- Design, synthesis, crystal structure, and herbicidal activity of novel pyrrolidine-2,4-dione derivatives incorporating an alkyl ether pharmacophore with natural tetramic acids as lead compounds
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In order to discover green herbicides with novel molecular scaffolds, natural tetramic acids were used as lead compounds to design and synthesize four pyrrolidine-2,4-dione derivatives incorporating a chainlike alkoxyalkyl moiety (4a-4d) and nineteen pyrrolidine-2,4-dione derivatives incorporating a substituted phenoxyethyl moiety (10a-10s)viasubstitution, acylation, cyclization, and acidification reactions. The synthesized target compounds were confirmed by FT-IR,1H NMR,13C NMR and HRMS spectral analyses. The single-crystal structure of compound10awas analyzed by X-ray diffraction, which revealed that the 1-hydroxyethylidene group links the third position of the pyrrolidine heterocycle through a double bond with theZ-configuration. The herbicidal activity was evaluated using barnyard grass (Echinochloa crus-galli) and rape (Brassica campestris) as model plants by a Petri dish culture method. Most target compounds were found to possess moderate to good inhibitory activities against the plant growth at 100 μg mL?1. Among them, the compounds10qand10nshowed the highest herbicidal activities against the roots of barnyard grass and rape seedlings with the corresponding inhibition rates of 65.6% and 84.0%, respectively. This result indicated that pyrrolidine-2,4-dione derivatives incorporating a substituted phenoxyethyl moiety are worthy of further structural optimization.
- Chen, Min,Geng, Chun-Wen,Han, Ling,Liu, Yu,Yu, Yong-Kai,Lu, Ai-Min,Yang, Chun-Long,Li, Guo-Hua
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p. 5621 - 5630
(2021/04/06)
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- Discovery of Novel pERK1/2- or β-Arrestin-Preferring 5-HT1AReceptor-Biased Agonists: Diversified Therapeutic-like versus Side Effect Profile
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Novel 1-(1-benzoylpiperidin-4-yl)methanamine derivatives with high affinity and selectivity for serotonin 5-HT1A receptors were obtained and tested in four functional assays: ERK1/2 phosphorylation, adenylyl cyclase inhibition, calcium mobilization, and β-arrestin recruitment. Compounds 44 and 56 (2-methylaminophenoxyethyl and 2-(1H-indol-4-yloxy)ethyl derivatives, respectively) were selected as biased agonists with highly differential "signaling fingerprints"that translated into distinct in vivo profiles. In vitro, 44 showed biased agonism for ERK1/2 phosphorylation and, in vivo, it preferentially exerted an antidepressant-like effect in the Porsolt forced swimming test in rats. In contrast, compound 56 exhibited a first-in-class profile: it preferentially and potently activated β-arrestin recruitment in vitro and potently elicited lower lip retraction in vivo, a component of "serotonergic syndrome". Both compounds showed promising developability properties. The presented 5-HT1A receptor-biased agonists, preferentially targeting various signaling pathways, have the potential to become drug candidates for distinct central nervous system pathologies and possessing accentuated therapeutic activity and reduced side effects.
- Sniecikowska, Joanna,Gluch-Lutwin, Monika,Bucki, Adam,Wi?ckowska, Anna,Siwek, Agata,Jastrzebska-Wiesek, Magdalena,Partyka, Anna,Wilczyńska, Daria,Pytka, Karolina,Latacz, Gniewomir,Przejczowska-Pomierny, Katarzyna,Wyska, El?bieta,Weso?owska, Anna,Paw?owski, Maciej,Newman-Tancredi, Adrian,Kolaczkowski, Marcin
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supporting information
p. 10946 - 10971
(2020/11/09)
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- 1-(4-Substituted phenyl)-1H-imidazoles compounds
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Novel 1-(4-substituted phenyl)-1H-imidazoles and their use as antiarrhythmic, anti-hypertensive and anti-ischemic agents is described. Pharmaceutical formulations containing such compounds are also discussed.
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