3-(1H-benzimidazol-2-ylthio)-5,5-dimethyl-3-(1-oxopropyl)-2-oxolanone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 3-(1H-benzimidazol-2-ylthio)-5,5-dimethyl-3-(1-oxopropyl)-2-oxolanone
• 英文别名: 3-(1H-benzimidazol-2-ylsulfanyl)-5,5-dimethyl-3-propanoyloxolan-2-one
• 化学式: C₁₆H₁₈N₂O₃S
• 分子量: 318.4
• InChiKey: QBYZXABEUVABIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  97.4
• 氢给体数：
  1
• 氢受体数：
  5

文献信息

• ACTIVATORS OF CLASS 1 HISTONE DEACETYLASES (HDACS) AND USES THEREOF
  申请人：Massachusetts Institute Of Technology

  公开号：EP3483150A1

  公开（公告）日：2019-05-15

  The present invention provides compounds of Formulae (A), (B), (C), and (D), pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof, pharmaceutical compositions thereof, and kits thereof. The present invention further provides methods of using the compounds to treat or prevent neurological disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, ALS (amyotrophic lateral sclerosis), traumatic brain injury, ischemic brain injury, stroke, frontal temporal dementia, Pick's disease, corticobasal degeneration, supra cerebral palsy, prion diseases (e.g., Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome, Fatal Familial Insomnia, and Kuru), Nieman Pick type C, spinal cerebellar ataxia, spinal muscular dystrophy, ataxia telangiectasia, hippocampal sclerosis, Cockayne syndrome, Werner syndrome, xeroderma pigmentosaum, and Bloom syndrome. In one aspect, the methods include administering to a subject in need of treatment for a neurological disorder a therapeutically effective amount of DAC-001, DAC-002, DAC-003, DAC-009, or DAC-012, or a compound of Formula (A), (B), (C), or (D).

  本发明提供了式(A)、(B)、(C)和(D)化合物、其药学上可接受的盐、溶液剂、水合物、多晶型、共晶体、同分异构体、立体异构体、同位素标记的衍生物和原药、其药物组合物及其试剂盒。本发明进一步提供了使用这些化合物治疗或预防神经系统疾病的方法，这些疾病包括阿尔茨海默病、帕金森病、亨廷顿病、肌萎缩侧索硬化症（ALS）、创伤性脑损伤、缺血性脑损伤、中风、额颞叶痴呆症、皮克病、皮质基底变性、上脑瘫、朊病毒病（如、C型、脊髓小脑共济失调、脊髓性肌萎缩症、共济失调毛细血管扩张症、海马硬化症、科凯恩综合征、维尔纳综合征、色素性角化症和布卢姆综合征。在一个方面，所述方法包括向需要治疗神经系统疾病的受试者施用治疗有效量的 DAC-001、DAC-002、DAC-003、DAC-009 或 DAC-012 或式 (A)、(B)、(C) 或 (D) 的化合物。
• Activators of class I histone deacetlyases (HDACs) and uses thereof
  申请人：Massachusetts Institute of Technology

  公开号：US10167277B2

  公开（公告）日：2019-01-01

  The present invention provides compounds of Formulae (A), (B), (C), and (D), pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof, pharmaceutical compositions thereof, and kits thereof. The present invention further provides methods of using the compounds to treat or prevent neurological disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, ALS (amyotrophic lateral sclerosis), traumatic brain injury, ischemic brain injury, stroke, frontal temporal dementia, Pick's disease, corticobasal degeneration, supra cerebral palsy, prion diseases (e.g., Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome, Fatal Familial Insomnia, and Kuru), Nieman Pick type C, spinal cerebellar ataxia, spinal muscular dystrophy, ataxia telangiectasia, hippocampal sclerosis, Cockayne syndrome, Werner syndrome, xeroderma pigmentosaum, and Bloom syndrome. In one aspect, the methods include administering to a subject in need of treatment for a neurological disorder a therapeutically effective amount of DAC-001, DAC-002, DAC-003, DAC-009, or DAC-012, or a compound of Formula (A), (B), (C), or (D).

