10.1007/s00044-010-9411-5
The research focuses on the design, synthesis, and evaluation of novel substituted-piperazine analogues for their antiplatelet aggregation activity, which is crucial for managing cardiovascular and thromboembolic diseases. The study involves the synthesis of new carbamoylpyridine and carbamoylpiperidine analogues containing a nipecotic acid scaffold, with a series of chemical reactions utilizing reactants such as nicotinoyl chloride, various aryl and aroyl-piperazines, alkyl or aroylhalides, and potassium carbonate. The synthesized compounds were evaluated for their inhibitory activity against platelet aggregation using different agonists like ADP, adrenaline, collagen, arachidonic acid, and ristocetin. The experiments included quaternization, catalytic hydrogenation, and molecular modeling investigations to understand the structure-activity relationship and the impact of lipophilicity on activity. The most active compounds identified were N1-[1-(4-bromobenzyl)-3-piperidino-carbonyl]-N4-(2-chlorophenyl)-piperazine hydrobromide (20) and 1,4-bis-[3-[N4-(2-chlorophenyl)-N1-(piperazino-carbonyl)]-piperidin-1-yl-methyl]-benzene dibromide (30), both exhibiting significant antiplatelet aggregating effects at a concentration of 0.06 μM. The analyses included NMR spectroscopy, mass spectrometry, and molecular docking studies to elucidate the compounds' structures and their interactions with the thrombin receptor.
10.1002/hlca.19500330323
This study focuses on the synthesis and analysis of various derivatives of p-aminosalicylic acid. The key chemicals involved include 2-nitro-p-toluidine, ethyl chloroformate, and sodium methoxide, which are used to produce 2-nitro-4-methoxytoluidine (I). This compound is then oxidized with potassium permanganate to give 2-nitro-4-carboxyaminobenzoic acid (II). Other derivatives synthesized include p-nitro-o-acetylsalicylic acid (III), ethyl p-acetylamidosalicylate (IV), and ethyl p-N-nicotinamidosalicylate (V), each of which is generated through specific reactions involving acetic anhydride, acetyl chloride, nicotinic chloride, and other reagents. The study also discusses esters of methionine and other specific amino acids, which react with crystalline chymotrypsin to form peptides, highlighting potential relevance to biological peptide synthesis. The study details the synthetic procedures and properties of the resulting compounds, and provides yields and melting points for each derivative, demonstrating chemical transformations and their analytical significance.
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