4-chlorobiphenylethane bromide | 344597-13-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-chlorobiphenylethane bromide
• 英文别名: 4-chlorobiphenylethanebromide；1-(2-Bromoethyl)-4-(4-chlorophenyl)benzene
• CAS: 344597-13-3
• 化学式: C₁₄H₁₂BrCl
• 分子量: 295.606
• InChiKey: VGXJFQIEQWMDTH-UHFFFAOYSA-N

物化性质

• 沸点：
  368.6±30.0 °C(Predicted)
• 密度：
  1.389±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  4-chlorobiphenylethane bromide 在 五氯化磷 、 四丁基碘化铵 、 sodium sulfite 作用下， 以 乙醇 、 水 为溶剂， 反应 22.0h， 生成 4-chloro-biphenylethanesulfonyl chloride
  参考文献：
  名称：

  Tetrahydroisoquinoline-3-carboxylate based matrix-metalloproteinase inhibitors: design, synthesis and structure–activity relationship

  摘要：

  The design, synthesis and structure-activity relationship (SAR) of a series of nonpeptidic 2-arylsulfonyl-1,2,3,4-tetra-hydro-isoquinoline-3-carboxylates and-hydroxamates as inhibitors of the matrix metalloproteinase human neutrophil collagenase (MMP-8) is described here. Based on available X-ray structures of MMP-8/inhibitor complexes, our structure-based design strategy was directed to complement major protein-ligand interaction regions mainly in the S1' hydrophobic specificity pocket close to the catalytic zinc ion. Here, the rigid 1,2,3,4-tetrahydroisoquinoline scaffold (Tic) provides ideal geometry to combine hydroxamates and carboxylates as typical zinc complexing functionalities, with a broad variety of S1' directed mono- and biaryl substituents consisting of aromatic rings perfectly accommodated within this more hydrophobic region of the MMP-8 inhibitor binding site. The effect of different S1' directed substituents, zinc-complexing groups, chirality and variations of the tetrahydroisoquinoline ring-system is investigated by systematic studies. X-ray structure analyses in combination with 3D-QSAR studies provided an additional understanding of key determinants for MMP-8 affinity in this series. The hypothetical binding mode for a typical molecule as basis for our inhibitor design was found in good agreement with a 1.7 Angstrom X-ray structure of this candidate in complex with the catalytic domain of human MMP-8. After analysis of all systematic variations, 3D-QSAR and X-ray structure analysis, novel S1' directed substituents were designed and synthesized and biologically evaluated. This finally results in inhibitors, which do not only show high biological affinity for MMP-8, but also exhibit good oral bioavailability in several animal species. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00215-8
• 作为产物：
  描述：

  4-氯联苯 在 三氯化铝 、 borane tert-butylamine 作用下， 以 二硫化碳 、 二氯甲烷 为溶剂， 反应 7.0h， 生成 4-chlorobiphenylethane bromide
  参考文献：
  名称：

  Tetrahydroisoquinoline-3-carboxylate based matrix-metalloproteinase inhibitors: design, synthesis and structure–activity relationship

  摘要：

  The design, synthesis and structure-activity relationship (SAR) of a series of nonpeptidic 2-arylsulfonyl-1,2,3,4-tetra-hydro-isoquinoline-3-carboxylates and-hydroxamates as inhibitors of the matrix metalloproteinase human neutrophil collagenase (MMP-8) is described here. Based on available X-ray structures of MMP-8/inhibitor complexes, our structure-based design strategy was directed to complement major protein-ligand interaction regions mainly in the S1' hydrophobic specificity pocket close to the catalytic zinc ion. Here, the rigid 1,2,3,4-tetrahydroisoquinoline scaffold (Tic) provides ideal geometry to combine hydroxamates and carboxylates as typical zinc complexing functionalities, with a broad variety of S1' directed mono- and biaryl substituents consisting of aromatic rings perfectly accommodated within this more hydrophobic region of the MMP-8 inhibitor binding site. The effect of different S1' directed substituents, zinc-complexing groups, chirality and variations of the tetrahydroisoquinoline ring-system is investigated by systematic studies. X-ray structure analyses in combination with 3D-QSAR studies provided an additional understanding of key determinants for MMP-8 affinity in this series. The hypothetical binding mode for a typical molecule as basis for our inhibitor design was found in good agreement with a 1.7 Angstrom X-ray structure of this candidate in complex with the catalytic domain of human MMP-8. After analysis of all systematic variations, 3D-QSAR and X-ray structure analysis, novel S1' directed substituents were designed and synthesized and biologically evaluated. This finally results in inhibitors, which do not only show high biological affinity for MMP-8, but also exhibit good oral bioavailability in several animal species. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00215-8

文献信息

• SUBSTITUTED TETRAHYDROISOQUINOLINES USED IN THE FORM OF MMP INHIBITORS, METHOD FOR THE PRODUCTION AND USE THEREOF IN THE FORM OF DRUGS
  申请人：Hofmeister Armin

  公开号：US20070203118A1

  公开（公告）日：2007-08-30

  The present invention is directed to a compound of formula (I) wherein R 1 , R 2 , R 3 , R 4 , A, L and n are as defined herein, or a pharmacologically acceptable salt thereof, its pharmaceutical composition and it use as a MMP inhibitor.

