4-bromo-2-isopropyl-6-nitrophenol | 127293-44-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 4-bromo-2-isopropyl-6-nitrophenol
• 英文别名: 5-Brom-3-nitro-2-hydroxy-cumol；4-Brom-2-isopropyl-6-nitro-phenol；5-Brom-3-nitro-2-oxy-1-isopropyl-benzol；4-bromo-2-nitro-6-propan-2-ylphenol
• CAS: 127293-44-1
• 化学式: C₉H₁₀BrNO₃
• 分子量: 260.087
• InChiKey: VWDURPCLGFBXNX-UHFFFAOYSA-N

物化性质

• 沸点：
  280.4±40.0 °C(Predicted)
• 密度：
  1.567±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  66
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-bromo-2-isopropyl-6-nitrophenol 在 palladium-carbon 氢气 作用下， 以 甲醇 为溶剂， 生成 2-氨基-6-异丙基苯酚
  参考文献：
  名称：

  Nitrogen-containing fused ring compounds and use thereof

  摘要：

  一种包含氮含有融合环化合物的URAT1活性抑制剂，其化学式如下所示[1]： 其中每个符号如描述中所定义。本发明对于预防或治疗显示尿酸参与的病理学，如高尿酸血症、痛风石、急性痛风性关节炎、慢性痛风性关节炎、痛风性肾脏、尿路结石、肾功能障碍、冠状动脉疾病、缺血性心脏病等方面具有用处。

  公开号：

  US20070010670A1
• 作为产物：
  描述：

  异丙苯酚 在 溴 、 硝酸 、 溶剂黄146 作用下， 生成 4-bromo-2-isopropyl-6-nitrophenol
  参考文献：
  名称：

  The Effects of Growth Hormone Replacement Therapy on Bone Metabolism in Adult-Onset Growth Hormone Deficiency: A 2-Year Open Randomized Controlled Multicenter Trial

  摘要：

  成人生长激素缺乏症（GHD）患者表现出骨量显著减少和骨折率增加。生长激素（GH）替代治疗能够增加骨代谢率。关于骨矿含量（BMC）和骨密度（BMD）的长期数据主要来自于开放式的非对照试验，涉及患者人数有限。为了确定尽管骨代谢率增加但长期GH治疗是否对骨骼有益，研究将100名（59名男性和41名女性），年龄介于25至65岁（平均年龄49.7岁）且具有成年起病GHD的患者随机分配至GH治疗组（40名男性和28名女性；平均剂量为0.18 IU/kg每周）或未治疗对照组（19名男性和13名女性），持续24个月。尽管GH治疗组男性和女性患者的骨代谢参数（骨钙素[OC]，I型前胶原羧端前肽[PICP]，和吡啶醇[PYD]）与对照组相比均有类似的增加，但通过双能X射线吸收测定法评估的BMC和BMD的效果在性别上有所差异。与对照组的变化相比，男性GH治疗组患者的脊柱BMC和BMD及总髋BMD显著增加，超远端桡骨BMD则有所减少（24个月的平均±标准误变化：+6.8 ± 1.1%，p = 0.009；+5.1 ± 0.8%，p = 0.005；+3.5 ± 0.7%，p = 0.02；和−2.6 ± 0.8%，p = 0.008）。在女性患者中未观察到显著的治疗效果。尽管GH治疗导致总重塑空间增加，成年起病GHD的长期GH治疗对骨平衡有积极影响，在两年内能够维持女性的骨量，甚至在男性中增加骨量。

  DOI：

  10.1359/jbmr.2002.17.6.1081

文献信息

• Pharmaceutical Compositions Comprising Nitrogen-Containing Fused Ring Coumpounds
  申请人：Miki Kazuki

  公开号：US20080305169A1

  公开（公告）日：2008-12-11

  [Problems] The present invention provides pharmaceutical composition which is effective for the prophylaxis or treatment of pathology showing involvement of uric acid (hyperuricemia, gouty tophus, acute gout arthritis, chronic gout arthritis, gouty kidney, urolithiasis, renal function disorder, coronary arterial disease, ischemic heart disease and the like) and the like, and is superior in the time-course stability and dissolution property (disintegration property). [Solving Means] The pharmaceutical composition of the present invention is a pharmaceutical composition comprising a nitrogen-containing fused ring compound represented by the following formula [1] or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable additives, wherein the nitrogen-containing fused ring compound or a pharmaceutically acceptable salt thereof is not in contact with a basic additive: wherein each symbol is as described in the specification.

