4-chloro-5-hydroxy-2-(tetrahydro-2H-pyran-2-yl)-3(2H)-pyridazinone | 645405-18-1

• 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: 4-chloro-5-hydroxy-2-(tetrahydro-2H-pyran-2-yl)-3(2H)-pyridazinone
• 英文别名: 4-Chloro-5-hydroxy-2-(2-tetrahydropyranyl)pyridazin-3(2H)-one；4-chloro-5-hydroxy-2-(oxan-2-yl)pyridazin-3-one
• CAS: 645405-18-1
• 化学式: C₉H₁₁ClN₂O₃
• 分子量: 230.651
• InChiKey: XZBUPOMTNWZPKD-UHFFFAOYSA-N

物化性质

• 熔点：
  135-137 °C(Solv: methanol (67-56-1); hexane (110-54-3))
• 沸点：
  330.1±52.0 °C(Predicted)
• 密度：
  1.57±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  62.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-chloro-5-hydroxy-2-(tetrahydro-2H-pyran-2-yl)-3(2H)-pyridazinone 在 TEA bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 TEA 、 四丁基碘化铵 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 5.5h， 生成 4-(Methylamino)-2-(oxan-2-yl)-5-[2-[4-(trifluoromethyl)phenyl]ethynyl]pyridazin-3-one
  参考文献：
  名称：

  A Thienopyridazinone-Based Melanin-Concentrating Hormone Receptor 1 Antagonist with Potent in Vivo Anorectic Properties

  摘要：

  Melanin-concentrating hormone receptor antagonists containing thieno- and a benzopyridazinone cores were designed and tested as potential anorectic agents. These ligands showed high affinity for the receptor, potent functional activity in vitro, and good oral bioavailabilty in rats. The thiophene analogue exhibited low iv clearance, long half-life, and high brain penetration. In obese rats, the thienopyridazinone demonstrated a dose-dependent reduction in feeding and body weight with doses between 1 and 10 mg kg(-1).

  DOI：

  10.1021/jm051263c
• 作为产物：
  描述：

  4,5-二氯-2-(四氢-吡喃-2-基)-2H-吡嗪-3-酮 在 potassium hydroxide 作用下， 以 水 为溶剂， 反应 22.5h， 生成 4-chloro-5-hydroxy-2-(tetrahydro-2H-pyran-2-yl)-3(2H)-pyridazinone
  参考文献：
  名称：

  缺乏脂肪胺的黑色素浓缩激素受体1拮抗剂：新型1-（咪唑并[1,2 - a ]吡啶-6-基）吡啶-2（1 H）-一衍生物的合成与结构-活性关系

  摘要：

  为了发现具有改善的安全性的黑色素浓缩激素受体1（MCHR1）拮抗剂，我们假设，如果化合物支架的双环基序与Asp123和/或Tyr272相互作用，则迄今为止报道的大多数拮抗剂中使用的脂肪胺都可以被去除。 MCHR1。我们从化合物设计中排除了p K a <8的临界值的脂族胺，并在面向CNS的化学空间（受四个描述符（TPSA，ClogP，MW和HBD计数）限制）中探索了不含脂族胺的MCHR1拮抗剂。 。对具有高固有结合亲和力的MCHR1新型双环基序的筛选确定了咪唑并[1,2- a ]吡啶环（以化合物6a和6b表示），然后对中央脂肪族酰胺键进行环化，导致发现了一种有效的，口服可生物利用的MCHR1拮抗剂4-[（（4-氯苄基）氧基] -1-（2-环丙基-3-甲基咪唑并[1,2- a] ] pyridin-6-yl）pyridin-2（1 H）-one 10a。它在饮食诱导的肥胖大鼠中表现出低的hER

  DOI：

  10.1021/acs.jmedchem.5b01704

文献信息

• [EN] PYRIDONE AND PYRIDAZINONE DERIVATIVES AS MCH ANTAGONISTS<br/>[FR] DÉRIVÉS DE PYRIDONE ET DE PYRIDAZINONE COMME ANTAGONISTES DE LA MCH
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2009103478A1

  公开（公告）日：2009-08-27

  The present invention relates to pyridone and pyridazinone derivatives as listed in claim 1 including their salts. 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.

