Refernces
10.1016/j.bmc.2013.10.040
The research focused on the synthesis and evaluation of imatinib mesylate (STI-571) analogs as potential agents for PET imaging of Bcr-Abl and c-KIT expression at the kinase level. The study involved molecular modeling to predict binding configurations, followed by the synthesis of STI-571 and its analogs using various reactants such as 2-methyl-5-nitroaniline, cyanamide, and 3-acetylpyridine derivatives. Radiolabeling with [18F] and [131I] was performed to prepare PET imaging agents. In vitro kinase assays were conducted to assess the potency of the analogs in inhibiting Bcr-Abl and c-KIT kinase activities. The uptake rates of [18F]-STI-571 in K562 cells (expressing Abl) and U87WT cells (overexpressing c-KIT) were measured and compared with those in U87 cells. PET scans were conducted on tumor-bearing mice to visualize tumor uptake and contrast. The research utilized various analytical techniques, including HPLC, MS, NMR, and radio-TLC, to monitor reactions, assess radiochemical purity, and characterize compounds. The results showed that the [18F]-STI-571 analog could serve as a marker for sensitivity to Bcr-Abl and c-KIT inhibitors, potentially aiding in patient selection for targeted therapies.
10.1021/op700270n
The study presents an improved method for synthesizing Imatinib and its analogues. Imatinib is a tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GISTs). The researchers developed a more cost-effective and environmentally friendly approach to synthesize Imatinib by avoiding the use of toxic cyanamide and expensive palladium compounds. Key chemicals involved include enaminone, guanidine nitrate, and copper salts. Enaminone reacts with guanidine nitrate to form pyrimidinyl amine, a crucial intermediate. Copper salts are used as catalysts in the C-N bond-forming reaction to produce another key intermediate. The nitro compound intermediate is reduced using a N2H4·H2O/FeCl3/C system. The final steps involve acylation and amination reactions to yield Imatinib base. This method achieves good yields and avoids hazardous reagents, making it suitable for industrial applications.
10.1002/ejoc.201501084
The study investigates the use of a sterically congested α-cyanoamine as an effective cyanating reagent for the cyanation of acetals and orthoesters. The key chemicals used in the study include α-cyanoamines, which were prepared from secondary amines and α-bromoacetonitrile, and trichlorosilyl triflate (SiCl3OTf), which acts as a catalyst. These chemicals serve the purpose of facilitating the cyanation reaction, leading to the production of cyanated adducts in high yields. The α-cyanoamines were found to be influenced by steric effects, with more hindered amines improving the product yield, suggesting that they prevent the formation of unfavorable complexes with the catalyst and retain their cyanating functionality. The study also detected oxocarbenium cations as intermediates through NMR spectroscopy, providing insights into the reaction mechanism.
10.1016/j.tetlet.2009.03.017
The research focuses on the efficient synthesis of cyanamide from amine, utilizing a hypervalent iodine(III) reagent, specifically diacetoxyiodobenzene (DIB), as a non-metallic, non-toxic, and eco-friendly desulfurizing agent. The purpose of this study was to develop an alternative method to the traditional synthesis of cyanamides, which often involves the use of highly toxic cyanogen halides or other harmful reagents. The researchers achieved this by employing a one-pot strategy that starts with dithiocarbamic acid salts/amines, generates alkyl or aryl isothiocyanates in situ through desulfurization with DIB, and then reacts these with aqueous ammonia to form alkyl or aryl thiourea. Further oxidative desulfurization with DIB leads to the formation of the corresponding cyanamide in good yields. The conclusions drawn from the study highlight the mild reaction conditions, shorter reaction times, and environmentally benign protocol as significant advantages, making this methodology a suitable alternative for the preparation of various organic cyanamides. The chemicals used in the process include dithiocarbamic acid salts, amines, aqueous ammonia, and DIB, with the latter serving as a key reagent for both desulfurization steps and the oxidation of thiourea to cyanamide.
10.1021/jf802802g
The research focuses on the synthesis and insecticidal activity of N-substituted (1,3-thiazole)alkyl sulfoximine derivatives, a new chemical family of neonicotinoid insecticides. The purpose of this study was to design and synthesize 10 such derivatives and evaluate their insecticidal activities against Myzus persicae, a common pest known as the peach aphid. The researchers used various chemicals in the synthesis process, including 5-halomethyl-1,3-thiazole, iodobenzene diacetate, cyanamide, and 3-chloroperoxy-benzoid acid, among others. The synthesized compounds were characterized using techniques like NMR, IR, and elemental analysis. The bioassays revealed that some of the synthesized compounds exhibited good insecticidal activities at a concentration of 10 mg/L. The study concluded that the N-cyano sulfoximine pharmacophore (S(O)dN-CN) with a 2-chloro-4-trifluoromethyl-5-thiazolyl moiety was the most promising structure for insecticidal activity, and the nature and position of the substitutes on the thiazolyl ring significantly influenced the efficacy.