  本发明提供了一种药物组合物，用于预防或治疗涉及尿酸的病理（高尿酸血症、痛风石、急性痛风性关节炎、慢性痛风性关节炎、痛风性肾脏、尿路结石、肾功能障碍、冠状动脉疾病、缺血性心脏病等），并且在时间稳定性和溶解性（分解性）方面具有优越性。 【解决手段】本发明的药物组合物是一种药物组合物，包括下式【1】所表示的含氮融合环化合物或其药学上可接受的盐，以及一种或多种药学上可接受的添加剂，其中所述的含氮融合环化合物或其药学上可接受的盐与碱性添加剂不接触： 其中每个符号如说明书中所述。
• Production Method of Nitrogen-Containing Fused Ring Compounds
  申请人：Hirata Kazuyuki

  公开号：US20080064871A1

  公开（公告）日：2008-03-13

  [Problems] The present invention provides a superior production method and a superior purification method of compounds effective for the treatment or prophylaxis of pathology showing involvement of uric acid, such as hyperuricemia, gouty tophus, acute gouty arthritis, chronic gouty arthritis, gouty kidney, urolithiasis, renal function disorder, coronary artery disease, ischemic heart disease and the like. [Means] A compound represented by the following formula [2] or a pharmaceutically acceptable salt thereof can be produced by reacting a compound represented by the following formula [3] or a salt thereof with a compound represented by the following formula [4], a salt thereof or a reactive derivative thereof. Moreover, crystallization of a compound represented by the formula [2] can be performed with industrially superior workability, and high quality crystals of a compound represented by the formula [2] can be obtained. wherein each symbol is as defined in the description.

  本发明提供了一种优越的化合物生产方法和优越的纯化方法，用于治疗或预防涉及尿酸的病理学，如高尿酸血症、痛风石、急性痛风性关节炎、慢性痛风性关节炎、痛风性肾脏、尿路结石、肾功能障碍、冠状动脉疾病、缺血性心脏病等。 [手段] 通过将以下式[3]所代表的化合物或其盐与以下式[4]所代表的化合物、其盐或其反应衍生物反应，可以制备以下式[2]所代表的化合物或其药用可接受的盐。此外，可以以工业上优越的可操作性进行以下式[2]所代表的化合物的结晶，并且可以获得以下式[2]所代表的化合物的高质量晶体。 其中每个符号如描述中所定义。
• Carboxylic Acid Compounds and Use Thereof
  申请人：Inoue Teruhiko

  公开号：US20070197512A1

  公开（公告）日：2007-08-23

  Provision of a superior URAT1 activity inhibitor effective for the treatment and the like of a pathology involving uric acid, such as hyperuricemia, gouty tophus, acute gouty arthritis, chronic gouty arthritis, gouty kidney, urinary lithiasis, renal dysfunction, coronary heart disease, ischemic cardiac diseases and the like. A URAT1 activity inhibitor containing a compound represented by the following formula [1] or a pharmaceutically acceptable salt thereof, or a solvate thereof as an active ingredient: wherein each symbol is as defined in the specification.

  提供一种优越的URAT1活性抑制剂，用于治疗与尿酸有关的病理，如高尿酸血症、痛风石、急性痛风性关节炎、慢性痛风性关节炎、痛风性肾病、尿路结石、肾功能障碍、冠心病、缺血性心脏病等。 一种包含下式[1]所表示的化合物或其药学上可接受的盐，或其溶剂化合物的URAT1活性抑制剂作为活性成分： 其中每个符号如规范中定义。
• Process for producing nitrophenol compound
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04943666A1

  公开（公告）日：1990-07-24

  An improved industrial process for producing a compound of the general formula: ##STR1## wherein R is an alkyl group having 1 to 4 carbon atoms which comprises reacting a compound of the general formula: ##STR2## wherein R is as defined above with nitrous acid in a mixed solvent of water and a water-insoluble or slightly soluble organic solvent.

