2-(benzyloxy)-4-chlorophenol | 381220-85-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-(benzyloxy)-4-chlorophenol
• 英文别名: 4-chloro-2-phenylmethoxyphenol
• CAS: 381220-85-5
• 化学式: C₁₃H₁₁ClO₂
• 分子量: 234.682
• InChiKey: HAXUWXPBXVMAKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(benzyloxy)-4-chlorophenol 在 4-二甲氨基吡啶 、 copper(l) iodide 、 palladium on activated charcoal 、 氢气 、 N,N-二甲基甘氨酸盐酸盐 、 potassium carbonate 、 caesium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 、 苯酚 为溶剂， 反应 49.5h， 生成
  参考文献：
  名称：

  Picomolar Inhibitors of HIV Reverse Transcriptase Featuring Bicyclic Replacement of a Cyanovinylphenyl Group

  摘要：

  Members of the catechol diether class are highly potent non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs). The most active compounds yield EC50 values below 0.5 nM in assays using human T-cells infected by wild-type HIV-1. However, these compounds such as rilpivirine, the most recently FDA-approved NNRTI, bear a cyanovinylphenyl (CVP) group. This is an uncommon substructure in drugs that gives reactivity concerns. In the present work, computer simulations were used to design bicyclic replacements for the CVP group. The predicted viability of a 2-cyanoindolizinyl alternative was confirmed experimentally and provided compounds with 0.4 nM activity against the wild-type virus. The compounds also performed well with EC50 values of 10 nM against the challenging HIV-1 variant that contains the Lys103Asn/Tyr181Cys double mutation in the RT enzyme. Indolyl and benzofuranyl analogues were also investigated; the most potent compounds in these cases have EC50 values toward wild-type HIV-1 near 10 nM and high-nanomolar activities toward the double-variant. The structural expectations from the modeling were much enhanced by obtaining an X-ray crystal structure at 2.88 Å resolution for the complex of the parent 2-cyanoindolizine 10b and HIV-1 RT. The aqueous solubilities of the most potent indolizine analogues were also measured to be ~40 μg/mL, which is similar to that for the approved drug efavirenz and ~1000-fold greater than for rilpivirine.

  DOI：

  10.1021/ja408917n
• 作为产物：
  描述：

  邻苯二酚 在 磺酰氯 、 potassium carbonate 作用下， 以 丙酮 、 甲苯 为溶剂， 反应 4.0h， 生成 2-(benzyloxy)-4-chlorophenol
  参考文献：
  名称：

  Syntheses and characterization of nimesulide derivatives for dual enzyme inhibitors of both cyclooxygenase-1/2 and 5-lipoxygenase

  摘要：

  Cyclooxygenase-1/2 (COX-1/2) and 5-lipoxygenase (5-LOX) are enzymes in two different pathways in the inflammatory process. In the present study, a variety of new nimesulide derivatives were synthesized through incorporation of a 5-LOX pharmacophore into nimesulide followed with some structural modifications, which were then characterized for dual enzyme inhibitors for these two types of enzymes. Their structure-activity relationships (SARs) were studied, and compound 20f was found to be an excellent dual enzyme inhibitor. Its binding conformation and interaction mode were studied with molecular docking experiments. Compound 20f could become a lead compound for further development for potential anti-inflammatory drugs. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.01.043

文献信息

• [EN] 1,3 DI-SUBSTITUTED CYCLOBUTANE OR AZETIDINE DERIVATIVES AS HEMATOPOIETIC PROSTAGLANDIN D SYNTHASE INHIBITORS<br/>[FR] DÉRIVÉS D'AZÉTIDINE OU DE CYCLOBUTANE 1,3-DISUBSTITUÉS UTILISÉS COMME INHIBITEURS DE LA PROSTAGLANDINE D SYNTHASE HÉMATOPOÏÉTIQUE (H-PGDS)
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2018069863A1

  公开（公告）日：2018-04-19

  A compound of formula (I), wherein R, R1, R2, R3, Y, Y1, a, X, and Z are as defined herein. The compounds of the present invention are inhibitors of hematopoietic prostaglandin D synthase (H-PGDS) and can be useful in the treatment of Duchenne Muscular Dystrophy. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting H-PGDS activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  式（I）的化合物，其中R、R1、R2、R3、Y、Y1、a、X和Z的定义如本文所述。本发明的化合物是造血前列腺素D合成酶（H-PGDS）的抑制剂，可用于治疗杜兴氏肌肉萎缩症。因此，本发明进一步涉及包含本发明化合物的药物组合物。本发明还进一步涉及使用本发明化合物或包含本发明化合物的药物组合物来抑制H-PGDS活性和治疗相关疾病的方法。
• Phenoxiacetic acid derivatives
  申请人：Bonnert Victor Roger

  公开号：US20060293352A1

  公开（公告）日：2006-12-28

  The invention relates to certain 2-substituted phenoxyacetic acid derivatives of formula (I), in which the variables are as defined in the claims, useful in the treatment of diseases or conditions in which modulation of the CRTh2 receptor is beneficial, such as asthma and rhinitis.

