5-氯-2-氰基-苯磺酰氯 | 411210-92-9

• 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: 5-氯-2-氰基-苯磺酰氯
• 中文别名: 5-氯-2-氰基苯磺酰氯
• 英文名称: 5-chloro-2-cyanobenzenesulfonyl chloride
• 英文别名: 5-Chloro-2-cyanobenzene-1-sulfonyl chloride
• CAS: 411210-92-9
• 化学式: C₇H₃Cl₂NO₂S
• mdl: MFCD09739347
• 分子量: 236.078
• InChiKey: PHNDFODTTWOSSX-UHFFFAOYSA-N

物化性质

• 沸点：
  379.4±32.0 °C(Predicted)
• 密度：
  1.65±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-氯-2-氰基-苯磺酰氯 在 一水合肼 作用下， 以 乙醇 为溶剂， 生成 4-Hydrazino-7-chlor-2H-1.2.3-benzothiadiazin-1.1-dioxid
  参考文献：
  名称：

  杂环研究中的化学研究。31. Mitteilung。苯并1,2,3-噻二嗪降压药和利尿药

  摘要：

  描述了4-肼基-苯并-1,2,3-噻二嗪1,1-二氧化物的合成。讨论了这些化合物的化学反应和性质。一些衍生物显示出降压和利尿活性。

  DOI：

  10.1002/hlca.19620450327
• 作为产物：
  描述：

  甲基2-胺-4-氯苯酚酯 在 盐酸 、 五氯化磷 、 溶剂黄146 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 11.0h， 生成 5-氯-2-氰基-苯磺酰氯
  参考文献：
  名称：

  Studies of non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 2: Synthesis and structure–activity relationships of 2-cyano and 2-hydroxy thiazolidenebenzenesulfonamide derivatives

  摘要：

  In a previous study, we described the structure-activity relationships (SARs) for a series of thiazolidenebenzenesulfonamide derivatives. These compounds were found to be highly potent inhibitors of the wild type (WT) and Y181C mutant reverse transcriptases (RTs) and modest inhibitors of K 103N RT. These molecules are thus considered to be a novel class of non-nucleoside HIV-1 RT inhibitors (NNRTIs). In this paper, we have examined the effects of substituents on both the thiazolidene and benzenesulfonamide moieties. Introduction of a 2-cyanophenyl ring into these moieties significantly enhanced anti-HIV-1 activity, whereas a 2-hydroxyphenyl group endowed potent activity against RTs, including K103N and Y181C mutants. Among the series of molecules examined, 101 and 18b (YM-228855), combinations of 2-cyanophenyl and 4-methyl-5-isopropylthiazole moieties, showed extremely potent anti-HIV-1 activity. The EC50 values of 101 and 18b were 0.0017 and 0.0018 muM, respectively. These values were lower than that of efavirenz (3). Compound 11g (YM-215389), a combination of 2-hydroxyphenyl and 4-chloro-5-isopropylthiazole moieties, proved to be the most active against both K103N and Y181C RTs with IC50 values of 0.043 and 0.013 muM, respectively. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.11.045

文献信息

• Rational Design of Highly Potent, Selective, and Bioavailable SGK1 Protein Kinase Inhibitors for the Treatment of Osteoarthritis
  作者：Nis Halland、Friedemann Schmidt、Tilo Weiss、Ziyu Li、Jörg Czech、Joachim Saas、Danping Ding-Pfennigdorff、Matthias K. Dreyer、Carsten Strübing、Marc Nazare

  DOI：10.1021/acs.jmedchem.1c01601

  日期：2022.1.27

  high requirements for the drug selectivity, pharmacokinetic, and safety profile. We describe the identification of a highly selective druglike 1H-pyrazolo[3,4-d]pyrimidine SGK1 inhibitor 17a that matches both safety and pharmacokinetic requirements for oral dosing. Rational compound design was facilitated by a novel hSGK1 co-crystal structure, and multiple ligand-based computer models were applied to guide

  丝氨酸/苏氨酸激酶 SGK1 是 β-连环蛋白途径的激活剂，是软骨降解的强大刺激剂，在患病的骨关节炎软骨中被发现在基因组控制下被上调。今天，没有口服疾病缓解治疗可用，并且该适应症中的慢性治疗对药物选择性、药代动力学和安全性提出了很高的要求。我们描述了一种高选择性药物样 1 H-吡唑并[3,4- d ]嘧啶 SGK1 抑制剂17a的鉴定符合口服给药的安全性和药代动力学要求。新的 hSGK1 共晶结构促进了合理的化合物设计，并应用了多个基于配体的计算机模型来指导化合物 ADMET 的化学优化和选择性曲线。选择化合物用于小鼠股骨头软骨外植体模型中的亚慢性机制研究，化合物17a成为药物样 SGK1 抑制剂，具有高度优化的特性，适合口服给药，作为一种新型的、潜在的骨关节炎疾病缓解剂。
• Discovery of <i>N</i>-[4-(1<i>H</i>-Pyrazolo[3,4-<i>b</i>]pyrazin-6-yl)-phenyl]-sulfonamides as Highly Active and Selective SGK1 Inhibitors
  作者：Nis Halland、Friedemann Schmidt、Tilo Weiss、Joachim Saas、Ziyu Li、Jörg Czech、Matthias Dreyer、Armin Hofmeister、Katharina Mertsch、Uwe Dietz、Carsten Strübing、Marc Nazare

