Refernces
10.1023/A:1015334703526
The research focuses on the chemistry of urea nitro derivatives, specifically the synthesis of nitramide from N,N'-dinitrourea and subsequent reactions of nitramide. The study developed convenient procedures for synthesizing nitramide based on urea through the hydrolysis of N,N'-dinitrourea, which is highly reactive and sensitive to mechanical disturbance. The experiments involved various reactants such as urea, N,N'-dinitrourea, water, sulfuric acid, ammonium nitrate, and water-saturated solvents with low dielectric constants. The analyses used to monitor the reactions and characterize the products included infrared (IR) and ultraviolet (UV) spectroscopy, as well as kinetic measurements to determine the rate constants of the hydrolysis reactions. The study also explored nitramide's decomposition in acid media and its reactions with formaldehyde, ethyl acetate, and acetic anhydride, leading to the formation of various compounds like dinitramide, methylenedinitramine, and N-nitroacetamide.
10.1135/cccc19740333
The research focused on the synthesis of 9-chloro-10-(4-methylpiperazino)-10,11-dihydrodibenzo[b,f]thiepin (I), a compound belonging to the neurotropic and psychotropic agents class. The study aimed to understand the impact of molecular substitution on the activity of the compound, particularly exploring the effects of chlorine substitution at different positions on the perathiepin molecule. The researchers concluded that substitution at the 9th position of the perathiepin molecule negatively affects the neuroleptic activity, rendering compound I practically inactive as a central depressant and cataleptic agent. Key chemicals used in the synthesis process included 1-chloro-9-methylenethioxanthene (IX), thallic nitrate, methanol, 1-chlorothioxanthone (VI), and various derivatives of dibenzo[b,f]thiepin. The synthesis involved multiple steps, such as oxidation, hydrolysis, and substitution reactions, and utilized various reagents like methylmagnesium iodide, hydrochloric acid, and sulfuric acid, among others.
10.1021/ja01334a060
The study explores the synthesis and properties of various naphthyl derivatives of barbituric acid. The research focuses on creating compounds where the naphthyl group is either directly attached to the 5-carbon atom or connected via methylene groups. The chemicals involved include a-naphthylmethyl bromide and a-naphthylethyl bromide, which were used for alkylation to introduce naphthylmethyl and naphthylethyl groups into barbituric acids. The study also utilized alkyl barbituric acids, sodium acetate, and urea in the synthesis processes. The goal was to investigate the potential therapeutic properties of these derivatives as sedatives and hypnotics, similar to known compounds like barbital and amytal. The study reports the successful synthesis of several derivatives, including 5,5-ethyl-a-naphthylmethylbarbituric acid, 5,5-n-butyl-a-naphthylmethylbarbituric acid, and 5,5-allyl-a-naphthylmethylbarbituric acid, among others. However, none of the synthesized compounds exhibited desirable physiological effects comparable to barbital or amytal. The study also details the preparation methods and the physical and analytical data of the synthesized compounds.
10.1016/S0040-4039(02)01451-X
The research focuses on the conversion of O-succinimidyl carbamates to N-(O-carbamoyl)-succinmonoamides and ureas, exploring the effects of N-substituents and reaction conditions on the reaction pathway. The study investigates how N-monoalkyl-O-succinimidyl carbamates react with primary and secondary amines to form ureas, while N,N-dialkyl-O-succinimidyl carbamates yield N-(O-carbamoyl)-succinmonoamides under the same conditions. Experiments involved model reactions with N,N-dibenzyl-O-succinimidyl carbamate and N-3,3-diphenylpropyl-O-succinimidyl carbamate, using 3,3-diphenylpropylamine as a nucleophile. The reactions were conducted with varying solvents and base concentrations to assess their impact on product formation. Analytical techniques such as high-resolution mass spectrometry (HRMS) and reverse-phase high-performance liquid chromatography (RP-HPLC) were employed to characterize the products and monitor reaction progress. The findings suggest that electronic effects of N-substituents play a significant role in determining the reaction pathway, with N-aryl-N-alkyl carbamates tending to produce a mixture of both urea and hydroxylamine derivatives.
10.1016/j.bmcl.2011.02.111
The research focuses on the development of pyrrolidine-pyrazole ureas as potent and selective inhibitors of 11b-hydroxysteroid-dehydrogenase type 1 (11b-HSD1), an enzyme that converts inactive glucocorticoids into their active forms, contributing to insulin resistance and metabolic disorders. The study involved high-throughput screening to identify novel ureas as 11b-HSD1 inhibitors, followed by rational chemical optimization to enhance potency and selectivity while ensuring a favorable ADME profile and ex vivo activity in target tissues. Experiments included in vitro testing using recombinant human and mouse 11b-HSD1 enzymes, where the conversion of radiolabeled cortisone into cortisol was measured using an anti-cortisol antibody in a miniaturized scintillation proximity assay (SPA). The researchers synthesized and tested various compounds, replacing imidazole rings with alternative heterocyclic moieties to avoid CYP3A4 inhibition, and modifying the tetrahydroquinoline urea structure to improve metabolic stability and enzyme inhibition potency. The analyses involved measuring IC50 values, metabolic lability in human and mouse liver microsomes, and intestinal permeability. The study culminated in the identification of compound 33e, which showed significant ex vivo inhibition of 11b-HSD1 in both liver and fat tissue in mice, serving as a promising lead for further optimization.
10.1135/cccc19823134
The research explores the synthesis and pharmacological properties of various thioxanthene and dibenzo[b,f]thiepin derivatives. The study involves the use of chemicals such as 3-methylthiophenol, 3-ethylthiophenol, 2-iodobenzoic acid, (2-iodophenyl)acetic acid, potassium hydroxide, copper, sulfuric acid, polyphosphoric acid, 3-dimethylaminopropylmagnesium chloride, and various piperazine derivatives. These chemicals are used in a series of reactions to produce compounds with potential antihistamine and psychotropic activities. The synthesized compounds are tested for their pharmacological effects, including antihistamine activity, central depressant effects, cataleptic activity, and antireserpine activity. The research aims to investigate the impact of substituents in unusual positions on the pharmacological profiles of these compounds, with potential applications in treating conditions like gastric hyperacidity, ulcers, and central nervous system disorders.
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