二噁沙利 | 87495-31-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 二噁沙利
• 中文别名: 二恶沙利
• 英文名称: disoxaril
• 英文别名: 5-{7-[4-(4,5-dihydro-2-oxazolyl)phenoxy]-heptyl}-3-methylisoxazole；5-(7-(4-(4,5-dihydro-2-oxazolyl)phenoxy)heptyl)-3-methylisoxazole；5-[7-[4-(4,5-dihydro-2-oxazolyl)phenoxy]heptyl]-3-methylisoxazole；WIN 51711；5-[7-[4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]heptyl]-3-methyl-1,2-oxazole
• CAS: 87495-31-6
• 化学式: C₂₀H₂₆N₂O₃
• 分子量: 342.438
• InChiKey: FKLJPTJMIBLJAV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  56.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  二噁沙利 在 phosphate buffer 作用下， 以 甲醇 、 水 为溶剂， 反应 36.0h， 生成 4-[7-(3-Methyl-isoxazol-5-yl)-heptyloxy]-benzoic acid 2-amino-ethyl ester
  参考文献：
  名称：

  Physico-chemical characterization of disoxaril–dimethyl-β-cyclodextrin inclusion complex and in vitro permeation studies

  摘要：

  In this work we evaluated the ability of 2,6-di-O-methyl-beta-cyclodextrin (DM-beta-Cyd) to include the anti-rhinovirus drug Disoxaril (WIN 51711), increasing its water solubility and stability. The complex, prepared by kneading method, was characterized in the solid state by differential scanning calorimetry and in aqueous solution using circular dichroism and NMR spectroscopy. The formation of 1:1 and 1:2 drug-Cyd complexes was hypothesized. Stability constants for both complexes were determined on the basis of an Ap-type phase solubility diagrams and evidenced a very high stability for the 1:1 complex. Thermodynamic parameters of the binding process showed the existence of classical hydrophobic interactions in the 1:1 complex with the formation of a less ordered system after complexation. An enthalpic contribution rather than an entropic one accompanied the association of the second Cyd molecule. DM-beta-Cyd was able to significantly increase water solubility of WIN 51711, from 0.000123 to 0.47142 mg/ml. Free drug shows a very low water stability, it is completely hydrolyzed after 36 h in PBS (pH 7.0), at 4 degrees C. In the presence of DM-beta-Cyd only a 10% of WIN 51711 was degraded, to the same conditions, after 12 days. DM-beta-Cyd increases the permeation of WIN 51711 across excised bovine nasal mucosa mounted on Franz cells, with respect to the free drug. Nevertheless, the permeation process had a lag time of 2 h so that the drug might assure its pharmacological activity on the outer surface of the mucosa. In vivo studies on rabbits evidenced that WIN 51711 is well tolerated, having no observable effect on the nasal mucosa following repeated administration. (c) 2006 Elsevier SAS. All fights reserved.

  DOI：

  10.1016/j.ejmech.2005.11.002
• 作为产物：
  描述：

  3,5-二甲基异唑 在 盐酸 、 正丁基锂 、 TEA 作用下， 以 乙醚 为溶剂， 反应 7.0h， 生成 二噁沙利
  参考文献：
  名称：

  [[(4,5-Dihydro-2-oxazolyl)phenoxy]alkyl]isoxazoles. Inhibitors of picornavirus uncoating

  摘要：

  A series of [[(4,5-dihydro-2-oxazolyl)phenoxy]alkyl]isoxazoles has been synthesized and evaluated as antipicornavirus agents. The effect of alkyl groups in the 4- and 5-position of the oxazoline ring, as well as the alkyl chain length, on antiviral activity was examined. Compound 14 was evaluated in vivo and was found to significantly reduce mortality at an oral dose of 4 mg/kg in mice infected intracerebrally with poliovirus-2. Compound 14 was also effective in preventing paralysis when administered intraperitoneally to mice infected subcutaneously with a lethal dose of ECHO-9 virus. On the basis of the results of these studies, compound 14 is a strong candidate for clinical evaluation as a systemic agent for the treatment of picornavirus infections.

  DOI：

  10.1021/jm00150a025

文献信息

• Immunosuppressive effects of pteridine derivatives
  申请人：——

  公开号：US20040077859A1

  公开（公告）日：2004-04-22

  This invention relates to a group of trisubstituted and tetrasubstituted pteridine derivatives, their pharmaceutically acceptable salts, N-oxides, solvates, dihydro- and tetrahydroderivatives and enantiomers, possessing unexpectedly desirable pharmaceutical properties, in particular which are highly active immunosuppressive agents, and as such are useful in the treatment in transplant rejection and/or in the treatment of certain inflammatory diseases. These compounds are also useful in preventing or treating cardiovascular disorders, allergic conditions, disorders of the central nervous system and cell proliferative disorders.

