ABSTRACT
Heterocyclization of functionalized vinylic derivatives of imidazo[1,2-a]pyridines was explored experimentally and theoretically using semiempirical AM1 and ab initio methods. A range of functionalized vinylic derivatives (azido, amino, and carbodiimide groups) were prepared for conversion into pyrroloazaindoles 19-22, imidazo[1,x]-, (x = 5, 6, 7, 8), [2,6]-, and [2,7]naphthyridines 28-30, 35-38 by thermal reaction. In the case of vinylic groups in the 5 position, peri annulation also was observed. The experimental and theoretical data are compared and discussed.
Subject(s)
Heterocyclic Compounds/chemical synthesis , Pyridines/chemical synthesis , Animals , Antineoplastic Agents/chemical synthesis , Antiviral Agents/chemical synthesis , Humans , Models, Molecular , Neurodegenerative Diseases/drug therapyABSTRACT
Access to the original series of pyrido[1',2':1,2]imidazo[4,5-h]quinazoline was developed from a 1,3-dicarbonyl unit with some "N-C-N" bisnucleophilic reagents and the derivatives obtained were evaluated for in vitro cytotoxic activities against HL60 and A2780 cells. All compounds exhibited cytotoxic activities on resistant cell lines (MDR+; HL60R and A2780R) with no resistance phenomena.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Benzimidazoles/chemical synthesis , Benzimidazoles/pharmacology , Quinazolines/chemical synthesis , Quinazolines/pharmacology , Animals , Cell Survival/drug effects , Drug Resistance, Neoplasm , Genes, MDR/genetics , HL-60 Cells , Humans , Immunohistochemistry , Indicators and Reagents , Mice , Tumor Cells, CulturedABSTRACT
Ten 2-aryl or heteroaryl-3-nitrosoimidazo[1,2-a]pyridine derivatives were synthesised as potential antiretroviral agents. The new compounds were characterized by elemental analysis, 1H NMR, and by crystallography for (14). The compounds were devoid of any activity against HIV-1 or HIV-2.
Subject(s)
Anti-HIV Agents/chemical synthesis , Antiviral Agents/chemical synthesis , Imidazoles/chemical synthesis , Imidazoles/pharmacology , Nitroso Compounds/chemical synthesis , Nitroso Compounds/pharmacology , Pyridines/chemical synthesis , Pyridines/pharmacology , Retroviridae/drug effects , Cells, Cultured , Crystallography, X-Ray , Humans , Magnetic Resonance SpectroscopyABSTRACT
This work reports the synthesis and the antiviral activities of 3-benzamido, 3-phenylureido and 3-phenylthioureido derivatives in the imidazo[1,2-a]pyridine series. The structure was proven by NMR spectroscopy. The synthesized compounds were evaluated against a large number of viruses. The 3-phenylthioureido derivative 7 showed moderate activity against human cytomegalovirus (HCMV) in vitro. The crystallographic data for 8 are also reported and explain the absence of activity against human immunodeficiency virus (HIV).
Subject(s)
Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , Imidazoles/chemical synthesis , Imidazoles/pharmacology , Phenylurea Compounds/chemical synthesis , Phenylurea Compounds/pharmacology , Thiourea/analogs & derivatives , Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/pharmacology , Cells, Cultured , Crystallography, X-Ray , Cytomegalovirus/drug effects , Humans , Magnetic Resonance Spectroscopy , Models, Molecular , Structure-Activity Relationship , Thiourea/chemical synthesis , Thiourea/pharmacology , Viral Plaque AssayABSTRACT
Several diaza-analogs of phenanthrene derived from 3-amino, 5-amino, 6-amino, 8-aminoquinolines, and 5-aminoisoquinoline were prepared to evaluate their antiplasmodial activities. All compounds showed mild to good activitiy in vitro, both on a Nigerian chloroquino-sensitive strain and on the chloroquino-resistant FcB1-Columbia and FcM29 strains. The position of the intracyclic nitrogen atom is shown to be crucial for the activities (best results are obtained with a 1,10-phenanthroline skeleton). In regard to the particular properties of this structure (metalloprotease inhibition activitiy by chelating divalent metal ions), the potential chelating site of the molecule was blocked. In this case, the biological activity of the compound was greatly enhanced, showing that the mechanism of action of such a compound is probably not correlated to metalloprotease inhibition activity.
Subject(s)
Antimalarials/chemical synthesis , Phenanthrenes/pharmacology , Animals , Antimalarials/chemistry , Antimalarials/pharmacology , Chelating Agents/chemistry , Drug Evaluation, Preclinical , HeLa Cells , Humans , Inhibitory Concentration 50 , Phenanthrenes/chemical synthesis , Phenanthrenes/chemistry , Phenanthrolines/chemistry , Plasmodium falciparum/drug effectsABSTRACT
The synthesis of original imidazo[1,2-a]pyridines bearing a thioether side chain at the 3 position and their antiviral activity are reported. From the synthesized compounds, 4, 15, and 21 were highly active against human cytomegalovirus with a therapeutic index superior to 150. These compounds also showed pronounced activity against varicella-zoster virus. Their structure-activity relationship is discussed.
Subject(s)
Antiviral Agents/chemical synthesis , Imidazoles/chemical synthesis , Pyridines/chemical synthesis , Animals , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Cell Line , Chlorocebus aethiops , Cytomegalovirus/drug effects , Drug Evaluation, Preclinical , HeLa Cells , Herpesvirus 3, Human/drug effects , Humans , Imidazoles/chemistry , Imidazoles/pharmacology , Inhibitory Concentration 50 , Pyridines/chemistry , Pyridines/pharmacology , Structure-Activity Relationship , Vero CellsABSTRACT
N-1 and N-2 substituted pyrazolo[4,5-g]pyrido[1,2-a]benzimidazoles were prepared regioselectively, and cytotoxicities evaluated in vitro against K562 and HL60 cells. All compounds displayed weaker activity than doxorubicin against sensitive lines, but showed the same activity against resistant cell lines (multidrug resistance+, (MDR+); K562R and HL60R) indicating no resistance phenomena.
Subject(s)
Antineoplastic Agents/chemical synthesis , Benzimidazoles/chemical synthesis , Antibiotics, Antineoplastic/pharmacology , Antineoplastic Agents/pharmacology , Benzimidazoles/pharmacology , Doxorubicin/pharmacology , HL-60 Cells , Humans , K562 Cells , Magnetic Resonance Spectroscopy , Tumor Cells, CulturedABSTRACT
The synthesis and the antiviral activities of C-3 acyclic nucleoside analogues of imidazo[1,2-a]pyridine and pyrimidine are reported. From these compounds, 20, 21, 22, 23, 28, and 34 showed a specific activity against cytomegalovirus and/or varicella-zoster virus.