2'-trifluoromethylbiphenyl-4-sulfonic acid-(5-hydroxypentyl)-amide | 871113-95-0

• 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: 2'-trifluoromethylbiphenyl-4-sulfonic acid-(5-hydroxypentyl)-amide
• 英文别名: 2'-trifluoromethylbiphenyl-4-sulfonic acid-(5-hydroxypentyl)amide；[1,1'-Biphenyl]-4-sulfonamide, N-(5-hydroxypentyl)-2'-(trifluoromethyl)-；N-(5-hydroxypentyl)-4-[2-(trifluoromethyl)phenyl]benzenesulfonamide
• CAS: 871113-95-0
• 化学式: C₁₈H₂₀F₃NO₃S
• 分子量: 387.423
• InChiKey: HXVIIIDKXQBWDK-UHFFFAOYSA-N

物化性质

• 熔点：
  55-57 °C
• 沸点：
  512.3±60.0 °C(Predicted)
• 密度：
  1.281±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  74.8
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-氨基-1-戊醇 在 四(三苯基膦)钯 吡啶 、 sodium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 2.0h， 生成 2'-trifluoromethylbiphenyl-4-sulfonic acid-(5-hydroxypentyl)-amide
  参考文献：
  名称：

  Development and Characterization of Biphenylsulfonamides as Novel Inhibitors of Bone Resorption

  摘要：

  Increased osteoclastic bone resorption plays a central role in the pathogenesis of many bone diseases, and osteoclast inhibitors are the most widely used treatments for these diseases. We have identified and characterized a series of novel biphenylsulfonamide derivatives that have potent inhibitory effects on osteoclastic bone resorption in vitro and that prevent ovariectomy-induced bone loss in vivo. A number of aromatic substituted derivatives were prepared and a QSAR model was generated, which allowed accurate prediction of compound potency. Using this model, we have prepared compounds able to inhibit osteoclast formation and bone resorption in vitro at concentrations in the nanomolar range. One such compound, 55 (ABD295) (Greig, I. R.; Mohamed, A. I.; Ralston, S. H.; van't Hof, R. J. Alkyl Aryl Sulfonamides as Therapeutic Agents for the Treatment of Bone Conditions. GB Patent WO2005118528, 2005), fully reversed ovariectomy-induced bone loss in mice at a dose of 5 (mg/kg)/day. In conclusion, biphenylsulfonamides like 55 form a new class of potent antiresorptive agents with possible therapeutic use in diseases characterized by increased bone resorption.

  DOI：

  10.1021/jm051236m

文献信息

• [EN] N-(4-HYDROXY-4-METHYL-CYCLOHEXYL)-4-PHENYL-BENZENESULFONAMIDES AND N-(4-HYDROXY-4-METHYL-CYCLOHEXYL)-4-(2-PYRIDYL)BENZENESULFONAMIDES AND THEIR THERAPEUTIC USE<br/>[FR] N-(4-HYDROXY-4-MÉTHYLCYCLOHEXYL)-4-PHÉNYLBENZÈNESULFONAMIDES ET N-(4-HYDROXY-4-MÉTHYLCYCLOHEXYL)-4-(2-PYRIDYL)BENZÈNESULFONAMIDES ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：PIMCO 2664 LTD

  公开号：WO2014207445A1

  公开（公告）日：2014-12-31

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain substituted N-(4-hydroxy-4- methyl-cyclohexyl)-4-phenyl-benzenesulfonamide and N-(4-hydroxy-4-methyl- cyclohexyl)-4-(2-pyridyl)benzenesulfonamide compounds (collectively referred to herein as HMC compounds) that are useful, for example, in the treatment of disorders (e.g., diseases) including, inflammation and/or joint destruction and/or bone loss; disorders mediated by excessive and/or inappropriate and/or prolonged activation of the immune system; inflammatory and autoimmune disorders, for example, rheumatoid arthritis; psoriasis; psoriatic arthritis; chronic obstructive pulmonary disease (COPD); asthma; atherosclerosis; inflammatory bowel disease; ankylosing spondylitis; multiple sclerosis; systemic lupus erythematosus; Sjogren's syndrome; a disorder associated with bone loss, such as bone loss associated with excessive osteoclast activity in rheumatoid arthritis, osteoporosis, cancer-associated bone disease, or Paget's disease; cancer, such as a haematological malignancy, such as multiple myeloma, leukemia, or lymphoma, or a solid tumour cancer, such as bladder cancer, breast cancer (female and / or male), colon cancer, renal cell carcinoma, kidney cancer, lung cancer, pancreatic cancer, gastric cancer, prostate cancer, brain cancer, skin cancer, thyroid cancer, basal cell ameloblastoma, or melanoma; a disorder associated with fibrosis, such as systemic sclerosis or scleroderma; or a rare vasculitide, such as Behçet's disease. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, for example, in therapy.

