4-tert-butoxycarbonylamino-1-(3-nitrobenzyl)piperidine | 323578-32-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-tert-butoxycarbonylamino-1-(3-nitrobenzyl)piperidine
• 英文别名: tertbutyl N-{1-(3-nitrobenzyl)piperidin-4-yl}carbamate；tert-butyl (1-(3-nitrobenzyl)piperidin-4-yl)carbamate；tert-Butyl 1-(3-nitrobenzyl)piperidin-4-ylcarbamate；tert-butyl N-[1-[(3-nitrophenyl)methyl]piperidin-4-yl]carbamate
• CAS: 323578-32-1
• 化学式: C₁₇H₂₅N₃O₄
• 分子量: 335.403
• InChiKey: PAPJULZEPRQBDR-UHFFFAOYSA-N

物化性质

• 熔点：
  124-125 °C(Solv: hexane (110-54-3); ethyl acetate (141-78-6))
• 沸点：
  471.6±40.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  87.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-tert-butoxycarbonylamino-1-(3-nitrobenzyl)piperidine 在 10percent Pd/C 氢气 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以88%的产率得到4-tert-butoxycarbonylamino-1-(3-aminobenzyl)piperidine
  参考文献：
  名称：

  A Potent, Long-Acting, Orally Active (2R)-2-[(1R)-3,3-Difluorocyclopentyl]-2-hydroxy-2-phenylacetamide:  A Novel Muscarinic M₃ Receptor Antagonist with High Selectivity for M₃ over M₂ Receptors

  摘要：

  A novel series of (2R)-2-[(1R)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetamides was designed and synthesized based on the structure and biological profiles of an active metabolite 2 of our prototype muscarinic M-3 receptor selective antagonist 1, to develop a potent, long-acting, orally active M-3 antagonist for the treatment of urinary tract disorders, irritable bowel syndrome, and respiratory disorders. Investigation of (2R)-2-[(IR)-3,3-difluorocyclopentyl] -2-hydroxy-2-phenylacetamides containing a phenyl or heterocyclic ring as the piperidinyl side chain in place of the 4-methyl-3-pentenyl moiety of 15a revealed that this acid moiety was a versatile template for improving the selectivity for M-3 over M-2 receptors in comparison With the corresponding cyclopentylphenylacetic acid group: However, since the in vitro metabolic stability of these analogues was insufficient compared with that of 2, further derivatization was performed by introducing an appropriate hydrophilic group into the phenyl or 2-pyridyl ring. Thus, the 1;(6-aminopyridin-2-ylmethyl)piperidine analogue 15y exhibiting 190-fold selectivity for M-3 receptors (K-i = 2.8 nM) over M-2 receptors (K-i = 530 nM) in a human binding assay and-good in vitro metabolic stability in dog and human hepatic microsomes:was identified; This compound has excellent oral activity at 4 h after oral dosing (1 mg/kg), inhibiting methacholine-induced : bronchoconstriction in dogs, and may be useful in clinical situations in which M-3 over M-2 selectivity is desirable.

  DOI：

  10.1021/jm0003135
• 作为产物：
  描述：

  间硝基苯甲醛 、 4-叔丁氧羰基氨基哌啶 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 以76%的产率得到4-tert-butoxycarbonylamino-1-(3-nitrobenzyl)piperidine
  参考文献：
  名称：

  [EN] NOVEL ROCK INHIBITORS
  [FR] NOUVEAUX INHIBITEURS DE ROCK

  摘要：

  本发明涉及新型激酶抑制剂，更具体地说是ROCK抑制剂，包括含有此类抑制剂的组合物，尤其是药物，以及此类抑制剂在治疗和预防疾病中的用途。特别是，本发明涉及新型ROCK抑制剂，包括含有此类抑制剂的组合物，尤其是药物，以及此类抑制剂在治疗和预防疾病中的用途。此外，本发明还涉及治疗方法和使用所述化合物在制造药剂中的应用，用于治疗包括性功能障碍、炎症性疾病、眼科疾病和呼吸系统疾病等多种治疗适应症。本发明的化合物表现出软药特性，即它们在进入系统循环后迅速失活。因此，它们允许减少对功能活性ROCK抑制剂的系统性暴露。

  公开号：

  WO2014068035A1

文献信息

• Structure–Activity Relationship, Pharmacological Characterization, and Molecular Modeling of Noncompetitive Inhibitors of the Betaine/γ-Aminobutyric Acid Transporter 1 (BGT1)
  作者：Lars Jørgensen、Anas Al-Khawaja、Stefanie Kickinger、Stine B. Vogensen、Jonas Skovgaard-Petersen、Emil Rosenthal、Nrupa Borkar、Rebekka Löffler、Karsten K. Madsen、Hans Bräuner-Osborne、Arne Schousboe、Gerhard F. Ecker、Petrine Wellendorph、Rasmus P. Clausen

  DOI：10.1021/acs.jmedchem.7b00924

  日期：2017.11.9

  4-dichlorobenzamide 5 (BPDBA) is a noncompetitive inhibitor of the betaine/GABA transporter 1 (BGT1). We here report the synthesis and structure–activity relationship of 71 analogues. We identify 26m as a more soluble 2,4-Cl substituted 3-pyridine analogue with retained BGT1 activity and an improved off-target profile compared to 5. We performed radioligand-based uptake studies at chimeric constructs between BGT1

