3-(5-formylfuran-2-yl)-2-methylbenzoic acid | 462068-41-3

• 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-(5-formylfuran-2-yl)-2-methylbenzoic acid
• 英文别名: 3-(5-Formyl-furan-2-yl)-2-methyl-benzoic acid
• CAS: 462068-41-3
• 化学式: C₁₃H₁₀O₄
• mdl: MFCD02629515
• 分子量: 230.22
• InChiKey: ABNPGQRDALSXCP-UHFFFAOYSA-N

物化性质

• 熔点：
  140-142 °C(Solv: ethanol (64-17-5))
• 沸点：
  439.5±45.0 °C(Predicted)
• 密度：
  1.293±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  67.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(5-formylfuran-2-yl)-2-methylbenzoic acid 、 2-肼基苯并噻唑 以 乙醇 为溶剂， 以40%的产率得到3-(5-((2-(benzo[d]thiazol-2-yl)hydrazono)methyl)furan-2-yl)-2-methylbenzoic acid
  参考文献：
  名称：

  Discovery of Potent and Selective Benzothiazole Hydrazone Inhibitors of Bcl-X_L

  摘要：

  Developing potent molecules that inhibit Bcl-2 family mediated apoptosis affords opportunities to treat cancers via reactivation of the cell death machinery. We describe the hit-to-lead development of selective Bcl-X-L inhibitors originating from a high-throughput screening campaign. Small structural changes to the hit compound increased binding affinity more than 300-fold (to IC50 < 20 nM). This molecular series exhibits drug-like characteristics, low molecular weights (M-w < 450) and unprecedented selectivity for Bcl-X-L. Surface plasmon resonance experiments afford strong evidence of binding affinity within the hydrophobic groove of Bcl-X-L. Biological experiments using engineered Mcl-1 deficient mouse embryonic fibroblasts (MEFs, reliant only on Bcl-X-L, for survival) and Bax/Bak deficient MEFs (insensitive to selective activation of Bcl-2-driven apoptosis) support a mechanism-based induction of apoptosis. This manuscript describes the first series of selective small-molecule inhibitors of Bcl-X-L and provides promising leads for the development of efficacious therapeutics against solid tumors and chemoresistant cancer cell lines.

  DOI：

  10.1021/jm400556w
• 作为产物：
  描述：

  5-甲醛基呋喃-2-硼酸 、 3-溴-2-甲基苯甲酸 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 反应 1.0h， 以80%的产率得到3-(5-formylfuran-2-yl)-2-methylbenzoic acid
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationship of a Novel Series of 2-Aryl 5-(4-Oxo-3-phenethyl-2-thioxothiazolidinylidenemethyl)furans as HIV-1 Entry Inhibitors

  摘要：

  We previously identified two small molecules targeting the HIV-1 gp41, N-(4-carboxy-3-hydroxy)phenyl-2,5-dimethylpyrrole 12 (NB-2) and N-(3-carboxy-4-chloro)phenylpyrrole 13 (NB-64), that inhibit HIV-1 infection at low micromolar levels. Oil the basis of molecular docking analysis, we designed a series of 2-aryl 5-(4-oxo-3-phenethyl-2-thioxothiazolidinylidenemethyl)furans. Compared with 12 and 13, these compounds have bigger molecular size (437-515 Da) and could occupy more space in the deep hydrophobic pocket oil the gp41 NHR trimer. Fifteen 2-aryl 5-(4-oxo-3-phenethyl-2-thioxothiazolidinylidenemethyl)furans (11a-o) were synthesized by Suzuki-Miyaura cross-coupling followed by a Knoevenagel condensation and tested for their anti-HIV-1 activity and cytotoxicity on MT-2 cells. We found that all 15 compounds had improved anti-HIV-1 activity and 3 of them (11a, 11b, and 11d) exhibited inhibitory activity against replication of HIB-1(IIIB) and 94UG103 at < 100 nM range, more than 20-fold more potent than 12 and 13, suggesting that these Compounds can serve as leads for development of novel small molecule HIV fusion inhibitors.

  DOI：

  10.1021/jm900450n

文献信息

• Bi-functional complexes and methods for making and using such complexes
  申请人：Gouliaev Alex Haahr

  公开号：US11225655B2

  公开（公告）日：2022-01-18

  The present invention is directed to a method for the synthesis of a bi-functional complex comprising a molecule part and an identifier oligonucleotide part identifying the molecule part. A part of the synthesis method according to the present invention is preferably conducted in one or more organic solvents when a nascent bi-functional complex comprising an optionally protected tag or oligonucleotide identifier is linked to a solid support, and another part of the synthesis method is preferably conducted under conditions suitable for enzymatic addition of an oligonucleotide tag to a nascent bi-functional complex in solution.

