(4RS,5R,6S)-N-[(tert-butyloxy)carbonyl]-6-amino-5-(triisopropylsilyloxy)-7-cyclohexyl-1-heptyn-4-ol | 217468-11-6

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: (4RS,5R,6S)-N-[(tert-butyloxy)carbonyl]-6-amino-5-(triisopropylsilyloxy)-7-cyclohexyl-1-heptyn-4-ol
• 英文别名: (4RS,5R,6S)-N-[(tert-butyloxy)carbonyl]-6-amino-5-(triisopropylsilioxy)-7-cyclohexyl-1-heptyn-4-ol；tert-butyl N-[(2S,3R)-1-cyclohexyl-4-hydroxy-3-tri(propan-2-yl)silyloxyhept-6-yn-2-yl]carbamate
• CAS: 217468-11-6
• 化学式: C₂₇H₅₁NO₄Si
• 分子量: 481.792
• InChiKey: LEDOWTYUKMCWTL-QNRWSGHRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  33
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4RS,5R,6S)-N-[(tert-butyloxy)carbonyl]-6-amino-5-(triisopropylsilyloxy)-7-cyclohexyl-1-heptyn-4-ol 在 n-butyloammonium fluoride 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以53%的产率得到(4S,5R,6S)-N-[(tert-Butyloxy)carbonyl]-6-amino-7-cyclohexyl-4,5-dihydroxyhept-1-yne
  参考文献：
  名称：

  Use of propargyl glycine amino propargyl diol compounds for inhibiting plasma renin activity

  摘要：

  通常被描述为丙炔基甘氨酸氨基丙炔二醇衍生物的化合物，可用于治疗通过抑制血浆肾素活性介导的疾病。特别感兴趣的化合物是符合以下式I的化合物 其中A从CO和SO2中选择，X从氧原子和亚甲基中选择；R1和R9中的每一个独立选择自氢、甲基、乙基、正丙基、异丙基、苄基、三氟乙基、叔丁氧羰基和甲氧甲基羰基的基团，R1和R9附着的氮原子可以与氧结合形成N-氧化物；R2从氢、甲基、乙基和异丙基中选择；R3从苄基、环己基甲基、苯乙基、咪唑基甲基、吡啶基甲基和2-吡啶基乙基中选择；R5和R8中的每一个独立地是丙炔基或含丙炔基的基团；R7是环己基甲基；R4和R6中的每一个独立选择自氢和甲基；R11和R12中的每一个独立选择自氢、烷基和苯基；m为零；n为从零到三中选择的数字；或其药用可接受盐。

  公开号：

  US06342624B1
• 作为产物：
  描述：

  ammonium chloride 、 3-溴丙炔 在 mercury (II) chloride 作用下， 以 乙醚 、 正己烷 、 乙酸乙酯 、 甲苯 为溶剂， 以66.5%的产率得到(4RS,5R,6S)-N-[(tert-butyloxy)carbonyl]-6-amino-5-(triisopropylsilyloxy)-7-cyclohexyl-1-heptyn-4-ol
  参考文献：
  名称：

  Amino acyl amino propargyl diol compounds for treatment of hypertension

  摘要：

  通常被描述为氨基酰氨基丙炔二醇衍生物的化合物可用作肾素抑制剂，用于治疗高血压。特别感兴趣的化合物是公式I中的化合物：其中A从CO和SO.sub.2中选择；其中X从氧原子和亚甲基中选择；其中R.sub.1和R.sub.9中的每一个都是独立选择的基团，包括氢、甲基、乙基、正丙基、异丙基、苄基、β，β，β-三氟乙基、t-丁氧羰基和甲氧基甲氧基羰基，R.sub.1和R.sub.9连接的氮原子可以与氧结合形成N-氧化物；其中R.sub.2从氢、甲基、乙基和异丙基中选择；其中R.sub.3从苄基、环己基甲基、苯乙基、咪唑基甲基、吡啶基甲基和2-吡啶基乙基中选择；其中R.sub.5从氢、烷基、吡唑基烷基、吡啶基烷基、噻唑基烷基、咪唑基烷基、噻吩基烷基、呋喃基烷基、噁唑基烷基、异噁唑基烷基、嘧啶基烷基、吡嗪基烷基和吡咯基烷基中选择；其中R.sub.4和R.sub.6中的每一个都是独立选择的氢和甲基；其中R.sub.7是环己基甲基；其中R.sub.8是丙炔基或含丙炔基的基团；其中R.sub.11和R.sub.12中的每一个都是独立选择的氢、烷基和苯基；其中m为零；其中n是从零到三的数字；或其药学上可接受的盐。

  公开号：

  US05849773A1

文献信息

• Propargyl glycine amino use of propargyl diol compounds for treatment of
  申请人：G.D. Searle & Co.

