2-(3-benzyloxypropoxy)ethanol | 178872-69-0

• 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: 2-(3-benzyloxypropoxy)ethanol
• 英文别名: 2-(3-(benzyloxy)propoxy)ethan-1-ol；Ethanol, 2-[3-(phenylmethoxy)propoxy]-；2-(3-phenylmethoxypropoxy)ethanol
• CAS: 178872-69-0
• 化学式: C₁₂H₁₈O₃
• 分子量: 210.273
• InChiKey: BSFGWMKHFPAUFE-UHFFFAOYSA-N

物化性质

• 沸点：
  329.6±27.0 °C(Predicted)
• 密度：
  1.059±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  15
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(3-benzyloxypropoxy)ethanol 在 palladium on activated charcoal 氢气 、 silver salicylate 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 34.0h， 生成 methyl {3-[2-(2,3,4-tri-O-acetyl-β-L-fucopyranosyloxy)ethoxy]propyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-α-D-glycero-D-galacto-2-nonulopyranoside}onate
  参考文献：
  名称：

  Synthesis of Sialyl Lewis x Analogues 2

  摘要：

  Sialyl Lewis X (SLe(X) analogues) containing beta-1-fucopyranosyl residues with an alkyl [-(CH2)(6)-] (1a), a heteroalkyl [-(CH2)(2)-O-(CH2)(3)-] (Ib)or a heterocycloalkyl [-2-cyclohexyl-O-(CH,),-] (2a) moiety were synthesised by silver ion promoted glycosylation. Further analogues where sialic acid was replaced by a second beta-L-fucopyranosyl (3a, 3b) or hydrogensulphate unit (4a, 4b) were also prepared.

  DOI：

  10.1080/07328309708006507
• 作为产物：
  描述：

  3-苄氧基-1-丙醇 在 4-二甲氨基吡啶 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 mineral oil 为溶剂， 生成 2-(3-benzyloxypropoxy)ethanol
  参考文献：
  名称：

  XL01126 的发现：一种有效、快速、协同、选择性、口服生物可利用且血脑屏障渗透性的富含亮氨酸重复激酶 2 的 PROTAC 降解剂

  摘要：

  富含亮氨酸重复激酶 2 (LRRK2) 是帕金森病最有希望的靶点之一。 LRRK2 靶向策略主要集中于 1 型激酶抑制剂，但其具有局限性，因为受抑制的蛋白质会干扰自然机制，从而可能导致不良副作用。在此，我们报告了 LRRK2 蛋白水解靶向嵌合体 (PROTAC) 的开发，最终发现了降解剂 XL01126，作为替代 LRRK2 靶向策略。基于 E3 连接酶 von Hippel-Lindau (VHL)、Cereblon (CRBN) 和细胞凋亡抑制剂 (cIAP) 配体的 PROTAC 的初步设计和筛选确定了含有硫醚缀合的 VHL 配体 VH101 的最佳降解剂。第二轮药物化学探索使 XL01126 成为多种细胞系中 LRRK2 的快速有效降解剂，其 DC 50值在 15-72 nM 范围内， D最大值范围在 82% 至 90% 之间，降解半衰期跨越0.6 至 2.4 小时。 XL01126

  DOI：

  10.1021/jacs.2c05499

文献信息

• TAU-PROTEIN TARGETING PROTACS AND ASSOCIATED METHODS OF USE
  申请人：Arvinas, Inc.

  公开号：US20180125821A1

  公开（公告）日：2018-05-10

  The present disclosure relates to bifunctional compounds, which find utility as modulators of tau protein. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tau protein, such that tau protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tau. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tau protein. Diseases or disorders that result from aggregation or accumulation of tau protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，其作为tau蛋白的调节剂具有实用性。具体而言，本公开涉及含有一端结合到E3泛素连接酶的VHL或cereblon配体，另一端结合到tau蛋白的双功能化合物，使得tau蛋白与泛素连接酶靠近，以实现tau蛋白的降解（和抑制）。本公开展示了与tau蛋白降解/抑制相关的广泛药理活性。本公开的化合物和组合物用于治疗或预防由tau蛋白聚集或积累导致的疾病或紊乱。
• [EN] COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF BROMODOMAIN-CONTAINING PROTEINS<br/>[FR] COMPOSÉS ET PROCÉDÉS POUR LA DÉGRADATION CIBLÉE DE PROTÉINES CONTENANT UN BROMODOMAINE
  申请人：ARVINAS INC

  公开号：WO2017030814A1

  公开（公告）日：2017-02-23

  The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of targeted polypeptides.

