methyl 5-(4-chlorophenyl)-3-((dimethylamino)methyleneamino)thiophene-2-carboxylate | 515142-62-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: methyl 5-(4-chlorophenyl)-3-((dimethylamino)methyleneamino)thiophene-2-carboxylate
• 英文别名: 5-(4-chlorophenyl)-3-(dimethylaminomethyleneamino)thiophene-2-carboxylic acid methyl ester；methyl 5-(4-chlorophenyl)-3-(dimethylaminomethyleneamino) thiophene-2-carboxylate；methyl 5-(4-chlorophenyl)-3-(dimethylaminomethyleneamino)thiophene-2-carboxylate；methyl 5-(4-chlorophenyl)-3-(dimethylaminomethylideneamino)thiophene-2-carboxylate
• CAS: 515142-62-8
• 化学式: C₁₅H₁₅ClN₂O₂S
• 分子量: 322.815
• InChiKey: ALWFLYMKFZJTBB-UHFFFAOYSA-N

物化性质

• 沸点：
  478.6±55.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  70.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 5-(4-chlorophenyl)-3-((dimethylamino)methyleneamino)thiophene-2-carboxylate 在 TEA 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 41.0h， 生成 (S)-3-(6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl)-N-methyl-N-((S)-pyrrolidin-3-yl)pyrrolidine-1-carboxamide
  参考文献：
  名称：

  Thienopyrimidinone bis-aminopyrrolidine ureas as potent melanin-concentrating hormone receptor-1 (MCH-R1) antagonists

  摘要：

  A series of thienopyrimidinone bis-aminopyrrolidine ureas were designed, synthesized, and evaluated for their ability to bind melanin-concentrating hormone receptor-1. These compounds exhibit potent binding affinity (K-i = 3 nM) and good in vitro metabolic stability. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.02.012
• 作为产物：
  描述：

  3-氨基-5-(4-氯苯基)噻吩-2-羧酸甲酯 、 N,N-二甲基甲酰胺二甲基缩醛 在 水 、 乙酸乙酯 、 magnesium sulfate 、 C15H15ClN2O2S 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 methyl 5-(4-chlorophenyl)-3-((dimethylamino)methyleneamino)thiophene-2-carboxylate
  参考文献：
  名称：

  Azacyclyl-substituted arylthienopyrimidinones, process for their preparation and their use as medicaments

  摘要：

  该发明涉及一种含有氮杂环取代的芳基噻唑嘧啶酮及其衍生物，其化学式为(I)；及其生理上可耐受的盐和生理上功能性衍生物，其制备方法，包含至少一种符合化学式(I)或其衍生物的氮杂环取代的芳基噻唑嘧啶酮的药物，以及将符合化学式(I)及其衍生物的氮杂环取代的芳基噻唑嘧啶酮用作MCH受体拮抗剂的用途。

  公开号：

  US08828991B2

文献信息

• Synthesis and Antiobesity Properties of 6-(4-Chlorophenyl)-3-(4-((3,3-difluoro-1-hydroxycyclobutyl)methoxy)-3-methoxyphenyl)thieno[3,2-<i>d</i>]pyrimidin-4(3<i>H</i>)-one (BMS-814580): A Highly Efficacious Melanin Concentrating Hormone Receptor 1 (MCHR1) Inhibitor
  作者：Saleem Ahmad、William N. Washburn、Andres S. Hernandez、Sharon Bisaha、Khehyong Ngu、Wei Wang、Mary Ann Pelleymounter、Daniel Longhi、Neil Flynn、Anthony V. Azzara、Kenneth Rohrbach、James Devenny、Suzanne Rooney、Michael Thomas、Susan Glick、Helen Godonis、Susan Harvey、Hongwei Zhang、Brian Gemzik、Evan B. Janovitz、Christine Huang、Lisa Zhang、Jeffrey A. Robl、Brian J. Murphy

  DOI：10.1021/acs.jmedchem.6b00676

  日期：2016.10.13

  The potent MCHR1 in vitro and in vivo antagonist activity of a series of cyclic tertiary alcohols derived from compound 2b is described. Subsequent pharmacokinetic and pharmacodynamic studies identified BMS-814580 (compound 10) as a highly efficacious antiobesity agent with a relatively clean in vitro and in vivo safety profile.

