[Ncy(methyl)4]acyline | 937389-80-5

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: [Ncy(methyl)4]acyline
• 英文别名: (2S)-1-[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-acetamido-3-naphthalen-2-ylpropanoyl]amino]-3-(4-chlorophenyl)propanoyl]amino]-3-pyridin-3-ylpropanoyl]amino]-2-methylsulfanylacetyl]amino]-3-(4-acetamidophenyl)propanoyl]amino]-3-(4-acetamidophenyl)propanoyl]amino]-4-methylpentanoyl]amino]-6-(propan-2-ylamino)hexanoyl]-N-[(2R)-1-amino-1-oxopropan-2-yl]pyrrolidine-2-carboxamide
• CAS: 937389-80-5
• 化学式: C₈₀H₁₀₂ClN₁₅O₁₃S
• 分子量: 1549.3
• InChiKey: HPTFWQIEIVLQOX-CYCWPGSHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  110
• 可旋转键数：
  40
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  434
• 氢给体数：
  13
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  [Ncy(methyl)4]acyline 在 sodium periodate 作用下， 以 水 、 乙腈 为溶剂， 反应 16.0h， 生成 (2S)-1-[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-3-(4-chlorophenyl)-1-hydroxy-2-[[(2R)-1-hydroxy-2-(1-hydroxyethylideneamino)-3-naphthalen-2-ylpropylidene]amino]propylidene]amino]-1-hydroxy-3-pyridin-3-ylpropylidene]amino]-1-hydroxy-2-methylsulfinylethylidene]amino]-1-hydroxy-3-[4-(1-hydroxyethylideneamino)phenyl]propylidene]amino]-1-hydroxy-3-[4-(1-hydroxyethylideneamino)phenyl]propylidene]amino]-1-hydroxy-4-methylpentylidene]amino]-6-(propan-2-ylamino)hexanoyl]-N-[(2R)-1-hydroxy-1-iminopropan-2-yl]pyrrolidine-2-carboximidic acid
  参考文献：
  名称：

  Structure−Activity Relationship Studies of Gonadotropin-Releasing Hormone Antagonists Containing S-Aryl/Alkyl Norcysteines and Their Oxidized Derivatives

  摘要：

  A series of acyline analogues incorporating L- and D-isomers of S-arylated/alkylated norcysteines [Ncy(R), where R is 2-naphthyl, methyl, and isopropyl] at positions 1, 4, 7, and 10 were synthesized. Some of these analogues were mono- and dioxidized to sulfoxides and sulfones. All of the analogues of acyline were screened for the antagonism of the GnRH-induced response in a reporter gene assay in HEK-293 cells expressing the human GnRH receptor. Nine of the analogues (9, 11, 15, 16, 17, 19, 20 21, and 22) had antagonistic potency (IC50 < 2 nM) similar to that of acyline (IC50 = 0.52 nM) in this assay. Selected analogues (9, 11, 15, 16, 19, and 21) were tested in vitro for their antagonism at the rat GnRH-R in a reporter gene assay as well as in an in vivo intact male rat assay. Analogues 9 and 15 were the most potent in suppressing testosterone levels.

  DOI：

  10.1021/jm0613931
• 作为产物：
  描述：

  (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-2-methylsulfanylacetic acid 、 Boc-3-(2-萘基)-D-丙氨酸 、 Boc-4-(Fmoc-氨基)-L-苯丙氨酸 、 Boc-D-4Aph(Fmoc)-OH 、 alkaline earth salt of/the/ methylsulfuric acid 、 alkaline earth salt of/the/ methylsulfuric acid 生成 [Ncy(methyl)4]acyline
  参考文献：
  名称：

  Structure−Activity Relationship Studies of Gonadotropin-Releasing Hormone Antagonists Containing S-Aryl/Alkyl Norcysteines and Their Oxidized Derivatives

  摘要：

  A series of acyline analogues incorporating L- and D-isomers of S-arylated/alkylated norcysteines [Ncy(R), where R is 2-naphthyl, methyl, and isopropyl] at positions 1, 4, 7, and 10 were synthesized. Some of these analogues were mono- and dioxidized to sulfoxides and sulfones. All of the analogues of acyline were screened for the antagonism of the GnRH-induced response in a reporter gene assay in HEK-293 cells expressing the human GnRH receptor. Nine of the analogues (9, 11, 15, 16, 17, 19, 20 21, and 22) had antagonistic potency (IC50 < 2 nM) similar to that of acyline (IC50 = 0.52 nM) in this assay. Selected analogues (9, 11, 15, 16, 19, and 21) were tested in vitro for their antagonism at the rat GnRH-R in a reporter gene assay as well as in an in vivo intact male rat assay. Analogues 9 and 15 were the most potent in suppressing testosterone levels.

  DOI：

  10.1021/jm0613931