4-(4-(2-(tert-butyl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)butan-1-amine

• 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: 4-(4-(2-(tert-butyl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)butan-1-amine
• 英文别名: 4-(4-(2-(Tert-butyl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)butan-1-amine；4-[4-[2-tert-butyl-6-(trifluoromethyl)pyrimidin-4-yl]piperazin-1-yl]butan-1-amine
• 化学式: C₁₇H₂₈F₃N₅
• 分子量: 359.438
• InChiKey: YRATXPOXRFWIPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  58.3
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-(4-(2-(tert-butyl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)butan-1-amine 在 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 N-(4-(4-(2-(tert-butyl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)butyl)piperazine-1-carboxamide
  参考文献：
  名称：

  [EN] UREA AND AMIDE DERIVATIVES OF AMINOALKYLPIPERAZINES AND USE THEREOF
  [FR] DÉRIVÉS URÉE ET AMIDE D'AMINOALKYLPIPÉRAZINES ET LEUR UTILISATION

  摘要：

  本文提供的化合物的化学式为：其中Y、Ri和R2在本文中有定义；它们的药物可接受的盐、氘代形式、异构体、溶剂化物和混合物。这些化合物可用于治疗患有部分多巴胺D2/D3受体的激动剂或拮抗剂治疗的疾病的患者，特别适用于患有精神分裂症、抑郁症、神经退行性疾病（如帕金森病）、运动障碍、物质滥用和复发物质滥用以及对可卡因、甲基苯丙胺、尼古丁和酒精等物质上瘾的患者、青光眼、认知障碍、不宁腿综合症、注意力缺陷多动障碍、高泌乳素血症、自闭症、运动障碍（如不安、僵硬、肌张力障碍）以及各种泌尿道和其他神经系统疾病的患者。此外，还提供了制备本文所述化合物的方法。

  公开号：

  WO2014059265A1
• 作为产物：
  描述：

  2-叔丁基-4-氯-6-(三氟甲基)嘧啶 在 potassium carbonate 、 一水合肼 作用下， 以 甲醇 、 乙醇 、 乙腈 为溶剂， 反应 16.0h， 生成 4-(4-(2-(tert-butyl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)butan-1-amine
  参考文献：
  名称：

  一系列 [4-(4-Carboxamidobutyl)]-1-arylpiperazines 的设计、合成和结构-活性关系研究：洞察有助于多巴胺 D3 与 D2 受体亚型选择性的结构特征

  摘要：

  多巴胺 D3 受体 (D3R) 的拮抗剂和部分激动剂调节剂已成为治疗药物滥用和神经精神疾病的有希望的疗法。然而，由于 D3R 和多巴胺 D2 受体 (D2R) 之间的高度序列同源性，开发对 D3 受体具有选择性的药物样先导化合物一直具有挑战性。在这项工作中，我们合成了一系列包含氮杂芳族单元的酰基氨基丁基哌嗪，并评估了它们对 D3 和 D2 受体的结合和功能活性。对接研究和对一组嵌合和突变受体的评估结果表明，TM7 细胞外末端的相互作用有助于这些配体的 D3R 与 D2R 选择性。

  DOI：

  10.1021/jm500801r

文献信息

• Pyrimidin-2-one compounds and their use as dopamine d3 receptor ligands
  申请人：Geneste Herve

  公开号：US20060235004A1

  公开（公告）日：2006-10-19

  The invention relates to pyrimidin 2-one compounds of general formula (I), in addition to the derivatives and tautomers of (I) and the physiologically acceptable salts of said compounds. In said formula, A represents linear or branched C 3 -C 6 alkene, which can have a double bond or triple bond and/or a group Z, which is not adjacent to the nitrogen atom of the pyrimidinone ring and is selected from O, S, C(O), NR 3 , C(O)NR 3 , NR 3 C(O), OC(O) and C(O)O; B represents a group of the formula (II), in which X stands for CH 2 or N and Y stands for CH 2 or CH 2 CH 2 , or X—Y can also jointly represent C═CH, C═CH—CH 2 or CH—CH═CH; R 1 and R 2 are defined as cited in the description and the claims; and Ar represents an optionally substituted aromatic group. The invention also relates to a pharmaceutical agent, containing at least one compound (I) and the tautomers, derivatives and/or acid addition salts of said compound, optionally together with physiologically acceptable carriers and/or auxiliary agents. The invention also relates to the use of compounds of formula (I), and their tautomers, derivatives and pharmacologically acceptable acid addition salts for producing a phrmaceutical agent for treating diseases which respond to the influence of dopamine D 3 receptor ligands.

