3-hydroxy-1-phenyl-1H-pyrazole-4-carbaldehyde

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-hydroxy-1-phenyl-1H-pyrazole-4-carbaldehyde
• 英文别名: 5-oxo-2-phenyl-1H-pyrazole-4-carbaldehyde
• 化学式: C₁₀H₈N₂O₂
• 分子量: 188.186
• InChiKey: KXCPVJMZLIDHKZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-hydroxy-1-phenyl-1H-pyrazole-4-carbaldehyde 在 potassium phosphate 、 四(三苯基膦)钯 、 三乙胺 、 potassium bromide 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 3-(naphthalen-2-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde
  参考文献：
  名称：

  通过 Pd 催化的交叉偶联反应合成 3-取代的 1-苯基-1H-吡唑-4-甲醛和相应的乙酮

  摘要：

  描述了从 1-苯基-1H-吡唑-3-醇开始构建邻位取代的 1-苯基-1H-吡唑-4甲醛和相应的乙酮的有效合成路线。碳-碳键形成 Pd 催化的交叉偶联反应用于中间体吡唑三氟甲磺酸酯的官能化。对所有获得的产品进行了详细的 NMR 光谱研究。

  DOI：

  10.3998/ark.5550190.0012.b01
• 作为产物：
  描述：

  1-苯基-1,5-二氢-4H-咪唑-4-酮 在 sodium hydride 、 三氟乙酸 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 61.25h， 生成 3-hydroxy-1-phenyl-1H-pyrazole-4-carbaldehyde
  参考文献：
  名称：

  通过 Pd 催化的交叉偶联反应合成 3-取代的 1-苯基-1H-吡唑-4-甲醛和相应的乙酮

  摘要：

  描述了从 1-苯基-1H-吡唑-3-醇开始构建邻位取代的 1-苯基-1H-吡唑-4甲醛和相应的乙酮的有效合成路线。碳-碳键形成 Pd 催化的交叉偶联反应用于中间体吡唑三氟甲磺酸酯的官能化。对所有获得的产品进行了详细的 NMR 光谱研究。

  DOI：

  10.3998/ark.5550190.0012.b01

文献信息

• FIVE-MEMBERED HETEROCYCLIC COMPOUNDS
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1541564A1

  公开（公告）日：2005-06-15

  The present invention provides a compound represented by the formula: wherein R1 is an optionally substituted 5-membered heterocyclic group; X, Y and V are the same or different and each is a bond, an oxygen atom, a sulfur atom and the like; Q is a divalent hydrocarbon group having 1 to 20 carbon atoms; ring A is an aromatic ring optionally further having 1 to 3 substituents; Z is -(CH2)n-Z1- or -Z1-(CH2)n- (n is an integer of 0 to 8, Z1 is a bond, an oxygen atom, a sulfur atom and the like); ring B is a nitrogen-containing heterocycle optionally further having 1 to 3 substituents; W is a bond or a divalent hydrocarbon group having 1 to 20 carbon atoms; R2 is a hydrogen atom, a cyano group, -PO(OR9)(OR10) (R9 and R10 are the same or different and each is a hydrogen atom or an optionally substituted hydrocarbon group, and R9 and R10 are optionally bonded to form an optionally substituted ring) and the like, or a salt thereof, which has a superior adipose tissue weight decreasing action, a hypoglycemic action and a hypolipidemic action, and which is useful as an agent for the prophylaxis or treatment of obesity, diabetes mellitus, hyperlipidemia, impaired glucose tolerance, hypertension and the like.

  本发明提供了一种由以下式表示的化合物： 其中R1是可选择地取代的5-成员杂环基团；X、Y和V相同或不同，每个都是键，氧原子，硫原子等；Q是具有1到20个碳原子的二价碳氢基团；环A是一个芳香环，可选择地进一步具有1到3个取代基；Z是-(CH2)n-Z1-或-Z1-( )n-（n是0到8的整数，Z1是键，氧原子，硫原子等）；环B是一个含氮杂环，可选择地进一步具有1到3个取代基；W是键或具有1到20个碳原子的二价碳氢基团；R2是氢原子，氰基，-PO(OR9)(OR10)（R9和R10相同或不同，每个是氢原子或可选择地取代的碳氢基团，R9和R10可选择地结合形成可选择地取代的环）等，或其盐，具有优越的减少脂肪组织重量的作用，降糖作用和降脂作用，并且作为预防或治疗肥胖症，糖尿病，高脂血症，糖耐量受损，高血压等的药剂是有用的。
• Synthesis and Antiproliferative Activity of 2,4,6,7-Tetrasubstituted-2H-pyrazolo[4,3-c]pyridines
  作者：Beatričė Razmienė、Eva Řezníčková、Vaida Dambrauskienė、Radek Ostruszka、Martin Kubala、Asta Žukauskaitė、Vladimír Kryštof、Algirdas Šačkus、Eglė Arbačiauskienė

