2-(1H-pyrazol-1-yl)pyridine-6-carbaldehyde | 217657-66-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-(1H-pyrazol-1-yl)pyridine-6-carbaldehyde
• 英文别名: 6-pyrazol-1-yl-pyridine-2-carboxaldehyde；6-(pyrazol-1-yl)pyridine-2-carbaldehyde；6-pyrazol-1-ylpyridine-2-carboxaldehyde；6-(1H-pyrazol-1-yl)picolinaldehyde；6-pyrazol-1-ylpyridine-2-carbaldehyde
• CAS: 217657-66-4
• 化学式: C₉H₇N₃O
• 分子量: 173.174
• InChiKey: BSBJWZBKEYTLDC-UHFFFAOYSA-N

物化性质

• 熔点：
  75-76 °C
• 沸点：
  324.5±27.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  13
• 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：
  47.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(1H-pyrazol-1-yl)pyridine-6-carbaldehyde 在 钾硼氢 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 20.0h， 生成 (3,4-Dichlorophenyl)-[4-methyl-4-[[(6-pyrazol-1-ylpyridin-2-yl)methylamino]methyl]piperidin-1-yl]methanone
  参考文献：
  名称：

  2-吡啶甲胺的新型衍生物作为对5-HT1A受体的选择性，有效和口服活性激动剂。

  摘要：

  这项工作的目的是提高最近发现的新颖结构的5-HT1A受体激动剂的口服生物利用度：芳基-{[4-（6-R-吡啶-2-基甲基）-氨基]-甲基}-哌啶-1-基-甲基无。在侧链氨基位置的β位置引入氟原子会导致类似物在口服后在大鼠中表现出增强的和持久的5-HT1A激动剂活性。氟原子在哌啶环的C-4位上的位置是最有利的，并且在测试的各种取代基中，氟的能力在改善该配体家族的口腔活性方面是独特的。因此，导数39、46，61和61与5-HT1A受体（与多巴胺能D2和肾上腺素α1受体相比）具有更高的亲和力和选择性，并且在体外和体内比其C-4脱氟类似物具有更强的5-HT1A激动剂活性。为了检查药效基团的构象与这种配体的激动活性水平之间的关系，我们合成了一系列的3-氯-4-氟苯基-（4-氟-4 {[（5-（H或CH3 ）-6-R-吡啶-2-基甲基）-氨基]-哌啶-1-基-++ ++甲酮衍生物，发现吡啶环上有5-甲

  DOI：

  10.1021/jm9806906
• 作为产物：
  描述：

  2-(1,3-dioxolan-2-yl)-6-fluoropyridin 在 甲酸 、 sodium hydride 、 copper(II) sulfate 作用下， 以 水 为溶剂， 反应 15.0h， 生成 2-(1H-pyrazol-1-yl)pyridine-6-carbaldehyde
  参考文献：
  名称：

  Design and Synthesis of a Series of 6-Substituted-2-pyridinylmethylamine Derivatives as Novel, High-Affinity, Selective Agonists at 5-HT_1A Receptors

  摘要：

  A search for novel, selective agonists with high intrinsic activity at the 5-HT1A subtype of serotonin (5-HT) receptors was undertaken. Mechanistic and thermodynamic considerations led to the design of 6-substituted-2-pyridinylmethylamine as a potential 5-HT1A pharmacophore. Various adducts derived from the 6-substituted-2-pyridinylmethylamine moiety were tested for their affinity at 5-HT1A, alpha(1)-adrenergic, and D-2-dopaminergic receptors. Compounds with high affinity for 5-HT1A receptors (pK(i) greater than or equal to 8) were examined for agonist properties by measuring their ability to inhibit forskolin-stimulated cAMP production in HA7 cells (i.e., HeLa cells permanently transfected with the h5-HT1A receptor gene and expressing the h5-HT1A receptor protein). Several compounds of the type aryl{4-[(6-substituted-pyridin-2-ylmethylamino)methyl]piperidin-1-yl}methanone had nanomolar affinity for 5-HT1A binding sites and were more than 500-fold selective with respect to alpha(1) and D-2 sites. Importantly, their 5-HT1A agonist properties were demonstrated in HA7 cells where they behaved as potent inhibitors of cAMP accumulation. In particular, (3,4-dichlorophenyl){4-[(6-oxazol-5-ylpyridin-2-ylmethylamino)methyl]piperidin-1-yl}methanone (70) and (3,4-dichlorophenyl){4-[(6-azetidinopyridin-2-ylmethylamino)methyl]piperidin-1-yl}methanone (36) appeared to be more potent than, and at least as efficacious as, the prototypical 5-HT1A agonist (+/-)-8-OH-DPAT. SAR studies revealed that the pyridine nitrogen atom and the nature and the position of the substituents on the pyridine ring were critically involved in the ability of the compounds to recognize and activate 5-HT1A receptors. Structural modifications of the nonpharmacophoric part of the molecule showed, however, that the entire structure was required for affinity at 5-HT1A binding sites.

