1-(2,3-二氢-1-苯并呋喃-2-基甲基)哌嗪 | 876717-03-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 中文名称: 1-(2,3-二氢-1-苯并呋喃-2-基甲基)哌嗪
• 英文名称: 1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazine
• 英文别名: 1-(2,3-dihydro-1-benzofuran-2-ylmethyl)piperazine；LINS01001；1-(2,3-Dihydro-benzofuran-2-ylmethyl)-piperazine
• CAS: 876717-03-2
• 化学式: C₁₃H₁₈N₂O
• mdl: MFCD06751853
• 分子量: 218.299
• InChiKey: DNZIVLPHTKLWQR-UHFFFAOYSA-N

物化性质

• 溶解度：
  >32.7 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  24.5
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  1-(2,3-二氢-1-苯并呋喃-2-基甲基)哌嗪 、 [4-(4-nitro-3-trifluoromethyl-phenylamino)-cyclohexyloxy]-acetic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以36%的产率得到1-[4-(2,3-dihydro-1-benzofuran-2-ylmethyl)piperazin-1-yl]-2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]ethan-1-one
  参考文献：
  名称：

  ANTHELMINTIC COMPOUNDS AND COMPOSITIONS AND METHOD OF USING THEREOF

  摘要：

  本发明涉及以下式（I）的新型驱虫化合物： 其中 Y和Z分别是双环碳环或双环杂环基团，或者Y或Z中的一个是双环碳环或双环杂环基团，另一个是烷基，烯基，炔基，环烷基，苯基，杂环基或杂芳基，以及变量X 1 ，X 2 ，X 3 ，X 4 ，X 5 ，X 6 ，X 7 和X 8 如本文所定义。本发明还提供了包含本发明的驱虫化合物的兽药组合物，以及它们用于治疗和预防动物寄生虫感染的用途。

  公开号：

  US20140142114A1
• 作为产物：
  描述：

  2-烯丙基酚 在 碘 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 1-(2,3-二氢-1-苯并呋喃-2-基甲基)哌嗪
  参考文献：
  名称：

  在人多巴胺D 2和D 3受体上分析LINS01化合物

  摘要：

  摘要 组胺和多巴胺的神经元通路在中枢神经系统（尤其是在边缘区域）表现出有趣的重叠，这使其在设计具有协同和/或累加作用的药物时非常有吸引力。这些系统在治疗精神分裂症，药物成瘾，帕金森氏症和阿尔茨海默氏病等方面的作用广为人知。LINS01化合物先前被报道为组胺H 3受体（H 3 R）拮抗剂，其中一些正在啮齿动物记忆模型中评估。考虑到它们的药理学潜力以及与文献中的多巴胺D 2受体（D 2 R）和多巴胺D 3受体（D 3R）配体，这项工作旨在通过使用[ 3 H] spiperone置换试验评估这些化合物作为这些受体的配体。检验了一组11种化合物，这些化合物包含在二氢苯并呋喃环的5位和哌嗪氮带有取代基的二氢苯并呋喃基-哌嗪核。所述化合物显示低到在两个中等亲和力，d 2 R和d 3 R. ñ -苯基化合物LINS01005（ 1D ），LINS01011（ 1H ），LINS01012（ 1I ）和LINS01016（

  DOI：

  10.1007/s12039-019-1694-6

文献信息

• 1-[(2,3-Dihydro-1-benzofuran-2-yl) methyl]piperazines as novel anti-inflammatory compounds: Synthesis and evaluation on H₃R/H₄R
  作者：Michelle Fidelis Corrêa、Marina Themoteo Varela、Aleksandro Martins Balbino、Ana Claudia Torrecilhas、Richardt Gama Landgraf、Lanfranco Ranieri Paolo Troncone、João Paulo dos Santos Fernandes

  DOI：10.1111/cbdd.12947

  日期：2017.8

  for novel anti-inflammatory agents in several conditions such as asthma and other chronic inflammatory diseases. Due to similarity with previously reported ligands of HRs, a set of 1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazines were synthesized and evaluated in competitive binding assays as H3 R/H4 R ligands herein. The results showed the compounds presented affinity (Ki ) for H3 R/H4 R in micromolar

  组胺受体（HRs）是G蛋白偶联受体（GPCR）超家族的成员，是具有巨大治疗兴趣的传统靶标。近来，已经将H3R和H4R作为药物发现的靶标进行了探索，包括在寻找双重作用的H3R / H4R配体中。H4 R是最新的组胺受体，在哮喘和其他慢性炎症等多种疾病中，是新型抗炎药的有希望的靶标。由于与先前报道的HR配体相似，因此合成了一组1-[（（2,3-二氢-1-苯并呋喃-2-基）甲基]哌嗪，并在竞争性结合试验中作为H3 R / H4 R配体进行了评估。结果表明，该化合物对H3 R / H4 R的亲和力（Ki）在微摩尔范围内，并且对H3 R的选择性更高。所有化合物对哺乳动物细胞均无重要的细胞毒性。苯基取代的化合物LINS01005已显示该化合物对H4R具有更高的亲和力，但对该受体的选择性不超过H3R。LINS01005在鼠哮喘模型中显示出令人感兴趣的抗炎活性，从而降低了支气管肺泡灌洗液中的嗜酸性粒细胞计
• Anthelmintic compounds and compositions and method of using thereof
  申请人：MERIAL INC.

