1-methylimidazole-5-sulfonyl chloride | 479552-18-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-methylimidazole-5-sulfonyl chloride
• 英文别名: 1-Methyl-1H-imidazole-5-sulfonyl chloride；3-methylimidazole-4-sulfonyl chloride
• CAS: 479552-18-6
• 化学式: C₄H₅ClN₂O₂S
• mdl: MFCD03094628
• 分子量: 180.615
• InChiKey: IUCGUPGXVCRGRV-UHFFFAOYSA-N

物化性质

• 沸点：
  366.9±15.0 °C(Predicted)
• 密度：
  1.60±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  60.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-methylimidazole-5-sulfonyl chloride 在 sodium azide 作用下， 以 水 、 丙酮 为溶剂， 反应 20.0h， 以82%的产率得到1-methyl-1H-imidazole-4-sulfonyl azide
  参考文献：
  名称：

  钯（0）催化的区域选择性酰化羰基合成N-酰基磺酰胺

  摘要：

  N-酰基磺酰胺代表了重要的羧酸生物等排体，可实现更大的分子精细化和增强的氢键能力。在本文中，我们提出了一种温和且方便的经由磺酰叠氮化物和富电子杂环的羰基偶合的钯（0）催化合成N-酰基磺酰胺。该反应通过原位产生磺酰基异氰酸酯，然后对吲哚或吡咯亲核试剂进行区域选择性酰化而进行。该方法已用于合成34个吲哚和吡咯取代的N-酰基磺酰胺的产率高达95％。重要的是，该方法是无配体的，并且与异位固体CO源相容，并且仅需要稍微升高的温度，这使其成为制备这一重要类别化合物的极具吸引力的方法。这项研究进一步研究了用碳11标记N-酰基磺酰胺的可能性，以促进生物学评估和正电子发射断层扫描的体内研究。

  DOI：

  10.1021/acs.joc.9b00740

文献信息

• Design, Synthesis, and Biological Evaluation of Androgen Receptor Degrading and Antagonizing Bifunctional Steroidal Analogs for the Treatment of Advanced Prostate Cancer
  作者：Ao Wang、Xianggang Luo、Yawan Wang、Xin Meng、Zhengyu Lu、Yushe Yang

  DOI：10.1021/acs.jmedchem.2c01164

  日期：2022.9.22

  Metastatic castration-resistant prostate cancer (mCRPC) with high mortality has seriously threatened men’s health. Bifunctional agents simultaneously degrade and antagonize androgen receptor (AR), display robust AR signaling pathway blockade, and show the therapeutic prospect for mCRPC. Herein, systemic structural modifications on the C-3, C-6, and C-17 positions of galeterone led to the discovery

  高死亡率的转移性去势抵抗性前列腺癌（mCRPC）严重威胁男性健康。双功能药物同时降解和拮抗雄激素受体 (AR)，显示出强大的 AR 信号通路阻断作用，并显示出 mCRPC 的治疗前景。在此，对galeterone的C-3，C-6和C-17位置的系统结构修饰导致发现具有AR拮抗和降解双重功能的67-b 。在体外，67-b在不同的 PCa 细胞（LNCaP 和 22RV1）中表现出优异的抗增殖活性和有效的 AR 降解活性，以及​​对野生型和突变体（W741L、T877A 和 F876L）ARs 的出色拮抗活性。体内, 67-b在 Hershberger 试验中有效抑制激素敏感器官的生长，并在恩杂鲁胺抗性（c4-2b-ENZ）异种移植模型中表现出肿瘤消退。这些结果证实67-b是一种有前途的 AR 降解剂和拮抗剂，可用于治疗 mCRPC 患者。
• Second Generation Tetrahydroquinoline-Based Protein Farnesyltransferase Inhibitors as Antimalarials
  作者：Pravin Bendale、Srinivas Olepu、Praveen Kumar Suryadevara、Vivek Bulbule、Kasey Rivas、Laxman Nallan、Brian Smart、Kohei Yokoyama、Sudha Ankala、Prakash Rao Pendyala、David Floyd、Louis J. Lombardo、David K. Williams、Frederick S. Buckner、Debopam Chakrabarti、Christophe L. M. J. Verlinde、Wesley C. Van Voorhis、Michael H. Gelb

