benzyl N^α-(benzyloxycarbonyl)-D-lysine toluenesulfonate | 89662-37-3

• 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: benzyl N^α-(benzyloxycarbonyl)-D-lysine toluenesulfonate
• 英文别名: benzyl N^α-(benzyloxycarbonyl)-D-lysinate*TsOH；Benzyl ((benzyloxy)carbonyl)-D-lysinate 4-methylbenzenesulfonate；benzyl (2R)-6-amino-2-(phenylmethoxycarbonylamino)hexanoate;4-methylbenzenesulfonic acid
• CAS: 89662-37-3
• 化学式: C₇H₈O₃S*C₂₁H₂₆N₂O₄
• 分子量: 542.653
• InChiKey: PERBHXHGFSEBTK-FSRHSHDFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  38
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  153
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  benzyl N^α-(benzyloxycarbonyl)-D-lysine toluenesulfonate 在 palladium on activated charcoal 三正丁胺 、 氢气 作用下， 以 乙醇 、 叔丁醇 为溶剂， 反应 22.0h， 生成 (2R)-2-amino-6-[bis(butylamino)methylideneamino]hexanoic acid;4-methylbenzenesulfonic acid
  参考文献：
  名称：

  高效，长效的促黄体生成激素释放激素拮抗剂，含有新的合成氨基酸：N，N'-二烷基-D-高精氨酸。

  摘要：

  基于以下假设，制备了一系列新的非天然氨基酸并将其掺入促黄体生成素释放激素（LH-RH）的拮抗类似物中：假设拟议的磷脂膜相互作用的稳定化可能产生具有高效力和延长效价的类似物持续时间。因此，一系列的NG，NG′-二烷基-D-高精氨酸类似物[HD-hArg（R2）-OH; R ＝ Me，Et，Pr，i-Pr，Bu，己基，环己基，（Et，Me2NPr）]是通过使用适当的二烷基碳二亚胺由D-Lys半合成而方便地制备的。通过使用这些新的氨基酸类似物制备的许多类似物表现出非常高的效力和延长的作用持续时间。该系列中最强大的成员之一，[N-Ac-D-Nal（2）1，D-pCl-Phe2，D-Trp3，D-hArg（Et2）6，D-Ala10] LH-RH（detirelix ）的ED50为0。在大鼠抗排卵试验中，当在中午时分在前雌激素中给药时为7微克，而在24小时之前（在雌性不育II中）给药时仅为2.5微克

  DOI：

  10.1021/jm00396a011

文献信息

• Potent gonadotropin releasing hormone antagonists with low histamine-releasing activity
  作者：John J. Nestor、Ram Tahilramani、Teresa L. Ho、Jessie C. Goodpasture、Brian H. Vickery、Pierre Ferrandon

  DOI：10.1021/jm00099a023

  日期：1992.10

  The incorporation of Arg residues into position 6 of gonadotropin releasing hormone antagonists had resulted in compounds with increased in vivo potency but also made these analogues potent mast cell degranulators. We have focused on the substitution of position 8 by hArg(R)2 (N(G),N(G)'-dialkylhomoarginine) substitutions, based on the hypotheses that the Arg-Pro sequence is of major importance for this side effect and that shielding of the charge may be an effective way to block degranulation. Analogues in four series were evaluated: (A) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal-(3)3,6,Arg5,hArg(R)2(8),D-Ala10]GnRH, (B) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,6,hArg(R)2(5,8),D-Ala10]-GnRH, (C) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,6,hArg(R)28,D-Ala10]GnRH, (D) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,D-hArg(R)2(6),hArg(R)2(8),D-Ala10]GnRH. Although substitution by hArg(Et)2, hArg(Bu), hArg(CH2)3, and hArg(CH2CF3)2 was tested, in each series the hArg(Et)2 residue was superior. Two compounds were considered for clinical evaluation: [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,6,hArg(Et)2(8),D-Ala10]GnRH and [N-AC-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,D-hArg(Et)26,hArg-(Et)28,D-Ala10]GnRH (ganirelix acetate). These compounds had high potency for ovulation suppression and low histamine-releasing potency in vitro (ED50 = 0.6,0.29 mug/rat and EC50 = 196, 13 mug/mL, respectively). Ganirelix is currently in Phase II clinical trials and appears to be the most potent GnRH antagonist tested in humans (based upon ED50 for 24-h suppression of testosterone levels).
• NESTOR, JOHN J. , JR.;TAHILRAMANI, RAM;HO, TERESA L.;MCRAE, GEORGIA I.;VI+, J. MED. CHEM., 31,(1988) N 1, 65-72
  作者：NESTOR, JOHN J. , JR.、TAHILRAMANI, RAM、HO, TERESA L.、MCRAE, GEORGIA I.、VI+

  DOI：——

  日期：——