6-(二甲基氨基)-3-吡啶羧醛 | 149805-92-5

• 物质功能分类: 医药中间体 - 吡啶类化合物
• 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
• 中文名称: 6-(二甲基氨基)-3-吡啶羧醛
• 中文别名: 6-(二甲基氨基)烟碱醛
• 英文名称: 6-(dimethylamino)nicotinaldehyde
• 英文别名: 6-(dimethylamino)pyridine-3-carbaldehyde；6-(N,N-dimethylamino)nicotinaldehyde
• CAS: 149805-92-5
• 化学式: C₈H₁₀N₂O
• mdl: MFCD08272100
• 分子量: 150.18
• InChiKey: IRDPUZWWWIDFQX-UHFFFAOYSA-N

物化性质

• 熔点：
  57-59°
• 沸点：
  286.2±25.0 °C(Predicted)
• 密度：
  1.135±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  33.2
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933399090
• 危险性防范说明：
  P280
• 危险性描述：
  H302,H317

反应信息

• 作为反应物：
  描述：

  6-(二甲基氨基)-3-吡啶羧醛 在 potassium tert-butylate 、 sodium hydride 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙酸乙酯 为溶剂， 生成 2-(6-Dimethylamino-pyridin-3-yl)-3-oxo-butyronitrile
  参考文献：
  名称：

  Design of 2,5-Dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7-dipropylaminopyrazolo[1,5-a]pyrimidine (NBI 30775/R121919) and Structure−Activity Relationships of a Series of Potent and Orally Active Corticotropin-Releasing Factor Receptor Antagonists

  摘要：

  We have previously shown that 3-phenylpyrazolo[1,5-a]pyrimidines exemplified by 8 were potent antagonists of the human corticotropin-releasing factor-1 receptor. A series of 3-pyridylpyrazolo[1,5-a]pyrimidines 15, 25-30, 34, and 35 containing a weakly basic pyridine ring at the 3-position of the bicyclic nucleus was designed to reduce lipophilicity from the initial leads such as 7. Here, we showed that these 3-pyridyl compounds exhibited potent antagonists at the human CRF1, receptor. Moreover, the hydrophilic and weakly basic pyridine moiety increased the water solubility of some analogues. Compound 26h exhibited good binding affinity at the human CRF1 receptor with a K-i value of 3.5 nM. As a functional antagonist, it dose-dependently inhibited CRF-stimulated cAMP production in cells expressing the CRF1 receptor [IC50 = 50 nM), and CRF-stimulated ACTH release from cultured rat pituitary cells [IC50 = 20 nM). 26h had a log P value of 4.9 and water solubility of greater than 10 mg/mL. Pharmacokinetic studies in rats showed that 26h was orally bioavailable and able to penetrate into the brain. 26h has been demonstrated in vivo efficacy in animal behavioral models that measure anxiolytic activity. These results suggest that analogues from this series were potent CRF1, receptor antagonists with proper physicochemical properties and good pharmacokinetic profiles. 26h was developed into a clinical compound and exhibited efficacy in patients with major depression.

  DOI：

  10.1021/jm040058e
• 作为产物：
  描述：

  2-二甲氨基吡啶 在 溴 、 sodium carbonate 、 magnesium 、 1,2-二溴乙烷 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 6-(二甲基氨基)-3-吡啶羧醛
  参考文献：
  名称：

  Design of 2,5-Dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7-dipropylaminopyrazolo[1,5-a]pyrimidine (NBI 30775/R121919) and Structure−Activity Relationships of a Series of Potent and Orally Active Corticotropin-Releasing Factor Receptor Antagonists

  摘要：

  We have previously shown that 3-phenylpyrazolo[1,5-a]pyrimidines exemplified by 8 were potent antagonists of the human corticotropin-releasing factor-1 receptor. A series of 3-pyridylpyrazolo[1,5-a]pyrimidines 15, 25-30, 34, and 35 containing a weakly basic pyridine ring at the 3-position of the bicyclic nucleus was designed to reduce lipophilicity from the initial leads such as 7. Here, we showed that these 3-pyridyl compounds exhibited potent antagonists at the human CRF1, receptor. Moreover, the hydrophilic and weakly basic pyridine moiety increased the water solubility of some analogues. Compound 26h exhibited good binding affinity at the human CRF1 receptor with a K-i value of 3.5 nM. As a functional antagonist, it dose-dependently inhibited CRF-stimulated cAMP production in cells expressing the CRF1 receptor [IC50 = 50 nM), and CRF-stimulated ACTH release from cultured rat pituitary cells [IC50 = 20 nM). 26h had a log P value of 4.9 and water solubility of greater than 10 mg/mL. Pharmacokinetic studies in rats showed that 26h was orally bioavailable and able to penetrate into the brain. 26h has been demonstrated in vivo efficacy in animal behavioral models that measure anxiolytic activity. These results suggest that analogues from this series were potent CRF1, receptor antagonists with proper physicochemical properties and good pharmacokinetic profiles. 26h was developed into a clinical compound and exhibited efficacy in patients with major depression.

  DOI：

  10.1021/jm040058e

文献信息

• [EN] NMDA RECEPTOR MODULATORS AND USES THEREOF<br/>[FR] MODULATEURS DES RÉCEPTEURS NMDA ET UTILISATIONS DE CEUX-CI
  申请人：CADENT THERAPEUTICS

  公开号：WO2018119374A1

  公开（公告）日：2018-06-28

  Disclosed herein, in part, are heteroaromatic compounds and methods of use in treating neuropsychiatric disorders, e.g., schizophrenia and major depressive disorder. Pharmaceutical compositions and methods of making heteroaromatic compounds are provided. The compounds are contemplated to modulate the NMDA receptor.