  本发明涉及一种合成双功能复合物的方法，该复合物包括分子部分和识别分子部分的识别寡核苷酸部分。根据本发明的合成方法的一部分优选在一种或多种有机溶剂中进行，此时包含可选保护标签或寡核苷酸标识符的新生双功能复合物与固体支持物相连接，合成方法的另一部分优选在适合于将寡核苷酸标签酶加到溶液中的新生双功能复合物的条件下进行。
• BI-FUNCTIONAL COMPLEXES AND METHODS FOR MAKING AND USING SUCH COMPLEXES
  申请人：Nuevolution A/S

  公开号：EP2558577B1

  公开（公告）日：2018-12-12
• BI-FUNCTINAL COMPLEXES AND METHODS FOR MAKING AND USING SUCH COMPLEXES
  申请人：Gouliaev Alex Haahr

  公开号：US20130281324A1

  公开（公告）日：2013-10-24

  The present invention is directed to a method for the synthesis of a bi-functional complex comprising a molecule part and an identifier oligonucleotide part identifying the molecule part. A part of the synthesis method according to the present invention is preferably conducted in one or more organic solvents when a nascent bi-functional complex comprising an optionally protected tag or oligonucleotide identifier is linked to a solid support, and another part of the synthesis method is preferably conducted under conditions suitable for enzymatic addition of an oligonucleotide tag to a nascent bi-functional complex in solution.
• Design, Synthesis, and Structure−Activity Relationship of a Novel Series of 2-Aryl 5-(4-Oxo-3-phenethyl-2-thioxothiazolidinylidenemethyl)furans as HIV-1 Entry Inhibitors
  作者：Alan R. Katritzky、Srinivasa R. Tala、Hong Lu、Anatoliy V. Vakulenko、Qi-Yin Chen、Jothilingam Sivapackiam、Keyur Pandya、Shibo Jiang、Asim K. Debnath

  DOI：10.1021/jm900450n

  日期：2009.12.10

  We previously identified two small molecules targeting the HIV-1 gp41, N-(4-carboxy-3-hydroxy)phenyl-2,5-dimethylpyrrole 12 (NB-2) and N-(3-carboxy-4-chloro)phenylpyrrole 13 (NB-64), that inhibit HIV-1 infection at low micromolar levels. Oil the basis of molecular docking analysis, we designed a series of 2-aryl 5-(4-oxo-3-phenethyl-2-thioxothiazolidinylidenemethyl)furans. Compared with 12 and 13, these compounds have bigger molecular size (437-515 Da) and could occupy more space in the deep hydrophobic pocket oil the gp41 NHR trimer. Fifteen 2-aryl 5-(4-oxo-3-phenethyl-2-thioxothiazolidinylidenemethyl)furans (11a-o) were synthesized by Suzuki-Miyaura cross-coupling followed by a Knoevenagel condensation and tested for their anti-HIV-1 activity and cytotoxicity on MT-2 cells. We found that all 15 compounds had improved anti-HIV-1 activity and 3 of them (11a, 11b, and 11d) exhibited inhibitory activity against replication of HIB-1(IIIB) and 94UG103 at < 100 nM range, more than 20-fold more potent than 12 and 13, suggesting that these Compounds can serve as leads for development of novel small molecule HIV fusion inhibitors.
• Discovery of Potent and Selective Benzothiazole Hydrazone Inhibitors of Bcl-X_L
  作者：Brad E. Sleebs、Wilhemus J. A. Kersten、Sanji Kulasegaram、George Nikolakopoulos、Effie Hatzis、Rebecca M. Moss、John P. Parisot、Hong Yang、Peter E. Czabotar、W. Douglas Fairlie、Erinna F. Lee、Jerry M. Adams、Lin Chen、Mark F. van Delft、Kym N. Lowes、Andrew Wei、David C.S. Huang、Peter M. Colman、Ian P. Street、Jonathan B. Baell、Keith Watson、Guillaume Lessene

  DOI：10.1021/jm400556w

  日期：2013.7.11

  Developing potent molecules that inhibit Bcl-2 family mediated apoptosis affords opportunities to treat cancers via reactivation of the cell death machinery. We describe the hit-to-lead development of selective Bcl-X-L inhibitors originating from a high-throughput screening campaign. Small structural changes to the hit compound increased binding affinity more than 300-fold (to IC50 < 20 nM). This molecular series exhibits drug-like characteristics, low molecular weights (M-w < 450) and unprecedented selectivity for Bcl-X-L. Surface plasmon resonance experiments afford strong evidence of binding affinity within the hydrophobic groove of Bcl-X-L. Biological experiments using engineered Mcl-1 deficient mouse embryonic fibroblasts (MEFs, reliant only on Bcl-X-L, for survival) and Bax/Bak deficient MEFs (insensitive to selective activation of Bcl-2-driven apoptosis) support a mechanism-based induction of apoptosis. This manuscript describes the first series of selective small-molecule inhibitors of Bcl-X-L and provides promising leads for the development of efficacious therapeutics against solid tumors and chemoresistant cancer cell lines.