4-(3-acetamidopropyl)benzenesulfonyl chloride | 53199-94-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(3-acetamidopropyl)benzenesulfonyl chloride
• CAS: 53199-94-3
• 化学式: C₁₁H₁₄ClNO₃S
• 分子量: 275.756
• InChiKey: ZLBXTJOXROCVNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  71.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(3-acetamidopropyl)benzenesulfonyl chloride 在 吡啶 、 sodium hydroxide 、 sodium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 45.0h， 生成 4-(3-Amino-propyl)-N-(3-hydroxy-propyl)-N-(2-phenyl-2H-pyrazol-3-yl)-benzenesulfonamide
  参考文献：
  名称：

  Synthesis of Sulfaphenazole Derivatives and Their Use as Inhibitors and Tools for Comparing the Active Sites of Human Liver Cytochromes P450 of the 2C Subfamily

  摘要：

  Twenty-three new derivatives of sulfaphenazole (SPA) were synthesized to further explore the topology of the active sites of human liver cytochromes P450 of the 2C subfamily and to find new selective inhibitors of these cytochromes. These compounds are derived from SPA by replacement of the NH2 and H (of the SO2NH function) substituents of SPA with various R-1 and R-2 groups, respectively. Their inhibitory effects were studied on recombinant CYP 2C8, 2C9, 2C18, and 2C19 expressed in yeast. High affinities for CYP 2C9 (IC50 < 1 muM) were only observed for SPA derivatives having the SO2NH function and a relatively small R-1 substituent (R-1 = NH2, CH3). Any increase in the size of R-1 led to a moderate decrease of the affinity, and the N-alkylation of the SO2NH function of SPA to a greater decrease of this affinity. The same structural changes led to opposite effects on molecular recognition by CYP 2C8 and 2C18, which generally exhibited similar behaviors. Thus, contrary to CYP 2C9, CYP 2C8 and 2C18 generally prefer neutral compounds with relatively large R-1 and R2 substituents. CYP 2C19 showed an even lower affinity for anionic compounds than CYP 2C8 and 2C18. However, as CYP 2C8 and 2C18, CYP 2C19 showed a much better affinity for neutral compounds derived ftom N-alkylation of SPA and for anionic compounds bearing a larger R, substituent. One of the new compounds (R-1 = methyl, R-2 = propyl) inhibited all human CYP 2Cs with IC50 values between 10 and 20 muM, while another one (R-1 = allyl, R-2 = methyl) inhibited all CYP 2Cs except CYP 2C9, and a third one (R-1 = R-2 = methyl) inhibited all CYP 2Cs except CYP 2C8. Only 2 compounds of the 25 tested derivatives were highly selective toward one human CYP 2C; these are SPA and compound I (Ri = CH3, R2 = H), which acted as selective CYP 2C9 inhibitors. However, some SPA derivatives selectively inhibited CYP 2C8 and 2C18. Since CYP 2C18 is hardly detectable in human liver, these derivatives could be interesting molecules to selectively inhibit CYP 2C8 in human liver microsomes. Thus, compound 11 (R-1 = NH2, R-2 = (CH2)(2)CH(CH3)(2)) appears to be particularly interesting for that purpose as its IC50 value for CYP 2C8 is low (3 muM) and 20-fold smaller than those found for CYP 2C9 and 2C19.

  DOI：

  10.1021/jm010861y
• 作为产物：
  描述：

  N-(3-苯基丙基)乙酰胺 在 氯磺酸 作用下， 反应 3.67h， 以63%的产率得到4-(3-acetamidopropyl)benzenesulfonyl chloride
  参考文献：
  名称：

