ZK-994 | 524714-13-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: ZK-994
• 英文别名: Acetic acid, (((2S,3R,4E,6E,10E,12S)-13-(4-fluorophenoxy)-2,3,12-trihydroxy-4,6,10-tridecatrien-8-ynyl)oxy)-；2-[(2S,3R,4E,6E,10E,12S)-13-(4-fluorophenoxy)-2,3,12-trihydroxytrideca-4,6,10-trien-8-ynoxy]acetic acid
• CAS: 524714-13-4
• 化学式: C₂₁H₂₃FO₇
• 分子量: 406.408
• InChiKey: HLADOSSHOHRFMH-ZXOMLLCBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  116
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ZK-994 生成 2-((2S,3R,4E,6E,10E,12S)-13-(4-fluorophenoxy)-2,3,12-trihydroxytrideca-4,6,10-trien-8-ynyloxy)acetic acid hydrate
  参考文献：
  名称：

  Crystalline acid of lipoxin A4 analogs and method of making

  摘要：

  本发明涉及一种晶体酸，其为公式（II）中的脂氧素A4类似物，其中：R1为—O—，—S（O）t—（其中t为0、1或2），或直链或支链烷基链；R2为芳基（可选地被一种或多种取代基所取代，所述取代基选择自烷基、烷氧基、卤、卤代烷基和卤代烷氧基）或芳基烷基（可选地被一种或多种取代基所取代，所述取代基选择自烷基、烷氧基、卤、卤代烷基和卤代烷氧基）；并且公式（II）化合物是单一立体异构体或任何立体异构体混合物。该晶体酸在治疗炎症等疾病状态方面具有用途，例如人类的炎症性和自身免疫性疾病或肺部或呼吸道炎症。本文还描述了制备该晶体酸的方法。

  公开号：

  US20080182901A1
• 作为产物：
  描述：

  (2S,3E)-4-溴-1-(4-氟苯氧基)-3-丁烯-2-醇 在 sodium hydroxide 、 copper(l) iodide 、 四(三苯基膦)钯 、 溶剂黄146 、 二乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 为溶剂， 反应 23.0h， 生成 ZK-994
  参考文献：
  名称：

  Novel 3-Oxa Lipoxin A₄ Analogues with Enhanced Chemical and Metabolic Stability Have Anti-inflammatory Activity in Vivo

  摘要：

  Lipoxin A(4) (LXA(4)) is a structurally and functionally distinct natural product called an eicosanoid, which displays immunomodulatory and anti-inflammatory activity but is rapidly metabolized to inactive catabolites in vivo. A previously described analogue of LXA(4), methyl (5R,6R,7E,9E,11Z,13E,15S)-16-(4-fluorophenoxy)-5,6,15-trihydroxy-7,9,11,13-hexadecatetraenoate (2, ATLa), was shown to have a poor pharmacokinetic profile after both oral and intravenous administration, as well as sensitivity to acid and light. The chemical stability of the corresponding E,E,E-trien-11-yne analogue, 3, was improved over 2 without loss of efficacy in the mouse air pouch model of inflammation. Careful analysis of the plasma samples from the pharmacokinetic assays for both 2 and 3 identified a previously undetected metabolite, which is consistent with metabolism by beta-oxidation. The formation of the oxidative metabolites was eliminated with the corresponding 3-oxatetraene, 4, and the 3-oxatrien-11-yne, 5, analogues of 2. Evaluation of 3-oxa analogues 4 and 5 in calcium ionophore-induced acute skin inflammation model demonstrated similar topical potency and efficacy compared to 2. The 3-oxatrien-11-yne analogue, 5, is equipotent to 2 in an animal model of inflammation but has enhanced metabolic and chemical stability and a greatly improved pharmacokinetic profile.

  DOI：

  10.1021/jm030569l

文献信息

• Lipoxin A4 analogs
  申请人：Schering Aktiengesellschaft

  公开号：US20040162433A1

  公开（公告）日：2004-08-19

  This invention is directed to lipoxin A 4 analogs of the following formula (I) and (II): 1 wherein R 1 , R 2 , R 3 , R 4 and R 5 are described herein. These analogs are useful in treating inflammatory and autoimmune disorders in humans. These analogs are also useful in treating pulmonary or respiratory tract inflammation in humans.

  本发明涉及以下公式（I）和（II）的脂氧素A4类似物：1其中R1，R2，R3，R4和R5如本文所述。这些类似物在治疗人类的炎症和自身免疫性疾病方面非常有用。这些类似物还在治疗人类的肺部或呼吸道炎症方面非常有用。
• Intermediates for the preparation of lipoxin A4 analogs
  申请人：Grossbach Danja

  公开号：US20070105949A1

  公开（公告）日：2007-05-10

  This invention is directed to compounds useful as intermediates in the synthesis of lipoxin A 4 analogs of the following formulas (I) and (II): wherein R 1 , R 2 , R 3 , R 4 and R 5 are described herein. These analogs are useful in treating inflammatory and autoimmune disorders in humans. These analogs are also useful in treating pulmonary or respiratory tract inflammation in humans.

  本发明涉及化合物，其作为合成脂氧素A4类似物的中间体有用，该类似物的化学式为(I)和(II)，其中R1、R2、R3、R4和R5如本文所述。这些类似物对于治疗人体内的炎症和自身免疫性疾病有用。这些类似物也对于治疗人体内的肺部或呼吸道炎症有用。
• [EN] LIPOXIN A4 ANALOGS AND USES THEREOF<br/>[FR] ANALOGUES DE LIPOXINE A4 ET UTILISATIONS ASSOCIÉES
  申请人：BRIGHAM & WOMENS HOSPITAL INC

  公开号：WO2020086704A1

  公开（公告）日：2020-04-30

  The invention relates to (S)-6-((1 R,2E,4E,8E,10S)-11 -(4-fluorophenoxy)-1,10-dihydroxyundeca- 2,4,8-trien-6-yn-1-yl)-1,4-dioxan-2-one (compound (1)), which is a lactone-containing analog of lipoxin A4 (LXA4). In particular, the invention features pharmaceutical compositions including compound (1) and the use of compound (1) for the treatment of a disorder (e.g., a fibrotic disorder or an inflammatory disorder, such as an autoimmune disorder) in a subject in need thereof.

  本发明涉及(S)-6-((1R,2E,4E,8E,10S)-11-(4-氟苯氧基)-1,10-二羟基十一烯-2,4,8-三炔-6-炔基)-1,4-二噁烷-2-酮(化合物(1))，它是脂氧素A4(LXA4)的含有内酯的类似物。特别地，本发明涉及包括化合物(1)的药物组合物以及将化合物(1)用于治疗患有某种疾病(例如纤维化性疾病或炎症性疾病，如自身免疫性疾病)的患者的用途。
• LIPOXIN A4 ANALOGS
  申请人：Bayer Schering Pharma Aktiengesellschaft

  公开号：EP1472209B1

  公开（公告）日：2009-03-04
• CRYSTALLINE POTASSIUM SALT OF LIPOXIN A4 ANALOGS
  申请人：Bayer Intellectual Property GmbH

  公开号：EP2089350B1

  公开（公告）日：2018-08-22