  这项发明涉及一组三取代和四取代的嘌呤衍生物，它们的药用盐、N-氧化物、溶剂化物、二氢和四氢衍生物及对映异构体，具有意想不到的、令人满意的药理性质，尤其是作为高度活性的免疫抑制剂，因此可用于治疗移植排斥反应和/或治疗某些炎症性疾病。这些化合物还用于预防或治疗心血管疾病、过敏性疾病、中枢神经系统疾病和细胞增殖紊乱。
• ANTIVIRAL 1,3-DI-OXO-INDENE COMPOUNDS
  申请人：Novartis AG

  公开号：US20210323947A1

  公开（公告）日：2021-10-21

  The invention provides compounds of Formula (I): as described herein, along with pharmaceutically acceptable salts, pharmaceutical compositions containing such compounds, and methods to use these compounds, salts and compositions for treating viral infections.

  这项发明提供了如下式（I）的化合物： 如本文所述，以及包含这些化合物的药用盐、含有这些化合物的药物组合物，以及治疗病毒感染的方法。
• INDANONE DERIVATIVES, PHARMACEUTICALLY ACCEPTABLE SALTS OR OPTICAL ISOMERS THEREOF, PREPARATION METHOD FOR SAME, AND PHARMACEUTICAL COMPOSITIONS CONTAINING SAME AS ACTIVE INGREDIENT FOR PREVENTING OR TREATING VIRAL DISEASES
  申请人：Jung Young Sik

  公开号：US20140114068A1

  公开（公告）日：2014-04-24

  Disclosed are novel indanone derivatives, pharmaceutically acceptable salts thereof or enantiomers, a preparation method thereof, and a pharmaceutical composition for the prevention or treatment of viral diseases, comprising the same as an active ingredient. The indanone derivatives have excellent inhibitory activity against picornaviruses including coxsackie-, entero-, echo-, Polio-, and rhinoviruses, as well as exhibiting low cytotoxicity, so that they can be useful as an active ingredient of a pharmaceutical composition for the prevention or treatment of viral diseases including poliomyelitis, paralysis, acute hemorrhagic conjunctivitis, viral meningitis, hand-foot-and-mouth disease, vesicular disease, hepatitis A, myositis, myocarditis, pancreatitis, diabetes, epidemic myalgia, encephalitis, flu, herpangina, foot-and-mouth disease, asthma, chronic obstructive pulmonary disease, pneumonia, sinusitis or otitis media.

  揭示了新颖的茚酮衍生物，其药用盐或对映体，以及其制备方法和作为活性成分的用于预防或治疗病毒性疾病的药物组合物。这些茚酮衍生物对包括柯萨奇病毒、肠道病毒、回声病毒、脊髓灰质炎病毒和鼻病毒在内的小RNA病毒具有出色的抑制活性，并且具有低细胞毒性，因此它们可用作预防或治疗包括小儿麻痹症、瘫痪、急性出血性结膜炎、病毒性脑膜炎、手足口病、水疱病、甲型肝炎、肌炎、心肌炎、胰腺炎、糖尿病、流行性肌痛、脑炎、流感、手足口病、哮喘、慢性阻塞性肺病、肺炎、鼻窦炎或中耳炎等病毒性疾病的药物组合物的活性成分。
• Di-heterocyclic compounds and their use as antiviral agents
  申请人：Sterling Drug Inc.

  公开号：US04843087A1

  公开（公告）日：1989-06-27

  Compounds of the formulas: ##STR1## wherein Het is an oxazole or oxazine moiety; X is O, S or SO, n is an integer from 3 to 9, Y is an aliphatic bridge; and the various R groups represent hydrogen or various substituents as described herein, are useful as antiviral agents, especially against picornaviruses. N-(Chloroalkyl)amide intermediates for the compounds of Formula I are also active as antiviral agents. Related compounds outside the scope of the above formulas are also disclosed.

  公式化合物：##STR1## 其中Het是噁唑或噁唑啉基团；X是O、S或SO，n是从3到9的整数，Y是脂肪桥；各种R基团代表氢或如本文所述的各种取代基，可用作抗病毒剂，特别是对抗小RNA病毒。用于公式I化合物的N-(氯烷基)酰胺中间体也作为抗病毒剂活性。还披露了超出上述公式范围的相关化合物。
• [EN] TRICYCLIC INHIBITORS OF INFLUENZA VIRUS ENDONUCLEASE<br/>[FR] INHIBITEURS TRICYCLIQUES DE L'ENDONUCLÉASE DU VIRUS DE LA GRIPPE
  申请人：WEBB THOMAS R

  公开号：WO2021195278A1

  公开（公告）日：2021-09-30

  The present disclosure is concerned with 9-hydroxy-6-(pyrrolidin-2-yl)-3,4-dihydro-2H-pyrazino[ 1,2-c]pyrimidine- 1, 8-dione compounds for the treatment of various viral infections such as, for example, influenza virus. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  本公开涉及用于治疗各种病毒感染的9-羟基-6-(吡咯啉-2-基)-3,4-二氢-2H-吡嗪并[1,2-c]嘧啶-1,8-二酮化合物，例如流感病毒。本摘要旨在作为在特定领域搜索的扫描工具，并不意在限制本发明。