2-(1-pyrrolidinylmethyl)-6-quinolinylamine | 372149-54-7

• 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: 2-(1-pyrrolidinylmethyl)-6-quinolinylamine
• 英文别名: 2-(pyrrolidin-1-ylmethyl)quinolin-6-amine
• CAS: 372149-54-7
• 化学式: C₁₄H₁₇N₃
• 分子量: 227.309
• InChiKey: VJKXQVIKIJCJQZ-UHFFFAOYSA-N

物化性质

• 沸点：
  387.7±27.0 °C(Predicted)
• 密度：
  1.210±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  42.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(1-pyrrolidinylmethyl)-6-quinolinylamine 生成 4-(4-chlorophenyl)-N-[2-(1-pyrrolidinylmethyl)-6-quinolinyl]-1-piperidinecarboxamide
  参考文献：
  名称：

  MELANIN CONCENTRATING HORMONE ANTAGONISTS

  摘要：

  公开号：

  EP1285651B1
• 作为产物：
  描述：

  N-[2-(1-pyrrolidinylmethyl)-6-quinolinyl]acetamide 在 乙酸乙酯 、 potassium carbonate 、 氯化钠 、 Sodium sulfate-III 、 ethyl acetate n-hexane 作用下， 以 盐酸 为溶剂， 反应 1.0h， 以to obtain the titled compound (4.56 g) as a powder from ethyl acetate-hexane的产率得到2-(1-pyrrolidinylmethyl)-6-quinolinylamine
  参考文献：
  名称：

  Melanin-concentrating hormone antagonist

  摘要：

  一种黑色素浓集激素拮抗剂，包括式(I)的化合物：其中Ar1是可以被取代的环状基团；X和Y相同或不同，是具有1至6个原子的主链间隔基团；Ar是可以被取代的紧凑多环芳香环；R1和R2相同或不同，是氢原子或可以被取代的碳氢基团；或者R1和R2，与相邻的氮原子一起，可以形成可以被取代的含氮杂环；或者R2，与相邻的氮原子和Y一起，可以形成可以被取代的含氮杂环；或者R2，与相邻的氮原子、Y和Ar一起，可以形成紧凑环；或其盐，可用作预防或治疗肥胖症等的药物。

  公开号：

  US06930185B2

文献信息

• Melanin-concentrating hormone antagonist
  申请人：——

  公开号：US20040077628A1

  公开（公告）日：2004-04-22

  A melanin-concentrating hormone antagonist comprising a compound of the formula (I): 1 wherein Ar 1 is a cyclic group which may be substituted; X and Y are the same or different and are a spacer having a main chain of 1 to 6 atoms; Ar is a condensed polycyclic aromatic ring which may be substituted; R 1 and R 2 are the same or different and are hydrogen atom or a hydrocarbon group which may be substituted; or R 1 and R 2 , together with the adjacent nitrogen atom, may form a nitrogen-containing heterocyclic ring which may be substituted; or R 2 , together with the adjacent nitrogen atom and Y, may form a nitrogen-containing heterocyclic ring which may be substituted; or R 2 , together with the adjacent nitrogen atom, Y and Ar, may form a condensed ring; or a salt thereof is useful as an agent for preventing or treating obesity, etc.

  一种黑色素浓集激素拮抗剂，包括化合物(I)的一种，其中Ar1是一个可以被取代的环状基团；X和Y相同或不同，是具有1至6个原子的主链间隔物；Ar是一个可以被取代的紧凑多环芳香环；R1和R2相同或不同，是氢原子或可以被取代的碳氢基团；或者R1和R2与相邻的氮原子一起可以形成一个可以被取代的含氮杂环；或者R2与相邻的氮原子和Y一起可以形成一个可以被取代的含氮杂环；或者R2与相邻的氮原子、Y和Ar一起可以形成一个紧凑环；或其盐，可用作预防或治疗肥胖等药物。
• Potent, Selective, and Orally Efficacious Antagonists of Melanin-Concentrating Hormone Receptor 1
  作者：Francis X. Tavares、Kamal A. Al-Barazanji、Eric C. Bigham、Michael J. Bishop、Christy S. Britt、David L. Carlton、Paul L. Feldman、Aaron S. Goetz、Mary K. Grizzle、Yu C. Guo、Anthony L. Handlon、Donald L. Hertzog、Diane M. Ignar、Daniel G. Lang、Ronda J. Ott、Andrew J. Peat、Hui-Qiang Zhou

