6-(1H-pyrrol-2-yl)pyridine-2-carboxaldehyde | 208110-99-0

• 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: 6-(1H-pyrrol-2-yl)pyridine-2-carboxaldehyde
• 英文别名: 6-(1H-pyrrol-2-yl)pyridine-2-carbaldehyde
• CAS: 208110-99-0
• 化学式: C₁₀H₈N₂O
• 分子量: 172.186
• InChiKey: XOBKZSYPCZGOSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 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：
  45.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-(1H-pyrrol-2-yl)pyridine-2-carboxaldehyde 在 钾硼氢 、 TEA 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 8.0h， 生成 (3,4-Dichloro-phenyl)-[4-({[6-(1H-pyrrol-2-yl)-pyridine-2-ylmethyl]-amino}-methyl)-piperidine-1-yl]-methanone
  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
• 作为产物：
  描述：

  6-氯-2-羟甲基吡啶 在 镍 盐酸 、 六甲基磷酰三胺 、 4-二甲氨基吡啶 、 manganese(IV) oxide 、 四(三苯基膦)钯 、 Ti₂CO₃ 、 4 A molecular sieve 、 氢气 、 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 吡啶 、 乙醇 、 二氯甲烷 、 苯 为溶剂， 反应 58.0h， 生成 6-(1H-pyrrol-2-yl)pyridine-2-carboxaldehyde
  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

• Pyridin-2-yl-methylamine derivatives, method of preparing and
  申请人：Pierre Fabre Medicament

  公开号：US06020345A1

  公开（公告）日：2000-02-01

  The invention concerns novel pyridin-2-yl-methylamine derivatives of formula (I): ##STR1## in which: u represents hydrogen or methyl; v represents hydrogen, chlorine, or methyl; w represents hydrogen, fluorine, or methyl; x represents hydrogen or fluorine; y represents chlorine or methyl; z represents hydrogen, fluorine, chlorine, or methyl; A represents hydrogen, fluorine, chlorine, C.sub.1 -C.sub.5 alkyl, fluoroalkyl, cyclopropyl, a 5-membered aromatic heterocyclic group, alkoxy or alkythio, amino, cyclic amino, or alkoxycarbonyl. These compounds are useful as medicines, in particular as antidepressants or analgesics.

  本发明涉及一种新颖的吡啶-2-基甲胺衍生物，其通式为(I)：##STR1## 其中：u代表氢或甲基；v代表氢、氯或甲基；w代表氢、氟或甲基；x代表氢或氟；y代表氯或甲基；z代表氢、氟、氯或甲基；A代表氢、氟、氯、C1-C5烷基、氟代烷基、环丙基、5元芳香杂环基团、烷氧基、硫代烷基、氨基、环状氨基或烷氧羰基。这些化合物可作为药物使用，特别是作为抗抑郁药或镇痛药。
• Efficient Electrochemical Water Oxidation Mediated by Pyridylpyrrole-Carboxylate Ruthenium Complexes
  作者：Guo Chen、Ze-Wen Chen、Yuan-Mei Wang、Piao He、Chao Liu、Hai-Xia Tong、Xiao-Yi Yi

  DOI：10.1021/acs.inorgchem.1c02251

  日期：2021.10.18

  behaves as a WOC as determined by electrochemical measurement and has an ultrahigh electrocatalytic current density of 8.17 mA cm–2 at 1.55 V (vs NHE) with a low onset potential of 0.352 V (vs NHE), a turnover number of 241, a turnover frequency of 203.39 s–1, and kcat of 16.34 s–1 under neutral conditions. The H2O/pic exchange of the complexes accompanied by oxidation of a ruthenium center is the initial

