3-methyl-3-phenyl-2-oxobutanoic acid | 91133-59-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-methyl-3-phenyl-2-oxobutanoic acid
• 英文别名: 3-methyl-2-oxo-3-phenylbutanoic acid；Taltobulin intermediate-2
• CAS: 91133-59-4
• 化学式: C₁₁H₁₂O₃
• 分子量: 192.214
• InChiKey: ULDLCYGZHGFPIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

制备方法与用途

Taltobulin 中间体-2 是合成 Taltobulin（HY-15584）的中间产物。Taltobulin 是一种常用于ADC制备中的毒素成分，同时也是强有力的微管蛋白抑制剂。它可以破坏微管蛋白聚合、诱导有丝分裂停滞，并引发凋亡。

反应信息

• 作为反应物：
  描述：

  3-methyl-3-phenyl-2-oxobutanoic acid 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 溴 、 铁粉 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 四氯化碳 、 二氯甲烷 为溶剂， 反应 22.0h， 生成 4-bromo-N-β,β-trimethylphenylalanyl-N¹-[(1S,2E)-4-ethoxy-1-isopropyl-3-methyl-4-oxo-2-butenyl]-N¹,3-dimethyl-valinamide
  参考文献：
  名称：

  Probing the Interaction of HTI-286 with Tubulin Using a Stilbene Analogue

  摘要：

  HTI-286 is a synthetic analogue of the natural product hemiasterlin. HTI-286 is a potent antitumor agent that induces tubulin oligomerization. To investigate the binding stoichiometry and the binding site during this ligand-induced tubulin association, we synthesized an analogue of HTI-286 containing the chromophore stilbene. Using the distinct absorbance of the stilbene analogue, we determined the amounts of inhibitors bound to different tubulin oligomers by analytical ultracentrifugation. Herein we describe our findings based on these experiments. At the ratio of inhibitor to protein equal to or greater than 1, the stilbene analogue induces oligomerization of tubulin to a ring structure. The binding stoichiometry in the ring is one inhibitor per tubulin monomer (defined as an alpha/beta-heterodimer). At the ratio of inhibitor to protein less than 1, tubulin forms multiple intermediates, with the binding stoichiometry less than one inhibitor per tubulin monomer for all intermediates. The stable complex between the inhibitor and tubulin monomer was not detected under our experimental conditions. The binding site of the stilbene analogue does not overlap with the classic tubulin-binding agent, colchicine.

  DOI：

  10.1021/ja048619e
• 作为产物：
  描述：

  苯丙酮酸 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 3-methyl-3-phenyl-2-oxobutanoic acid
  参考文献：
  名称：

  Probing the Interaction of HTI-286 with Tubulin Using a Stilbene Analogue

  摘要：

  HTI-286 is a synthetic analogue of the natural product hemiasterlin. HTI-286 is a potent antitumor agent that induces tubulin oligomerization. To investigate the binding stoichiometry and the binding site during this ligand-induced tubulin association, we synthesized an analogue of HTI-286 containing the chromophore stilbene. Using the distinct absorbance of the stilbene analogue, we determined the amounts of inhibitors bound to different tubulin oligomers by analytical ultracentrifugation. Herein we describe our findings based on these experiments. At the ratio of inhibitor to protein equal to or greater than 1, the stilbene analogue induces oligomerization of tubulin to a ring structure. The binding stoichiometry in the ring is one inhibitor per tubulin monomer (defined as an alpha/beta-heterodimer). At the ratio of inhibitor to protein less than 1, tubulin forms multiple intermediates, with the binding stoichiometry less than one inhibitor per tubulin monomer for all intermediates. The stable complex between the inhibitor and tubulin monomer was not detected under our experimental conditions. The binding site of the stilbene analogue does not overlap with the classic tubulin-binding agent, colchicine.

  DOI：

  10.1021/ja048619e

文献信息

• Compounds for treating tumors
  申请人：Zask Arie

  公开号：US20050037977A1

  公开（公告）日：2005-02-17

  The invention provides compounds of formula (I): wherein E, A, B′, R 6 , R 7 , R 8 , and R 9 are defined in the specification which compounds exhibit anticancer activity and are useful for treating cancer.

