洛硫嗪 | 72141-57-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 洛硫嗪
• 中文别名: 罗苏拉净
• 英文名称: 1-<(4-fluorophenyl)sulfonyl>-4-<4-<<7-(trifluoromethyl)-4-quinolinyl>amino>benzoyl>piperazine
• 英文别名: 1[(4-fluorophenyl)sulfonyl]-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine；Losulazine；[4-(4-fluorophenyl)sulfonylpiperazin-1-yl]-[4-[[7-(trifluoromethyl)quinolin-4-yl]amino]phenyl]methanone
• CAS: 72141-57-2
• 化学式: C₂₇H₂₂F₄N₄O₃S
• 分子量: 558.556
• InChiKey: SYJKIRZBDWNJSB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  39
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  91
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4-氟苯磺酰氯 、 哌嗪-1-基-[4-[[7-(三氟甲基)喹啉-4-基]氨基]苯基]甲酮 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以92%的产率得到洛硫嗪
  参考文献：
  名称：

  7-（三氟甲基）-4-氨基喹啉降压药：新型外周交感神经药。

  摘要：

  描述了一族7-（三氟甲基）-4-氨基喹啉，它们是降压药并且通过新的交感神经机制起作用。已经阐明了该系列中的构效关系。对一些更有效的降压药在小鼠中的安全性进行了评估。候选的1-[（（4-氟苯基）磺酰基] -4- [4-[[7-（三氟甲基）-4-喹啉基]氨基]苯甲酰基]哌嗪盐酸盐（氯洛嗪盐酸盐）已被选择用于临床开发。盐酸洛苏拉嗪是大鼠，猫和狗中的降压药。在急性有效降压剂量下，它不会阻止交感神经系统对刺激的反应。

  DOI：

  10.1021/jm00151a021

文献信息

• Antihypertensive 4-aminoquinolines
  申请人：The Upjohn Company

  公开号：US04167567A1

  公开（公告）日：1979-09-11

  Antihypertensive compounds of the formula ll ##STR1## wherein X is chloro or trifluoromethyl; wherein R is an aromatic heterocyclic radical selected from the group consisting of triazinyl, pyrazinyl, pyridinyl, pyrimidinyl or the above radicals substituted by one or two trifluoromethyl, alkyl, alkoxy, dialkylamino, alkylthio, or halo, or 1 to 4 halo atoms for pyridine, or combinations of substituents, in which alkyl and alkoxy are each of 1 to 3 carbon atoms, inclusive, and halo is fluoro, bromo or chloro, or R is the group ##STR2## in which R.sub.1 is phenyl, phenyl-substituted with one or two halogens, trifluoromethylphenyl, phenyl-substituted with one or two alkoxy or alkyl groups, or alkylphenylsulfonyl, in which alkyl, alkoxy, and halo are defined as above; or R is the group SO.sub.2 R.sub.2, in which R.sub.1 is dialkylamino, phenyl, phenyl-substituted with one or two halogens, alkyl, trifluoromethyl or alkoxy groups, in which alkyl, alkoxy and halo are defined as hereinabove, are prepared from compounds of the formula ##STR3## WHEREIN X has the significance as above, by reaction with the selected cyclic amine or by reaction of ##STR4## wherein X is defined as above and a selected R.sub.2 -sulfonyl chloride or R.sub.1 -isocyanate. The compounds of formula ll and their pharmacologically acceptable acid addition salts are hypotensive agents which are useful for the treatment of hypertension in mammals, including man.

  公式为ll的降压化合物##STR1##，其中X为氯或三氟甲基；其中R为从三嗪基、吡嗪基、吡啶基、嘧啶基或上述基团中选择的芳香杂环基团，该基团被一个或两个三氟甲基、烷基、烷氧基、二烷基氨基、烷基硫基或卤素取代，或对于吡啶，为1至4个卤素原子，或取代基的组合，其中烷基和烷氧基各自为1至3个碳原子，包括，卤素为氟、溴或氯，或R为该基团##STR2##，其中R.sub.1为苯基，苯基取代一个或两个卤素、三氟甲基苯基、取代一个或两个烷氧基或烷基基团的苯基，或烷基苯基磺酰基，其中烷基、烷氧基和卤素如上定义；或R为该基团SO.sub.2 R.sub.2，其中R.sub.1为二烷基氨基、苯基、取代一个或两个卤素、烷基、三氟甲基或烷氧基的苯基，其中烷基、烷氧基和卤素如上定义；从公式##STR3##的化合物制备，其中X具有如上所述的含义，通过与选择的环胺反应或与##STR4##其中X如上定义和选择的R.sub.2-磺酰氯或R.sub.1-异氰酸酯反应。公式ll的化合物及其药理学上可接受的酸盐是降压剂，可用于治疗哺乳动物，包括人类的高血压。
• 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。
• [EN] PROCESS FOR 4-AMINO QUINOLINES
  申请人：THE UPJOHN COMPANY

  公开号：WO1986005489A1

  公开（公告）日：1986-09-25

  (EN) Novel process for preparing known pharmacological agents useful in the treatment of hypertension of formula C-7.(FR) Nouveau procédé de préparation d'agents pharmacologiques connus utiles dans le traitement de l'hypertension et correspondant à la formule C-7.

  （中文）一种用于制备公式C-7的已知药理活性剂，用于治疗高血压的新型工艺。
• 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。
• Controlled absorption water-soluble pharmaceutically active organic compound formulation for once-daily administration
  申请人：Counts David F.

  公开号：US10463611B2

  公开（公告）日：2019-11-05

  The present disclosure provides a once-daily water-soluble pharmaceutically active formulation for oral administration. In certain embodiments, the composition comprises a water-soluble pharmaceutically active organic compound incorporated into a small particulate, each particulate having a core of the water-soluble pharmaceutically active organic compound or an acceptable salt thereof in reversible association with a pharmaceutically acceptable drug-binding polymer. The core of the composition being surrounded by an insoluble water permeable membrane that is capable of delaying the dissolution of the pharmaceutically active compound therewithin and providing for extended release of the pharmaceutically active compound. In some embodiments, the formulation of the invention are designed to extend release of the pharmaceutically active organic compound for about 3 hours to about 8 hours, thereby enabling preparation of an extended release formulation for any pharmaceutically active compound with a half-life of from about 16 hours to about 21 hours.

  本公开提供了一种用于口服的每日一次水溶性药用活性制剂。在某些实施方案中，该组合物包括掺入小颗粒中的水溶性药用活性有机化合物，每个颗粒都有一个水溶性药用活性有机化合物或其可接受盐的核心，该核心与药学上可接受的药物结合聚合物可逆结合。组合物的核心由不溶性透水膜包围，该膜能够延迟其中的药用活性化合物的溶解，并延长药用活性化合物的释放时间。在某些实施方案中，本发明的制剂可将药用活性有机化合物的释放时间延长约 3 小时至约 8 小时，从而能够制备半衰期为约 16 小时至约 21 小时的任何药用活性化合物的缓释制剂。