HEPA | 52839-87-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: HEPA
• 英文别名: (+/-)-2-hydroxy-2-phenyl-butyric acid amide；2-Hydroxy-2-phenyl-buttersaeure-amid；DL-2-hydroxy-2-phenyl butyramide；(+/-)-2-hydroxy-2-phenylbutyramide；2-Hydroxy-2-phenylbutyramide；2-hydroxy-2-phenylbutanamide
• CAS: 52839-87-9
• 化学式: C₁₀H₁₃NO₂
• 分子量: 179.219
• InChiKey: KHJLUGZFVDFOKZ-UHFFFAOYSA-N

物化性质

• 熔点：
  93-95 °C
• 沸点：
  358.5±35.0 °C(Predicted)
• 密度：
  1.160±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  HEPA 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以1.24 g的产率得到2-hydroxy-2-phenylbutanoic acid
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship Studies for Hydantoins and Analogues as Voltage-Gated Sodium Channel Ligands

  摘要：

  We previously developed a preliminary 3-D QSAR model for the binding of 14 hydantoins to the neuronal voltage-gated sodium channel; this model was successful in designing,an effective non-hydantoin ligand. To further understand structural features that result in optimum binding. here we synthesized a variety of compound classes and evaluated their binding affinities to the neuronal voltage-gated sodium channel using the [H-3]-batrachotoxinin A 20-a-benzoate ([H-3]BTX-B) binding assay. In order to understand the importance of the hydantoin ring for good sodium channel binding, related non-hydantoins such as hydroxy amides, oxazolidinediones, hydroxy acids, and amino acids were included. Two major conclusions were drawn: (1) The hydantoin ring is not critical for compounds with long alkyl side chains, but it is important for compounds with shorter side chains. (2) Relative to Khodorov's pharmacophore. which contains two hydrophobic regions, a third hydrophobic region may enhance binding to provide nanomolar inhibitors.

  DOI：

  10.1021/jm040077o
• 作为产物：
  描述：

  2-羟基-2-乙基-2-苯基乙腈 在 盐酸 作用下， 以2.03 g的产率得到HEPA
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship Studies for Hydantoins and Analogues as Voltage-Gated Sodium Channel Ligands

  摘要：

  We previously developed a preliminary 3-D QSAR model for the binding of 14 hydantoins to the neuronal voltage-gated sodium channel; this model was successful in designing,an effective non-hydantoin ligand. To further understand structural features that result in optimum binding. here we synthesized a variety of compound classes and evaluated their binding affinities to the neuronal voltage-gated sodium channel using the [H-3]-batrachotoxinin A 20-a-benzoate ([H-3]BTX-B) binding assay. In order to understand the importance of the hydantoin ring for good sodium channel binding, related non-hydantoins such as hydroxy amides, oxazolidinediones, hydroxy acids, and amino acids were included. Two major conclusions were drawn: (1) The hydantoin ring is not critical for compounds with long alkyl side chains, but it is important for compounds with shorter side chains. (2) Relative to Khodorov's pharmacophore. which contains two hydrophobic regions, a third hydrophobic region may enhance binding to provide nanomolar inhibitors.

  DOI：

  10.1021/jm040077o

文献信息

• Dl-hydroxy-alkyl-phenylamides having anticonvulsive activity
  申请人：Meza Toledo Enrique Sergio

  公开号：US20060287397A1

  公开（公告）日：2006-12-21

  New anticonvulsant compounds were synthesized and they include the compounds: DL-2-hydroxy-2-(3′,5′-bistrifluoromethylphenyl)butyramide, DL-2-hydroxy-2-(4′-trifluoromethylphenyl)butyramide, DL-2-hydroxy-2-(3′,4′-dichlorophenyl)butyramide, DL-2-hydroxy-2-(3′-bromophenyl)butyramide, DL-2-hydroxy-2-(4′-bromophenyl)butyramide, DL-2-hydroxy-2-(3′-nitrophenyl)butyramide, DL-3-hydroxy-3-(3′,4′-dichlorophenyl)pentanamide, DL-3-hydroxy-3-(4′-bromophenyl)pentanamide, DL-4-hydroxy-4-(3′,4′-dichlorophenyl) hexanamide and DL-4-hydroxy-4-(4′-bromophenyl)hexanamide. They have a significant anticonvulsant activity against pentylenetetrazol-induced seizures as well as unexpected differences in anticonvulsant activity respect those of the non-halogenated compounds. The invention further provides methods for the synthesis of the DL-hydroxy-alkyl-phenyl amides as exemplified in the examples.

