ABSTRACT
A ligand/additive/Pd-free Cu-mediated coupling/cyclization strategy afforded the first practical, one-pot and general approach towards synthesis of N-(un)substituted isoquinolin-1(2H)-ones. Both the catalyst and the solvent used are recyclable. The use of the Cu reagent in excess led to the unusual formation of regioisomeric and uncommon isoquinolin-1(4H)-ones.
Subject(s)
Isoquinolines/chemical synthesis , Catalysis , Copper/chemistry , Cyclization , Indicators and Reagents , Isomerism , Magnetic Resonance SpectroscopyABSTRACT
The intramolecular 1,3-dipolar cycloaddition of isovanillin derived N-aryl hydroxylamines possessing ortho-allylic dipolarophiles affords novel benzo analogues of tricyclic isoxazolidines that can be readily transformed into functionalized lactams, γ-aminoalcohols and oxazepines. The corresponding N-unsubstituted hydroxylamines give rise to tetrahydroisoquinolines. Anxiogenic properties of these compounds are tested in zebra fish.
Subject(s)
Anxiety/chemically induced , Benzaldehydes/chemistry , Heterocyclic Compounds/pharmacology , Hydroxylamines/chemistry , Motor Activity/drug effects , Animals , Cyclization , Dose-Response Relationship, Drug , Heterocyclic Compounds/chemical synthesis , Heterocyclic Compounds/chemistry , Models, Molecular , Molecular Structure , ZebrafishABSTRACT
A series of 3-(hetero)aryl substituted 3-[(prop-2-ynyloxy)(thiophen-2-yl)methyl]pyridine derivatives were designed as potential anticancer agents. These compounds were conveniently prepared by using Pd/C-Cu mediated Sonogashira type coupling as a key step. Many of these compounds were found to be promising when tested for their in vitro anti-proliferative properties against six cancer cell lines. All these compounds were found to be selective towards the growth inhibition of cancer cells with IC50 values in the range of 0.9-1.7 µM (against MDA-MB 231 and MCF7 cells), comparable to the known anticancer drug doxorubicin.
Subject(s)
Antineoplastic Agents/chemical synthesis , Pyridines/chemistry , Thiophenes/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/toxicity , Binding Sites , Carbon/chemistry , Catalysis , Catalytic Domain , Cell Line, Tumor , Cell Proliferation/drug effects , Copper/chemistry , Cyclin-Dependent Kinase 2/chemistry , Cyclin-Dependent Kinase 2/metabolism , Drug Screening Assays, Antitumor , HEK293 Cells , Humans , MCF-7 Cells , Molecular Docking Simulation , Palladium/chemistry , Pyridines/chemical synthesis , Pyridines/toxicity , Structure-Activity RelationshipABSTRACT
A series of functionalized phenyl oxazole derivatives was designed, synthesized and screened in vitro for their activities against LSD1 and for effects on viability of cervical and breast cancer cells, and in vivo for effects using zebrafish embryos. These compounds are likely to act via multiple epigenetic mechanisms specific to cancer cells including LSD1 inhibition.
Subject(s)
Antineoplastic Agents/pharmacology , Enzyme Inhibitors/pharmacology , Guanidine/chemistry , Histone Demethylases/antagonists & inhibitors , Oxazoles/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Histone Demethylases/metabolism , Humans , Molecular Dynamics Simulation , Molecular Structure , Oxazoles/chemical synthesis , Oxazoles/chemistry , Structure-Activity Relationship , ZebrafishABSTRACT
A series of fused and functionalized pyridine derivatives were designed, synthesized and tested for their potential antitubercular properties. All these novel compounds were prepared by using multistep methods involving the construction of pyridine ring as a key synthetic step. Some of these compounds were found to be interesting when tested for their antitubercular properties in vitro and one of them appeared as an attractive and potential antitubercular agent.
Subject(s)
Antitubercular Agents/chemical synthesis , Pyridines/chemistry , Animals , Antitubercular Agents/pharmacology , Chlorocebus aethiops , Ligands , Models, Molecular , Molecular Structure , Pyridines/pharmacology , Structure-Activity Relationship , Vero CellsABSTRACT
Functionalized ß-aryl alanine ester derivatives were found to undergo rapid C-N and C-O bond formation with quinol carbonyl compounds to afford 2H-benzo[b][1,4]oxazines in good to excellent yields. This unprecedented finding reported herein offers a straightforward, highly efficient, and rapid method for the synthesis of 2H-benzo[b][1,4]oxazines.
