2-(4-methylpiperazin-1-yl)nicotinaldehyde | 872882-89-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-(4-methylpiperazin-1-yl)nicotinaldehyde
• 英文别名: 2-(4-methyl-piperazin-1-yl)-pyridine-3-carbaldehyde；2-(4-Methylpiperazin-1-yl)pyridine-3-carbaldehyde
• CAS: 872882-89-8
• 化学式: C₁₁H₁₅N₃O
• mdl: MFCD07381409
• 分子量: 205.26
• InChiKey: ILKHLPMNIKYZHG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  36.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2-氨基苯基)吡咯 、 2-(4-methylpiperazin-1-yl)nicotinaldehyde 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 以53%的产率得到4-(2-(4-methylpiperazin-1-yl)pyridin-3-yl)-4,5-dihydropyrrolo[1,2-a]quinoxaline
  参考文献：
  名称：

  作为有效和选择性 Sirt6 激活剂的吡咯并[1,2-a]喹喔啉基衍生物的设计、合成和药理学评价

  摘要：

  Sirt6 激活已成为治疗各种人类疾病的有前景的药物靶点，但目前仅报道了有限的 Sirt6 激活剂。在此，一系列新型吡咯并[1,2- a ]喹喔啉衍生物已被鉴定为具有低细胞毒性的有效、选择性Sirt6激活剂。 Sirt6 敲低研究结果验证了此类 Sirt6 激活剂的靶向作用。对接研究表明， 38侧链上的质子化氮与 Trp188 形成 π 阳离子相互作用，进一步将其稳定在这个扩展的结合袋中。新化合物35、36、38、46、47和50强烈抑制 LPS 诱导的促炎细胞因子/趋化因子的产生，而38也显着抑制 SARS - CoV -2 感染，EC 50值为 9.3 μM。此外，化合物36显着抑制癌细胞集落形成。这些新分子可以作为有用的药理学工具或针对癌症、炎症和传染病的潜在疗法。

  DOI：

  10.1016/j.ejmech.2022.114998
• 作为产物：
  描述：

  N-甲基哌嗪 、 2-氯-3-吡啶甲醛 以 甲苯 为溶剂， 生成 2-(4-methylpiperazin-1-yl)nicotinaldehyde
  参考文献：
  名称：

  作为有效和选择性 Sirt6 激活剂的吡咯并[1,2-a]喹喔啉基衍生物的设计、合成和药理学评价

  摘要：

  Sirt6 激活已成为治疗各种人类疾病的有前景的药物靶点，但目前仅报道了有限的 Sirt6 激活剂。在此，一系列新型吡咯并[1,2- a ]喹喔啉衍生物已被鉴定为具有低细胞毒性的有效、选择性Sirt6激活剂。 Sirt6 敲低研究结果验证了此类 Sirt6 激活剂的靶向作用。对接研究表明， 38侧链上的质子化氮与 Trp188 形成 π 阳离子相互作用，进一步将其稳定在这个扩展的结合袋中。新化合物35、36、38、46、47和50强烈抑制 LPS 诱导的促炎细胞因子/趋化因子的产生，而38也显着抑制 SARS - CoV -2 感染，EC 50值为 9.3 μM。此外，化合物36显着抑制癌细胞集落形成。这些新分子可以作为有用的药理学工具或针对癌症、炎症和传染病的潜在疗法。

  DOI：

  10.1016/j.ejmech.2022.114998

文献信息

• Pyridyl piperazines for the treatment of CNS disorders
  申请人：Brodney A. Michael

  公开号：US20060025421A1

  公开（公告）日：2006-02-02

  This invention is directed to compounds of Formula I and to pharmaceutical compositions comprising the compound of Formula I. where the dashed line represents an optional double bond; and where n is 1 or 2, and Ar 1 , Ar 2 , . . . and Z are as defined in the specification. The invention is also directed to a method of treating a disorder or condition that can be treated by altering serotonin-mediated neurotransmission, such as migraine, headache, cluster headache, anxiety, depression, etc. This invention is also directed to intermediates useful in the synthesis of compounds of Formula I.