  在作为分子水氧化催化剂 (WOC) 的 Ru 基配合物快速增长的推动下，我们提出了带有吡啶基吡咯 - 羧酸盐 (H 2 pPC) 配体的新型钌 (II) 配合物作为 WOC 家族的成员。这些复合物的结构具有4-甲基吡啶（PIC）/二甲亚砜（DMSO）中的[Ru（PPC）（PIC）2（DMSO）]和PIC / PIC中的[Ru（PPC）（PIC）3 ]作为轴向配体. 另一个 pPC 2-配体和一个 PIc 配体位于赤道位置。[Ru(pPC)(PIc) 2 (DMSO)]表现为电化学测量所确定的 WOC，并具有 8.17 mA cm –2的超高电催化电流密度在 1.55 V (vs NHE) 下具有 0.352 V (vs NHE) 的低起始电位、241 的周转次数、203.39 s –1的周转频率和16.34 s –1在中性条件下的k cat。配合物的 H 2 O/PIc 交换伴随着钌中心的
• [EN] PYRIDIN-2-YL-METHYLAMINE DERIVATIVES, METHOD OF PREPARING AND APPLICATION AS MEDICINE<br/>[FR] DERIVES DE LA PYRIDIN-2-YL-METHYLAMINE, LEUR PROCEDE DE PREPARATION ET LEUR APPLICATION COMME MEDICAMENTS
  申请人：PIERRE FABRE MEDICAMENT

  公开号：WO1998022459A1

  公开（公告）日：1998-05-28

  (EN) The invention concerns novel pyridin-2-yl-methylamine derivatives of formula (I) in which: u represents a hydrogen atom or a methyl radical; v represents a hydrogen atom or a chlorine atom or a methyl radical; w represents a hydrogen atom or a fluorine atom or a methyl radical; x represents a hydrogen atom or a fluorine atom; y represents a chlorine atom or a methyl radical; z represents a hydrogen atom or a fluorine atom or a chlorine atom or a methyl radical; A represents a hydrogen atom or a fluorine atom or a chlorine atom; a C1-C5 alkyl radical; a fluoroalkyl radical; a cyclopropyl radical; an aromatic heterocyclic group with 5 chains; an alkoxy or alkythio group; an amine group; an amino cyclic group; an alkoxycarbonyl group. These compounds are useful as medicine in particular as antidepressant or analgesic.(FR) La présente invention concerne de nouveaux dérivés de la pyridin-2-yl-méthylamine de formule (I) dans laquelle: u représente un atome d'hydrogène ou un radical méthyl; v représente un atome d'hydrogène ou un atome de chlore ou un radical méthyl; w représente un atome d'hydrogène ou un atome de fluor ou un radical méthyl; x représente un atome d'hydrogène ou un atome de fluor; y représente un atome de chlore ou un radical méthyl; z représente un atome d'hydrogène ou un atome de fluor ou un atome de chlore ou un radical méthyl; A représente: un atome d'hydrogène ou un atome de fluor ou un atome de chlore; un radical alkyl en C1-C5; un radical fluoroalkyl; un radical cyclopropyl; un groupe hétérocyclique aromatique à 5 chaînons; un groupe alkoxy ou alkylthio; un groupe amino; un groupe amino cyclique; un groupe alkoxycarbonyl. Ces composés sont utiles comme médicaments notamment comme antidépresseurs et analgésiques.

  该发明涉及公式（I）的新型吡啶-2-基甲胺衍生物：其中，u代表氢原子或甲基基团；v代表氢原子或氯原子或甲基基团；w代表氢原子或氟原子或甲基基团；x代表氢原子或氟原子；y代表氯原子或甲基基团；z代表氢原子或氟原子或氯原子或甲基基团；A代表氢原子或氟原子或氯原子；C1-C5烷基基团；氟烷基基团；环丙基基团；带有5个链的芳香杂环基团；烷氧基或烷硫基团；胺基团；氨基环基团；烷氧羰基团。这些化合物在医学上有用，特别是作为抗抑郁剂或镇痛剂。
• DERIVES DE LA PYRIDIN-2-YL-METHYLAMINE, LEUR PROCEDE DE PREPARATION ET LEUR APPLICATION COMME MEDICAMENTS
  申请人：PIERRE FABRE MEDICAMENT

  公开号：EP0946546A1

  公开（公告）日：1999-10-06
• US6020345A
  申请人：——

  公开号：US6020345A

  公开（公告）日：2000-02-01