6-(甲硫基)-2-吡啶甲醛 | 217657-76-6

• 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-(甲硫基)-2-吡啶甲醛
• 英文名称: 6-(methylthio)pyridine-2-carboxaldehyde
• 英文别名: 6-(methylthio)pyridine-2-carbaldehyde；6-(Methylthio)picolinaldehyde；6-methylsulfanylpyridine-2-carbaldehyde
• CAS: 217657-76-6
• 化学式: C₇H₇NOS
• 分子量: 153.205
• InChiKey: QVYAMTAWGBAROE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  55.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(甲硫基)-2-吡啶甲醛 在 TEA 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 4.0h， 生成
  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：

  2-(1,3-dioxolan-2-yl)-6-fluoropyridin 在 甲酸 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 6-(甲硫基)-2-吡啶甲醛
  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

• RET选择性抑制剂及其制备方法和用途
  申请人：首药控股（北京）有限公司

  公开号：CN112209925A

  公开（公告）日：2021-01-12

  本发明提供了RET选择性抑制剂及其制备方法和用途；本发明提供了式(I)化合物及其药学上可接受的盐、溶剂化物、多晶型物或异构体、包含这些化合物的药物组合物，以及此类化合物在治疗跟RET相关的疾病中的用途。
• Hydroxy alkyl substituted 1,3,8-triazaspiro[4.5]decan-4-one derivatives useful for the treatment of ORL-1receptor mediated disorders
  申请人：——

  公开号：US20040142955A1

  公开（公告）日：2004-07-22

  The present invention is directed to novel hydroxy alkyl substituted 1,3,8-triazaspiro[4.5]decan-4-one derivatives of the general formula 1 wherein all variables are as defined herein, useful in the treatment of disorders and conditions mediated by the ORL-1 G-protein coupled receptor. More particularly, the compounds of the present invention are useful in the treatment of disorders and conditions such as anxiety, depression, panic, dementia, mania, bipolar disorder, substance abuse, neuropathic pain, acute pain, chronic pain, migraine, asthma, cough, psychosis, schizophrenia, epilepsy, hypertension, obesity, eating disorders, cravings, diabetes, cardiac arrhythmia, irritable bowel syndrome, Crohn's disease, urinary incontinence, adrenal disorders, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), Alzheimer's disease, for improved cognition or memory and for mood stabilization.

  本发明涉及一种新型的羟基烷基取代的1,3,8-三氮杂螺[4.5]癸烷-4-酮衍生物，其一般式为1，其中所有变量如本文所定义，可用于治疗由ORL-1 G蛋白偶联受体介导的疾病和症状。特别地，本发明的化合物可用于治疗焦虑、抑郁、恐慌、痴呆、躁狂、双相情感障碍、物质滥用、神经病性疼痛、急性疼痛、慢性疼痛、偏头痛、哮喘、咳嗽、精神病、精神分裂症、癫痫、高血压、肥胖症、进食障碍、渴望、糖尿病、心律失常、肠易激综合征、克罗恩病、尿失禁、肾上腺疾病、注意力缺陷障碍（ADD）、注意力缺陷多动障碍（ADHD）、阿尔茨海默病，用于改善认知或记忆能力和情绪稳定。
• Hydroxy alkyl substituted 1,3,8-triazaspiro[4.5]decan-4-one derivatives useful for the treatment of ORL-1 receptor mediated disorders
  申请人：Battista Kathleen

  公开号：US20060030577A1

  公开（公告）日：2006-02-09

  The present invention is directed to novel hydroxy alkyl substituted 1,3,8-triazaspiro[4.5]decan-4-one derivatives of the general formula wherein all variables are as defined herein, useful in the treatment of disorders and conditions mediated by the ORL-1 G-protein coupled receptor. More particularly, the compounds of the present invention are useful in the treatment of disorders and conditions such as anxiety, depression, panic, dementia, mania, bipolar disorder, substance abuse, neuropathic pain, acute pain, chronic pain, migraine, asthma, cough, psychosis, schizophrenia, epilepsy, hypertension, obesity, eating disorders, cravings, diabetes, cardiac arrhythmia, irritable bowel syndrome, Crohn's disease, urinary incontinence, adrenal disorders, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), Alzheimer's disease, for improved cognition or memory and for mood stabilization.

  本发明涉及一种新的羟基烷基取代的1,3,8-三氮杂螺[4.5]癸酮衍生物，其通式如下： 其中所有变量如本文所定义，可用于治疗由ORL-1 G蛋白偶联受体介导的疾病和病症。更具体地，本发明的化合物可用于治疗焦虑、抑郁、惊恐、痴呆、躁狂、双相障碍、物质滥用、神经病性疼痛、急性疼痛、慢性疼痛、偏头痛、哮喘、咳嗽、精神病、精神分裂症、癫痫、高血压、肥胖症、进食障碍、渴望、糖尿病、心脏心律失常、肠易激综合征、克罗恩病、尿失禁、肾上腺疾病、注意力缺陷障碍（ADD）、注意力缺陷多动障碍（ADHD）、阿尔茨海默病，以改善认知或记忆，并用于情绪稳定。
• HYDROXY ALKYL SUBSTITUTED 1,3,8-TRIAZASPIRO[4.5]DECAN-4-ONE DERIVATIVES USEFUL FOR THE TREATMENT OF ORL-1 RECEPTOR MEDIATED DISORDERS
  申请人：BATTISTA Kathleen

  公开号：US20090124614A1

  公开（公告）日：2009-05-14

  The present invention is directed to novel hydroxy alkyl substituted 1,3,8-triazaspiro[4.5]decan-4-one derivatives of the general formula wherein all variables are as defined herein, useful in the treatment of disorders and conditions mediated by the ORL-1 G-protein coupled receptor. More particularly, the compounds of the present invention are useful in the treatment of disorders and conditions such as anxiety, depression, panic, dementia, mania, bipolar disorder, substance abuse, neuropathic pain, acute pain, chronic pain, migraine, asthma, cough, psychosis, schizophrenia, epilepsy, hypertension, obesity, eating disorders, cravings, diabetes, cardiac arrhythmia, irritable bowel syndrome, Crohn's disease, urinary incontinence, adrenal disorders, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), Alzheimer's disease, for improved cognition or memory and for mood stabilization.

  本发明涉及一种新型的羟基烷基取代的1,3,8-三氮杂螺[4.5]癸酮衍生物，其通式如下：其中所有变量均如本文所定义，可用于治疗由ORL-1 G蛋白偶联受体介导的疾病和症状。更具体地，本发明的化合物可用于治疗焦虑、抑郁、惊恐、痴呆、躁狂、双相情感障碍、物质滥用、神经病性疼痛、急性疼痛、慢性疼痛、偏头痛、哮喘、咳嗽、精神病、精神分裂症、癫痫、高血压、肥胖症、进食障碍、渴望、糖尿病、心律失常、肠易激综合征、克罗恩病、尿失禁、肾上腺疾病、注意力缺陷障碍（ADD）、注意力缺陷多动障碍（ADHD）、阿尔茨海默病，以改善认知或记忆，并用于情绪稳定。
• HYDROXY ALKYL SUBSTITUTED 1,3,8-TRIAZASPIRO 4.5]DECAN-4-ONE DERIVATIVES USEFUL FOR THE TREATMENT OF ORL-1 RECEPTOR MEDIATED DISORDERS
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP1601674A2

  公开（公告）日：2005-12-07