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New N-substituted α-aminonitrile derivatives from menthol were synthesized by consecutive succinic ester formation, propargylation, 1,3-dipolar Huisgen cycloaddition and Strecker reaction. The structures of the synthesized compounds were confirmed by diverse spectroscopic techniques including 1HNMR, 13C-NMR, ESI-MS and IR. The novel synthesized compounds were evaluated for their in vitro antibacterial activities against Staphylococcus aureus as Gram-positive and Escherichia coli as Gram-negative bacteria. These compounds demonstrated a strong inhibitory effect against S. aureus with the minimum inhibitory concentration (MIC) values ranged from 32–128 μg mL-1. Derivatives 6a2, 6b1, 6b4 and 6b5 with a MIC value of 32 μg mL-1 exhibited the best inhibitory effects.

Novel 1,2,3-triazole-tethered N-norbuprenorphine derivatives with an OMe or OH group at the C3 position were synthesized alongside with evaluation of their analgesic properties. The analgesic activities of the resulting library were investigated via tail flick test in mice. Our results indicated that 10b and 10e were as effective as the starting compounds 8 and 9 with [ED.sub.50] equal to 16.59 and 19.44 mg/kg, respectively. To investigate the effect of a methyl group at C3 on biological properties, the most active compounds were O-demethylated and their anti-nociceptive effects were assessed. The new O-demethylated derivatives (11b and 11e) showed better analgesic properties than the parent compounds with [ED.sub.50] of 14.73 and 15.80 mg/kg, respectively. Naloxone prevented the analgesic effect of the synthesized compounds, indicating that the opioid receptors are highly involved in the anti-nociceptive effects. The potential dependency effects of the most potent derivatives were studied by condition place preference test in mice and compared with morphine and buprenorphine. Interestingly, 10b, 10e, 11b, and 11e did not show any dependency effect, similar to buprenorphine. Key words: 1,2,3-triazole, partial agonist, anti-nociceptive, addiction withdrawal, dependency. Nous avons synthetise de nouveaux derives de la N-norbuprenorphine attaches a un cycle 1,2,3-triazole et portant un groupe OMe ou OH en position C3, et nous avons evalue leurs proprietes analgesiques. Nous avons evalue l'activite anal-gesique des composes de la chimiotheque resultante au moyen du test de latence de retraction de la queue chez la souris. Nos resultats ont indique que les composes 10b et 10e etaient aussi efficacesque lescomposesde depart 8 et 9, leur [DE.sub.50] etant de 16,59 et de 19,44 mg/kg, respectivement. Pour etudier l'effet d'un groupe methyle a la position C3 sur les proprietes biologiques, nous avons effectue une O-demethylation des composes les plus actifs et nous avons evalue leurs effets antino-ciceptifs. Les nouveaux derives O-demethyles (11b et 11e) ont montre de meilleures proprietes analgesiques que les composes d'origine, leur [DE.sub.50] etant de 14,73 et de 15,80 mg/kg, respectivement. La naloxone a inhibe l'effet analgesique des composes que nous avons synthetises, ce qui indique que les recepteurs des opio'ides jouent un role tres important dans l'ef-fet antinociceptif de ces composes. Nous avons etudie le potentiel de dependance aux derives les plus puissants au moyen du test de preference de place conditionnee chez la souris et l'avons compare a celui de la morphine et de la buprenorphine. Il est interessant de noter que les composes 10b, 10e, 11b et 11e n'ont montre aucun effet de dependance, de maniere semblable a ce qui est observe pour la buprenorphine. [Traduit par la Redaction] Mots-cles: 1,2,3-triazole, agoniste partiel, antinociceptif, sevrage de la toxicomanie, dependance., Introduction Based on the mechanism of action, most medicines for pain relief are divided into two major groups: opioids such as oxycodone and morphine and non-steroidal anti-inflammatory drugs (NSAIDs) such [...]

Novel 1,2,3-triazole-tethered 9-bromonoscapine derivatives were synthesized by the propargylation of N-nornoscapine followed by Huisgen's 1,3-dipolar cycloaddition of the terminal alkynes with different azides. Cytotoxicity of the products was studied by MTT assay against the MCF-7 breast cancer cell line. Most of the compounds revealed a better cytotoxicity than N-nornoscapine and 9-bromonornoscapine as the parent compounds. Among the synthesized compounds, those with a hydroxylated aliphatic side chain (5p, 5q, and 5r) showed the highest activities (IC50s: 47.2, 37.9, and 32.3 µg/mL, respectively). Molecular docking studies showed that these compounds also had the highest docking scores and effective interactions with binding sites equal to -8.074, -7.425 and -7.820 kcal/mol, respectively. [ABSTRACT FROM AUTHOR]

An efficient palladium-catalyzed protocol was developed for the synthesis of 3-arylidene-2-oxindoles. The synthesis involved a sequential one-pot six-component reaction via Ugi/Heck carbocyclization/Sonogashira/nucleophilic addition to yield desired skeleton.

Noscapine, a natural alkaloid, has never been used as a parent scaffold in chiral induction. The first examples of noscapinoid compounds as efficient catalysts in asymmetric synthesis are now reported. Three derivatives of noscapine were synthesized from its reaction with different Grignard reagents. Asymmetric addition of diethylzinc to aldehydes was performed in the presence of these catalysts in high yields and good to excellent ees. [ABSTRACT FROM AUTHOR]

Novel substituted amino acid tethered norsufentanil derivatives were synthesized by the four‐component Ugi reaction. Norsufentanil was reacted with succinic anhydride to produce the corresponding carboxylic acid. The resulting carboxylic acid has undergone a multicomponent reaction with different aldehydes, amines, and isocyanides to produce a library of the desired compounds. In all cases, amide bond rotation was observed in the NMR spectra. In vivo analgesic activity of the synthesized compounds was evaluated by a tail flick test. Very encouraging results were obtained for a number of the synthesized products. Some of the synthesized compounds such as 5a, 5b, 5h, 5j, and 5r were found to be more potent than sufentanil, sufentanil citrate, and norsufentanil. Binding modes between the compounds and mu and delta‐opioid receptors were studied by molecular docking method. The relationship between the molecular structural features and the analgesic activity was investigated by a quantitative structure–activity relationship model. The results of the molecular modeling studies and the in vivo analgesic activity suggested that the majority of the synthesized compounds were more potent than sufentanil and norsufentanil. [ABSTRACT FROM AUTHOR]