(2E)-3-phenyl-N-(4-phenylbutyl)prop-2-enamide

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (2E)-3-phenyl-N-(4-phenylbutyl)prop-2-enamide
• 英文别名: (E)-3-phenyl-N-(4-phenylbutyl)prop-2-enamide
• 化学式: C₁₉H₂₁NO
• 分子量: 279.382
• InChiKey: POGCSVZYJQGNCG-CCEZHUSRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  肉桂酸 、 苯基-4-丁胺 在 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以36%的产率得到(2E)-3-phenyl-N-(4-phenylbutyl)prop-2-enamide
  参考文献：
  名称：

  Structure−Activity Relationship of N-(Phenylalkyl)cinnamides as Novel NR2B Subtype-Selective NMDA Receptor Antagonists

  摘要：

  A novel series of N-(phenylalkyl)cinnamides related to N-(4-phenylbutyl)-3,4-dihydroxy-beta-cyanocinnamide (6, an EGFR-K inhibitor with high antiproliferative activity) was synthesized and tested for antagonism at N-methyl-D-aspartate (NMDA) receptor subtypes. Potency and subunit selectivity were assayed by electrical recordings in Xenopus oocytes expressing three binary combinations of cloned rat NMDA receptor subunits: NR1A expressed in combination with either NR2A, NR2B, or NR2C. The N-(phenylalkyl)cinnamides are selective antagonists of NR1A/2B receptors. Assayed under steady-state conditions, N-(4-phenylbutyl)-4-hydroxycinnamide (16) has an IC50 value of 77 nM and >1000-fold selectivity with respect to NR1A/2A and NR1A/2C receptors. Potency at alpha(1) adrenergic receptors is low for the four cinnamides tested. Inhibition of NR1A/2B receptors does not correlate with EGFR and ErbB2/neu tyrosine kinase inhibitor activity. The N-(phenylalkyl)cinnamide series we describe provides a novel and structurally diverse framework for designing new NR2B-selective NMDA antagonists as potential CNS therapeutics.

  DOI：

  10.1021/jm990199u

文献信息

• [EN] SUBTYPE-SELECTIVE NMDA RECEPTOR LIGANDS AND THE USE THEREOF<br/>[FR] LIGANDS DU RECEPTEUR N-METHYL-D-ASPARTATE SELECTIFS DE SOUS-TYPE
  申请人：STATE OF OREGON, acting by and through THE OREGON STATE BOARD OF HIGHER EDUCATION, acting for and on behalf of THE OREGON HEALTH SCIENCES UNIVERSITYA ND THE UNIVERSITY OF OREGON, EUGENE OREGON

  公开号：WO1997023202A1

  公开（公告）日：1997-07-03

  (EN) The invention relates to subtype-selective NMDA receptor ligands and the use thereof for treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia and surgery, as well as treating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's diseae, Parkinson's disease and Down's syndrome, treating or preventing the adverse consequences of the overstimulation of the excitatory amino acids, treating anxiety, psychosis, convulsions, chronic pain, glaucoma, CMV retinitis, urinary incontinence and inducing anesthesia, as well as for enhancing cognition, treating or preventing opiate tolerance, treating or preventing aminoglycoside antibiotic induced hearing loss, and treating opiate withdrawal.(FR) Cette invention a trait à des ligands du récepteur N-méthyl-D-aspartate (NMDA) sélectifs de sous-type et à leur utilisation dans le traitement ou la prévention de la dépopulation neuronale associée à un ictus, une ischémie, une lésion du système nerveux central, une hypoglycémie et à un acte chirurgical, ainsi que dans le traitement de maladies neurodégénérescentes, au nombre desquelles la maladie d'Alzheimer, la sclérose latérale amyotrophique, les maladies d'Huntington et de Parkinson ainsi que le syndrome de Down. Ces ligands sont également utilisés dans le traitement et la prévention des conséquences préjudiciables d'une stimulation excessive d'acides aminés excitateurs, le traitement de l'anxiété, de psychoses, de convulsions, de douleurs chroniques, du glaucome, de la rétinite à cytomégalovirus, de l'incontinence urinaire et pour le déclenchement de l'anesthésie ainsi que comme tonique cérébro-actif. Ces ligands sont, en outre, utilisés dans le traitement et la prévention de l'accoutumance opiacée et le traitement du sevrage des dépendances aux opiacés ainsi que pour le traitement et la prévention du déficit auditif provoqué par des aminoglycosides.

