1-(2',4'-dichlorobiphenyl-4-yl)hexane-1,6-diol | 1055896-24-6

• 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: 1-(2',4'-dichlorobiphenyl-4-yl)hexane-1,6-diol
• 英文别名: (R,S)-1-(2',4'-Dichloro-biphenyl-4-yl)-hexane-1,6-diol；1-[4-(2,4-Dichlorophenyl)phenyl]hexane-1,6-diol
• CAS: 1055896-24-6
• 化学式: C₁₈H₂₀Cl₂O₂
• 分子量: 339.262
• InChiKey: XSRUFIHKQNWPAD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1-(4-bromophenyl)hexane-1,6-diol 、 2,4-二氯苯硼酸 在 四(三苯基膦)钯 sodium carbonate 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 3.0h， 生成 1-(2',4'-dichlorobiphenyl-4-yl)hexane-1,6-diol
  参考文献：
  名称：

  2',4'-DICHLORO-BIPHENYL-4-YL-HYDROXY-KETONES AND RELATED COMPOUNDS AND THEIR USE AS THERAPEUTIC AGENTS

  摘要：

  本发明涉及治疗化合物领域，更具体地涉及某些2′，4′-二氯联苯基-4-羟基酮类化合物及相关化合物（以下统称为“DCBP化合物”），更进一步地，涉及选择自以下公式化合物及其药学上可接受的盐、溶剂和水合物的化合物：其中：n独立地为1、2、3或4；W独立地为—C(═O)—、—CH(OH)—或—C(═NOROX)—；ROX独立地为—H或C1-3烷基；J独立地为：—H、—RE1、—C(═O)—RE2、—C(═O)—O—RE3、—C(═O)—O—S(═O)2ORE4、—C(═O)—(CH2)n—C(═O)ORE5、—C(═O)—(CH2)n—NRNE1RNE2、—C(═O)—(CH2)n—NRNE3—C(═O)RE6、—C(═O)—(CH2)n—C(═O)—NRNE4RNE5或—P(═O)(ORE7)(ORE8)；其中，RE1、RE2、RE3、RE4、RE5、RE6和RE7中的每一个独立地为：—H、C1-3烷基、-Ph或—CH2-Ph。本发明还涉及包含这样的化合物的制剂，以及这样的化合物和制剂的使用，无论是体外还是体内，在治疗和/或预防方面，例如：炎症和/或关节破坏和/或骨质丢失；由免疫系统过度和/或不适当和/或持续激活引起的疾病；炎症和自身免疫性疾病，例如：类风湿性关节炎、银屑病、银屑病性关节炎、炎症性肠病、强直性脊柱炎等；与骨质丢失有关的疾病，例如：类风湿性关节炎中过度破骨细胞激活引起的骨质丢失、骨质疏松症、与癌症相关的骨病、帕吉特病等。

  公开号：

  US20080221220A1

文献信息

• 2',4'-DICHLORO-BIPHENYL-4-YL-HYDROXY-KETONES AND RELATED COMPOUNDS AND THEIR USE AS THERAPEUTIC AGENTS
  申请人：Greig Iain Robert

  公开号：US20080221220A1

  公开（公告）日：2008-09-11

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain 2′,4′-dichloro-biphenyl-4-yl-hydroxy-ketones and related compounds (collectively referred to herein as “DCBP compounds”), and more particularly to compounds selected from compounds of the following formula and pharmaceutically acceptable salts, solvates, and hydrates thereof: wherein: n is independently 1, 2, 3, or 4; W is independently —C(═O)—, —CH(OH)—, or —C(═NOR OX )—; R OX is independently —H or C 1-3 alkyl; J is independently: —H, —R E1 , —C(═O)—R E2 , —C(═O)—O—R E3 , —C(═O)—O—S(═O) 2 OR E4 , —C(═O)—(CH 2 ) n —C(═O)OR E5 , —C(═O)—(CH 2 ) n —NR NE1 R NE2 , —C(═O)—(CH 2 ) n —NR NE3 —C(═O)R E6 , —C(═O)—(CH 2 ) n —C(═O)—NR NE4 R NE5 , or —P(═O)(OR E7 )(OR E8 ); wherein each of R E1 , R E2 , R E3 , R E4 , R E5 , R E6 , and R E7 is independently: —H, C 1-3 alkyl, -Ph, or —CH 2 -Ph. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, in treatment and/or prevention, for example, of inflammation and/or joint destruction and/or bone loss; of disorders mediated by excessive and/or inappropriate and/or prolonged activation of the immune system; of, inflammatory and autoimmune disorders, for example, rheumatoid arthritis, psoriasis, psoriatic arthritis, inflammatory bowel disease, ankylosing spondylitis, and the like; of disorders associated with bone loss, such as bone loss associated with excessive osteoclast activation in rheumatoid arthritis, osteoporosis, cancer associated bone disease, Paget's disease and the like.

  本发明涉及治疗化合物领域，更具体地涉及某些2′，4′-二氯联苯基-4-羟基酮类化合物及相关化合物（以下统称为“DCBP化合物”），更进一步地，涉及选择自以下公式化合物及其药学上可接受的盐、溶剂和水合物的化合物：其中：n独立地为1、2、3或4；W独立地为—C(═O)—、—CH(OH)—或—C(═NOROX)—；ROX独立地为—H或C1-3烷基；J独立地为：—H、—RE1、—C(═O)—RE2、—C(═O)—O—RE3、—C(═O)—O—S(═O)2ORE4、—C(═O)—(CH2)n—C(═O)ORE5、—C(═O)—(CH2)n—NRNE1RNE2、—C(═O)—(CH2)n—NRNE3—C(═O)RE6、—C(═O)—(CH2)n—C(═O)—NRNE4RNE5或—P(═O)(ORE7)(ORE8)；其中，RE1、RE2、RE3、RE4、RE5、RE6和RE7中的每一个独立地为：—H、C1-3烷基、-Ph或—CH2-Ph。本发明还涉及包含这样的化合物的制剂，以及这样的化合物和制剂的使用，无论是体外还是体内，在治疗和/或预防方面，例如：炎症和/或关节破坏和/或骨质丢失；由免疫系统过度和/或不适当和/或持续激活引起的疾病；炎症和自身免疫性疾病，例如：类风湿性关节炎、银屑病、银屑病性关节炎、炎症性肠病、强直性脊柱炎等；与骨质丢失有关的疾病，例如：类风湿性关节炎中过度破骨细胞激活引起的骨质丢失、骨质疏松症、与癌症相关的骨病、帕吉特病等。
• US7560597B2
  申请人：——

  公开号：US7560597B2

  公开（公告）日：2009-07-14
• Discovery of biphenylketones as dual modulators of inflammation and bone loss
  作者：Iain R. Greig、Emmanuel Coste、Stuart H. Ralston、Rob J. van’t Hof

  DOI：10.1016/j.bmcl.2010.07.055

  日期：2010.9

  Biphenylketones were identified as novel inhibitors of NF kappa B activation. Structure-activity studies led to the identification of compound 4c, which had good potency against osteoclasts (IC(50) = 0.8 mu M), showed oral activity, and was able to completely prevent inflammation and bone loss in vivo. (C) 2010 Elsevier Ltd. All rights reserved.