methyl 2-[(5-oxo-2-phenyloxazol-4(5H)-ylidene)methyl]benzoate | 88590-43-6

• 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: methyl 2-[(5-oxo-2-phenyloxazol-4(5H)-ylidene)methyl]benzoate
• 英文别名: Methyl 2-[(5-oxo-2-phenyl-4,5-dihydro-1,3-oxazol-4-ylidene)methyl]benzoate；methyl 2-[(5-oxo-2-phenyl-1,3-oxazol-4-ylidene)methyl]benzoate
• CAS: 88590-43-6
• 化学式: C₁₈H₁₃NO₄
• 分子量: 307.306
• InChiKey: BAVSJELVCICTGP-UHFFFAOYSA-N

物化性质

• 沸点：
  462.2±55.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  65
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 2-[(5-oxo-2-phenyloxazol-4(5H)-ylidene)methyl]benzoate 在 potassium carbonate 、 potassium hydroxide 、 三溴氧磷 作用下， 以 乙腈 为溶剂， 生成 1-溴-3-异喹啉羧酸甲酯
  参考文献：
  名称：

  含有非平面四齿配体，二异喹啉二羧酸（biqaH 2）的钌水氧化催化剂†

  摘要：

  制备了两种含有四齿配体[1，1′-二异喹啉] -3，3′-二羧酸和4-甲基吡啶或6-溴异喹啉作为轴向配体的钌配合物。已经对该配合物进行了充分的表征，并且已经对其作为分子水氧化催化剂的潜力进行了初步研究。两种配合物均通过Ce IV催化酸性介质中水的氧化作为化学计量的化学氧化剂，尽管与密切相关的Ru-bda和Ru-pda类似物相比，转换数和转换频率适中。通过密度泛函理论计算获得了水亲核攻击和分子间偶联途径的障碍，并且通过对理论和实验结果的综合分析，阐明了配体构架对于确定最有利的反应途径的关键影响。

  DOI：

  10.1039/c6dt03880h
• 作为产物：
  描述：

  邻羧基苯甲醛 在 potassium acetate 、 potassium carbonate 作用下， 以 乙酸酐 、 丙酮 为溶剂， 生成 methyl 2-[(5-oxo-2-phenyloxazol-4(5H)-ylidene)methyl]benzoate
  参考文献：
  名称：

  含有非平面四齿配体，二异喹啉二羧酸（biqaH 2）的钌水氧化催化剂†

  摘要：

  制备了两种含有四齿配体[1，1′-二异喹啉] -3，3′-二羧酸和4-甲基吡啶或6-溴异喹啉作为轴向配体的钌配合物。已经对该配合物进行了充分的表征，并且已经对其作为分子水氧化催化剂的潜力进行了初步研究。两种配合物均通过Ce IV催化酸性介质中水的氧化作为化学计量的化学氧化剂，尽管与密切相关的Ru-bda和Ru-pda类似物相比，转换数和转换频率适中。通过密度泛函理论计算获得了水亲核攻击和分子间偶联途径的障碍，并且通过对理论和实验结果的综合分析，阐明了配体构架对于确定最有利的反应途径的关键影响。

  DOI：

  10.1039/c6dt03880h

文献信息

• [EN] COMPOUNDS FOR INDUCING CELLULAR APOPTOSIS<br/>[FR] COMPOSÉS ENTRAÎNANT L'APOPTOSE
  申请人：QUEEN MARY & WESTFIELD COLLEGE

  公开号：WO2010125343A1

  公开（公告）日：2010-11-04

  The present invention provides isoquinoline, tetrahydroisoquinoline and tetrahydropyridopyrimidine compounds that induce cell death by apoptosis and uses of the compounds in medicine, expecially their use for treating cancer and other diseases.

  本发明提供了诱导细胞凋亡的异喹啉、四氢异喹啉和四氢吡啶吡咯啉化合物，以及这些化合物在医学上的用途，尤其是它们用于治疗癌症和其他疾病的用途。
• Design, syntheses, and pharmacological characterization of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3′-carboxamido)morphinan analogues as opioid receptor ligands
  作者：Yunyun Yuan、Saheem A. Zaidi、David L. Stevens、Krista L. Scoggins、Philip D. Mosier、Glen E. Kellogg、William L. Dewey、Dana E. Selley、Yan Zhang