  脂蛋白相关的磷脂酶A2的新型，有效和口服生物利用抑制剂的结构指导的发现。

  摘要：

  脂蛋白相关的磷脂酶A2（Lp-PLA2）是动脉粥样硬化，阿尔茨海默氏病和糖尿病性黄斑水肿的有希望的治疗靶标。在这里，我们报告鉴定衍生自相对较弱的片段的新型磺酰胺支架Lp-PLA2抑制剂。在该片段上进行相似搜索，然后进行分子对接，导致发现了一种微摩尔抑制剂，其效价提高了300倍。随后，通过应用结构指导的设计策略，成功实现了从头至尾的优化，并获得了许多具有单位数纳摩尔效价的Lp-PLA2抑制剂。在初步评估了体内和体外的药物相似性后，将化合物37该同类抑制剂系列在雄性Sprague-Dawley大鼠中具有良好的抑制活性和良好的口服生物利用度，从而脱颖而出，为进一步开发提供了良好的候选者。因此，本研究清楚地证明了在有效的铅发现项目中整合使用片段筛选，晶体结构确定，虚拟筛选和药物化学的功能和优势，为基于结构的药物设计提供了一个很好的例子。

  DOI：

  10.1021/acs.jmedchem.7b01530

文献信息

• Design and synthesis of sulfonamidophenylethylureas as novel cardiac myosin activator
  作者：Manoj Manickam、Hitesh B. Jalani、Thanigaimalai Pillaiyar、Pulla Reddy Boggu、Niti Sharma、Eeda Venkateswararao、You-Jung Lee、Eun-Seok Jeon、Min-Jeong Son、Sun-Hee Woo、Sang-Hun Jung

  DOI：10.1016/j.ejmech.2017.10.077

  日期：2018.1

  of urea derivatives have been synthesized to explore its structure activity relationship. Among them N,N-dimethyl-4-(2-(3-(3-phenylpropyl)ureido)ethyl)benzenesulfonamide (13, CMA = 91.6%, FS = 17.62%; EF = 11.55%), N,N-dimethyl-4-(2-(1-methyl-3-(3-phenylpropyl)ureido)ethyl)benzene sulfonamide (40, CMA = 52.3%, FS = 38.96%; EF = 24.19%) and N,N-dimethyl-4-(2-(3-methyl-3-(3-phenylpropyl)ureido)ethyl)benzenesulfonamide

  为了优化尿素铅支架1和2作为选择性心肌肌球蛋白ATPase激活剂，已合成了一系列尿素衍生物以探索其结构活性关系。其中N，N-二甲基-4-（2-（3-（3-（3-苯基丙基）脲基）乙基）苯磺酰胺（13，CMA = 91.6％，FS = 17.62％; EF = 11.55％），N，N-二甲基-4-（2-（1-甲基-3-（3-苯基丙基）脲基）乙基）苯磺酰胺（40，CMA = 52.3％，FS = 38.96％; EF = 24.19％）和N，N-二甲基-4 -（2-（3-甲基-3-（3-苯基丙基）脲基）乙基）苯磺酰胺（41，CMA = 47.6％，FS = 23.19％; EF = 15.47％）被证明可在体外激活心肌肌球蛋白和体内。此外，在5μM的13（47.9±3.2），40（45.5±2.4）和41（63.5±2.2）的心室细胞收缩百分比变化在离体大鼠心室肌细胞中表现出正性肌力作用。的有效
• 一种异硫氰酸酯衍生物及其制备方法和用途
  申请人：厦门倍博特医学科技有限公司

  公开号：CN114890928A

  公开（公告）日：2022-08-12

  本申请公开了一种异硫氰酸酯衍生物及其制备方法和用途，涉及医药技术的领域；其中，一种异硫氰酸酯衍生物，结构式如下所示： 其中，R1和R2独立选自氢原子、卤素、烷基以及卤代烷基中的一种，n表示不同的碳链链长。本申请提供的异硫氰酸酯衍生物对于血液恶性肿瘤以及实体恶性肿瘤有较强的抑制活性，可用于制备抗肿瘤药物，为研究与开发新的抗肿瘤药物提供了候选化合物。
• SHEVCHENKO, L. I.;LOZINSKIJ, M. O.;KUTSENKO, T. A.;TATAROVA, T. A.;OZERYA+, FIZIOL. AKTIV. VESHCHESTVA,(1990) N2, S. 26-30
  作者：SHEVCHENKO, L. I.、LOZINSKIJ, M. O.、KUTSENKO, T. A.、TATAROVA, T. A.、OZERYA+

  DOI：——

  日期：——