5-chloro-6-[(4-methoxyphenyl)methoxy]-3H-1,3-benzoxazol-2-one | 1046816-41-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶唑类
• 英文名称: 5-chloro-6-[(4-methoxyphenyl)methoxy]-3H-1,3-benzoxazol-2-one
• CAS: 1046816-41-4
• 化学式: C₁₅H₁₂ClNO₄
• 分子量: 305.718
• InChiKey: KYQXANQVFMWOJU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  56.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-chloro-6-[(4-methoxyphenyl)methoxy]-3H-1,3-benzoxazol-2-one 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 1-[5-chloro-4-[(4-methoxyphenyl)methoxy]-2-[[(2S)-oxiran-2-yl]methoxy]phenyl]-3-cyclopropylurea
  参考文献：
  名称：

  Structure activity relationships of fused bicyclic and urea derivatives of spirocyclic compounds as potent CCR1 antagonists

  摘要：

  A series of fused bicyclic and urea derivatives of spirocyclic compounds were designed, synthesised and evaluated in vitro as potent CCR1 antagonists. In particular, 4 (7 nM), 44 (1.3 nM), 48 (0.89 nM) and 50 (0.63 nM) were the most potent hCCR1 antagonists in this series of compounds. Moreover, some of these substances demonstrated good rodent cross-over, especially 46 which exhibited very high rat CCR1 binding affinity with an IC50 value of 16 nM. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.11.062

文献信息

• Novel Combination of Compounds to be Used in the Treatment of Airway Diseases, Especially Chronic Obstructive Pulmonary Disease (COPD) and Asthma
  申请人：Eriksson Tomas

  公开号：US20110136843A1

  公开（公告）日：2011-06-09

  The present invention relates to a combination of (a) a chemokine receptor 1 (CCR1) antagonist and (b) a muscarinic antagonist. The invention further relates to pharmaceutical compositions comprising said combination and to methods of treatment of airway diseases, such as chronic obstructive pulmonary disease (COPD) and asthma in mammals by administrating said combination. The invention further relates to a kit comprising the combination and use of said kit in treatment of airway diseases.

  本发明涉及一种（a）化学趋化因子受体1（CCR1）拮抗剂和（b）肌动蛋白受体拮抗剂的组合。本发明还涉及包含该组合的制药组合物以及通过给予该组合来治疗哺乳动物的气道疾病，例如慢性阻塞性肺疾病（COPD）和哮喘的方法。本发明还涉及一种包含该组合的工具箱以及使用该工具箱治疗气道疾病的用途。
• NOVEL COMBINATION OF COMPOUNDS TO BE USED IN THE TREATMENT OF AIRWAY DISEASES, ESPECIALLY CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AND ASTHMA
  申请人：AstraZeneca AB

  公开号：EP2125728A1

  公开（公告）日：2009-12-02
• [EN] COMBINATIONS WITH A MUSCARINIC RECEPTOR ANTAGONIST<br/>[FR] COMBINAISON INÉDITE
  申请人：ARGENTA DISCOVERY LTD

  公开号：WO2008096136A1

  公开（公告）日：2008-08-14

  [EN] The invention provides a pharmaceutical product, kit or composition comprising a first active ingredient which is a selected muscarinic receptor antagonist, and a second active ingredient which is selected from a phosphodiesterase inhibitor, a modulator of chemokine receptor function, an inhibitor of kinase function, a protease inhibitor, a steroidal glucocorticoid receptor agonist, a non-steroidal glucocorticoid receptor agonist and a purinoceptor antagonist, of use in the treatment of respiratory diseases such as chronic obstructive pulmonary disease and asthma.
  [FR] La présente invention a trait à un produit, une trousse ou une composition pharmaceutique comprenant un premier principe actif, qui est un antagoniste d'un récepteur muscarinique sélectionné, et un second principe actif, qui est choisi parmi un inhibiteur de la phosphodiestérase, un modulateur de l'action du récepteur des chimiokines, un inhibiteur de l'activité kinase, un inhibiteur des protéases, un agoniste stéroïdien du récepteur des glucocorticoïdes, un agoniste non stéroïdien du récepteur des glucocorticoïdes et un antagoniste du purinocepteur, utilisable dans le cadre du traitement de maladies respiratoires comme la bronchopneumopathie chronique obstructive et l'asthme.
• [EN] NOVEL COMBINATION OF COMPOUNDS TO BE USED IN THE TREATMENT OF AIRWAY DISEASES, ESPECIALLY CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AND ASTHMA<br/>[FR] NOUVELLE COMBINAISON DE COMPOSÉS UTILISÉS DANS LE TRAITEMENT DES MALADIES DES VOIES AÉRIENNES, EN PARTICULIER LA BRONCHOPNEUMOPATHIE CHRONIQUE OBSTRUCTIVE (COPD) ET L'ASTHME
  申请人：ASTRAZENECA AB

  公开号：WO2008103125A1

  公开（公告）日：2008-08-28

  [EN] The present invention relates to a combination of (a) a chemokine receptor 1 (CCR1) antagonist and (b) a muscarinic antagonist. The invention further relates to pharmaceutical compositions comprising said combination and to methods of treatment of airway diseases, such as chronic obstructive pulmonary disease (COPD) and asthma in mammals by administrating said combination. The invention further relates to a kit comprising the combination and use of said kit in treatment of airway diseases.
  [FR] La présente invention concerne une combinaison (a) d'un antagoniste du récepteur 1 des chimiokines (CCR1) et (b) d'un antagoniste muscarinique. L'invention concerne également des compositions pharmaceutiques contenant ladite combinaison et des méthodes de traitement des maladies des voies aériennes, telles que la bronchopneumopathie chronique obstructive (COPD) et l'asthme chez des mammifères par administration de ladite combinaison. L'invention concerne également un kit contenant ladite combinaison et l'utilisation dudit kit dans le traitement des maladies des voies aériennes.
• Structure activity relationships of fused bicyclic and urea derivatives of spirocyclic compounds as potent CCR1 antagonists
  作者：Nafizal Hossain、Marguérite Mensonides-Harsema、Martin E. Cooper、Tomas Eriksson、Svetlana Ivanova、Lena Bergström

  DOI：10.1016/j.bmcl.2013.11.062

  日期：2014.1

  A series of fused bicyclic and urea derivatives of spirocyclic compounds were designed, synthesised and evaluated in vitro as potent CCR1 antagonists. In particular, 4 (7 nM), 44 (1.3 nM), 48 (0.89 nM) and 50 (0.63 nM) were the most potent hCCR1 antagonists in this series of compounds. Moreover, some of these substances demonstrated good rodent cross-over, especially 46 which exhibited very high rat CCR1 binding affinity with an IC50 value of 16 nM. (C) 2013 Elsevier Ltd. All rights reserved.