  本发明涉及亚型选择性NMDA受体配体及其在治疗或预防与中风、缺血、中枢神经系统创伤、低血糖和手术相关的神经元丢失，以及治疗包括阿尔茨海默病、肌萎缩侧索硬化症、亨廷顿病、帕金森病和唐氏综合症在内的神经退行性疾病，治疗或预防兴奋性氨基酸过度刺激的不良后果，治疗焦虑、精神病、癫痫、慢性疼痛、青光眼、CMV视网膜炎、尿失禁和诱导麻醉，以及增强认知能力，治疗或预防阿片类药物耐受性，治疗或预防氨基糖苷类抗生素引起的听力损失，和治疗阿片类药物戒断症状的用途。
• Solid-phase synthesis of an N -(phenylalkyl)cinnamide library via Horner–Wadsworth–Emmons reaction
  作者：Csaba Wéber、Attila Bielik、Györgyi I. Szendrei、György M. Keserû、István Greiner

  DOI：10.1016/j.bmcl.2003.12.038

  日期：2004.3

  A readily automated solid-phase approach to the synthesis of diverse N-(phenylalkyl)cinnamides, analogues of the NR2B antagonist 2, is described. The procedure utilizes polymer supported N-(phenylalkyl)amines, (diethylphosphono)acetic acid and a wide range of commercially available hydroxybenzaldehydes. The key step, a Horner-Wadsworth-Emmons reaction is achieved under mild conditions and was found to be general for a large number of benzaldehydes. A 225-member focused library was synthesized using a Tecan Combitec synthesizer. (C) 2003 Elsevier Ltd. All rights reserved.
• [EN] COMPOUND HAVING CARDIOTONIC ACTIVITY AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING HEART FAILURE, CONTAINING SAME<br/>[FR] COMPOSÉ DOTÉ D'UNE ACTION CARDIOTONIQUE ET COMPOSITION PHARMACEUTIQUE PERMETTANT DE PRÉVENIR OU DE TRAITER L'INSUFFISANCE CARDIAQUE ET CONTENANT LEDIT COMPOSÉ<br/>[KO] 강심 활성을 갖는 화합물 및 이를 함유하는 심부전 예방 또는 치료용 약학적 조성물
  申请人：IAC IN NAT UNIV CHUNGNAM

  公开号：WO2015142001A2

  公开（公告）日：2015-09-24

  본 발명은 강심 활성을 지니는 화합물 및 이를 함유하는 약학적 조성물을 개시하며, 본 발명에 따른 화합물을 포함하는 조성물은 심부전의 예방 및 치료에 유용하다.
• Structure−Activity Relationship of <i>N</i>-(Phenylalkyl)cinnamides as Novel NR2B Subtype-Selective NMDA Receptor Antagonists
  作者：Amir P. Tamiz、Sui Xiong Cai、Zhang-Lin Zhou、Po-Wai Yuen、Robert M. Schelkun、Edward R. Whittemore、Eckard Weber、Richard M. Woodward、John F. W. Keana

  DOI：10.1021/jm990199u

  日期：1999.8.1

  A novel series of N-(phenylalkyl)cinnamides related to N-(4-phenylbutyl)-3,4-dihydroxy-beta-cyanocinnamide (6, an EGFR-K inhibitor with high antiproliferative activity) was synthesized and tested for antagonism at N-methyl-D-aspartate (NMDA) receptor subtypes. Potency and subunit selectivity were assayed by electrical recordings in Xenopus oocytes expressing three binary combinations of cloned rat NMDA receptor subunits: NR1A expressed in combination with either NR2A, NR2B, or NR2C. The N-(phenylalkyl)cinnamides are selective antagonists of NR1A/2B receptors. Assayed under steady-state conditions, N-(4-phenylbutyl)-4-hydroxycinnamide (16) has an IC50 value of 77 nM and >1000-fold selectivity with respect to NR1A/2A and NR1A/2C receptors. Potency at alpha(1) adrenergic receptors is low for the four cinnamides tested. Inhibition of NR1A/2B receptors does not correlate with EGFR and ErbB2/neu tyrosine kinase inhibitor activity. The N-(phenylalkyl)cinnamide series we describe provides a novel and structurally diverse framework for designing new NR2B-selective NMDA antagonists as potential CNS therapeutics.