(7-(benzyloxy)chroman-2-yl)methanol | 180716-16-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: (7-(benzyloxy)chroman-2-yl)methanol
• 英文别名: 3,4-dihydro-7-(phenylmethoxy)-2H-1-benzopyran-2-methanol；(7-Benzyloxy-chroman-2-yl)-methanol；(7-phenylmethoxy-3,4-dihydro-2H-chromen-2-yl)methanol
• CAS: 180716-16-9
• 化学式: C₁₇H₁₈O₃
• 分子量: 270.328
• InChiKey: JFRDQNOCPSMPFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (7-(benzyloxy)chroman-2-yl)methanol 在 四溴化碳 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 反应 14.0h， 生成 3-{[(2S)-7-benzyloxy-chroman-2-ylmethyl]-amino}-propan-1-ol
  参考文献：
  名称：

  New Generation Dopaminergic Agents. 1. Discovery of a Novel Scaffold Which Embraces the D₂ Agonist Pharmacophore. Structure−Activity Relationships of a Series of 2-(Aminomethyl)chromans

  摘要：

  A series of 2-(aminomethyl)chromans (2-AMCs) was synthesized and evaluated for their affinity and selectivity for both the high-and low-affinity agonist states (D-2(High) and D-2(Low), respectively) of the dopamine (DA) D-2 receptor. The 7-hydroxy-2-(aminomethyl)chroman moiety was observed to be the primary D-2 agonist pharmacophore. The 2-methylchroman moiety was discovered to be an entirely novel scaffold which could be used to access the D-2 agonist pharmacophore. Attaching various simple alkyl and arylalkyl side chains to the 7-hydroxy 2-AMC nucleus had significant effects on selectivity for the D-2(High) receptor vs the 5HT(1A) and alpha(1) receptors. A novel DA partial agonist, (R)-(-)-2-(benzylamino)methyl)chroman-7-ol [R-(-)-35c], was identified as having the highest affinity and best selectivity for the D-2(High) receptor vs the alpha(1) and 5HT(1A) receptors. Several regions of the 2-AMC nucleus were modified and recognized as potential sites to modulate the level of intrinsic activity. The global minimum conformer of the 7-hydroxy-2-AMC moiety was identified as fulfilling the McDermed model D-2 agonist pharmacophoric criteria and was proposed as the D-2 receptor-bound conformation. Structure-activity relationships gained from these studies have aided in the synthesis of D-2 partial agonists of varying intrinsic activity levels. These agents should be of therapeutic value in treating disorders resulting from hypo-and hyperdopaminergic activity, without the side effects associated with complete D-2 agonism or antagonism.

  DOI：

  10.1021/jm9703653
• 作为产物：
  描述：

  ethyl 7-hydroxychromane-2-carboxylate 在 lithium aluminium tetrahydride 、 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 生成 (7-(benzyloxy)chroman-2-yl)methanol
  参考文献：
  名称：

  设计和优化2,3-二氢苯并[b] [1,4]二恶英丙酸作为新型GPR40激动剂，具有改善的药代动力学和安全性

  摘要：

  由于GPR40介导低血糖风险低的胰腺β细胞中葡萄糖刺激的胰岛素分泌的增强作用，因此它已成为治疗糖尿病的新的潜在治疗靶标。为了扩大化学空间并鉴定具有改善的肝脏安全性的结构不同的GPR40激动剂，设计了一系列新的稠环苯基丙酸类似物。围绕新型支架进行了全面的构效关系研究，并导致几种类似物表现出有效的GPR40激动活性和对其他脂肪酸受体的高选择性。药代动力学（PK）谱和体内功效的进一步评估确定了化合物40a在口服葡萄糖耐量试验期间具有出色的PK特性和显着的降糖功效。另外，化合物40a显示出较低的肝胆转运蛋白抑制作用和良好的可药物性。所有结果表明，化合物40a是有希望的进一步开发的候选物。

  DOI：

  10.1016/j.bmc.2018.10.019

文献信息

• [EN] BENZENE-FUSED 6-MEMBERED OXYGEN-CONTAINING HETEROCYCLIC DERIVATIVES OF BICYCLIC HETEROARYLS<br/>[FR] DÉRIVÉS HÉTÉROCYCLIQUES D'HÉTÉROARYLES BICYCLIQUES À 6 CYCLES BENZÉNIQUES ACCOLÉS DE BENZÈNE CONTENANT DE L'OXYGÈNE
  申请人：NOVARTIS AG

  公开号：WO2011064211A1

  公开（公告）日：2011-06-03

  The invention relates to new derivatives of formula I, wherein the substituents are as defined in the specification; to processes for the preparation of such derivatives; pharmaceutical compositions comprising such derivatives; such derivatives as a medicament; such derivatives for the treatment of a proliferative disease.

  这项发明涉及公式I的新衍生物，其中取代基如规范中所定义；制备这种衍生物的方法；包括这种衍生物的药物组合物；这种衍生物作为药物；这种衍生物用于治疗增殖性疾病。
• Chroman and benzofuran derivatives as 5-hydroxytryptamine-6 ligands
  申请人：Wyeth

  公开号：US20030153599A1

  公开（公告）日：2003-08-14

  The present invention provides a compound of formula I and the use thereof for the therapeutic treatment of disorders relating to or affected by the 5-HT6 receptor. 1

  本发明提供了一种I式化合物及其用途，用于治疗与或受5-HT6受体相关的疾病。
• Benzene-fused 6-membered oxygen-containing heterocyclic derivatives of bicyclic heteroaryls
  申请人：Chen Bei

  公开号：US20120289501A1

  公开（公告）日：2012-11-15

  The invention relates to new derivatives of formula I, wherein the substituents are as defined in the specification; to processes for the preparation of such derivatives; pharmaceutical compositions comprising such derivatives; such derivatives as a medicament; such derivatives for the treatment of a proliferative disease.

  本发明涉及I式的新衍生物，其中取代基如规范中定义；制备这种衍生物的方法；包含这种衍生物的药物组合物；这种衍生物作为药物；这种衍生物用于治疗增生性疾病。
• BENZENE-FUSED 6-MEMBERED OXYGEN-CONTAINING HETEROCYCLIC DERIVATIVES OF BICYCLIC HETEROARYLS
  申请人：Novartis AG

  公开号：EP2504339A1

  公开（公告）日：2012-10-03
• US5541199A
  申请人：——

  公开号：US5541199A

  公开（公告）日：1996-07-30