cyclohexyl[4-(naphthalene-1-sulfonyl)piperazin-1-yl]methanone

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: cyclohexyl[4-(naphthalene-1-sulfonyl)piperazin-1-yl]methanone
• 英文别名: 1-(cyclohexylcarbonyl)-4-(1-naphthylsulfonyl)piperazine；4-(cyclohexyl-carbonyl)-1-(1-naphthylsulfonyl)piperazine；Cyclohexyl(4-(naphthalen-1-ylsulfonyl)piperazin-1-yl)methanone；cyclohexyl-(4-naphthalen-1-ylsulfonylpiperazin-1-yl)methanone
• 化学式: C₂₁H₂₆N₂O₃S
• 分子量: 386.515
• InChiKey: YCYPTKGWJASRLD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  66.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(naphthalen-1-ylsulfonyl)piperazine 、 环己甲酸 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯氟甲烷 为溶剂， 反应 2.0h， 以66%的产率得到cyclohexyl[4-(naphthalene-1-sulfonyl)piperazin-1-yl]methanone
  参考文献：
  名称：

  1-Sulfonyl-4-acylpiperazines as Selective Cannabinoid-1 Receptor (CB1R) Inverse Agonists for the Treatment of Obesity

  摘要：

  A novel series of 1-sulfonyl-4-acylpiperazines as selective cannabinoid-1 receptor (CB1R) inverse agonists was discovered through high throughput screening (HTS) and medicinal chemistry lead optimization. Potency and in vivo properties were systematically optimized to afford orally bioavailable, highly efficacious, and selective CB1R inverse agonists that caused food intake suppression and body weight reduction in diet-induced obese rats and dogs. It was found that the receptor binding assay predicted in vivo efficacy better than functional antagonist/inverse agonist activities. This observation expedited the structure-activity relationship (SAR) analysis and may have implications beyond the series Of Compounds presented herein.

  DOI：

  10.1021/jm900063x

文献信息

• Synthesis and Structure–Activity relationship of 1-(5-isoquinolinesulfonyl)piperazine analogues as inhibitors of Mycobacterium tuberculosis IMPDH
  作者：Vinayak Singh、Angela Pacitto、Stefano Donini、Davide M. Ferraris、Sándor Boros、Eszter Illyés、Bálint Szokol、Menico Rizzi、Tom L. Blundell、David B. Ascher、Janos Pato、Valerie Mizrahi

  DOI：10.1016/j.ejmech.2019.04.027

  日期：2019.7

  Tuberculosis (TB) is a major infectious disease associated increasingly with drug resistance. Thus, new anti-tubercular agents with novel mechanisms of action are urgently required for the treatment of drug-resistant TB. In prior work, we identified compound 1 (cyclohexyl(4-(isoquinolin-5-ylsulfonyl)piperazin-1-yl)methanone) and showed that its anti-tubercular activity is attributable to inhibition

  结核病（TB）是一种越来越多的与耐药性相关的主要传染病。因此，迫切需要具有新颖作用机制的新抗结核药来治疗耐药性TB。在先前的工作中，我们鉴定了化合物1（环己基（4-（异喹啉-5-基磺酰基）哌嗪-1-基）甲酮），并显示其抗结核活性可归因于肌苷5'-单磷酸脱氢酶（IMPDH）的抑制作用。 ）在结核分枝杆菌中。在本研究中，我们通过在生化和全细胞分析中合成和评估类似物对结核分枝杆菌IMPDH的抑制活性，探索了化合物1周围的构效关系。进行X射线晶体学分析以阐明所选类似物与IMPDH的结合方式。我们确定了环己基的重要性，
• SULFONYLATED PIPERAZINES AS CANNABINOID-1 RECEPTOR MODULATORS
  申请人：Fletcher Joan M.

  公开号：US20090247499A1

  公开（公告）日：2009-10-01

  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 sequalae 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，可用于治疗、预防和抑制由CB1受体介导的疾病。本发明的化合物可作为中枢作用药物治疗精神病、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格林-巴利综合征）以及病毒性脑炎、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、肥胖症或进食障碍、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）以及促进清醒。
• [EN] SULFONYLATED PIPERAZINES AS CANNABINOID-1 RECEPTOR MODULATORS<br/>[FR] PIPÉRAZINES SULFONYLÉES EN TANT QUE MODULATEURS DU RÉCEPTEUR DE CANNABINOÏDE-1
  申请人：MERCK & CO INC

  公开号：WO2008024284A2

  公开（公告）日：2008-02-28

  [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 de nouveaux composés selon la formule structurelle (I), qui sont des antagonistes et/ou des agonistes inverses du récepteur de cannabinoïde 1 (CB1) et sont utiles dans le traitement, la prévention et la suppression de maladies induites par le récepteur de CB1. Les composés selon la présente invention sont utiles en tant que médicaments à action centrale dans le traitement des psychoses, des défauts de mémoire, des troubles cognitifs, de la maladie d'Alzheimer, de la migraine, des neuropathies, des troubles neuro-inflammatoires tels que la sclérose en plaques et le syndrome de Guillain-Barré et les séquelles inflammatoires des encéphalites virales, les accidents cérébrovasculaires et les traumatismes crâniens, les trouble anxieux, le stress, l'épilepsie, la maladie de Parkinson, les dyskinésies et la schizophrénie. Ces composés sont également utiles dans le traitement des troubles de pharmacodépendance, dans le traitement de l'obésité ou des troubles de l'alimentation, ainsi que dans le traitement de l'asthme, de la constipation, de la pseudo-obstruction intestinale chronique et de la cirrhose du foie, de la maladie adipeuse hépatique non alcoolique (NAFLD), de la stéatohépatite non alcoolique (NASH), et pour favoriser la veille.