  公开号：US05484812A1

  公开（公告）日：1996-01-16

  Compounds characterized generally as propargyl glycine amino propargyl diol derivatives are useful as renin inhibitors for the treatment of ophthalmic disorders. Compounds of particular interest are those of Formula I ##STR1## wherein A is selected from CO and SO.sub.2 wherein X is selected from oxygen atom and methylene; wherein each of R.sub.1 and R.sub.9 is a group independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, benzyl, b, b, b-trifluoroethyl, t-butyloxycarbonyl and methoxymethylcarbonyl, and wherein the nitrogen atom to which R.sub.1 and R.sub.9 are attached may be combined with oxygen to form an N-oxide; wherein R.sub.2 is selected from hydrido, methyl, ethyl and isopropyl; wherein R.sub.3 is selected from benzyl, cyclohexylmethyl, phenethyl, imidazolemethyl, pyridylmethyl and 2-pyridylethyl; wherein R.sub.5 is propargyl or a propargyl-containing moiety; wherein R.sub.7 is cyclohexylmethyl; wherein each of R.sub.4 and R.sub.6 is independently selected from hydrido and methyl; wherein R.sub.8 is selected from ethyl, n-propyl, isobutyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclohexylmethyl, cyclohexylethyl, allyl, vinyl and fluorovinyl; wherein each of R.sub.11 and R.sub.12 is independently selected from hydrido, alkyl and phenyl; wherein m is zero; and wherein n is a number selected from zero through three; or a pharmaceutically-acceptable salt thereof.

  一般被表征为丙炔基甘氨酸氨基丙炔基二醇衍生物的化合物，可用作治疗眼科疾病的肾素抑制剂。特别感兴趣的化合物是公式I所示的那些##STR1##，其中A选自CO和SO.sub.2，X选自氧原子和亚甲基；其中R.sub.1和R.sub.9各自独立地选自氢、甲基、乙基、正丙基、异丙基、苄基、b, b, b-三氟乙基、t-丁氧羰基和甲氧基甲氧基羰基，并且R.sub.1和R.sub.9所连接的氮原子可以与氧结合形成一个N-氧化物；其中R.sub.2选自氢、甲基、乙基和异丙基；其中R.sub.3选自苄基、环己基甲基、苯乙基、咪唑烷基甲基、吡啶基甲基和2-吡啶基乙基；其中R.sub.5是丙炔基或含丙炔基的基团；其中R.sub.7是环己基甲基；其中R.sub.4和R.sub.6各自独立地选自氢和甲基；其中R.sub.8选自乙基、正丙基、异丁基、环丙基、环丁基、环戊基、环己基、环丙基甲基、环己基甲基、环己基乙基、烯丙基、乙烯基和氟乙烯基；其中R.sub.11和R.sub.12各自独立地选自氢、烷基和苯基；其中m为零；并且n是从零到三的数字；或其药物可接受的盐。
• Propargyl glycine amino propargyl diol compounds for treatment of hypertension
  申请人：G.D. Searle & Co.

  公开号：US20040220272A1

  公开（公告）日：2004-11-04

  Compounds characterized generally as propargyl glycine amino propargyl diol derivatives are useful as renin inhibitors for the treatment of hypertension. Compounds of particular interest are those of Formula I 1 wherein A is selected from CO and SO 2 wherein X is selected from oxygen atom and methylene; wherein each of R 1 and R 9 is a group independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, benzyl, b, b, b-trifluoroethyl, t-butyloxycarbonyl and methoxymethylcarbonyl, and wherein the nitrogen atom to which R 1 and R 9 are attached may be combined with oxygen to form an N-oxide; wherein R 2 is selected from hydrido, methyl, ethyl and isopropyl; wherein R 3 is selected from benzyl, cyclohexylmethyl, phenethyl, imidazolemethyl, pyridylmethyl and 2-pyridylethyl; wherein each of R 5 and R 8 is independently propargyl or a propargyl-containing moiety; wherein R 7 is cyclohexylmethyl; wherein each of R 4 and R 6 is independently selected from hydrido and methyl; wherein each of R 11 and R 12 is independently selected from hydrido, alkyl and phenyl; wherein m is zero; and wherein n is a number selected from zero through three; or a pharmaceutically-acceptable salt thereof.

