(R)-1-(5'-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-yl)-2-(methylsulfonyl)ethanone | 1398609-00-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异香豆素
• 英文名称: (R)-1-(5'-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-yl)-2-(methylsulfonyl)ethanone
• 英文别名: 1-(5'-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-yl)-2-(methylsulfonyl)ethanone；sarolaner；1-[6-[(5R)-5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4H-1,2-oxazol-3-yl]spiro[1H-2-benzofuran-3,3'-azetidine]-1'-yl]-2-methylsulfonylethanone
• CAS: 1398609-00-1
• 化学式: C₂₃H₁₈Cl₂F₄N₂O₅S
• 分子量: 581.372
• InChiKey: FLEFKKUZMDEUIP-JOCHJYFZSA-N

物化性质

• 沸点：
  722.7±70.0 °C(Predicted)
• 密度：
  1.65±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  37
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  93.6
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (Z)-tert-butyl 5'-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-2-enoyl)-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate 在 (2S)-1-(acridin-9-ylmethyl)-2-((R)-hydroxy(6-methoxyquinolin-4-yl)methyl)-5-vinylquinuclidin-1-ium bromide 、 羟胺 、 N,N'-羰基二咪唑 、 sodium hydroxide 作用下， 以 乙醇 、 甲基叔丁基醚 、 水 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.25h， 生成 (R)-1-(5'-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-yl)-2-(methylsulfonyl)ethanone
  参考文献：
  名称：

  SPIROCYCLIC ISOXAZOLINE DERIVATIVES AS ANTIPARASITIC AGENTS

  摘要：

  本发明涉及螺环异恶唑啉衍生物，包括式(V.1)、式(V.2)、式(V.1.1)和式(1)的衍生物，以及它们的对映异构体、兽医可接受的盐、组合物、制备过程，以及它们作为动物用杀寄生虫药的用途。其中变量A、V、Z、W1、W2、W3、W、Y、X、R1a、R1b、R1c、R2、R3、R4、n和“”的定义如本文所述。

  公开号：

  US20120232026A1

文献信息

• [EN] CRYSTALLINE FORMS OF 1-(5'-(5-(3,5-DICHLORO-4-FLUOROPHENYL)-5-(TRIFLUOROMETHYL)-4,5-DIHYDROISOXAZOL-3-YL)-3'H-SPIRO[AZETIDINE-3,1'-ISOBENZOFURAN]-1-YL)-2-(METHYLSULFONYL)ETHANONE<br/>[FR] FORMES CRISTALLINES DE LA 1-(5'-(5-(3,5-DICHLORO-4-FLUOROPHÉNYL)-5-(TRIFLUOROMÉTHYL)-4,5-DIHYDROISOXAZOL-3-YL)-3'H-SPIRO[AZÉTIDINE-3,1'-ISOBENZOFURAN]-1-YL)-2-(MÉTHYLSULFONYL)ÉTHANONE
  申请人：ZOETIS LLC

  公开号：WO2014036056A1

  公开（公告）日：2014-03-06

  The present invention relates to novel crystalline modifications of 1-(5'-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-yl)-2-(methylsulfonyl)ethanone. The present invention also describes compositions and methods of treating a parasitic infection or infestation in an animal in need thereof. The present invention also relates to processes for making the crystalline forms.

  本发明涉及1-(5'-(5-(3,5-二氯-4-氟苯基)-5-(三氟甲基)-4,5-二氢异噁唑基-3-基)-3'H-螺[氮杂环丁烷-3,1'-异苯并呋喃]-1-基)-2-(甲磺基)乙酮的新晶体形态。本发明还描述了治疗动物寄生感染或寄生虫侵染的组合物和方法。本发明还涉及制备这些晶体形态的方法。
• [EN] SPIROCYCLIC ISOXAZOLINE DERIVATIVES FOR TREATMENT OF SEA LICE<br/>[FR] DÉRIVÉS D'ISOXAZOLINE SPIROCYCLIQUE POUR LE TRAITEMENT DES POUX DE MER
  申请人：ZOETIS LLC

  公开号：WO2014039422A1

  公开（公告）日：2014-03-13

  The invention recites a method of treating a parasitic infection in fish comprising administering an effective amount of a spirocyclic isoxazoline compound of Formula 1, stereoisomers thereof, and veterinary acceptable salts thereof, for use against sea lice in a fish, and compositions thereof, (formula I), wherein W, X, R1a, R1b, R1c, R2, R3, R4, n, and "*" are as defined herein.

