N'-((4-aminophenyl)sulfonyl)-N,N-dimethylformimidamide | 6912-49-8

• 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: N'-((4-aminophenyl)sulfonyl)-N,N-dimethylformimidamide
• 英文别名: N'-(p-aminophenylsulfonyl)-N,N-dimethylformamidine；N'-(4-aminophenyl)sulfonyl-N,N-dimethylmethanimidamide
• CAS: 6912-49-8
• 化学式: C₉H₁₃N₃O₂S
• 分子量: 227.287
• InChiKey: UOWKCYAYYSXICW-UHFFFAOYSA-N

物化性质

• 熔点：
  168.5-170 °C
• 沸点：
  396.3±44.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  84.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N'-((4-aminophenyl)sulfonyl)-N,N-dimethylformimidamide 在 铜 、 四甲基氯化铵 、 potassium carbonate 、 异丙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 、 甲苯 、 叔丁醇 为溶剂， 生成 4-(bis((1-(2-(hydroxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)amino)benzenesulfonamide
  参考文献：
  名称：

  Azidothymidine “Clicked” into 1,2,3-Triazoles: First Report on Carbonic Anhydrase–Telomerase Dual-Hybrid Inhibitors

  摘要：

  Cancer cells rely on the enzyme telomerase (EC 2.7.7.49) to promote cellular immortality. Telomerase inhibitors (i.e., azidothymidine) can represent promising antitumor agents, although showing high toxicity when administered alone. Better outcomes were observed within a multipharmacological approach instead. In this context, we exploited the validated antitumor targets carbonic anhydrases (CAs; EC 4.2.1.1) IX and XII to attain the first proof of concept on CA-telomerase dual-hybrid inhibitors. Compounds 1b, 7h, 8b, and 11b showed good in vitro inhibition potency against the CAs IX and XII, with K-I values in the low nanomolar range, and strong antitelomerase activity in PC-3 and HT-29 cells (IC(50 )values ranging from 5.2 to 9.1 mu M). High-resolution X-ray crystallography on selected derivatives in the adduct with hCA II as a model study allowed to determine their binding modes and thus to set the structural determinants necessary for further development of compounds selectively targeting the tumoral cells.

  DOI：

  10.1021/acs.jmedchem.0c00636
• 作为产物：
  描述：

  N,N-二甲基甲酰胺二甲基缩醛 、 磺胺 以 neat (no solvent) 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 0.25h， 以98%的产率得到N'-((4-aminophenyl)sulfonyl)-N,N-dimethylformimidamide
  参考文献：
  名称：

  Metal- and solvent-free synthesis of N-sulfonylformamidines

  摘要：

  报道了一种无溶剂的绿色合成N-磺酰基甲酰胺的方案，通过在室温下直接冷凝N,N-二甲基甲酰胺二甲基缩醛(DMF-DMA)和磺酰胺衍生物。该方法避免了使用金属催化剂以及对药物生产不允许的危险溶剂，从而用于反应或产品的分离。因此，目前的工作提供了一种比之前报道的方法更快速高效的替代方案。该程序的温和特性通过不同功能团的耐受性得到了验证。

  DOI：

  10.1039/c3gc40797g

文献信息

• Magenta image-providing phenylazo-naphthyl dyes
  申请人：Eastman Kodak Company

  公开号：US03932381A1

  公开（公告）日：1976-01-13

  Magenta image dye-providing compound having formulas as follows: ##SPC1## Wherein: Car represents a carrier moiety which, as a function of oxidation under alkaline conditions, releases a diffusible dye from said compound; m and q each represent an integer having a value of 0 or 1; X represents a bivalent linking group; R represents hydrogen or alkyl; J represents a bivalent radical selected from sulfonyl or carbonyl; Q represents hydrogen, hydroxy or an acylamino radical; G represents hydroxy, a salt thereof, or a hydrolyzable acyloxy group; r represents an integer having a value of 1 or 2; Z represents cyano, trifluoromethyl, a carboxy, a carboxylic acid ester, nitro in the 2- or 3- position relative to the azo radical, fluorosulfonyl, sulfo, halogen, an alkylsulfonyl radical; a phenylsulfonyl radical, alkylcarbonyl, a sulfamoyl radical; a carbamoyl radical, and, in formulas I or II when r is 1, Z may represent a radical having the formula Car-[X--(NR--J).sub.q ].sub.m -- wherein Car, X, J, R, q and m are as described previously; R.sup.1 represents hydrogen, an alkyl radical, an alkoxy radical or a halogen atom; E is in the 5-, 6- or 7- position relative to G and represents hydrogen, carboxy, a carboxylic acid ester, sulfo, a sulfamoyl radical, a carbamoyl radical, alkylsulfonyl radical or a phenylsulfonyl radical; Z.sup.1 represents hydrogen or Z; with the proviso that there be no more than one sulfo radical and no more than one carboxy radical present in said compound.

