4-(3-phenylisoxazol-5-yl)piperidine-1-carboxylic acid tert-butyl ester | 885609-18-7

• 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: 4-(3-phenylisoxazol-5-yl)piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 4-(3-phenylisoxazol-5-yl)piperidine-1-carboxylate；tert-butyl 4-(3-phenyl-1,2-oxazol-5-yl)piperidine-1-carboxylate
• CAS: 885609-18-7
• 化学式: C₁₉H₂₄N₂O₃
• 分子量: 328.411
• InChiKey: RHKKSJUHWWPNKI-UHFFFAOYSA-N

物化性质

• 沸点：
  478.3±45.0 °C(Predicted)
• 密度：
  1.131±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  55.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(3-phenylisoxazol-5-yl)piperidine-1-carboxylic acid tert-butyl ester 在 三氟乙酸 、 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 1.0h， 以76%的产率得到4-(3-Phenylisoxazol-5-yl)piperidine
  参考文献：
  名称：

  CONSTRAINED COMPOUNDS AS CGRP-RECEPTOR ANTAGONISTS

  摘要：

  这项发明涵盖了受限的双环和三环CGRP受体拮抗剂，用于识别它们的方法，包括它们的药物组合物，以及在治疗偏头痛和其他头痛、神经源性血管舒张、神经源性炎症、热损伤、循环性休克、与绝经期相关的潮红、气道炎症性疾病（如哮喘和慢性阻塞性肺病（COPD））以及其他可以通过CGRP受体拮抗来治疗的疾病的治疗方法。

  公开号：

  US20070259850A1
• 作为产物：
  描述：

  tert-butyl 4-(5-hydroxy-3-phenyl-4,5-dihydroisoxazol-5-yl)piperidine-1-carboxylate 在 sodium carbonate 作用下， 以 甲醇 、 水 为溶剂， 反应 2.0h， 以86%的产率得到4-(3-phenylisoxazol-5-yl)piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  CONSTRAINED COMPOUNDS AS CGRP-RECEPTOR ANTAGONISTS

  摘要：

  这项发明涵盖了受限的双环和三环CGRP受体拮抗剂，用于识别它们的方法，包括它们的药物组合物，以及在治疗偏头痛和其他头痛、神经源性血管舒张、神经源性炎症、热损伤、循环性休克、与绝经期相关的潮红、气道炎症性疾病（如哮喘和慢性阻塞性肺病（COPD））以及其他可以通过CGRP受体拮抗来治疗的疾病的治疗方法。

  公开号：

  US20070259850A1

文献信息

• Constrained compounds as CGRP-receptor antagonists
  申请人：Chaturvedula V. Prasad

  公开号：US20060094707A1

  公开（公告）日：2006-05-04

  The invention encompasses constrained bicyclic and tricyclic CGRP-receptor antagonists, methods for identifying them, pharmaceutical compositions comprising them, and methods for their use in therapy for treatment of migraine and other headaches, neurogenic vasodilation, neurogenic inflammation, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), and other conditions the treatment of which can be effected by the antagonism of CGRP-receptors.

  这项发明涵盖了受限的双环和三环CGRP受体拮抗剂，用于识别它们的方法，包含它们的药物组合物，以及它们在治疗偏头痛和其他头痛、神经源性血管舒张、神经源性炎症、热损伤、循环性休克、与绝经期相关的潮红、气道炎症性疾病（如哮喘和慢性阻塞性肺病（COPD））以及其他可以通过CGRP受体拮抗来治疗的疾病的治疗方法。
• Constrained Compounds as CGRP-Receptor Antagonists
  申请人：Chaturvedula Prasad V.

  公开号：US20080287422A1

  公开（公告）日：2008-11-20

  The invention encompasses constrained bicyclic and tricyclic CGRP-receptor antagonists, methods for identifying them, pharmaceutical compositions comprising them, and methods for their use in therapy for treatment of migraine and other headaches, neurogenic vasodilation, neurogenic inflammation, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), and other conditions the treatment of which can be effected by the antagonism of CGRP-receptors.

  该发明涵盖了受限的双环和三环CGRP受体拮抗剂，其识别方法，包含它们的药物组合物，以及将其用于治疗偏头痛和其他头痛，神经源性血管扩张，神经源性炎症，热伤害，循环性休克，与更年期有关的潮红，气道炎症性疾病（如哮喘和慢性阻塞性肺疾病（COPD））以及其他通过抗CGRP受体作用进行治疗的疾病的治疗方法。
• Ethionamide Boosters. 2. Combining Bioisosteric Replacement and Structure-Based Drug Design To Solve Pharmacokinetic Issues in a Series of Potent 1,2,4-Oxadiazole EthR Inhibitors
  作者：Marion Flipo、Matthieu Desroses、Nathalie Lecat-Guillet、Baptiste Villemagne、Nicolas Blondiaux、Florence Leroux、Catherine Piveteau、Vanessa Mathys、Marie-Pierre Flament、Juergen Siepmann、Vincent Villeret、Alexandre Wohlkönig、René Wintjens、Sameh H. Soror、Thierry Christophe、Hee Kyoung Jeon、Camille Locht、Priscille Brodin、Benoit Déprez、Alain R. Baulard、Nicolas Willand

  DOI：10.1021/jm200825u

  日期：2012.1.12

  Mycobacterial transcriptional repressor EthR controls the expression of EthA, the bacterial monooxygenase activating ethionamide, and is thus largely responsible for the low sensitivity of the human pathogen Mycobacterium tuberculosis to this antibiotic. We recently reported structure-activity relationships of a series of 1,2,4-oxadiazole EthR inhibitors leading to the discovery of potent ethionamide boosters. Despite high metabolic stability, pharmacokinetic evaluation revealed poor mice exposure; therefore, a second phase of optimization was required. Herein a structure-property relationship study is reported according to the replacement of the two aromatic heterocycles: 2-thienyl and 1,2,4-oxadiazolyl moieties. This work was done using a combination of structure-based drug design and in vitro/ex vivo evaluations of ethionamide boosters on the targeted protein EthR and on the human pathogen Mycobacterium tuberculosis. Thanks to this process, we identified compound 42 (BDM41906), which displays improved efficacy in addition to high exposure to mice after oral administration.
• Syntheses and SAR studies of 4-(heteroarylpiperdin-1-yl-methyl)-pyrrolidin-1-yl-acetic acid antagonists of the human CCR5 chemokine receptor
  作者：K. Shankaran、Karla L. Donnelly、Shrenik K. Shah、Ravindra N. Guthikonda、Malcolm MacCoss、Sander G. Mills、Sandra L. Gould、Lorraine Malkowitz、Salvatore J. Siciliano、Martin S. Springer、Anthony Carella、Gwen Carver、Daria Hazuda、Karen Holmes、Joseph Kessler、Janet Lineberger、Michael D. Miller、Emilio A. Emini、William A. Schleif

  DOI：10.1016/j.bmcl.2004.04.078

  日期：2004.7

  Efforts toward the exploration of the title compounds as CCR5 antagonists are disclosed. The basis for such work stems from the fact that cellular proliferation of HIV-1 requires the cooperative assistance of both CCR5 and CD4 receptors. The synthesis and SAR of pyrrolidineacetic acid derivatives as CCR5 antagonists displaying potent binding and antiviral properties in a HeLa cell-based HIV-1 infectivity assay are discussed. (C) 2004 Elsevier Ltd. All rights reserved.
• US7384930B2
  申请人：——

  公开号：US7384930B2

  公开（公告）日：2008-06-10