4-[chloro(8-quinolinyl)methyl]-N,N-diethylbenzamide | 346722-42-7

• 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: 4-[chloro(8-quinolinyl)methyl]-N,N-diethylbenzamide
• 英文别名: 4-[chloro(quinolin-8-yl)methyl]-N,N-diethylbenzamide
• CAS: 346722-42-7
• 化学式: C₂₁H₂₁ClN₂O
• 分子量: 352.864
• InChiKey: CFYPMHGZSZPTDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  33.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-苄基哌嗪 、 4-[chloro(8-quinolinyl)methyl]-N,N-diethylbenzamide 在 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 生成 4-[(4-benzyl-1-piperazinyl)(8-quinolinyl)methyl]-N,N-diethylbenzamide dihydrochloride
  参考文献：
  名称：

  Novel compounds

  摘要：

  通式（I）的化合物，其中R1选择自苯基、吡啶基、噻吩基、呋喃基、咪唑基；每个苯环和杂环可能且独立地进一步被1、2或3个取代基所取代，所述取代基选择自直链和支链的C1-C6烷基、NO2、CF3、C1-C6烷氧基、氯、氟、溴和碘；在本申请中披露并声明了这些化合物及其药学上可接受的盐、包含这些新化合物的药物组合物以及它们在治疗中的用途，特别是在疼痛管理中的用途。

  公开号：

  US20030119845A1
• 作为产物：
  描述：

  N,N-二乙基苯甲酰胺-4-羧醛 在 氯化亚砜 、 仲丁基锂 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 2.5h， 生成 4-[chloro(8-quinolinyl)methyl]-N,N-diethylbenzamide
  参考文献：
  名称：

  New Diarylmethylpiperazines as Potent and Selective Nonpeptidic δ Opioid Receptor Agonists with Increased In Vitro Metabolic Stability

  摘要：

  Nonpeptide delta opioid agonists are analgesics with a potentially improved side-effect and abuse liability profile, compared to classical opioids. Andrews analysis of the NIH nonpeptide lead SNC-80 suggested the removal of substituents not predicted to contribute to binding. This approach led to a simplified lead, N,N-diethyl-4-[phenyl( 1-piperazinyl)methyl]benzamide (1), which retained potent binding affinity and selectivity to the human delta receptor (IC50 = 11 nM, mu/delta = 740, kappa/delta > 900) and potency as a full agonist (EC50 = 36 nM) but had a markedly reduced molecular weight, only one chiral center, and increased in vitro metabolic stability. From this lead, the key pharmacophore groups for delta receptor affinity and activation were more clearly defined by SAR and mutagenesis studies. Further structural modifications on the basis of 1 confirmed the importance of the N,N-diethylbenzamide group and the piperazine lower basic nitrogen for delta binding, in agreement with mutagenesis data. A number of piperazine N-alkyl substituents were tolerated. In contrast, modifications of the phenyl group led to the discovery of a series of diarylmethylpiperazines exemplified by N,N-diethyl-4-[1-piperazinyl(8-quinolinyl)- methyl]benzamide (56) which had an improved in vitro binding profile (IC50 = 0.5 nM, mu/delta = 1239, EC50 = 3.6 nM) and increased in vitro metabolic stability compared to SNC-80.

  DOI：

  10.1021/jm000228x

文献信息

• Piperazine-containing compounds useful in the treatment of pain
  申请人：AstraZeneca AB

  公开号：US06784181B2

  公开（公告）日：2004-08-31

  The present invention is directed to a compound of general formula (I), wherein R1 is selected from phenyl, pyridinyl, thiophenyl, furanyl, imidazolyl; each phenyl ring and heteroaromatic ring optionally and independently being further substituted by 1, 2 or 3 substituents selected from straight and branched C1-C6 alkyl, NO2, CF3, C1-C6 alkoxy, chloro, fluoro, bromo, and iodo, as well as their pharmaceutically acceptable salts. The invention includes pharmaceutical compositions comprising these compounds and the use of the compounds in therapy, in particular in the management of pain.

