85629-18-1Relevant 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.
Antipsoriatic Anthrones with Modulated Redox Properties. 1. Novel 10-Substituted 1,8-Dihydroxy-9(10H)-anthracenones as Inhibitors of 5-Lipoxygenase
Mueller, Klaus,Guerster, Dieter,Piwek, Susanne,Wiegrebe, Wolfgang
, p. 4099 - 4107 (2007/10/02)
The syntheses, the biological evaluation, and the structure-activity relationships of a novel series of 1,8-dihydroxy-9(10H)-anthracenones bearing acyl-, alkyl-, or alkylidene-linked aromatic substituents in the 10-position are described.The phenylacyl and phenylalkylidene analogs were far more potent inhibitors of 5-lipoxygenase (5-LO) from bovine polymorphonuclear leukocytes (IC50 values in the 10-7 M range) than the antipsoriatic drug anthralin, whereas phenylalkyl analogs were only weak inhibitors.Among the active compounds were both potent generators of hydroxyl radicals, as determined by deoxyribose degradation, and strong reducers of the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH).However, several derivatives of this series maintained 5-LO inhibitory activity but did not generate hydroxyl radicals and were not reactive with DPPH.In particular, phenylacyl analogs were also 6 times more efficient in inhibition of lipid peroxidation in model membranes than anthralin.Structure-activity relationships have shown that the presence of free phenolic groups in the attached aromatic ring is beneficial but not required for 5-LO inhibitory potency.The inhibitory potency in the 10-phenylacyl series increased with the length of the acyl chain with three methylene units being the optimum, suggesting a specific enzyme interaction which would not be expected for nonspecific redox inhibitors.
(Benzotriazol-1-yl)methoxymethyl anion: A novel methylal anion equivalent
Katritzky,Yang,Cundy
, p. 3061 - 3071 (2007/10/02)
The title anion readily reacts with a variety of electrophiles to give adducts which, upon treatment with methanol in the presence of p-toluenesulfonic acid, afford the corresponding α-functionalized dimethyl acetals.
Bifunctional compounds from reaction of alkoxy hydroperoxides with metal salts
Cardinale,Laan,Van Der Steen,Ward
, p. 6051 - 6054 (2007/10/02)
Alkoxy hydroperoxides, obtained by ozonizing olefins in alcoholic solution, were treated with ferrous sulfate. C-C bond scission and radical formation was followed by dimerization of the radicals formed. Ozonides reacted similarly. Acyclic and cyclic olefins, including a cyclic enol ether, gave rise to a range of α,ω-disubstituted products in modest yields. By using ferric chloride, ω-chloro esters were obtained from the alkoxy hydroperoxides derived from olefinic esters.
