MT-802

• 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: MT-802
• 英文别名: 2-(2-(2-(4-(4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)ethoxy)ethoxy)-N-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)acetamide；2-[2-[2-[4-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]ethoxy]ethoxy]-N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]acetamide
• 化学式: C₄₁H₄₁N₉O₈
• 分子量: 787.832
• InChiKey: AJTLGUJXIKEZCQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  58
• 可旋转键数：
  14
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  213
• 氢给体数：
  3
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  4,5-二甲氧基-2-硝基苄基氯甲酸酯 、 MT-802 、 三氟乙酸 在 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙腈 为溶剂， 以6%的产率得到4,5-dimethoxy-2-nitrobenzyl 3-(5-{2-[2-(2-{4-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl}ethoxy)ethoxy]acetamido}-1,3-dioxoisoindolin-2-yl)-2,6-dioxopiperidine-1-carboxylate trifluoroacetic acid salt
  参考文献：
  名称：

  Light-Induced Protein Degradation with Photocaged PROTACs

  摘要：

  Induction of protein degradation is emerging as a powerful strategy to modulate protein functions and alter cellular signaling pathways. Proteolysis-targeting chimeras (PROTACs) have been used to degrade a range of diverse proteins in vitro and in vivo. Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light. Photo-removable blocking groups were added to a degrader of Brd4, and the resulting molecule pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation. Furthermore, this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish. Additionally, this approach was successfully applied to construct pc-PROTAC3 of BTK. Thus, a general strategy to induce protein degradation with light was established to augment the chemists' toolbox to study disease-relevant protein targets.

  DOI：

  10.1021/jacs.9b06422
• 作为产物：
  描述：

  泊马度胺 在 三乙胺 、 sodium iodide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 24.0h， 生成 MT-802
  参考文献：
  名称：

  MODULATORS OF BTK PROTEOLYSIS AND METHODS OF USE

  摘要：

  本公开涉及双功能化合物，其作为Burton的酪氨酸激酶（BTK）的调节剂而有用。特别是，本公开是针对双功能化合物的。双功能化合物的一端包括Von Hippel-Lindau、Cereblon、Inhibitors of Apotosis Proteins或Mouse Double-Minute Homolog 2配体，该配体结合到相应的E3泛素连接酶。双功能化合物的另一端包括结合到目标蛋白质的部分，使目标蛋白质靠近泛素连接酶，以促进目标蛋白质的降解（和抑制）。本公开的化合物和组合物可用于治疗或预防由目标蛋白质的聚集、积累和/或过度活化引起的疾病或障碍。

  公开号：

  US20190276459A1

文献信息

• Modulators of BTK proteolysis and methods of use
  申请人：Yale University

  公开号：US11028088B2

  公开（公告）日：2021-06-08

  The present disclosure relates to bifunctional compounds, which find utility as modulators of Burton's Tyrosine Kinase (BTK). In particular, the present disclosure is directed to bifunctional compounds. One end of a bifunctional compound includes a Von Hippel-Lindau, Cereblon, Inhibitors of Apotosis Proteins, or Mouse Double-Minute Homolog 2 ligand that binds to the respective E3 ubiquitin ligase. The other end of a bifunctional compound includes a moiety that binds a target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. Diseases or disorders that result from aggregation, accumulation, and/or overactivation of the target protein can be treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，这些化合物可用作伯顿酪氨酸激酶（BTK）的调节剂。特别是，本公开涉及双功能化合物。双功能化合物的一端包括与相应 E3 泛素连接酶结合的 Von Hippel-Lindau、Cereblon、抑制细胞凋亡蛋白或小鼠双敏同源物 2 配体。双功能化合物的另一端包括与靶蛋白结合的分子，这样靶蛋白就会被置于泛素连接酶附近，以实现对靶蛋白的降解（和抑制）。本公开的化合物和组合物可以治疗或预防由于靶蛋白的聚集、积累和/或过度激活而导致的疾病或失调。
• [EN] SMALL MOLECULE PROTEOLYSIS-TARGETING CHIMERAS AND METHODS OF USE THEREOF<br/>[FR] CHIMÈRES CIBLANT LA PROTÉOLYSE À PETITES MOLÉCULES ET LEURS MÉTHODES D'UTILISATION
  申请人：BAYLOR COLLEGE MEDICINE

  公开号：WO2020252397A8

  公开（公告）日：2021-02-18
• [EN] MODULATORS OF BTK PROTEOLYSIS AND METHODS OF USE<br/>[FR] MODULATEURS DE PROTÉOLYSE DE BTK ET PROCÉDÉS D'UTILISATION
  申请人：UNIV YALE

  公开号：WO2019177902A1

  公开（公告）日：2019-09-19

  The present disclosure relates to bifunctional compounds, which find utility as modulators of Burton's Tyrosine Kinase (BTK). In particular, the present disclosure is directed to bifunctional compounds. One end of a bifunctional compound includes a Von Hippel-Lindau, Cereblon, Inhibitors of Apotosis Proteins, or Mouse Double-Minute Homolog 2 ligand that binds to the respective E3 ubiquitin ligase. The other end of a bifunctional compound includes a moiety that binds a target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. Diseases or disorders that result from aggregation, accumulation, and/or overactivation of the target protein can be treated or prevented with compounds and compositions of the present disclosure.
• [EN] METHODS AND COMPOSITIONS FOR TREATING AN OPHTHALMIC CONDITION<br/>[FR] MÉTHODES ET COMPOSITIONS POUR LE TRAITEMENT D'UNE AFFECTION OPHTALMIQUE
  申请人：[en]TELIOS PHARMA, INC.

  公开号：WO2022120015A1

  公开（公告）日：2022-06-09

  Therapeutic methods and pharmaceutical compositions for treating an ophthalmic condition including dry eye syndrome and uveitis in a human subject are described. In certain embodiments, the disclosure includes therapeutic methods using a BTK inhibitor.
• [EN] TREATMENT OF SYMPTOMS ASSOCIATED WITH MYELOPROLIFERATIVE NEOPLASMS<br/>[FR] TRAITEMENT DE SYMPTÔMES ASSOCIÉS À DES NÉOPLASMES MYÉLOPROLIFÉRATIFS
  申请人：[en]TELIOS PHARMA INC.

  公开号：WO2022266285A1

  公开（公告）日：2022-12-22

  Therapeutic methods and pharmaceutical compositions for treating symptoms associated with myeloproliferative neoplasms in a human subject are described. In certain embodiments, the disclosure includes therapeutic methods of treating symptoms associated with myeloproliferative neoplasms using a BTK inhibitor.