1-(3-methyl-4-triisopropylsilyloxyphenyl)-2-(4-(4-fluorophenyl)-4-hydroxypiperidin-1-yl)-propan-1-one | 178375-24-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(3-methyl-4-triisopropylsilyloxyphenyl)-2-(4-(4-fluorophenyl)-4-hydroxypiperidin-1-yl)-propan-1-one
• 英文别名: 2-[4-(4-fluorophenyl)-4-hydroxypiperidin-1-yl]-1-[3-methyl-4-tri(propan-2-yl)silyloxyphenyl]propan-1-one
• CAS: 178375-24-1
• 化学式: C₃₀H₄₄FNO₃Si
• 分子量: 513.768
• InChiKey: IUOYOURBFXKOKH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.24
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(3-methyl-4-triisopropylsilyloxyphenyl)-2-(4-(4-fluorophenyl)-4-hydroxypiperidin-1-yl)-propan-1-one 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 以74%的产率得到
  参考文献：
  名称：

  Discovery of (−)-6-[2-[4-(3-fluorophenyl)-4-hydroxy-1-piperidinyl]-1-hydroxyethyl]-3,4-dihydro-2(1H)-quinolinone—A potent NR2B-selective N-methyl d-aspartate (NMDA) antagonist for the treatment of pain

  摘要：

  (-)-6-[2-[4-(3-氟苯基)-4-羟基-1-哌啶基]-1-羟乙基]-3,4-二氢-2(1H)-喹啉酮被鉴定为一种口服活性的、选择性作用于NR2B亚基的N-甲基-D-天冬氨酸（NMDA）受体拮抗剂。该化合物对含有NR2B亚基的NMDA受体显示出极高的选择性，相对于HERG通道抑制作用（治疗指数=4200 vs NR2B结合IC50）。与原型化合物CP-101,606相比，该化合物具有改进的药代动力学特性。（c）2007 Elsevier Ltd. 保留所有权利。

  DOI：

  10.1016/j.bmcl.2007.08.014
• 作为产物：
  描述：

  3-methyl-4-triisopropylsilyloxy-a-bromopropiophenone 、 4-(4-氟苯基)-哌啶-4-醇盐酸盐 在 三乙胺 作用下， 以 乙醇 为溶剂， 以65%的产率得到1-(3-methyl-4-triisopropylsilyloxyphenyl)-2-(4-(4-fluorophenyl)-4-hydroxypiperidin-1-yl)-propan-1-one
  参考文献：
  名称：

  Discovery of (−)-6-[2-[4-(3-fluorophenyl)-4-hydroxy-1-piperidinyl]-1-hydroxyethyl]-3,4-dihydro-2(1H)-quinolinone—A potent NR2B-selective N-methyl d-aspartate (NMDA) antagonist for the treatment of pain

  摘要：

  (-)-6-[2-[4-(3-氟苯基)-4-羟基-1-哌啶基]-1-羟乙基]-3,4-二氢-2(1H)-喹啉酮被鉴定为一种口服活性的、选择性作用于NR2B亚基的N-甲基-D-天冬氨酸（NMDA）受体拮抗剂。该化合物对含有NR2B亚基的NMDA受体显示出极高的选择性，相对于HERG通道抑制作用（治疗指数=4200 vs NR2B结合IC50）。与原型化合物CP-101,606相比，该化合物具有改进的药代动力学特性。（c）2007 Elsevier Ltd. 保留所有权利。

  DOI：

  10.1016/j.bmcl.2007.08.014

文献信息

• Neuroprotective 3-(piperidinyl-1)-chroman-4,7-diol and
  申请人：Pfizer Inc.

