[1-(4-Nitro-benzenesulfonyl)-piperidin-4-yl]-methanol | 392690-90-3

• 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: [1-(4-Nitro-benzenesulfonyl)-piperidin-4-yl]-methanol
• 英文别名: [1-(4-nitrophenyl)sulfonylpiperidin-4-yl]methanol
• CAS: 392690-90-3
• 化学式: C₁₂H₁₆N₂O₅S
• 分子量: 300.335
• InChiKey: XSXOQQWHNFZPKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [1-(4-Nitro-benzenesulfonyl)-piperidin-4-yl]-methanol 在 tin(II) chloride dihdyrate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 6.0h， 生成
  参考文献：
  名称：

  Non-nucleoside Inhibitors of the Measles Virus RNA-Dependent RNA Polymerase: Synthesis, Structure–Activity Relationships, and Pharmacokinetics

  摘要：

  The measles virus (MeV), a member of the paramyxovirus family, is an important cause of pediatric morbidity and mortality worldwide. In an effort to provide therapeutic treatments for improved measles management, we previously identified a small, non-nucleoside organic inhibitor of the viral RNA-dependent RNA polymerase by means of high-throughput screening. Subsequent structure-activity relationship (SAR) studies around the corresponding pyrazole carboxamide scaffold led to the discovery of 2 (AS-136a), a first generation lead with low nanomolar potency against life MeV and attractive physical properties suitable for development. However, its poor water solubility and low oral bioavailability (F) in rat suggested that the lead could benefit from further SAR studies to improve the biophysical characteristics of the compound. Optimization of in vitro potency and aqueous solubility led to the discovery of 2o (ERDRP-00519), a potent inhibitor of MeV (EC50 = 60 nM) with an aqueous solubility of approximately 60 mu g/mL. The agent shows a 10-fold exposure (AUC/C-max) increase in the rat model relative to 2, displays near dose proportionality in the range of 10-50 mg/kg and exhibits good oral bioavailability (F = 39%). The significant solubility increase appears linked to the improved oral bioavailability.

  DOI：

  10.1021/jm201699w
• 作为产物：
  描述：

  ethyl 1-(4-nitrophenylsulfonyl)piperidin-4-carboxylate 在 二异丁基氢化铝 作用下， 以 乙醚 、 正己烷 为溶剂， 以80 %的产率得到[1-(4-Nitro-benzenesulfonyl)-piperidin-4-yl]-methanol
  参考文献：
  名称：

  Nms-酰胺：具有独特稳定性和选择性的胺保护基团

  摘要：

  对甲苯磺酰基 (Tosyl) 和硝基苯磺酰基 (Nosyl)是当代有机合成中最常见的两种胺磺酰基保护基团。虽然对甲苯磺酰胺以其高稳定性和稳健性而闻名，但它们在多步合成中的使用却受到难以去除的困扰。另一方面，硝基苯磺酰胺很容易裂解，但对各种反应条件的稳定性有限。为了解决这个难题，我们在此提出了最初通过计算机研究开发的 Nms-酰胺，它克服了之前的这些限制并且没有妥协的余地，从而实现了传统磺酰胺保护基团不可能实现的一系列转化。

  DOI：

  10.1002/chem.202301312

文献信息

• Substituted 2- (S) -hydroxy-3- (piperidin-4-yl-methylamino) -propyl ethers and substituted 2-aryl-2- (R) - hydroxy-1- (piperidin-4-yl-methyl) -ethylamine beta-3 adrenergic receptor agonists
  申请人：American Home Products Corporation

  公开号：US20020037907A1

  公开（公告）日：2002-03-28

  This invention provides compounds of Formula I having the structure 1 wherein A, B, Z, R and R 1 are as defined hereinbefore, or a pharmaceutically acceptable salt thereof, which are useful in treating or inhibiting metabolic disorders related to insulin resistance or hyperglycemia (typically associated with obesity or glucose intolerance), atherosclerosis, gastrointestinal disorders, neurogenetic inflammation, glaucoma, ocular hypertension and frequent urination; and are particularly useful in the treatment or inhibition of type II diabetes.

