3-(4-Chloro-phenyl)-3-[3-(6-isopropyl-quinolin-8-yl)-phenyl]-2-pyridin-4-yl-propionic acid ethyl ester | 481680-49-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 3-(4-Chloro-phenyl)-3-[3-(6-isopropyl-quinolin-8-yl)-phenyl]-2-pyridin-4-yl-propionic acid ethyl ester
• 英文别名: ethyl 3-(4-chlorophenyl)-3-[3-(6-propan-2-ylquinolin-8-yl)phenyl]-2-pyridin-4-ylpropanoate
• CAS: 481680-49-3
• 化学式: C₃₄H₃₁ClN₂O₂
• 分子量: 535.085
• InChiKey: HYLUCMVPIPOEJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  52.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-Chloro-phenyl)-3-[3-(6-isopropyl-quinolin-8-yl)-phenyl]-2-pyridin-4-yl-propionic acid ethyl ester 在 sodium hydroxide 作用下， 生成 8-{3-[1-(4-Chloro-phenyl)-2-pyridin-4-yl-ethyl]-phenyl}-6-isopropyl-quinoline
  参考文献：
  名称：

  Discovery of a substituted 8-arylquinoline series of PDE4 inhibitors: Structure–activity relationship, optimization, and identification of a highly potent, well tolerated, PDE4 inhibitor

  摘要：

  The discovery and SAR of a new series of substituted 8-arylquinoline PDE4 inhibitors are herein described. This work has led to the identification of several compounds with excellent in vitro and in vivo profiles, including a good therapeutic window of emesis to efficacy in several animal models. Typical optimized compounds from this series are potent inhibitors of PDE4 (IC50 < 1 nM) and also of LPS-induced TNF-alpha release in human whole blood (IC50 < 0.5 mu M). The same compounds are potent inhibitors of ovalbumin-induced bronchoconstriction in conscious guinea pigs (EC50 < 0.1 mg/kg ip) but require a dose of about 10 mg/kg po in the squirrel monkey to produce an emetic response. From this series of compounds, 23a (L-454,560) was identified as an optimized compound. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.08.036
• 作为产物：
  描述：

  8-{3-[Chloro-(4-chloro-phenyl)-methyl]-phenyl}-6-isopropyl-quinoline 、 4-吡啶乙酸乙酯 在 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 、 六甲基磷酰三胺 为溶剂， 生成 3-(4-Chloro-phenyl)-3-[3-(6-isopropyl-quinolin-8-yl)-phenyl]-2-pyridin-4-yl-propionic acid ethyl ester
  参考文献：
  名称：

  Discovery of a substituted 8-arylquinoline series of PDE4 inhibitors: Structure–activity relationship, optimization, and identification of a highly potent, well tolerated, PDE4 inhibitor

  摘要：

  The discovery and SAR of a new series of substituted 8-arylquinoline PDE4 inhibitors are herein described. This work has led to the identification of several compounds with excellent in vitro and in vivo profiles, including a good therapeutic window of emesis to efficacy in several animal models. Typical optimized compounds from this series are potent inhibitors of PDE4 (IC50 < 1 nM) and also of LPS-induced TNF-alpha release in human whole blood (IC50 < 0.5 mu M). The same compounds are potent inhibitors of ovalbumin-induced bronchoconstriction in conscious guinea pigs (EC50 < 0.1 mg/kg ip) but require a dose of about 10 mg/kg po in the squirrel monkey to produce an emetic response. From this series of compounds, 23a (L-454,560) was identified as an optimized compound. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.08.036

文献信息

• [EN] SUBSTITUTED 8-ARYLQUINOLINE PDE4 INHIBITORS<br/>[FR] ARYLQUINONES INHIBITEURS DE PDE4 A SUBSTITUTION EN POSITION 8
  申请人：MERCK FROSST CANADA INC

  公开号：WO2003002118A1

  公开（公告）日：2003-01-09

  8-arylquinolines of formula(I) wherein the aryl group at the 8-position contains a meta two atom bridge to an optionally substituted phenyl or pyridyl group, are PDE4 inhibitors useful to treat asthma, chronic bronchitis, chronic obstructive pulmonary disease, arthritis, respiratory distress syndrome, allergic rhinitis, neurogenic inflammation, pain, rheumatoid arthritis, and other diseases. R1-R7 and Ar are as in claim 1.

  公式(I)中的8-arylquinolines，其中8位的芳基基团含有一个与可选取代的苯基或吡啶基团形成的间位两原子桥，是PDE4抑制剂，可用于治疗哮喘、慢性支气管炎、慢性阻塞性肺疾病、关节炎、呼吸窘迫综合症、过敏性鼻炎、神经源性炎症、疼痛、类风湿性关节炎和其他疾病。其中R1-R7和Ar如权利要求1所述。
• Substituted 8-arylquinolune pde4 inhibitors
  申请人：——

  公开号：US20040162314A1

  公开（公告）日：2004-08-19

  8-arylquinolines of formula (I) wherein the aryl group at the 8-position contains a meta two atom bridge to an optionally substituted phenyl or pyridyl group, are PDE4 inhibitors useful to treat asthma, chronic bronchitis, chronic obstructive pulmonary disease, arthritis, respiratory distress syndrome, allergic rhinitis, neurogenic inflammation, pain, rheumatoid arthritis, and other diseases. R 1 -R 7 and Ar are as in claim 1. 1

  公式(I)中的8-芳基喹啉，其中8位处的芳基团含有与可选取代苯基或吡啶基相连接的间位两个原子桥，是PDE4抑制剂，可用于治疗哮喘、慢性支气管炎、慢性阻塞性肺病、关节炎、呼吸窘迫综合症、过敏性鼻炎、神经源性炎症、疼痛、类风湿性关节炎和其他疾病。其中R1-R7和Ar如权利要求1.1所述。
• Substituted 8-arylquinolune PDE4 inhibitors
  申请人：Dube Daniel

  公开号：US06919353B2

  公开（公告）日：2005-07-19

  8-arylquinolines of formula (I) wherein the aryl group at the 8-position contains a meta two atom bridge to an optionally substituted phenyl or pyridyl group, are PDE4 inhibitors useful to treat asthma, chronic bronchitis, chronic obstructive pulmonary disease, arthritis, respiratory distress syndrome, allergic rhinitis, neurogenic inflammation, pain, rheumatoid arthritis, and other diseases. R 1 -R 7 and Ar are as in claim 1.

  公式（I）中的8-芳基喹啉，其中8-位置的芳基基团含有一个与可选取代的苯基或吡啶基团相连的间位二原子桥，是PDE4抑制剂，可用于治疗哮喘、慢性支气管炎、慢性阻塞性肺病、关节炎、呼吸窘迫综合征、过敏性鼻炎、神经源性炎症、疼痛、类风湿性关节炎和其他疾病。其中R1-R7和Ar如权利要求1所述。
• SUBSTITUTED 8-ARYLQUINOLINE PDE4 INHIBITORS
  申请人：MERCK FROSST CANADA & CO.

  公开号：EP1404330A1

  公开（公告）日：2004-04-07
• US6919353B2
  申请人：——

  公开号：US6919353B2

  公开（公告）日：2005-07-19