  该发明提供了以下式（I）的化合物： 其中E、A、B′、R6、R7、R8和R9在规范中定义，这些化合物表现出抗癌活性，并可用于治疗癌症。
• 聚（ADP-核糖）聚合酶抑制剂、制备方法及其 用途
  申请人：上海迪诺医药科技有限公司

  公开号：CN102952118B

  公开（公告）日：2016-03-23

  本发明涉及一种聚(ADP-核糖)聚合酶抑制剂、制备方法及其用途，具体涉及一系列结构如式(I)、(IA)、(IB)、(IC)、(ID)、(IE)、(IF)、(IG)、(IH)、(II)、(IJ)、(IK)、(IL)、(IM)、(IN)、(IO)和(IP)所示的杂环化合物作为聚(ADP-核糖)聚合酶抑制剂、制备方法，以及包含所述杂环化合物的药物组合物和用途；特别涉及所述杂环化合物在制备PARP抑制剂药物中的应用。本发明的杂环化合物还可作为有效成分用于制备治疗个体中癌症的药物，所述杂环化合物还可同放射疗法或化学治疗药物联合使用用于癌症的治疗。
• Absolute configurations of tubulin inhibitors taltobulin (HTI-286) and HTI-042 characterized by X-ray diffraction analysis and NMR studies
  作者：Chuansheng Niu、Douglas M. Ho、Arie Zask、Semiramis Ayral-Kaloustian

  DOI：10.1016/j.bmcl.2010.01.047

  日期：2010.3

  The stereochemistry of the tubulin inhibitors taltobulin HTI-286 (2) and HTI-042 (3) was determined by utilizing the DPFGSE 1D NOE experiment. Single crystal X-ray diffraction analysis further confirmed the absolute configuration of these two compounds, which carry the (S,S,S)-configuration necessary for biological activity.

  微管蛋白抑制剂taltobulin HTI-286（2）和HTI-042（3）的立体化学是通过DPFGSE 1D NOE实验确定的。单晶X射线衍射分析进一步证实了这两种化合物的绝对构型，它们具有生物活性所必需的（S，S，S）构型。
• Hemiasterlin Derivative Having Cysteine Residue
  申请人：Sumitomo Dainippon Pharma Co., Ltd.

  公开号：US20220144889A1

  公开（公告）日：2022-05-12

  A compound represented by formula (1): wherein b represents an integer of 1 to 5; X represents —NH— or —CO—; Z represents a group represented, for example, by formula (Z-1); R 1 represents a hydrogen atom or (AB) m ; AB represents a particular amino acid residue, and when there is a plurality of ABs, each AB may be the same as or different from each other and ABs are bonded to each other via an amide bond; m represents an integer of 1 to 9; R 2 represents a hydroxy group or (AC) g ; AC represents a particular amino acid residue, and when there is a plurality of ACs, each AC may be the same as or different from each other and ACs are bonded to each other via an amide bond; and g represents an integer of 1 to 9, or a salt thereof.

  化合物的化学式为（1）：其中b表示1至5的整数；X表示—NH—或—CO—；Z表示由化学式（Z-1）表示的基团；R1表示氢原子或(AB)m；AB表示特定的氨基酸残基，当存在多个AB时，每个AB可以相同或不同，并且AB通过酰胺键相互连接；m表示1至9的整数；R2表示羟基或(AC)g；AC表示特定的氨基酸残基，当存在多个AC时，每个AC可以相同或不同，并且AC通过酰胺键相互连接；g表示1至9的整数；或其盐。
• Process for producing 2-oxo-3-aromatic carboxylic acid derivatives
  申请人：Sagami Chemical Research Center

  公开号：US05028738A1

  公开（公告）日：1991-07-02

  There is a process for producing 2-oxo-3-aromatic carboxylic acid derivatives which comprises reacting aromatic pyruvic acid derivatives with electrophilic compounds in the presence of bases in a protic solvent. According to this process, 2-oxo-3-aromatic carboxylic acid derivatives which can be easily converted to aromatic amino acid derivatives or 2-aromatic carboxylic acid derivatives as important synthetic intermediates of medicines and agricultural chemicals can be produced in good yields with high selectivity.

  有一个生产2-氧代-3-芳香羧酸衍生物的过程，其中包括在质子溶剂中存在碱的情况下，用亲电性化合物反应芳香丙酮酸衍生物。根据这个过程，可以以高选择性的良好产率生产2-氧代-3-芳香羧酸衍生物，这些衍生物可以轻松转化为芳香氨基酸衍生物或2-芳香羧酸衍生物，作为药物和农业化学品的重要合成中间体。