3,5-dichloro-N-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]benzenesulfonamide | 1261277-13-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3,5-dichloro-N-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]benzenesulfonamide
• CAS: 1261277-13-7
• 化学式: C₁₇H₁₅Cl₂N₃O₃S
• 分子量: 412.296
• InChiKey: VOQGFUMSCUTNRR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  81.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3,5-二氯苯磺酰氯 、 3-甲氧基-4-(4-甲基-1H-咪唑-1-基)苯胺 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 21.0h， 生成 3,5-dichloro-N-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]benzenesulfonamide
  参考文献：
  名称：

  Discovery of 2-methylpyridine-based biaryl amides as γ-secretase modulators for the treatment of Alzheimer’s disease

  摘要：

  gamma-Secretase modulators (GSMs) are potentially disease-modifying treatments for Alzheimer's disease. They selectively lower pathogenic A beta 42 levels by shifting the enzyme cleavage sites without inhibiting gamma-secretase activity, possibly avoiding known adverse effects observed with complete inhibition of the enzyme complex. A cell-based HTS effort identified the sulfonamide 1 as a GSM lead. Lead optimization studies identified compound 25 with improved cell potency, PKDM properties, and it lowered A beta 42 levels in the cerebrospinal fluid ( CSF) of Sprague-Dawley rats following oral administration. Further optimization of 25 to improve cellular potency is described. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.09.041

文献信息

• PHARMACEUTICAL PRODUCT CONTAINING LACTAM OR BENZENE SULFONAMIDE COMPOUND
  申请人：Shionogi & Co., Ltd.

  公开号：EP2455370A1

  公开（公告）日：2012-05-23

  The present invention provides, for example, the following compounds as a pharmaceutical composition for treating diseases induced by production, secretion or deposition of amyloid β proteins. The present invention provides a pharmaceutical composition for suppressing amyloid β production comprising a compound of the formula: wherein A is a benzene ring, a pyridine ring or a pyrimidine ring, X is sultam, lactam, sulfonamide or the like, C is substituted or unsubstituted imidazolyl, substituted or unsubstituted oxazolyl or the like, R2, R3 and R4 are each independently hydrogen, halogen, hydroxy, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy or the like, its pharmaceutically acceptable salt or a solvate thereof.

  本发明提供了以下化合物作为治疗由淀粉样蛋白产生、分泌或沉积引起的疾病的药物组合物。本发明提供了一种用于抑制淀粉样蛋白产生的药物组合物，其包括以下化合物：其中A为苯环、吡啶环或嘧啶环，X为磺胺、内酰胺、磺酰胺等，C为取代或未取代的咪唑基、取代或未取代的噁唑基等，R2、R3和R4分别独立地为氢、卤素、羟基、羧基、取代或未取代的烷基、取代或未取代的烷氧基等，其药学上可接受的盐或溶剂化合物。
• PHARMACEUTICAL COMPOSITION COMPRISING A LACTAM OR BENZENESULFONAMIDE COMPOUND
  申请人：Kato Issei

  公开号：US20120135997A1

  公开（公告）日：2012-05-31

  The present invention provides, for example, the following compounds as a pharmaceutical composition for treating diseases induced by production, secretion or deposition of amyloid β proteins. The present invention provides a pharmaceutical composition for suppressing amyloid β production comprising a compound of the formula: wherein A is a benzene ring, a pyridine ring or a pyrimidine ring, X is sultam, lactam, sulfonamide or the like, C is substituted or unsubstituted imidazolyl, substituted or unsubstituted oxazolyl or the like, R 2 , R 3 and R 4 are each independently hydrogen, halogen, hydroxy, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy or the like, its pharmaceutically acceptable salt or a solvate thereof.
• [EN] PHARMACEUTICAL PRODUCT CONTAINING LACTAM OR BENZENE SULFONAMIDE COMPOUND<br/>[FR] PRODUIT PHARMACEUTIQUE CONTENANT UN COMPOSÉ LACTAME OU BENZÈNE SULFONAMIDE
  申请人：SHIONOGI & CO

  公开号：WO2011007819A1

  公开（公告）日：2011-01-20

  アミロイドβタンパク質の産生、分泌または沈着により誘発される疾患の治療剤として、例えば以下の化合物を提供する。（式中、Ａはベンゼン環、ピリジン環またはピリミジン環であり、 Ｘはスルタム、ラクタム、スルホンアミド等であり、 Ｃは置換もしくは非置換のイミダゾリル、置換もしくは非置換のオキサゾリル等であり、 Ｒ２、Ｒ３およびＲ４は各々独立して水素、ハロゲン、ヒドロキシ、カルボキシ、置換もしくは非置換のアルキル、置換もしくは非置換のアルコキシ等である。） で示される化合物、もしくはその製薬上許容される塩またはそれらの溶媒和物を含有するアミロイドβ産生抑制用医薬組成物を提供する。
• Discovery of 2-methylpyridine-based biaryl amides as γ-secretase modulators for the treatment of Alzheimer’s disease
  作者：Jian Jeffrey Chen、Wenyuan Qian、Kaustav Biswas、Chester Yuan、Albert Amegadzie、Qingyian Liu、Thomas Nixey、Joe Zhu、Mqhele Ncube、Robert M. Rzasa、Frank Chavez、Ning Chen、Frenel DeMorin、Shannon Rumfelt、Christopher M. Tegley、Jennifer R. Allen、Stephen Hitchcock、Randy Hungate、Michael D. Bartberger、Leeanne Zalameda、Yichin Liu、John D. McCarter、Jianhua Zhang、Li Zhu、Safura Babu-Khan、Yi Luo、Jodi Bradley、Paul H. Wen、Darren L. Reid、Frank Koegler、Charles Dean、Dean Hickman、Tiffany L. Correll、Toni Williamson、Stephen Wood

  DOI：10.1016/j.bmcl.2013.09.041

  日期：2013.12

  gamma-Secretase modulators (GSMs) are potentially disease-modifying treatments for Alzheimer's disease. They selectively lower pathogenic A beta 42 levels by shifting the enzyme cleavage sites without inhibiting gamma-secretase activity, possibly avoiding known adverse effects observed with complete inhibition of the enzyme complex. A cell-based HTS effort identified the sulfonamide 1 as a GSM lead. Lead optimization studies identified compound 25 with improved cell potency, PKDM properties, and it lowered A beta 42 levels in the cerebrospinal fluid ( CSF) of Sprague-Dawley rats following oral administration. Further optimization of 25 to improve cellular potency is described. (C) 2013 Elsevier Ltd. All rights reserved.