  新的抗惊厥化合物已经合成，它们包括以下化合物：DL-2-羟基-2-(3′,5′-双三氟甲基苯基)丁酰胺，DL-2-羟基-2-(4′-三氟甲基苯基)丁酰胺，DL-2-羟基-2-(3′,4′-二氯苯基)丁酰胺，DL-2-羟基-2-(3′-溴苯基)丁酰胺，DL-2-羟基-2-(4′-溴苯基)丁酰胺，DL-2-羟基-2-(3′-硝基苯基)丁酰胺，DL-3-羟基-3-(3′,4′-二氯苯基)戊酰胺，DL-3-羟基-3-(4′-溴苯基)戊酰胺，DL-4-羟基-4-(3′,4′-二氯苯基)己酰胺和DL-4-羟基-4-(4′-溴苯基)己酰胺。它们对戊巴比妥诱导的癫痫发作具有显著的抗惊厥活性，同时与非卤代化合物相比具有意想不到的抗惊厥活性差异。该发明还提供了合成DL-羟基-烷基-苯胺的方法，如示例中所示。
• Phenyl alcohol amides having anticonvulsant activity
  申请人：——

  公开号：US05463125A1

  公开（公告）日：1995-10-31

  New anticonvulsant compounds include (.+-.)-2-hydroxy-2-phenylbutyramide and (.+-.)-3-hydroxy-3-phenylpentamide. These homologues of (.+-.)-4-hydroxy-4-phenylhexanamide have anticonvulsant activity as well as unexpected properties, particularly low neurotoxicity and pharmacological differences. The invention further provides methods for the synthesis of (.+-.)-2-hydroxy-2-phenylbutyramide and (.+-.)-3-hydroxy-3-phenylpentamide as exemplified in the examples.

  新的抗惊厥化合物包括(.+-.)-2-羟基-2-苯基丁酰胺和(.+-.)-3-羟基-3-苯基戊酰胺。这些与(.+-.)-4-羟基-4-苯基己酰胺同系物具有抗惊厥活性，以及意外的特性，特别是低神经毒性和药理学差异。该发明还提供了合成(.+-.)-2-羟基-2-苯基丁酰胺和(.+-.)-3-羟基-3-苯基戊酰胺的方法，如示例所示。
• [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。
• Hydroquinonylphenyl butyric acid amide derivative
  申请人：SUNTORY LIMITED

  公开号：EP0298758A2

  公开（公告）日：1989-01-11

  A hydroquinonylphenyl butyric acid amide derivative having the formula (I): wherein R¹ represents an aromatic or heterocyclic group which may be substituted, R² represents a hydrogen atom, a lower alkylcarbonyl group, an aromatic carbonyl or heterocyclic carbonyl group which may be substituted, and X represents an oxygen atom or sulfur atom or a pharmaceutically acceptable salt thereof, which has a cerebral insufficiency improving activity.

  一种具有式(I)的氢醌基苯基丁酸酰胺衍生物： 其中 R¹ 代表可被取代的芳基或杂环基，R² 代表氢原子、低级烷基羰基、可被取代的芳基羰基或杂环羰基，X 代表氧原子或硫原子或其药学上可接受的盐，具有改善脑供血不足的活性。
• Pyridylethylated Oxazolidinediones. II¹
  作者：Seymour L. Shapiro、Ira M. Rose、Eric Roskin、Louis Freedman

  DOI：10.1021/ja01511a028

  日期：1959.1

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