3-butyl-2-(5-ethylthiophen-2-yl)-2,3-dihydroquinazolin-4(1H)-one | 1542097-88-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 3-butyl-2-(5-ethylthiophen-2-yl)-2,3-dihydroquinazolin-4(1H)-one
• 英文别名: 3-Butyl-2-(5-ethylthiophen-2-yl)-1,2-dihydroquinazolin-4-one；3-butyl-2-(5-ethylthiophen-2-yl)-1,2-dihydroquinazolin-4-one
• CAS: 1542097-88-0
• 化学式: C₁₈H₂₂N₂OS
• 分子量: 314.451
• InChiKey: APIXBRWYSGGSPH-UHFFFAOYSA-N

物化性质

• 沸点：
  495.0±45.0 °C(predicted)
• 密度：
  1.135±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  60.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  靛红酸酐 在 scandium tris(trifluoromethanesulfonate) 作用下， 以 四氢呋喃 为溶剂， 生成 3-butyl-2-(5-ethylthiophen-2-yl)-2,3-dihydroquinazolin-4(1H)-one
  参考文献：
  名称：

  Structural optimization of a retrograde trafficking inhibitor that protects cells from infections by human polyoma- and papillomaviruses

  摘要：

  Human polyoma- and papillomaviruses are non-enveloped DNA viruses that cause severe pathologies and mortalities. Under circumstances of immunosuppression, JC polyomavirus causes a fatal demyelinating disease called progressive multifocal leukoencephalopathy (PML) and the BK polyomavirus is the etiological agent of polyomavirus-induced nephropathy and hemorrhagic cystitis. Human papillomavirus type 16, another non-enveloped DNA virus, is associated with the development of cancers in tissues like the uterine cervix and oropharynx. Currently, there are no approved drugs or vaccines to treat or prevent polyomavirus infections. We recently discovered that the small molecule Retro-2(cycl), an inhibitor of host retrograde trafficking, blocked infection by several human and monkey polyomaviruses. Here, we report diversity-oriented syntheses of Retro-2(cycl) and evaluation of the resulting analogs using an assay of human cell infections by JC polyomavirus. We defined structure-activity relationships and also discovered analogs with significantly improved potency as suppressors of human polyoma- and papillomavirus infection in vitro. Our findings represent an advance in the development of drug candidates that can broadly protect humans from non-enveloped DNA viruses and toxins that exploit retrograde trafficking as a means for cell entry.

  DOI：

  10.1016/j.bmc.2014.06.053

文献信息

• [EN] COMPOUNDS FOR THE TREATMENT AND PREVENTION OF INFECTIONS<br/>[FR] COMPOSÉS DESTINÉS AU TRAITEMENT ET À LA PRÉVENTION D'INFECTIONS
  申请人：UNIV BROWN

  公开号：WO2014014814A1

  公开（公告）日：2014-01-23

  Provided herein are compounds of Formula (I) or (II): (I) (II) harmaceutically acceptable salts, tautomers, prodrugs, and stereoisomers thereof, and pharmaceutical compositions thereof, wherein X, RN, R1,R3,R4, p, and m are as defined herein. Such compounds and compositions have been found useful in the treatment or prevention of viral infections, e.g., polyomaviral infections, and are further envisioned useful in treatment or prevention of other pathogenic conditions associated with endosomal trafficking. Methods of treating or preventing an infection by a pathogen secreting an AB5 toxin is also contemplated.

  本文提供了化合物的公式(I)或(II)：(I) (II) 其药用可接受的盐、互变异构体、前药和立体异构体，以及药物组合物，其中X、RN、R1、R3、R4、p和m如本文所定义。已发现这些化合物和组合物在治疗或预防病毒感染，例如聚病毒感染方面具有用处，并且进一步被认为在治疗或预防与溶酶体运输相关的其他病原体条件方面有用。还考虑了通过治疗或预防分泌AB5毒素的病原体感染的方法。
• COMPOUNDS FOR THE TREATMENT AND PREVENTION OF INFECTIONS
  申请人：Brown University

  公开号：US20150166517A1

  公开（公告）日：2015-06-18

  Provided herein are compounds of Formula (I) or (II): (I) (II) pharmaceutically acceptable salts, tautomers, prodrugs, and stereoisomers thereof, and pharmaceutical compositions thereof, wherein X, R N , R 1 , R 3 , R 4 , p, and m are as defined herein. Such compounds and compositions have been found useful in the treatment or prevention of viral infections, e.g., polyomaviral infections, and are further envisioned useful in treatment or prevention of other pathogenic conditions associated with endosomal trafficking. Methods of treating or preventing an infection by a pathogen secreting an AB 5 toxin is also contemplated.
• US9695156B2
  申请人：——

  公开号：US9695156B2

  公开（公告）日：2017-07-04
• Structural optimization of a retrograde trafficking inhibitor that protects cells from infections by human polyoma- and papillomaviruses
  作者：Daniel W. Carney、Christian D.S. Nelson、Bennett D. Ferris、Julia P. Stevens、Alex Lipovsky、Teymur Kazakov、Daniel DiMaio、Walter J. Atwood、Jason K. Sello

  DOI：10.1016/j.bmc.2014.06.053

  日期：2014.9

  Human polyoma- and papillomaviruses are non-enveloped DNA viruses that cause severe pathologies and mortalities. Under circumstances of immunosuppression, JC polyomavirus causes a fatal demyelinating disease called progressive multifocal leukoencephalopathy (PML) and the BK polyomavirus is the etiological agent of polyomavirus-induced nephropathy and hemorrhagic cystitis. Human papillomavirus type 16, another non-enveloped DNA virus, is associated with the development of cancers in tissues like the uterine cervix and oropharynx. Currently, there are no approved drugs or vaccines to treat or prevent polyomavirus infections. We recently discovered that the small molecule Retro-2(cycl), an inhibitor of host retrograde trafficking, blocked infection by several human and monkey polyomaviruses. Here, we report diversity-oriented syntheses of Retro-2(cycl) and evaluation of the resulting analogs using an assay of human cell infections by JC polyomavirus. We defined structure-activity relationships and also discovered analogs with significantly improved potency as suppressors of human polyoma- and papillomavirus infection in vitro. Our findings represent an advance in the development of drug candidates that can broadly protect humans from non-enveloped DNA viruses and toxins that exploit retrograde trafficking as a means for cell entry.