  本发明涉及双功能化合物，其作为靶向泛素化的调节剂具有实用性，特别是根据本发明抑制各种多肽和其他蛋白质的化合物。具体而言，本发明涉及一端含有结合泛素连接酶的VHL配体，另一端含有结合靶蛋白的基团的化合物，使得靶蛋白靠近泛素连接酶以促使该蛋白的降解（和抑制）。根据本发明的化合物表现出与靶向多肽的降解/抑制一致的广泛的药理活性。
• [EN] INHIBITORS OF CYCLIN-DEPENDENT KINASES AND USES THEREOF<br/>[FR] INHIBITEURS DE KINASES DÉPENDANTES DES CYCLINES ET LEURS UTILISATIONS
  申请人：LES LABORATOIRES SERVIER SAS

  公开号：WO2021155006A1

  公开（公告）日：2021-08-05

  Provided are novel compounds of Formula (I); pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful in the treatment of diseases and disorders mediated by CDK such as cancer.

  提供了式（I）的新化合物；其药用盐，以及药物组合物，可用于治疗由CDK介导的癌症等疾病和疾病。
• [EN] AGENTS FOR USE IN THE TREATMENT OF AMYLOIDOSIS<br/>[FR] AGENTS DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DE L'AMYLOÏDOSE
  申请人：UCL BUSINESS PLC

  公开号：WO2022058733A1

  公开（公告）日：2022-03-24

  The present invention relates to compounds for stabilising the native tetrameric form of transthyretin and protecting it from proteolytic cleavage; compounds for use in the prevention and treatment of transthyretin amyloidosis; and agents and medicaments comprising such compounds. The compounds are based on a general structure A-L-B, wherein A is a group of formula (II) or of formula (III): or of formula (IV) or of formula (V) B is a group of formula (III), (IV), or (V), or a group of formula (VI) or a group of formula –R10Z, wherein: Z is selected from -CO2R', -CONR'R'', -SO2R' wherein R' and R'' are independently H or C1-C4 alkyl; and R10 is a C1-C4 alkylene or alkenylene group; and L represents a linker group which is a saturated or unsaturated chain of 5 to 13 carbon atoms.

  本发明涉及用于稳定甲状腺素前体蛋白的四聚体形式并保护其免受蛋白水解切割的化合物；用于预防和治疗甲状腺素前体蛋白淀粉样变性的化合物；以及包含此类化合物的药剂和药物。这些化合物基于一般结构A-L-B，其中A是公式(II)或公式(III)的基团：或公式(IV)或公式(V) B是公式(III)、(IV)或(V)的基团，或公式(VI)的基团或公式-R10Z的基团，其中：Z从-CO2R'、-CONR'R''、-SO2R'中选择，其中R'和R''分别是H或C1-C4烷基；而R10是C1-C4烷基或烯基基团；L代表一个由5到13个碳原子组成的饱和或不饱和链的连接基团。
• FUSED NITROGEN-COMPRISING HETEROCYCLIC COMPOUND
  申请人：Seto Masaki

  公开号：US20100234351A1

  公开（公告）日：2010-09-16

  A compound of the formula: wherein ring A is a 7-membered or 8-membered nitrogen-containing ring optionally further substituted, ring B is an optionally substituted aryl group or an optionally substituted heteroaryl group, X 1 is a group represented by —NR 3 —Y 1 —, —O—, —S—, —SO—, —SO 2 — or —CHR 3 — wherein R 3 is a hydrogen atom or an optionally substituted aliphatic hydrocarbon group, or R 3 may be bonded to the carbon atom of ring B to form an optionally substituted ring structure, and Y 1 is a bond or an optionally substituted alkylene, R 1 is a hydrogen atom, or an optionally substituted group bonded via a carbon atom or a sulfur atom, the formula shows a single bond or a double bond, when R 2 is —R 2 , R 2 is a hydrogen atom, or an optionally substituted group bonded via a carbon atom, a nitrogen atom, an oxygen atom or a sulfur atom, and when R 2 is ═R 2 , R 2 is an oxo group, an optionally substituted alkylidene group, or an optionally substituted imino group.

  该化合物的化学式为：其中环A是一个7-或8-成员的含氮环，可选择进一步取代，环B是一个可选择取代的芳基或杂芳基，X1是一个由—NR3—Y1—、—O—、—S—、—SO—、—SO2—或—CHR3—表示的基团，其中R3是氢原子或可选择取代的脂肪烃基团，或R3可与环B的碳原子结合形成可选择取代的环结构，Y1是一个键或可选择取代的烷基，R1是氢原子或通过碳原子或硫原子结合的可选择取代的基团，化学式中显示单键或双键，当R2是—R2时，R2是氢原子或通过碳原子结合的可选择取代的基团，氮原子、氧原子或硫原子，当R2是═R2时，R2是一个氧代基团、可选择取代的烷基亚甲基基团或可选择取代的亚胺基团。