  DOI：10.1021/jm060572f

  日期：2006.11.30

  The high expression of MCH in the hypothalamus with the lean hypophagic phenotype coupled with increased resting metabolic rate and resistance to high fat diet-induced obesity of MCH KO mice has spurred considerable efforts to develop small molecule MCHR1 antagonists. Starting from a lead thienopyrimidinone series, structure-activity studies at the 3- and 6-positions of the thienopyrimidinone core afforded potent and selective MCHR1 antagonists with representative examples having suitable pharmacokinetic properties. Based on structure-activity relationships, a structural model for MCHR1 was constructed to explain the binding mode of these antagonists. In general, a good correlation was observed between pK(a)s and activity in the right-hand side of the template, with Asp123 playing an important role in the enhancement of binding affinity. A representative example when evaluated chronically in diet-induced obese mice resulted in good weight loss effects. These antagonists provide a viable lead series in the discovery of new therapies for the treatment of obesity.
• US6930185B2
  申请人：——

  公开号：US6930185B2

  公开（公告）日：2005-08-16
• [EN] HETEROCYCLIC MCHR1 ANTAGONISTS<br/>[FR] ANTAGONISTES HETEROCYCLIQUES DE MCHR1
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2004092181A9

  公开（公告）日：2005-01-27

  [EN] This invention relates to novel heterocycles which are antagonists at the melanin-concentrating hormone receptor 1 (MCHR1), also referred to as 11CBy, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in medicines. Compounds of the invention have formula (I).
  [FR] L'invention concerne des dérivés de benzopyrane substitués, des stéréoisomères et des sels pharmaceutiquement acceptables desdits composés, ainsi que des procédés appropriés pour les préparer. Les composés de la présente invention s'utilisent comme agonistes du récepteur beta des oestrogènes. De tels agonistes s'utilisent dans le traitement d'affections induites par le récepteur beta des oestrogènes, telles que le cancer de la prostate ou l'hyperplasie prostatique bénigne (HPB).
• Melanin-Concentrating Hormone Receptor 1 Antagonists. Synthesis and Structure–Activity Relationships of Novel 3-(Aminomethyl)quinolines
  作者：Makoto Kamata、Toshiro Yamashita、Toshihiro Imaeda、Toshio Tanaka、Shinichi Masada、Masahiro Kamaura、Shizuo Kasai、Ryoma Hara、Shigekazu Sasaki、Shiro Takekawa、Asano Asami、Tomoko Kaisho、Nobuhiro Suzuki、Shuntaro Ashina、Hitomi Ogino、Yoshihide Nakano、Yasutaka Nagisa、Koki Kato、Kaneyoshi Kato、Yuji Ishihara

  DOI：10.1021/jm201596h

  日期：2012.3.8

  It was found that 3-(aminomethyl)quinoline derivatives showed high binding affinities for melanin-concentrating hormone receptor 1 (MCHR1) with reduced affinity for serotonin receptor 2c (5-HT2c) when the dihydronaphthalene nucleus of compound 1 (human MCHR1, IC50 = 1.9 nM; human 5-HT2c receptor, IC50 = 0.53 nM) was replaced by other bicyclic core scaffolds. Among the synthesized compounds, 8-methylquinoline derivative 5v especially showed high binding affinity (IC50 = 0.54 nM), potent in vitro antagonistic activity (IC50 = 2.8 nM) for MCHR1, and negligible affinity for 5-HT2c receptor (IC50 > 1000 nM). Oral administration of 5v significantly and dose-dependently suppressed nocturnal food intake in diet-induced obese rats and did not affect food intake in MCHR1-deficient mice. These results and rat pharmacokinetic study findings suggested that compound 5v is a highly potent, orally bioavailable, and centrally acting nonpeptide MCHR1 antagonist.