4-(3-Chloro-2-pyridinyl)-N-[4-(isopropyl)phenyl]-1-piperazinecarboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(3-Chloro-2-pyridinyl)-N-[4-(isopropyl)phenyl]-1-piperazinecarboxamide
• 英文别名: 4-(3-Chloro-pyridin-2-yl)-piperazine-1-carboxylic acid (4-isopropyl-phenyl)-amide；4-(3-chloropyridin-2-yl)-N-(4-propan-2-ylphenyl)piperazine-1-carboxamide
• 化学式: C₁₉H₂₃ClN₄O
• 分子量: 358.871
• InChiKey: AAYTUXCYPCIBAM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  48.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2,3-二氯吡啶 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 8.0h， 生成 4-(3-Chloro-2-pyridinyl)-N-[4-(isopropyl)phenyl]-1-piperazinecarboxamide
  参考文献：
  名称：

  4-(2-Pyridyl)piperazine-1-carboxamides: potent vanilloid receptor 1 antagonists

  摘要：

  A series of 4-(2-pyridyl)piperazine-1-carboxamide analogues based on the lead compound 1 was synthesized and evaluated for VR1 antagonist activity in capsaicin-induced (CAP) and pH (5.5)-induced (pH) FLIPR assays in a rat VR1-expressing HEK293 cell line. Potent VR1 antagonists were identified through SAR studies. From these studies, 18 was found to be very potent in the in vitro assay [IC50 = 4.8 nM (pH) and 35 nM (CAP)] and orally available in rat (F% = 15.1). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00759-5

文献信息

• Capsaicin receptor ligands
  申请人：——

  公开号：US20020132853A1

  公开（公告）日：2002-09-19

  Disclosed are diaryl piperazines and related compounds. These compounds are selective modulators of capsaicin receptors, including human capsaicin receptors, that are, therefore, useful in the treatment of a chronic and acute pain conditions, itch and urinary incontinence. Methods of treatment of such disorders and well as packaged pharmaceutical compositions are also provided. Compounds of the invention are also useful as probes for the localization of capsaicin receptors and as standards in assays for capsaicin receptor binding and capsaicin receptor mediated cation conductance. Methods of using the compounds in receptor localization studies are given.

  揭示了二芳基哌嗪和相关化合物。这些化合物是辣椒素受体的选择性调节剂，包括人类辣椒素受体，在慢性和急性疼痛症状、瘙痒和尿失禁的治疗中非常有用。还提供了治疗这些疾病的方法以及包装的药物组合物。该发明的化合物还可用作辣椒素受体的定位探针，并作为辣椒素受体结合和辣椒素受体介导的阳离子传导的测定中的标准。提供了使用这些化合物进行受体定位研究的方法。
• Combination therapy for the treatment of pain
  申请人：Neurogen Corporation

  公开号：US20040142958A1

  公开（公告）日：2004-07-22

  Compositions and methods are provided for the treatment of pain. Compositions and methods are further provided for inhibiting the development of tolerance to addictive therapeutic agents (especially narcotic analgesics) in patients treated with such agents; for minimizing adverse effects (e.g., dependence) resulting from treatment with such addictive agents; and for enhancing pain relief resulting from narcotic analgesic administration. The compositions generally comprise a nontoxic VR1 antagonist, optionally in combination with an addictive therapeutic agent. Patients may be treated with a VR1 antagonist before, during or after administration of the addictive therapeutic agent to prevent, decrease the severity of, delay or treat tolerance and/or other adverse effects of the addictive agent in the patient.

  提供了用于治疗疼痛的组合物和方法。还提供了用于抑制接受此类药物（特别是麻醉镇痛剂）治疗的患者对成瘾性治疗剂量的耐受性发展，减少因使用此类成瘾性药物治疗而导致的不良反应（例如成瘾），以及增强因使用麻醉镇痛剂而产生的疼痛缓解的组合物和方法。这些组合物通常包括无毒的VR1拮抗剂，可选地与成瘾性治疗剂量结合使用。患者可以在接受成瘾性治疗剂量之前、期间或之后接受VR1拮抗剂治疗，以预防、减轻、延迟或治疗患者对成瘾性药物的耐受和/或其他不良反应。
• Use of capsaicin receptor antagonists to treat symptoms of tear gas exposure
  申请人：Bakthavatchalam Rajagopal

  公开号：US20090082362A1

  公开（公告）日：2009-03-26

  Disclosed are diaryl piperazines and related compounds. These compounds are selective modulators of capsaicin receptors, including human capsaicin receptors, that are, therefore, useful in the treatment of a chronic and acute pain conditions, itch and urinary incontinence. Methods of treatment of such disorders and well as packaged pharmaceutical compositions are also provided. Compounds of the invention are also useful as probes for the localization of capsaicin receptors and as standards in assays for capsaicin receptor binding and capsaicin receptor mediated cation conductance. Methods of using the compounds in receptor localization studies are given.

  本发明涉及二芳基哌嗪和相关化合物。这些化合物是辣椒素受体的选择性调节剂，包括人类辣椒素受体，因此在治疗慢性和急性疼痛、瘙痒和尿失禁等疾病方面非常有用。本发明还提供了治疗这些疾病的方法以及药物组合物的包装。本发明的化合物还可用作辣椒素受体定位的探针和辣椒素受体结合和辣椒素受体介导的阳离子传导的测定标准。给出了使用这些化合物进行受体定位研究的方法。
• 2-Piperazine-pyridines useful for treating pain
  申请人：EURO-CELTIQUE S.A.

  公开号：EP2033951A2

  公开（公告）日：2009-03-11

  A compound of formula (I) (wherein X is O or S and R1-R5 are disclosed herein) or a pharmaceutically acceptable salt thereof (each being a "Piperazine Compound"), pharmaceutical compositions comprising a Piperazine Compound and methods for treating or preventing pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, amyotrophic lateral sclerosis, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression in an animal comprising administering to an animal in need thereof an effective amount of a Piperazine Compound are disclosed.

  式（I）化合物（其中 X 为 O 或 S，R1-R5 在本文中公开）或其药学上可接受的盐（各为 "哌嗪化合物"）、包含哌嗪化合物的药物组合物以及用于治疗或预防疼痛、UI、溃疡、IBD、IBS、成瘾性疾病、帕金森病、帕金森氏症、焦虑症、癫痫、中风、瘙痒症、精神病、认知障碍、记忆缺失、脑功能受限、亨廷顿舞蹈症、肌萎缩侧索硬化症、痴呆症、视网膜病变、嗜铬细胞瘤、本发明公开了用于治疗或预防动物的疼痛、UI、溃疡、肠道疾病、肠易激综合征、成瘾性疾病、帕金森病、帕金森氏症、焦虑症、癫痫、中风、瘙痒症、精神病、认知障碍、记忆缺陷、脑功能受限、亨廷顿舞蹈症、肌萎缩侧索硬化症、痴呆症、视网膜病变、肌肉痉挛、偏头痛、呕吐、运动障碍或抑郁症的方法，包括向有需要的动物施用有效量的哌嗪化合物。
• CAPSAICIN RECEPTOR LIGANDS
  申请人：NEUROGEN CORPORATION

  公开号：EP1301484A2

  公开（公告）日：2003-04-16