  公开号：US06046213A1

  公开（公告）日：2000-04-04

  This invention relates to compounds of formula (I), or pharmaceutically acceptable acid addition salts thereof, wherein: (a) R.sup.2 and R.sup.5 are taken separately and R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are each independently hydrogen, (C.sub.1 -C.sub.6) alkyl, halo, CF.sub.3, OH or OR.sup.7 and R.sup.5 is methyl or ethyl; or (b) R.sup.2 and R.sup.5 are taken together, forming a chroman-4-ol ring, and R.sup.1, R.sup.3 and R.sup.4 are each independently hydrogen, (C.sub.1 -C.sub.6) alkyl, halo, CF.sub.3, OH or OR.sup.7 ; and R.sup.6 is a substituted piperidinyl, pyrrolidinyl or 8-azabicyclo(3.2.1)octanyl derivative; provided that (a) when R.sup.2 and R.sup.5 are taken separately, at least one of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 is not hydrogen; and (b) when R.sup.2 and R.sup.5 are taken together, at least one of R.sup.1, R.sup.3 and R.sup.4 is not hydrogen; pharmaceutical compositions thereof; and methods of treating mammals suffering from stroke, spinal cord trauma, traumatic brain injury, multiinfarct dementia, CNS degenerative diseases such as Alzheimer's disease, senile dementia of the Alzheimer's type, Huntington's disease, Parkinson's disease, epilepsy, amyotrophic lateral sclerosis, pain, AIDS dementia, psychotic conditions, drug addictions, migraine, hypoglycemia, anxiolytic conditions, urinary incontinence and an ischemic event arising from CNS surgery, open heart surgery or any procedure during which the function of the cardiovascular system is compromised with a compound of formula (I) hereinabove or a pharmaceutically acceptable salt thereof. ##STR1##

  这项发明涉及化合物的结构式(I)，或其药学上可接受的酸盐，其中：(a) R.sup.2和R.sup.5分别取，R.sup.1，R.sup.2，R.sup.3和R.sup.4各自独立地为氢，(C.sub.1 -C.sub.6)烷基，卤素，三氟甲基，羟基或OR.sup.7，R.sup.5为甲基或乙基；或者(b) R.sup.2和R.sup.5取在一起，形成一个色苷-4-醇环，R.sup.1，R.sup.3和R.sup.4各自独立地为氢，(C.sub.1 -C.sub.6)烷基，卤素，三氟甲基，羟基或OR.sup.7；而R.sup.6为取代的哌啶基，吡咯啉基或8-氮杂双环(3.2.1)辛基衍生物；条件是(a)当R.sup.2和R.sup.5分开取时，R.sup.1，R.sup.2，R.sup.3和R.sup.4中至少有一个不是氢；(b)当R.sup.2和R.sup.5取在一起时，R.sup.1，R.sup.3和R.sup.4中至少有一个不是氢；其中包括其药物组成；以及治疗患有中风，脊髓创伤，创伤性脑损伤，多梗塞性痴呆，中枢神经系统退行性疾病如阿尔茨海默病，老年性阿尔茨海默病，亨廷顿病，帕金森病，癫痫，肌萎缩侧索硬化，疼痛，艾滋病痴呆，精神病症，药物成瘾，偏头痛，低血糖，抗焦虑症状，尿失禁以及由中枢神经系统手术，开心脏手术或心血管系统功能受损的任何过程引起的缺血事件的方法，使用上述的结构式(I)中的化合物或其药学上可接受的盐。
• Combinations for the treatment of parkinsonism containing selective NMDA antagonists
  申请人：Pfizer Inc.

  公开号：US06258827B1

  公开（公告）日：2001-07-10

  This invention relates to a method of treating Parkinson's Disease whereby a mammal suffering from Parkinson's Disease is treated with a combination of a forebrain selective NMDA antagonist and a compound which is capable of increasing the excitatory feedback from the ventral lateral nucleus of the thalamus into the cortex. This invention also relates to pharmaceutical compositions containing the synergistic combination.

