8-(4-硝基苯基)-1,4-二氧杂-8-氮杂螺[4.5]癸烷 | 79421-42-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 8-(4-硝基苯基)-1,4-二氧杂-8-氮杂螺[4.5]癸烷
• 英文名称: 8-(4-nitrophenyl)-1,4-dioxa-8-azaspiro[4.5]decane
• 英文别名: 8-(4-nitro-phenyl)-1,4-dioxa-8-aza-spiro[4.5]decane；8-(4-nitrophenyl)-1,4-dioxa-8-azaspiro[4,5]decane；N-(4-nitrophenyl)-4-piperidone ethylene ketal
• CAS: 79421-42-4
• 化学式: C₁₃H₁₆N₂O₄
• mdl: MFCD08061261
• 分子量: 264.281
• InChiKey: SHLUSCRJQRVCSR-UHFFFAOYSA-N

物化性质

• 熔点：
  156-157 °C
• 沸点：
  449.9±45.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.538
• 拓扑面积：
  67.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-(4-硝基苯基)-1,4-二氧杂-8-氮杂螺[4.5]癸烷 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、206.84 kPa 条件下， 反应 19.0h， 生成 N-{4-[4-(4-oxopiperidin-1-yl)phenylsulfamoyl]phenyl}acetamide
  参考文献：
  名称：

  Novel (4-Piperidin-1-yl)-phenyl Sulfonamides as Potent and Selective Human β3 Agonists

  摘要：

  A series of novel (4-piperidin-1-yl)-phenyl sulfonamides was prepared and evaluated for their biological activity on the human beta (3)-adrenergic receptor (AR). Replacement of the 3,4-dihydroxyl group of the catechol moiety with 4-hydroxyl-3-methyl sulfonamide on the left-hand side of the compounds resulted in a number of potent full agonists at the beta (3) receptor. Modification of the right-hand side of the compounds by incorporation of a free carboxylic acid resulted in a few potent human beta (3) agonists with low affinities for beta (1)- and beta (2)-ARs. N-Alkyl substitution on the 4-piperidin-1-yl-phenylamine further increased the beta (3) potency while maintaining the selectivity. For example, sulfonamide 48 is a potent full beta (3) agonist (EC50 = 0.004 muM, IA = 1.0) with > 500-fold selectivity over beta (1)- and beta (2)-ARs. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00114-6
• 作为产物：
  描述：

  4-哌啶酮缩乙二醇 、 对氟硝基苯 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 生成 8-(4-硝基苯基)-1,4-二氧杂-8-氮杂螺[4.5]癸烷
  参考文献：
  名称：

  鉴定一种新型 2,8-Diazaspiro[4.5]decan-1-one 衍生物作为治疗炎症性肠病的有效和选择性双 TYK2/JAK1 抑制剂

  摘要：

  在这项研究中，我们描述了一系列 2,8-diazaspiro[4.5]decan-1-one 衍生物作为选择性 TYK2/JAK1 抑制剂。通过引入基于报道的选择性 TYK2 抑制剂14l的螺环支架系统探索结构-活性关系导致发现了优越的衍生化合物48。化合物48对 TYK2/JAK1 激酶表现出优异的效力，IC 50值分别为 6 和 37 nM，对 JAK2 的选择性超过 23 倍。化合物48在急性溃疡性结肠炎模型中，还表现出比托法替尼更好的代谢稳定性和更有效的抗炎功效。此外，化合物48优异的抗炎作用是通过调节相关 TYK2/JAK1 调节基因的表达以及 Th1、Th2 和 Th17 细胞的形成来介导的。总之，这些发现表明化合物48是一种选择性的 TYK2/JAK 双重抑制剂，值得开发为临床候选药物。

  DOI：

  10.1021/acs.jmedchem.1c01137

文献信息

• [EN] BRM TARGETING COMPOUNDS AND ASSOCIATED METHODS OF USE<br/>[FR] COMPOSÉS CIBLANT BRM ET PROCÉDÉS D'UTILISATION ASSOCIÉS
  申请人：PRELUDE THERAPEUTICS INC

  公开号：WO2022099117A1

  公开（公告）日：2022-05-12

  The present disclosure provides bifunctional compounds comprising a target protein binding moiety and a E3 ubiquitin ligase binding moiety, and associated methods of use.