  DOI：10.1021/ml5003376

  日期：2015.1.8

  From a virtual screening starting point, inhibitors of the serum and glucocorticoid regulated kinase 1 were developed through a combination of classical medicinal chemistry and library approaches. This resulted in highly active small molecules with nanomolar activity and a good overall in vitro and ADME profile. Furthermore, the compounds exhibited unusually high kinase and off-target selectivity due

  从虚拟筛选的起点出发，通过结合经典药物化学和文库方法开发了血清和糖皮质激素调节激酶1抑制剂。这产生了具有纳摩尔活性并具有良好的整体体外和ADME谱的高活性小分子。此外，由于其刚性结构，这些化合物显示出异常高的激酶和脱靶选择性。
• N-[4-(1H-吡唑并[3,4-b]吡嗪-6-基)-苯基]-磺 酰胺类及其作为药物的用途
  申请人：赛诺菲

  公开号：CN103012407B

  公开（公告）日：2016-06-29

  本发明涉及具有式I的N-[4-(1H-吡唑并[3，4-b]吡嗪-6-基)-苯基]-磺酰胺类，其中，Ar，R1，R2和n具有如权利要求中所示含义。式I的化合物是有价值的具有药理学活性的化合物，其调节蛋白激酶活性，特别是血清及糖皮质激素调节激酶的活性(SGK)，尤其是血清及糖皮质激素调节激酶同工型1(SGK-1，SGK1)的活性，并且这些化合物适合于治疗SGK活性不适当的疾病，例如退化性关节疾病或炎症过程如骨关节炎或风湿病。本发明进一步涉及制备式I的化合物的方法，它们作为药物的用途以及包含它们的药物组合物。
• HETEROCYCLIC COMPOUND
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US20190169166A1

  公开（公告）日：2019-06-06

  Provided is a heterocyclic compound that may have a GCN2 inhibitory action, and is expected to be useful for the prophylaxis or treatment of GCN2 associated diseases including cancer and the like. A compound represented by the formula (I): wherein each symbol is as described in the DESCRIPTION, or a salt thereof.

  提供的是一种可能具有GCN2抑制作用的杂环化合物，预计可用于预防或治疗与GCN2相关的疾病，包括癌症等。一种由以下式（I）表示的化合物： 其中每个符号如描述中所述，或其盐。
• [EN] N-(4-(AZAINDAZOL-6-YL)-PHENYL)-SULFONAMIDES AND THEIR USE AS PHARMACEUTICALS<br/>[FR] N-(4-(AZAINDAZOL-6-YL)PHÉNYL)SULFONAMIDES ET LEUR UTILISATION COMME PRODUITS PHARMACEUTIQUES
  申请人：SANOFI SA

  公开号：WO2014140065A1

  公开（公告）日：2014-09-18

  N-(4-(Azaindazol-6-yl)-phenyl)-sulfonamides and their use as pharmaceuticals The present invention relates to N-(4-(azaindazol-6-yl)-phenyl)-sulfonamides of the formula I, wherein Ar, n, X, Z, R1, R2 and R3 have the meanings indicated in the claims. The compounds of the formula I are valuable pharmacologically active compounds which modulate protein kinase activity, specifically the activity of serum and glucocorticoid regulated kinase (SGK), in particular of serum and glucocorticoid regulated kinase isoform 1 (SGK-1, SGK1), and are suitable for the treatment of diseases in which SGK activity is inappropriate, for example degenerative joint disorders or inflammatory processes such as osteoarthritis or rheumatism. The invention furthermore relates to processes for the preparation of the compounds of the formula I, their use as pharmaceuticals, and pharmaceutical compositions comprising them.

  本发明涉及公式I的N-(4-(吡唑吲唑-6-基)-苯基)-磺酰胺，其中Ar、n、X、Z、R1、R2和R3具有索引中指示的含义。公式I的化合物是有价值的药理活性化合物，可以调节蛋白激酶活性，特别是血清和糖皮质激素调节激酶（SGK）的活性，特别是血清和糖皮质激素调节激酶同工酶1（SGK-1，SGK1）的活性，并适用于治疗SGK活性不当的疾病，例如退行性关节疾病或炎症过程，如骨关节炎或风湿病。本发明还涉及公式I的化合物的制备方法，它们作为药物的用途，以及包含它们的药物组合物。