2-<(S)-1-amino-2-methylpropyl>-4-ethoxycarbonylthiazole | 220717-59-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-<(S)-1-amino-2-methylpropyl>-4-ethoxycarbonylthiazole
• 英文别名: (S)-2-(1-amino-2-methylpropyl)thiazole-4-carboxylic acid ethyl ester；H-Val-Thz-OEt；ethyl 2-[(1S)-1-amino-2-methylpropyl]-1,3-thiazole-4-carboxylate
• CAS: 220717-59-9
• 化学式: C₁₀H₁₆N₂O₂S
• 分子量: 228.315
• InChiKey: FMFFCNPPDJRMEX-QMMMGPOBSA-N

物化性质

• 沸点：
  310.9±22.0 °C(Predicted)
• 密度：
  1.157±0.06 g/cm3(Predicted)
• 溶解度：
  溶于二氯甲烷

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  93.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-<(S)-1-amino-2-methylpropyl>-4-ethoxycarbonylthiazole 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 12.17h， 生成 N-[(1R)-1-(4-methoxyphenyl)ethyl]-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
• 作为产物：
  描述：

  (R)-(R)-2-((tert-butoxycarbonyl)amino)-3-methylbutanoic (ethyl carbonic) anhydride 在 劳森试剂 、 2,6-二甲基吡啶 、 ammonium hydroxide 、 乙醇 、 potassium hydrogencarbonate 、 乙酰氯 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 甲苯 为溶剂， 生成 2-<(S)-1-amino-2-methylpropyl>-4-ethoxycarbonylthiazole
  参考文献：
  名称：

  Structure-based design of agents targeting the bacterial ribosome

  摘要：

  Rational structure-based drug design has been applied to the antibiotic thiostrepton, in an attempt to overcome some of its limitations. The identification of a proposed binding fragment allowed construction of a number of key fragments, which were derivatised to generate a library of potential antibiotics. These were then evaluated to determine their ability to bind to the L11 binding domain of the prokaryotic ribosome and inhibit bacterial protein translation. (C) 200 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00495-5

文献信息

• An expeditious synthesis of bistratamide H using a new fluorous protecting group
  作者：Yutaka Nakamura、Kazuo Okumura、Masaru Kojima、Seiji Takeuchi

  DOI：10.1016/j.tetlet.2005.10.144

  日期：2006.1

  A total synthesis of bistratamide H has been achieved using a new ‘highly’ fluorous amino protecting group, tris(perfluorodecyl)silylethoxylcarbonyl (FTeoc) group. The synthetic intermediates were easily isolated by liquid–liquid extraction with fluorous solvent. The fluorous protecting group was demonstrated to be recycled.

  使用新的“高度”氟氨基保护基三（全氟癸基）甲硅烷基乙氧基羰基（F Teoc）基团可实现双链酰胺H的全合成。合成中间体很容易通过用氟溶剂进行液-液萃取来分离。氟保护基被证明是可再循环的。
• Total Syntheses of the Thiopeptides Amythiamicin C and D
  作者：Carolin Ammer、Thorsten Bach

  DOI：10.1002/chem.201002144

  日期：2010.12.17

  fragment of the amythiamicins by a Negishi cross‐coupling. For the synthesis of amythiamicin C, this step was followed by a Negishi cross‐coupling at C‐6 of the pyridine core. Subsequent attachment of the Eastern fragment was achieved by amide bond formation and macrolactam ring closure by a Stille cross‐coupling at C‐2. The Eastern bithiazole fragment of the amythiamins was constructed also by regioselective

  通过使用酰胺键形成，Stille交叉偶联反应和两个Negishi交叉偶联反应作为关键转化，合成了硫肽链霉菌素C和D。将目标化合物的中心2,3,6-三取代吡啶环引入2,6-二溴-3-3-碘吡啶，该环在3位选择性地金属化，并通过环糊精与链霉菌素的完整Southern片段相连。 Negishi交叉耦合。对于合成霉菌素C，此步骤之后是在吡啶核的C-6处进行Negishi交叉偶联。东部片段的后续附着是通过酰胺键的形成和大内酰胺环的封闭（通过C-2处的Stille交叉偶联）来实现的。也通过区域选择性金属化和交叉偶联反应构建了淀粉酶的东部联苯噻唑片段。关键的步骤涉及将4-溴苯并噻唑-2-溴化镁非对映选择性地添加到手性亚磺酰基亚胺中。对于霉菌素D的合成，改变了C-6处的交叉偶联，酰胺键形成和C-2处的交叉偶联的顺序。首先进行与东部片段的酰胺键形成，然后尝试通过在C-2分子内区域选择性Stille交叉偶联来
• Design, Synthesis, and Biological Evaluation of (<i>S</i>)-Valine Thiazole-Derived Cyclic and Noncyclic Peptidomimetic Oligomers as Modulators of Human P-Glycoprotein (ABCB1)
  作者：Satyakam Singh、Nagarajan Rajendra Prasad、Khyati Kapoor、Eduardo E. Chufan、Bhargav A. Patel、Suresh V. Ambudkar、Tanaji T. Talele

  DOI：10.1002/cbic.201300565

  日期：2014.1.3

  Circles and lines: Synthesis of isosteric analogues of QZ59Se‐SSS to inhibit the efflux activity of human P‐glycoprotein (P‐gp) resulted in cyclic trimer and linear trimer compounds as the most potent in the series. These compounds can be further optimized by replacing the thiazole unit with privileged fragments.

  圆圈和线条：合成 QZ59Se- SSS的等排类似物以抑制人 P-糖蛋白 (P-gp) 的外排活性导致环状三聚体和线性三聚体化合物成为该系列中最有效的化合物。这些化合物可以通过用特权片段替换噻唑单元来进一步优化。
• Total Synthesis of the Thiazolyl Peptide GE2270 A
  作者：H. Martin Müller、Oscar Delgado、Thorsten Bach

  DOI：10.1002/anie.200700684

  日期：2007.6.18
• Total Synthesis of Bistratamide D
  作者：Susan V. Downing、Enrique Aguilar、A. I. Meyers

  DOI：10.1021/jo981664i

  日期：1999.2.1

  The total synthesis of the macrocyclic hexapeptide bistratamide D is reported. The synthetic strategy involved assembly of enantiomerically pure oxazole, thiazole, and oxazoline segments derived from amino acids. Macrocyclization of the hexapeptidic aminooxazoline-oxazole-thiazole carboxylic acid fragment was accomplished by activation with O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU).