(3-trifluoromethanesulfonyloxynaphthalen-1-yl)acetic acid ethyl ester | 425638-83-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (3-trifluoromethanesulfonyloxynaphthalen-1-yl)acetic acid ethyl ester
• 英文别名: (3-trifluoromethanesulfonyloxy-naphthalen-1-yl)-acetic acid ethyl ester；ethyl 2-[3-(trifluoromethylsulfonyloxy)naphthalen-1-yl]acetate
• CAS: 425638-83-1
• 化学式: C₁₅H₁₃F₃O₅S
• 分子量: 362.326
• InChiKey: MKSVLDDZTHRBMJ-UHFFFAOYSA-N

物化性质

• 沸点：
  435.8±45.0 °C(Predicted)
• 密度：
  1.424±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  78
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (3-trifluoromethanesulfonyloxynaphthalen-1-yl)acetic acid ethyl ester 在 potassium phosphate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 sodium methylate 、 silica gel 、 formamide 、 2-(二叔丁基膦)联苯 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 2-[3-(4-methylpiperazin-1-yl)naphthalen-1-yl]acetamide acetate
  参考文献：
  名称：

  Structure–Activity Relationship and Pharmacokinetic Studies of Sotrastaurin (AEB071), a Promising Novel Medicine for Prevention of Graft Rejection and Treatment of Psoriasis

  摘要：

  Protein kinase C (PKC) isotypes have emerged as key targets for the blockade of early T-cell activation. Herein, we report on the structure - activity relationship and the detailed physicochemical and in vivo pharmacokinetic properties of sotrastaurin (AEB071, 1), a novel maleimide-based PKC inhibitor currently in phase II clinical trials. Most notably, the preferred uptake of sotrastaurin into lymphoid tissues is an important feature, which is likely to contribute to its in vivo efficacy.

  DOI：

  10.1021/jm200469u
• 作为产物：
  描述：

  1-溴-3-羟基萘 在 吡啶 、 二氯双(三邻甲苯膦)合钯(II) 、 palladium 10% on activated carbon 、 氢气 、 sodium hydride 、 zinc dibromide 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 80.0 ℃ 、101.33 kPa 条件下， 反应 35.0h， 生成 (3-trifluoromethanesulfonyloxynaphthalen-1-yl)acetic acid ethyl ester
  参考文献：
  名称：

  Structure–Activity Relationship and Pharmacokinetic Studies of Sotrastaurin (AEB071), a Promising Novel Medicine for Prevention of Graft Rejection and Treatment of Psoriasis

  摘要：

  Protein kinase C (PKC) isotypes have emerged as key targets for the blockade of early T-cell activation. Herein, we report on the structure - activity relationship and the detailed physicochemical and in vivo pharmacokinetic properties of sotrastaurin (AEB071, 1), a novel maleimide-based PKC inhibitor currently in phase II clinical trials. Most notably, the preferred uptake of sotrastaurin into lymphoid tissues is an important feature, which is likely to contribute to its in vivo efficacy.

  DOI：

  10.1021/jm200469u

文献信息

• Discovery of 3-(1<i>H</i>-Indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione (AEB071), a Potent and Selective Inhibitor of Protein Kinase C Isotypes
  作者：Jürgen Wagner、Peter von Matt、Richard Sedrani、Rainer Albert、Nigel Cooke、Claus Ehrhardt、Martin Geiser、Gabriele Rummel、Wilhelm Stark、Andre Strauss、Sandra W. Cowan-Jacob、Christian Beerli、Gisbert Weckbecker、Jean-Pierre Evenou、Gerhard Zenke、Sylvain Cottens

  DOI：10.1021/jm901108b

  日期：2009.10.22

  A series of novel maleimide-based inhibitors of protein kinase C (PKC) were designed, synthesized, and evaluated. AEB071 (1) was found to be a potent, selective inhibitor of classical and novel PKC isotypes. 1 is a highly efficient immunomodulator, acting via inhibition of early T cell activation. The binding mode of maleimides to PKCs, proposed by molecular modeling, was confirmed by X-ray analysis

  设计，合成和评估了一系列新型的基于马来酰亚胺的蛋白激酶C（PKC）抑制剂。发现AEB071（1）是经典和新型PKC同种型的有效选择性抑制剂。图1是高效的免疫调节剂，其通过抑制早期T细胞活化而起作用。通过分子建模提出的马来酰亚胺与PKCs的结合模式，通过对PKCα活性位点中结合的1个X射线分析进行了证实。
• [EN] INDOLYLMALEIMIDE DERIVATIVES<br/>[FR] DÉRIVÉS D'INDOLYLMALÉIMIDE
  申请人：NOVARTIS AG

  公开号：WO2003082859A1

  公开（公告）日：2003-10-09

  Provided are compounds of Formula (I), which are useful in the treatment and/or prevention of diseases or disorders mediated by T lymphocytes and/or PKC, e.g. acute or chronic rejection of organ or tissue allo- or xenografts, graft versus host diseases, atherosclerosis, vascular occlusion due to vascular injury such as angioplasty, restenosis, obesity, syndrome X, impaired glucose tolerance, polycystic ovary syndrome, hypertension, heart failure, chronic obstructive pulmonary disease, CNS diseases such as Alzheimer disease or amyotrophic lateral sclerosis, cancer, infectious diseases such as AIDS, septic shock or adult respiratory distress syndrome, ischemia/reperfusion injury e.g. myocardial infraction, stroke, gut ischemia, renal failure or hemorrhage shock, or traumatic shock, e.g. traumatic brain injury. The compounds of (I) are also useful in the treatment and/or prevention of T-cell mediated acute or chronic inflammatory diseases or disorders or autoimmune diseases e.g. rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, Hashimoto’s thyroidis, multiple sclerosis, myasthenia gravis, diabetes type I or II and the disorders associated therewith, e.g. angiopathy, diabetic proliferative retinopathy, diabetic macular edema, nephropathy, neuropathy and dawn phenomenon, respiratory diseases such as asthma or inflammatory lung injury, inflammatory liver injury, inflammatory glomerular injury, cutaneous manifestations of immunologically-mediated disorders or illnesses, inflammatory and hyperproliferative skin diseases (such as psoriasis, atopic dermatitis, allergic contact dermatitis, irritant contact dermatitis and further eczematous dermatitises, seborrhoeic dermatitis), inflammatory eye diseases, e.g. Sjoegren’s syndrome, keratoconjunctivitis or uveitis, inflammatory bowel disease, Crohn’s disease or ulcerative colitis.

  提供的是化合物的化学式（I），可用于治疗和/或预防由T淋巴细胞和/或PKC介导的疾病或紊乱，例如器官或组织同种异体或异种移植的急性或慢性排斥、移植物抗宿主病、动脉粥样硬化、由血管损伤引起的血管闭塞，如血管成形术后的再狭窄、肥胖、X综合征、糖耐量受损、多囊卵巢综合征、高血压、心力衰竭、慢性阻塞性肺疾病、中枢神经系统疾病，如阿尔茨海默病或肌萎缩侧索硬化、癌症、感染性疾病，如艾滋病、脓毒性休克或成人呼吸窘迫综合征、缺血/再灌注损伤，例如心肌梗死、中风、肠道缺血、肾功能衰竭或出血性休克，或创伤性休克，例如创伤性脑损伤。化合物（I）也可用于治疗和/或预防T细胞介导的急性或慢性炎症性疾病或紊乱或自身免疫性疾病，例如类风湿性关节炎、骨关节炎、系统性红斑狼疮、Hashimoto甲状腺炎、多发性硬化症、重症肌无力、糖尿病I型或II型及相关疾病，例如血管病、糖尿病性增生性视网膜病变、糖尿病性黄斑水肿、肾病、神经病和晨间现象、呼吸系统疾病，如哮喘或炎症性肺损伤、炎症性肝损伤、炎症性肾小球损伤、免疫介导疾病或疾病的皮肤表现、炎症性和过度增生性皮肤疾病（如银屑病、特应性皮炎、过敏性接触性皮炎、刺激性接触性皮炎和其他湿疹性皮炎、脂溢性皮炎）、炎症性眼部疾病，如干燥综合征、角膜结膜炎或葡萄膜炎、炎症性肠疾病、克罗恩病或溃疡性结肠炎。
• Indolylmaleimide derivatives
  申请人：Evenou Jean-Pierre

  公开号：US20050119274A1

  公开（公告）日：2005-06-02

  Provided are compounds of formula (I) which are useful in the treatment and/or prevention of diseases or disorders mediated by T lymphocytes and/or PKC, e.g. acute or chronic rejection of organ or tissue allo- or xenografts, graft versus host diseases, atherosclerosis, vascular occlusion due to vascular injury such as angioplasty, restenosis, obesity, syndrome X, impaired glucose tolerance, polycystic ovary syndrome, hypertension, heart failure, chronic obstructive pulmonary disease, CNS diseases such as Alzheimer disease or amyotrophic lateral sclerosis, cancer, infectious diseases such as AIDS, septic shock or adult respiratory distress syndrome, ischemia/reperfusion injury e.g. myocardial infarction, stroke, gut ischemia, renal failure or hemorrhage shock, or traumatic shock, e.g. traumatic brain injury. The compounds of formula I are also useful in the treatment and/or prevention of T-cell mediated acute or chronic inflammatory disease or disorders or autoimmune diseases e.g. rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, Hashimoto's thyroidis, multiple sclerosis, myasthenia gravis, diabetes type I or II and the disorders associated therewith, e.g. angiopathy, diabetic proliferative retinopathy, diabetic macular edema, nephropathy, neuropathy and dawn phenomenon, respiratory diseases such as asthma or inflammatory lung injury, inflammatory liver injury, inflammatory glomerular injury, cutaneous manifestations of immunologically-mediated disorders or illnesses, inflammatory and hyperproliferative skin diseases (such as psoriasis, atopic dermatitis, allergic contract dermatitis, irritant contact dermatitis and further eczematous dermatitises, seborrhoeic dermatitis), inflammatory eye diseases, e.g. Sjoegren's syndrome, keratoconjunctivitis or uveitis, inflammatory bowel disease, Crohn's disease or ulcerative colitis.

  提供的化合物式(I)可用于治疗和/或预防由T淋巴细胞和/或PKC介导的疾病或疾病，例如器官或组织同种或异种移植的急性或慢性排斥反应，移植物抗宿主病，动脉粥样硬化，由于血管损伤如血管成形术而导致的血管闭塞，再狭窄，肥胖，综合征X，糖耐量受损，多囊卵巢综合症，高血压，心力衰竭，慢性阻塞性肺疾病，中枢神经系统疾病，例如阿尔茨海默病或肌萎缩侧索硬化，癌症，传染病，例如艾滋病，脓毒症或成人呼吸窘迫综合征，缺血/再灌注损伤，例如心肌梗塞，中风，肠道缺血，肾衰竭或出血性休克，或创伤性休克，例如创伤性脑损伤。公式I的化合物也可用于治疗和/或预防T细胞介导的急性或慢性炎症性疾病或疾病或自身免疫性疾病，例如类风湿性关节炎，骨关节炎，系统性红斑狼疮，桥本甲状腺炎，多发性硬化症，重症肌无力，糖尿病I型或II型及其相关疾病，例如血管病，糖尿病增生性视网膜病变，糖尿病黄斑水肿，肾病，神经病和黎明现象，呼吸道疾病，例如哮喘或炎性肺损伤，炎性肝损伤，炎性肾小球损伤，免疫介导疾病或疾病的皮肤表现，炎症和过度增生性皮肤疾病（例如银屑病，特应性皮炎，过敏性接触性皮炎，刺激性接触性皮炎和进一步的湿疹性皮炎，脂溢性皮炎），炎症性眼疾，例如干燥综合征，角膜结膜炎或葡萄膜炎，炎症性肠病，克隆氏病或溃疡性结肠炎。
• INDOLYLMALEIMIDE DERIVATIVES
  申请人：Evenou Jean-Pierre

