ABSTRACT
A set of arylpiperazine derivatives with imide fragments, 1-(1H-pyrrol-1-ylmethyl)-10-oxa-4-azatricyclo[5.2.1.0(2,6)-]dec-8-ene-3,5-dione connected by propyl and butyl linkers, were synthesized and tested for the potential anxiolytic and antidepressant activities. Compounds 3a and 3b demonstrated antidepressant activity in the forced swimming tests in mice and were devoid of neurotoxic effects. (chimney test in mice).
Subject(s)
Anti-Anxiety Agents/chemical synthesis , Antidepressive Agents/chemical synthesis , Piperazines/chemical synthesis , Animals , Anti-Anxiety Agents/chemistry , Anti-Anxiety Agents/pharmacology , Antidepressive Agents/chemistry , Antidepressive Agents/pharmacology , Male , Mice , Motor Activity/drug effects , Piperazines/chemistry , Piperazines/pharmacologyABSTRACT
The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of 1,7,8,9-tetrachloro-10,10-dimethoxy-4-{3-[4-(3-methoxyphenyl) piperazin-1-yl]propyl}-4-azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione have been investigated experimentally and theoretically using Gaussian09 software package. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. Gauge-including atomic orbital (1)H NMR chemical shifts calculations were carried out and compared with experimental data. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. Molecular Electrostatic Potential was performed by the DFT method and the infrared and Raman intensities have also been reported. First hyperpolarizability is calculated in order to find its role in non-liner optics. The calculated geometrical parameters (SDD) are in agreement with that of similar derivatives. Mulliken's net charges have been calculated and compared with the atomic natural charges.
Subject(s)
Aza Compounds/chemistry , Heterocyclic Compounds, 3-Ring/chemistry , Piperazines/chemistry , Halogenation , Models, Molecular , Quantum Theory , Spectroscopy, Fourier Transform Infrared , Spectrum Analysis, RamanABSTRACT
The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of 1,7,8,9-Tetrachloro-4-(4-bromo-butyl)-10,10-dimethoxy-4-aza-tricyclo[5.2.1.0(2,6)] dec-8-ene-3,5-dione (TDAD) have been investigated experimentally and theoretically using Gaussian09 software package. Potential energy distribution of normal modes of vibrations was done using GAR2PED program. Gauge-including atomic orbital (1)H NMR chemical shifts calculations were carried out and compared with experimental data. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. Molecular Electrostatic Potential was performed by the DFT method and infrared intensities and Raman activities are also reported. Mulliken's net charges have been calculated and compared with the atomic natural charges. First hyperpolarizability is calculated in order to find its role in non-liner optics. The calculated geometrical parameters are in agreement with that of similar derivatives.
Subject(s)
Heterocyclic Compounds, 3-Ring/chemistry , Imides/chemistry , Models, Molecular , Spectrum Analysis, Raman , Vibration , Molecular Conformation , Proton Magnetic Resonance Spectroscopy , Spectroscopy, Fourier Transform Infrared , Static Electricity , ThermodynamicsABSTRACT
The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of 1,7,8,9-tetrachloro-10,10-dimethoxy-4-[3-(4-phenylpiperazin-1-yl)propyl]-4-azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione (TDPPAD) have been investigated experimentally and theoretically using Gaussian09 software package. Gauge-including atomic orbital (1)H NMR chemical shifts calculations were carried out and compared with experimental data. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. Molecular Electrostatic Potential was performed by the DFT method and the infrared and Raman intensities have also been reported. Mulliken's net charges have been calculated and compared with the atomic natural charges. Fist hyperpolarizability is calculated in order to find its role in non-liner optics. The calculated geometrical parameters (SDD) are in agreement with that of similar derivatives.
Subject(s)
Heterocyclic Compounds, 3-Ring/chemistry , Imides/chemistry , Models, Molecular , Quantum Theory , Spectrum Analysis, Raman , Proton Magnetic Resonance Spectroscopy , Spectroscopy, Fourier Transform Infrared , Static Electricity , ThermodynamicsABSTRACT
The synthesis and pharmacological activity of N-substituted derivatives of 1,8,11,11-tetramethyl-4-azatricyclo[5.2.2.0(2,6)]undec-8-ene-3,5-dione (1) are described. The molecular structure of starting compound (1) was confirmed by elemental analysis, 13C NMR and X-ray crystallography. The structures of derivatives were confirmed by 1H NMR and mass spectra. The compounds were investigated for antibacterial activity, including Gram-positive cocci, Gram-negative rods, and antifungal activity. Studied compounds were evaluated also for their cytotoxicity and anti-HIV-1 activity in MT-4 cells.
Subject(s)
Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Crystallography, X-Ray , HIV-1/drug effects , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Structure-Activity RelationshipABSTRACT
In the title compound, C20H17NO3 (alternative name: N-hy-droxy-9,10-dimethyl-9,10-ethano-anthracene-11,12-dicarboximide), the rigid ethano-anthracene-dicarboximide moiety has a roof-shaped geometry, the inter-planar angle between the two terminal phenyl rings being 124.9â (6)°. In the crystal, mol-ecules are linked via O-Hâ¯O hydrogen bonds, forming chains along [010]. C-Hâ¯O and C-Hâ¯π inter-actions link adjacent chains, leading to the formation of a three-dimensional structure.
ABSTRACT
A series of twenty arylpiperazine derivatives of 1,7,8,9-tetrachloro-10,10-dimethoxy-4-azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione have been prepared. These derivatives were tested in vitro with the aim of identifying novel lead compounds active against emergent and re-emergent human and cattle infectious diseases (AIDS, hepatitis B and C, tuberculosis, bovine viral diarrhea). In particular, these compounds were evaluated in vitro against representatives of different virus classes, such as a HIV-1 (Retrovirus), a HBV (Hepadnavirus) and the single-stranded RNA(+) viruses Yellow fever virus (YFV) and Bovine viral diarrhea virus (BVDV), both belonging to the Flaviridae. Compounds 2c, 2g and 3d showed a modest activity against CVB-2. The molecular structures of the starting imide 1 and one of propyl-piperazine derivatives, 3b, have been determined by an X-ray crystallography study.
Subject(s)
Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , Heterocyclic Compounds, 3-Ring/chemical synthesis , Heterocyclic Compounds, 3-Ring/pharmacology , Animals , Cell Line , Crystallography, X-Ray , Drug Evaluation, Preclinical , In Vitro Techniques , Microbial Sensitivity Tests , Models, Molecular , Molecular StructureABSTRACT
The preparation of a number of new N-substituted derivatives of 1-acetyldibenzo-[e.h]-bicyclo[2.2.2]-octane-2,3-dicarboximide with an expected anxiolytic activity is described.