  本文披露了部分杂芳化合物及其在治疗神经精神障碍，例如精神分裂症和重度抑郁症中的用途方法。提供了药物组合物和制备杂芳化合物的方法。这些化合物被认为可以调节NMDA受体。
• Synthesis and evaluation of analogues of the tuberculosis drug bedaquiline containing heterocyclic B-ring units
  作者：Peter J. Choi、Hamish S. Sutherland、Amy S.T. Tong、Adrian Blaser、Scott G. Franzblau、Christopher B. Cooper、Manisha U. Lotlikar、Anna M. Upton、Jerome Guillemont、Magali Motte、Laurence Queguiner、Koen Andries、Walter Van den Broeck、William A. Denny、Brian D. Palmer

  DOI：10.1016/j.bmcl.2017.10.042

  日期：2017.12

  bedaquiline where the phenyl B-unit was replaced with monocyclic heterocycles of widely differing lipophilicity (thiophenes, furans, pyridines) were synthesised and evaluated. While there was an expected broad positive correlation between lipophilicity and anti-TB activity, the 4-pyridyl derivatives appeared to have an additional contribution to antibacterial potency. The majority of the compounds were (desirably)

  合成并评估了苯达喹啉的类似物，其中苯B单元被亲脂性差异很大的单环杂环（噻吩，呋喃，吡啶）取代。虽然亲脂性和抗结核活性之间存在广泛的正相关关系，但4-吡啶基衍生物似乎对抗菌效力具有额外的贡献。与贝达喹啉相比，大多数化合物的极性更大（清除率更高），清除率更高，并显示出可接受的口服生物利用度，但其hERG耐受性的改善有限（且无法预测）。
• [EN] VIRAL REPLICATION INHIBITORS<br/>[FR] INHIBITEURS DE REPLICATION VIRALE
  申请人：UNIV LEUVEN KATH

  公开号：WO2013045516A1

  公开（公告）日：2013-04-04

  The present invention relates to a series of novel compounds, methods to prevent or treat viral infections in animals by using the novel compounds and to said novel compounds for use as a medicine, more preferably for use as a medicine to treat or prevent viral infections, particularly infections with RNA viruses, more particularly infections with viruses belonging to the family of the Flaviviridae, and yet more particularly infections with the Dengue virus. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the novel compounds, to the compositions or preparations for use as a medicine, more preferably for the prevention or treatment of viral infections. The invention also relates to processes for preparation of the compounds.

  本发明涉及一系列新化合物，通过使用这些新化合物来预防或治疗动物的病毒感染的方法，以及将这些新化合物用作药物，更好地用于治疗或预防病毒感染，特别是感染RNA病毒，更特别是感染属于黄病毒科的病毒，更特别是感染登革病毒。本发明还涉及这些新化合物的药物组合或混合制剂，用作药物的组合或制剂，更好地用于预防或治疗病毒感染。该发明还涉及这些化合物的制备方法。
• [EN] 1-(6 MEMBERS AZO-HETEROCYCLIC)-PYRROLIN-2-ONE COMPOUNDS AS INHIBITORS OF HEPATITIS C NS5B POLYMERASE, THE PHARMACEUTICAL COMPOSITION THEREOF AND THEIR THERAPEUTIC USE<br/>[FR] COMPOSÉS 1-(AZO-HÉTÉROCYCLE À 6 CHAÎNONS)-PYRROLIN-2-ONE COMME INHIBITEURS DE POLYMÉRASE NS5B D'HÉPATITE C, LEUR COMPOSITION PHARMACEUTIQUE ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：VIVALIS

  公开号：WO2011004017A1

  公开（公告）日：2011-01-13

  The present invention concerns a l-(6 members azo-heterocyclic)-pyrrolin-2-one compound of the following formula I or a salt, solvate, tautomer, isotope, enantiomer, diastereoisomer or racemic mixture thereof: the pharmaceutical composition thereof and their therapeutic use as inhibitors of Hepatitis C NS5B polymerase.

  本发明涉及以下式I的l-(6成员偶氮杂环)-吡咯烷-2-酮化合物或其盐、溶剂合物、互变异构体、同位素、对映体、非对映异构体或其外消旋混合物：以及其药物组合物及作为丙型肝炎NS5B聚合酶抑制剂的治疗用途。
• [EN] SUBSTITUTED PYRAZOLO[1,5-A]PYRIDINE COMPOUNDS AS RET KINASE INHIBITORS<br/>[FR] COMPOSÉS SUBSTITUÉS DE PYRAZOLO[1,5-A]PYRIDINES COMME INHIBITEURS DE LA KINASE RET
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2017011776A1

  公开（公告）日：2017-01-19

  Provided herein are compounds of the General Formula I: and stereoisomers and pharmaceutically acceptable salts or solvates thereof, in which A, B, D, E, X1, X2, X3 and X4 have the meanings given in the specification, which are inhibitors of RET kinase and are useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including diseases or disorders mediated by a RET kinase.

  本文提供了一般式I的化合物及其立体异构体和药用可接受的盐或溶剂，其中A、B、D、E、X1、X2、X3和X4的含义如规范中所述，这些化合物是RET激酶的抑制剂，可用于治疗和预防可以用RET激酶抑制剂治疗的疾病，包括由RET激酶介导的疾病或紊乱。