2'-(羟甲基)-[1,1'-联苯]-4-甲醛 | 1228594-41-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2'-(羟甲基)-[1,1'-联苯]-4-甲醛
• 英文名称: 2'-(hydroxymethyl)[1,1'-biphenyl]-4-carbaldehyde
• 英文别名: 2'-hydroxymethyl-biphenyl-4-carbaldehyde；2'-(Hydroxymethyl)-[1,1'-biphenyl]-4-carbaldehyde；4-[2-(hydroxymethyl)phenyl]benzaldehyde
• CAS: 1228594-41-9
• 化学式: C₁₄H₁₂O₂
• 分子量: 212.248
• InChiKey: UBQIRFAQMBAOQO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(氯甲基)-4,5-二甲氧基-2-硝基苯 、 2'-(羟甲基)-[1,1'-联苯]-4-甲醛 在 四(二甲氨基)乙烯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 以51%的产率得到2-(4,5-dimethoxy-2-nitrophenyl)-1-(2'-(hydroxymethyl)[1,1'-biphenyl]-4-yl)ethanol
  参考文献：
  名称：

  VP1 crystal structure-guided exploration and optimization of 4,5-dimethoxybenzene-based inhibitors of rhinovirus 14 infection

  摘要：

  Human rhinoviruses (HRV) are the predominant cause of common colds and flu-like illnesses, but are also responsible for virus-induced exacerbations of asthma and chronic obstructive pulmonary disease. However, to date, no drug has been approved yet for clinical use. In this study, we present the results of the structure-based lead optimization of a class of new small-molecule inhibitors that we previously reported to bind into the pocket beneath the canyon of the VP1 protein. A small series of analogues that we designed based on the available structure and interaction data were synthesized and evaluated for their potency to inhibit the replication of HRV serotype 14. 2-(4,5-Dimethoxy-2-nitrophenyI)-1-(4-(pyridin-4-yl)phenyl)ethanol (3v) was found to be a potent inhibitor exhibiting micromolar activity (EC50 = 3.4 +/- 1.0 mu M) with a toxicity for HeLa cells that was significantly lower than that of our previous hit (LPCRW_0005, CC50 = 104.0 +/- 22.2 mu M: 3v, CC50 > 263 mu M). (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.03.049
• 作为产物：
  描述：

  2-溴苄醇 、 4-甲酰基苯硼酸 在 四(三苯基膦)钯 碳酸氢钠 作用下， 以 乙二醇甲醚 、 水 为溶剂， 反应 17.0h， 生成 2'-(羟甲基)-[1,1'-联苯]-4-甲醛
  参考文献：
  名称：

  1-(BIPHENYL-4-YLMETHYL)IMIDAZOLIDINE-2,4-DIONE

  摘要：

  该发明涉及具有通式I的1-(联苯基-4-基甲基)咪唑烷二酮衍生物，其中R1为H，(C1-6)烷基（可选地取代为氧代、OR4、COOR5、卤素或CN），(C2-6)烯基，(C2-6)炔基，(C3-6)环烷基或(C3-6)环烷基(C1-3)烷基；R2和R2'独立地为H或(C1-3)烷基；或R2和R2'与它们连接的碳原子一起形成一个(C3-5)环烷基基团；R3代表H或1至4个F取代基；Y代表或NR8R9；X代表CHR6，CF2，O，S，SO或SO2；R4和R5为(C1-6)烷基；R6为H，OR7或CN；R7为(C1-3)烷基；R8为含有来自O、S、SO和SO2的杂原子的(C5-7)环烷基；R9为H或(C1-4)烷基；o和m表示取代基Y-CH2的邻位或间位；或其药学上可接受的盐；以及所述1-(联苯基-4-基甲基)咪唑烷二酮衍生物在治疗疼痛方面的应用，例如围手术期疼痛、慢性疼痛、神经痛、癌症疼痛以及与多发性硬化症相关的疼痛和痉挛。

  公开号：

  US20100144723A1

文献信息

• 1-(biphenyl-4-ylmethyl)imidazolidine-2,4-dione
  申请人：N.V. Organon

  公开号：US07960560B2

  公开（公告）日：2011-06-14

  The invention relates to A 1-(biphenyl-4-ylmethyl)imidazolidine-2,4-dione derivative having the general Formula I wherein R1 is H, (C1-6)alkyl (optionally substituted with oxo, OR4, COOR5, halogen or CN), (C2-6)alkenyl, (C2-6)alkynyl, (C3-6)cycloalkyl or (C3-6)cycloalkyl(C1-3)alkyl; R2 and R2′ are independently H or (C1-3)alkyl; or R2 and R2′ form together with the carbon atom to which they are bound a (C3-5)cycloalkyl group; R3 represents H or 1 to 4 F substituents; Y represents or NR8R9; X represents CHR6, CF2, O, S, SO or SO2; R4 and R5 are (C1-6)alkyl; R6 is H, OR7 or CN; R7 is (C1-3)alkyl; R8 is (C5-7)cycloalkyl comprising a heteroatom selected from O, S, SO and SO2; R9 is H or (C1-4)alkyl; o and m represent the ortho or meta position of the substituent Y—CH2; or a pharmaceutically acceptable salt thereof; as well as to the use of said 1-(biphenyl-4-ylmethyl)imidazolidine-2,4-dione derivatives in the treatment of pain such as for example peri-operative pain, chronic pain, neuropathic pain, cancer pain and pain and spasticity associated with multiple sclerosis.