  通常被描述为丙炔基甘氨酸氨基丙炔二醇衍生物的化合物可用作肾素抑制剂，用于治疗高血压。特别感兴趣的化合物是公式I1中的化合物，其中A从CO和SO2中选择，X从氧原子和亚甲基中选择；其中R1和R9分别是从氢基，甲基，乙基，正丙基，异丙基，苯甲基，b，b，b-三氟乙基，t-丁氧羰基和甲氧甲酰基中独立选择的基团，R1和R9连接的氮原子可以与氧结合形成N-氧化物；其中R2从氢基，甲基，乙基和异丙基中选择；其中R3从苯甲基，环己基甲基，苯乙基，咪唑甲基，吡啶基甲基和2-吡啶基乙基中选择；其中R5和R8各自独立地为丙炔基或含丙炔基的基团；其中R7为环己基甲基；其中R4和R6各自独立地选择从氢基和甲基中选择；其中R11和R12各自独立地选择从氢基，烷基和苯基中选择；其中m为零；其中n是从零到三选择的数字；或其药学上可接受的盐。
• Propargyl glycine amino propargyl diol compounds for treatment of
  申请人：G. D. Searle & Co.

  公开号：US05223535A1

  公开（公告）日：1993-06-29

  Compounds characterized generally as propargyl glycine amino propargyl diol derivatives are useful as renin inhibitors for the treatment of hypertension. Compounds of particular interest are those of Formula I ##STR1## wherein A is selected from CO and SO.sub.2 wherein X is selected from oxygen atom and methylene; wherein each of R.sub.1 and R.sub.9 is a group independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, benzyl, .beta.,.beta.,.beta.-trifluoroethyl, t-butyloxycarbonyl and methoxymethylcarbonyl, and wherein the nitrogen atom to which R.sub.1 and R.sub.9 are attached may be combined with oxygen to form an N-oxide; wherein R.sub.2 is selected from hydrido, methyl, ethyl and isopropyl; wherein R.sub.3 is selected from benzyl, cyclohexylmethyl, phenethyl, imidazolemethyl, pyridylmethyl and 2-pyridylethyl; wherein each of R.sub.5 and R.sub.8 is independently propargyl or a propargyl-containing moiety; wherein R.sub.7 is cyclohexylmethyl; wherein each of R.sub.4 and R.sub.6 is independently selected from hydrido and methyl; wherein each of R.sub.11 and R.sub.12 is independently selected from hydrido, alkyl and phenyl; wherein m is zero; and wherein n is a number selected from zero through three; or a pharmaceutically-acceptable salt thereof.

  通常被描述为丙炔基甘氨酸氨基丙炔二醇衍生物的化合物可用作肾素抑制剂，用于治疗高血压。特别感兴趣的化合物是式I的化合物##STR1##其中A从CO和SO.sub.2中选择，X从氧原子和亚甲基中选择；其中R.sub.1和R.sub.9中的每一个独立地选择自氢基，甲基，乙基，正丙基，异丙基，苯甲基，.beta.，.beta.，.beta.-三氟乙基，t-丁氧羰基和甲氧甲基羰基，R.sub.1和R.sub.9所连接的氮原子可以与氧结合形成N-氧化物；其中R.sub.2从氢基，甲基，乙基和异丙基中选择；其中R.sub.3从苯甲基，环己基甲基，苯乙基，咪唑甲基，吡啶基甲基和2-吡啶基乙基中选择；其中R.sub.5和R.sub.8各自独立地为丙炔基或含丙炔基的基团；其中R.sub.7为环己基甲基；其中R.sub.4和R.sub.6各自独立地选择自氢基和甲基；其中R.sub.11和R.sub.12各自独立地选择自氢基，烷基和苯基；其中m为零；其中n为从零到三的数字；或其药学上可接受的盐。
• Use of propargyl glycine amino propargyl diol compounds for prevention of hypertension
  申请人：——

