NPS 846 | 144451-98-9

• 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: NPS 846
• 英文别名: 3-fluoro-γ-(3-fluorophenyl)benzenepropanamine；3,3-bis(3-fluorophenyl)-propanamine；3,3-Bis-(3-fluoro-phenyl)-propylamine；3,3-Bis(3-fluorophenyl)propan-1-amine
• CAS: 144451-98-9
• 化学式: C₁₅H₁₅F₂N
• 分子量: 247.288
• InChiKey: RYGVSIREAYKXBQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  NPS 846 以99的产率得到N-[3,3-bis(3-fluorophenyl)propyl]formamide
  参考文献：
  名称：

  Compounds active at a novel site on receptor-operated calcium channels

  摘要：

  治疗神经系统疾病或障碍的方法和组合物，如中风、头部外伤、脊髓损伤、脊髓缺血、缺血或低氧引起的神经细胞损伤、癫痫、焦虑症、神经心理或认知缺陷，由于缺血或低氧而经常发生于心脏手术下心肺旁路的后果，或神经退行性疾病，如阿尔茨海默病、亨廷顿病、帕金森病或肌萎缩性侧索硬化症（ALS）。

  公开号：

  US06017965A1
• 作为产物：
  描述：

  methyl 2-cyano-3-(3-fluorophenyl)-2-propenoate 在 sodium hydroxide 、 lithium aluminium tetrahydride 作用下， 以 苯 为溶剂， 反应 1.0h， 生成 NPS 846
  参考文献：
  名称：

  Synthesis and histamine H2 agonistic activity of arpromidine analogues: replacement of the pheniramine-like moiety by non-heterocyclic groups

  摘要：

  Analogues of the potent histamine H-2 agonist arpromidine, characterized by non-heterocyclic groups (phenyl, cyclo-hexyl, alkyl) instead of the pheniramine-like portion, were prepared and tested for their H-2 agonistic and H-1 antagonistic activity in the isolated guinea pig right atrium and ileum, respectively. In the diphenylpropylguanidine series an increase in H-2 agonistic potency resulted from mono- or difluorination at one or both phenyl rings in the meta and/or para position (pD2 less-than-or-equal-to 7.75 vs pD2 = 7.15 for the unsubstituted parent compound). Compounds chlorinated at both phenyl rings were considerably less potent. Highest combined H-2 agonistic/H-1 antagonistic potency was found in the 4-fluorophenyl series. The arpromidine analogue with cyclohexyl and methyl group instead of phenyl and pyridine ring proved to be 30 times more potent than histamine in the atrium. The H-1 antagonistic potency in cyclohexyl compounds was lower than in the diaryl series. Thus, aromatic rings appear not to be required for high H-2 agonistic potency but are useful for combined H-2 agonistic/H-1 antagonistic activity.

  DOI：

  10.1016/0223-5234(92)90145-q

文献信息

• Soluble Epoxide Hydrolase Inhibitors and Methods of Using Same
  申请人：Cywin Lawrence Charles

  公开号：US20060276515A1

  公开（公告）日：2006-12-07

  Disclosed are compounds active against soluble epoxide hydrolase (sEH), compositions thereof and methods of using and making same.

  揭示了对可溶性环氧化物酶（sEH）具有活性的化合物，以及其组合物和使用和制备这些化合物的方法。
• Silver-Catalyzed Long-Distance Aryl Migration from Carbon Center to Nitrogen Center
  作者：Taigang Zhou、Fei-Xian Luo、Ming-Yu Yang、Zhang-Jie Shi

  DOI：10.1021/jacs.5b10267

  日期：2015.11.25

  Selective cleavage of an inert C-C bond followed by C-O/N bond formation through a long-distance aryl migration from a carbon to a nitrogen center via Ag catalysis is reported. The migration products were easily converted into γ-hydroxy amines and tetrahydroquinoline derivatives in quantitative yields. Preliminary mechanistic studies indicated a radical pathway.