  本发明涉及一种治疗鱼类寄生虫感染的方法，包括向鱼类施用公式1的螺环异噁唑化合物及其立体异构体和兽医可接受的盐的有效量，用于对抗鱼类体内的海虱及其组成部分，(公式I)，其中W、X、R1a、R1b、R1c、R2、R3、R4、n和“*”如本文所定义。
• CRYSTALLINE FORMS OF 1-(5'-(5-(3,5-DICHLORO-4-FLUOROPHENYL)-5-(TRIFLUORO-METHYL)-4,5-DIHYDROISOXAZOL-3-YL)-3'H-SPIRO[AZETIDINE-3,1'-ISOBENZOFURAN]-1-YL)-2-(METHYLSULFONYL)ETHANONE
  申请人：Zoetis LLC

  公开号：US20150183795A1

  公开（公告）日：2015-07-02

  The present invention relates to novel crystalline modifications of 1-(5′-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoro-methyl)-4,5-dihydroisoxazol-3-yl)-3′H-spiro[azetidine-3,1′-isobenzofuran]-1-yl)-2-(methylsulfonyl)ethanone. The present invention also describes compositions and methods of treating a parasitic infection or infestation in an animal in need thereof. The present invention also relates to processes for making the crystalline forms.

  本发明涉及1-(5'-(5-(3,5-二氯-4-氟苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-3'H-螺[氮杂环丙烷-3,1'-异苯并呋喃]-1-基)-2-(甲磺酰基)乙酮的新晶体形态。本发明还描述了治疗需要动物体内寄生感染或寄生虫侵染的组合物和方法。本发明还涉及制备晶态形式的工艺。
• ANTIPARASITIC ISOXAZOLINE COMPOUNDS, LONG-ACTING INJECTABLE FORMULATIONS COMPRISING THEM, METHODS AND USES THEREOF
  申请人：Boehringer Ingelheim Animal Health USA Inc.

  公开号：EP3763211A1

  公开（公告）日：2021-01-13

  This invention relates to long-acting injectable compositions for combating parasites in animals, comprising at least one isoxazoline active agent, a liquid PEG and/or a neutral oil, optionally a co-solvent, and optionally a pharmaceutically acceptable additive or excipient. This invention also provides new isoxazoline active agents with long-lasting efficacy against ectoparasites. The invention also provides for improved methods for eradicating, controlling, and preventing parasite infections and infestations in an animal comprising administering the novel isoxazoline compounds and long-acting injectable compositions of the invention to the animal in need thereof.

  本发明涉及用于防治动物体内寄生虫的长效注射组合物，该组合物由至少一种异噁唑啉活性剂、液态 PEG 和/或中性油、可选助溶剂以及可选药学上可接受的添加剂或赋形剂组成。本发明还提供了对体外寄生虫具有持久疗效的新型异噁唑啉活性剂。本发明还提供了根除、控制和预防动物体内寄生虫感染和侵扰的改进方法，包括向有需要的动物施用本发明的新型异噁唑啉化合物和长效注射组合物。
• Design and synthesis of sarolaner, a novel, once-a-month, oral isoxazoline for the control of fleas and ticks on dogs
  作者：Michael P. Curtis、Valerie Vaillancourt、Richard M. Goodwin、Nathan A.L. Chubb、William Howson、Tom L. McTier、Aleah Pullins、Erich W. Zinser、Patrick F.M. Meeus、Debra J. Woods、Laura Hedges、Tim Stuk、Jeffrey E. Price、Jason D. Koch、Sanjay R. Menon

  DOI：10.1016/j.bmcl.2016.02.027

  日期：2016.4

  Over the last decade, the isoxazoline motif has become the intense focus of crop protection and animal health companies in their search for novel pesticides and ectoparasiticides. Herein we report the discovery of sarolaner, a proprietary, optimized-for-animal health use isoxazoline, for once-a-month oral treatment of flea and tick infestation on dogs. (C) 2016 Elsevier Ltd. All rights reserved.