phenyl(7-hydroxy-5,6,7,8-tetrahydronaphtalen-1-yl) carbamate | 624729-72-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: phenyl(7-hydroxy-5,6,7,8-tetrahydronaphtalen-1-yl) carbamate
• 英文别名: (7-hydroxy-5,6,7,8-tetrahydro-naphthalen-1-yl)-carbamic acid phenyl ester；phenyl (7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)carbamate；phenyl N-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)carbamate
• CAS: 624729-72-2
• 化学式: C₁₇H₁₇NO₃
• 分子量: 283.327
• InChiKey: CKOREQQRNUUBJO-UHFFFAOYSA-N

物化性质

• 沸点：
  439.1±45.0 °C(Predicted)
• 密度：
  1.298±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  phenyl(7-hydroxy-5,6,7,8-tetrahydronaphtalen-1-yl) carbamate 在 四(三苯基膦)钯 碳酸氢钠 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 19.0h， 生成 N-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)-N'-(4'-methylbiphenyl-3-yl)urea
  参考文献：
  名称：

  [EN] TETRAHYDRO-NAPHTHALENE DERIVATIVES
  [FR] DERIVES DE TETRAHYDRO-NAPHTHALENE

  摘要：

  这项发明涉及四氢萘衍生物及其盐，可用作药物制剂的活性成分。本发明的四氢萘衍生物具有出色的VR1拮抗活性，适用于预防和治疗与VR1活性相关的疾病，特别是用于治疗尿失禁、膀胱过度活跃、急迫性尿失禁、慢性疼痛、神经病痛、术后疼痛、类风湿性关节炎疼痛、神经痛、神经病、疼痛、神经损伤、缺血、神经退行性疾病、中风、炎症性疾病、哮喘和慢性阻塞性肺疾病的治疗。

  公开号：

  WO2004052846A1
• 作为产物：
  描述：

  1-氨基-7-萘酚 在 吡啶 、 盐酸 、 platinum(IV) oxide 、 氢气 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 15.0h， 生成 phenyl(7-hydroxy-5,6,7,8-tetrahydronaphtalen-1-yl) carbamate
  参考文献：
  名称：

  Discovery of dual-acting opioid ligand and TRPV1 antagonists as novel therapeutic agents for pain

  摘要：

  In order to discover a novel type of analgesic, we investigated dual activity ligands with TRPV1 antagonism and mu-opioid receptor affinity with the goal of eliciting synergistic analgesia while avoiding the side effects associated with single targeting. Based on a combination approach, a series of 4-benzyl-4-(dimethylamino)piperidinyl analogues were designed, synthesized and evaluated for their receptor activities. Among them, compound 49 exhibited the most promising dual-acting activity toward TRPV1 and the mu-opioid receptor in vitro. In vivo, 49 displayed potent, dose-dependent antinociceptive activity in both the 1st and 2nd phases in the formalin assay. Consistent with its postulated mechanism, we confirmed that in vivo, as in vitro, compound 49 both antagonized TRPV1 and functioned as a mu-opioid agonist. This result indicates that dual-acting TRPV1 antagonist/mu-opioid ligands can be made and represent a new and promising class of analgesic. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111634

文献信息

• [EN] TETRAHYDRO-NAPHTHALENE AND UREA DERIVATIVES<br/>[FR] DERIVES DE TETRAHYDRO-NAPHTHALENE ET D'UREE
  申请人：BAYER HEALTHCARE AG

  公开号：WO2005040100A1

  公开（公告）日：2005-05-06

  This invention relates to tetrahydro-naphthalene and urea derivatives and salts thereof which are useful as active ingredients of pharmaceutical preparations. The tetrahydro-naphthalene and urea derivatives of the present invention have vanilloid receptor (VR1) antagonistic activity, and can be used for the prophylaxis and treatment of diseases associated with VR1 activity, in particular for the treatment of urological diseases or disorders, such as detrusor overactivity (overactive bladder), urinary incontinence, neurogenic detrusor oeractivity (detrusor hyperflexia), idiopathic detrusor overactivity (detrusor instability), benign prostatic hyperplasia, and lower urinary tract symptoms; chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, and inflammatory disorders such as asthma and chronic obstructive pulmonary (or airways) disease (COPD). BHC 03 2 001-Foreign-Countries - 66 - BHC 03 2 001-Foreign-Countries - 65 -

  这项发明涉及四氢萘和脲衍生物及其盐，这些物质可作为药物制剂的活性成分。本发明的四氢萘和脲衍生物具有辣椒素受体（VR1）拮抗活性，可用于预防和治疗与VR1活性相关的疾病，特别是用于治疗与VR1活性相关的泌尿系统疾病或紊乱，如膀胱过度活动（过度活跃膀胱）、尿失禁、神经源性膀胱过度活动（膀胱过度反射）、特发性膀胱过度活动（膀胱不稳定）、良性前列腺增生、下尿路症状；慢性疼痛、神经病性疼痛、术后疼痛、类风湿性关节炎疼痛、神经痛、神经病、疼痛、神经损伤、缺血、神经退行性疾病、中风，以及哮喘和慢性阻塞性肺病（COPD）等炎症性疾病。BHC 03 2 001-外国国家 - 66 - BHC 03 2 001-外国国家 - 65 -
• [EN] TETRAHYDRO-NAPHTHALENE DERIVATIVES AS VANILLOID RECEPTOR ANTAGONISTS<br/>[FR] DERIVES TETRAHYDRO-NAPHTALENE SERVANT D'ANTAGONISTES DU RECEPTEUR VANILLOIDE
  申请人：BAYER HEALTHCARE AG

  公开号：WO2004052845A1

  公开（公告）日：2004-06-24

  This invention relates to tetrahydro-naphthalene derivatives and salts thereof which is useful as an active ingredient of pharmaceutical preparations. The tetrahydro-naphthalene derivatives of the present invention have an excellent activity as VR1 antagonist and useful for the prophylaxis and treatment of diseases associated with VR1 activity, in particular for the treatment of urinary incontinence, urge urinary incontinence, overactive bladder, chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, inflammatory disorders, asthma and COPD.

