[(2R,3S,7R,10S,13S)-13-((S)-2-Amino-3-methyl-butyrylamino)-7-((S)-1-carbamoyl-3-methyl-butylcarbamoyl)-10-isobutyl-2-methyl-4,9,12,15-tetraoxo-1-oxa-5,11-diaza-cyclopentadec-3-yl]-carbamic acid benzyl ester | 713497-10-0

• 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: [(2R,3S,7R,10S,13S)-13-((S)-2-Amino-3-methyl-butyrylamino)-7-((S)-1-carbamoyl-3-methyl-butylcarbamoyl)-10-isobutyl-2-methyl-4,9,12,15-tetraoxo-1-oxa-5,11-diaza-cyclopentadec-3-yl]-carbamic acid benzyl ester
• CAS: 713497-10-0
• 化学式: C₃₇H₅₇N₇O₁₀
• 分子量: 759.9
• InChiKey: UJFVSESQXQXFMF-XFPOLMAISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.32
• 重原子数：
  54.0
• 可旋转键数：
  13.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  267.21
• 氢给体数：
  7.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  丁二酸酐 、 [(2R,3S,7R,10S,13S)-13-((S)-2-Amino-3-methyl-butyrylamino)-7-((S)-1-carbamoyl-3-methyl-butylcarbamoyl)-10-isobutyl-2-methyl-4,9,12,15-tetraoxo-1-oxa-5,11-diaza-cyclopentadec-3-yl]-carbamic acid benzyl ester 在 吡啶 、 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 N-{(S)-1-[(2R,3S,7R,10S,13S)-3-Benzyloxycarbonylamino-7-((S)-1-carbamoyl-3-methyl-butylcarbamoyl)-10-isobutyl-2-methyl-4,9,12,15-tetraoxo-1-oxa-5,11-diaza-cyclopentadec-13-ylcarbamoyl]-2-methyl-propyl}-succinamic acid
  参考文献：
  名称：

  Synthesis and Evaluation of Macrocyclic Transition State Analogue Inhibitors for α-Chymotrypsin

  摘要：

  Lactams 1 and 2 are readily formed from acyclic precursors in the presence of trypsin and chymotrypsin, respectively, identifying the macrocyclic ring system as a potential motif for constrained transition state analogue inhibitors of the serine peptidases. Ketone 3 was synthesized and shown to be a modest inhibitor of chymotrypsin (K-i = 220 muM), albeit 4-fold more potent than the acyclic hydroxy acid 25 (K-i = 1.5 mM as a mixture of epimers). A precursor (31) to the amino boronic acid 4 was also prepared; although this derivative was a potent inhibitor of chymotrypsin (K-i = 130 nM) by virtue of the boronic acid moiety, it showed no advantage over the des-amino analogue 32 (K-i = 120 nM), which is not capable of cyclizing.

  DOI：

  10.1021/jo034837z
• 作为产物：
  描述：

  methyl (2SR,5S)-5-[N-(tert-butoxycarbonyl)amino]-2-cyano-7-methyl-4-oxooctanoate 在 platinum(IV) oxide 、 四(三苯基膦)钯 盐酸 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 氢气 、 tin(II) acetate 、 三氧化硫吡啶 、 1-羟基苯并三唑 、 溶剂黄146 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 二乙胺 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 乙二醇甲醚 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 226.58h， 生成 [(2R,3S,7R,10S,13S)-13-((S)-2-Amino-3-methyl-butyrylamino)-7-((S)-1-carbamoyl-3-methyl-butylcarbamoyl)-10-isobutyl-2-methyl-4,9,12,15-tetraoxo-1-oxa-5,11-diaza-cyclopentadec-3-yl]-carbamic acid benzyl ester
  参考文献：
  名称：

  Synthesis and Evaluation of Macrocyclic Transition State Analogue Inhibitors for α-Chymotrypsin

  摘要：

  Lactams 1 and 2 are readily formed from acyclic precursors in the presence of trypsin and chymotrypsin, respectively, identifying the macrocyclic ring system as a potential motif for constrained transition state analogue inhibitors of the serine peptidases. Ketone 3 was synthesized and shown to be a modest inhibitor of chymotrypsin (K-i = 220 muM), albeit 4-fold more potent than the acyclic hydroxy acid 25 (K-i = 1.5 mM as a mixture of epimers). A precursor (31) to the amino boronic acid 4 was also prepared; although this derivative was a potent inhibitor of chymotrypsin (K-i = 130 nM) by virtue of the boronic acid moiety, it showed no advantage over the des-amino analogue 32 (K-i = 120 nM), which is not capable of cyclizing.

  DOI：

  10.1021/jo034837z