  蓝紫色图像染料提供化合物的化学式如下：其中：Car代表一个载体基团，根据碱性条件下的氧化作用，从该化合物中释放出可扩散的染料；m和q分别代表取值为0或1的整数；X代表双价连接基团；R代表氢或烷基；J代表从磺酰基或羰基中选择的双价基团；Q代表氢、羟基或酰胺基团；G代表羟基、其盐，或可水解的酰氧基团；r代表取值为1或2的整数；Z代表氰基、三氟甲基、一个羧基、一个羧酸酯、在与偶氮基团相对的2-或3-位上的硝基、氟磺酰基、磺酰基、卤素、一个烷基磺酰基团、苯基磺酰基团、烷基羰基、磺胺基、氨基基团；以及在化学式I或II中，当r为1时，Z可以表示具有化学式Car-[X--(NR--J).sub.q ].sub.m --的基团，其中Car、X、J、R、q和m如前所述；R.sup.1代表氢、烷基基团、烷氧基团或卤素原子；E位于与G相对的5-、6-或7-位上，表示氢、羧基、羧酸酯、磺酰基、磺胺基、羰基基团、烷基磺酰基团或苯基磺酰基团；Z.sup.1代表氢或Z；但前提是该化合物中不得有超过一个磺酰基团和一个羧基团。
• Inhibition Profiles of Some Novel Sulfonamide-Incorporated α-Aminophosphonates on Human Carbonic Anhydrases
  作者：Marjan Sobati、Morteza Abdoli、Alessandro Bonardi、Paola Gratteri、Claudiu T. Supuran、Raivis Žalubovskis

  DOI：10.1021/acsmedchemlett.3c00200

  日期：2023.8.10

  unknown sulfonamide-incorporated α-aminophosphonate derivatives were synthesized through the one-pot, two-step FeCl3-catalyzed coupling of 4-aminobenzenesulfonamide with the appropriate benzaldehydes and diethyl phosphite. The new sulfonamides inhibition studies were performed on four carbonic anhydrase isoforms, i.e., the cytosolic human (h) hCA I and II (off-targets) as well as transmembrane cancer-related

  通过一锅两步FeCl 3催化4-氨基苯磺酰胺与适当的苯甲醛和亚磷酸二乙酯的偶联，合成了一系列迄今为止未知的磺酰胺掺入的α-氨基膦酸酯衍生物。新的磺胺类药物抑制研究针对四种碳酸酐酶异构体进行，即胞质人 (h) hCA I 和 II（脱靶）以及跨膜癌相关的 hCA IX 和 XII（靶标）。在合成的化合物中，与脱靶 hCA I (hCA I/IX = 78; hCA I/XII = 458) 和 hCA II (hCA II/IX = 10；hCA II/XII = 56）并通过计算机研究了对映异构体R和S的结合模式。
• Synthesis and reactions of amide mercaptals
  作者：I. A. Ivanova、B. P. Fedorov、F. M. Stoyanovich

  DOI：10.1007/bf00846003

  日期：1965.12
• Metal- and solvent-free synthesis of N-sulfonylformamidines
  作者：Nisha Chandna、Navneet Chandak、Pawan Kumar、Jitander K. Kapoor、Pawan K. Sharma

  DOI：10.1039/c3gc40797g

  日期：——

  A solvent-free green synthesis of N-sulfonylformamidines is reported via the direct condensation of N,N-dimethylformamide dimethyl acetal (DMF-DMA) and sulfonamide derivatives at room temperature. The described method avoids the use of metal catalysts as well as hazardous solvents, which are not permitted for pharmaceutical manufacture, for the reactions or isolation of products. Hence, the current work presents a fast and efficient alternative to earlier reported methods. The mild nature of the procedure is demonstrated by varied functional group tolerance.

  报道了一种无溶剂的绿色合成N-磺酰基甲酰胺的方案，通过在室温下直接冷凝N,N-二甲基甲酰胺二甲基缩醛(DMF-DMA)和磺酰胺衍生物。该方法避免了使用金属催化剂以及对药物生产不允许的危险溶剂，从而用于反应或产品的分离。因此，目前的工作提供了一种比之前报道的方法更快速高效的替代方案。该程序的温和特性通过不同功能团的耐受性得到了验证。
• Azidothymidine “Clicked” into 1,2,3-Triazoles: First Report on Carbonic Anhydrase–Telomerase Dual-Hybrid Inhibitors
  作者：Emanuela Berrino、Andrea Angeli、Dmitry D. Zhdanov、Anna P. Kiryukhina、Andrea Milaneschi、Alessandro De Luca、Murat Bozdag、Simone Carradori、Silvia Selleri、Gianluca Bartolucci、Thomas S. Peat、Marta Ferraroni、Claudiu T. Supuran、Fabrizio Carta

  DOI：10.1021/acs.jmedchem.0c00636

  日期：2020.7.9

  Cancer cells rely on the enzyme telomerase (EC 2.7.7.49) to promote cellular immortality. Telomerase inhibitors (i.e., azidothymidine) can represent promising antitumor agents, although showing high toxicity when administered alone. Better outcomes were observed within a multipharmacological approach instead. In this context, we exploited the validated antitumor targets carbonic anhydrases (CAs; EC 4.2.1.1) IX and XII to attain the first proof of concept on CA-telomerase dual-hybrid inhibitors. Compounds 1b, 7h, 8b, and 11b showed good in vitro inhibition potency against the CAs IX and XII, with K-I values in the low nanomolar range, and strong antitelomerase activity in PC-3 and HT-29 cells (IC(50 )values ranging from 5.2 to 9.1 mu M). High-resolution X-ray crystallography on selected derivatives in the adduct with hCA II as a model study allowed to determine their binding modes and thus to set the structural determinants necessary for further development of compounds selectively targeting the tumoral cells.