  DOI：10.3390/molecules26216747

  日期：——

  A library of 2,4,6,7-tetrasubstituted-2H-pyrazolo[4,3-c]pyridines was prepared from easily accessible 1-phenyl-3-(2-phenylethynyl)-1H-pyrazole-4-carbaldehyde via an iodine-mediated electrophilic cyclization of intermediate 4-(azidomethyl)-1-phenyl-3-(phenylethynyl)-1H-pyrazoles to 7-iodo-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridines followed by Suzuki cross-couplings with various boronic acids and alkylation reactions. The compounds were evaluated for their antiproliferative activity against K562, MV4-11, and MCF-7 cancer cell lines. The most potent compounds displayed low micromolar GI50 values. 4-(2,6-Diphenyl-2H-pyrazolo[4,3-c]pyridin-7-yl)phenol proved to be the most active, induced poly(ADP-ribose) polymerase 1 (PARP-1) cleavage, activated the initiator enzyme of apoptotic cascade caspase 9, induced a fragmentation of microtubule-associated protein 1-light chain 3 (LC3), and reduced the expression levels of proliferating cell nuclear antigen (PCNA). The obtained results suggest a complex action of 4-(2,6-diphenyl-2H-pyrazolo[4,3-c]pyridin-7-yl)phenol that combines antiproliferative effects with the induction of cell death. Moreover, investigations of the fluorescence properties of the final compounds revealed 7-(4-methoxyphenyl)-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridine as the most potent pH indicator that enables both fluorescence intensity-based and ratiometric pH sensing.

  一种2,4,6,7-四取代-2H-吡唑并[4,3-c]吡啶类化合物库是通过易得的1-苯基-3-(2-苯基乙炔基)-1H-吡唑-4-甲醛经过碘介导的中间体4-(叠氮甲基)-1-苯基-3-(苯基乙炔基)-1H-吡唑向7-碘-2,6-二苯基-2H-吡唑并[4,3-c]吡啶的电泳环化反应制备的，随后与各种硼酸和烷基化反应进行Suzuki交叉偶联。这些化合物被评估其对K562、MV4-11和MCF-7癌细胞系的抗增殖活性。最有效的化合物显示出低微摩尔GI50值。4-(2,6-二苯基-2H-吡唑并[4,3-c]吡啶-7-基)酚被证明是最活跃的，诱导聚(ADP-核糖)聚合酶1 (PARP-1)裂解，激活凋亡级联启动酶卡斯帕9，诱导微管相关蛋白1-轻链3 (LC3)的碎裂，并降低增殖细胞核抗原 (PCNA)的表达水平。获得的结果表明4-(2,6-二苯基-2H-吡唑并[4,3-c]吡啶-7-基)酚具有复杂的作用，结合了抗增殖效应和诱导细胞死亡。此外，对最终化合物的荧光性质的研究显示，7-(4-甲氧基苯基)-2,6-二苯基-2H-吡唑并[4,3-c]吡啶是最有效的pH指示剂，可以实现基于荧光强度和比色法的pH检测。
• Synthesis and anti-mitotic activity of 2,4- or 2,6-disubstituted- and 2,4,6-trisubstituted-2H-pyrazolo[4,3-c]pyridines
  作者：Vaida Milišiūnaitė、Eglė Arbačiauskienė、Eva Řezníčková、Radek Jorda、Veronika Malínková、Asta Žukauskaitė、Wolfgang Holzer、Algirdas Šačkus、Vladimír Kryštof

  DOI：10.1016/j.ejmech.2018.03.037

  日期：2018.4

  An efficient synthetic route for the synthesis of 2H-pyrazolo[4,3-c]pyridines, primarily varying by the substituents at the 2-, 4- and 6-positions, is described here. A Sonogashira-type cross-coupling reaction was employed to yield 3-alkynyl-1H-pyrazole-4-carbaldehydes, ethanones and propanones from the corresponding 1H-pyrazol-3-yl trifluoromethanesulfonates. Subsequent treatment of the coupling products

