N-(2,3-dihydro-1H-inden-2-yl)-2-[(1S)-2-methyl-1-[(3,4,5-trimethoxybenzoyl)amino]propyl]-1,3-thiazole-4-carboxamide | 1609138-47-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: N-(2,3-dihydro-1H-inden-2-yl)-2-[(1S)-2-methyl-1-[(3,4,5-trimethoxybenzoyl)amino]propyl]-1,3-thiazole-4-carboxamide
• CAS: 1609138-47-7
• 化学式: C₂₇H₃₁N₃O₅S
• 分子量: 509.626
• InChiKey: QZFJWNBZVUPDCV-QHCPKHFHSA-N

物化性质

• 熔点：
  74-78 °C
• 沸点：
  673.618±55.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.289±0.10 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (S)-2-[2-methyl-1-(3,4,5-trimethoxybenzoylamino)propyl]-thiazole-4-carboxylic acid ethyl ester 在 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基乙酰胺 、 水 为溶剂， 反应 0.17h， 生成 N-(2,3-dihydro-1H-inden-2-yl)-2-[(1S)-2-methyl-1-[(3,4,5-trimethoxybenzoyl)amino]propyl]-1,3-thiazole-4-carboxamide
  参考文献：
  名称：

  Design and Synthesis of Human ABCB1 (P-Glycoprotein) Inhibitors by Peptide Coupling of Diverse Chemical Scaffolds on Carboxyl and Amino Termini of (S)-Valine-Derived Thiazole Amino Acid

  摘要：

  P-glycoprotein (P-gp) serves as a therapeutic target for the development of multidrug resistance reversal agents. In this study, we synthesized 21 novel compounds by peptide coupling at corresponding carboxyl and amino termini of (S)-valine-based bis-thiazole and monothiazole derivatives with diverse chemical scaffolds. Using calcein-AM efflux assay, we identified compound 28 (IC50 = 1.0 mu M) carrying 3,4,5-trimethoxybenzoyl and 2-aminobenzophenone groups, respectively, at the amino and carboxyl termini of the monothiazole zwitter-ion. Compound 28 inhibited the photolabeling of P-gp with [I-125]-iodoarylazidoprazosin with IC50 = 0.75 mu M and stimulated the basal ATP hydrolysis of P-gp in a concentration-dependent manner (EC50 ATPase = 0.027 mu M). Compound 28 at 3 mu M reduced resistance in cytotoxicity assay to paclitaxel in P-gp-expressing SW620/Ad300 and HEK/ABCB1 cell lines. Biochemical and docking studies showed site-1 to be the preferable binding site for 28 within the drug-binding pocket of human P-gp.

  DOI：

  10.1021/jm401966m

文献信息

• Design and Synthesis of Human ABCB1 (P-Glycoprotein) Inhibitors by Peptide Coupling of Diverse Chemical Scaffolds on Carboxyl and Amino Termini of (<i>S</i>)-Valine-Derived Thiazole Amino Acid
  作者：Satyakam Singh、Nagarajan Rajendra Prasad、Eduardo E. Chufan、Bhargav A. Patel、Yi-Jun Wang、Zhe-Sheng Chen、Suresh V. Ambudkar、Tanaji T. Talele

  DOI：10.1021/jm401966m

  日期：2014.5.22

  P-glycoprotein (P-gp) serves as a therapeutic target for the development of multidrug resistance reversal agents. In this study, we synthesized 21 novel compounds by peptide coupling at corresponding carboxyl and amino termini of (S)-valine-based bis-thiazole and monothiazole derivatives with diverse chemical scaffolds. Using calcein-AM efflux assay, we identified compound 28 (IC50 = 1.0 mu M) carrying 3,4,5-trimethoxybenzoyl and 2-aminobenzophenone groups, respectively, at the amino and carboxyl termini of the monothiazole zwitter-ion. Compound 28 inhibited the photolabeling of P-gp with [I-125]-iodoarylazidoprazosin with IC50 = 0.75 mu M and stimulated the basal ATP hydrolysis of P-gp in a concentration-dependent manner (EC50 ATPase = 0.027 mu M). Compound 28 at 3 mu M reduced resistance in cytotoxicity assay to paclitaxel in P-gp-expressing SW620/Ad300 and HEK/ABCB1 cell lines. Biochemical and docking studies showed site-1 to be the preferable binding site for 28 within the drug-binding pocket of human P-gp.