7-(1-((4'-fluorobiphenyl-4-yl)methyl)piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one | 1630951-38-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 7-(1-((4'-fluorobiphenyl-4-yl)methyl)piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one
• 英文别名: 7-[1-[[4-(4-fluorophenyl)phenyl]methyl]piperidin-4-yl]-3,4-dihydro-1H-quinazolin-2-one
• CAS: 1630951-38-0
• 化学式: C₂₆H₂₆FN₃O
• 分子量: 415.51
• InChiKey: HLLMAOYUPDCCBI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  44.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N-(3-bromophenyl)-2-hydroxyiminacetamide 在 2,6-二甲基吡啶 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 硼烷四氢呋喃络合物 、 三氟甲磺酸酐 、 硫酸 、 palladium 10% on activated carbon 、 盐酸羟胺 、 氢气 、 potassium acetate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 133.0h， 生成 7-(1-((4'-fluorobiphenyl-4-yl)methyl)piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one
  参考文献：
  名称：

  Synthesis and Dual D₂ and 5-HT_1A Receptor Binding Affinities of 7-piperazinyl and 7-piperidinyl-3,4-dihydroquinazolin-2(1H)-ones

  摘要：

  一系列新的7-哌嗪基和7-哌啶基-3,4-二氢喹唑啉-2(1H)-酮已被合成。所述化合物在结构上与阿多拉嗪相关，后者是一种潜在的不典型抗精神病药物，具有强效的D2受体拮抗剂和5-HT1A受体激动剂特性。制备了适当修饰的芳基溴化物，并与叔丁基哌嗪-1-羧酸酯缩合，得到高级中间体哌嗪基-3,4-二氢喹唑啉-2(1H)-酮。同样，Suzuki-Miyaura交叉偶联反应中，环状乙烯基硼酸盐与适当的芳基溴化物反应，得到哌啶基-3,4-二氢喹唑啉-2(1H)-酮。通过哌嗪基和哌啶基-3,4-二氢喹唑啉-2(1H)-酮与适当设计的联芳基醛的还原胺化反应，完成了这些目标化合物的合成。所述化合物被筛选为D2和5-HT1A受体结合亲和力。结构-活性关系研究表明，环戊烯基吡啶和环戊烯基苄基对这些化合物的双重D2和5-HT1A受体结合亲和力有显著贡献。

  DOI：

  10.2174/15734064113096660046

文献信息

• DIHYDROQUINONE DERIVATIVES OF PIPERIDINE AND PIPERAZINE
  申请人：KING FAHD UNIVERSITY OF PETROLEUM AND MINERALS

  公开号：US20150094467A1

  公开（公告）日：2015-04-02

  The dihydroquinone derivatives of piperidine and piperazine are 7-piperazinyl and 7-piperadinyl-3,4-dihydroquinazolin-2(1H)-ones that exhibit D 2 and 5-HT 1A receptor binding affinities, making them suitable for use as the active ingredient of pharmaceuticals for the treatment of schizophrenia. The derivatives have the general formula: where X is carbon or nitrogen and R is a group selected from a through f having the formula: or a pharmaceutically acceptable salt thereof. The piperazine compounds are prepared by condensing 4-bromo-2-nitro-benzonitrile with 1-Boc-piperazine (1-tert-butoxycarbonyl-piperazine) to form an intermediate that is converted to a piperazinyl-3,4-dihydroquinazolin-2(1H)-one. Subsequent reductive amination with the biarylaldehydes a through f completes the synthesis of the 7-piperadinyl-3,4-dihydroquinazolin-2(1H)-ones. The piperadinyl compounds are prepared from tert-butyl-4-(2-oxo-1,2,3,4-tetradihydroquinazolin-7-yl)piperidine-1-carboxylate, which is converted to 7-(piperidin-4-yl)-3,4-dihyroquinazolin-2(1H)-one. Subsequent reductive amination with the biarylaldehydes a through f completes the synthesis of the 7-piperidinyl-3,4-dihydroquinazolin-2(1H)-ones.

