D. Windass、Fergus G. P. Earley

  DOI：10.1002/(sici)1096-9063(199812)54:4<345::aid-ps825>3.0.co;2-h

  日期：1998.12

  The syntheses of seven novel synthetic analogues of the naturally occurring insecticide ryanodine are described. These, and other synthetic and naturally occurring analogues, have been used to characterise the selectivity of a monoclonal antibody which has been produced by immunisation with 9-hydroxy-21-(4-azidobenzyloxy)-9-epiryanodine photo-conjugated to keyhole limpet haemocyanin. The antibody binds [H-3]ryanodine with a dissociation constant of 0.37 nM. The specificity of this antibody in terms of its ability to recognise 11 natural and synthetic analogues of ryanodine has been determined by [H-3]ryanodine displacement and shown to be similar (for a partially overlapping set of analogues) to that determined earlier for a rabbit polyclonal antibody (Kahl, S. D., er al., Anal. Biochem., 218 (1994) 55-62). The selectivity of the antibodies is shown to be related to that of the sarcoplasmic reticulum Ca2+ release channel from rabbit skeletal muscle, both for this set of ryanodine analogues and for three structurally dissimilar, low-molecular-weight compounds identified by high-throughput screening. The advantages of these antibody models of the Ca2+ release channel for screening are illustrated by their superior performance in a homogeneous binding assay. (C) 1998 Society of Chemical Industry.