LK-935 | 648930-55-6

• 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: LK-935
• 英文别名: 2-{[2-(3,4-dichlorophenyl)ethyl]propylamino}-1-pyridin-3-ylethanol；2-((3,4-dichlorophenethyl)(propyl)amino)-1-(pyridin-3-yl)ethanol；1-(3-pyridyl)-2-(N-(2-(3,4-dichlorophenyl)ethyl)-N-propylamino)ethanol；2-[2-(3,4-Dichlorophenyl)ethyl-propylamino]-1-pyridin-3-ylethanol
• CAS: 648930-55-6
• 化学式: C₁₈H₂₂Cl₂N₂O
• 分子量: 353.291
• InChiKey: SDOVHKUEMQAISV-UHFFFAOYSA-N

物化性质

• 沸点：
  493.1±45.0 °C(Predicted)
• 密度：
  1.226±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  36.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  LK-935 在 氢溴酸 作用下， 以 乙醚 、 乙醇 、 丙酮 为溶剂， 反应 2.0h， 以85%的产率得到2-{[2-(3,4-dichlorophenyl)ethyl]propylamino}-1-pyridin-3-ylethanol dihydrobromide
  参考文献：
  名称：

  [EN] NOVEL DERIVATIVES OF PYRIDYLETHANOL (PHENYLETHYL) AMINES AS INHIBITORS OF CHOLESTEROL BIOSYNTHESIS, PROCESSES FOR THEIR PREPARATION, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
  [FR] NOUVEAUX DERIVES D'AMINES PYRIDYLETHANOL (PHENYLETHYL) UTILES COMME INHIBITEURS DE LA BIOSYNTHESE DU CHOLESTEROL, LEURS PROCEDES DE PREPARATION ET COMPOSITIONS PHARMACEUTIQUES LES CONTENANT

  摘要：

  描述了式I的吡啶乙醇（苯乙基）胺的新颖衍生物，其中n是1到4的整数，R1是氢原子、羟基或较低的C1-6烷氧基团，R2是氢原子或直链或支链的较低的C1-6烷基团，X是氢、氟、氯、溴、羟基、三氟甲基、3,4-二氯、2,4-二氯或较低的C1-6烷氧基团，其对映体、二对映异构体或混合物或其生理上可接受的酸盐是sigma受体的配体，用于抑制胆固醇生物合成，因此适用于治疗人类高胆固醇血症和高脂血症。1-(d-吡啶基)-2-(N-(2-(3,4-二氯苯基)乙基-N-丙基氨基)乙醇在二氢溴化物盐形式中观察到了最大的胆固醇降低作用（签名BK-35.2HBr）。

  公开号：

  WO2004007456A1
• 作为产物：
  描述：

  2-丙氨基-1-吡啶-3-乙醇 在 N-甲基吗啉 、 dimethyl sulfide borane 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 LK-935
  参考文献：
  名称：

  Synthesis, Conformation, and Stereodynamics of a Salt of 2-{[2-(3,4-Dichlorophenyl)- ethyl]propylamino}-1-pyridin-3-ylethanol

  摘要：

  [GRAPHIC]A novel synthetic route was developed for 2-{[2-(3,4-dichlorophenyl)ethyl]propylamino}-1-pyridin-3-yiethanol (4). A dynamic process due to nitrogen inversion at the central amine nitrogen has been identified by NMR spectroscopy for the dihydrobromide salt of this compound. The conformational properties of the diastereomeric pair were determined by analysis of NOE connectivities and MO calculations.

  DOI：

  10.1021/jo051455f

文献信息

• Novel cholesterol biosynthesis inhibitors targeting human lanosterol 14α-demethylase (CYP51)
  作者：Tina Korošec、Jure Ačimovič、Matej Seliškar、Darko Kocjan、Klementina Fon Tacer、Damjana Rozman、Uroš Urleb

  DOI：10.1016/j.bmc.2007.10.001

  日期：2008.1

  Novel cholesterol biosynthesis inhibitors, a group of pyridylethanol(phenylethyl)amine derivatives, were synthesized. Sterol profiling assay in the human hepatoma HepG2 cells revealed that compounds target human lanosterol 14alpha-demethylase (CYP51). Structure-activity relationship study of the binding with the overexpressed human CYP51 indicates that the pyridine binds within the heme binding pocket

  合成了新型胆固醇生物合成抑制剂，一组吡啶基乙醇（苯乙基）胺衍生物。在人肝癌HepG2细胞中的甾醇谱分析表明该化合物靶向人羊毛甾醇14α-脱甲基酶（CYP51）。与过量表达的人CYP51结合的结构-活性关系研究表明，吡啶与唑类类似物在血红素结合口袋中结合。
• Novel derivatives of pyridilethanol (phenylethyl) amines as inhibitors of cholesterol biosynthesis, process for their preparation and pharmaceutical compositions containing them
  申请人：Rode Breda

  公开号：US20050256172A1

  公开（公告）日：2005-11-17

  The novel derivatives of pyridilethanol (phenylethyl) amines of formula I are described wherein n is an integer from 1 to 4, R 1 is a hydrogen atom, hydroxyl group or lower C 1-6 alkoxy group R 2 is a hydrogen atom or a straight or branched lower C 1-6 alkyl group X, is hydrogen, fluorine, chlorine, bromine, hydroxyl group, trifluoromethyl group, 3,4-di-Cl,2,4-di-Cl or lower C 1-6 alkoxy group, the enantiomers, diastereoisomers or racemates thereof or the physiologically acceptable acid addition salts thereof which are ligands of sigma receptors for inhibiting cholesterol biosynthesis and are thus appropriate for the treatment of hypercholesterolemia and hyperlipemia in humans. The greatest lowering of cholesterol was observed by 1-(d-pyridyl)-2-(N-(2-(3,4-dicholorophenyl)ethyl-N-propylamino)ethanol in the form of dihydrobromide salt (signature BK-35, 2HBr).

