2,2,4-trimethyl-1,2-dihydroquinoline-6-yl acetate | 71043-64-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2,2,4-trimethyl-1,2-dihydroquinoline-6-yl acetate
• 英文别名: 6-Acetoxy-1,2-dihydro-2,2,4-trimethylquinolin；1,2-dihydro-2,2,4-trimethylquinolin-6-yl acetate；6-acetoxy-2,2,4-trimethyl-1,2-dihydro-quinoline；(2,2,4-trimethyl-1H-quinolin-6-yl) acetate
• CAS: 71043-64-6
• 化学式: C₁₄H₁₇NO₂
• mdl: MFCD00689688
• 分子量: 231.294
• InChiKey: PDPJYLYRJOHRGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  2,2,4-trimethyl-1,2-dihydroquinoline-6-yl acetate 、 碘甲烷 在 三乙胺 作用下， 以 甲苯 为溶剂， 以84%的产率得到1-acetyl-1,2-dihydro-1,2,2,4-tetramethylquinolin-6-yl acetate
  参考文献：
  名称：

  Antitrypanosomal Activity of 1,2-Dihydroquinolin-6-ols and Their Ester Derivatives

  摘要：

  The current chemotherapy for second stage human African trypanosomiasis is unsatisfactory. A synthetic optimization study based on the lead antitrypanosomal compound 1,2-dihydro-2,2,4-trimethylquinolin-6-yl 3,5-dimethoxybenzoate (TDR20364, 1a) was undertaken in an attempt to discover new trypanocides with potent in vivo activity. While 6-ether derivatives were less active than the lead compound, several N1-substituted derivatives displayed nanomolar IC50 values against T. b. rhodesiense STIB900 in vitro, with selectivity indexes up to > 18000. 1-Benzyl-1, 2-dlhydro-2,2,4-trimethylquinolin-6-yl acetate (10a) displayed an IC50 value of 0.014 mu M against these parasites and a selectivity index or 1700. Intraperitoneal administration of 10a at 50 (mg/kg)/day for 4 days caused a promising prolongation of lifespan in T. b. brucei STIB795-infected mice (> 14 days vs 7.75 days for untreated controls). Reactive oxygen species were produced when T. b. brucei were exposed to 10a in vitro, implicating oxidative stress in the trypanocidal mode of action of these 1,2-dihydroquinoline derivatives.

  DOI：

  10.1021/jm900723w
• 作为产物：
  描述：

  2,2,4-三甲基-1,2-二氢-喹啉-6-醇 、 乙酰氯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 2,2,4-trimethyl-1,2-dihydroquinoline-6-yl acetate
  参考文献：
  名称：

  Antitrypanosomal Activity of 1,2-Dihydroquinolin-6-ols and Their Ester Derivatives

  摘要：

  The current chemotherapy for second stage human African trypanosomiasis is unsatisfactory. A synthetic optimization study based on the lead antitrypanosomal compound 1,2-dihydro-2,2,4-trimethylquinolin-6-yl 3,5-dimethoxybenzoate (TDR20364, 1a) was undertaken in an attempt to discover new trypanocides with potent in vivo activity. While 6-ether derivatives were less active than the lead compound, several N1-substituted derivatives displayed nanomolar IC50 values against T. b. rhodesiense STIB900 in vitro, with selectivity indexes up to > 18000. 1-Benzyl-1, 2-dlhydro-2,2,4-trimethylquinolin-6-yl acetate (10a) displayed an IC50 value of 0.014 mu M against these parasites and a selectivity index or 1700. Intraperitoneal administration of 10a at 50 (mg/kg)/day for 4 days caused a promising prolongation of lifespan in T. b. brucei STIB795-infected mice (> 14 days vs 7.75 days for untreated controls). Reactive oxygen species were produced when T. b. brucei were exposed to 10a in vitro, implicating oxidative stress in the trypanocidal mode of action of these 1,2-dihydroquinoline derivatives.