  本发明提供了式(A)、(B)、(C)和(D)化合物、其药学上可接受的盐、溶液剂、水合物、多晶型、共晶体、同分异构体、立体异构体、同位素标记的衍生物和原药、其药物组合物及其试剂盒。本发明进一步提供了使用这些化合物治疗或预防神经系统疾病的方法，这些疾病包括阿尔茨海默病、帕金森病、亨廷顿病、肌萎缩侧索硬化症（ALS）、创伤性脑损伤、缺血性脑损伤、中风、额颞叶痴呆症、皮克病、皮质基底变性、上脑瘫、朊病毒病（如、C型、脊髓小脑共济失调、脊髓性肌萎缩症、共济失调毛细血管扩张症、海马硬化症、科凯恩综合征、维尔纳综合征、色素性角化症和布卢姆综合征。在一个方面，所述方法包括向需要治疗神经系统疾病的受试者施用治疗有效量的 DAC-001、DAC-002、DAC-003、DAC-009 或 DAC-012 或式 (A)、(B)、(C) 或 (D) 的化合物。
• Activators of class I histone deacetylases (HDACs) and uses thereof
  申请人：Massachusetts Institute of Technology

  公开号：US11084803B2

  公开（公告）日：2021-08-10

  The present invention provides compounds of Formulae (A), (B), (C), and (D), pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof, pharmaceutical compositions thereof, and kits thereof. The present invention further provides methods of using the compounds to treat or prevent neurological disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, ALS (amyotrophic lateral sclerosis), traumatic brain injury, ischemic brain injury, stroke, frontal temporal dementia, Pick's disease, corticobasal degeneration, supra cerebral palsy, prion diseases (e.g., Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome, Fatal Familial Insomnia, and Kuru), Nieman Pick type C, spinal cerebellar ataxia, spinal muscular dystrophy, ataxia telangiectasia, hippocampal sclerosis, Cockayne syndrome, Werner syndrome, xeroderma pigmentosaum, and Bloom syndrome. In one aspect, the methods include administering to a subject in need of treatment for a neurological disorder a therapeutically effective amount of DAC-001, DAC-002, DAC-003, DAC-009, or DAC-012, or a compound of Formula (A), (B), (C), or (D).

  本发明提供了式(A)、(B)、(C)和(D)化合物、其药学上可接受的盐、溶液剂、水合物、多晶型、共晶体、同分异构体、立体异构体、同位素标记的衍生物和原药、其药物组合物及其试剂盒。本发明进一步提供了使用这些化合物治疗或预防神经系统疾病的方法，这些疾病包括阿尔茨海默病、帕金森病、亨廷顿病、肌萎缩侧索硬化症（ALS）、创伤性脑损伤、缺血性脑损伤、中风、额颞叶痴呆症、皮克病、皮质基底变性、上脑瘫、朊病毒病（如、C型、脊髓小脑共济失调、脊髓性肌萎缩症、共济失调毛细血管扩张症、海马硬化症、科凯恩综合征、维尔纳综合征、色素性角化症和布卢姆综合征。在一个方面，所述方法包括向需要治疗神经系统疾病的受试者施用治疗有效量的 DAC-001、DAC-002、DAC-003、DAC-009 或 DAC-012 或式 (A)、(B)、(C) 或 (D) 的化合物。
• ACTIVATORS OF CLASS I HISTONE DEACETLYASES (HDACS) AND USES THEREOF
  申请人：Tsai Li-Huei

  公开号：US20130096129A1

  公开（公告）日：2013-04-18

  The present invention provides compounds of Formulae (A), (B), (C), and (D), pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof, pharmaceutical compositions thereof, and kits thereof. The present invention further provides methods of using the compounds to treat or prevent neurological disorders. In one aspect, the methods include administering to a subject in need of treatment for a neurological disorder a therapeutically effective amount of DAC-001, DAC-002, DAC-003, DAC-009, or DAC-012, or a compound of Formula (A), (B), (C), or (D).
• ACTIVATORS OF CLASS I HISTONE DEACETYLASES (HDACS) AND USES THEREOF
  申请人：Massachusetts Institute of Technology

  公开号：US20190211000A1

  公开（公告）日：2019-07-11

  The present invention provides compounds of Formulae (A), (B), (C), and (D), pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof, pharmaceutical compositions thereof, and kits thereof. The present invention further provides methods of using the compounds to treat or prevent neurological disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, ALS (amyotrophic lateral sclerosis), traumatic brain injury, ischemic brain injury, stroke, frontal temporal dementia, Pick's disease, corticobasal degeneration, supra cerebral palsy, prion diseases (e.g., Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome, Fatal Familial Insomnia, and Kuru), Nieman Pick type C, spinal cerebellar ataxia, spinal muscular dystrophy, ataxia telangiectasia, hippocampal sclerosis, Cockayne syndrome, Werner syndrome, xeroderma pigmentosaum, and Bloom syndrome. In one aspect, the methods include administering to a subject in need of treatment for a neurological disorder a therapeutically effective amount of DAC-001, DAC-002, DAC-003, DAC-009, or DAC-012, or a compound of Formula (A), (B), (C), or (D).