N-(4-(3-((4-octylphenyl)sulfonamido)phenyl)thiazol-2-yl)acetamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(4-(3-((4-octylphenyl)sulfonamido)phenyl)thiazol-2-yl)acetamide
• 英文别名: N-[4-[3-[(4-octylphenyl)sulfonylamino]phenyl]-1,3-thiazol-2-yl]acetamide
• 化学式: C₂₅H₃₁N₃O₃S₂
• 分子量: 485.671
• InChiKey: AGOFYHZTUBIECV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  33
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  125
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-[4-(3-氨基苯基)-2-噻唑基]乙酰胺 在 copper(l) iodide 、 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 、 苯 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~80.0 ℃ 、100.0 kPa 条件下， 反应 2.0h， 生成 N-(4-(3-((4-octylphenyl)sulfonamido)phenyl)thiazol-2-yl)acetamide
  参考文献：
  名称：

  Structure activity relationship and optimization of N -(3-(2-aminothiazol-4-yl)aryl)benzenesulfonamides as anti-cancer compounds against sensitive and resistant cells

  摘要：

  We recently described a new family of bioactive molecules with interesting anti-cancer activities: the N(4-(3-aminophenyl)thiazol-2-yl)acetamides. The lead compound of the series (1) displays significant anti-proliferative and cytotoxic activities against a panel of cancer cell lines, either sensitive or resistant to standard treatments. This molecule also shows a good pharmacological profile and high in vivo potency towards mice xenografts, without signs of toxicity on the animals. In the present article, we disclose the structure-activity relationships of this lead compound, which have provided clear information about the replacement of the acetamide function and the substitution pattern of the benzenesulfonamide ring. An improved high-yielding synthetic procedure towards these compounds has also been developed. Our drug design resulted in potency enhancement of 1, our new optimized lead compound being 19. These findings are of great interest to further improve this scaffold for the development of future clinical candidates. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.03.054

文献信息

• [EN] SUBSTITUTED HYDROPHOBIC BENZENE SULFONAMIDE THIAZOLE COMPOUNDS FOR USE IN TREATING CANCER<br/>[FR] COMPOSÉS DE THIAZOLE SULFONAMIDE DE BENZÈNE HYDROPHOBE SUBSTITUÉ UTILISABLES DANS LE TRAITEMENT DU CANCER
  申请人：INSERM (INSTITUT NAT DE LA SANTÉ ET DE LA RECH MÉDICALE)

  公开号：WO2017017004A1

  公开（公告）日：2017-02-02

  The present invention relates to compound of general formula (I) R1 is selected from H, aryl and alkyl, R2 is selected from H, alkyl, aryl and CO-R6; R3 is selected from H, halogen, alkyl, alkenyl, alkynyl, aryl, NHR7, NR7R8, OR7 and SR7; R4 is selected from(C6-C12) alkyl, (C2-C12) alkenyl, (C2-C12) alkynyl and (C6-C10) aryl, R5 represents H, R6, aryl, OH, OR6, O-aryl, SH, SR6, S-aryl, CN, NO2, CF3, COOR6, SO2NR6R7, CONR6R7, NH2, NHR6, NH-aryl, NR6R7, NHCOR6 or aminoacyl; R6 is alkyl optionally substituted with halogen, OH, SH, NH2, O-alkyl, S-alkyl, NH- alkyl or NH-di(alkyl); R7 and R8 identical or different are H or alkyl optionally substituted with halogen, OH, SH, NH2, O-alkyl, S-alkyl, NH-alkyl or NH-di (alkyl), their pharmaceutically acceptable salts and/or isomers, tautomers, solvates or isotopic variations thereof. The compounds are useful for the treatment of cancers.

  本发明涉及通式（I）的化合物，其中R1可选自H、芳基和烷基，R2可选自H、烷基、芳基和CO-R6；R3可选自H、卤素、烷基、烯基、炔基、芳基、NHR7、NR7R8、OR7和SR7；R4可选自（C6-C12）烷基、（C2-C12）烯基、（C2-C12）炔基和（C6-C10）芳基，R5代表H、R6、芳基、OH、OR6、O-芳基、SH、SR6、S-芳基、CN、NO2、CF3、COOR6、SO2NR6R7、CONR6R7、NH2、NHR6、NH-芳基、NR6R7、NHCOR6或氨基酰基；R6是烷基，可选地取代卤素、OH、SH、NH2、O-烷基、S-烷基、NH-烷基或NH-二（烷基）；R7和R8相同或不同，是H或可选地取代卤素、OH、SH、NH2、O-烷基、S-烷基、NH-烷基或NH-二（烷基）的烷基，其药用可接受的盐和/或同分异构体、互变异构体、溶剂合物或同位素变体。这些化合物对治疗癌症有用。
• Substituted hydrophobic benzene sulfonamide thiazole compounds for use in treating cancer
  申请人：INSERM (Institut National de la Sante et de la Recherche Medicale)

