罗卡斯汀 | 91833-49-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 罗卡斯汀
• 英文名称: AHR 11325
• 英文别名: 2-[2-(dimethylamino)ethyl]-2,3-dihydro-4-methylpyrido[3,2-f][1,4]oxazepine-5(4H)-thione；rocastine；2-(dimethylamino)ethyl-2,3-dihydro-4-methylpyrido-[3,2-f]-1,4-oxazepine-5(4 H)-thione；2-[2-(dimethylamino)ethyl]-4-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepine-5-thione
• CAS: 91833-49-7
• 化学式: C₁₃H₁₉N₃OS
• 分子量: 265.379
• InChiKey: DPPDPATYPQFYDL-UHFFFAOYSA-N

物化性质

• 熔点：
  130-133 °C
• 沸点：
  379.0±52.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  60.7
• 氢给体数：
  0
• 氢受体数：
  4

制备方法与用途

生物活性

Rocastine 是一种选择性的、非镇静的 H1 拮抗剂，属于抗组胺剂。

体内研究

罗卡定在 15 分钟和 1 小时预处理时间下均有效（半数有效剂量 PD₅₀ 分别为 0.13 mg/kg 和 0.12 mg/kg）。它能保护豚鼠免受气雾抗原诱导的休克；Rocastine 的效力约为异丙嗪的 36 倍，与奥他唑和特非那定相当。Rocastine 在剂量远超过其抗组胺作用（150 倍）时不会改变猫的脑电图 (EEG)，也不会增强 yohimbine 对小鼠的毒性。

反应信息

• 作为反应物：
  描述：

  罗卡斯汀 、 碘甲烷 以 various solvent(s) 为溶剂， 以78%的产率得到2-(2,3,4,5-tetrahydro-4-methyl-5-thioxo-pyrido[3,2-f]-1,4-oxazepin-2-yl)trimethylethanaminium iodide
  参考文献：
  名称：

  Benzo- and pyrido-1,4-oxazepin-5-ones and -thiones: synthesis and structure-activity relationships of a new series of H1-antihistamines

  摘要：

  A series of novel benzo- and pyrido-1,4-oxazepinones and -thiones which represents a new structural class of compounds possessing H1 antihistaminic activity was synthesized, and the SARs were evaluated. The antihistaminic activity was determined by blockade of histamine-induced lethality in guinea pigs. The sedative potential was determined by comparison of the EEG profiles of the compounds with those of known sedating and nonsedating antihistamines. Several of the compounds were shown to possess potent H1 antihistaminic activity and to be free of the cortical slowing with synchronized waves and spindling activity found in the EEG of sedative antihistamines. One compound, 2-[2-(dimethylamino)ethyl]-3,4-dihydro-4-methylpyrido[3,2-f]-1,4- oxazepine-5(2H)-thione (rocastine) is currently undergoing clinical evaluation as a nonsedating H1 antihistamine.

  DOI：

  10.1021/jm00129a026
• 作为产物：
  描述：

  2-氯烟酸 在 盐酸 、 四氯化碳 、 tetraphosphorus decasulfide 、 sodium hydride 、 三苯基膦 作用下， 以 乙醇 、 氯仿 、 水 、 二甲基亚砜 为溶剂， 反应 39.0h， 生成 罗卡斯汀
  参考文献：
  名称：

  Benzo- and pyrido-1,4-oxazepin-5-ones and -thiones: synthesis and structure-activity relationships of a new series of H1-antihistamines

  摘要：

  A series of novel benzo- and pyrido-1,4-oxazepinones and -thiones which represents a new structural class of compounds possessing H1 antihistaminic activity was synthesized, and the SARs were evaluated. The antihistaminic activity was determined by blockade of histamine-induced lethality in guinea pigs. The sedative potential was determined by comparison of the EEG profiles of the compounds with those of known sedating and nonsedating antihistamines. Several of the compounds were shown to possess potent H1 antihistaminic activity and to be free of the cortical slowing with synchronized waves and spindling activity found in the EEG of sedative antihistamines. One compound, 2-[2-(dimethylamino)ethyl]-3,4-dihydro-4-methylpyrido[3,2-f]-1,4- oxazepine-5(2H)-thione (rocastine) is currently undergoing clinical evaluation as a nonsedating H1 antihistamine.

  DOI：

  10.1021/jm00129a026

文献信息

• COMPOSITIONS AND METHODS FOR TREATMENT OF VIRAL DISEASES
  申请人：Johansen Lisa M.

  公开号：US20100009970A1

  公开（公告）日：2010-01-14

  The present invention features compositions, methods, and kits useful in the treatment of viral diseases. In certain embodiments, the viral disease is caused by a single stranded RNA virus, a flaviviridae virus, or a hepatic virus. In particular embodiments, the viral disease is viral hepatitis (e.g., hepatitis A, hepatitis B, hepatitis C, hepatitis D, hepatitis E) and the agent or combination of agents includes sertraline, a sertraline analog, UK-416244, or a UK-416244 analog. Also featured are screening methods for identification of novel compounds that may be used to treat a viral disease.

