N-(4-methoxyphenyl)retinamide

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: N-(4-methoxyphenyl)retinamide
• 英文别名: 4-Methoxyfenretinide；N-(4-Methoxyphenyl)-all-trans-retinamide；(2E,4E,6E,8E)-N-(4-methoxyphenyl)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenamide
• 化学式: C₂₇H₃₅NO₂
• 分子量: 405.58
• InChiKey: DBQHWMPFMCOGIW-ABRSJASVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.6
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  维A酸 在 吡啶 、 六氯丙酮 、 triphenylphosphine-resin 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 N-(4-methoxyphenyl)retinamide
  参考文献：
  名称：

  Solid phase-assisted synthesis and screening of a small library of N-(4-hydroxyphenyl)retinamide (4-HPR) analogs

  摘要：

  Using solid phase-assisted synthesis and purification, a 49 member library of analogs of the main mammary tumor chemopreventive retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) has been prepared. After prescreening for growth inhibitory activity in human mammary tumor cells (MCF-7) in culture, most of those analogs which showed activity (12 of them) were assayed for apoptosis-inducing activity in the MCF-7 cells. At least 3 of the analogs (13, 24, and 28) showed activity approaching that of 4-HPR. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.10.050

文献信息

• Characterization of the metabolism of fenretinide by human liver microsomes, cytochrome P450 enzymes and UDP‐glucuronosyltransferases
  作者：NA Illingworth、AV Boddy、AK Daly、GJ Veal

  DOI：10.1111/j.1476-5381.2010.01104.x

  日期：2011.2

  in oncology. Metabolism of 4-HPR is of particular interest due to production of the active metabolite 4'-oxo 4-HPR and the clinical challenge of obtaining consistent 4-HPR plasma concentrations in patients. Here, we assessed the enzymes involved in various 4-HPR metabolic pathways. EXPERIMENTAL APPROACH Enzymes involved in 4-HPR metabolism were characterized using human liver microsomes (HLM), supersomes

  背景和目的 芬维A胺 (4-HPR) 是一种视黄酸类似物，目前用于肿瘤学的临床试验。由于活性代谢物 4'-氧代 4-HPR 的产生以及在患者中获得一致的 4-HPR 血浆浓度的临床挑战，4-HPR 的代谢特别令人感兴趣。在这里，我们评估了参与各种 4-HPR 代谢途径的酶。实验方法 使用人肝微粒体 (HLM)、过度表达单个人细胞色素 P450 (CYP)、尿苷 5'-二磷酸-葡萄糖醛酸转移酶 (UGT) 和 CYP2C8 变体的超体来表征参与 4-HPR 代谢的酶，这些酶在大肠杆菌中表达。通过高效液相色谱法和液相色谱法/质谱法分析样品并确定代谢物形成的动力学参数。还用CYPs抑制剂和甲基化酶进行孵育。主要结果 发现 HLM 主要产生 4'-氧代 4-HPR，以及由个别 CYP 产生的额外极性代谢物 4'-羟基 4-HPR (4'-OH 4-HPR)。发现 CYP 2C8、3A4 和 3A5
• [EN] 4-OXO-FENRETINIDE, ADMINISTERED ALONE AND IN COMBINATION WITH FENRETINIDE, AS PREVENTIVE AND THERAPEUTIC AGENT FOR CANCER<br/>[FR] 4-OXO-FENRETINIDE, ADMINISTRE SEUL ET EN COMBINAISON AVEC LE FENRETINIDE, COMME AGENT PREVENTIF ET THERAPEUTIQUE CONTRE LE CANCER
  申请人：IST NAZ STUD CURA DEI TUMORI

  公开号：WO2005092314A1

  公开（公告）日：2005-10-06

  A drug based on a metabolite of fenretinide, or N-(4­hydroxyphenyl)retinamide (4-HPR), specifically 4-oxo-N-(4­hydroxyphenyl)retinamide (4-oxo-4-HPR), is used in the treatment of different kinds of tumors, in particular in the treatment of ovarian carcinoma, breast tumor and neuroblastoma. The drug is more potent than fenretinide alone, and enhances the effects of fenretinide when administered together with fenretinide.

  一种基于芬烯酸代谢物或N-(4-羟基苯基)维甲酰胺(4-HPR)的药物，特别是4-氧代-N-(4-羟基苯基)维甲酰胺(4-oxo-4-HPR)，用于治疗不同类型的肿瘤，特别是卵巢癌、乳腺肿瘤和神经母细胞瘤。该药物比单独使用芬烯酸更具有强效，当与芬烯酸一起使用时，可以增强芬烯酸的效果。
• FENRETINIDE DERIVATIVES AND USES THEREOF AS THERAPEUTIC, DIAGNOSTIC AND IMAGING AGENTS
  申请人：Kalpana Ganjam V.

  公开号：US20110091383A1

  公开（公告）日：2011-04-21

  Synthetic peptidomimetic derivatives and phenyl group derivatives of Fenretinide (4-HPR) are disclosed, as are their uses as therapeutic, diagnostic and imaging agents for cancer and other diseases.

  本发明涉及Fenretinide（4-HPR）的合成肽类模拟衍生物和苯基衍生物，以及它们作为治疗、诊断和肿瘤及其他疾病成像剂的用途。
• Retinol binding protein and transthyretin modulators for treating diabetes
  申请人：Sirion Therapeutics, Inc.

  公开号：EP1930046A1

  公开（公告）日：2008-06-11

  Described herein are methods and compositions for treating certain retionol-related diseases and conditions by modulation of transthyretin (TTR) and retinol binding protein (RBP) availability in the subject. For example, the methods and compositions provide for therapeutic agents for the treatment and/or prevention of age-related macular degeneration and/or dystrophies, metabolic disorders, idiopathic intracranial hypertension, hyperostosis, and protein misfolding and aggregation diseases. The compositions disclosed may be used as single agent therapy or in combination with other agents or therapies. In addition, described herein are methods and assays for selecting appropriate agents that can modulate the TTR and RBP availability in a subject.

  本文描述了通过调节受试者体内转甲状腺素（TTR）和视黄醇结合蛋白（RBP）的可用性来治疗某些视黄醇相关疾病和病症的方法和组合物。例如，这些方法和组合物提供了治疗和/或预防老年性黄斑变性和/或营养不良、代谢紊乱、特发性颅内高压、骨质疏松症以及蛋白质错误折叠和聚集疾病的治疗剂。所公开的组合物可用作单剂疗法，也可与其他制剂或疗法联合使用。此外，本文还描述了用于选择可调节受试者体内 TTR 和 RBP 可用性的适当制剂的方法和检测方法。
• Retinyl derivatives for treating ophtalmic conditions
  申请人：Sirion Therapeutics, Inc.

  公开号：EP2025336A1

  公开（公告）日：2009-02-18

  Compounds that cause reversible night blindness may be used to treat ophthalmic conditions associated with the overproduction of waste products that accumulate during the course of the visual cycle. We describe methods and compositions using such compounds and their derivatives to treat, for example, the macular degenerations and dystrophies or to alleviate symptoms associated with such ophthalmic conditions. Such compounds and their derivatives may be used as single agent therapy or in combination with other agents or therapies.

  导致可逆性夜盲症的化合物可用于治疗与视觉周期过程中积累的废物过度产生有关的眼科疾病。我们描述了使用此类化合物及其衍生物治疗黄斑变性和营养不良等眼科疾病或缓解与此类眼科疾病相关的症状的方法和组合物。此类化合物及其衍生物可用作单药治疗，也可与其他药物或疗法联合使用。