  据报道，惰性 CC 键的选择性裂解，然后通过银催化从碳到氮中心的长距离芳基迁移形成 CO/N 键。迁移产物很容易转化为定量产率的 γ-羟基胺和四氢喹啉衍生物。初步的机理研究表明了一种激进的途径。
• Synthesis and Brain Regional Distribution of [11C]NPS 1506 in Mice and Rat: an N-Methyl-D-aspartate (NMDA) Receptor Antagonist
  作者：Takeshi Fuchigami、Terushi Haradahira、Takuya Arai、Takashi Okauchi、Jun Maeda、Kazutoshi Suzuki、Fumihiko Yamamoto、Tetsuya Suhara、Shigeki Sasaki、Minoru Maeda

  DOI：10.1248/bpb.26.1570

  日期：——

  NPS 1506 [3-fluoro-γ-(3-fluorophenyl)-N-methylbenzenepropamine] is representative of a non-psychotomimetic class of N-methyl-D-aspartate (NMDA) receptor antagonists. [11C]NPS 1506 was prepared at high radiochemical purity (>98%) with a specific activity of around 50 GBq/μmol at the end of synthesis by methylation of the desmethyl precursor with [11C]methyl iodide in the presence of NaH. Biodistribution of [11C]NPS 1506 in mice and rat demonstrated that uptake into the brain was rapid and occurred at high levels. [11C]NPS 1506 showed no appreciable specific binding in rodent brains under in vivo conditions, possibly because of both a large non-specific bound fraction and low in vitro binding affinity for NMDA receptors.

  NPS 1506 [3-氟-γ-(3-氟苯基)-N-甲基苯丙胺]是一类非拟精神药物 N-甲基-<小>D-天冬氨酸（NMDA）受体拮抗剂的代表。[11C]NPS 1506 是在 NaH 存在下，用[11C]甲基碘对去甲基前体进行甲基化而制备的，放射化学纯度高（>98%），合成结束时的比活度约为 50 GBq/μmol。[11C]NPS1506在小鼠和大鼠体内的生物分布表明，大脑摄取速度快，摄取量高。在体内条件下，[11C]NPS 1506 在啮齿类动物大脑中没有显示出明显的特异性结合，这可能是由于非特异性结合部分较大以及体外与 NMDA 受体的结合亲和力较低。
• Methods and compounds for treating depression and other disorders
  申请人：NPS PHARMACEUTICALS, INC.

  公开号：EP1790337A2

  公开（公告）日：2007-05-30

  The present invention features compounds active at both the serotonin reuptake site and the N-methyl-D-aspartate (NMDA) receptor and the use of such compounds for treating different disorders. Compounds having activity at the serotonin reuptake site and the NMDA receptor ("multi-active compounds") can be used to treat different types of disorders such as obsessive-compulsive disorders (OCD), sleep disorders, sexual dysfunction, and eating disorders.

  本发明的特点是具有在血清素再摄取位点和N-甲基-D-天门冬氨酸（NMDA）受体活性的化合物，并使用这些化合物治疗不同的疾病。具有在血清素再摄取位点和NMDA受体（“多功能化合物”）的活性的化合物可用于治疗不同类型的疾病，如强迫症障碍（OCD），睡眠障碍，性功能障碍和进食障碍。
• Compounds active at a novel site on receptor-operated calcium channels useful for treatment of neurological disorders and diseases
  申请人：Mueller L. Alan

  公开号：US20060142594A1

  公开（公告）日：2006-06-29

  Method and compositions for treating a patient having a neurological disease or disorder, such as stroke, head trauma, spinal cord injury, spinal cord ischemia, ischemia- or hypoxia-induced nerve cell damage, epilepsy, anxiety, neuropsychiatric or cognitive deficits due to ischemia or hypoxia such as those that frequently occur as a consequence of cardiac surgery under cardiopulmonary bypass, or neurodegenerative diseases such as Alzheimer's Disease, Huntington's Disease, Parkinson's Disease, or amyotrophic lateral sclerosis (ALS).

  治疗患有神经系统疾病或障碍的患者的方法和组合物，例如中风、头部创伤、脊髓损伤、脊髓缺血、缺血或低氧引起的神经细胞损伤、癫痫、焦虑、由缺血或低氧引起的神经精神或认知功能障碍，例如经常作为体外循环下心脏手术后的后果发生的，或者神经退行性疾病，例如阿尔茨海默病、亨廷顿病、帕金森病或肌萎缩性侧索硬化症（ALS）。