  本发明涉及一种治疗帕金森病的方法，通过给患有帕金森病的哺乳动物使用前脑选择性NMDA拮抗剂和一种能够增加来自丘脑腹侧核对皮层的兴奋性反馈的化合物的组合来治疗。本发明还涉及含有这种协同组合的药物组合物。
• METHOD OF TREATING ACUTE, CHRONIC AND/OR NEUROPATHIC PAIN
  申请人：——

  公开号：US20010007872A1

  公开（公告）日：2001-07-12

  This invention relates to a method of treating acute, chronic and/or neuropathic pain in which a mammal suffering from acute, chronic and/or neuropathic pain is treated with an effective amount of an NR2B selective NMDA antagonist having a ratio of NR2B receptor activity to &agr; 1 -adrenergic receptor activity of at least about 3:1.

  本发明涉及一种治疗急性、慢性和/或神经病理性疼痛的方法，其中使用具有NR2B选择性NMDA拮抗剂的有效量来治疗患有急性、慢性和/或神经病理性疼痛的哺乳动物，所述NR2B选择性NMDA拮抗剂的NR2B受体活性与α1肾上腺素能受体活性的比率至少为约3:1。
• Pharmaceutical combinations for the treatment of stroke and traumatic brain injury
  申请人：——

  公开号：US20020045656A1

  公开（公告）日：2002-04-18

  This invention relates to methods of treating traumatic brain injury (TBI) or hypoxic or ischemic stroke, comprising administering to a patient in need of such treatment an NR2B subtype selective N-methyl-D-aspartate (NMDA) receptor antagonist in combination with either: (a) a neutrophil inhibitory factor (NIF); (b) a sodium channel antagonist; (c) a nitric oxide synthase (NOS) inhibitor; (d) a glycine site antagonist; (e) a potassium channel opener; (f) an AMPA/kainate receptor antagonist; (g) a calcium channel antagonist; (h) a GABA-A receptor modulator (e.g., a GABA-A receptor agonist); or (i) an antiinflammatory agent.

  本发明涉及治疗创伤性脑损伤（TBI）或缺氧性或缺血性中风的方法，包括向需要此类治疗的患者注射NR2B亚型选择性N-甲基-D-天门冬氨酸（NMDA）受体拮抗剂，与以下任一组合：（a）中性粒细胞抑制因子（NIF）；（b）钠通道拮抗剂；（c）一氧化氮合酶（NOS）抑制剂；（d）甘氨酸位点拮抗剂；（e）钾通道开放剂；（f）AMPA / kainate受体拮抗剂；（g）钙通道拮抗剂；（h）GABA-A受体调节剂（例如，GABA-A受体激动剂）；或（i）抗炎药物。
• Prophylactic use of N-methyl-D-aspartate (NMDA) antagonists
  申请人：——

  公开号：US20020072485A1

  公开（公告）日：2002-06-13

  This invention provides a method of inhibiting in a mammal neurological damage resulting from impairment of glucose and/or oxygen supply to the brain, which method comprises administering to the mammal prior to the impairment of glucose and/or oxygen supply to the brain an amount of an NR2B subunit selective NMDA antagonist, which amount is effective in inhibiting neurological damage. This invention also provides a method of preventing primary hyperalgesia, secondary hyperalgesia, primary allodynia, secondary allodynia, or other pain caused by central sensitization, in a mammal, which method comprises administering to the mammal, prior to affliction with said pain, an amount of an NR2B subunit selective NMDA antagonist, which amount is effective in preventing said pain.

  该发明提供了一种抑制哺乳动物神经系统损伤的方法，该损伤是由于葡萄糖和/或氧气供应不足引起的，该方法包括在葡萄糖和/或氧气供应不足之前向哺乳动物注射一定量的NR2B亚单位选择性NMDA拮抗剂，该量足以抑制神经系统损伤。该发明还提供了一种预防哺乳动物发生由中枢敏化引起的原发性疼痛、继发性疼痛、原发性触发痛、继发性触发痛或其他疼痛的方法，该方法包括在哺乳动物患有该疼痛之前向其注射一定量的NR2B亚单位选择性NMDA拮抗剂，该量足以预防该疼痛。