碘-四乙二醇-丙酸叔丁酯 | 1291090-31-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 碘-四乙二醇-丙酸叔丁酯
• 英文名称: tert-butyl 1-iodo-3,6,9,12-tetraoxapentadecan-15-oate
• 英文别名: tert-butyl 3-[2-[2-[2-(2-iodoethoxy)ethoxy]ethoxy]ethoxy]propanoate
• CAS: 1291090-31-7
• 化学式: C₁₅H₂₉IO₆
• 分子量: 432.296
• InChiKey: DDPBZNSGUXPBOY-UHFFFAOYSA-N

物化性质

• 沸点：
  431.2±40.0 °C(Predicted)
• 密度：
  1.334±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  16
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  63.2
• 氢给体数：
  0
• 氢受体数：
  6

安全信息

• 危险性防范说明：
  P261,P264,P271,P280,P302+P352,P304+P340,P305+P351+P338,P312,P362,P403+P233,P501
• 危险性描述：
  H315,H319,H335

反应信息

• 作为反应物：
  描述：

  碘-四乙二醇-丙酸叔丁酯 在 caesium carbonate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 4-[2-[2-[2-[2-[3-[4-[5-[6-Amino-5-[[3-(3-hydroxy-3-methylbut-1-ynyl)phenyl]methoxy]pyridin-3-yl]-1,3-thiazol-2-yl]piperidin-1-yl]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione
  参考文献：
  名称：

  一种PROTAC小分子化合物及其应用

  摘要：

  本发明公开了一种通式为Ⅰ的化合物，或其药学上可接受的盐、立体异构体、酯、前药、溶剂化物和氘代化合物，及含有通式为Ⅰ的化合物的组合物，以及通式为Ⅰ的化合物，或其药学上可接受的盐、立体异构体、酯、前药、溶剂化物和氘代化合物在制备治疗与丝氨酸/苏氨酸激酶家族(MAP4Ks)相关的疾病的药物中的应用，优选的，与造血干细胞激酶1(HPK1)相关的疾病的药物中的应用。

  公开号：

  CN112552293A
• 作为产物：
  描述：

  丙烯酸叔丁酯 在 咪唑 、 碘 、 苄基三甲基氢氧化铵 、 三苯基膦 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 51.0h， 生成 碘-四乙二醇-丙酸叔丁酯
  参考文献：
  名称：

  一种PROTAC小分子化合物及其应用

  摘要：

  本发明公开了一种通式为Ⅰ的化合物，或其药学上可接受的盐、立体异构体、酯、前药、溶剂化物和氘代化合物，及含有通式为Ⅰ的化合物的组合物，以及通式为Ⅰ的化合物，或其药学上可接受的盐、立体异构体、酯、前药、溶剂化物和氘代化合物在制备治疗与丝氨酸/苏氨酸激酶家族(MAP4Ks)相关的疾病的药物中的应用，优选的，与造血干细胞激酶1(HPK1)相关的疾病的药物中的应用。

  公开号：

  CN112552293A

文献信息

• [EN] BIFUNCTIONAL SUBSTITUED PYRIMIDINES AS MODULATORS OF FAK PROTEOLYSE<br/>[FR] PYRIMIDINES SUBSTITUÉES BIFONCTIONNELLES EN TANT QUE MODULATEURS DU PROTÉOLYSE DE FAK
  申请人：UNIV YALE

  公开号：WO2020023851A1

  公开（公告）日：2020-01-30

  The present disclosure relates to bifunctional compounds, which find utility as modulators of focal adhesion kinase (FAK) or protein tyrosine kinase 2 (PTK2). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，其作为调节焦粘附激酶（FAK）或蛋白酪氨酸激酶2（PTK2）的调节剂。具体而言，本公开涉及包含一端为Von Hippel-Lindau、cereblon、凋亡抑制蛋白或鼠双分子同源物2配体的双功能化合物，该配体结合到相应的E3泛素连接酶，另一端为结合目标蛋白的基团，使目标蛋白靠近泛素连接酶以实现目标蛋白的降解（和抑制）。本公开展示了与目标蛋白的降解/抑制相关的广泛药理活性范围。本公开的化合物和组合物用于治疗或预防由目标蛋白聚集或积累导致的疾病或紊乱。
• Syntheses and characterizations of novel pyrrolocoumarin probes for SNAP-tag labeling technology
  作者：De-Sheng Mei、Yi Qu、Jin-Xiang He、Lei Chen、Zhu-Jun Yao