  一种改进的工业生产通式为：##STR1##的化合物的过程，其中R是具有1至4个碳原子的烷基，该过程包括将通式为：##STR2##的化合物（其中R如上定义）与亚硝酸在混合溶剂中反应，该混合溶剂由水和一种水不溶性或微溶性有机溶剂组成。
• The Effects of Growth Hormone Replacement Therapy on Bone Metabolism in Adult-Onset Growth Hormone Deficiency: A 2-Year Open Randomized Controlled Multicenter Trial
  作者：Marie Bex、Roger Abs、Dominique Maiter、Albert Beckers、Gerard Lamberigts、Roger Bouillon

  DOI：10.1359/jbmr.2002.17.6.1081

  日期：——

  Adult hypopituitary patients with growth hormone deficiency (GHD) show a significant decrease in bone mass and an increased fracture rate. Replacement therapy with GH increases bone turnover. Most of the long‐term data on bone mineral content (BMC) and bone mineral density (BMD) have been acquired in open, noncontrolled trials involving limited numbers of patients. To determine whether long‐term GH therapy is beneficial for bone despite the increased bone turnover, 100 patients (59 men and 41 women), aged 25‐65 years (mean, 49.7 years) with adult‐onset GHD were randomized to treatment with GH (40 men and 28 women; mean dose, 0.18 IU/kg per week) or to a nontreated control group (19 men and 13 women) for 24 months. Despite a similar increase in parameters of bone turnover (osteocalcin [OC], procollagen type I carboxy‐terminal propeptide [PICP], and pyridinolines ([PYD]) in male and female GH‐treated patients compared with controls, the effects on BMC and BMD as evaluated by dual‐energy X‐ray absorptiometry were gender specific. A significant increase in spine BMC and BMD and total hip BMD and a decrease in BMD at the ultradistal radius over time was observed in male GH‐treated patients compared with the evolution in controls (mean ± SEM change at 24 months: +6.8 ± 1.1% and p = 0.009, +5.1 ± 0.8% and p = 0.005, +3.5 ± 0.7% and p = 0.02, and −2.6 ± 0.8% and p = 0.008, respectively). No significant treatment effects were observed in female patients. Despite the increase in the total remodeling space induced by GH treatment, prolonged GH therapy in adult‐onset GHD has a positive effect on bone balance, maintaining bone mass in women, and even increasing it in men over a 2 year‐period.

  成人生长激素缺乏症（GHD）患者表现出骨量显著减少和骨折率增加。生长激素（GH）替代治疗能够增加骨代谢率。关于骨矿含量（BMC）和骨密度（BMD）的长期数据主要来自于开放式的非对照试验，涉及患者人数有限。为了确定尽管骨代谢率增加但长期GH治疗是否对骨骼有益，研究将100名（59名男性和41名女性），年龄介于25至65岁（平均年龄49.7岁）且具有成年起病GHD的患者随机分配至GH治疗组（40名男性和28名女性；平均剂量为0.18 IU/kg每周）或未治疗对照组（19名男性和13名女性），持续24个月。尽管GH治疗组男性和女性患者的骨代谢参数（骨钙素[OC]，I型前胶原羧端前肽[PICP]，和吡啶醇[PYD]）与对照组相比均有类似的增加，但通过双能X射线吸收测定法评估的BMC和BMD的效果在性别上有所差异。与对照组的变化相比，男性GH治疗组患者的脊柱BMC和BMD及总髋BMD显著增加，超远端桡骨BMD则有所减少（24个月的平均±标准误变化：+6.8 ± 1.1%，p = 0.009；+5.1 ± 0.8%，p = 0.005；+3.5 ± 0.7%，p = 0.02；和−2.6 ± 0.8%，p = 0.008）。在女性患者中未观察到显著的治疗效果。尽管GH治疗导致总重塑空间增加，成年起病GHD的长期GH治疗对骨平衡有积极影响，在两年内能够维持女性的骨量，甚至在男性中增加骨量。