((9S,10S,13R)-10-(furan-2-yl)-2,2,9,11-tetramethyl-12-oxo-3,3-diphenyl-4,7-dioxa-11-aza-3-silatetradecan-13-yl)(methyl)carbamic acid benzyl ester

• 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: ((9S,10S,13R)-10-(furan-2-yl)-2,2,9,11-tetramethyl-12-oxo-3,3-diphenyl-4,7-dioxa-11-aza-3-silatetradecan-13-yl)(methyl)carbamic acid benzyl ester
• 英文别名: benzyl((9S,10S,13R)-10-(furan-2-yl)-2,2,9,11-tetramethyl-12-oxo-3,3-diphenyl-4,7-dioxa-11-aza-3-silatetradecan-13-yl)(methyl)carbamate；benzyl N-[(2R)-1-[[(1S,2S)-3-[2-[tert-butyl(diphenyl)silyl]oxyethoxy]-1-(furan-2-yl)-2-methylpropyl]-methylamino]-1-oxopropan-2-yl]-N-methylcarbamate
• 化学式: C₃₉H₅₀N₂O₆Si
• 分子量: 670.921
• InChiKey: OLCIUNPOVRHVDP-OQFWUBAYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.67
• 重原子数：
  48
• 可旋转键数：
  17
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  81.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ((9S,10S,13R)-10-(furan-2-yl)-2,2,9,11-tetramethyl-12-oxo-3,3-diphenyl-4,7-dioxa-11-aza-3-silatetradecan-13-yl)(methyl)carbamic acid benzyl ester 在 ruthenium trichloride 、 sodium periodate 作用下， 以 正庚烷 、 水 、 乙酸乙酯 为溶剂， 反应 0.75h， 生成 (2S,3S)-2-((R)-2-(((benzyloxy)carbonyl)(methyl)amino)-N-methylpropanamido)-4-(2-((tert-butyldiphenylsilyl)oxy)ethoxy)-3-methylbutanoic acid
  参考文献：
  名称：

  Potent Nonimmunosuppressive Cyclophilin Inhibitors With Improved Pharmaceutical Properties and Decreased Transporter Inhibition

  摘要：

  Nonimmunosuppressive cyclophilin inhibitors have demonstrated efficacy for the treatment of hepatitis C infection (HCV). However, alisporivir, cyclosporin A, and most other cyclosporins are potent inhibitors of OATP1B1, MRP2, MDR1, and other important drug transporters. Reduction of the side chain hydrophobicity of the P4 residue preserves cyclophilin binding and antiviral potency while decreasing transporter inhibition. Representative inhibitor 33 (NIM258) is a less potent transporter inhibitor relative to previously described cyclosporins, retains anti-HCV activity in cell culture, and has an acceptable pharmacokinetic profile in rats and dogs. An X-ray structure of 33 bound to rat cyclophilin D is reported.

  DOI：

  10.1021/jm500862r
• 作为产物：
  描述：

  N-(2-呋喃亚甲基)氨基甲酸叔丁酯 在 咪唑 、 盐酸 、 sodium tetrahydroborate 、 四丁基氟化铵 、 sodium hydride 、 N,N-二异丙基乙胺 、 反-4-(叔丁基二苯基硅氧基)-L-脯氨酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium iodide 、 三甲基硅烷化重氮甲烷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 82.5h， 生成 ((9S,10S,13R)-10-(furan-2-yl)-2,2,9,11-tetramethyl-12-oxo-3,3-diphenyl-4,7-dioxa-11-aza-3-silatetradecan-13-yl)(methyl)carbamic acid benzyl ester
  参考文献：
  名称：

  Potent Nonimmunosuppressive Cyclophilin Inhibitors With Improved Pharmaceutical Properties and Decreased Transporter Inhibition

  摘要：

  Nonimmunosuppressive cyclophilin inhibitors have demonstrated efficacy for the treatment of hepatitis C infection (HCV). However, alisporivir, cyclosporin A, and most other cyclosporins are potent inhibitors of OATP1B1, MRP2, MDR1, and other important drug transporters. Reduction of the side chain hydrophobicity of the P4 residue preserves cyclophilin binding and antiviral potency while decreasing transporter inhibition. Representative inhibitor 33 (NIM258) is a less potent transporter inhibitor relative to previously described cyclosporins, retains anti-HCV activity in cell culture, and has an acceptable pharmacokinetic profile in rats and dogs. An X-ray structure of 33 bound to rat cyclophilin D is reported.

  DOI：

  10.1021/jm500862r

文献信息

• Potent Nonimmunosuppressive Cyclophilin Inhibitors With Improved Pharmaceutical Properties and Decreased Transporter Inhibition
  作者：Jiping Fu、Meiliana Tjandra、Christopher Becker、Dallas Bednarczyk、Michael Capparelli、Robert Elling、Imad Hanna、Roger Fujimoto、Markus Furegati、Subramanian Karur、Theresa Kasprzyk、Mark Knapp、Kwan Leung、Xiaolin Li、Peichao Lu、Wosenu Mergo、Charlotte Miault、Simon Ng、David Parker、Yunshan Peng、Silvio Roggo、Alexey Rivkin、Robert L. Simmons、Michael Wang、Brigitte Wiedmann、Andrew H. Weiss、Linda Xiao、Lili Xie、Wenjian Xu、Aregahegn Yifru、Shengtian Yang、Bo Zhou、Zachary K. Sweeney

  DOI：10.1021/jm500862r

  日期：2014.10.23

  Nonimmunosuppressive cyclophilin inhibitors have demonstrated efficacy for the treatment of hepatitis C infection (HCV). However, alisporivir, cyclosporin A, and most other cyclosporins are potent inhibitors of OATP1B1, MRP2, MDR1, and other important drug transporters. Reduction of the side chain hydrophobicity of the P4 residue preserves cyclophilin binding and antiviral potency while decreasing transporter inhibition. Representative inhibitor 33 (NIM258) is a less potent transporter inhibitor relative to previously described cyclosporins, retains anti-HCV activity in cell culture, and has an acceptable pharmacokinetic profile in rats and dogs. An X-ray structure of 33 bound to rat cyclophilin D is reported.