  本发明涉及公式（I）中某些2-取代的苯氧基乙酸衍生物，其中变量如权利要求所定义，在调节CRTh2受体有益的疾病或病症的治疗中有用，例如哮喘和鼻炎。
• PHENOXIACETIC ACID DERIVATIVES
  申请人：Bonnert Roger Victor

  公开号：US20110281898A1

  公开（公告）日：2011-11-17

  The invention relates to substituted phenoxyacetic acids as useful pharmaceutical compounds for treating respiratory disorders, pharmaceutical compositions containing them, and processes for their preparation.

  本发明涉及用于治疗呼吸系统疾病的取代苯氧乙酸类药物化合物，包含它们的制药组合物以及它们的制备方法。
• Ethers alkyliques ou benzyliques du phénol, leurs procédés de préparation et leur application en thérapeutique
  申请人：DELALANDE S.A.

  公开号：EP0327455A1

  公开（公告）日：1989-08-09

  Composés de formule : dans laquelle : - R représente un groupe alkyle en C₃-C₆ ou un groupe benzyle substitué par R₃, avec R₃ = H, halogène, alkyle en C₁-C₄, alkoxy en C₁-C₄, CF₃, NO₂ ou CN ; et - R₂ représente : . un groupe alkoxy en C₁-C₄, auquel cas le couple (X, R₁) = (O, OH), (O, alkoxy en C₁-C₄), (CHOH, H), (O, H), (CH₂, H) ou (CO, H) ; . un groupe OH, auquel cas le couple (X, R₁) = (O, OH), (O, alkoxy en C₁-C₄), (O, H) ou (CH₂, H), avec les réserves que : * lorsque (X, R₁) = (O, OH), R est différent de alkyle en C₃-C₆ et de benzyle, et * lorsque (X, R₁) = (O, H), RO est différent de et de o-benzyloxy ; . un groupe CN, auquel cas le couple (X,R₁)=(O, H) ou (CH₂, H); ou . un groupe NH-alkyle en C₁-C₄, auquel cas le couple (X, R₁)=(O,H) ou (CH₂, H), avec la réserve que lorsque (X, R₁) = (O, H), et R₂ = NH-CH₃ ou RO est différent de p-benzyloxy.

  式.的化合物 其中 - R 代表 C₃-C₆ 烷基或被 R₃ 取代的苄基，其中 R₃ = H、卤素、C₁-C₄ 烷基、C₁-C₄ 烷氧基、CF₃、NO₂ 或 CN；以及 - R₂ 代表： C₁-C₄ 烷氧基，在这种情况下，配对 (X，R₁) = (O，OH)、(O，C₁-C₄ 烷氧基)、(CHOH，H)、(O，H)、(CH₂，H) 或 (CO，H)； .OH 基团，在这种情况下，配对 (X, R₁) = (O, OH)、(O, C₁-C₄ 烷氧基)、(O, H) 或 (CH₂, H)，但前提是 * 当 (X，R₁) = (O，OH) 时，R 不是 C₃-C₆ 烷基和苄基，以及 * 当 (X，R₁) = (O，H) 时，RO 不同于 和邻苄氧基 ； .CN 基团，在这种情况下，(X, R₁)=(O, H) 或 (CH₂, H) 对；或 C₁-C₄ NH-烷基，在这种情况下，配对 (X, R₁)=(O, H) 或 (CH₂, H)，但当 (X, R₁) = (O, H) 和 R₂ = NH-CH₃ 或 RO 与对苄氧基不同。
• 1,3 di-substituted cyclobutane or azetidine derivatives as hematopoietic prostaglandin D synthase inhibitors
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：US11053234B2

  公开（公告）日：2021-07-06

  A compound of formula (I) wherein R, R1, R2, R3, Y, Y1, a, X, and Z are as defined herein. The compounds of the present invention are inhibitors of hematopoietic prostaglandin D synthase (H-PGDS) and can be useful in the treatment of Duchenne Muscular Dystrophy. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting H-PGDS activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  式 (I) 的化合物 其中 R、R1、R2、R3、Y、Y1、a、X 和 Z 如本文所定义。 本发明的化合物是造血前列腺素 D 合酶（H-PGDS）的抑制剂，可用于治疗杜氏肌肉萎缩症。因此，本发明进一步涉及包含本发明化合物的药物组合物。本发明还进一步涉及使用本发明化合物或包含本发明化合物的药物组合物抑制 H-PGDS 活性和治疗相关疾病的方法。