  本公开提供了一种具有靶蛋白结合基团和E3泛素连接酶结合基团的双功能化合物，以及相关的使用方法。
• Proline derivatives and use thereof as drugs
  申请人：Kitajima Hiroshi

  公开号：US20050245538A1

  公开（公告）日：2005-11-03

  The present invention aims at providing compounds having therapeutic effects due to a DPP-IV inhibitory action, and satisfactory as pharmaceutical products. The present inventors have found that derivatives having a substituent introduced into the γ-position of proline represented by the formula (I) wherein each symbol is as defined in the specification, have a potent DPP-IV inhibitory activity, and completed the present invention by increasing the stability.

  本发明旨在提供具有治疗效果的化合物，其作用是通过DPP-IV的抑制作用，并且作为药物产品具有令人满意的效果。本发明人发现，在丙氨酸的γ位上引入取代基的衍生物具有强效的DPP-IV抑制活性，并通过增加稳定性完成了本发明。
• Cyclic amine phenyl beta-3 adrenergic receptor agonists
  申请人：——

  公开号：US20020028835A1

  公开（公告）日：2002-03-07

  This invention provides compounds of Formula I having the structure 1 wherein, R 1 , R 2 , R 3 , R 4 , R 5 , T, T 1 , T 2 , and X 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.

  本发明提供了具有结构1的化合物，其中R1、R2、R3、R4、R5、T、T1、T2和X如前所定义，或其药学上可接受的盐，其在治疗或抑制与胰岛素抵抗或高血糖有关的代谢紊乱（通常与肥胖或葡萄糖不耐症有关）、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；尤其适用于治疗或抑制2型糖尿病。
• Proline derivatives and the use thereof as drugs
  申请人：——

  公开号：US20040106655A1

  公开（公告）日：2004-06-03

  The present invention aims at providing compounds having therapeutic effects due to a DPP-IV inhibitory action, and satisfactory as pharmaceutical products. The present inventors have found that derivatives having a substituent introduced into the &ggr;-position of proline represented by the formula (I) 1 wherein each symbol is as defined in the specification, have a potent DPP-IV inhibitory activity, and completed the present invention by increasing the stability.

  本发明旨在提供具有治疗作用的化合物，由于DPP-IV抑制作用而具有满意的药物产品。本发明人发现，具有引入取代基的脯氨酸γ-位置的衍生物，其化学式为(I)1，其中每个符号如规范中所定义，具有强效的DPP-IV抑制活性，并通过增加稳定性完成了本发明。
• 2- [ (2-SUBSTITUTED) -IND0LIZIN-3-YL] -2-OXO-ACETAMIDE DERIVATIVES AS ANTIFUNGAL AGENTS
  申请人：Downham Robert

  公开号：US20100056511A1

  公开（公告）日：2010-03-04

  The invention provides compounds of formula (I), and pharmaceutically acceptable salts thereof wherein: R1, R2, R3, R4, R5, R6, R7, X and X 1 are as defined herein. These compounds are useful in the manufacture of medicaments for use in the prevention or treatment of a fungal disease. Compounds of formula (I), and agriculturally acceptable salts thereof, may also be used as agricultural fungicides.

  该发明提供了公式（I）的化合物及其药学上可接受的盐，其中：R1，R2，R3，R4，R5，R6，R7，X和X1如本文所定义。这些化合物在制造用于预防或治疗真菌病的药物方面是有用的。公式（I）的化合物及其农业上可接受的盐也可用作农业杀真菌剂。