2-[3-[(14S,20S,23S,26R,29S,32S,35S,38S,41S)-32-(hydroxymethyl)-38-(1H-imidazol-5-ylmethyl)-35-(1H-indol-3-ylmethyl)-29-[(4-methoxyphenyl)methyl]-11-methyl-23,26-bis(2-methylpropyl)-2,9,13,19,22,25,28,31,34,37,40-undecaoxo-1,8,12,18,21,24,27,30,33,36,39-undecazatricyclo[39.3.0.014,18]tetratetracontan-20-yl]propyl]guanidine | 1415716-46-9

• 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: 2-[3-[(14S,20S,23S,26R,29S,32S,35S,38S,41S)-32-(hydroxymethyl)-38-(1H-imidazol-5-ylmethyl)-35-(1H-indol-3-ylmethyl)-29-[(4-methoxyphenyl)methyl]-11-methyl-23,26-bis(2-methylpropyl)-2,9,13,19,22,25,28,31,34,37,40-undecaoxo-1,8,12,18,21,24,27,30,33,36,39-undecazatricyclo[39.3.0.014,18]tetratetracontan-20-yl]propyl]guanidine
• CAS: 1415716-46-9
• 化学式: C₆₈H₉₉N₁₇O₁₃
• 分子量: 1362.64
• InChiKey: IKIPJHJNVLDRLQ-YYBFZQJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  98
• 可旋转键数：
  16
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  441
• 氢给体数：
  14
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  1-[3-[(14S,20S,23S,26R,29S,32S,35S,38S,41S)-35-(1H-indol-3-ylmethyl)-29-[(4-methoxyphenyl)methyl]-11-methyl-32-[(2-methylpropan-2-yl)oxymethyl]-23,26-bis(2-methylpropyl)-2,9,13,19,22,25,28,31,34,37,40-undecaoxo-38-[(1-tritylimidazol-4-yl)methyl]-1,8,12,18,21,24,27,30,33,36,39-undecazatricyclo[39.3.0.014,18]tetratetracontan-20-yl]propyl]-3-[(2,2,4,6,7-pentamethyl-3H-1-benzofuran-5-yl)sulfonyl]guanidine 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 2-[3-[(14S,20S,23S,26R,29S,32S,35S,38S,41S)-32-(hydroxymethyl)-38-(1H-imidazol-5-ylmethyl)-35-(1H-indol-3-ylmethyl)-29-[(4-methoxyphenyl)methyl]-11-methyl-23,26-bis(2-methylpropyl)-2,9,13,19,22,25,28,31,34,37,40-undecaoxo-1,8,12,18,21,24,27,30,33,36,39-undecazatricyclo[39.3.0.014,18]tetratetracontan-20-yl]propyl]guanidine
  参考文献：
  名称：

  Rationally designed cyclic analogues of luteinizing hormone-releasing hormone: Enhanced enzymatic stability and biological properties

  摘要：

  This article describes the rational design, synthesis and pharmacological properties of amide-linked cyclic analogues of Luteinizing Hormone-Releasing Hormone (LHRH) with substitutions at positions 1 (Pro), 6 (D-Leu/D-Trp), 9 (Aze) and 10 (BABA/Acp). These LHRFI analogues fulfil the conformational requirements that are known in the literature (bend in the 5-8 segment) to be essential for receptor recognition and activation. Although, they are characterised by an overall low binding affinity to the LHRH-I receptor, the cyclic analogues that were studied and especially the cyclo(1-10)[Pro(1), D-Leu(6), BABA(10)]LHRH, exhibit a profoundly enhanced in vitro and in vivo stability and improved pharmacokinetics in comparison with their linear counterpart and leuprolide. Upon receptor binding, cyclo(1-10) [Pro(1), D-Leu(6), BABA(1)0] LHRH causes testosterone release in C57/B16 mice (in vivo efficacy) that is comparable to that of leuprolide. Testosterone release is an acutely dose dependent effect that is blocked by the LHRH-I receptor antagonist, cetrorelix. The pharmacokinetic advantages and efficacy of cyclo(1-10)[Pro(1), D-Leu(6), BABA(10)] LHRH render this analogue a promising platform for future rational drug design studies towards the development of non-peptide LHRH mimetics. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.09.043