[3-(6-chloro-pyridazin-3-yl)-propyl]-carbamic acid tert-butyl ester | 935692-92-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: [3-(6-chloro-pyridazin-3-yl)-propyl]-carbamic acid tert-butyl ester
• 英文别名: [3-(6-Chloro-pyridazin-3-yl)-propyl]-carbamic acid tert-butyl ester；tert-butyl N-[3-(6-chloropyridazin-3-yl)propyl]carbamate
• CAS: 935692-92-5
• 化学式: C₁₂H₁₈ClN₃O₂
• 分子量: 271.747
• InChiKey: CLKXCUJZMGAXAP-UHFFFAOYSA-N

物化性质

• 沸点：
  441.3±35.0 °C(Predicted)
• 密度：
  1.171±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  64.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [3-(6-chloro-pyridazin-3-yl)-propyl]-carbamic acid tert-butyl ester 在 bis-triphenylphosphine-palladium(II) chloride 、 tris-(dibenzylideneacetone)dipalladium(0) 、 碳酸氢钠 、 三氟乙酸 、 2-(二叔丁基膦)联苯 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 4-[6-[3-[4-(Piperidin-1-ylmethyl)anilino]propyl]pyridazin-3-yl]benzonitrile
  参考文献：
  名称：

  Design, synthesis and evaluation of MCH receptor 1 antagonists—Part II: Optimization of pyridazines toward reduced phospholipidosis and hERG inhibition

  摘要：

  Despite recent success there remains a high therapeutic need for the development of drugs targeting diseases associated with the metabolic syndrome. As part of our search for safe and effective MCH-R1 antagonists for the treatment of obesity, a series of 3,6-disubstituted pyridazines was evaluated. During optimization several issues of the initial lead structures had to be resolved, such as selectivity over related GPCRs, inhibition of the hERG channel as well as the potential to induce phospholipidosis. Utilizing property-based design, we could demonstrate that all parameters can significantly be improved by consequently increasing the polarity of the compounds. By this strategy, we succeeded in identifying potent and orally available MCH-R1 antagonists with good selectivity over M1 and 5-HT2A and an improved safety profile with respect to hERG inhibition and phospholipidosis. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.05.074
• 作为产物：
  描述：

  N-Boc-氨基丙炔 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 氢气 、 二异丙胺 作用下， 以 四氢呋喃 、 乙醇 、 乙酸乙酯 为溶剂， -10.0~20.0 ℃ 、344.75 kPa 条件下， 生成 [3-(6-chloro-pyridazin-3-yl)-propyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Design, synthesis and evaluation of MCH receptor 1 antagonists—Part II: Optimization of pyridazines toward reduced phospholipidosis and hERG inhibition

  摘要：

  Despite recent success there remains a high therapeutic need for the development of drugs targeting diseases associated with the metabolic syndrome. As part of our search for safe and effective MCH-R1 antagonists for the treatment of obesity, a series of 3,6-disubstituted pyridazines was evaluated. During optimization several issues of the initial lead structures had to be resolved, such as selectivity over related GPCRs, inhibition of the hERG channel as well as the potential to induce phospholipidosis. Utilizing property-based design, we could demonstrate that all parameters can significantly be improved by consequently increasing the polarity of the compounds. By this strategy, we succeeded in identifying potent and orally available MCH-R1 antagonists with good selectivity over M1 and 5-HT2A and an improved safety profile with respect to hERG inhibition and phospholipidosis. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.05.074

文献信息

• New (hetero)aryl compounds with MCH antagonistic activity and medicaments comprising these compounds
  申请人：Roth Juergen Gerald

  公开号：US20070111981A1

  公开（公告）日：2007-05-17

  The present invention relates to (hetero)aryl compounds of general formula I wherein the groups and radicals A, B, Q, W, X, Y, Z, R 1 , R 2 , R 4a , R 4b , R 5a , R 5b , have the meanings given in claim 1 . Moreover the invention relates to pharmaceutical compositions containing at least one compound according to the invention. By virtue of their MCH-receptor antagonistic activity the pharmaceutical compositions according to the invention are suitable for the treatment of metabolic disorders and/or eating disorders, particularly obesity, bulimia, anorexia, hyperphagia and diabetes.

  本发明涉及一般式I的（杂）芳基化合物，其中A、B、Q、W、X、Y、Z、R1、R2、R4a、R4b、R5a和R5b基团和基团具有权利要求1中给出的含义。此外，本发明涉及至少含有本发明中的一种化合物的制药组合物。由于其MCH受体拮抗活性，根据本发明的制药组合物适用于治疗代谢紊乱和/或进食障碍，尤其是肥胖症、贪食症、厌食症、暴食症和糖尿病。
• WO2007/48802
  申请人：——

  公开号：——

  公开（公告）日：——
• Design, synthesis and evaluation of MCH receptor 1 antagonists—Part II: Optimization of pyridazines toward reduced phospholipidosis and hERG inhibition
  作者：Gerald J. Roth、Armin Heckel、Jörg T. Kley、Thorsten Lehmann、Stephan G. Müller、Thorsten Oost、Klaus Rudolf、Kirsten Arndt、Ralph Budzinski、Martin Lenter、Ralf R.H. Lotz、Marcus Schindler、Leo Thomas、Dirk Stenkamp

  DOI：10.1016/j.bmcl.2015.05.074

  日期：2015.8

  Despite recent success there remains a high therapeutic need for the development of drugs targeting diseases associated with the metabolic syndrome. As part of our search for safe and effective MCH-R1 antagonists for the treatment of obesity, a series of 3,6-disubstituted pyridazines was evaluated. During optimization several issues of the initial lead structures had to be resolved, such as selectivity over related GPCRs, inhibition of the hERG channel as well as the potential to induce phospholipidosis. Utilizing property-based design, we could demonstrate that all parameters can significantly be improved by consequently increasing the polarity of the compounds. By this strategy, we succeeded in identifying potent and orally available MCH-R1 antagonists with good selectivity over M1 and 5-HT2A and an improved safety profile with respect to hERG inhibition and phospholipidosis. (C) 2015 Elsevier Ltd. All rights reserved.