  描述了衍生自化合物2b的一系列环状叔醇在体外和体内的有效MCHR1拮抗活性。随后的药代动力学和药效学研究确定BMS-814580（化合物10）为高效抗肥胖药，具有相对干净的体外和体内安全性。
• Pyrimidinones as melanin concentrating hormone receptor 1
  申请人：——

  公开号：US20040220404A1

  公开（公告）日：2004-11-04

  A compound of formula (Ia) comprising a pharmaceutically acceptable salt or solvate thereof, formulations, processes of preparing, and methods of administering to mammals are provided 1

  提供了一种化合物(Ia)的配方，包括其药用可接受的盐或溶剂，制备过程以及对哺乳动物的给药方法。
• Non-basic melanin concentrating hormone receptor-1 antagonists
  申请人：Ahmad Saleem

  公开号：US20070093508A1

  公开（公告）日：2007-04-26

  The present application provides compounds, including all stereoisomers, solvates, prodrugs and pharmaceutically acceptable forms thereof according to Formula I. Additionally, the present application provides pharmaceutical compositions containing at least one compound according to Formula I and optionally at least one additional therapeutic agent. Finally, the present application provides methods for treating a patient suffering from an MCHR-1 modulated disease or disorder such as, for example, obesity, diabetes, depression or anxiety by administration of a therapeutically effective dose of a compound according to Formula I.

  本申请提供了根据式I提供的化合物，包括所有立体异构体、溶剂化物、前药和药学上可接受的形式。此外，本申请提供了含有至少一种式I化合物和可选的至少一种额外治疗剂的制药组合物。最后，本申请提供了使用根据式I的化合物的治疗方法，用于治疗患有MCHR-1调节的疾病或障碍，如肥胖症、糖尿病、抑郁症或焦虑症的患者，通过给予治疗有效剂量的根据式I的化合物。
• Therapeutic Agents
  申请人：Giordanetto Fabrizio

  公开号：US20080051405A1

  公开（公告）日：2008-02-28

  The present invention provides compounds of formula I, processes for preparing such compounds, their use in the treatment of obesity, psychiatric disorders, cognitive disorders, memory disorders, schizophrenia, epilepsy, and related conditions, type II diabetes, Metabolic syndrome and neurological disorders such as dementia, multiple sclerosis, Parkinson's disease, Huntington's chorea, Alzheimer's disease, and pain related disorders, and to pharmaceutical compositions containing them.

  本发明提供了I式化合物，制备这些化合物的过程，以及它们在治疗肥胖症、精神障碍、认知障碍、记忆障碍、精神分裂症、癫痫和相关疾病、2型糖尿病、代谢综合征和神经疾病（如痴呆、多发性硬化症、帕金森病、亨廷顿舞蹈症、阿尔茨海默病和与疼痛有关的疾病）中的应用，以及含有它们的制药组合物。
• NOVEL AZACYCLYL-SUBSTITUTED ARYLTHIENOPYRIMIDINONES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS MEDICAMENTS
  申请人：SCHWINK Lothar

  公开号：US20090082339A1

  公开（公告）日：2009-03-26

  The invention relates to azacyclyl-substituted arylthienopyrimidinones and their derivatives, and their physiologically tolerated salts and physiologically functional derivatives, their preparation, medicaments comprising at least one azacyclyl-substituted arylthienopyrimidinone of the invention or its derivative, and the use of the azacyclyl-substituted arylthienopyrimidinones of the invention and their derivatives as MCH antagonists.

  本发明涉及氮杂环取代芳基噻唑嘧啶酮及其衍生物、其生理上耐受的盐和生理上功能性衍生物、其制备方法、包含本发明中至少一种氮杂环取代芳基噻唑嘧啶酮或其衍生物的药物以及将本发明中的氮杂环取代芳基噻唑嘧啶酮及其衍生物用作MCH拮抗剂的用途。