- General Acid Catalyzed Addition of Anilines to Dicyanamide Ion through a Concerted Mechanism
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The addition of anilines to dicyanamide ion in aqueous solution is shown to be general acid catalyzed.The Broensted exponent for the reaction where aniline substituent is varied and the acid is retained constant is βnuc=0.63 for acetic acid and βnuc=0.66 for oxonium ion.The Broensted exponent for varying the general acid when the aniline is kept constant is -0.54 for 4-sulfanilic acid.The data are consistent with a mechanism where neutral aniline attacks the anionic dicyanamide assisted by concerted proton transfer from the general acid to the substrate nitrogen.
- Hill, Steven V.,Longridge, Jethro L.,Williams, Andrew
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- Discovery of Novel Inhibitors Targeting Human O-GlcNAcase: Docking-Based Virtual Screening, Biological Evaluation, Structural Modification, and Molecular Dynamics Simulation
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β-N-Acetylhexosaminidases have emerged as promising targets for drug and pesticide discovery due to their critical physiological functions in various cellular processes. In particular, human O-GlcNAcase (hOGA) from the glycoside hydrolase family 84 (GH84) has gained significant attention. This enzyme was found to be linked to various diseases such as diabetes, cancer, and Alzheimer's disease (AD). In this study, to develop novel hOGA inhibitors with suitable pharmaceutical properties, virtual screening of the Drugbank database was performed using a docking-based approach targeting hOGA. Chlorhexidine (4, Ki = 4.0 μM) was identified as a potent hOGA inhibitor with excellent selectivity (Ki > 200 μM against human β-N-acetylhexosaminidase B) and subjected to structural modifications and SAR studies. Furthermore, molecular dynamics simulations as well as binding free energy and free energy decomposition calculations were carried out to investigate the basis for the efficiency of potent inhibitors against hOGA. This present work revealed the new application of the disinfectant chlorhexidine and provided useful information for the future design of hOGA inhibitors.
- Dong, Lili,Shen, Shengqiang,Chen, Wei,Xu, Dongdong,Yang, Qing,Lu, Huizhe,Zhang, Jianjun
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- Synthesis method of 4-chlorobenzene cyanoguanidine
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The invention provides a synthetic method of 4-chlorobenzene cyanoguanidine. According to the method, diazonium p-chlorobenzene chloride and dicyandiamide are taken as main raw materials, and a targetcompound is synthesized by two steps. The preparation method comprises the following steps: carrying out coupling reaction on the diazonium p-chlorobenzene chloride and the dicyandiamide in the presence of sodium carbonate to obtain an intermediate 4-chlorphenyl azo cyanoguanidine; then putting the intermediate into diluted hydrochloric acid, performing heating and discharging nitrogen to obtaina crude product; and dissolving the crude product in a dilute sodium hydroxide solution, removing color by activated carbon, performing neutralizing by adding acid, carrying out suction filtration andwashing, and performing drying to obtain a final product 4-chlorobenzene cyanoguanidine. Chlorinated diazonium p-chlorobenzene needs to be prepared for immediate use and is prepared by reacting 4-chloroaniline with sodium nitrite under an acidic condition. The preparation method is simple, mild in reaction condition, free of organic solvent, simple and convenient in subsequent treatment, safe andenvironmentally friendly; and meanwhile, the obtained product is relatively good in purity and relatively high in yield, and the method is a relatively good and safe method for synthesizing the aromatic guanidino compound, namely, the 4-chlorobenzene cyanoguanidine.
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Paragraph 0011-0017
(2021/02/10)
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- Repurposing N,N'-bis-(arylamidino)-1,4-piperazinedicarboxamidines: An unexpected class of potent inhibitors of cholinesterases
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Drug repurposing (=drug repositioning) is an effective way to cut costs for the development of new therapeutics and to reduce the time-to-market time-span. Following this concept a small library of compounds was screened for their ability to act as inhibitors of acetyl- and butyrylcholinesterase. Picloxydine, an established antiseptic, was shown to be an inhibitor for both enzymes. Systematic variation of the aryl substituents led to analogs possessing almost the same good properties as gold standard galantamine hydrobromide.
- Loesche, Anne,Wiese, Jana,Sommerwerk, Sven,Simon, Vivienne,Brandt, Wolfgang,Csuk, René
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supporting information
p. 430 - 434
(2016/10/04)
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- BRIDGED POLYCYCLIC COMPOUND BASED COMPOSITIONS FOR RENAL THERAPY
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A pharmaceutically active agent, a pharmaceutically active agent carrier and method of use thereof are described. In some embodiments, a system may include a composition. The composition may include one or more bridged polycyclic compounds. At least one of the bridged polycyclic compounds may include at least two cyclic groups, and at least two pharmaceutically active agents may be associated with the bridged polycyclic compound. In some embodiments, one or more bridged polycyclic compounds may be administered to a subject to control fluid and/or waste levels.
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Page/Page column 47
(2010/02/16)
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- BRIDGED POLYCYCLIC COMPOUND BASED COMPOSITIONS FOR CONTROLLING CHOLESTEROL LEVELS
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A pharmaceutically active agent, a pharmaceutically active agent carrier and method of use thereof are described. In some embodiments, a system may include a composition. The composition may include one or more bridged polycyclic compounds. At least one of the bridged polycyclic compounds may include at least two cyclic groups, and at least two pharmaceutically active agents may be associated with the bridged polycyclic compound. In some embodiments, one or more bridged polycyclic compounds may be administered to a subject to improve cardiac and/or cardiovascular health. In some embodiments, one or more bridged polycyclic compounds may be administered to a subject to control cholesterol levels.
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Page/Page column 39; 47
(2010/02/17)
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- BRIDGED POLYCYCLIC COMPOUND BASED COMPOSITIONS FOR THE INHIBITION AND AMELIORATION OF DISEASE
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A pharmaceutically active agent, a pharmaceutically active agent carrier and method of use thereof are described. In some embodiments, a system may include a composition. The composition may include one or more bridged polycyclic compounds. At least one of the bridged polycyclic compounds may include at least two cyclic groups, and at least two pharmaceutically active agents may be associated with the bridged polycyclic compound. In some embodiments, a bridged polycyclic compound may be pharmaceutically active. In some embodiments, a bridged polycyclic compound may be function as a carrier for pharmaceutically active agents.
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Page/Page column 81-82
(2008/12/08)
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- Synthesis and structure-activity relationships of novel antiseptics
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For the purpose of developing new antiseptics, we searched for compounds having high biocidal activity covering both gram-positive and gram-negative bacteria. Accordingly, we designed 1,5-disubstituted biguanides and synthesized them using two alternative efficient reaction schemes. The bactericidal activity of these biguanides was assayed by the micro titration plate method. Among the biguanides synthesized, 3,4-dichlorobenzyl derivatives were found to exhibit particularly high bactericidal activity. Ultimately, compound II was chosen as a candidate novel antiseptic, which is currently under continued evaluation.
- Tsubouchi, Hidetsugu,Ohguro, Kinue,Yasumura, Koichi,Ishikawa, Hiroshi,Kikuchi, Mikio
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p. 1721 - 1724
(2007/10/03)
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