  公开号：US20030130522A1

  公开（公告）日：2003-07-10

  Compounds characterized generally as propargyl glycine amino propargyl diol derivatives are useful as renin inhibitors for the treatment of hypertension. Compounds of particular interest are those of Formula I 1 wherein A is selected from CO and SO 2 wherein X is selected from oxygen atom and methylene; wherein each of R 1 and R 9 is a group independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, benzyl, b, b, b-trifluoroethyl, t-butyloxycarbonyl and methoxymethylcarbonyl, and wherein the nitrogen atom to which R 1 and R 9 are attached may be combined with oxygen to form an N-oxide; wherein R 2 is selected from hydrido, methyl, ethyl and isopropyl; wherein R 3 is selected from benzyl, cyclohexylmethyl, phenethyl, imidazolemethyl, pyridylmethyl and 2-pyridylethyl; wherein each of R 5 and R 8 is independently propargyl or a propargyl-containing moiety; wherein R 7 is cyclohexylmethyl; wherein each of R 4 and R 6 is independently selected from hydrido and methyl; wherein each of R 11 and R 12 is independently selected from hydrido, alkyl and phenyl; wherein m is zero; and wherein n is a number selected from zero through three; or a pharmaceutically-acceptable salt thereof.

  一般被描述为丙炔基甘氨酸氨基丙炔二醇衍生物的化合物可用作肾素抑制剂，用于治疗高血压。特别感兴趣的化合物是公式I1中的化合物，其中A从CO和SO2中选择，X从氧原子和亚甲基中选择；其中R1和R9中的每一个独立地选择自氢基，甲基，乙基，正丙基，异丙基，苯甲基，b，b，b-三氟乙基，t-丁氧羰基和甲氧甲基羰基，R1和R9连接的氮原子可以与氧结合形成N-氧化物；其中R2从氢基，甲基，乙基和异丙基中选择；其中R3从苯甲基，环己基甲基，苯乙基，咪唑甲基，吡啶基甲基和2-吡啶基乙基中选择；其中R5和R8中的每一个都是丙炔基或含丙炔基的基团；其中R7是环己基甲基；其中R4和R6中的每一个独立地选择自氢基和甲基；其中R11和R12中的每一个独立地选择自氢基，烷基和苯基；其中m为零；其中n为从零到三的数字；或其药学上可接受的盐。
• Use of propargyl glycine amino propargyl diol compounds for treatment of congestive heart failure
  申请人：——

  公开号：US20030135066A1

  公开（公告）日：2003-07-17

  Compounds characterized generally as propargyl glycine amino propargyl diol derivatives are useful as renin inhibitors for the treatment of hypertension. Compounds of particular interest are those of Formula I 1 wherein A is selected from CO and SO 2 wherein X is selected from oxygen atom and methylene; wherein each of R 1 and R 9 is a group independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, benzyl, b, b, b-trifluoroethyl, t-butyloxycarbonyl and methoxymethylcarbonyl, and wherein the nitrogen atom to which R 1 and R 9 are attached may be combined with oxygen to form an N-oxide; wherein R 2 is selected from hydrido, methyl, ethyl and isopropyl; wherein R 3 is selected from benzyl, cyclohexylmethyl, phenethyl, imidazolemethyl, pyridylmethyl and 2-pyridylethyl; wherein each of R 5 and R 8 is independently propargyl or a propargyl-containing moiety; wherein R 7 is cyclohexylmethyl; wherein each of R 4 and R 6 is independently selected from hydrido and methyl; wherein each of R 11 and R 12 is independently selected from hydrido, alkyl and phenyl; wherein m is zero; and wherein n is a number selected from zero through three; or a pharmaceutically-acceptable salt thereof.

  一般被描述为丙炔基甘氨酸氨基丙炔二醇衍生物的化合物，可用作肾素抑制剂治疗高血压。特别感兴趣的化合物是公式I1中的化合物，其中A从CO和SO2中选择，X从氧原子和亚甲基中选择；其中每个R1和R9分别是从氢基，甲基，乙基，正丙基，异丙基，苯甲基，b，b，b-三氟乙基，t-丁氧羰基和甲氧甲基羰基中独立选择的基团，R1和R9连接的氮原子可以与氧结合形成N-氧化物；其中R2从氢基，甲基，乙基和异丙基中选择；其中R3从苯甲基，环己基甲基，苯乙基，咪唑甲基，吡啶甲基和2-吡啶基乙基中选择；其中每个R5和R8独立地为丙炔基或含丙炔基的基团；其中R7为环己基甲基；其中每个R4和R6独立地从氢基和甲基中选择；其中每个R11和R12独立地从氢基，烷基和苯基中选择；其中m为零；其中n为从零到三的数字；或其药物可接受的盐。