  本发明涉及权利要求1中所列的吡啶酮和吡啶并二嗪酮衍生物及其盐。此外，本发明还涉及含有至少一种根据本发明的化合物的药物组合物。凭借其黑色素细胞刺激素受体拮抗活性，根据本发明的药物组合物适用于治疗代谢紊乱和/或饮食失调，特别是肥胖、贪食症、厌食症、过食和糖尿病。
• [EN] 2- (3-AMINOPYRROLIDIN-1-YL) PYRIDINES AS MELANIN-CONCENTRATING HORMONE RECEPTOR AN TAGONISTS<br/>[FR] 2- (3-AMINOPYRROLIDIN-1-YL) PYRIDINES UTILISEES COMME ANTAGONISTES DU RECEPTEUR DE L'HORMONE CONCENTRANT LA MELANINE, ET COMPOSITIONS ET PROCEDES ASSOCIES
  申请人：NEUROCRINE BIOSCIENCES INC

  公开号：WO2005103039A1

  公开（公告）日：2005-11-03

  Melanin-concentrating hormone (MCH) receptor antagonists are disclosed having utility for the treatment of MCH receptor-based disorders such as obesity. The compounds of this invention have the following structure: including stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein R1, R2, R5, Het, X and Cyc are as defined herein. Also disclosed are compositions containing a compound of this invention, as well as methods relating to the use thereof.

  黑色素浓缩激素（MCH）受体拮抗剂被披露具有治疗基于MCH受体的疾病如肥胖的效用。本发明的化合物具有以下结构：包括立体异构体、前药和其药用盐，其中R1、R2、R5、Het、X和Cyc如本文所定义。还披露了含有本发明化合物的组合物，以及与其使用相关的方法。
• Novel synthesis of pyridazino[4,5-b][1,4]oxazin-3,8-diones☆
  作者：Su-Dong Cho、Sang-Yong Song、Yong-Dae Park、Jeum-Jong Kim、Woo-Hong Joo、Motoo Shiro、J.R. Falck、Dong-Soo Shin、Yong-Jin Yoon

  DOI：10.1016/j.tetlet.2003.09.216

  日期：2003.12.8

  A novel and effective synthesis of pyridazino[4,5-b][1,4]oxazin-3,8-diones via Smiles rearrangement is presented. Treatment of N-substituted 2-chloro(or hydroxy)acetamide, 2-tetrahydropyranyl-4-chloro-5-hydroxy(or chloro)pyridazin-3-one and cesium carbonate in refluxing acetonitrile was afforded the corresponding pyridazino[4,5-b][1,4]oxazin-3,8-diones in excellent yield.

  提出了一种通过Smiles重排合成新颖有效的哒嗪并[4,5- b ] [1,4]恶嗪-3,8-二酮的方法。在回流的乙腈中处理N-取代的2-氯（或羟基）乙酰胺，2-四氢吡喃基-4-氯-5-羟基（或氯）哒嗪-3-酮和碳酸铯，得到相应的哒嗪[4,5-]。b ] [1,4]恶嗪-3,8-二酮，收率高。
• NEW PYRIDONE DERIVATES WITH MCH ANTAGONISTIC ACTIVITY AND MEDICAMENTS COMPRISING THESE COMPOUNDS
  申请人：Stenkamp Dirk

  公开号：US20080255083A1

  公开（公告）日：2008-10-16

  The present invention relates to compounds of general formula I wherein the groups and radicals B, k, L, U, V, W, X, Y, Z, R 1 , R 2 , 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的化合物，其中B、k、L、U、V、W、X、Y、Z、R1、R2的基团和基团具有权利要求1中所给出的含义。此外，本发明涉及含有至少一种根据本发明的化合物的制药组合物。由于它们的MCH受体拮抗活性，本发明的制药组合物适用于治疗代谢障碍和/或进食障碍，特别是肥胖症、暴食症、厌食症、过度进食和糖尿病。
• Pyridone derivates with MCH antagonistic activity and medicaments comprising these compounds
  申请人：Boehringer Ingelheim International GmbH

  公开号：US08067590B2

  公开（公告）日：2011-11-29

  The present invention relates to compounds of general formula I wherein the groups and radicals B, k, L, U, V, W, X, Y, Z, R1, R2, 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.

  本发明涉及通式I的化合物，其中B、k、L、U、V、W、X、Y、Z、R1、R2的基团和基团具有权利要求1所给出的含义。此外，本发明涉及含有至少一种根据本发明的化合物的制药组合物。由于它们的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，特别是肥胖症、暴食症、厌食症、过度进食和糖尿病。