  哌啶和哌嗪的二氢喹啉衍生物是7-哌嗪基和7-哌啶基-3,4-二氢喹唑啉-2(1H)-酮，具有D2和5-HT1A受体结合亲和力，适合用作治疗精神分裂症的药物的活性成分。这些衍生物的通用公式为：其中X为碳或氮，R为从a到f的选择性基团，其公式为：或其药学上可接受的盐。哌嗪类化合物是通过将4-溴-2-硝基苯腈与1-Boc-哌嗪(1-叔丁氧羰基哌嗪)缩合形成中间体，然后转化为哌嗪基-3,4-二氢喹唑啉-2(1H)-酮来制备的。随后，与双芳基醛a到f进行还原胺化反应，完成了7-哌嗪基-3,4-二氢喹唑啉-2(1H)-酮的合成。哌啶类化合物是从叔丁基-4-(2-氧代-1,2,3,4-四氢喹唑啉-7-基)哌啶-1-羧酸酯开始制备的，该化合物转化为7-(哌啶-4-基)-3,4-二氢喹唑啉-2(1H)-酮。随后，与双芳基醛a到f进行还原胺化反应，完成了7-哌啶基-3,4-二氢喹唑啉-2(1H)-酮的合成。
• US8916704B1
  申请人：——

  公开号：US8916704B1

  公开（公告）日：2014-12-23
• US9073900B2
  申请人：——

  公开号：US9073900B2

  公开（公告）日：2015-07-07
• Synthesis and Dual D<sub>2</sub> and 5-HT<sub>1A</sub> Receptor Binding Affinities of 7-piperazinyl and 7-piperidinyl-3,4-dihydroquinazolin-2(1H)-ones
  作者：Nisar Ullah

  DOI：10.2174/15734064113096660046

  日期：2014.5.31

  A series of new 7-piperazinyl and 7-piperidinyl-3,4-dihydroquinazolin-2(1H)-ones has been synthesized. The described compounds are structurally related to adoprazine, a potential atypical antipsychotic bearing potent D2 receptor antagonist and 5-HT1A receptor agonist properties. Suitably modified aryl bromides were prepared and condensed with tert-butyl piperazine-1-carboxylate to afford the advanced intermediate piperazinyl-3,4-dihydroquinazolin-2(1H)-one. Likewise Suzuki-Miyaura cross-coupling reaction of cyclic vinyl boronate with appropriate aryl bromides rendered piperidinyl-3,4-dihydroquinazolin-2(1H)-one. The reductive amination of the piperazinyl and piperidinyl-3,4- dihydroquinazolin-2(1H)-ones with suitably designed biarylaldehydes accomplished the synthesis of these title compounds. The described compounds were screened for D2 and 5-HT1A receptors binding affinities. The structure-activity relationship studies revealed that cyclopentenylpyridine and cyclopentenylbenzyl groups contribute significantly to the dual D2 and 5-HT1A receptor binding affinities of these compounds.

  一系列新的7-哌嗪基和7-哌啶基-3,4-二氢喹唑啉-2(1H)-酮已被合成。所述化合物在结构上与阿多拉嗪相关，后者是一种潜在的不典型抗精神病药物，具有强效的D2受体拮抗剂和5-HT1A受体激动剂特性。制备了适当修饰的芳基溴化物，并与叔丁基哌嗪-1-羧酸酯缩合，得到高级中间体哌嗪基-3,4-二氢喹唑啉-2(1H)-酮。同样，Suzuki-Miyaura交叉偶联反应中，环状乙烯基硼酸盐与适当的芳基溴化物反应，得到哌啶基-3,4-二氢喹唑啉-2(1H)-酮。通过哌嗪基和哌啶基-3,4-二氢喹唑啉-2(1H)-酮与适当设计的联芳基醛的还原胺化反应，完成了这些目标化合物的合成。所述化合物被筛选为D2和5-HT1A受体结合亲和力。结构-活性关系研究表明，环戊烯基吡啶和环戊烯基苄基对这些化合物的双重D2和5-HT1A受体结合亲和力有显著贡献。