97294-89-8Relevant academic research and scientific papers
Non-imidazole histamine H3 ligands. Part VI. Synthesis and preliminary pharmacological investigation of thiazole-type histamine H3-receptor antagonists with lacking a nitrogen nucleus in the side chain
Guryn, Roman,Staszewski, Marek,Kopczacki, Piotr,Walczyński, Krzysztof
, p. 65 - 76 (2017/06/05)
Background: Antagonists to the H3 receptor are considered to be potential drugs for the treatment of Alzheimer's disease, attention deficit-hyperactive disorder, memory and learning deficits, and epilepsy. The initial development of potent H3 receptor antagonists focused on extensive modification of the natural ligand histamine. However, it has appeared that imidazole-containing ligands are associated with inhibition of cytochrome P450 enzymes, caused by imidazole nitrogen complexation to heme iron in the active site of the enzyme. For these reasons, the development of potent non-imidazole H3 receptor antagonists was eagerly awaited. Objective: Previously, we reported the synthesis and pharmacological in vitro characterization of series of potent histamine H3-receptor non-imidazole antagonists belonging to the class of substituted 2-thiazol-4-n-propylpiperazines. A lead compound 1 of this family was a derivative carrying the ethylaminomethylpropyl chain. Methods: With the aim of increasing lipophilicity, that will help the ligands to cross the blood-brain barrier, we synthesized a series of new 2-thiazol-4-n-propylpiperazines where the ethylaminomethylpropyl moiety was replaced by a p-substituted-, an unsubstituted benzene ring, and ω-phenylalkyl substituent at positions 4 and 5 of thiazole ring, respectively. All compounds were tested for H3 antagonistic effects in vitro using the electrically contracting guinea pig jejunum. Results: The most active compounds of presented series 3d, 3e, and 3j showed lower affinity than the lead compound 1 and additionally, derivatives 3d and 3j possessed weak, competitive H1-antagonistic activity. This is in contrast to the lead compound 1 that has no affinity at H1 receptor. Conclusion: We can conclude that a side chain in the 2-thiazol-4-n-propylpiperazine scaffold should contain a basic center and should be present at a favorable position 5 of thiazole ring.
Novel Preparation of α,β-Unsaturated Aldehydes. Benzeneselenolate Promotes Elimination of HBr from α-Bromoacetals
Vasil'ev, Andrei,Engman, Lars
, p. 2151 - 2162 (2007/10/03)
Acetalization, α-bromination, nucleophilic phenylselenenylation, oxidative elimination/hydrolysis was investigated as a novel protocol for the α,β-dehydrogenation of aldehydes. Treatment of acetals with bromine in methylene chloride afforded the corresponding α-bromoacetals in 80-90% yields. Nucleophilic phenylselenenylation was then conveniently effected by treatment with benzenese-lenolate generated in situ in dimethyl sulfoxide from diphenyl diselenide, hydrazine and potassium carbonate. Unbranched α-bromoacetals cleanly afforded substitution products whereas β- and γ-branched ones gave substantial amounts of α,β-unsaturated acetals via formal loss of hydrogen bromide. Oxidative elimination/hydrolysis of these mixtures afforded α,β-unsaturated aldehydes in 50-80% overall yields. In the case of tertiary α-bromoacetals, treatment with benzeneselenolate afforded only dehydrobromination products as mixtures of isomers. The presence of at least a catalytic amount of the organoselenium reagent was found to be crucial for olefin formation. A SET-mechanism, involving benzeneselenolate-induced electron transfer to the halide, loss of bromide ion, and hydrogen atom or proton/electron was proposed for the benzenselenolate-promoted elimination reaction. Experiments designed to trap carbon-centered radicals in intramolecular cyclization or ring-opening reactions failed to provide any evidence for free-radical intermediates.
BROMINATION OF DIMETHYLACETALS WITH Br2-CHLOROTRIMETHYLSILANE-NaBr
Bellesia, Franco,Boni, Monica,Ghelfi, Franco,Pagnoni, Ugo Maria
, p. 629 - 632 (2007/10/02)
α-Bromodimethylacetals are obtained in excellent yields by treating dimethylacetals with Br2-NaBr-chlorotrimethylsilane in CH3OH/CH3CN (2:1). The method is suitable for large scale preparation.
Ketene Chemistry 2. A General Procedure for the Synthesis of 2-Alkoxycyclopropanecarboxylic Esters and Acids Starting from Aldehydes and Ketene
Rasmussen, Preben Boedstrup,Boewadt, Soeren
, p. 114 - 117 (2007/10/02)
Alkyl 3-alkoxy-4-bromocarboxylates are prepared by the Lewis acid-catalyzed reaction of α-bromoaldehyde acetals with ketene.Base-catalyzed cyclization of these intermediates affords 2-alkoxycyclopropanecarboxylic esters.
