benzyl (3S,4R)-4-[(tert-butoxycarbonyl)(methyl)amino]-3-fluoropiperidine-1-carboxylate | 847041-33-2

• 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: benzyl (3S,4R)-4-[(tert-butoxycarbonyl)(methyl)amino]-3-fluoropiperidine-1-carboxylate
• 英文别名: benzyl-4-[(tert-butoxycarbonyl)(methyl)amino]-3-fluoropiperidine-1-carboxylate；benzyl (3S,4R)-3-fluoro-4-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]piperidine-1-carboxylate
• CAS: 847041-33-2
• 化学式: C₁₉H₂₇FN₂O₄
• 分子量: 366.433
• InChiKey: RIGJXXYFALIGAF-JKSUJKDBSA-N

物化性质

• 沸点：
  462.0±45.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl (3S,4R)-4-[(tert-butoxycarbonyl)(methyl)amino]-3-fluoropiperidine-1-carboxylate 在 1,4-环己二烯 、 palladium 10% on activated carbon 作用下， 以 乙醇 为溶剂， 生成 cis-tert-butyl (3-fluoropiperidin-4-yl)(methyl)carbamate
  参考文献：
  名称：

  Kinesin Spindle Protein (KSP) Inhibitors. 9. Discovery of (2S)-4-(2,5-Difluorophenyl)-N-[(3R,4S)-3-fluoro-1-methylpiperidin-4-yl]-2-(hydroxymethyl)-N-methyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide (MK-0731) for the Treatment of Taxane-Refractory Cancer

  摘要：

  Inhibition of kinesin spindle protein (KSP) is a novel mechanism for treatment of cancer with the potential to overcome limitations associated with currently employed cytotoxic agents. Herein, we describe a C2-hydroxymethyl dihydropyrrole KSP inhibitor ( 11) that circumvents hERG channel binding and poor in vivo potency, issues that limited earlier compounds from our program. However, introduction of the C2-hydroxymethyl group caused 11 to be a substrate for cellular efflux by P-glycoprotein (Pgp). Utilizing knowledge garnered from previous KSP inhibitors, we found that beta-fluorination modulated the p K a of the piperidine nitrogen and reduced Pgp efflux, but the resulting compound ( 14) generated a toxic metabolite in vivo. Incorporation of fluorine in a strategic, metabolically benign position by synthesis of an N-methyl-3-fluoro-4-(aminomethyl)piperidine urea led to compound 30 that has an optimal in vitro and metabolic profile. Compound 30 (MK-0731) was recently studied in a phase I clinical trial in patients with taxane-refractory solid tumors.

  DOI：

  10.1021/jm800386y
• 作为产物：
  描述：

  3-氟-1-甲基哌啶-4-酮 在 sodium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 醋酸异丙酯 、 水 为溶剂， 反应 17.75h， 生成 benzyl (3S,4R)-4-[(tert-butoxycarbonyl)(methyl)amino]-3-fluoropiperidine-1-carboxylate
  参考文献：
  名称：

  WO2006/101780

  摘要：

  公开号：

文献信息

• Mitotic kinesin inhibitors
  申请人：Coleman J. Paul

  公开号：US20050038074A1

  公开（公告）日：2005-02-17

  The present invention relates to dihydropyrrole compounds that are useful for treating cellular proliferative diseases, for treating disorders associated with KSP kinesin activity, and for inhibiting KSP kinesin. The invention is also related to compositions which comprise these compounds, and methods of using them to treat cancer in mammals.

  本发明涉及对治疗细胞增殖性疾病、治疗与KSP动力蛋白活性相关的疾病以及抑制KSP动力蛋白的二氢吡咯化合物。该发明还涉及包含这些化合物的组合物，以及利用它们治疗哺乳动物癌症的方法。
• [EN] 1,4 DISUBSTITUTED PYRROLIDINE - 3 - YL -AMINE DERIVATIVES AND THEIR USE FOR THE TREATMENT OF METABOLIC DISORDERS<br/>[FR] DÉRIVÉS DE PYROLIDIN-3-YL-AMINE 1,4 DISUBSTITUÉE ET LEUR UTILISATION POUR LE TRAITEMENT DE TROUBLES MÉTABOLIQUES
  申请人：PROSIDION LTD

  公开号：WO2013026587A1

  公开（公告）日：2013-02-28

  Therapeutic compounds are disclosed having the general formula (I) that are useful for the treatment of metabolic disorders, including type II diabetes. The compounds have activity as agonists of GPR1 19. Compounds having stereochemistry of formula (la) may also demonstrate DPP-IV inhibitory activity.

  揭示了具有一般式(I)的治疗化合物，可用于治疗代谢性疾病，包括2型糖尿病。这些化合物具有作为GPR1 19激动剂的活性。具有一般式(la)立体化学的化合物也可能表现出DPP-IV抑制活性。
• Mitotic Kinesin Inhibitors
  申请人：Coleman Paul J.

  公开号：US20080207693A1

  公开（公告）日：2008-08-28

  The present invention relates to dihydropyrazole compounds that are useful for treating cellular proliferative diseases, for treating disorders associated with KSP kinesin activity, and for inhibiting KSP kinesin. The invention also related to compositions which comprise these compounds, and methods of using them to treat cancer in mammals.

  本发明涉及二氢吡唑化合物，对于治疗细胞增殖性疾病，治疗与KSP动力蛋白活性相关的疾病，以及抑制KSP动力蛋白具有用处。该发明还涉及包含这些化合物的组合物，以及使用它们治疗哺乳动物癌症的方法。
• [EN] A PROCESS FOR THE PREPARATION OF 2,2-DISUBSTITUTED PYRROLES<br/>[FR] PROCEDE DE PREPARATION DE PYRROLES DISUBSTITUES EN 2,2
  申请人：MERCK & CO INC

  公开号：WO2005102996A3

  公开（公告）日：2006-01-19
• MITOTIC KINESIN INHIBITORS
  申请人：Merck & Co., Inc.

  公开号：EP1664026B1

  公开（公告）日：2009-01-21