  本文介绍了式子I中的吡啶乙醇（苯乙基）胺的新衍生物，其中n是1到4的整数，R1是氢原子、羟基或较低的C1-6烷氧基，R2是氢原子或直链或支链较低的C1-6烷基，X是氢、氟、氯、溴、羟基、三氟甲基、3,4-二氯、2,4-二氯或较低的C1-6烷氧基，它们的对映体、非对映异构体或外消旋体或其生理上可接受的酸盐，是sigma受体的配体，用于抑制胆固醇生物合成，因此适用于治疗人体内的高胆固醇血症和高脂血症。在以二氢溴酸盐（签名BK-35，2HBr）形式的1-（d-吡啶基）-2-（N-（2-（3,4-二氯苯基）乙基-N-丙基氨基）乙醇中观察到最大的降低胆固醇。
• COMPOUNDS AND METHODS OF PROMOTING MYELINATION
  申请人：Case Western Reserve University

  公开号：EP3838287A2

  公开（公告）日：2021-06-23

  A method of promoting the generation of oligodendrocytes from oligodendrocyte precursor cells by enhancing their survival and/or maturation includes administering to the cell an effective amount of an agent that enhances and/or induces accumulation of Δ8,9-unsaturated sterol intermediates of the cholesterol biosynthesis pathway in the oligodendrocyte precursor cells.

  一种通过提高少突胶质细胞前体细胞的存活率和/或成熟度来促进少突胶质细胞生成的方法，包括向细胞施用有效量的制剂，该制剂可提高和/或诱导胆固醇生物合成途径的Δ8,9-不饱和固醇中间体在少突胶质细胞前体细胞中的积累。
• Compositions and methods for the treatment and prevention of neurological disorders
  申请人：Yumanity Therapeutics, Inc.

  公开号：US11241417B2

  公开（公告）日：2022-02-08

  The invention provides compositions and methods for treating neurological disorders, such as amyotrophic lateral sclerosis, frontotemporal degeneration, and Alzheimer's disease, among others. Using the compositions and methods described herein, a patient having a neurological disorder, such as a neurological disorder associated with TAR-DNA binding protein (TDP)-43 aggregation, may be administered an inhibitor of cytochrome P450 (CYP450) isoform 51A1 (CYP51A1), also referred to herein as lanosterol 14-alpha demethylase, so as to treat an underlying etiology of the disorder and/or to alleviate one or more symptoms of the disease. The inhibitor of CYP51A1 may be a small molecule, anti-CYP51A1 antibody or antigen-binding fragment thereof, or a compound, such as an interfering RNA molecule, that attenuates CYP51A1 expression. Patients that may be treated using the compositions and methods described herein include those that express a mutant TDP-43 isoform containing a mutation associated with TDP-43-promoted aggregation and toxicity.

  本发明提供了治疗神经系统疾病的组合物和方法，如肌萎缩侧索硬化症、额颞变性和阿尔茨海默病等。使用本文所述的组合物和方法，可以给患有神经系统疾病（如与TAR-DNA结合蛋白（TDP）-43聚集相关的神经系统疾病）的患者施用细胞色素P450（CYP450）同工酶51A1（CYP51A1）的抑制剂，CYP51A1在本文中也称为羊毛甾醇14-α去甲基化酶，从而治疗该疾病的潜在病因和/或减轻该疾病的一种或多种症状。CYP51A1的抑制剂可以是小分子、抗CYP51A1抗体或其抗原结合片段，或者是减弱CYP51A1表达的化合物，如干扰RNA分子。可使用本文所述组合物和方法治疗的患者包括那些表达突变型 TDP-43 同工酶的患者，这种突变与 TDP-43 促进的聚集和毒性有关。
• Compounds and methods of promoting myelination
  申请人：Case Western Reserve University

  公开号：US11344511B2

  公开（公告）日：2022-05-31

  A method of promoting the generation of oligodendrocytes from oligodendrocyte precursor cells by enhancing their survival and/or maturation includes administering to the cell an effective amount of an agent that enhances and/or induces accumulation of Δ8,9-unsaturated sterol intermediates of the cholesterol biosynthesis pathway in the oligodendrocyte precursor cells.

  一种通过提高少突胶质细胞前体细胞的存活率和/或成熟度来促进少突胶质细胞生成的方法，包括向细胞施用有效量的制剂，该制剂可提高和/或诱导胆固醇生物合成途径的Δ8,9-不饱和固醇中间体在少突胶质细胞前体细胞中的积累。