(5-methoxybenzofuran-3-yl)methanol | 221905-32-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: (5-methoxybenzofuran-3-yl)methanol
• 英文别名: (5-Methoxy-1-benzofuran-3-yl)methanol
• CAS: 221905-32-4
• 化学式: C₁₀H₁₀O₃
• 分子量: 178.188
• InChiKey: PUCLTBFTMSCAIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  42.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (5-methoxybenzofuran-3-yl)methanol 在 氯化亚砜 作用下， 以 乙醚 为溶剂， 反应 3.0h， 以76%的产率得到3-chloromethyl-5-methoxybenzofuran
  参考文献：
  名称：

  Structure−Activity Relationships for a Novel Series of Dopamine D2-like Receptor Ligands Based on N-Substituted 3-Aryl-8-azabicyclo[3.2.1]octan-3-ol

  摘要：

  Discovering dopamine D2-like receptor subtype-selective ligands has been a focus of significant investigation. The D2R-selective antagonist 3-[4-(4-chlorophenyl)-4-hydroxypiperidinyl]methylindole (1, L741,626; K-i(D2R/MR) = 11.2:163 nM) has previously provided a lead template for chemical modification. Herein, analogues have been synthesized where the piperidine was replaced by a tropane ring that reversed the selectivity seen in the parent compound, in human hD2(L)R- or hD3R-transfected HEK 293 cells (31, K-i(D2R/D3R) = 33.4: 15.5 nM). Further exploration of both N-substituted and aryl ring-substituted analogues resulted in the discovery of several high affinity D2R/D3R ligands with 3-benzofurylmethyl-substituents (e.g., 45, K-i(D2R/D3R) = 1.7:0.34 nM) that induced high affinity not achieved in similarly N-substituted piperidine analogues and significantly (470-fold) improved D3R binding affinity compared to the parent ligand 1. X-ray crystallographic data revealed a distinctive spatial arrangement of pharmacophoric elements in the piperidinol vs tropine analogues, providing clues for the diversity in SAR at the D2 and D3 receptor subtypes.

  DOI：

  10.1021/jm800532x
• 作为产物：
  描述：

  5-methoxybenzofuran-3-carbaldehyde 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以97%的产率得到(5-methoxybenzofuran-3-yl)methanol
  参考文献：
  名称：

  Structure−Activity Relationships for a Novel Series of Dopamine D2-like Receptor Ligands Based on N-Substituted 3-Aryl-8-azabicyclo[3.2.1]octan-3-ol

  摘要：

  Discovering dopamine D2-like receptor subtype-selective ligands has been a focus of significant investigation. The D2R-selective antagonist 3-[4-(4-chlorophenyl)-4-hydroxypiperidinyl]methylindole (1, L741,626; K-i(D2R/MR) = 11.2:163 nM) has previously provided a lead template for chemical modification. Herein, analogues have been synthesized where the piperidine was replaced by a tropane ring that reversed the selectivity seen in the parent compound, in human hD2(L)R- or hD3R-transfected HEK 293 cells (31, K-i(D2R/D3R) = 33.4: 15.5 nM). Further exploration of both N-substituted and aryl ring-substituted analogues resulted in the discovery of several high affinity D2R/D3R ligands with 3-benzofurylmethyl-substituents (e.g., 45, K-i(D2R/D3R) = 1.7:0.34 nM) that induced high affinity not achieved in similarly N-substituted piperidine analogues and significantly (470-fold) improved D3R binding affinity compared to the parent ligand 1. X-ray crystallographic data revealed a distinctive spatial arrangement of pharmacophoric elements in the piperidinol vs tropine analogues, providing clues for the diversity in SAR at the D2 and D3 receptor subtypes.

  DOI：

  10.1021/jm800532x

文献信息

• Gold(I)-Catalyzed<i>endo</i>-Selective Intramolecular α-Alkenylation of β-Yne-Furans: Synthesis of Seven-Membered-Ring-Fused Furans and DFT Calculations
  作者：Zhe Dong、Cheng-Hang Liu、Yi Wang、Mu Lin、Zhi-Xiang Yu

  DOI：10.1002/anie.201306965

  日期：2013.12.23

  Alkenylation of furans: An efficient gold‐catalyzed endo‐selective intramolecular α‐alkenylation of β‐alkyne‐substituted furans has been developed to synthesize challenging seven‐membered‐ring‐fused furans in good to excellent yields. Preliminary DFT calculations have been carried out to understand the experimentally observed regioselectivity. DME=1,2‐dimethoxyethane, Ts=p‐toluenesulfonyl.

