2',4'-difluoro-biphenyl-4-sulfonic acid (3-hydroxymethyl-2-methyl-phenyl)-amide | 1062213-39-1

• 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',4'-difluoro-biphenyl-4-sulfonic acid (3-hydroxymethyl-2-methyl-phenyl)-amide
• 英文别名: 4-(2,4-difluorophenyl)-N-[3-(hydroxymethyl)-2-methylphenyl]benzenesulfonamide
• CAS: 1062213-39-1
• 化学式: C₂₀H₁₇F₂NO₃S
• 分子量: 389.423
• InChiKey: XLELBGJNRPBOIX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  74.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-溴苯磺酰氯 在 吡啶 、 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 6.0h， 生成 2',4'-difluoro-biphenyl-4-sulfonic acid (3-hydroxymethyl-2-methyl-phenyl)-amide
  参考文献：
  名称：

  Development of triarylsulfonamides as novel anti-inflammatory agents

  摘要：

  Triaylsulfonamides were identified as novel anti-inflammatory agents, acting by inhibition of RANKL and TNF alpha signaling. Structure-activity studies led to the identification of compounds with in vitro potencies of <100 nM against J774 macrophages and osteoclasts, but with little activity against osteoblasts or hepatocytes (IC50 >50 mu M). A representative compound (4k, ABD455) was able to completely prevent inflammation in vivo in a prevention model and was highly effective at controlling inflammation in a treatment model. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.11.067

文献信息

• [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。
• Biphenyl-4-yl-sulfonic acid arylamides and their use as therapeutic agents
  申请人：Greig Iain Robert

  公开号：US20100286266A1

  公开（公告）日：2010-11-11

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain aryl sulfonamides and related compounds (collectively referred to herein as ‘BPSAAA compounds’), as described herein, and including, for example, biphenyl-4-sulfonic acid (hydroxyalkyl-phenyl)-amides and related compounds. 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, chronic obstructive pulmonary disease (COPD), atherosclerosis, 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，更具体地涉及某些芳基磺酰胺和相关化合物（统称为“BPSAAA化合物”），如本文所述，包括例如联苯基-4-磺酸（羟基烷基-苯基）-酰胺和相关化合物。本发明还涉及包含这些化合物的制药组合物，以及这些化合物和组合物在体内外治疗和/或预防炎症、关节破坏和/或骨质流失等方面的使用，包括过度和/或不适当和/或持续激活免疫系统介导的疾病，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）、动脉粥样硬化、炎症性肠病、强直性脊柱炎等，以及与骨质流失相关的疾病，例如类风湿性关节炎中过度成骨破骨细胞激活、骨质疏松症、癌症相关骨病、帕吉特病等。
• 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。
• 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：US10029979B2

  公开（公告）日：2018-07-24

  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 tumor 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.

  本发明一般涉及治疗化合物领域。更具体地说，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（在此统称为 HMC 化合物），这些化合物可用于治疗各种疾病（例如疾病），包括炎症和/或关节破坏和/或骨质流失；免疫系统过度和/或不适当和/或长期激活引起的疾病；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；斯约格伦综合征；与骨质流失有关的疾病，如类风湿性关节炎、骨质疏松症、癌症相关骨病或帕吉特氏病中与破骨细胞过度活动有关的骨质流失；癌症，如血液恶性肿瘤，如多发性骨髓瘤、白血病或淋巴瘤，或实体瘤癌症，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、基底细胞母细胞瘤或黑色素瘤；与纤维化相关的疾病，如系统性硬化症或硬皮病；或罕见的血管性疾病，如白塞氏病。本发明还涉及包含此类化合物的药物组合物，以及此类化合物和组合物在治疗等方面的用途。
• 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
  申请人：PIMCO 2664 LIMITED

  公开号：US10005733B2

  公开（公告）日：2018-06-26

  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 tumor 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.

  本发明一般涉及治疗化合物领域。更具体地说，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（在此统称为 HMC 化合物），这些化合物可用于治疗各种疾病（例如疾病），包括炎症和/或关节破坏和/或骨质流失；免疫系统过度和/或不适当和/或长期激活引起的疾病；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；斯约格伦综合征；与骨质流失有关的疾病，如类风湿性关节炎、骨质疏松症、癌症相关骨病或帕吉特氏病中与破骨细胞过度活动有关的骨质流失；癌症，如血液恶性肿瘤，如多发性骨髓瘤、白血病或淋巴瘤，或实体瘤癌症，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、基底细胞母细胞瘤或黑色素瘤；与纤维化相关的疾病，如系统性硬化症或硬皮病；或罕见的血管性疾病，如白塞氏病。本发明还涉及包含此类化合物的药物组合物，以及此类化合物和组合物在治疗等方面的用途。