1-(2-苯基乙基)-3-(1,3-噻唑-2-基)硫脲 | 149485-30-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-(2-苯基乙基)-3-(1,3-噻唑-2-基)硫脲
• 英文名称: 1-phenethyl-3-(thiazol-2-yl)thiourea
• 英文别名: LY73497；Thiourea, N-(2-phenylethyl)-N'-2-thiazolyl-；1-(2-phenylethyl)-3-(1,3-thiazol-2-yl)thiourea
• CAS: 149485-30-3
• 化学式: C₁₂H₁₃N₃S₂
• 分子量: 263.387
• InChiKey: ANUSGJXVCFPWMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  97.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-氨基噻唑 、 2-苯基乙基异硫代氰酸酯 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以42%的产率得到1-(2-苯基乙基)-3-(1,3-噻唑-2-基)硫脲
  参考文献：
  名称：

  苯乙基噻唑硫脲（PETT）化合物，一类新的HIV-1逆转录酶抑制剂。1. PETT类似物的合成及其基本的构效关系研究。

  摘要：

  描述了一系列新的有效的特异性HIV-1抑制化合物。该系列中的主要化合物N-（2-苯乙基）-N'-（2-噻唑基）硫脲（1）使用rCdG作为模板抑制HIV-1 RT，IC50为0.9 microM。在MT-4细胞中，化合物1抑制HIV-1的ED50为1.3 microM。细胞培养物中50％的细胞毒性剂量> 380 microM。通过将铅化合物概念上划分为四个象限来建立化学结构-活性关系（SAR）。搜救战略分为两个阶段。第一阶段涉及通过象限1-4的独立变化来优化抗病毒活性。第二阶段涉及制备结合了这些取代基中最好的杂化结构。进一步的SAR研究和药代动力学考虑导致鉴定N-（2-吡啶基）-N' -（5-溴-2-吡啶基）-硫脲（62; LY300046.HCl）可作为临床评估的候选药物。LY300046.HCl抑制HIV-1 RT的IC50为15 nM，在细胞培养中的ED50为20 nM。

  DOI：

  10.1021/jm00025a010

文献信息

• BRM TARGETING COMPOUNDS AND ASSOCIATED METHODS OF USE
  申请人：Arvinas Operations, Inc.

  公开号：US20190300521A1

  公开（公告）日：2019-10-03

  The present disclosure relates to bifunctional compounds, which find utility as modulators of SMARCA2 or BRM (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a ligand that binds to the Von Hippel-Lindau 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SMARCA2或BRM（靶蛋白）的调节剂具有实用性。具体而言，本公开涉及包含一端结合Von Hippel-Lindau E3泛素连接酶的配体，另一端结合靶蛋白的双功能化合物，使得靶蛋白与泛素连接酶靠近以实现靶蛋白的降解（和抑制）。本公开展示了与靶蛋白降解/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靶蛋白聚集或积累导致的疾病或紊乱。
• [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。
• 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] AMINE-LINKED C3-GLUTARIMIDE DEGRONIMERS FOR TARGET PROTEIN DEGRADATION<br/>[FR] DÉGRONIMÈRES DE C3-GLUTARIMIDE LIÉS À UNE AMINE POUR LA DÉGRADATION DE PROTÉINES CIBLES
  申请人：C4 THERAPEUTICS INC

  公开号：WO2017197051A1

  公开（公告）日：2017-11-16

  This invention provides amine-linked C3-glutarimide Degronimers and Degrons for therapeutic applications as described further herein, and methods of use and compositions thereof as well as methods for their preparation.

  这项发明提供了胺连接的C3-戊二酰亚胺Degronimers和Degrons，用于治疗应用，如本文进一步描述的，以及它们的使用方法、组合物以及它们的制备方法。
• 1-(Alkyl/Arylthiocarbamoyl)benzotriazoles as Stable Isothiocyanate Equivalents:  Synthesis of Di- and Trisubstituted Thioureas
  作者：Alan R. Katritzky、Stephane Ledoux、Rachel M. Witek、Satheesh K. Nair

  DOI：10.1021/jo035680d

  日期：2004.4.1

  1-(Alkyl/arylthiocarbamoyl)benzotriazoles 4a−i were synthesized in yields of 91−99% from bis(benzotriazolyl)methanethione (3). Reagents 4a−g were then used as isothiocyanate equivalents for the efficient synthesis of 10 secondary and 14 tertiary thioureas in high-yielding, convenient processes.

  从双（苯并三唑基）甲烷硫酮（3）合成1-（烷基/芳基硫代氨基甲酰基）苯并三唑4a - i的产率为91-99％。然后将试剂4a - g用作异硫氰酸酯等效物，以高产率，方便的方法有效合成10个仲和14个叔硫脲。