  本发明涉及一般式(I)的嘧啶2-酮化合物，以及(I)的衍生物和互变异构体以及所述化合物的生理上可接受的盐。 在该式中，A代表线性或支链C3-C6烯烃，可以具有双键或三键和/或Z基团，该基团不靠近嘧啶酮环的氮原子，并从O，S，C（O），NR3，C（O）NR3，NR3C（O），OC（O）和C（O）O中选择; B代表式（II）的基团，其中X代表CH2或N，Y代表CH2或CH2CH2，或X-Y也可以共同表示C═CH，C═CH-CH2或CH-CH═CH; R1和R2如描述和权利要求中所述; Ar代表可选的取代芳香族基团。 本发明还涉及一种制药剂，其中包含至少一种化合物(I)和所述化合物的互变异构体，衍生物和/或酸加成盐，可选地与生理上可接受的载体和/或辅助剂一起使用。 本发明还涉及使用化合物(I)及其互变异构体，衍生物和药理学上可接受的酸加成盐制备用于治疗对多巴胺D3受体配体影响有反应的疾病的制药剂。
• UREA AND AMIDE DERIVATIVES OF AMINOALKYLPIPERAZINES AND USE THEREOF
  申请人：SOUTHERN RESEARCH INSTITUTE

  公开号：US20150232435A1

  公开（公告）日：2015-08-20

  Provided are compounds represented by the formula: with Y, Ri, and R2 being defined in the present disclosure; pharmaceutically acceptable salts thereof, deuterated forms thereof, isomers thereof, solvates thereof, and mixtures thereof. The compounds can be used for treating a patient suffering from a condition capable of treatment with a partial agonist or antagonist of the dopamine D2/D3 receptors and are especially useful for patients suffering from schizophrenia, depressions, neurodegenerative diseases such as Parkinson's, dyskinesias, substance abuse and relapse to substance abuse and addiction to substances such as cocaine, methamphetamine, nicotine and alcohol, glaucoma, cognitive disorders, restless leg syndrome, attention deficit hyperactivity disorders, hyperprolactinemia, autism, motor disturbances such as akathisia, rigor, dystonias as well as various disorders of the urinary tract and other neurologic disorders. Also provided are processes for the preparation of compounds of the present disclosure.

  本文提供了一种以公式表示的化合物：其中Y，Ri和R2在本公开中被定义；其药物可接受的盐，氘代形式，同分异构体，溶剂合物以及它们的混合物。这些化合物可用于治疗患有可用部分激动剂或拮抗剂治疗的病症的患者，尤其适用于患有精神分裂症，抑郁症，神经退行性疾病（如帕金森病），运动障碍，物质滥用和复发以及对可卡因，甲基苯丙胺，尼古丁和酒精等物质上瘾的患者，青光眼，认知障碍，不宁腿综合症，注意力缺陷多动症，高泌乳素血症，自闭症，运动障碍（如不安，僵硬，痉挛）以及各种泌尿道和其他神经疾病的病症。本文还提供了制备本公开化合物的方法。
• Synthesis and SAR of highly potent and selective dopamine D3-receptor antagonists: Variations on the 1H-pyrimidin-2-one theme
  作者：Hervé Geneste、Wilhelm Amberg、Gisela Backfisch、Armin Beyerbach、Wilfried M. Braje、Jürgen Delzer、Andreas Haupt、Charles W. Hutchins、Linda L. King、Daryl R. Sauer、Liliane Unger、Wolfgang Wernet

  DOI：10.1016/j.bmcl.2005.12.079

  日期：2006.4

  In our efforts to further pursue one of the most selective dopamine D-3-receptor antagonists reported to date, we now describe the synthesis and SAR of novel and highly selective dopamine D-3 antagonists based on a 1H-pyridin-2-one or on a urea scaffold. The most potent compounds exhibited K-i values toward the D-3 receptor in the nano- to subnanomolar range and high selectivity versus the related D-2 dopamine receptor. Thus, 1H-pyridin-2-one 7b displays oral bioavailability (F = 37%) as well as brain penetration (brain plasma ratio 3.7) in rat. Within the urea series, an excellent D-3 versus D-2 selectivity (>100-fold) could be achieved by removal of one NH group (compound 6), although bioavailability (rat) was suboptimal (F < 10%). These data significantly enhance our understanding of the D-3 Pharmacophore and are expected to lead to novel approaches for the treatment of schizophrenia. (C) 2006 Elsevier Ltd. All rights reserved.
• Development of molecular tools based on the dopamine D3 receptor ligand FAUC 329 showing inhibiting effects on drug and food maintained behavior
  作者：Anne Stößel、Regine Brox、Nirupam Purkayastha、Harald Hübner、Carsten Hocke、Olaf Prante、Peter Gmeiner

  DOI：10.1016/j.bmc.2017.04.036

  日期：2017.7

  Dopamine D-3 receptor-mediated networks have been associated with a wide range of neuropsychiatric diseases, drug addiction and food maintained behavior, which makes D-3 a highly promising biological target. The previously described dopamine D-3 receptor ligand FAUC 329 (1) showed protective effects against dopamine depletion in a MPTP mouse model of Parkinson's disease. We used the radioligand [F-18]2, a [(18)]fluoroethoxy substituted analog of the lead compound 1 as a molecular tool for visualization of D-3-rich brain regions including the islands of Calleja. Furthermore, structural modifications are reported leading to the pyrimidylpiperazine derivatives 3 and 9 displaying superior subtype selectivity and preference over serotonergic receptors. Evaluation of the lead compound 1 on cocaine-seeking behavior in non-human primates showed a substantial reduction in cocaine self-administration behavior and food intake. (C) 2017 Elsevier Ltd. All rights reserved.
• US8008488B2
  申请人：——

  公开号：US8008488B2

  公开（公告）日：2011-08-30