  DOI：10.1021/jm0703340

  日期：2007.9.1

  Substituted tetrahydroquinolines (THQs) have been previously identified as inhibitors of mammalian protein farnesyltransferase (PFT). Previously we showed that blocking PFT in the malaria parasite led to cell death and that THQ-based inhibitors are the most potent among several structural classes of PFT inhibitors (PFTIs). We have prepared 266 THQ-based PFTIs and discovered several compounds that inhibit the malarial enzyme in the sub- to low-nanomolar range and that block the growth of the parasite (P. falciparum) in the lownanomolar ran-e. This body of structure- activity data can be rationalized in most cases by consideration of the X-ray structure of one of the THQs bound to mammalian PFT together with a homology structural model of the malarial enzyme. The results of this study provide the basis for selection of antimalarial PFTIs for further evaluation in preclinical drug discovery assays.
• Potent Targeting of the STAT3 Protein in Brain Cancer Stem Cells: A Promising Route for Treating Glioblastoma
  作者：Sina Haftchenary、H. Artee Luchman、Andriana O. Jouk、Anthony J. Veloso、Brent D. G. Page、Xin Ran Cheng、Sean S. Dawson、Natalie Grinshtein、Vijay M. Shahani、Kagan Kerman、David R. Kaplan、Carly Griffin、Ahmed M. Aman、Rima Al-awar、Samuel Weiss、Patrick T. Gunning

  DOI：10.1021/ml4003138

  日期：2013.11.14

  The STAT3 gene is abnormally active in glioblastoma (GBM) and is a critically important mediator of tumor growth and therapeutic resistance in GBM. Thus, for poorly treated brain cancers such as gliomas, astrocytomas, and glioblastomas, which harbor constitutively activated STAT3, a STAT3-targeting therapeutic will be of significant importance. Herein, we report a most potent, small molecule, nonphosphorylated STAT3 inhibitor, 31 (SH-4-54) that strongly binds to STAT3 protein (K-D = 300 nM). Inhibitor 31 potently kills glioblastoma brain cancer stem cells (BTSCs) and effectively suppresses STAT3 phosphorylation and its downstream transcriptional targets at low nM concentrations. Moreover, in vivo, 31 exhibited blood brain barrier permeability, potently controlled glioma tumor growth, and inhibited pSTAT3 in vivo. This work, for the first time, demonstrates the power of STAT3 inhibitors for the treatment of BTSCs and validates the therapeutic efficacy of a STAT3 inhibitor for GBM clinical application.
• Design of Novel 3-Pyrimidinylazaindole CDK2/9 Inhibitors with Potent In Vitro and In Vivo Antitumor Efficacy in a Triple-Negative Breast Cancer Model
  作者：Umed Singh、Gousia Chashoo、Sameer U. Khan、Priya Mahajan、Amit Nargotra、Girish Mahajan、Amarinder Singh、Anjna Sharma、Mubashir J. Mintoo、Santosh Kumar Guru、Hariprasad Aruri、Thanusha Thatikonda、Promod Sahu、Pankaj Chibber、Vikas Kumar、Sameer A. Mir、Sonali S. Bharate、Sreedhar Madishetti、Utpal Nandi、Gurdarshan Singh、Dilip Manikrao Mondhe、Shashi Bhushan、Fayaz Malik、Serge Mignani、Ram A. Vishwakarma、Parvinder Pal Singh

  DOI：10.1021/acs.jmedchem.7b00663

  日期：2017.12.14

  In the present study, a novel series of 3-pyrimidinylazaindoles were designed and synthesized using a bioinformatics strategy as cyclin-dependent kinases CDK2 and CDK9 inhibitors, which play critical roles in the cell cycle control and regulation of cell transcription. The present approach gives new dimensions to the existing SAR and opens a new opportunity for the lead optimizations from comparatively inexpensive starting materials. The study led to the identification of the alternative lead candidate 4ab with a nanomolar potency against CDK2 and CDK9 and potent antiproliferative activities against a panel of tested tumor cell lines along with a better safety ratio of similar to 33 in comparison to reported leads. In addition, the identified lead 4ab demonstrated a good solubility and an acceptable in vivo PK profile. The identified lead 4ab showed an in vivo efficacy in mouse triple-negative breast cancer (TNBC) syngeneic models with a TGI (tumor growth inhibition) of 90% without any mortality growth inhibition in comparison to reported leads.