  N -(1-Benzyl-4-piperidinyl)-2,4-dichlorobenzamide 5 (BPDBA) 是一种甜菜碱/GABA 转运蛋白 1 (BGT1) 的非竞争性抑制剂。我们在这里报告了 71 种类似物的合成和构效关系。我们将26m鉴定为更易溶解的 2,4-Cl 取代的 3-吡啶类似物，与5相比具有保留的 BGT1 活性和改善的脱靶特征. 我们在 BGT1 和 GAT3 之间的嵌合构建体上进行了基于放射性配体的摄取研究、定点突变转运蛋白实验以及基于新确定的人血清素转运蛋白 (hSERT) 的 X 射线晶体结构的 BGT1 同源模型中的计算对接。在这些实验的基础上，我们提出了一种结合模式，该模式涉及 BGT1 中变构位点中 TM10 内的残基，该位点对应于 hSERT 晶体结构所揭示的变构结合袋。我们的研究为 BGT1 中提出的变构结合袋提供了初步见解，该袋可容纳一系列新型非竞争性抑制剂的结合位点。
• HETEROMAROMATIC COMPOUNDS USEFUL FOR THE TREATMENT OF PROLFERATIVE DISEASES
  申请人：SYROS PHARMACEUTICALS, INC.

  公开号：US20160264552A1

  公开（公告）日：2016-09-15

  The present invention provides novel compounds of Formula (I) and Formula (II), and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g., cyclin-dependent kinase 7 (CDK7)), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject. (I)

  本发明提供了公式（I）和公式（II）的新型化合物，以及其药学上可接受的盐，溶剂合物，水合物，互变异构体，立体异构体，同位素标记衍生物和组合物。还提供了涉及这些化合物或组合物的方法和套件，用于治疗或预防主体中的增殖性疾病（例如，癌症（例如，白血病，黑色素瘤，多发性骨髓瘤），良性肿瘤，血管生成，炎症性疾病，自身炎症性疾病和自身免疫性疾病）。使用本发明的化合物或组合物治疗具有增殖性疾病的主体，可以抑制激酶的异常活性，例如细胞周期依赖性激酶（CDK）（例如细胞周期依赖性激酶7（CDK7）），从而在主体中诱导细胞凋亡和/或抑制转录。(I)
• NOVEL ROCK INHIBTORS
  申请人：Amakem NV

  公开号：US20150299173A1

  公开（公告）日：2015-10-22

  The present invention relates to new kinase inhibitors, more specifically ROCK inhibitors, compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and prophylaxis of disease. In particular, the present invention relates to new ROCK inhibitors, compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and prophylaxis of disease. In addition, the invention relates to methods of treatment and use of said compounds in the manufacture of a medicament for the application to a number of therapeutic indications including sexual dysfunction, inflammatory diseases, ophthalmic diseases and Respiratory diseases. Compounds of the invention display soft drug characteristics, i.e. they are rapidly inactivated upon entry in the systemic circulation. Therefore, they allow for reduced systemic exposure to functionally active ROCK inhibitors.

  本发明涉及新的激酶抑制剂，更具体地涉及ROCK抑制剂，包括此类抑制剂的组合物，特别是制药组合物，以及使用此类抑制剂治疗和预防疾病的用途。具体而言，本发明涉及新的ROCK抑制剂，包括此类抑制剂的组合物，特别是制药组合物，以及使用此类抑制剂治疗和预防疾病的用途。此外，本发明还涉及治疗和使用所述化合物制备药物，用于多种治疗适应症，包括性功能障碍、炎症性疾病、眼科疾病和呼吸系统疾病。本发明的化合物显示出软药特性，即它们在进入系统循环后很快失活。因此，它们允许减少对功能活性ROCK抑制剂的系统曝露。
• Rock inhibitors
  申请人：Amakem NV

  公开号：US09394286B2

  公开（公告）日：2016-07-19

  The present invention relates to new kinase inhibitors, more specifically ROCK inhibitors, compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and prophylaxis of disease. In particular, the present invention relates to new ROCK inhibitors, compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and prophylaxis of disease. In addition, the invention relates to methods of treatment and use of said compounds in the manufacture of a medicament for the application to a number of therapeutic indications including sexual dysfunction, inflammatory diseases, ophthalmic diseases and Respiratory diseases. Compounds of the invention display soft drug characteristics, i.e. they are rapidly inactivated upon entry in the systemic circulation. Therefore, they allow for reduced systemic exposure to functionally active ROCK inhibitors.

  本发明涉及新的激酶抑制剂，更具体地说是ROCK抑制剂，包括这种抑制剂的组合物，特别是制药组合物，以及使用这种抑制剂治疗和预防疾病的用途。特别是，本发明涉及新的ROCK抑制剂，包括这种抑制剂的组合物，特别是制药组合物，以及使用这种抑制剂治疗和预防疾病的用途。此外，本发明还涉及治疗方法和使用所述化合物制造药物，适用于多种治疗指示，包括性功能障碍、炎症性疾病、眼科疾病和呼吸系统疾病。本发明的化合物具有软药特性，即它们在进入系统循环后会迅速失活。因此，它们允许减少对功能活性ROCK抑制剂的全身暴露。
• NOVEL ROCK INHIBITORS
  申请人：Amakem NV

  公开号：EP2914590A1

  公开（公告）日：2015-09-09