  呋喃的烯基：一个有效的金催化内切-选择性分子内β -炔基取代的呋喃的α烯基化已发展到合成具有挑战性良好7元环稠合的呋喃，以优异的产率。已经进行了初步的DFT计算以了解实验观察到的区域选择性。DME = 1,2-二甲氧基乙烷，Ts =对甲苯磺酰基
• Synthesis and biological evaluation of paeoveitol D derivatives as new melatonin receptor agonists with antidepressant activities
  作者：Tian-Ze Li、Jing Hu、Jin-Jin Sun、Xiao-Yan Huang、Chang-An Geng、Shu-Bai Liu、Xue-Mei Zhang、Ji-Jun Chen

  DOI：10.1039/d2md00156j

  日期：——

  displayed activity on MT1 and MT2 receptors with agonistic ratios of 57.5% and 51.6% at a concentration of 1 mM. To explore the structure–activity relationships, 34 paeoveitol D derivatives were synthesized and evaluated for their MT1 and MT2 agonistic activities using the Fluo-8 calcium assay. Among them, 16 and 18 derivatives increased agonistic activities on the MT1 and MT2 receptors, respectively

  我们之前的研究表明，paeoveitol D（一种从牡丹皮中分离出来的苯并呋喃化合物）对 MT 1和 MT 2受体表现出活性，在浓度为 1 mM 时，激动比率分别为 57.5% 和 51.6%。为了探索结构-活性关系，合成了 34 种 Paeoveitol D 衍生物，并使用 Fluo-8 钙测定法评估了它们的 MT 1和 MT 2激动活性。其中，16和18种衍生物分别增加了对MT 1和MT 2受体的激动活性。在 Tango试验的激动剂量反应曲线中，化合物18对 MT 1和 MT 2受体的EC 50值分别为 21.0 和 298.9 μM ，并且在强迫游泳测试中缩短了不动时间。初步的作用机制研究表明，化合物18的抗抑郁活性可能是通过提高小鼠大脑中的血清素（5-HT）和多巴胺（DA）水平来介导的。化合物18还表现出良好的药代动力学特征和体内低毒性。这些结果表明化合物18可能是一种潜在的抗抑郁药。
• Structure−Activity Relationships for a Novel Series of Dopamine D2-like Receptor Ligands Based on N-Substituted 3-Aryl-8-azabicyclo[3.2.1]octan-3-ol
  作者：Noel M. Paul、Michelle Taylor、Rakesh Kumar、Jeffrey R. Deschamps、Robert R. Luedtke、Amy Hauck Newman

  DOI：10.1021/jm800532x

  日期：2008.10.9

  Discovering dopamine D2-like receptor subtype-selective ligands has been a focus of significant investigation. The D2R-selective antagonist 3-[4-(4-chlorophenyl)-4-hydroxypiperidinyl]methylindole (1, L741,626; K-i(D2R/MR) = 11.2:163 nM) has previously provided a lead template for chemical modification. Herein, analogues have been synthesized where the piperidine was replaced by a tropane ring that reversed the selectivity seen in the parent compound, in human hD2(L)R- or hD3R-transfected HEK 293 cells (31, K-i(D2R/D3R) = 33.4: 15.5 nM). Further exploration of both N-substituted and aryl ring-substituted analogues resulted in the discovery of several high affinity D2R/D3R ligands with 3-benzofurylmethyl-substituents (e.g., 45, K-i(D2R/D3R) = 1.7:0.34 nM) that induced high affinity not achieved in similarly N-substituted piperidine analogues and significantly (470-fold) improved D3R binding affinity compared to the parent ligand 1. X-ray crystallographic data revealed a distinctive spatial arrangement of pharmacophoric elements in the piperidinol vs tropine analogues, providing clues for the diversity in SAR at the D2 and D3 receptor subtypes.