  本发明涉及用于治疗病毒性疾病的组合物、方法和试剂盒。在某些实施方式中，病毒性疾病是由单链RNA病毒、黄病毒科病毒或肝病毒引起的。在特定实施方式中，病毒性疾病是病毒性肝炎（例如甲型肝炎、乙型肝炎、丙型肝炎、丁型肝炎、戊型肝炎），药剂或药剂组合包括舍曲林、舍曲林类似物、UK-416244或UK-416244类似物。还包括用于鉴定可用于治疗病毒性疾病的新化合物的筛选方法。
• Pharmaceutical preparation comprising an active dispersed on a matrix
  申请人：——

  公开号：US20040058896A1

  公开（公告）日：2004-03-25

  The present invention relates to the field of pharmaceutical technology and describes a novel advantageous preparation for an active ingredient. The novel preparation is suitable for producing a large number of pharmaceutical dosage forms. In the new preparation an active ingredient is present essentially uniformly dispersed in an excipient matrix composed of one or more excipients selected from the group of fatty alcohol, triglyceride, partial glyceride and fatty acid ester.

  本发明涉及制药技术领域，描述了一种新的有利的活性成分制备方法。这种新的制备方法适用于生产大量的药物剂型。在这种新的制备方法中，活性成分基本上均匀地分散在由脂肪醇、甘油三酯、部分甘油酯和脂肪酸酯等多种赋形剂中选择的一种或多种赋形剂组成的赋形剂基质中。
• Nitrate prodrugs able to release nitric oxide in a controlled and selective way and their use for prevention and treatment of inflammatory, ischemic and proliferative diseases
  申请人：Scaramuzzino, Giovanni

  公开号：EP1336602A1

  公开（公告）日：2003-08-20

  New pharmaceutical compounds of general formula (I): F-(X)q where q is an integer from 1 to 5, preferably 1; -F is chosen among drugs described in the text, -X is chosen among 4 groups -M, -T, -V and -Y as described in the text. The compounds of general formula (I) are nitrate prodrugs which can release nitric oxide in vivo in a controlled and selective way and without hypotensive side effects and for this reason they are useful for the preparation of medicines for prevention and treatment of inflammatory, ischemic, degenerative and proliferative diseases of musculoskeletal, tegumental, respiratory, gastrointestinal, genito-urinary and central nervous systems.

  通式（I）的新药物化合物：F-（X）q，其中q是1到5的整数，最好是1；-F是在文本中描述的药物中选择的，-X是在文本中描述的4个组-M，-T，-V和-Y中选择的。通式（I）的化合物是硝酸盐前药，可以在体内以受控和选择性的方式释放一氧化氮，而不会产生降压副作用，因此它们非常适用于制备用于预防和治疗肌肉骨骼，皮肤，呼吸，消化，泌尿和中枢神经系统的炎症，缺血，退行性和增生性疾病的药物。
• [EN] CERTAIN PAF ANTAGONIST ANTIHISTAMINE COMBINATIONS AND METHODS
  申请人：SCHERING CORPORATION

  公开号：WO1989010143A1

  公开（公告）日：1989-11-02

  (EN) Methods and compositions are disclosed employing combinations of antihistamines with certain diaryl tetrahydrofuran, diaryl tetrahydrothiophene, triazolobenzodiazepine or thienotriazolodiazepine PAF-antagonist compounds in the treatment of allergic reactions.(FR) On a mis au point des procédés et des compositions employant des combinaisons d'antihistamines avec certains composés antagonistes du PAF, de diaryle tétrahydrofurane, diaryle tétrahydrothiophène, triazolobenzodiazépine ou thiénotriazolodiazépine, dans le traitement de réactions allergiques.

  （中文翻译）本发明揭示了在治疗过敏反应中使用抗组胺药与某些二芳基四氢呋喃、二芳基四氢噻吩、三唑苯并二氮平或噻唑三唑二氮平PAF-拮抗剂化合物的组合的方法和组合物。
• Diagnostic/therapeutic agents
  申请人：Klaveness Jo

  公开号：US20050002865A1

  公开（公告）日：2005-01-06

  Targetable diagnostic and/or therapeutically active agents, e.g. ultrasound contrast agents, comprising a suspension in an aqueous carrier liquid of a reporter comprising gas-containing or gas-generating material, said agent being capable of forming at least two types of binding pairs with a target.

  可定位的诊断和/或治疗活性剂，例如超声对比剂，包括悬浮在水载体液中的报告物，该报告物包含含气体或生成气体的材料，该剂能够与目标形成至少两种结合对。