  本发明涉及一种具有通式I的1-(联苯基-4-甲基)咪唑啉-2,4-二酮衍生物，其中R1为H、(C1-6)烷基（可选地被氧代、OR4、COOR5、卤素或CN取代）、(C2-6)烯基、(C2-6)炔基、(C3-6)环烷基或(C3-6)环烷基(C1-3)烷基；R2和R2'分别为H或(C1-3)烷基；或R2和R2'与它们所连接的碳原子一起形成一个(C3-5)环烷基；R3代表H或1至4个F取代基；Y代表或NR8R9；X代表CHR6、CF2、O、S、SO或SO2；R4和R5为(C1-6)烷基；R6为H、OR7或CN；R7为(C1-3)烷基；R8为包含从O、S、SO和SO2中选择的杂原子的(C5-7)环烷基；R9为H或(C1-4)烷基；o和m表示取代基Y—CH2的邻位或间位；或其药学上可接受的盐；以及所述1-(联苯基-4-甲基)咪唑啉-2,4-二酮衍生物在治疗疼痛方面的用途，例如围手术期疼痛、慢性疼痛、神经病理性疼痛、癌症疼痛以及与多发性硬化相关的疼痛和痉挛。
• 1- (BIPHENYL-4-YLMETHYL) IMIDAZOLIDINE-2, 4-DIONE DERIVATIVES AND THEIR USE AS CB2 RECEPTOR AGONISTS
  申请人：N.V. Organon

  公开号：EP2373627A1

  公开（公告）日：2011-10-12
• US7960560B2
  申请人：——

  公开号：US7960560B2

  公开（公告）日：2011-06-14
• [EN] 1- (BIPHENYL-4-YLMETHYL) IMIDAZOLIDINE-2, 4-DIONE DERIVATIVES AND THEIR USE AS CB2 RECEPTOR AGONISTS<br/>[FR] DÉRIVÉS DE 1-(BIPHÉNYL-4-YLMÉTHYL)IMIDAZOLIDINE-2,4-DIONE ET LEUR EMPLOI EN TANT QU'AGONISTES DE RÉCEPTEUR CB2
  申请人：ORGANON NV

  公开号：WO2010063721A1

  公开（公告）日：2010-06-10

  The invention relates to A 1 -(biphenyl-4-ylmethyl)imidazolidine-2,4-dione derivative having the general Formula (I) wherein R1 is H, (C1-6)alkyl (optionally substituted with oxo, OR4, COOR5, halogen or CN), (C2-6)alkenyl, (C2-6)alkynyl, (C3-6)cycloalkyl or (C3-6)cycloalkyl(C1-3)alkyl; R2 and R2' are independently H or (C1-3)alkyl; or R2 and R2' form together with the carbon atom to which they are bound a (C3-5)cycloalkyl group;R3 represents H or 1 to 4 F substituents; Y represents Formula (II) or NR8R9; X represents CHR6, CF2, O, S, SO or SO2; R4 and R5 are (C1-6)alkyl; R6 is H, OR7 or CN; R7 is (C1-3)alkyl; R8 is (C5-7)cycloalkyl comprising a heteroatom selected from O, S, SO and SO2; R9 is H or (C1-4)alkyl; o and m represent the ortho or meta position of the substituent Y-CH2; or a pharmaceutically acceptable salt thereof; as well as to the use of said 1 -(biphenyl-4-ylmethyl)imidazolidine-2,4-dione derivatives as CB2 receptor agonists in the treatment of pain such as for example peri-operative pain, chronic pain, neuropathic pain, cancer pain and pain and spasticity associated with multiple sclerosis.
• VP1 crystal structure-guided exploration and optimization of 4,5-dimethoxybenzene-based inhibitors of rhinovirus 14 infection
  作者：Laurène Da Costa、Manon Roche、Els Scheers、Antonio Coluccia、Johan Neyts、Thierry Terme、Pieter Leyssen、Romano Silvestri、Patrice Vanelle

  DOI：10.1016/j.ejmech.2016.03.049

  日期：2016.6

  Human rhinoviruses (HRV) are the predominant cause of common colds and flu-like illnesses, but are also responsible for virus-induced exacerbations of asthma and chronic obstructive pulmonary disease. However, to date, no drug has been approved yet for clinical use. In this study, we present the results of the structure-based lead optimization of a class of new small-molecule inhibitors that we previously reported to bind into the pocket beneath the canyon of the VP1 protein. A small series of analogues that we designed based on the available structure and interaction data were synthesized and evaluated for their potency to inhibit the replication of HRV serotype 14. 2-(4,5-Dimethoxy-2-nitrophenyI)-1-(4-(pyridin-4-yl)phenyl)ethanol (3v) was found to be a potent inhibitor exhibiting micromolar activity (EC50 = 3.4 +/- 1.0 mu M) with a toxicity for HeLa cells that was significantly lower than that of our previous hit (LPCRW_0005, CC50 = 104.0 +/- 22.2 mu M: 3v, CC50 > 263 mu M). (C) 2016 Elsevier Masson SAS. All rights reserved.