8-异氰酸基-2-萘酚 | 70615-55-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 8-异氰酸基-2-萘酚
• 英文名称: 8-isocyanato-2-naphthol
• 英文别名: 7-Hydroxy-1-naphthylisocyanat；7-hydroxy-1-naphthyl isocyanate；8-isocyanatonaphthalen-2-ol
• CAS: 70615-55-3
• 化学式: C₁₁H₇NO₂
• 分子量: 185.182
• InChiKey: QKRMLYBSICUJJS-UHFFFAOYSA-N

物化性质

• 熔点：
  103-104 °C
• 沸点：
  338.1±17.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-异氰酸基-2-萘酚 、 4-甲氧基苄醇 以 吡啶 、 二氯甲烷 为溶剂， 反应 5.0h， 以74%的产率得到(7-hydroxy-1-naphthyl)carbamic acid 4-methoxybenzyl ester
  参考文献：
  名称：

  [EN] NEW HYDROXYNAPHTHYL AMIDES
  [FR] HYDROXYNAPHTYLAMIDES

  摘要：

  本发明涉及公式I的新化合物，其中R1、R2、R3、R4和R5如公式I中所定义，或其盐、溶剂合物或溶剂化盐，以及它们的制备方法、含有所述化合物的药物组合物以及所述化合物在治疗中的应用。这些化合物是辣椒素受体1（VR1）抑制剂，对于治疗多种不同疾病，例如急性和慢性神经病理性和炎症性疼痛，具有用处。

  公开号：

  WO2004089877A1
• 作为产物：
  描述：

  1-氨基-7-萘酚 在 吡啶 、 三乙胺 作用下， 以 甲苯 为溶剂， 反应 1.17h， 生成 8-异氰酸基-2-萘酚
  参考文献：
  名称：

  Structure-Based Generation of a New Class of Potent Cdk4 Inhibitors:  New de Novo Design Strategy and Library Design

  摘要：

  As a first step in structure-based design of highly selective and potent Cdk4 inhibitors, we performed structure-based generation of a novel series of Cdk4 inhibitors. A Cdk4 homology model was constructed according to X-ray analysis of an activated form of Cdk2. Using this model, we applied a new de novo design strategy which combined the de novo design program LEGEND with our in-house structure selection supporting system SEEDS to generate new scaffold candidates. In this way, four classes of scaffold candidates including diarylurea were identified. By constructing diarylurea informer libraries based on the structural requirements of Cdk inhibitors in the ATP binding pocket of the Cdk4 model, we were able to identify a potent Cdk4 inhibitor N-(9-oxo-9H-fluoren-4-yl)-N'-pyridin-2-ylurea 15 (IC50 = 0.10 muM), together with preliminary SAR. We performed a docking study between 15 and the Cdk4 model and selected a reasonable binding mode which is consistent with the SAR. Further modification based on the proposed binding mode provided a more potent compound, N-[(9bR)-5-oxo2,3,5,9b-tetrahydro-1H-pyrrolo[2,1-a]isoindol-9-yl]-N'-pyridin-2-ylurea 26a (IC50 = 0.042 muM), X-ray analysis of which was accomplished by the soaking method. The predicted binding mode of 15 in Cdk4 was validated by X-ray analysis of the Cdk2-26a complex.

  DOI：

  10.1021/jm0103256

文献信息

• ULRICH H.; RICHTER R.; TUCKER B., SYNTHESIS, 1979, NO 4, 277-279
  作者：ULRICH H.、 RICHTER R.、 TUCKER B.

  DOI：——

  日期：——
• [EN] NEW SULFONYL DERIVATIVES OF AMINONAPHTOLS<br/>[FR] DERIVES SULFONYLE D'AMINONAPHTOLS
  申请人：ASTRAZENECA AB

  公开号：WO2004089881A1

  公开（公告）日：2004-10-21

  The present invention relates to new compounds of formula I, [Chemical formula should be inserted here. Please see paper copy] wherein R1, R2, R3, R4 and R5 are as defined as in formula I, or salts, solvates or solvated salts thereof, a process for their preparation, pharmaceutical compositions containing said compounds and to the use of said compounds in therapy. The compounds are vanilloid receptor 1 (VR1) inhibitors and are useful in the treatment of a number of different disorders, for example acute and chronic neuropathic and inflammatory pain.
• [EN] NEW HYDROXYNAPHTHYL AMIDES<br/>[FR] HYDROXYNAPHTYLAMIDES
  申请人：ASTRAZENECA AB

  公开号：WO2004089877A1

  公开（公告）日：2004-10-21

  The present invention relates to new compounds of formula I, [Chemical formula should be inserted here. Please see paper copy] wherein R1, R2, R3, R4 and R5 are as defined as in formula I, or salts, solvates or solvated salts thereof, a process for their preparation, pharmaceutical compositions containing said compounds and to the use of said compounds in therapy. The compounds are vanilloid receptor 1 (VR1) inhibitors and are useful in the treatment of a number of different disorders, for example acute and chronic neuropathic and inflammatory pain.

  本发明涉及公式I的新化合物，其中R1、R2、R3、R4和R5如公式I中所定义，或其盐、溶剂合物或溶剂化盐，以及它们的制备方法、含有所述化合物的药物组合物以及所述化合物在治疗中的应用。这些化合物是辣椒素受体1（VR1）抑制剂，对于治疗多种不同疾病，例如急性和慢性神经病理性和炎症性疼痛，具有用处。
• Structure-Based Generation of a New Class of Potent Cdk4 Inhibitors:  New <i>de Novo</i> Design Strategy and Library Design
  作者：Teruki Honma、Kyoko Hayashi、Tetsuya Aoyama、Noriaki Hashimoto、Takumitsu Machida、Kazuhiro Fukasawa、Toshiharu Iwama、Chinatsu Ikeura、Mari Ikuta、Ikuko Suzuki-Takahashi、Yoshikazu Iwasawa、Takashi Hayama、Susumu Nishimura、Hajime Morishima

  DOI：10.1021/jm0103256

  日期：2001.12.1

  As a first step in structure-based design of highly selective and potent Cdk4 inhibitors, we performed structure-based generation of a novel series of Cdk4 inhibitors. A Cdk4 homology model was constructed according to X-ray analysis of an activated form of Cdk2. Using this model, we applied a new de novo design strategy which combined the de novo design program LEGEND with our in-house structure selection supporting system SEEDS to generate new scaffold candidates. In this way, four classes of scaffold candidates including diarylurea were identified. By constructing diarylurea informer libraries based on the structural requirements of Cdk inhibitors in the ATP binding pocket of the Cdk4 model, we were able to identify a potent Cdk4 inhibitor N-(9-oxo-9H-fluoren-4-yl)-N'-pyridin-2-ylurea 15 (IC50 = 0.10 muM), together with preliminary SAR. We performed a docking study between 15 and the Cdk4 model and selected a reasonable binding mode which is consistent with the SAR. Further modification based on the proposed binding mode provided a more potent compound, N-[(9bR)-5-oxo2,3,5,9b-tetrahydro-1H-pyrrolo[2,1-a]isoindol-9-yl]-N'-pyridin-2-ylurea 26a (IC50 = 0.042 muM), X-ray analysis of which was accomplished by the soaking method. The predicted binding mode of 15 in Cdk4 was validated by X-ray analysis of the Cdk2-26a complex.