ethyl 4-(4-methyl-2-nitroanilino)-1-piperidinecarboxylate | 173843-49-7

• 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: ethyl 4-(4-methyl-2-nitroanilino)-1-piperidinecarboxylate
• 英文别名: ethyl 4-(4-methyl-2-nitroanilino)piperidine-1-carboxylate
• CAS: 173843-49-7
• 化学式: C₁₅H₂₁N₃O₄
• 分子量: 307.349
• InChiKey: RWIFOOGSCDYPTE-UHFFFAOYSA-N

物化性质

• 沸点：
  465.3±45.0 °C(Predicted)
• 密度：
  1.256±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 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：

  ethyl 4-(4-methyl-2-nitroanilino)-1-piperidinecarboxylate 在 platinum on activated charcoal sodium hydroxide 、 甲酸铵 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 1-(piperidin-4-yl)-5-methyl-1,3-dihydro-2H-benzimidazol-2-one
  参考文献：
  名称：

  Discovery and SAR studies of a novel series of noncovalent cathepsin S inhibitors

  摘要：

  A novel series of competitive, reversible cathepsin S (Cats) inhibitors was discovered and optimized. The 4-(2-keto-1-benzimidazolinyl)-piperidin-1-yl moiety was found to be an effective replacement for the 4-arylpiperazin-1-yl group found in our earlier series of Cats inhibitors. This replacement imparted improved PK properties as well as decreased off-target activity. Optimization of the ketobenzimidazole moiety led to the discovery of the lead compound JNJ 10329670, which represents a novel class of selective, noncovalent, reversible, and orally bioavailable inhibitors of cathepsin S. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.045
• 作为产物：
  描述：

  4-氨基-1-哌啶甲酸乙酯 、 alkaline earth salt of/the/ methylsulfuric acid 在 sodium carbonate 、 potassium iodide 作用下， 以 环己醇 为溶剂， 反应 0.17h， 生成 ethyl 4-(4-methyl-2-nitroanilino)-1-piperidinecarboxylate
  参考文献：
  名称：

  Benzodiazepine calcitonin gene-related peptide (CGRP) receptor antagonists: Optimization of the 4-substituted piperidine

  摘要：

  In our continuing effort to identify CGRP receptor antagonists for the acute treatment of migraine, we have undertaken a study to evaluate alternative 4-substituted piperidines to the lead dihydroquinazolinone 1. In this regard, we have identified the piperidinyl-azabenzimidazolone and phenylimidazolinone structures which, when incorporated into the benzodiazepine core, afford potent CGRP receptor antagonists (e.g., 18 and 29). These studies produced a potent analog (18) which overcomes the instability issues associated with the lead structure 1. A general pharmacophore for the 4-substituted piperidine component of these CGRP receptor antagonists is also presented. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.07.044

文献信息

• Alpha IC adrenergic receptor antagonists
  申请人：Merck & Co., Inc.

  公开号：US05760054A1

  公开（公告）日：1998-06-02

  This invention relates to certain novel compounds and derivatives thereof, their synthesis, and their use as selective alpha-1C adrenergic receptor antagonists. One application of these compounds is in the treatment of benign prostatic hypertrophy. These compounds are selective in their ability to relax smooth muscle tissue enriched in the alpha1C receptor subtype without at the same time inducing orthostatic hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved.

  这项发明涉及某些新型化合物及其衍生物，它们的合成以及它们作为选择性α-1C肾上腺素受体拮抗剂的用途。这些化合物的一个应用是治疗良性前列腺肥大。这些化合物在其能够放松富含α1C受体亚型的平滑肌组织方面具有选择性，同时不会引起直立性低血压。这样的组织之一是围绕尿道内衬的组织。因此，这些化合物的一个用途是通过减少阻碍尿液流动来为患有良性前列腺增生的男性提供急性缓解。这些化合物的另一个用途是与人类5α-还原酶抑制剂化合物结合，从而实现对良性前列腺增生影响的急性和慢性缓解。
• Muscarine antagonists
  申请人：Merck & Co., Inc.

  公开号：US05574044A1

  公开（公告）日：1996-11-12

  Compounds, 1,3-dihydro-1-1-[piperidin-4-yl]piperidin-4-yl}-2H-benzimidazol-2-ones and 1,3-dihydro-1-4-amino-1-cyclohexyl}-2H-benzimidazol-2-ones and derivatives thereof, their preparation, method of use and pharmaceutical compositions are described. These compounds are endowed with antimuscarinic activity and are useful in the treatment and/or prevention of myopia (commonly known as nearsightedness).

  描述了化合物，1,3-二氢-1-1-[哌啶-4-基]哌啶-4-基}-2H-苯并咪唑-2-酮和1,3-二氢-1-4-氨基-1-环己基}-2H-苯并咪唑-2-酮及其衍生物，它们的制备、使用方法和药物组合物。这些化合物具有抗胆碱能活性，可用于治疗和/或预防近视（通常称为近视）。
• Synthesis and neuroleptic activity of a series of 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]benzimidazolone derivatives
  作者：Rainer Henning、Rudolf Lattrell、Hermann J. Gerhards、Margret Leven

  DOI：10.1021/jm00388a012

  日期：1987.5

  A series of 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]benzimid azolones with various substituents in both aromatic rings have been synthesized and tested for neuroleptic activity (antiapomorphine effects and [3H]spiroperidol binding) as well as extrapyramidal effects (cataleptogenic effect). A strong dependence of activity on the 5-substituent in the benzimidazolone moiety could be demonstrated. Some compounds show a large split between the desired antiapomorphine and the undesired extrapyramidal effect. From these, 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]-5-chlor obenzimidazol-2-one hydrochloride (HR 723), 12, has been selected for further preclinical and toxicological profiling.
• Discovery and SAR studies of a novel series of noncovalent cathepsin S inhibitors
  作者：Darin J. Gustin、Clark A. Sehon、Jianmei Wei、Hui Cai、Steven P. Meduna、Haripada Khatuya、Siquan Sun、Yin Gu、Wen Jiang、Robin L. Thurmond、Lars Karlsson、James P. Edwards

  DOI：10.1016/j.bmcl.2005.01.045

  日期：2005.3

  A novel series of competitive, reversible cathepsin S (Cats) inhibitors was discovered and optimized. The 4-(2-keto-1-benzimidazolinyl)-piperidin-1-yl moiety was found to be an effective replacement for the 4-arylpiperazin-1-yl group found in our earlier series of Cats inhibitors. This replacement imparted improved PK properties as well as decreased off-target activity. Optimization of the ketobenzimidazole moiety led to the discovery of the lead compound JNJ 10329670, which represents a novel class of selective, noncovalent, reversible, and orally bioavailable inhibitors of cathepsin S. (c) 2005 Elsevier Ltd. All rights reserved.
• HENNING R.; LATTRELL R.; GARHARDS H. J.; LEVEN M., J. MED. CHEM., 30,(1987) N 5, 814-819
  作者：HENNING R.、 LATTRELL R.、 GARHARDS H. J.、 LEVEN M.

  DOI：——

  日期：——