7-(2-Chlorophenyl)-6-(4-chlorophenyl)-2-isopropylpyrido[2,3-d]pyrimidin-4-ol | 1067648-81-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 7-(2-Chlorophenyl)-6-(4-chlorophenyl)-2-isopropylpyrido[2,3-d]pyrimidin-4-ol
• 英文别名: 7-(2-chlorophenyl)-6-(4-chlorophenyl)-2-propan-2-yl-3H-pyrido[2,3-d]pyrimidin-4-one
• CAS: 1067648-81-0
• 化学式: C₂₂H₁₇Cl₂N₃O
• 分子量: 410.302
• InChiKey: KPEQDIMLMKNWLV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7-(2-Chlorophenyl)-6-(4-chlorophenyl)-2-isopropylpyrido[2,3-d]pyrimidin-4-ol 、 3-(氯甲基)-1,2,4-氧二唑 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以6%的产率得到7-(2-chlorophenyl)-6-(4-chlorophenyl)-2-isopropyl-4-(1,2,4-oxadiazol-3-ylmethoxy)pyrido[2,3-d]pyrimidine
  参考文献：
  名称：

  Pyridopyrimidine based cannabinoid-1 receptor inverse agonists: Synthesis and biological evaluation

  摘要：

  The synthesis, SAR and binding affinities are described for cannabinoid-1 receptor (CB1R) specific inverse agonists based on pyridopyrimidine and heterotricyclic scaffolds. Food intake and pharmacokinetic evaluation of several of these compounds indicate that they are effective orally active modulators of CB1R. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.005
• 作为产物：
  描述：

  7-(2-chlorophenyl)-6-(4-chlorophenyl)-2-isopropylpyrido[2,3-d]pyrimidin-4-amine 在 甲烷磺酸 、 水 作用下， 以95%的产率得到7-(2-Chlorophenyl)-6-(4-chlorophenyl)-2-isopropylpyrido[2,3-d]pyrimidin-4-ol
  参考文献：
  名称：

  Pyridopyrimidine based cannabinoid-1 receptor inverse agonists: Synthesis and biological evaluation

  摘要：

  The synthesis, SAR and binding affinities are described for cannabinoid-1 receptor (CB1R) specific inverse agonists based on pyridopyrimidine and heterotricyclic scaffolds. Food intake and pharmacokinetic evaluation of several of these compounds indicate that they are effective orally active modulators of CB1R. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.005

文献信息

• SUBSTITUTED PYRIDO[2,3-D]PYRIMIDINE DERIVATIVES AS CANNABINOID-1 RECEPTOR MODULATORS
  申请人：Debenham John S.

  公开号：US20100063032A1

  公开（公告）日：2010-03-11

  Novel compounds of the structural formula (I) are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present invention are useful as centrally acting drugs in the treatment of psychosis, memory deficits, cognitive disorders, Alzheimer s disease, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson s disease, movement disorders, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, the treatment of obesity or eating disorders, as well as the treatment of asthma, constipation, chronic intestinal pseudo-obstruction, cirrhosis of the liver, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and the promotion of wakefulness.

  结构式（I）的新型化合物是大麻素-1（CB1）受体的拮抗剂和/或反向激动剂，并且适用于治疗、预防和抑制由CB1受体介导的疾病。本发明的化合物可用作中枢作用药物，用于治疗精神病、记忆障碍、认知障碍、阿尔茨海默病、偏头痛、神经病、神经炎性疾病（包括多发性硬化症和吉兰-巴雷综合症）及病毒性脑炎、脑血管意外和头部创伤的炎症后遗症、焦虑症、压力、癫痫、帕金森病、运动障碍和精神分裂症。这些化合物还可用于治疗物质滥用障碍、肥胖或进食障碍的治疗，以及哮喘、便秘、慢性肠假性梗阻、肝硬化、非酒精性脂肪性肝病（NAFLD）、非酒精性脂肪性肝炎（NASH）和促进清醒。
• [EN] SUBSTITUTED PYRIDO[2,3-D]PYRIMIDINE DERIVATIVES AS CANNABINOID-1 RECEPTOR MODULATORS<br/>[FR] DÉRIVÉS DE PYRIDO[2,3-D]PYRIMIDINE SUBSTITUÉS EN TANT QUE MODULATEURS DE RÉCEPTEUR DE CANNABINOÏDE-1
  申请人：MERCK & CO INC

  公开号：WO2008121257A1

  公开（公告）日：2008-10-09

  [EN] Novel compounds of the structural formula (I) are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present invention are useful as centrally acting drugs in the treatment of psychosis, memory deficits, cognitive disorders, Alzheimer s disease, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson s disease, movement disorders, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, the treatment of obesity or eating disorders, as well as the treatment of asthma, constipation, chronic intestinal pseudo-obstruction, cirrhosis of the liver, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and the promotion of wakefulness.
  [FR] L'invention concerne des nouveaux composés de la formule structurelle (I) qui sont des antagonistes et/ou des agonistes inverses du récepteur de cannabinoïde-1 (CB1) et sont utiles pour le traitement, la prévention et la suppression de maladies favorisées par le récepteur de CB1. Les composés de la présente invention sont utiles comme médicament à action centrale dans le traitement de la psychose, de déficiences de la mémoire, de troubles cognitifs, de la maladie d'Alzheimer, de la migraine, de la neuropathie, de troubles neuro-inflammatoires comprenant une sclérose multiple et un syndrome de Guillain-Barre ainsi que de le traitement de séquelles inflammatoires d'encéphalite virale, d'accident vasculaire cérébral et de traumatismes crâniens, de troubles de l'anxiété, du stress, de l'épilepsie, de la maladie de Parkinson, de troubles moteurs et de la schizophrénie. Les composés sont également utiles pour le traitement de trouble d'abus de substance, le traitement de l'obésité ou de troubles de l'alimentation, de même que le traitement de l'asthme, de la constipation, de la pseudo-obstruction intestinale chronique, de la cirrhose du foie, d'une maladie adipeuse hépatique non alcoolique (NAFLD), d'une stéatohépatite non alcoolique (NAFH) et la stimulation de la veille.
• Pyridopyrimidine based cannabinoid-1 receptor inverse agonists: Synthesis and biological evaluation
  作者：John S. Debenham、Christina B. Madsen-Duggan、Junying Wang、Xinchun Tong、Julie Lao、Tung M. Fong、Marie-Therese Schaeffer、Jing Chen Xiao、Cathy C.R.-R. Huang、Chun-Pyn Shen、D. Sloan Stribling、Lauren P. Shearman、Alison M. Strack、D. Euan MacIntyre、Jeffrey J. Hale、Thomas F. Walsh

  DOI：10.1016/j.bmcl.2009.03.005

  日期：2009.5

  The synthesis, SAR and binding affinities are described for cannabinoid-1 receptor (CB1R) specific inverse agonists based on pyridopyrimidine and heterotricyclic scaffolds. Food intake and pharmacokinetic evaluation of several of these compounds indicate that they are effective orally active modulators of CB1R. (C) 2009 Elsevier Ltd. All rights reserved.