  该发明涉及四氢萘衍生物及其盐，作为药物制剂的活性成分。本发明的四氢萘衍生物作为VR1拮抗剂具有出色的活性，并且适用于预防和治疗与VR1活性相关的疾病，特别是用于治疗尿失禁、急迫性尿失禁、过度活动膀胱、慢性疼痛、神经病性疼痛、术后疼痛、类风湿性关节炎疼痛、神经痛、神经病、疼痛、神经损伤、缺血、神经退行性疾病、中风、炎症性疾病、哮喘和慢性阻塞性肺疾病的治疗。
• [EN] HYDROXY-TETRAHYDRO-NAPHTHALENYLUREA DERIVATIVES<br/>[FR] DERIVES D'HYDROXY-TETRAHYDRO-NAPHTALENYLUREE
  申请人：BAYER HEALTHCARE AG

  公开号：WO2004072020A1

  公开（公告）日：2004-08-26

  This invention relates to hydroxy-tetrahydro-naphthalenylurea derivatives and salts thereof which are useful as active ingredients of pharmaceutical preparations. The hydroxy-tetrahydro-naphthalenylurea derivatives of the present invention have an excellent activity as VRl antagonist and are useful for the prophylaxis and treatment of diseases associated with VRl activity, in particular for the treatment of urinary incontinence, urge urinary incontinence, overactive bladder, chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, inflammatory disorders, asthma and COPD.

  这项发明涉及羟基-四氢-萘尿素衍生物及其盐，可作为药物配方的有效成分。本发明的羟基-四氢-萘尿素衍生物具有优异的VRl拮抗活性，适用于预防和治疗与VRl活性相关的疾病，特别是用于治疗尿失禁、急迫性尿失禁、过度活跃膀胱、慢性疼痛、神经痛、术后疼痛、类风湿性关节炎疼痛、神经痛、神经病、疼痛、神经损伤、缺血、神经退行性疾病、中风、炎症性疾病、哮喘和COPD的治疗。
• [EN] HYDROXY TETRAHYDRO-NAPHTHALENYLUREA DERIVATIVES<br/>[FR] DERIVES HYDROXY-TETRAHYDRO-NAPHTALENYLUREE
  申请人：BAYER AG

  公开号：WO2003095420A1

  公开（公告）日：2003-11-20

  This invention relates to tetrahydro-naphthalene derivatives and salts thereof which is useful as an active ingredient of pharmaceutical preparations. The tetrahydro-naphthalene derivatives of the present invention have an excellent activity as VR1 antagonist and useful for the prophylaxis and treatment of diseases associated with VR1 activity, in particular for the treatment of urge urinary incontinence, overactive bladder, chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, incontinence, inflammatory disorders such as asthma and COPD.

  这项发明涉及四氢萘衍生物及其盐，可作为药物配方的有效成分。本发明的四氢萘衍生物作为VR1拮抗剂具有出色的活性，可用于预防和治疗与VR1活性相关的疾病，特别是用于治疗急迫性尿失禁、过度活跃膀胱、慢性疼痛、神经痛、术后疼痛、类风湿关节炎疼痛、神经痛、神经病、疼痛、神经损伤、缺血、神经退行性疾病、中风、失禁、哮喘和慢性阻塞性肺病等炎症性疾病的治疗。
• Vanilloid receptor (VR) inhibitors for treatment of Human Immunodeficiency Virus (HIV)-mediated pain states
  申请人：Bayer HealthCare AG

  公开号：EP1493438A1

  公开（公告）日：2005-01-05

  The invention relates to the application of Vanilloid receptor (VR) 1 inhibitors for drug development and for the treatment of HIV-mediated neuropathies and neuropathic pain states. Further, the inventor identified a novel signaling cascade connecting the HIV receptor CXCR4 to VR1. Thus, the invention provides molecular evidence that HIV-mediated pain states - initiated upon binding of the virus to CXCR4 - can be inhibited by VR1 antagonists blocking the final execution of the CXCR4NR1 pathway. In addition, the invention demonstrates that present standard therapies for HIV-mediated pain (which do not include VR1 inhibitors) can not interfere with the CXCR4/VR1 pathway thus explaining inefficient patient treatment in the clinics.

  本发明涉及Vanilloid受体（VR）1抑制剂在药物开发和治疗HIV介导的神经病变和神经病性疼痛状态中的应用。此外，发明人还发现了一种新的信号级联，将HIV受体CXCR4连接到VR1。因此，本发明提供了分子证据，证明HIV介导的疼痛状态 - 在病毒与CXCR4结合后启动 - 可以通过VR1拮抗剂阻断CXCR4NR1途径的最终执行来抑制。此外，本发明证明目前用于治疗HIV介导的疼痛的标准疗法（不包括VR1抑制剂）无法干扰CXCR4 / VR1途径，从而解释了临床上治疗效果不佳的原因。