  本发明涉及治疗化合物领域。更具体地，本发明涉及某些取代的N-(4-羟基-4- 甲基环己基)-4-苯基-苯磺酰胺和N-(4-羟基-4-甲基环己基)-4-(2-吡啶基)苯磺酰胺化合物（以下统称为HMC化合物），该化合物可用于治疗包括炎症和/或关节破坏和/或骨质流失等疾病的治疗，由过度和/或不适当和/或持续激活免疫系统引起的疾病；炎症性和自身免疫性疾病，例如类风湿性关节炎；牛皮癣；银屑病性关节炎；慢性阻塞性肺病（COPD）；哮喘；动脉粥样硬化；炎症性肠病；强直性脊柱炎；多发性硬化症；系统性红斑狼疮；干燥综合症；与骨质流失有关的疾病，例如类风湿性关节炎中与过度破坏骨细胞活性有关的骨质流失，骨质疏松症，癌症相关骨病或Paget病；癌症，如血液恶性肿瘤，如多发性骨髓瘤，白血病或淋巴瘤，或实体肿瘤癌，如膀胱癌，乳腺癌（女性和/或男性），结肠癌，肾细胞癌，肾癌，肺癌，胰腺癌，胃癌，前列腺癌，脑癌，皮肤癌，甲状腺癌，基底细胞颌骨癌或黑色素瘤；与纤维化有关的疾病，如系统性硬化症或硬皮病；或罕见的血管炎，如Behçet病。本发明还涉及包含这种化合物的药物组合物，以及这种化合物和组合物的用途，例如在治疗中的应用。
• [EN] N-(4-HYDROXY-4-METHYL-CYCLOHEXYL)-4-PHENYL-BENZENESULFONAMIDE AND N-(4-HYDROXY-4-METHYL-CYCLOHEXYL)-4-(2-PYRIDYL)-BENZENESULFONAMIDE COMPOUNDS AND THEIR THERAPEUTIC USE<br/>[FR] N-(4-HYDROXY-4-MÉTHYLCYCLOHEXYL)-4-PHÉNYLBENZÈNESULFONAMIDES ET N-(4-HYDROXY-4-MÉTHYLCYCLOHEXYL)-4-(2-PYRIDYL)BENZÈNESULFONAMIDES ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：PIMCO 2664 LTD

  公开号：WO2016097001A1

  公开（公告）日：2016-06-23

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain substituted N-(4-hydroxy-4- methyl-cyclohexyl)-4-phenyl-benzenesulfonamide and N-(4-hydroxy-4-methyl- cyclohexyl)-4-(2-pyridyl)benzenesulfonamide compounds (collectively referred to herein as HMC compounds) that are useful, for example, in the treatment of disorders (e.g., diseases) including, inflammation and/or joint destruction and/or bone loss; disorders mediated by excessive and/or inappropriate and/or prolonged activation of the immune system; inflammatory and autoimmune disorders, for example, rheumatoid arthritis; psoriasis; psoriatic arthritis; chronic obstructive pulmonary disease (COPD); asthma; atherosclerosis; inflammatory bowel disease; ankylosing spondylitis; multiple sclerosis; systemic lupus erythematosus; Sjogren's syndrome; a disorder associated with bone loss, such as bone loss associated with excessive osteoclast activity in rheumatoid arthritis, osteoporosis, cancer-associated bone disease, or Paget's disease; cancer, such as a haematological malignancy, such as multiple myeloma, leukemia, or lymphoma, or a solid tumour cancer, such as bladder cancer, breast cancer (female and / or male), colon cancer, renal cell carcinoma, kidney cancer, lung cancer, pancreatic cancer, gastric cancer, prostate cancer, brain cancer, skin cancer, thyroid cancer, basal cell ameloblastoma, or melanoma; a disorder associated with fibrosis, such as systemic sclerosis or scleroderma; or a rare vasculitide, such as Behçet's disease. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, for example, in therapy.

