2-[(3-Methyl-2-oxopiperidin-3-yl)carbamoyl]benzoic acid | 123979-17-9

• 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
• 英文名称: 2-[(3-Methyl-2-oxopiperidin-3-yl)carbamoyl]benzoic acid
• CAS: 123979-17-9
• 化学式: C₁₄H₁₆N₂O₄
• 分子量: 276.292
• InChiKey: WUBVRMPRZBVQNA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  95.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[(3-Methyl-2-oxopiperidin-3-yl)carbamoyl]benzoic acid 以89%的产率得到rac-2-(3-Methyl-2-oxo-3-piperidinyl)-1H-isoindol-1,3(2H)-dion
  参考文献：
  名称：

  (S)-Form of .ALPHA.-Methyl-N(.ALPHA.)-phthalimidoglutarimide, but Not Its (R)-Form, Enhanced Phorbol Ester-Induced Tumor Necrosis Factor-.ALPHA. Production by Human Leukemia Cell HL-60: Implication of Optical Resolution of Thalidomidal Effects.

  摘要：

  经测定，N(α)-邻苯二甲酰亚氨基戊二酰亚胺（沙利度胺）在 pH 值为 7.4/37°C 时的半衰期为 566 分钟。沙利度胺的这种快速外消旋化导致该化合物的(S)-型和(R)-型在增强人白血病 HL-60 细胞产生由光滑脂诱导的肿瘤坏死因子（TNF）-α 的活性方面没有明显差异。制备出了结构相关的沙利度胺类似物(S)-和(R)-α-甲基-N(α)-邻苯二甲酰亚胺戊二酰亚胺（甲基邻苯二甲酰亚胺）的光学纯形式，它们在生理条件下不会发生外消旋。只有(S)-形式的甲酞胺而不是其(R)-形式的甲酞胺能引起TNF-α生成增强效应，这表明甲酞胺的(S)-异构体是具有甲酞胺生物反应调节作用的活性形式。

  DOI：

  10.1248/cpb.42.1157
• 作为产物：
  描述：

  4-Cyano-2-methyl-2-{[1-phenyl-meth-(E)-ylidene]-amino}-butyric acid methyl ester 在 盐酸 、 platinum(IV) oxide 、 氢气 作用下， 生成 2-[(3-Methyl-2-oxopiperidin-3-yl)carbamoyl]benzoic acid
  参考文献：
  名称：

  (S)-Form of .ALPHA.-Methyl-N(.ALPHA.)-phthalimidoglutarimide, but Not Its (R)-Form, Enhanced Phorbol Ester-Induced Tumor Necrosis Factor-.ALPHA. Production by Human Leukemia Cell HL-60: Implication of Optical Resolution of Thalidomidal Effects.

  摘要：

  经测定，N(α)-邻苯二甲酰亚氨基戊二酰亚胺（沙利度胺）在 pH 值为 7.4/37°C 时的半衰期为 566 分钟。沙利度胺的这种快速外消旋化导致该化合物的(S)-型和(R)-型在增强人白血病 HL-60 细胞产生由光滑脂诱导的肿瘤坏死因子（TNF）-α 的活性方面没有明显差异。制备出了结构相关的沙利度胺类似物(S)-和(R)-α-甲基-N(α)-邻苯二甲酰亚胺戊二酰亚胺（甲基邻苯二甲酰亚胺）的光学纯形式，它们在生理条件下不会发生外消旋。只有(S)-形式的甲酞胺而不是其(R)-形式的甲酞胺能引起TNF-α生成增强效应，这表明甲酞胺的(S)-异构体是具有甲酞胺生物反应调节作用的活性形式。

  DOI：

  10.1248/cpb.42.1157

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。
• Synthese der Racemate und der Enantiomere von 3-Alkylthalidomidanaloga und Bestimmung ihrer absoluten Konfiguration
  作者：Joachim Knabe、Günter Omlor

  DOI：10.1002/ardp.19893220809

  日期：——

  Es wird über die Synthese der Racemate und der Enantiomere der 3‐Alkyl‐thalidomidanaloga 7a ‐ 7c und des racem. 1,3‐Dimethylthalidomids (8) berichtet. Die absolute Konfiguration der optisch aktiven Syntheseprodukte wird abgeleitet. Die Verbindungen 7a ‐ 7c, 8 und die Synthesezwischenprodukte 6a ‐ 6c sollen tierexperimentell auf ihre sedativ‐hypnotische Wirkung geprüft werden.

  它是关于 3-烷基-沙利度胺类似物 7a - 7c 和外消旋体的外消旋体和对映体的合成。1,3-二甲基沙利度胺 (8) 已有报道。推导出光学活性合成产物的绝对构型。化合物7a-7c、8和合成中间体6a-6c将在动物实验中测试其镇静催眠作用。
• 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 Operations, Inc.

  公开号：US10844021B2

  公开（公告）日：2020-11-24

  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。
• Imide-based modulators of proteolysis and associated methods of use
  申请人：YALE UNIVERSITY

  公开号：US11220515B2

  公开（公告）日：2022-01-11

  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.

  本说明涉及亚胺基化合物，包括包含亚胺基化合物的双官能化合物，这些化合物可用作靶向泛素化的调节剂，特别是各种多肽和其他蛋白质的抑制剂，根据本发明的双官能化合物可降解和/或以其他方式抑制这些多肽和蛋白质。具体而言，本发明提供的化合物一端含有与脑龙 E3 泛素连接酶结合的配体，另一端含有与靶蛋白结合的分子，从而使靶蛋白靠近泛素连接酶，以实现对该蛋白的降解（和抑制）。可以合成出具有广泛药理活性的化合物，这些化合物几乎可以降解/抑制任何类型的目标多肽。