  公开号：US10815207B2

  公开（公告）日：2020-10-27

  The present invention relates to compound of general formula (I) R1 is selected from H, aryl and alkyl, R2 is selected from H, alkyl, aryl and CO—R6; R3 is selected from H, halogen, alkyl, alkenyl, alkynyl, aryl, NHR7, NR7R8, OR7 and SR7; R4 is selected from (C6-C12) alkyl, (C2-C12) alkenyl, (C2-C12) alkynyl and (C6-C10) aryl, R5 represents H, R6, aryl, OH, OR6, O-aryl, SH, SR6, S-aryl, CN, NO2, CF3, COOR6, SO2NR6R7, CONR6R7, NH2, NHR6, NH-aryl, NR6R7, NHCOR6 or aminoacyl; R6 is alkyl optionally substituted with halogen, OH, SH, NH2, O-alkyl, S-alkyl, NH-alkyl or NH-di(alkyl); R7 and R8 identical or different are H or alkyl optionally substituted with halogen, OH, SH, NH2, O-alkyl, S-alkyl, NH-alkyl or NH-di (alkyl), their pharmaceutically acceptable salts and/or isomers, tautomers, solvates or isotopic variations thereof. The compounds are useful for the treatment of cancers.

  本发明涉及通式(I)的化合物 R1选自H、芳基和烷基，R2选自H、烷基、芳基和CO-R6；R3选自H、卤素、烷基、烯基、炔基、芳基、NHR7、NR7R8、OR7和SR7；R4 选自 (C6-C12)烷基、(C2-C12)烯基、(C2-C12)炔基和 (C6-C10)芳基，R5 代表 H、R6、芳基、OH、OR6、O-芳基、SH、SR6、S-芳基、CN、NO2、CF3、COOR6、SO2NR6R7、CONR6R7、NH2、NHR6、NH-芳基、NR6R7、NHCOR6 或氨基酰基；R6 是任选被卤素、OH、SH、NH2、O-烷基、S-烷基、NH-烷基或 NH-二（烷基）取代的烷基；R7 和 R8 相同或不同，是 H 或任选被卤素、OH、SH、NH2、O-烷基、S-烷基、NH-烷基或 NH-二（烷基）取代的烷基、它们的药学上可接受的盐和/或其异构体、同分异构体、溶解物或同位素变体。这些化合物可用于治疗癌症。
• SUBSTITUTED HYDROPHOBIC BENZENE SULFONAMIDE THIAZOLE COMPOUNDS FOR USE IN TREATING CANCER
  申请人：INSERM (Institut National de la Santé et de la Recherche Médicale)

  公开号：EP3325452A1

  公开（公告）日：2018-05-30
• Substituted Hydrophobic Benzene Sulfonamide Thiazole Compounds for Use in Treating Cancer
  申请人：INSERM (Institut National de la Sante et de la Recherche Medicale)

  公开号：US20180215723A1

  公开（公告）日：2018-08-02

  The present invention relates to compound of general formula (I) R 1 is selected from H, aryl and alkyl, R 2 is selected from H, alkyl, aryl and CO—R 6 ; R 3 is selected from H, halogen, alkyl, alkenyl, alkynyl, aryl, NHR 7 , NR 7 R 8 , OR 7 and SR 7 ; R 4 is selected from (C 6 -C 12 ) alkyl, (C 2 -C 12 ) alkenyl, (C 2 -C 12 ) alkynyl and (C 6 -C 10 ) aryl, R 5 represents H, R 6 , aryl, OH, OR 6 , O-aryl, SH, SR 6 , S-aryl, CN, NO 2 , CF 3 , COOR 6 , SO 2 NR 6 R 7 , CONR 6 R 7 , NH 2 , NHR 6 , NH-aryl, NR 6 R 7 , NHCOR 6 or aminoacyl; R 6 is alkyl optionally substituted with halogen, OH, SH, NH 2 , O-alkyl, S-alkyl, NH-alkyl or NH-di(alkyl); R 7 and R 8 identical or different are H or alkyl optionally substituted with halogen, OH, SH, NH 2 , O-alkyl, S-alkyl, NH-alkyl or NH-di (alkyl), their pharmaceutically acceptable salts and/or isomers, tautomers, solvates or isotopic variations thereof. The compounds are useful for the treatment of cancers.
• Structure activity relationship and optimization of N -(3-(2-aminothiazol-4-yl)aryl)benzenesulfonamides as anti-cancer compounds against sensitive and resistant cells
  作者：Cyril Ronco、Antoine Millet、Magali Plaisant、Patricia Abbe、Nedra Hamouda-Tekaya、Stéphane Rocchi、Rachid Benhida

  DOI：10.1016/j.bmcl.2017.03.054

  日期：2017.5

  We recently described a new family of bioactive molecules with interesting anti-cancer activities: the N(4-(3-aminophenyl)thiazol-2-yl)acetamides. The lead compound of the series (1) displays significant anti-proliferative and cytotoxic activities against a panel of cancer cell lines, either sensitive or resistant to standard treatments. This molecule also shows a good pharmacological profile and high in vivo potency towards mice xenografts, without signs of toxicity on the animals. In the present article, we disclose the structure-activity relationships of this lead compound, which have provided clear information about the replacement of the acetamide function and the substitution pattern of the benzenesulfonamide ring. An improved high-yielding synthetic procedure towards these compounds has also been developed. Our drug design resulted in potency enhancement of 1, our new optimized lead compound being 19. These findings are of great interest to further improve this scaffold for the development of future clinical candidates. (C) 2017 Elsevier Ltd. All rights reserved.