[(S)-2-Hydroxy-1-(2-methoxy-5-pentafluorobenzenesulfonylamino-phenylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester | 1026921-91-4

• 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: [(S)-2-Hydroxy-1-(2-methoxy-5-pentafluorobenzenesulfonylamino-phenylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(2S)-3-hydroxy-1-[2-methoxy-5-[(2,3,4,5,6-pentafluorophenyl)sulfonylamino]anilino]-1-oxopropan-2-yl]carbamate
• CAS: 1026921-91-4
• 化学式: C₂₁H₂₂F₅N₃O₇S
• 分子量: 555.48
• InChiKey: SUCBMPLTIHSJLX-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  151
• 氢给体数：
  4
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  [(S)-2-Hydroxy-1-(2-methoxy-5-pentafluorobenzenesulfonylamino-phenylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (S)-2-Amino-3-hydroxy-N-(2-methoxy-5-pentafluorobenzenesulfonylamino-phenyl)-propionamide
  参考文献：
  名称：

  Hydrophilic, Pro-Drug Analogues of T138067 Are Efficacious in Controlling Tumor Growth In Vivo and Show a Decreased Ability To Cross the Blood Brain Barrier

  摘要：

  The novel anticancer compound T138067 is an irreversible inhibitor of tubulin polymerization. Amides 3-6 were synthesized using standard methodologies and determined to be significantly less lipophilic than T138067 based on logP calculations. Tubulin polymerization and [H-3]-T138067 competition assays revealed that these amides are pro-drugs for parent aniline 2. Amides 3-5 showed no detectable signs of crossing the blood brain barrier, while amide 6 was found in extremely small amounts (12 ng/g of brain tissue). Aniline 2, which was formed in vivo from these amides, was found in significantly smaller amounts (approximately 20 to > 5000 times) in the brain than when 2 was administered directly. The in vivo efficacy of amide 6 approached that of T138067 and was better tolerated when administered to athymic. nude mice bearing MX-1 human mammary tumor xenografts.

  DOI：

  10.1021/jm000478d
• 作为产物：
  描述：

  2,3,4,5,6-五氟苯磺酰氯 在 10percent Pd/C 、 20percent palladium hydroxide N-甲基吗啉 、 氢气 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 以 甲醇 、 乙醇 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 20.0~65.0 ℃ 、101.33 kPa 条件下， 反应 27.0h， 生成 [(S)-2-Hydroxy-1-(2-methoxy-5-pentafluorobenzenesulfonylamino-phenylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Hydrophilic, Pro-Drug Analogues of T138067 Are Efficacious in Controlling Tumor Growth In Vivo and Show a Decreased Ability To Cross the Blood Brain Barrier

  摘要：

  The novel anticancer compound T138067 is an irreversible inhibitor of tubulin polymerization. Amides 3-6 were synthesized using standard methodologies and determined to be significantly less lipophilic than T138067 based on logP calculations. Tubulin polymerization and [H-3]-T138067 competition assays revealed that these amides are pro-drugs for parent aniline 2. Amides 3-5 showed no detectable signs of crossing the blood brain barrier, while amide 6 was found in extremely small amounts (12 ng/g of brain tissue). Aniline 2, which was formed in vivo from these amides, was found in significantly smaller amounts (approximately 20 to > 5000 times) in the brain than when 2 was administered directly. The in vivo efficacy of amide 6 approached that of T138067 and was better tolerated when administered to athymic. nude mice bearing MX-1 human mammary tumor xenografts.

  DOI：

  10.1021/jm000478d

文献信息

• Hydrophilic, Pro-Drug Analogues of T138067 Are Efficacious in Controlling Tumor Growth In Vivo and Show a Decreased Ability To Cross the Blood Brain Barrier
  作者：Steven M. Rubenstein、Vijay Baichwal、Holger Beckmann、David L. Clark、Walter Frankmoelle、Daniel Roche、Edit Santha、Susan Schwender、Martin Thoolen、Qiuping Ye、Juan C. Jaen

  DOI：10.1021/jm000478d

  日期：2001.10.1

  The novel anticancer compound T138067 is an irreversible inhibitor of tubulin polymerization. Amides 3-6 were synthesized using standard methodologies and determined to be significantly less lipophilic than T138067 based on logP calculations. Tubulin polymerization and [H-3]-T138067 competition assays revealed that these amides are pro-drugs for parent aniline 2. Amides 3-5 showed no detectable signs of crossing the blood brain barrier, while amide 6 was found in extremely small amounts (12 ng/g of brain tissue). Aniline 2, which was formed in vivo from these amides, was found in significantly smaller amounts (approximately 20 to > 5000 times) in the brain than when 2 was administered directly. The in vivo efficacy of amide 6 approached that of T138067 and was better tolerated when administered to athymic. nude mice bearing MX-1 human mammary tumor xenografts.