cyclo[Arg-Pro-bAla(3-Me)-Pro-His-Trp-Ser-Tyr-D-Leu-Leu] | 1415716-43-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: cyclo[Arg-Pro-bAla(3-Me)-Pro-His-Trp-Ser-Tyr-D-Leu-Leu]
• 英文别名: 2-[3-[(7S,13S,16S,19R,22S,25S,28S,31S,34S)-25-(hydroxymethyl)-22-[(4-hydroxyphenyl)methyl]-31-(1H-imidazol-5-ylmethyl)-28-(1H-indol-3-ylmethyl)-4-methyl-16,19-bis(2-methylpropyl)-2,6,12,15,18,21,24,27,30,33-decaoxo-1,5,11,14,17,20,23,26,29,32-decazatricyclo[32.3.0.07,11]heptatriacontan-13-yl]propyl]guanidine
• CAS: 1415716-43-6
• 化学式: C₆₁H₈₆N₁₆O₁₂
• 分子量: 1235.45
• InChiKey: HQMGUCSNMWQMAM-BPVQHCGTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  89
• 可旋转键数：
  15
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  423
• 氢给体数：
  14
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  cyclo[Arg(Pbf)(Pbf)-Pro-bAla(3-Me)-Pro-His(1-Trt)-Trp-Ser(tBu)-Tyr(tBu)-D-Leu-Leu] 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 cyclo[Arg-Pro-bAla(3-Me)-Pro-His-Trp-Ser-Tyr-D-Leu-Leu]
  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