  本发明涉及治疗化合物领域。更具体地，本发明涉及某些取代的N-(4-羟基-4-甲基-环己基)-4-苯基-苯磺酰胺和N-(4-羟基-4-甲基-环己基)-4-(2-吡啶基)苯磺酰胺化合物（以下统称为HMC化合物），例如用于治疗炎症和/或关节破坏和/或骨质流失等疾病；由免疫系统过度和/或不适当和/或持久激活引起的疾病；炎症和自身免疫性疾病，例如类风湿性关节炎；牛皮癣；银屑病性关节炎；慢性阻塞性肺疾病（COPD）；哮喘；动脉粥样硬化；炎症性肠病；强直性脊柱炎；多发性硬化症；全身性红斑狼疮；Sjogren综合征；与骨质流失有关的疾病，例如与类风湿性关节炎、骨质疏松症、癌症相关骨病或Paget病中过度破骨细胞活动有关的骨质流失；癌症，例如血液恶性肿瘤，例如多发性骨髓瘤、白血病或淋巴瘤，或实体肿瘤癌症，例如膀胱癌、乳腺癌（女性和/或男性）、结肠癌、肾细胞癌、肾癌、肺癌、胰腺癌、胃癌、前列腺癌、脑癌、皮肤癌、甲状腺癌、基底细胞颌骨瘤或黑色素瘤；与纤维化有关的疾病，例如系统性硬化或硬皮病；或罕见的血管炎，例如Behçet病。本发明还涉及包含此类化合物的制药组合物，以及这些化合物和组合物的使用，例如用于治疗。
• Aryl Alkyl Sulfonamides As Therapeutic Agents For The Treatment Of Bone Conditions
  申请人：Ralston Stuart Hamilton

  公开号：US20080119555A1

  公开（公告）日：2008-05-22

  The present invention pertains to certain aryl alkyl sulfonamides and derivatives thereof which, inter alia, inhibit osteoclast survival, formation, and/or activity; and/or inhibit bone resorption, and more particularly to compounds of the formula: wherein: Ar 1 is independently C 5-20 aryl (e.g., biphenyl, phenanthryl, fluorenyl, or carbazolyl, most preferably biphenyl), and is optionally substituted; R N is independently —H, acyl, C 5-20 aryl-C 1-7 alkyl, C 3-20 heterocyclyl, or C 1-7 alkyl, and is optionally substituted; R alk is a C 2-10 alkylene group, and is optionally substituted; and Q is independently —H or an organic group having from 1 to 30 atoms selected from carbon, nitrogen, oxygen, sulfur, phosphorus, fluorine, chlorine, bromine, and iodine (e.g., an oxy-type group, an amine-type group, etc.); and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. 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, to inhibit osteoclast survival, formation, and/or activity, and to inhibit conditions mediated by osteoclasts and/or characterised by bone resorption, in the treatment of bone disorders such as osteoporosis, rheumatoid arthritis, cancer associated bone disease, Paget's disease, and the like; and/or in the treatment of conditions associated with inflammation or activation of the immune system.

  本发明涉及某些芳基烷基磺酰胺及其衍生物，其中，它们抑制破骨细胞的存活、形成和/或活性；和/或抑制骨吸收，更具体地说，是式子的化合物： 其中：Ar1独立地是C5-20芳基（例如，联苯、菲、芴或咔唑基，最好是联苯），并且可以选择性地被取代；RN独立地是-H、酰基、C5-20芳基-C1-7烷基、C3-20杂环基或C1-7烷基，并且可以选择性地被取代；Ralk是C2-10烷基链，可以选择性地被取代；Q独立地是-H或具有1-30个由碳、氮、氧、硫、磷、氟、氯、溴和碘选择的有机基团（例如，氧型基团，胺型基团等）；以及其药学上可接受的盐、溶剂化合物、酰胺、酯、醚、化学保护形式和前药。本发明还涉及包含这样的化合物的制药组合物，以及在体外和体内使用这样的化合物和组合物来抑制破骨细胞的存活、形成和/或活性，并抑制由破骨细胞介导和/或通过骨吸收表征的骨疾病的治疗，例如骨质疏松症、类风湿性关节炎、与癌症相关的骨疾病、帕吉特病等；和/或用于治疗与炎症或免疫系统激活有关的疾病。
• Aryl alkyl sulfonamides as therapeutic agents for the treatment of bone conditions
  申请人：The University Court of the University of Aberdeen

  公开号：US07964643B2

  公开（公告）日：2011-06-21

  The present invention pertains to compounds of the following formula (wherein RP, r, q, RN, Ralk, and Q are as defined herein) and compositions comprising those compounds. The compounds may be used to inhibit osteoclast survival, formation, and/or activity; to inhibit conditions mediated by osteoclasts and/or characterised by bone resorption; in the treatment of bone disorders such as osteoporosis, rheumatoid arthritis, cancer associated bone disease, Paget's disease; and/or in the treatment of conditions associated with inflammation or activation of the immune system.

