(2S,5R,8S,11S,14S,19S,Z)-5-((1H-indol-3-yl)methyl)-19-((R)-2-amino-3-phenylpropanamido)-8-(4-aminobutyl)-2-benzyl-N-((2R,3R)-1,3-dihydroxybutan-2-yl)-11-(4-hydroxybenzyl)-3,6,9,12,20-pentaoxo-1,4,7,10,13-pentaazacycloicos-16-ene-14-carboxamide | 1241047-40-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,5R,8S,11S,14S,19S,Z)-5-((1H-indol-3-yl)methyl)-19-((R)-2-amino-3-phenylpropanamido)-8-(4-aminobutyl)-2-benzyl-N-((2R,3R)-1,3-dihydroxybutan-2-yl)-11-(4-hydroxybenzyl)-3,6,9,12,20-pentaoxo-1,4,7,10,13-pentaazacycloicos-16-ene-14-carboxamide
• CAS: 1241047-40-4
• 化学式: C₅₆H₇₀N₁₀O₁₀
• 分子量: 1043.23
• InChiKey: YNPCHSFLOVNTAY-CCUOWPAZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.72
• 重原子数：
  76.0
• 可旋转键数：
  18.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  332.22
• 氢给体数：
  13.0
• 氢受体数：
  12.0

反应信息

• 作为产物：
  描述：

  、 Fmoc-L-苯丙氨酸 、 N-alpha-芴甲氧羰基-N-epsilon-叔丁氧羰基-L-赖氨酸 、 Fmoc-O-苄基-L-酪氨酸 、 Fmoc-D-苯丙氨酸 、 Fmoc-L-烯丙基甘氨酸 、 Fmoc-L-色氨酸(Boc)-OH 在 N-甲基吗啉 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.25h， 生成 (2S,5R,8S,11S,14S,19S,Z)-5-((1H-indol-3-yl)methyl)-19-((R)-2-amino-3-phenylpropanamido)-8-(4-aminobutyl)-2-benzyl-N-((2R,3R)-1,3-dihydroxybutan-2-yl)-11-(4-hydroxybenzyl)-3,6,9,12,20-pentaoxo-1,4,7,10,13-pentaazacycloicos-16-ene-14-carboxamide 、 (2S,5R,8S,11S,14S,19S,E)-5-((1H-indol-3-yl)methyl)-19-((R)-2-amino-3-phenylpropanamido)-8-(4-aminobutyl)-2-benzyl-N-((2R,3R)-1,3-dihydroxybutan-2-yl)-11-(4-hydroxybenzyl)-3,6,9,12,20-pentaoxo-1,4,7,10,13-pentaazacycloicos-16-ene-14-carboxamide
  参考文献：
  名称：

  Novel Octreotide Dicarba-analogues with High Affinity and Different Selectivity for Somatostatin Receptors

  摘要：

  A limited set of novel octreotide dicarba-analogues with non-native aromatic side chains in positions 7 and/or 10 were synthesized. Their affinity toward the ssts(1-5) was determined. Derivative 4 exhibited a pan-somatostatin activity, except sst(4), and derivative 8 exhibited high affinity and selectivity toward sst(5). Actually, compound 8 has similar sst(5) affinity (IC(50) 4.9 nM) to SRIF-28 and octreotide. Structure activity relationships suggest that the Z geometry of the double-bond bridge is that preferred by the receptors. The NMR study on the conformations of these compounds in SDS(-d25) micelles solution shows that all these analogues have the pharmacophore beta-turn spanning Xaa(7)-D-Trp(8)-Lys(9)-Yaa(10) residues. Notably, the correlation between conformation families and affinity data strongly indicates that the sst(5) selectivity is favored by a helical conformation involving the C-terminus triad, while a pan-SRIF mimic activity is based mainly on a conformational equilibrium between extended and folded conformational states.

  DOI：

  10.1021/jm1005868