  DOI：10.1016/j.tet.2011.01.075

  日期：2011.3

  SNAP-tag technology is a revolutionary protein labeling technology employing in various biological studies. Since low signal/noise ratio and severe overlap between the FRET donors/acceptors often occurred in applying present fluorescent probes and thus limited the further applications, development of new fluorescent probes with excellent fluorescent properties is still of request by today's SNAP-tag technology. In this paper, a number of SNAP-tag protein probes have been developed by incorporating a novel pyrrolocoumarin fluorophore recently developed by our group. Examination of these novel synthetic compounds shows all these materials possess satisfactory fluorescent properties. Among these, probe 7 exhibits the most excellent characters, and its quantum yield, maximum emission wavelength and Stocks shift reach to 0.44, 534 nm and 112 nm, respectively. Further analysis of structure-property relationship indicates that the probes with a longer C3-substituted alkyl (such as pentyl) give stronger fluorescence. (C) 2011 Elsevier Ltd. All rights reserved.
• Addressing Kinase-Independent Functions of Fak via PROTAC-Mediated Degradation
  作者：Philipp M. Cromm、Kusal T. G. Samarasinghe、John Hines、Craig M. Crews

  DOI：10.1021/jacs.8b08008

  日期：2018.12.12

  Enzymatic inhibition has proven to be a successful modality for the development of many small-molecule drugs. In recent years, small-molecule-induced protein degradation has emerged as an orthogonal therapeutic strategy that has the potential to expand the druggable target space. Focal adhesion kinase (Fak) is a key player in tumor invasion and metastasis, acting simultaneously as a kinase and a scaffold for several signaling proteins. While previous efforts to modulate Fak activity were limited to kinase inhibitors with low success in clinical studies, protein degradation offers a possibility to simultaneously block Fak's kinase signaling and scaffolding capabilities. Here, we report the development of a selective and potent Fak degrader, PROTAC-3, which outperforms a clinical candidate, defactinib, with respect to Fak activation as well as Fak-mediated cell migration and invasion. These results underline the potential that PROTACs offer in expanding the druggable space and controlling protein functions that are not easily addressed by traditional small-molecule therapeutics.
• MODULATORS OF FAK PROTEOLYSIS AND ASSOCIATED METHODS OF USE
  申请人：ARVINAS OPERATIONS, INC.

  公开号：US20200038513A1

  公开（公告）日：2020-02-06

  The present disclosure relates to bifunctional compounds, which find utility as modulators of focal adhesion kinase (FAK) or protein tyrosine kinase 2 (PTK2). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
• [EN] PROTEIN KINASE DEGRADATION INDUCING COMPOUND, AND USE THEREOF<br/>[FR] COMPOSÉ INDUISANT LA DÉGRADATION DE PROTÉINES KINASES ET SON UTILISATION<br/>[KO] 단백질 키나아제 분해 유도 화합물 및 이의 용도
  申请人：VORONOI CO LTD

  公开号：WO2021162493A1

  公开（公告）日：2021-08-19

  본 발명은 단백질 키나아제 분해 유도 화합물 및 이의 용도에 관한 것이다. 구체적으로, 본 발명의 단백질 키나아제 분해 유도 화합물은 AURKA, FLT3 돌연변이, EGFR 돌연변이, 또는 c-KIT 돌연변이 단백질을 분해할 수 있고, 이를 통하여 AURKA, FLT3 돌연변이, EGFR 돌연변이, 또는 c-KIT 돌연변이 관련 질환을 치료할 수 있다.