  这项发明提供了具有结构式1的化合物，其中A、B、Z、R和R1如前文所定义，或其药学上可接受的盐，用于治疗或抑制与胰岛素抵抗或高血糖相关的代谢紊乱（通常与肥胖或葡萄糖不耐受有关）、动脉粥样硬化、胃肠道疾病、神经炎症、青光眼、眼压增高和频繁排尿；特别适用于治疗或抑制2型糖尿病。
• Substituted 2-(S)-hydroxy-3-(piperidin-4-yl-methylamino)-propyl ethers and substituted 2-aryl-2-(R)-hydroxy-1-(piperidin-4-yl-methyl)-ethylamine &bgr;-3 adrenergic receptor agonists
  申请人：Wyeth

  公开号：US06506901B2

  公开（公告）日：2003-01-14

  This invention provides compounds of Formula I having the structure wherein A, B, Z, R and R1 are as defined hereinbefore, or a pharmaceutically acceptable salt thereof, which are useful in treating or inhibiting metabolic disorders related to insulin resistance or hyperglycemia (typically associated with obesity or glucose intolerance), atherosclerosis, gastrointestinal disorders, neurogenetic inflammation, glaucoma, ocular hypertension and frequent urination; and are particularly useful in the treatment or inhibition of type II diabetes.

  本发明提供具有式I的化合物，其结构中A、B、Z、R和R1如前所定义，或其药学上可接受的盐，这些化合物在治疗或抑制与胰岛素抵抗或高血糖相关的代谢紊乱（通常与肥胖或葡萄糖耐受性不良有关）、动脉粥样硬化、胃肠道疾病、神经遗传性炎症、青光眼、眼压增高和频繁排尿方面非常有用；并且在治疗或抑制II型糖尿病方面特别有用。
• CDK2降解剂及其用途
  申请人：四川海思科制药有限公司

  公开号：CN116143766A

  公开（公告）日：2023-05-23

  本发明公开一种式(I)所示的化合物，其立体异构体或药学上可接受的盐，或含它们的药物组合物，及其作为CDK2降解剂在制备治疗相关疾病的药物中的用途，式(I)中各基团如说明书之定义。PTM‑L‑ULM(I)。
• US6506901B2
  申请人：——

  公开号：US6506901B2

  公开（公告）日：2003-01-14
• [EN] SUBSTITUTED 2-(S)-HYDROXY-3-(PIPERIDIN-4-YL-METHYLAMINO)-PROPYL ETHERS AND SUBSTITUTED 2-ARYL-2-(R)-HYDROXY-1-(PIPERIDIN-4-YL-METHYL)-ETHYLAMINE BETA-3 ADRENERGIC RECEPTOR AGONISTS<br/>[FR] AGONISTES VIS-A-VIS DE RECEPTEUR ADRENERGIQUE BETA 3 DE 2-(S)-HYDROXY-3-(PIPERIDINE-4-YL-METHYLAMINO)-PROPYL ETHERS SUBSTITUES ET DE 2-ARYL-2-(R)-HYDROXY-1-(PIPERIDINE-4-YL-METHYL)-ETHYLAMINE SUBSTITUEE
  申请人：AMERICAN HOME PROD

  公开号：WO2002006255A2

  公开（公告）日：2002-01-24

  The invention provides compounds of Formula (I) having the structure wherein A, B, Z, R and R1 are as defined hereinbefore, or a pharmaceutically acceptable salt thereof, which are useful in treating or inhibiting metabolic disorders related to insulin resistance or hyperglycemia (typically associated with obesity or glucose intolerance), atherosclerosis, gastrointestinal disorders, neurogenetic inflammation, glaucoma, ocular hypertension and frequent urination; and are particularly useful in the treatment or inhibition of type II diabetes.