  公开号：US20080146578A1

  公开（公告）日：2008-06-19

  Provided are compounds of Formula (I), which are useful in the treatment and/or prevention of diseases or disorders mediated by T lymphocytes and/or PKC, e.g. acute or chronic rejection of organ or tissue allo- or xenografts, graft versus host diseases, atherosclerosis, vascular occlusion due to vascular injury such as angioplasty, restenosis, obesity, syndrome X, impaired glucose tolerance, polycystic ovary syndrome, hypertension, heart failure, chronic obstructive pulmonary disease, CNS diseases such as Alzheimer disease or amyotrophic lateral sclerosis, cancer, infectious diseases such as AIDS, septic shock or adult respiratory distress syndrome, ischemia/reperfusion injury e.g. myocardial infraction, stroke, gut ischemia, renal failure or hemorrhage shock, or traumatic shock, e.g. traumatic brain injury. The compounds of (I) are also useful in the treatment and/or prevention of T-cell mediated acute or chronic inflammatory diseases or disorders or autoimmune diseases e.g. rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, Hashimoto's thyroidis, multiple sclerosis, myasthenia gravis, diabetes type I or II and the disorders associated therewith, e.g. angiopathy, diabetic proliferative retinopathy, diabetic macular edema, nephropathy, neuropathy and dawn phenomenon, respiratory diseases such as asthma or inflammatory lung injury, inflammatory liver injury, inflammatory glomerular injury, cutaneous manifestations of immunologically-mediated disorders or illnesses, inflammatory and hyperproliferative skin diseases (such as psoriasis, atopic dermatitis, allergic contact dermatitis, irritant contact dermatitis and further eczematous dermatitises, seborrhoeic dermatitis), inflammatory eye diseases, e.g. Sjoegren's syndrome, keratoconjunctivitis or uveitis, inflammatory bowel disease, Crohn's disease or ulcerative colitis.

  提供的化合物公式(I)，可用于治疗和/或预防由T淋巴细胞和/或PKC介导的疾病或障碍，例如器官或组织同种异体或异种移植的急性或慢性排斥、移植物抗宿主病、动脉粥样硬化、由血管损伤引起的血管闭塞，如血管成形术、再狭窄、肥胖、X综合症、糖耐量受损、多囊卵巢综合症、高血压、心力衰竭、慢性阻塞性肺疾病、中枢神经系统疾病，如阿尔茨海默病或肌萎缩侧索硬化症、癌症、感染性疾病，如艾滋病、脓毒性休克或成人呼吸窘迫综合症、缺血/再灌注损伤，例如心肌梗死、中风、肠道缺血、肾衰竭或出血性休克，或创伤性休克，例如创伤性脑损伤。公式(I)的化合物还可用于治疗和/或预防T细胞介导的急性或慢性炎症性疾病或障碍，或自身免疫疾病，例如类风湿性关节炎、骨关节炎、系统性红斑狼疮、桥本甲状腺炎、多发性硬化症、重症肌无力、糖尿病I或II及其相关疾病，例如血管病、糖尿病增生性视网膜病变、糖尿病黄斑水肿、肾病、神经病和黎明现象、呼吸道疾病，如哮喘或炎性肺损伤、炎性肝损伤、炎性肾小球损伤、免疫介导的皮肤表现或疾病、炎症和过度增生的皮肤疾病（如银屑病、特应性皮炎、过敏性接触性皮炎、刺激性接触性皮炎和其他湿疹性皮炎、脂溢性皮炎）、炎性眼部疾病，例如Sjogren综合症、角膜结膜炎或葡萄膜炎、炎性肠病、克罗恩病或溃疡性结肠炎。
• US7235555B2
  申请人：——

  公开号：US7235555B2

  公开（公告）日：2007-06-26