  这项发明涉及到式I化合物和包括式I化合物的药物组合物；其中虚线代表可选的双键；n为1或2，Ar1、Ar2等为规范中定义的化学基团。该发明还涉及一种治疗可以通过改变5-羟色胺介导的神经传递来治疗的疾病或症状的方法，如偏头痛、头痛、集群头痛、焦虑、抑郁等。该发明还涉及在合成式I化合物过程中有用的中间体。
• Structure-activity relationship studies on Bax activator SMBA1 for the treatment of ER-positive and triple-negative breast cancer
  作者：Gang Liu、Tao Yin、Hyejin Kim、Chunyong Ding、Zhuo Yu、Hong Wang、Haiying Chen、Ruping Yan、Eric A. Wold、Hao Zou、Xi Liu、Ye Ding、Qiang Shen、Jia Zhou

  DOI：10.1016/j.ejmech.2019.06.004

  日期：2019.9

  In an effort to develop novel Bax activators for breast cancer treatment, a series of diverse analogues have been designed and synthesized based on lead compound SMBA1 through several strategies, including introducing various alkylamino side chains to have a deeper access to S184 pocket, replacing carbon atoms with nitrogen, and reducing the nitro group of 9H-fluorene scaffold. Compounds 14 (CYD-2-11) and 49 (CYD-4-61) have been identified to exhibit significantly improved antiproliferative activity compared to SMBA1, with IC50 values of 3.22 mu M and 0.07 mu M against triple-negative breast cancer MDA-MB-231 and 3.81 mu M and 0.06 mu M against ER-positive breast cancer MCF-7 cell lines, respectively. Mechanism of action studies of compound 49 indicated that it can activate Bax protein to induce cytochrome c release and regulate apoptotic biomarkers, leading to cancer cell apoptosis. Further in vivo efficacy studies of compounds 14 and 49 in nude mice bearing MDA-MB-231 tumor xenografts demonstrated that these drug candidates can significantly suppress tumor growth, indicating their therapeutic potential for the treatment of breast cancer. (C) 2019 Elsevier Masson SAS. All rights reserved.
• PYRIDYL PIPERAZINES FOR THE TREATMENT OF CNS DISORDERS
  申请人：Pfizer Products Inc.

  公开号：EP1768975A2

  公开（公告）日：2007-04-04
• [EN] PYRIDYL PIPERAZINES FOR THE TREATMENT OF CNS DISORDERS<br/>[FR] PYRIDYLE PIPÉRAZINES POUR LE TRAITEMENT DES TROUBLES DU SNC
  申请人：PFIZER PROD INC

  公开号：WO2006000912A2

  公开（公告）日：2006-01-05

  This invention is directed to compounds of Formula (I) and to pharmaceutical compositions comprising the compound of Formula (I) or a prodrug thereof and a pharmaceutically effective carrier. where G is G 1 or G2; where the dashed line represents an optional double bond; and where n is 1 or 2, and Ar1, Ar2, ... and Z are as defined in the specification. The invention is also directed to a method of treating or preventing in mammals, including humans, a disorder or condition that can be treated by altering serotonin-mediated neurotransmission, including a disorder selected from the group consisting of migraine, headache, cluster headache, anxiety, depression, dysthymia, major depressive disorder, migraine, post-traumatic stress disorder, avoidant personality disorder, borderline personality disorder and phobias This invention is also directed to intermediates useful in the synthesis of compounds of Formula (I).
• [EN] PIPERAZINYLPHENALKYL LACTAM/AMINE LIGANDS FOR THE 5HT1B RECEPTOR<br/>[FR] LIGANDS DE LATAME/AMINE PIPERAZINYLPHENALKYLE POUR LE RECEPTEUR 5HT1B
  申请人：PFIZER PROD INC

  公开号：WO2006048727A1

  公开（公告）日：2006-05-11

  [EN] The present invention relates to novel derivatives, that are compounds of Formula (I), wherein R₁, R₂, R₃, R₁₄, X, Y, n and m are defined herein, their pharmaceutically acceptable salts, pharmaceutical compositions and methods using said compounds in treating or preventing depression, anxiety, obsessive compulsive disorder (OCD) and other disorders for which selective antagonists, inverse agonists and partial agonists of serotonin 1 (5-HT₁) receptors, specifically, antagonists of 5-HT_1B are useful.
  [FR] Nouveaux dérivés, qui sont des composés de formule (I), dans laquelle R₁, R₂, R₃, R₁₄, X, Y, n et m sont tels que définis dans le descriptif, leurs sels pharmaceutiquement acceptables, compositions pharmaceutiques et procédés utilisant de tels composés dans le traitement et la prévention de la dépression, de l'anxiété, du trouble obsessionnel-compulsif (OCD) et d'autres troubles pour lesquels on utilise des antagonistes sélectifs, des agonistes inverses et des agonistes partiels de récepteurs de la sérotonine 1 (5-HT₁), des antagonistes de récepteurs 5-HT_1B.