  本文描述了一种合成2 H-吡唑并[4,3- c ]吡啶的有效合成途径，主要由2、4-和6-位的取代基决定。利用Sonogashira型交叉偶联反应从相应的1 H-吡唑-3-基三氟甲烷磺酸酯产生3-炔基-1 H-吡唑-4-甲醛，乙酮和丙烷。随后用干燥的氨水处理偶联产物，得到了2 H-吡唑并[4,3- c ]吡啶的多功能文库，然后评估了其对K562和MCF-7癌细胞系的细胞毒性。这些化合物中最有效的化合物显示出低的微摩尔GI 50两个单元格行中的值。活性化合物在有丝分裂中诱导了剂量依赖性的细胞周期停滞，如流式细胞仪分析的DNA含量和丝氨酸10处组蛋白H3的磷酸化所示。此外，生化分析显示，caspases-3 / 7在处理过的细胞中具有增强的活性，PARP-1的特异性片段化，以及Bcl-2的磷酸化，共同证实了凋亡是细胞死亡的机制。
• Convenient Synthesis of Pyrazolo[4′,3′:5,6]pyrano[4,3-c][1,2]oxazoles via Intramolecular Nitrile Oxide Cycloaddition
  作者：Vaida Milišiūnaitė、Elena Plytninkienė、Roberta Bakšienė、Aurimas Bieliauskas、Sonata Krikštolaitytė、Greta Račkauskienė、Eglė Arbačiauskienė、Algirdas Šačkus

  DOI：10.3390/molecules26185604

  日期：——

  A simple and efficient synthetic route to the novel 3a,4-dihydro-3H,7H- and 4H,7H-pyrazolo[4′,3′:5,6]pyrano[4,3-c][1,2]oxazole ring systems from 3-(prop-2-en-1-yloxy)- or 3-(prop-2-yn-1-yloxy)-1H-pyrazole-4-carbaldehyde oximes has been developed by employing the intramolecular nitrile oxide cycloaddition (INOC) reaction as the key step. The configuration of intermediate aldoximes was unambiguously

  一种简单高效的新型3a,4-dihydro-3 H ,7 H - 和4 H ,7 H -pyrazolo[4',3':5,6]pyrano[4,3- c ][1]合成路线,2] 恶唑环系统由 3-(prop-2-en-1-yloxy)- 或 3-(prop-2-yn-1-yloxy)-1 H -pyrazole-4-carbaldehyde oximes 开发分子内氧化腈环加成 (INOC) 反应是关键步骤。中间醛肟的构型是使用 NOESY 实验数据和亚胺基部分的1 J CH偶联常数的大小的比较明确确定的，对于主要的合成，这些常数大了大约 13 Hz。异构体。所得杂环产物的结构通过详细的1 H、13 C 和15 N NMR 光谱实验和 HRMS 测量证实。
• Five-membered heterocyclic compounds
  申请人：Momose Yu

  公开号：US20060135578A1

  公开（公告）日：2006-06-22

  The present invention provides a compound represented by the formula: wherein R 1 is an optionally substituted 5-membered heterocyclic group; X, Y and V are the same or different and each is a bond, an oxygen atom, a sulfur atom and the like; Q is a divalent hydrocarbon group having 1 to 20 carbon atoms; ring A is an aromatic ring optionally further having 1 to 3 substituents; Z is —(CH 2 ) n -Z 1 - or -Z 1 -(CH 2 ) n — (n is an integer of 0 to 8, Z 1 is a bond, an oxygen atom, a sulfur atom and the like); ring B is a nitrogen-containing heterocycle optionally further having 1 to 3 substituents; W is a bond or a divalent hydrocarbon group having 1 to 20 carbon atoms; R 2 is a hydrogen atom, a cyano group, —PO(OR 9 )(OR 10 ) (R 9 and R 10 are the same or different and each is a hydrogen atom or an optionally substituted hydrocarbon group, and R 9 and R 10 are optionally bonded to form an optionally substituted ring) and the like, or a salt thereof, which has a superior adipose tissue weight decreasing action, a hypoglycemic action and a hypolipidemic action, and which is useful as an agent for the prophylaxis or treatment of obesity, diabetes mellitus, hyperlipidemia, impaired glucose tolerance, hypertension and the like.

  本发明提供一种化合物，其化学式表示为：其中，R1为可选取的取代的5-成员杂环基；X、Y和V相同或不同，每个都是键，氧原子，硫原子等；Q为具有1到20个碳原子的二价碳氢基团；环A为芳香环，可选地进一步具有1到3个取代基；Z为—(CH2)n-Z1-或-Z1-( )n—（n为0到8的整数，Z1为键，氧原子，硫原子等）；环B为含氮杂环，可选地进一步具有1到3个取代基；W为键或具有1到20个碳原子的二价碳氢基团；R2为氢原子，氰基，—PO(OR9)(OR10)（R9和R10相同或不同，每个都是氢原子或可选取的取代的碳氢基团，R9和R10可选择性地结合形成可选取的取代环）等，或其盐，具有优异的减轻脂肪组织重量、降血糖和降血脂作用，可用作预防或治疗肥胖症、糖尿病、高脂血症、糖耐量受损、高血压等的药剂。