4H-呋喃并[3,2-b]吡咯 | 250-91-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃吡咯
• 中文名称: 4H-呋喃并[3,2-b]吡咯
• 英文名称: furo<3,2-b>pyrrole
• 英文别名: 4H-furo[3,2-b]pyrrole；4H-furo[3,2-b]pyrrole；furo[3,2-b]pyrrole；4H-Furo<3,2-b>pyrrol；Furo<3.2-b>pyrrol
• CAS: 250-91-9
• 化学式: C₆H₅NO
• mdl: MFCD11870745
• 分子量: 107.112
• InChiKey: PLJIVNLEQUBQTH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  28.9
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4H-呋喃并[3,2-b]吡咯 、 L-丝氨酸 在 potassium phosphate buffer 、 Salmonella tryphimurium tryptophan synthase 、 磷酸吡哆醛 作用下， 以 水 为溶剂， 生成 6-(4H-furo<3,2-b>pyrrolyl)-L-alanine
  参考文献：
  名称：

  6-（4H-硒代[3,2-b]吡咯基）-L-丙氨酸，4-（6H-硒代[2,3-b]吡咯基）-L-丙氨酸和6-（4H-呋喃）的酶促合成[3，2-b]吡咯基-L-丙氨酸。

  摘要：

  6-（4H-硒代[3,2-b]吡咯基）-L-丙氨酸1、4-（6H-硒代[2,3-b]吡咯基）-L-丙氨酸2和6-（4H-呋喃[ 3,2-b]吡咯基）-L-丙氨酸是通过硒代[3,2-b]吡咯，硒代[2,3-b]吡咯和呋喃[3,2-b]吡咯的反应合成的，分别用L-丝氨酸。该反应由鼠伤寒沙门氏菌色氨酸合酶催化。

  DOI：

  10.1016/s0960-894x(99)00067-0
• 作为产物：
  描述：

  呋喃并吡咯甲酸 在 chromium(III) oxide 、 铜 作用下， 以 喹啉 为溶剂， 反应 0.5h， 生成 4H-呋喃并[3,2-b]吡咯
  参考文献：
  名称：

  Soth,S. et al., Canadian Journal of Chemistry, 1978, vol. 56, p. 1429 - 1434

  摘要：

  DOI：
• 作为试剂：
  描述：

  5-氯-2-糠醛 、 钠 、 、 叠氮乙酸乙酯 在 水 、 乙醚 、 丙-2-烯酸酯 、 4H-呋喃并[3,2-b]吡咯 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 ethyl 2-chloro-4H-furo[3,2-b]pyrrole-5-carboxylate
  参考文献：
  名称：

  Bicyclic pyrrolyl amides as glycogen phosphorylase inhibitors

  摘要：

  本发明涉及公式I或其立体异构体、药学上可接受的盐或前药的药学上可接受的盐，以及前药的制药组合物。本发明还涉及包含公式I化合物的制药组合物，以及治疗糖尿病、胰岛素抵抗、糖尿病神经病变、糖尿病肾病、糖尿病视网膜病变、白内障、高血糖、高胆固醇血症、高血压、高胰岛素血症、高脂血症、动脉硬化或组织缺血的治疗方法。

  公开号：

  US06576653B2

文献信息

• [EN] ALANINE-BASED MODULATORS OF PROTEOLYSIS AND ASSOCIATED METHODS OF USE<br/>[FR] MODULATEURS DE PROTÉOLYSE À BASE D'ALANINE ET PROCÉDÉS D'UTILISATION ASSOCIÉS
  申请人：ARVINAS INC

  公开号：WO2017011590A1

  公开（公告）日：2017-01-19

  The description relates to inhibitors of Apoptosis Proteins (TAPs) binding compounds, including Afunctional 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 IAP 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.

  描述涉及抑制凋亡蛋白（TAPs）结合化合物，包括包含相同的A功能化合物，这些化合物作为靶向泛素化的调节剂发挥作用，特别是根据本发明的双功能化合物抑制各种多肽和其他蛋白质的化合物。具体而言，描述提供了一端含有结合到IAP E3泛素连接酶的配体，另一端含有结合到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）。可以合成化合物，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。
• 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。
• COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE 4 POLYPEPTIDES
  申请人：Arvinas, Inc.

  公开号：US20190151295A1

  公开（公告）日：2019-05-23

  The present disclosure relates to bifunctional compounds, which find utility as modulators of Interleukin-1 Receptor-Associated Kinase 4 (IRAK-4); the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hppel-Lindau, cereblon, ligand which binds to the 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，其作为白细胞介素-1受体相关激酶4（IRAK-4；目标蛋白）的调节剂具有实用性。具体而言，本公开涉及包含一端结合E3泛素连接酶的Von Hppel-Lindau、cereblon配体的双功能化合物，另一端结合目标蛋白的部分，使得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。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。
• [EN] BI-FUNCTIONAL COMPOUNDS AND METHODS FOR TARGETED UBIQUITINATION OF ANDROGEN RECEPTOR<br/>[FR] COMPOSÉS BI-FONCTIONNELS ET PROCÉDÉS D'UBIQUITINATION CIBLÉE DU RÉCEPTEUR DES ANDROGÈNES
  申请人：MONTELINO THERAPEUTICS INC

  公开号：WO2021236695A1

  公开（公告）日：2021-11-25

  The present invention relates to bi-functional compounds which function to recruit endogenous proteins to an E3 ubiquitin ligase for degradation, and methods for using same. More specifically, the present disclosure provides specific proteolysis targeting chimera (PROTAC) molecules which find utility as modulators of targeted ubiquitination of a variety of polypeptides and other proteins, in particular the androgen receptor of a slice variant of AR which lacks the LBD, labelled as AR-V7, which are then degraded and/or otherwise inhibited by the compounds as described herein.

  本发明涉及具有双重功能的化合物，其功能是招募内源蛋白质到E3泛素连接酶进行降解，并使用相同的方法。更具体地，本公开提供了特定的蛋白质降解靶向嵌合物（PROTAC）分子，这些分子作为调节各种多肽和其他蛋白质的靶向泛素化的调节剂，特别是缺乏LBD的AR的一个切片变体的雄激素受体，标记为AR-V7，然后通过所述化合物进行降解和/或其他方式被抑制。

表征谱图