3-(1-甲基-1H-吡唑-5-基)异氰酸苯酯 | 941716-86-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 3-(1-甲基-1H-吡唑-5-基)异氰酸苯酯
• 英文名称: 5-(3-isocyanato-phenyl)-1-methyl-1H-pyrazole
• 英文别名: 5-(3-Isocyanatophenyl)-1-methyl-1H-pyrazole；5-(3-isocyanatophenyl)-1-methylpyrazole
• CAS: 941716-86-5
• 化学式: C₁₁H₉N₃O
• mdl: MFCD09817502
• 分子量: 199.212
• InChiKey: ZFRFBJVFEQIMLM-UHFFFAOYSA-N

物化性质

• 沸点：
  352.3±25.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  47.2
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933199090

反应信息

• 作为反应物：
  描述：

  3-(1-甲基-1H-吡唑-5-基)异氰酸苯酯 、 3-(5-(aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione methanesulfonate 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 22.0h， 以24%的产率得到1-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-3-[3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-urea
  参考文献：
  名称：

  [EN] ISOINDOLINE COMPOUNDS FOR USE IN THE TREATMENT OF CANCER
  [FR] COMPOSÉS D'ISOINDOLINE UTILISABLES DANS LE CADRE DU TRAITEMENT DU CANCER

  摘要：

  本文提供了诸如式(I)所示的异吲哚类化合物，包括含有一种或多种此类化合物的药物组合物，以及它们用于治疗、预防或管理各种疾病的方法。Formula (I)

  公开号：

  WO2010053732A1

文献信息

• [EN] METHODS AND COMPOSITIONS OF INHIBITING DCN1-UBC12 INTERACTION<br/>[FR] PROCÉDÉS ET COMPOSITIONS D'INHIBITION DE L'INTERACTION DCN1-UBC12
  申请人：ST JUDE CHILDREN'S RES HOSPITAL

  公开号：WO2017049295A1

  公开（公告）日：2017-03-23

  In one aspect, the invention relates to substituted l-phenyl-3-(piperidin-4-yl)urea analogs, derivatives thereof, and related compounds, which are useful as inhibitors of the DCN1-UBC12 interaction inhibitors of DCN1 -mediated cullin-RING ligase activity, methods of making same, pharmaceutical compositions comprising same, methods of treating disorders using the disclosed compounds and compositions, methods of treating disorders associated with a DCN1-UBC12 interaction dysfunction, methods of treating disorders associated with a DCN1-mediated cullin-RING ligase activity dysfunction, methods of male contraception comprising the disclosed compounds and compositions, and kits comprising the disclosed compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  在一个方面，本发明涉及替代的l-苯基-3-(哌啶-4-基)脲类似物，其衍生物和相关化合物，这些化合物可用作DCN1-UBC12相互作用抑制剂和DCN1介导的卡林-环形酶活性抑制剂，制备方法，包含这些化合物的药物组合物，使用所披露的化合物和组合物治疗疾病的方法，治疗与DCN1-UBC12相互作用功能障碍相关的疾病的方法，治疗与DCN1介导的卡林-环形酶活性功能障碍相关的疾病的方法，包含所披露的化合物和组合物的男性避孕方法，以及包含所披露的化合物和组合物的试剂盒。本摘要旨在作为在特定领域进行搜索的扫描工具，并不打算限制本发明。
• ISOINDOLINE COMPOUNDS AND METHODS OF THEIR USE
  申请人：MULLER George W.

  公开号：US20100204227A1

  公开（公告）日：2010-08-12

  Provided herein are isoindoline compounds, pharmaceutical compositions comprising one or more of such compounds, and methods of their use for treating, preventing, or managing various diseases.

  本文提供了异吲哚啉化合物，包括一个或多个这样的化合物的制药组合物，以及它们用于治疗、预防或管理各种疾病的方法。
• ISOINDOLINE COMPOUNDS FOR USE IN THE TREATMENT OF CANCER
  申请人：Celgene Corporation

  公开号：EP2985281A2

  公开（公告）日：2016-02-17

  Provided herein are isoindoline compounds, pharmaceutical compositions comprising one or more of such compounds, and methods of their use for treating, preventing, or managing various diseases or disorders.

  本文提供了异吲哚啉化合物、包含一种或多种此类化合物的药物组合物，以及使用它们治疗、预防或控制各种疾病或失调的方法。
• Methods and compositions of inhibiting DCN1-UBC12 interaction
  申请人：Memorial Sloan Kettering Cancer Center

  公开号：US11116757B2

  公开（公告）日：2021-09-14

  In one aspect, the invention relates to substituted 1-phenyl-3-(piperidin-4-yl)urea analogs, derivatives thereof, and related compounds, which are useful as inhibitors of the DCN1-UBC12 interaction inhibitors of DCN1-mediated cullin-RING ligase activity, methods of making same, pharmaceutical compositions comprising same, methods of treating disorders using the disclosed compounds and compositions, methods of treating disorders associated with a DCN1-UBC12 interaction dysfunction, methods of treating disorders associated with a DCN1-mediated cullin-RING ligase activity dysfunction, methods of male contraception comprising the disclosed compounds and compositions, and kits comprising the disclosed compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  在一个方面，本发明涉及取代的1-苯基-3-(哌啶-4-基)脲类似物、其衍生物和相关化合物，它们可用作DCN1-UBC12相互作用的抑制剂DCN1介导的cullin-RING连接酶活性的抑制剂、制造方法、包含它们的药物组合物、使用所公开的化合物和组合物治疗疾病的方法、治疗与DCN1-UBC12相互作用功能障碍相关的疾病的方法、治疗与DCN1介导的cullin-RING连接酶活性障碍相关的疾病的方法、包含所公开化合物和组合物的男性避孕方法，以及包含所公开化合物和组合物的试剂盒。本摘要旨在作为在特定技术领域进行搜索的扫描工具，并非对本发明的限制。
• Piperidinyl Ureas Chemically Control Defective in Cullin Neddylation 1 (DCN1)-Mediated Cullin Neddylation
  作者：Jared T. Hammill、Daniel C. Scott、Jaeki Min、Michele C. Connelly、Gloria Holbrook、Fangyi Zhu、Amy Matheny、Lei Yang、Bhuvanesh Singh、Brenda A. Schulman、R. Kiplin Guy

  DOI：10.1021/acs.jmedchem.7b01277

  日期：2018.4.12

  We previously discovered and validated a class of piperidinyl ureas that regulate defective in cullin neddylation 1 (DCN1)-dependent neddylation of cullins. Here, we report preliminary structure-activity relationship studies aimed at advancing our high-throughput screen hit into a tractable tool compound for dissecting the effects of acute DCN1-UBE2M inhibition on the NEDD8/cullin pathway. Structure-enabled optimization led to a 100-fold increase in biochemical potency and modestly increased solubility and permeability as compared to our initial hit. The optimized compounds inhibit the DCN1- UBE2M protein-protein interaction in our TR-FRET binding assay and inhibit cullin neddylation in our pulse-chase NEDD8 transfer assay. The optimized compounds bind to DCN1 and selectively reduce steady-state levels of neddylated CUL1 and CUL3 in a squamous cell carcinoma cell line. Ultimately, we anticipate that these studies will identify early lead compounds for clinical development for the treatment of lung squamous cell carcinomas and other cancers.