  DOI：10.1016/j.bmc.2015.02.055

  日期：2015.4

  A series of 17-cyclopropylmethyl-3,14 beta-dihydroxy-4,5 alpha-epoxy-6 alpha-(isoquinoline-3 '-carboxamido)morphinan (NAQ) analogues were synthesized and pharmacologically characterized to study their structure-activity relationship at the mu opioid receptor (MOR). The competition binding assay showed two-atom spacer and aromatic side chain were optimal for MOR selectivity. Meanwhile, substitutions at the 1 '- and/or 4 '-position of the isoquinoline ring retained or improved MOR selectivity over the kappa opioid receptor while still possessing above 20-fold MOR selectivity over the delta opioid receptor. In contrast, substitutions at the 6 '- and/or 7 '-position of the isoquinoline ring reduced MOR selectivity as well as MOR efficacy. Among this series of ligands, compound 11 acted as an antagonist when challenged with morphine in warm-water tail immersion assay and produced less significant withdrawal symptoms compared to naltrexone in morphine-pelleted mice. Compound 11 also antagonized the intracellular Ca2+ increase induced by DAMGO. Molecular dynamics simulation studies of 11 in three opioid receptors indicated orientation of the 6 '-nitro group varied significantly in the different 'address' domains of the receptors and played a crucial role in the observed binding affinities and selectivity. Collectively, the current findings provide valuable insights for future development of NAQ-based MOR selective ligands. Published by Elsevier Ltd.
• Structure activity relationship studies of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3′-carboxamido)morphinan (NAQ) analogues as potent opioid receptor ligands: Preliminary results on the role of electronic characteristics for affinity and function
  作者：Yunyun Yuan、Orgil Elbegdorj、Irina O. Beletskaya、Dana E. Selley、Yan Zhang

  DOI：10.1016/j.bmcl.2013.07.043

  日期：2013.9

  17-Cyclopropylmethyl-3,14 beta-dihydroxy-4,5 alpha-epoxy-6 alpha-(isoquinoline-3'-carboxamido)morphinan (NAQ) was previously designed following the 'message-address' concept and was identified as a potent and highly selective mu opioid receptor (MOR) ligand based on its pharmacological profile. We here report the preliminary structure activity relationship (SAR) studies of this novel lead compound. For the new ligands synthesized as NAQ analogues, their binding assay results showed that a longer spacer and a saturated ring system of the side chain were unfavorable for their MOR selectivity over the kappa and delta opioid receptors. In contrast, substitutions with different electronic properties at either 1'- or 4'-position of the isoquinoline ring of the side chain were generally acceptable for reasonable MOR selectivity. The majority of NAQanalogues retained low efficacy at the MOR compared to NAQin the S-35-GTP[gamma S] binding assays while electron-withdrawing groups at 1'-position of the isoquinoline ring induced higher MOR stimulation than electron-donating groups did. In summary, the electronic characteristics of substituents at 1'- or 4'-position of the isoquinoline ring in NAQ seem to be critical and need to be further tuned up to achieve higher MOR selectivity and lower MOR stimulation. Published by Elsevier Ltd.
• Ortho-Palladation of (<i>Z</i>)-2-Aryl-4-Arylidene-5(4<i>H</i>)-Oxazolones. Structure and Functionalization
  作者：Gheorghe-Doru Roiban、Elena Serrano、Tatiana Soler、Maria Contel、Ion Grosu、Carlos Cativiela、Esteban P. Urriolabeitia

  DOI：10.1021/om901068f

  日期：2010.3.22

  Ortho-palladated complexes of (Z)-2-aryl-4-arylidene-5(4H)-oxazolones have been prepared through oxidative addition. The reaction of (Z)-2-phenyl-4-(2-bromobenzylidene)-5(4H)-oxazolone (4) with Pd-2(dba)(3)center dot CHCl3 gives the six-membered cyclopalladated dinuclear complex [Pd(mu-Br)(o-C6H4CH=CNC(O)OCPh)](2) (7). The reaction of 7 with PPh3 gives dinuclear 9, which incorporates one phosphine per Pd atom through cleavage of the Pd-N bond, and preserves the bromide bridging system. However, reaction with PPh2Me gives mononuclear 8, which incorporates two phosphines as a results of the cleavage of the mu-Br system and N displacement. In contrast, the reaction of 7 with pyridine gives complex 12 due to Simple cleavage of the Br bridge, leaving the N-bonding intact. Therefore, three different reaction pathways have been characterized. The reactivity of the Pd-C bond in 7 has also been examined, and functionalized oxazolones can be obtained. The reaction of 7 With PhI(OAc)(2) in acetic acid gives the starting oxazolone C6H4-2-Br-CH=CNC(O)OCPh (4), through the presumed oxidation of the Pd center and C-Br bond formation by reductive coupling. In contrast, the reaction of the acetate dimer 14 with PhI(OAc)(2) in acetic acid gives C6H4-2-OAc-CH=CNC(O)OCPh (20) through C-O coupling. When treatment of 7 with PhI(OAc)(2) is performed in MeOH or EtOH, the oxazolones C6H4-2-OR-CH=CNC(O)OCPh (R = Me (18), Et (19)) are obtained. The reaction of 7 with CO in alcohols ROH gives cleanly the oxazolones C6H4-2-CO2R-CH=CNC(O)OCPh (R = Me (21), Pr-i (22)) through CO migratory insertion into the Pd-C bond and further nucleophilic attack of the RO- fragment.