  DOI：

  10.1021/jm900723w

文献信息

• Compounds for treating peripheral; neuropathies and other neurodegenerative; disorders
  申请人：Hoke Ahmet

  公开号：US09527817B2

  公开（公告）日：2016-12-27

  Compounds and methods for treating or preventing a neurodegenerative disease, disorder or condition associated with the overall activity of hsp90 but not with the ATPase activity of hsp90, including peripheral neuropathy, such as peripheral neuropathy caused by chemotherapy or diabetes, disorders 5 of the central nervous system, such as Alzheimer's disease and Parkinsons disease, and motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), in a subject are provided.

  本发明提供了用于治疗或预防与hsp90总体活性相关但与hsp90的ATP酶活性无关的神经退行性疾病、紊乱或病症的化合物和方法，包括周围神经病变，例如由化疗或糖尿病引起的周围神经病变，中枢神经系统的紊乱，例如阿尔茨海默病和帕金森病，以及运动神经元疾病，例如肌萎缩性侧索硬化症（ALS），在受试者中。
• COMPOUNDS FOR TREATING PERIPHERAL; NEUROPATHIES AND OTHER NEURODEGENERATIVE; DISORDERS
  申请人：Hoke Ahmet

  公开号：US20140303203A1

  公开（公告）日：2014-10-09

  Compounds and methods for treating or preventing a neurodegenerative disease, disorder or condition associated with the overall activity of hsp90 but not with the ATPase activity of hsp90, including peripheral neuropathy, such as peripheral neuropathy caused by chemotherapy or diabetes, disorders 5 of the central nervous system, such as Alzheimer's disease and Parkinsons disease, and motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), in a subject are provided.
• US9527817B2
  申请人：——

  公开号：US9527817B2

  公开（公告）日：2016-12-27
• [EN] COMPOUNDS FOR TREATING PERIPHERAL NEUROPATHIES AND OTHER NEURODEGENERATIVE DISORDERS<br/>[FR] COMPOSÉS POUR LE TRAITEMENT DE NEUROPATHIES PÉRIPHÉRIQUES ET D'AUTRES TROUBLES NEURODÉGÉNÉRATIFS
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2012177831A2

  公开（公告）日：2012-12-27

  Compounds and methods for treating or preventing a neurodegenerative disease, disorder or condition associated with the overall activity of hsp90 but not with the ATPase activity of hsp90, including peripheral neuropathy, such as peripheral neuropathy caused by chemotherapy or diabetes, disorders 5 of the central nervous system, such as Alzheimer's disease and Parkinsons disease, and motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), in a subject are provided.
• Antitrypanosomal Activity of 1,2-Dihydroquinolin-6-ols and Their Ester Derivatives
  作者：Jean Fotie、Marcel Kaiser、Dawn A. Delfín、Joshua Manley、Carolyn S. Reid、Jean-Marc Paris、Tanja Wenzler、Louis Maes、Kiran V. Mahasenan、Chenglong Li、Karl A. Werbovetz

  DOI：10.1021/jm900723w

  日期：2010.2.11

  The current chemotherapy for second stage human African trypanosomiasis is unsatisfactory. A synthetic optimization study based on the lead antitrypanosomal compound 1,2-dihydro-2,2,4-trimethylquinolin-6-yl 3,5-dimethoxybenzoate (TDR20364, 1a) was undertaken in an attempt to discover new trypanocides with potent in vivo activity. While 6-ether derivatives were less active than the lead compound, several N1-substituted derivatives displayed nanomolar IC50 values against T. b. rhodesiense STIB900 in vitro, with selectivity indexes up to > 18000. 1-Benzyl-1, 2-dlhydro-2,2,4-trimethylquinolin-6-yl acetate (10a) displayed an IC50 value of 0.014 mu M against these parasites and a selectivity index or 1700. Intraperitoneal administration of 10a at 50 (mg/kg)/day for 4 days caused a promising prolongation of lifespan in T. b. brucei STIB795-infected mice (> 14 days vs 7.75 days for untreated controls). Reactive oxygen species were produced when T. b. brucei were exposed to 10a in vitro, implicating oxidative stress in the trypanocidal mode of action of these 1,2-dihydroquinoline derivatives.