  本发明涉及一种具有以下化学式(I)的化合物，其中R1、R2、R3、R4、A、L和n如本文所定义，或其药理学上可接受的盐，以及其药物组合物及其作为MMP抑制剂的用途。
• [DE] BICYCLISCHE IMINOSÄUREDERIVATE ALS INHIBITOREN VON MATRIX-METALLOPROTEINASEN<br/>[EN] BICYCLIC IMINO ACID DERIVATIVES USED AS INHIBITORS OF MATRIX-METALLOPROTEINASES<br/>[FR] DERIVES D'IMINOACIDE BICYCLIQUES SERVANT D'INHIBITEURS DES METALLOPROTEINASES MATRICIELLES
  申请人：AVENTIS PHARMA GMBH

  公开号：WO2005030728A1

  公开（公告）日：2005-04-07

  Verbindungen der Formel (I) eignen sich zur Herstellung von Arzneimitteln zur Prophylaxe und Therapie von Erkrankungen,an deren Verlauf eine verstärkte Aktivität von Matrix-Metalloproteinasen beteiligt sind. Dazu gehören Erkrankungen wie eine degenerative Gelenkerkrankung beispielsweise Osteoarthrosen, Spondylosen, Knorpelschwund nach Gelenktrauma oder längerer Gelenksruhigstellung nach Meniskus- oder Patellaverletzungen oder Bänderrissen, oder eine Erkrankung des Bindegewebes wie Kollagenosen, Periodontalerkrankungen, Wundheilungsstörungen, oder eine chronische Erkrankung des Bewegungsapparates wie entzündliche, immunologisch oder stoffwechselbedingte akute oder chronische Arthritiden, Arthropathien, Myalgien oder Störungen des Knochenstoffwechsels oder eine Ulceration, Atherosklerose oder Stenose oder eine enzündliche Erkrankung oder eine Krebserkrankung, Tumormetastasenbildung, Kachexie, Anorexie oder septischer Schock.

  化学式（I）的连接物适用于制备用于预防和治疗与基质金属蛋白酶活性增强有关的疾病的药物。这些疾病包括退行性关节疾病，例如骨关节炎，脊椎病，关节创伤后的软骨流失或长期关节休息后的膝盖半月板或韧带损伤，或结缔组织疾病，如胶原病，牙周病，伤口愈合障碍，或慢性运动器官疾病，如炎症性，免疫学或代谢性急性或慢性关节炎，关节病，肌痛或骨代谢障碍或溃疡，动脉粥样硬化或狭窄，炎性疾病或癌症，肿瘤转移，恶病质，厌食或脓毒性休克。
• Procédé de préparation de dérives biphenylyl
  申请人：SANOFI-SYNTHELABO

  公开号：EP1216996A2

  公开（公告）日：2002-06-26

  L'invention concerne un procédé pour la préparation de dérivés biphénylyl par condensation entre des dérivés phényl substitués par un groupe partant et des acides benzèneboroniques, en présence d'un catalyseur, d'une base forte et d'un agent de transfert de phase.

  本发明涉及一种在催化剂、强碱和相转移剂存在下，通过被离去基团取代的苯基衍生物与苯硼酸缩合制备联苯衍生物的工艺。
• [DE] SUBSTITUIERTE TETRAHYDROISOCHINOLINE ALS MMP-INHIBITOREN, VERFAHREN ZU IHRER HERSTELLUNG UND IHRE VERWENDUNG ALS MEDIKAMENT<br/>[EN] SUBSTITUTED TETRAHYDROISOCHINOLINES USED IN THE FORM OF MMP INHIBITORS, METHOD FOR THE PRODUCTION AND USE THEREOF IN THE FORM OF DRAGS<br/>[FR] TETRAHYDRO-ISOQUINOLEINES SUBSTITUEES, UTILISEES COMME INHIBITEURS MMP, LEUR PROCEDE DE FABRICATION ET LEUR UTILISATION COMME MEDICAMENTS
  申请人：SANOFI AVENTIS DEUTSCHLAND

  公开号：WO2006002763A3

  公开（公告）日：2006-03-16
• 4-ARYL-1-PHENYLALKYL-1,2,3,6-TETRAHYDROPYRIDINES AYANT UNE ACTIVITE NEUROTROPHIQUE ET NEUROPROTECTRICE
  申请人：SANOFI

  公开号：EP0837848A1

  公开（公告）日：1998-04-29