The 3-[(2-ethoxyphenoxy)methyl]piperidine derivatives 3-5 were synthesized and screened as potential antidepressant agents by the reserpine interaction test in mice and the evaluation of reuptake inhibition of biogenic amines in pig brain synaptosomal fractions. In addition, their anticonvulsant activity, tested by pentyleneetrazole antagonism, and approximate acute toxicity were evaluated. In vivo and in vitro tests showed that compounds 3 and 5 possess a biological activity comparable to that of the antidepressant drug viloxazine.
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http://dx.doi.org/10.1021/jm00384a040 | DOI Listing |
J Org Chem
August 2023
Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China.
Spiro[indoline-3,3-pyrrolidine] and spiro[indoline-3,3-piperidine] derivatives were synthesized in a substitution-controlled manner under the catalysis of cationic gold(I) species in the presence of Hantzsch ester (HEH). The optimal reaction condition was determined by screening, and the functional group tolerances of these two pathways were examined by readily synthetic substrates. The and selectivities of these cyclizations were elucidated by density functional theory calculations, and a plausible mechanism for these transformations was proposed.
View Article and Find Full Text PDFOrg Biomol Chem
May 2023
Université Paris Cité, CNRS, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques, F-75006 Paris, France.
In recent years, spirocycles have been the focus of medicinal chemistry, and several drugs or drug candidates incorporating these "non-planar" chemical motifs have been developed. Herein, an unusual intramolecular Buchwald-Hartwig -arylation of bicyclic hydrazines is described. This key reaction gives access to various spiro[indoline-2,3'-piperidine] derivatives after reductive cleavage of a nitrogen-nitrogen bond.
View Article and Find Full Text PDFPharmaceutics
January 2022
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
Impaired mitochondrial function is associated with several metabolic diseases and health conditions, including insulin resistance and type 2 diabetes (T2DM), as well as ageing. The close relationship between the above-mentioned diseases and cardiovascular disease (CVD) (diabetic cardiomyopathy and age-related cardiovascular diseases) has long been known. Mitochondria have a crucial role: they are a primary source of energy produced in the form of ATP via fatty acid oxidation, tricarboxylic acid (TCA) cycle, and electron transport chain (ETC), and ATP synthase acts as a key regulator of cardiomyocyte survival.
View Article and Find Full Text PDFActa Crystallogr E Crystallogr Commun
October 2019
Department of Physics, Thiagarajar College, Madurai - 625 009, Tamilnadu, India.
Instances of crystal structures that remain isomorphous in spite of some minor changes in their respective mol-ecules, such as change in a substituent atom/group, can provide insights into the factors that govern crystal packing. In this context, an accurate description of the crystal structures of an isomorphous pair that differ from each other only by a chlorine-methyl substituent, 5''-(2-chloro-benzyl-idene)-4'-(2-chloro-phen-yl)-1'-methyl-dispiro-[acenaphthene-1,2'-pyrrolidine-3',3''-piperidine]-2,4''-dione, CHClNO, (I), and its analogue 1'-methyl-5''-(2-methyl-benzyl-idene)-4'-(2-methyl-phen-yl)di-spiro-[acenaphthene-1,2'-pyrrolidine-3',3''-piperidine]-2,4''-dione, CHNO, (II), is presented. While there are two C-H⋯O weak inter-molecular inter-actions present in both (I) and (II), the change of substituent from chlorine to methyl has given rise to an additional weak C-H⋯O inter-molecular inter-action that is relatively stronger than the other two.
View Article and Find Full Text PDFMagn Reson Chem
April 2019
Department of Chemistry, Faculty of Science, Tarbiat Modares University, Tehran, Iran.
A comprehensive investigation was performed on H, C, and P nuclear magnetic resonance (NMR) chemical shifts (CSs) of phosphoryl benzamide derivatives (C H C(O)NHP(O)R R ), (R , R = aziridine [L ], azetidine [L ], pyrrolidine [L ], piperidine [L ], azepane [L ], 4-methylpiperidine [L ], propane-2-amine [L ], and 2-methylpropane-2-amine [L ]) by the gauge-independent atomic orbital method (GIAO) to find the most accordant level of theory with the experimental values. To achieve this goal, all the structures were optimized using the B3LYP, BP86, PBE1PBE, M06-2X, MPWB1K, and MP2 methods with 6-31+G* basis set. Computed structural parameters demonstrate that BP86 has the best agreement to the experimental values between the other methods.
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