Studies on molecular properties prediction and histamine H3 receptor affinities of novel ligands with uracil-based motifs

Lipani, Luca; Odadzic, Dalibor; Weizel, Lilia; Schwed, J. Stephan; Sadek, Bassem; Stark, Holger

doi:10.1016/j.ejmech.2014.09.011

Cited by 9 publications

(3 citation statements)

References 38 publications

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“…In addition, the drug‐likeness score of Lipinski's rule of five for all 2‐phenylthiazole derivatives were calculated by using the Molinspiration online property calculation toolkit (http://www.molinspiration.com/cgi‐bin/properties). It has been suggested that compounds with a clog P less than 5 have a more favorable drug‐likeness profile . The clog P value of compound 5 b–8 was 3.70, suggesting it can be a potential candidate for the treatment of AD.…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis and Biological Evaluation of Novel 2‐Phenylthiazole Derivatives for the Treatment of Alzheimer's Disease

et al. 2017

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A new series of 2‐phenylthiazole derivatives were designed, synthesized, characterized and evaluated as potential candidates to treat Alzheimer's disease. Most of these compounds exhibited significant acetylcholinesterase inhibitory activities. Among them, compound ethyl 2‐[4‐(4‐{[2‐(pyrrolidin‐1‐yl)ethyl]amino}butoxy)phenyl]thiazole‐4‐carboxylate (5 b–8) exhibited the best acetylcholinesterase inhibition activity with IC50 values of 4.8 μM. Moreover, the compound ethyl 2‐(4‐{[5‐(cyclohexylamino)pentyl]oxy}phenyl)thiazole‐4‐carboxylate (5 c–6) had the best butyrylcholinesterase inhibitory activity, with an IC50 value of 0.16 μM. The docking studies demonstrated that compound 5 b–8 could interact with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of acetylcholinesterase. Compound 5 b–8 also showed biometal chelating abilities. These attributes highlight 5 b–8 as a promising candidate for further studies directed to the development of novel drugs against Alzheimer's disease.

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Section: Resultsmentioning

confidence: 99%

Design, Synthesis and Biological Evaluation of Novel 2‐Phenylthiazole Derivatives for the Treatment of Alzheimer's Disease

et al. 2017

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“…Recently, a group of novel histamine H3 receptor (H3R) ligands with uracil-based motifs (uracil, thymine, and 5,6-dimethyluracil) have been synthesized. Two compounds revealed promising physicochemical and drug-like properties, which were similar to those of the pitolisant . For other synthetic uracil analogues, SAR studies were carried out to find a more effective topical anti-inflammatory agent and then the diaminouracil lead compound CX-659S …”

Section: Introductionmentioning

confidence: 97%

“…Two compounds revealed promising physicochemical and drug-like properties, which were similar to those of the pitolisant. 7 For other synthetic uracil analogues, SAR studies were carried out to find a more effective topical anti-inflammatory agent and then the diaminouracil lead compound CX-659S. 8 Figure 1 presents some of the compounds mentiond above.…”

Section: ■ Introductionmentioning

confidence: 99%

Unexpected Reaction Products of Uracil and Its Methyl Derivatives with Acetic Anhydride and Methylene Chloride

et al. 2021

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New acetyl derivatives of uracil, 6-methyluracil, and thymine were obtained in the course of an unconventional synthesis in methylene chloride. It was shown that products with the acetyloxymethyl fragment are formed according to a mechanism different from that for products with the acetyloxyethyl group. In particular, for uracil it was proven that the reaction with Ac2O, TEA, and CH2Cl2 leads to 1-acetyloxymethyluracil, where the N 1 substituent is composed of the −CH2– fragment that originated from CH2Cl2 and the 1-acetyloxy moiety from Ac2O. The reaction of uracil with Ac2O, TEA, CH2Cl2, and DMAP leads to an acetyloxyethyl derivative in which the −CH2–CH2– fragment originates from TEA and the 1-acetyloxy moiety from Ac2O. A possible mechanism for the formation of new compounds was suggested and supported by the density functional theory/B3LYP quantum mechanical calculations. New compounds (39 in total, including seven deuterated) were fully characterized by nuclear magnetic resonance and high-resolution mass spectrometry techniques.

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Histamine H3R Antagonists: From Scaffold Hopping to Clinical Candidates

et al. 2016

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Studies on molecular properties prediction and histamine H3 receptor affinities of novel ligands with uracil-based motifs

Cited by 9 publications

References 38 publications

Design, Synthesis and Biological Evaluation of Novel 2‐Phenylthiazole Derivatives for the Treatment of Alzheimer's Disease

Design, Synthesis and Biological Evaluation of Novel 2‐Phenylthiazole Derivatives for the Treatment of Alzheimer's Disease

Unexpected Reaction Products of Uracil and Its Methyl Derivatives with Acetic Anhydride and Methylene Chloride

Histamine H3R Antagonists: From Scaffold Hopping to Clinical Candidates

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