5-phthalimidopyrimidine-2,4(1H,3H)-dione | 59007-52-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 5-phthalimidopyrimidine-2,4(1H,3H)-dione
• 英文别名: N-(2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl)-phthalimide；2-(2,4-dioxo-1H-pyrimidin-5-yl)isoindole-1,3-dione
• CAS: 59007-52-2
• 化学式: C₁₂H₇N₃O₄
• 分子量: 257.205
• InChiKey: DQCXJNJOELHPGW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  95.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-氨基尿嘧啶 、 邻苯二甲酸 在 吡啶 作用下， 反应 0.5h， 以100%的产率得到5-phthalimidopyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  一步法从邻苯二甲酸高效合成2-取代邻苯二甲酰亚胺

  摘要：

  已经通过实验设计开发了从邻苯二甲酸开始合成 2-取代邻苯二甲酰亚胺（异吲哚-1,3-二酮）类似物的有效程序。邻苯二甲酰亚胺中心...

  DOI：

  10.1002/ejoc.201300952

文献信息

• COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF ANDROGEN RECEPTOR
  申请人：Arvinas, Inc.

  公开号：US20180099940A1

  公开（公告）日：2018-04-12

  The present disclosure relates to bifunctional compounds, which find utility to degrade and (inhibit) Androgen Receptor. In particular, the present disclosure is directed to compounds, which contain on one end a cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds Androgen Receptor, such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present disclosure exhibits a broad range of pharmacological activities associated with compounds according to the present disclosure, consistent with the degradation/inhibition of Androgen Receptor.

  本公开涉及双功能化合物，其用于降解和（抑制）雄激素受体。具体而言，本公开涉及包含一端结合到E3泛素连接酶的谷氨酰腺苷环配体，另一端结合到雄激素受体的部分的化合物，使得雄激素受体与泛素连接酶靠近，以实现雄激素受体的降解（和抑制）。本公开展示了与根据本公开涉及的化合物相关的广泛的药理活性范围，与雄激素受体的降解/抑制一致。
• CEREBLON LIGANDS AND BIFUNCTIONAL COMPOUNDS COMPRISING THE SAME
  申请人：Arvinas, Inc.

  公开号：US20180215731A1

  公开（公告）日：2018-08-02

  The description relates to cereblon E3 ligase binding compounds, including bifunctional compounds comprising the same, 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 disclosure. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 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. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.

  该描述涉及cereblon E3连接酶结合化合物，包括包含相同成分的双功能化合物，这些化合物作为靶向泛素化的调节剂具有实用价值，尤其是抑制剂，可降解和/或以其他方式抑制根据本公开的双功能化合物。特别是，该描述提供了化合物，其一端含有与cereblon E3泛素连接酶结合的配体，另一端含有与目标蛋白结合的部分，使目标蛋白位于泛素连接酶附近以降解（和抑制）该蛋白。可以合成表现出广泛药理活性的化合物，与几乎所有类型的靶向多肽的降解/抑制一致。
• AROMATIC AMINE AR AND BET TARGETING PROTEIN DEGRADATION CHIMERA COMPOUND AND USE
  申请人：Hinova Pharmaceuticals Inc.

  公开号：EP3971176A1

  公开（公告）日：2022-03-23

  An aromatic amine androgen receptor (AR) and BET targeting protein degradation chimera compound and its use. Specifically provided is a compound represented by formula I. Experimental results show that the compound can target and degrade both AR and BRD4, and down-regulate the expression of AR and BRD4 proteins; the compound can inhibit the proliferation of a variety of prostate cancer cells; the compound can inhibit the proliferation of a prostate cancer cell line LNCaP/AR, which overexpresses the AR, and can achieve a good inhibition effect on a prostate cancer cell line 22RV1, which is resistant to a marketed prostate cancer drug (enzalutamide); the compound also shows good metabolic stability, and has a good application prospect in the preparation of an AR and/or BET protein degradation targeting chimera, and a drug for the treatment of related diseases regulated by the AR and BET.

  一种芳香胺雄激素受体（AR）和BET靶向蛋白降解嵌合物化合物及其用途。具体提供的是由式I表示的化合物。实验结果表明，该化合物可以靶向降解AR和BRD4，并下调AR和BRD4蛋白的表达；该化合物可以抑制多种前列腺癌细胞的增殖；该化合物可以抑制过表达AR的前列腺癌细胞系LNCaP/AR的增殖，并且对一种对市售前列腺癌药物（恩扎鲁胺）具有耐药性的前列腺癌细胞系22RV1具有良好的抑制效果；该化合物还表现出良好的代谢稳定性，在制备AR和/或BET蛋白降解靶向嵌合物和治疗由AR和BET调控的相关疾病的药物方面具有良好的应用前景。
• IMIDE-BASED MODULATORS OF PROTEOLYSIS AND ASSOCIATED METHODS OF USE
  申请人：Arvinas, Inc.

  公开号：US20150291562A1

  公开（公告）日：2015-10-15

  The description relates to imide-based compounds, including bifunctional compounds comprising the same, 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 description provides compounds, which contain on one end a ligand which binds to the cereblon E3 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. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.

  该描述涉及基于亚醰基的化合物，包括包含它们的双官能团化合物，这些化合物在靶向泛素化调节中发挥作用，特别是根据本发明的双官能团化合物抑制各种多肽和其他蛋白质的降解和/或抑制。具体来说，该描述提供了一种化合物，其中一端含有与小脑素E3泛素连接酶结合的配体，另一端含有结合目标蛋白的基团，使目标蛋白靠近泛素连接酶，以实现该蛋白的降解（和抑制）。可以合成表现出与几乎任何类型的靶向多肽的降解/抑制一致的广泛药理活性的化合物。
• Compounds and methods for the targeted degradation of androgen receptor
  申请人：Arvinas, Inc.

  公开号：US10584101B2

  公开（公告）日：2020-03-10

  The present disclosure relates to bifunctional compounds, which find utility to degrade and (inhibit) Androgen Receptor. In particular, the present disclosure is directed to compounds, which contain on one end a cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds Androgen Receptor, such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present disclosure exhibits a broad range of pharmacological activities associated with compounds according to the present disclosure, consistent with the degradation/inhibition of Androgen Receptor.

  本公开涉及双功能化合物，它们可用于降解和（抑制）雄激素受体。特别是，本公开涉及的化合物一端含有与 E3 泛素连接酶结合的脑龙配体，另一端含有与雄激素受体结合的分子，这样雄激素受体就被置于泛素连接酶附近，从而实现对雄激素受体的降解（和抑制）。本公开的化合物具有广泛的药理活性，与雄激素受体的降解/抑制作用相一致。