  DOI：

  10.1021/jm9804329

文献信息

• 6-O-acyl ketolide antibacterials
  申请人：——

  公开号：US20030220272A1

  公开（公告）日：2003-11-27

  6-O-Acyl ketolide antibacterials of the formula: 1 wherein R 1 , R 2 , R 3 , R 4 , W, X, X′, Y, and Y′ are as described herein and in which the substituents have the meaning indicated in the description. These compounds are useful as antibacterial agents.

  其中R1、R2、R3、R4、W、X、X'、Y和Y'如本文所述，并且其中取代基具有描述中指示的含义。这些化合物可用作抗菌剂。
• 6-0-carbamoyl ketolide antibacterials
  申请人：——

  公开号：US20020115620A1

  公开（公告）日：2002-08-22

  6-O-Carbamoyl ketolide antibacterials of the formula: 1 wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , X, X′, Y, and Y′ are as described herein and in which the substituents have the meaning indicated in the description. These compounds are useful as antibacterial agents.

  其中R1、R2、R3、R4、R5、R6、X、X'、Y和Y'如本文所述，并且其中取代基具有描述中指示的含义。这些化合物可用作抗菌剂。
• Biphenyl bridged hexadentate N6-ligands – a rigid ligand backbone for Fe(<scp>ii</scp>) spin crossover complexes
  作者：Silvio Heider、Holm Petzold、Guillaume Chastanet、Stephan Schlamp、Tobias Rüffer、Birgit Weber、Jean-François Létard

  DOI：10.1039/c2dt32451b

  日期：——

  The novel hexadentate nitrogen based ligand N,N′-bis-(2-(1H-pyrazol-1-yl)pyridine-6-ylmethyl)-2,2′-biphenylenediamine (3) was synthesized and used for the preparation of iron Spin Crossover (SCO) complexes [Fe(3)][BF4]2 (4) and [Fe(3)][ClO4]2 (5), which differ only by the respective counter ion. These complex salts show different spin transition temperatures T1/2 (135 and 157 K, respectively). This

  合成了新的六齿氮基配体N，N'-双-（2-（1H-吡唑-1-基）吡啶-6-甲基）-2,2'-联苯二胺（3）铁自旋交联（SCO）络合物[Fe（3）] [BF 4 ] 2（4）和[Fe（3）] [ClO 4 ] 2（5），它们的区别仅在于各自的抗衡离子。这些复合盐显示出不同的自旋转变温度T 1/2（分别为135 K和157 K）。通过研究不同的低和高自旋异构体的固态结构来研究这种效果。无论抗衡离子，金属（Zn / Fe）和自旋态如何，该系列的所有配合物均显示紧密相关的晶体堆积。还研究了具有较低转变温度（4）的异构体的光磁行为。可以监测LIESST过程中的这种复合物，但未观察到反向LIESST。光诱导态的弛豫发生在约。80 K，显示出复杂的三态弛豫机制。
• [EN] LACTAM DERIVATIVES USEFUL AS OREXIN RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS DE LACTAME UTILES EN TANT QU'ANTAGONISTES DU RÉCEPTEUR DE L'OREXINE
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2012063207A1

  公开（公告）日：2012-05-18

  The present invention relates to lactam derivatives of formula (I) wherein Y, R1, R2 and R3 are as described in the description, to their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of formula (I), and especially to their use as orexin receptor antagonists.

  本发明涉及公式（I）的内酰胺衍生物，其中Y、R1、R2和R3如描述中所述，以及它们的制备方法，其药学上可接受的盐，以及它们作为药物的用途，包括含有一个或多个公式（I）化合物的药物组合物，特别是它们作为促进睡眠的药物受体拮抗剂的用途。
• Synthesis, characterization, and cytotoxic properties of mono- and di-nuclear cobalt(<scp>ii</scp>)-polypyridyl complexes
  作者：Arvin Eskandari、Arunangshu Kundu、Chunxin Lu、Sushobhan Ghosh、Kogularamanan Suntharalingam

  DOI：10.1039/c8dt00577j

  日期：——

  We report the synthesis and characterisation of mono- and di-nuclear cobalt(II) complexes (1–3) containing L1, a polypyridyl ligand with pyrazole moieties. DNA binding studies suggest that the mono-nuclear complex, 1, binds to DNA via the grooves prior to inducing oxidative DNA cleavage whereas the larger di-nuclear complexes, 2 and 3, bind to DNA via the grooves and through intercalation prior to

  我们报告了单核和双核钴（II）配合物（1-3）的合成和表征，其中配合物L 1为带有吡唑基团的多吡啶基配体。DNA结合研究表明，单核复合物1在诱导氧化性DNA裂解之前通过凹槽与DNA结合，而较大的双核复合物2和3在诱导氧化性裂解之前通过凹槽并通过嵌入与DNA结合。DNA切割。钴（二）复合物对U2OS（骨骨肉瘤），HepG2（肝肝细胞癌）和GM05757（正常人成纤维细胞）细胞具有微摩尔效价，与临床使用的铂试剂，顺铂和卡铂相当。细胞作用机制研究表明，最有效的钴（II）复合物2进入U2OS细胞，穿透细胞核，诱导基因组DNA损伤，并以p53独立的方式触发caspase依赖性凋亡。这项研究强调了双核钴（II）复合物作为人工氧化金属核酸酶和有形癌细胞活性剂的潜力。