  公开号：US09249102B2

  公开（公告）日：2016-02-02

  The present invention relates to novel anthelmintic compounds of formula (I) below: wherein Y and Z are independently a bicyclic carbocyclic or a bicyclic heterocyclic group, or one of Y or Z is a bicyclic carbocyclic or a bicyclic heterocyclic group and the other of Y or Z is alkyl, alkenyl, alkynyl, cycloalkyl, phenyl, heterocyclyl or heteroaryl, and variables X1, X2, X3, X4, X5, X6, X7 and X8 are as defined herein. The invention also provides for veterinary compositions comprising the anthelmintic compounds of the invention, and their uses for the treatment and prevention of parasitic infections in animals.

  本发明涉及以下式子(I)的新型驱虫化合物： 其中Y和Z分别是双环碳环或双环杂环基团，或其中一个为双环碳环或双环杂环基团，另一个为烷基，烯基，炔基，环烷基，苯基，杂环基或杂环芳基；变量X1，X2，X3，X4，X5，X6，X7和X8如定义所述。本发明还提供包含本发明的驱虫化合物的兽医组合物，并且它们用于治疗和预防动物寄生虫感染。
• Novel potent vasodilating agents: Evaluation of the activity and potency of LINS01005 and derivatives in rat aorta
  作者：Milton Ginoza、Gustavo A.B. Fernandes、Michelle F. Corrêa、João Paulo S. Fernandes

  DOI：10.1016/j.ejps.2019.105171

  日期：2020.2

  Cardiovascular diseases (CVDs) present high prevalence rates in the current world. It is estimated that approximately one-third of the global deaths are related to CVD5, and thus there is still a need for novel drugs to treat these disorders. We serendipitously discovered that LINS01005 (5a) is a potent vasodilating agent in rat aorta, and therefore a set of analogues were evaluated for the vasodilating potency in Wistar and SHR rat thoracic aorta precontracted with norepinephrine, with endothelium intact (E+) or denuded (E-) aortic rings. Compounds 5a and 5b were the most potent, showing submicromolar potency for endothelium intact vessels (EC50 853 and 941 nM, respectively) and micromolar values for E- vessels (EC50 2.4 and 7.1 pM, respectively). These compounds were indeed significantly more potent vasodilating agents in SHR-derived aortic rings (p < 0.001), showing nanomolar potency for 5a [EC50 2.4 nM (E+) 9.0 nM (E-)] and 5b [EC50 20 nM (E+) 2.1 mu M (E-)]. SAR analysis though PCA and HCA were performed, suggesting that N-phenylpiperazine is essential to the activity, while increasing volume in the substituted aromatic moiety is detrimental to the potency. This is the first report of the vasodilating properties of such compounds, and studies regarding the mechanism of action are in progress in our group.
• Pharmacological and SAR analysis of the LINS01 compounds at the human histamine H₁ , H₂ , and H₃ receptors
  作者：Michelle Fidelis Corrêa、Álefe Jhonatas Ramos Barbosa、Gustavo Ariel Borges Fernandes、Jillian G. Baker、João Paulo dos Santos Fernandes

  DOI：10.1111/cbdd.13387

  日期：2019.1

  AbstractHistamine is a transmitter that activates the four receptors H1R to H4R. The H3R is found in the nervous system as an autoreceptor and heteroreceptor, and controls the release of neurotransmitters, making it a potential drug target for neuropsychiatric conditions. We have previously reported that the 1‐(2,3‐dihydro‐1‐benzofuran‐2‐yl)methylpiperazines (LINS01 compounds) have the selectivity for the H3R over the H4R. Here, we describe their pharmacological properties at the human H1R and H2R in parallel with the H3R, thus providing a full analysis of these compounds as histamine receptor ligands through reporter gene assays. Eight of the nine LINS01 compounds inhibited H3R‐induced histamine responses, but no inhibition of H2R‐induced responses was seen. Three compounds were weakly able to inhibit H1R‐induced responses. No agonist responses were seen to any of the compounds at any receptor. SAR analysis shows that the N‐methyl group improves H3R affinity while the N‐phenyl group is detrimental. The methoxy derivative, LINS01009, had the highest affinity.
• US9249102B2
  申请人：——

  公开号：US9249102B2

  公开（公告）日：2016-02-02