  本发明涉及以下式子的化合物（其中RP、r、q、RN、Ralk和Q的定义如下）以及含有这些化合物的组合物。这些化合物可以用于抑制破骨细胞的存活、形成和/或活性；抑制由破骨细胞介导的和/或以骨吸收为特征的疾病；用于治疗骨疾病，如骨质疏松、类风湿性关节炎、与癌症相关的骨病和Paget病；以及用于治疗与炎症或免疫系统激活相关的疾病。
• N-(4-HYDROXY-4-METHYL-CYCLOHEXYL)-4-PHENYL-BENZENESULFONAMIDES AND N-(4- HYDROXY-4-METHYL-CYCLOHEXYL)-4-(2-PYRIDYL)BENZENESULFONAMIDES AND THEIR THERAPEUTIC USE
  申请人：PIMCO 2664 LIMITED

  公开号：US20160145206A1

  公开（公告）日：2016-05-26

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain substituted N-(4-hydroxy-4-methyl-cyclohexyl)-4-phenyl-benzenesulfonamide and N-(4-hydroxy-4-methyl-cyclohexyl)-4-(2-pyridyl)benzenesulfonamide compounds (collectively referred to herein as HMC compounds) that are useful, for example, in the treatment of disorders (e.g., diseases) including, inflammation and/or joint destruction and/or bone loss; disorders mediated by excessive and/or inappropriate and/or prolonged activation of the immune system; inflammatory and autoimmune disorders, for example, rheumatoid arthritis; psoriasis; psoriatic arthritis; chronic obstructive pulmonary disease (COPD); asthma; atherosclerosis; inflammatory bowel disease; ankylosing spondylitis; multiple sclerosis; systemic lupus erythematosus; Sjogren's syndrome; a disorder associated with bone loss, such as bone loss associated with excessive osteoclast activity in rheumatoid arthritis, osteoporosis, cancer-associated bone disease, or Paget's disease; cancer, such as a haematological malignancy, such as multiple myeloma, leukemia, or lymphoma, or a solid tumour cancer, such as bladder cancer, breast cancer (female and/or male), colon cancer, renal cell carcinoma, kidney cancer, lung cancer, pancreatic cancer, gastric cancer, prostate cancer, brain cancer, skin cancer, thyroid cancer, basal cell ameloblastoma, or melanoma; a disorder associated with fibrosis, such as systemic sclerosis or scleroderma; or a rare vasculitide, such as Behçet's disease. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, for example, in therapy.

  本发明涉及治疗化合物领域。更具体地，本发明涉及某些取代的N-(4-羟基-4-甲基-环己基)-4-苯基-苯磺酰胺和N-(4-羟基-4-甲基-环己基)-4-(2-吡啶基)苯磺酰胺化合物（以下统称为HMC化合物），例如在治疗疾病中有用，包括炎症和/或关节破坏和/或骨质流失的疾病；由免疫系统过度和/或不适当和/或持续激活介导的疾病；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；慢性阻塞性肺疾病（COPD）；哮喘；动脉粥样硬化；炎症性肠病；强直性脊柱炎；多发性硬化症；系统性红斑狼疮；Sjogren综合症；与骨质流失有关的疾病，例如与类风湿性关节炎，骨质疏松症，癌症相关骨病或Paget病中过度破骨细胞活性有关的骨质流失；癌症，例如血液恶性肿瘤，例如多发性骨髓瘤，白血病或淋巴瘤，或实体肿瘤癌，例如膀胱癌，乳腺癌（女性和/或男性），结肠癌，肾细胞癌，肾癌，肺癌，胰腺癌，胃癌，前列腺癌，脑癌，皮肤癌，甲状腺癌，基底细胞上皮瘤或黑色素瘤；与纤维化有关的疾病，例如系统性硬化或硬皮病；或罕见的血管炎，例如Behçet病。本发明还涉及包含这种化合物的制药组合物以及这种化合物和组合物的使用，例如在治疗中。