(E)-N-hydroxy-4-(2-styrylthiazol-4-yl)butanamide

• 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: (E)-N-hydroxy-4-(2-styrylthiazol-4-yl)butanamide
• 英文别名: N-hydroxy-4-[2-[(E)-2-phenylethenyl]-1,3-thiazol-4-yl]butanamide
• 化学式: C₁₅H₁₆N₂O₂S
• 分子量: 288.37
• InChiKey: HJPIJALRLZVGMS-MDZDMXLPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  90.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  反-肉桂酰胺 在 吡啶 、 tetraphosphorus decasulfide 、 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 生成 (E)-N-hydroxy-4-(2-styrylthiazol-4-yl)butanamide
  参考文献：
  名称：

  Computer-aided identification of new histone deacetylase 6 selective inhibitor with anti-sepsis activity

  摘要：

  Histone deacetylase (HDAC) inhibitors have been recognized as promising approaches to the treatment of various human diseases including cancer, inflammation, neurodegenerative diseases, and metabolic disorders. Several pan-HDAC inhibitors are currently approved only as anticancer drugs. Interestingly, SAHA (vorinostat), one of clinically available pan-HDAC inhibitors, shows an anti-inflammatory effect at concentrations lower than those required for inhibition of tumor cell growth. It was also reported that HDAC6 selective inhibitor tubastatin A has anti-inflammatory and anti-rheumatic effect. In our efforts to develop novel HDAC inhibitors, we rationally designed various HDAC inhibitors based on the structures of two hit compounds identified by virtual screening of chemical database. Among them, 9a ((E)-N-hydroxy-4-(2-styrylthiazol-4-yl)butanamide) was identified as a HDAC6 selective inhibitor (IC50 values of 0.199 mu M for HDAC6 versus 13.8 mu M for HDAC1), and it did not show significant cytotoxicity against HeLa cells. In vivo biological evaluation of 9a was conducted on a lipopolysaccharide (LPS)-induced mouse model of sepsis. The compound 9a significantly improved 40% survival rate (P = 0.0483), and suppressed the LPS-induced increase of TNF-alpha and IL-6 mRNA expression in the liver of mice. Our study identified novel HDAC6 selective inhibitor 9a, which may serve as a potential lead for the development of anti-inflammatory or anti-sepsis agents. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.03.046

文献信息

• [EN] PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING SEPSIS<br/>[FR] COMPOSITION POUR LA PRÉVENTION OU LE TRAITEMENT DE LA SEPSIE<br/>[KO] 패혈증 예방 또는 치료용 약학적 조성물
  申请人：UNIV SUNGKYUNKWAN RES & BUS

  公开号：WO2015190700A1

  公开（公告）日：2015-12-17

  본 발명은, 히스톤 디아세틸라아제(HDAC) 저해제를 유효성분으로 함유하는, 염증성 질환의 예방 또는 치료용 약학적 조성물에 관한 것으로, 보다 구체적으로, 본 발명은 (E)-N-히드록시-4-(2-스티릴티아졸-4-일)부탄아미드, N-(4-플루오로페네틸)-2-(2-(5-메틸-1H-피라졸-3-카복사미도)에틸)티아졸-4-카복사미드 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 함유하는, 패혈증 및 패혈성 쇼크의 예방 또는 치료용 약학적 조성물에 관한 것이다. 본 발명에 의하면, 부작용이 거의 없고 패혈증 치료 효과가 뛰어난 신규 HDAC 저해제 화합물을 제공할 수 있다.
• Computer-aided identification of new histone deacetylase 6 selective inhibitor with anti-sepsis activity
  作者：Jakyung Yoo、So-Jin Kim、Dohyun Son、Heewon Seo、Seung Yeop Baek、Cheol-Young Maeng、Changsik Lee、In Su Kim、Young Hoon Jung、Sun-Mee Lee、Hyun-Ju Park

  DOI：10.1016/j.ejmech.2016.03.046

  日期：2016.6

  Histone deacetylase (HDAC) inhibitors have been recognized as promising approaches to the treatment of various human diseases including cancer, inflammation, neurodegenerative diseases, and metabolic disorders. Several pan-HDAC inhibitors are currently approved only as anticancer drugs. Interestingly, SAHA (vorinostat), one of clinically available pan-HDAC inhibitors, shows an anti-inflammatory effect at concentrations lower than those required for inhibition of tumor cell growth. It was also reported that HDAC6 selective inhibitor tubastatin A has anti-inflammatory and anti-rheumatic effect. In our efforts to develop novel HDAC inhibitors, we rationally designed various HDAC inhibitors based on the structures of two hit compounds identified by virtual screening of chemical database. Among them, 9a ((E)-N-hydroxy-4-(2-styrylthiazol-4-yl)butanamide) was identified as a HDAC6 selective inhibitor (IC50 values of 0.199 mu M for HDAC6 versus 13.8 mu M for HDAC1), and it did not show significant cytotoxicity against HeLa cells. In vivo biological evaluation of 9a was conducted on a lipopolysaccharide (LPS)-induced mouse model of sepsis. The compound 9a significantly improved 40% survival rate (P = 0.0483), and suppressed the LPS-induced increase of TNF-alpha and IL-6 mRNA expression in the liver of mice. Our study identified novel HDAC6 selective inhibitor 9a, which may serve as a potential lead for the development of anti-inflammatory or anti-sepsis agents. (C) 2016 Elsevier Masson SAS. All rights reserved.