(2S)-2-amino-5-((methoxycarbonylmethyl)cyclohexyl)pentanoic acid | 855527-21-8

• 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)-2-amino-5-((methoxycarbonylmethyl)cyclohexyl)pentanoic acid
• 英文别名: (2S)-2-amino-5-[1-(2-methoxy-2-oxoethyl)cyclohexyl]pentanoic acid
• CAS: 855527-21-8
• 化学式: C₁₄H₂₅NO₄
• 分子量: 271.357
• InChiKey: KFLBLZQIZZGMIX-NSHDSACASA-N

物化性质

• 沸点：
  398.9±17.0 °C(predicted)
• 密度：
  1.093±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  19
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  89.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S)-2-amino-5-((methoxycarbonylmethyl)cyclohexyl)pentanoic acid 、 氯甲酸-9-芴基甲酯 在 碳酸氢钠 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以38%的产率得到(2S)-2-(9H-fluorenylmethoxycarbonylamino)-5-(1-methoxycarbonylmethylcyclohexyl)pentanoic acid
  参考文献：
  名称：

  Synthesis of Oxytocin Analogues with Replacement of Sulfur by Carbon Gives Potent Antagonists with Increased Stability

  摘要：

  The neuropeptide oxytocin 1 controls mammary and uterine smooth muscle contraction. Atosiban 2, an oxytocin antagonist, is used for prevention of preterm labor and premature birth. However, the metabolic lifetimes of such peptide drugs are short because of in vivo degradation. Facile production of oxytocin analogues with varying ring sizes wherein sulfur is replaced by carbon (methylene or methine) could be achieved by standard solid-phase peptide synthesis using olefin-bearing amino acids followed by on-resin ring-closing metathesis (RCM). These were tested for agonistic and antagonistic uteronic activity using myometrial strips taken from nonpregnant female rats. Peptide 8 showed agonistic activity in vitro (EC50 = 1.4 x 10(3) +/- 4.4 x 10(2) nM) as compared to 1 (EC50 = 7.0 +/- 2.1 nM). Atosiban analogues 17 (pA(2) = 7.8 +/- 0.1) and 18 (pA(2) 8.0 +/- 0.1) showed substantial activity compared to the parent oxytocin antagonist 2 (pA(2) = 9.9 +/- 0.3). Carba analogue 35 (pA(2) = 6.1 +/- 0.1) had an agonistic activity over 2 orders of magnitude less than its parent 3 (8.8 +/- 10.5). A comparison of biological stabilities of 1,6-carba analogues of both an agonist 8 and antagonist 18 versus parent peptides 1 and 2 was conducted. The half-lives of peptides 8 and 18 in rat placental tissue were shown (Table 2) to be greatly improved versus their parents oxytocin 1 and atosiban 2, respectively. These results suggest that peptides 8 and 18 and analogues thereof may be important leads into the development of a long-lasting, commercially available therapeutic for initiation of parturition and treatment of preterm labor.

  DOI：

  10.1021/jo050539l
• 作为产物：
  描述：

  1,1-环己基二乙酸 在 palladium on activated charcoal dicyclohexyldicarboximide 、 硫酸 、 氢气 、 双氧水 、 乙酰氯 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， -78.0~60.0 ℃ 、101.33 kPa 条件下， 反应 63.0h， 生成 (2S)-2-amino-5-((methoxycarbonylmethyl)cyclohexyl)pentanoic acid
  参考文献：
  名称：

  Synthesis of Oxytocin Analogues with Replacement of Sulfur by Carbon Gives Potent Antagonists with Increased Stability

  摘要：

  The neuropeptide oxytocin 1 controls mammary and uterine smooth muscle contraction. Atosiban 2, an oxytocin antagonist, is used for prevention of preterm labor and premature birth. However, the metabolic lifetimes of such peptide drugs are short because of in vivo degradation. Facile production of oxytocin analogues with varying ring sizes wherein sulfur is replaced by carbon (methylene or methine) could be achieved by standard solid-phase peptide synthesis using olefin-bearing amino acids followed by on-resin ring-closing metathesis (RCM). These were tested for agonistic and antagonistic uteronic activity using myometrial strips taken from nonpregnant female rats. Peptide 8 showed agonistic activity in vitro (EC50 = 1.4 x 10(3) +/- 4.4 x 10(2) nM) as compared to 1 (EC50 = 7.0 +/- 2.1 nM). Atosiban analogues 17 (pA(2) = 7.8 +/- 0.1) and 18 (pA(2) 8.0 +/- 0.1) showed substantial activity compared to the parent oxytocin antagonist 2 (pA(2) = 9.9 +/- 0.3). Carba analogue 35 (pA(2) = 6.1 +/- 0.1) had an agonistic activity over 2 orders of magnitude less than its parent 3 (8.8 +/- 10.5). A comparison of biological stabilities of 1,6-carba analogues of both an agonist 8 and antagonist 18 versus parent peptides 1 and 2 was conducted. The half-lives of peptides 8 and 18 in rat placental tissue were shown (Table 2) to be greatly improved versus their parents oxytocin 1 and atosiban 2, respectively. These results suggest that peptides 8 and 18 and analogues thereof may be important leads into the development of a long-lasting, commercially available therapeutic for initiation of parturition and treatment of preterm labor.

  DOI：

  10.1021/jo050539l

文献信息

• Synthesis of Oxytocin Analogues with Replacement of Sulfur by Carbon Gives Potent Antagonists with Increased Stability
  作者：Jake L. Stymiest、Bryan F. Mitchell、Susan Wong、John C. Vederas

  DOI：10.1021/jo050539l

  日期：2005.9.1

  The neuropeptide oxytocin 1 controls mammary and uterine smooth muscle contraction. Atosiban 2, an oxytocin antagonist, is used for prevention of preterm labor and premature birth. However, the metabolic lifetimes of such peptide drugs are short because of in vivo degradation. Facile production of oxytocin analogues with varying ring sizes wherein sulfur is replaced by carbon (methylene or methine) could be achieved by standard solid-phase peptide synthesis using olefin-bearing amino acids followed by on-resin ring-closing metathesis (RCM). These were tested for agonistic and antagonistic uteronic activity using myometrial strips taken from nonpregnant female rats. Peptide 8 showed agonistic activity in vitro (EC50 = 1.4 x 10(3) +/- 4.4 x 10(2) nM) as compared to 1 (EC50 = 7.0 +/- 2.1 nM). Atosiban analogues 17 (pA(2) = 7.8 +/- 0.1) and 18 (pA(2) 8.0 +/- 0.1) showed substantial activity compared to the parent oxytocin antagonist 2 (pA(2) = 9.9 +/- 0.3). Carba analogue 35 (pA(2) = 6.1 +/- 0.1) had an agonistic activity over 2 orders of magnitude less than its parent 3 (8.8 +/- 10.5). A comparison of biological stabilities of 1,6-carba analogues of both an agonist 8 and antagonist 18 versus parent peptides 1 and 2 was conducted. The half-lives of peptides 8 and 18 in rat placental tissue were shown (Table 2) to be greatly improved versus their parents oxytocin 1 and atosiban 2, respectively. These results suggest that peptides 8 and 18 and analogues thereof may be important leads into the development of a long-lasting, commercially available therapeutic for initiation of parturition and treatment of preterm labor.