N-(4-hydroxybutyl)-6-methylpicolinamide

• 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: N-(4-hydroxybutyl)-6-methylpicolinamide
• 英文别名: N-(4-hydroxybutyl)-6-methylpyridine-2-carboxamide
• 化学式: C₁₁H₁₆N₂O₂
• 分子量: 208.26
• InChiKey: HWAFSDMZHJGSNA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  62.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(4-hydroxybutyl)-6-methylpicolinamide 在 四溴化碳 、 三乙胺 、 三苯基膦 作用下， 以 乙腈 为溶剂， 反应 14.0h， 生成 N-(4-(4-(3-methoxyphenyl)piperazin-1-yl)butyl)-6-methylpyridine-2-carboxamide
  参考文献：
  名称：

  Targeting Dopamine D₃ and Serotonin 5-HT_1A and 5-HT_2A Receptors for Developing Effective Antipsychotics: Synthesis, Biological Characterization, and Behavioral Studies

  摘要：

  Combination of dopamine D-3 antagonism, serotonin 5-HT1A partial agonism, and antagonism at 5-HT2A leads to a novel approach to potent atypical antipsychotics. Exploitation of the original structureactivity relationships resulted in the identification of safe and effective antipsychotics devoid of extrapyramidal symptoms liability, sedation, and catalepsy. The potential atypical antipsychotic 5bb was selected for further pharmacological investigation. The distribution of c-fos positive cells in the ventral striatum confirmed the atypical antipsychotic profile of 5bb in agreement with behavioral rodent studies. 5bb administered orally demonstrated a biphasic effect on the MK801-induced hyperactivity at dose levels not able to induce sedation, catalepsy, or learning impairment in passive avoidance. In microdialysis studies, 5bb increased the dopamine efflux in the medial prefrontal cortex. Thus, 5bb represents a valuable lead for the development of atypical antipsychotics endowed with a unique pharmacological profile for addressing negative symptoms and cognitive deficits in schizophrenia.

  DOI：

  10.1021/jm501119j
• 作为产物：
  描述：

  6-甲基-2-吡啶甲酸 、 4-氨基-1-丁醇 在 N-甲基吗啉 、 氯甲酸异丁酯 作用下， 以 二氯甲烷 为溶剂， 以83 %的产率得到N-(4-hydroxybutyl)-6-methylpicolinamide
  参考文献：
  名称：

  镍催化 1,2-烷基硼化和艾伦烯硅烷化生成 [1,3]-双有机金属试剂

  摘要：

  报道了一种镍催化的多组分反应，可以快速可靠地从丙二烯中获得[1,3]-双有机金属试剂。该方案表现出可预测的区域选择性模式，能够在温和条件下将 B,B(Si) 片段掺入丙二烯主链上，从而为从现成的前体中获取具有 sp 2和 sp 3杂交的多有机金属试剂提供了一个补充平台。

  DOI：

  10.1021/acs.orglett.3c03574

文献信息

• Targeting Dopamine D₃ and Serotonin 5-HT_1A and 5-HT_2A Receptors for Developing Effective Antipsychotics: Synthesis, Biological Characterization, and Behavioral Studies
  作者：Margherita Brindisi、Stefania Butini、Silvia Franceschini、Simone Brogi、Francesco Trotta、Sindu Ros、Alfredo Cagnotto、Mario Salmona、Alice Casagni、Marco Andreassi、Simona Saponara、Beatrice Gorelli、Pia Weikop、Jens D. Mikkelsen、Jorgen Scheel-Kruger、Karin Sandager-Nielsen、Ettore Novellino、Giuseppe Campiani、Sandra Gemma

  DOI：10.1021/jm501119j

  日期：2014.11.26

  Combination of dopamine D-3 antagonism, serotonin 5-HT1A partial agonism, and antagonism at 5-HT2A leads to a novel approach to potent atypical antipsychotics. Exploitation of the original structureactivity relationships resulted in the identification of safe and effective antipsychotics devoid of extrapyramidal symptoms liability, sedation, and catalepsy. The potential atypical antipsychotic 5bb was selected for further pharmacological investigation. The distribution of c-fos positive cells in the ventral striatum confirmed the atypical antipsychotic profile of 5bb in agreement with behavioral rodent studies. 5bb administered orally demonstrated a biphasic effect on the MK801-induced hyperactivity at dose levels not able to induce sedation, catalepsy, or learning impairment in passive avoidance. In microdialysis studies, 5bb increased the dopamine efflux in the medial prefrontal cortex. Thus, 5bb represents a valuable lead for the development of atypical antipsychotics endowed with a unique pharmacological profile for addressing negative symptoms and cognitive deficits in schizophrenia.
• Ni-Catalyzed 1,2-Alkyl Borylation and Silylation of Allenes En Route to [1,3]-Bis-Organometallic Reagents
  作者：Álvaro Velasco-Rubio、Fei Cong、Yubiao Tian、Ruben Martin

  DOI：10.1021/acs.orglett.3c03574

  日期：2023.12.29

  reaction that rapidly and reliably accesses [1,3]-bis-organometallic reagents from allenes is reported. The protocol exhibits a predictable regioselectivity pattern that enables the incorporation of B,B(Si) fragments across the allene backbone under mild conditions, thus offering a complementary platform for accessing polyorganometallic reagents possessing both sp2 and sp3 hybridization from readily available

  报道了一种镍催化的多组分反应，可以快速可靠地从丙二烯中获得[1,3]-双有机金属试剂。该方案表现出可预测的区域选择性模式，能够在温和条件下将 B,B(Si) 片段掺入丙二烯主链上，从而为从现成的前体中获取具有 sp 2和 sp 3杂交的多有机金属试剂提供了一个补充平台。