  本发明涉及一种通式(I)的化合物，其中R1从苯基、吡啶基、噻吩基、呋喃基、咪唑基中选择；每个苯环和杂环环可以选择地独立地进一步被1、2或3个取代基所取代，所述取代基选择自直链和支链C1-C6烷基、NO2、CF3、C1-C6烷氧基、氯、氟、溴和碘，以及其药学上可接受的盐。本发明还包括包含这些化合物的制药组合物以及这些化合物在治疗中的使用，特别是在疼痛管理中的使用。
• NOVEL COMPOUNDS
  申请人：AstraZeneca AB

  公开号：EP1242402B1

  公开（公告）日：2003-11-12
• US6784181B2
  申请人：——

  公开号：US6784181B2

  公开（公告）日：2004-08-31
• New Diarylmethylpiperazines as Potent and Selective Nonpeptidic δ Opioid Receptor Agonists with Increased In Vitro Metabolic Stability
  作者：Niklas Plobeck、Daniel Delorme、Zhong-Yong Wei、Hua Yang、Fei Zhou、Peter Schwarz、Lars Gawell、Hélène Gagnon、Benjamin Pelcman、Ralf Schmidt、Shi Yi Yue、Christopher Walpole、William Brown、Edward Zhou、Maryse Labarre、Kemal Payza、Stephane St-Onge、Augustus Kamassah、Pierre-Emmanuel Morin、Denis Projean、Julie Ducharme、Edward Roberts

  DOI：10.1021/jm000228x

  日期：2000.10.1

  Nonpeptide delta opioid agonists are analgesics with a potentially improved side-effect and abuse liability profile, compared to classical opioids. Andrews analysis of the NIH nonpeptide lead SNC-80 suggested the removal of substituents not predicted to contribute to binding. This approach led to a simplified lead, N,N-diethyl-4-[phenyl( 1-piperazinyl)methyl]benzamide (1), which retained potent binding affinity and selectivity to the human delta receptor (IC50 = 11 nM, mu/delta = 740, kappa/delta > 900) and potency as a full agonist (EC50 = 36 nM) but had a markedly reduced molecular weight, only one chiral center, and increased in vitro metabolic stability. From this lead, the key pharmacophore groups for delta receptor affinity and activation were more clearly defined by SAR and mutagenesis studies. Further structural modifications on the basis of 1 confirmed the importance of the N,N-diethylbenzamide group and the piperazine lower basic nitrogen for delta binding, in agreement with mutagenesis data. A number of piperazine N-alkyl substituents were tolerated. In contrast, modifications of the phenyl group led to the discovery of a series of diarylmethylpiperazines exemplified by N,N-diethyl-4-[1-piperazinyl(8-quinolinyl)- methyl]benzamide (56) which had an improved in vitro binding profile (IC50 = 0.5 nM, mu/delta = 1239, EC50 = 3.6 nM) and increased in vitro metabolic stability compared to SNC-80.
• Novel compounds
  申请人：——

  公开号：US20030119845A1

  公开（公告）日：2003-06-26

  Compounds of general formula (I), wherein R 1 is selected from phenyl, pyridinyl, thiophenyl, furanyl, imidazolyl; each phenyl ring and heteroaromatic ring optionally and independently being further substituted by 1, 2 or 3 substituents selected from straight and branched C 1 -C 6 alkyl, NO 2 , CF 3 , C 1 -C 6 alkoxy, chloro, fluoro, bromo, and iodo; are disclosed and claimed in the present application, as well as their pharmaceutically acceptable salts, pharmaceutical compositions comprising the novel compounds and their use in therapy, in particular in the management of pain.

  通式（I）的化合物，其中R1选择自苯基、吡啶基、噻吩基、呋喃基、咪唑基；每个苯环和杂环可能且独立地进一步被1、2或3个取代基所取代，所述取代基选择自直链和支链的C1-C6烷基、NO2、CF3、C1-C6烷氧基、氯、氟、溴和碘；在本申请中披露并声明了这些化合物及其药学上可接受的盐、包含这些新化合物的药物组合物以及它们在治疗中的用途，特别是在疼痛管理中的用途。