Synthesis and in vitro dual calcium channel antagonist-agonist activity of some 1,4-Dihydo-2,6-dimethyl-3-nitro and cyano-4-(1-methyl-5-nitro-1H-imidazol-2-yl)-5-pyridinecarboxylates

Background and purpose of the study: The vasorelaxant action of the dihydropyridines (DHPs) provides many useful clinical indications. However, their negative effects on cardiac contractility is still of a great concern especially in patients with heart failure. Design and synthesis of dual action compounds, i.e. smooth muscle calcium channel antagonist/cardiac muscle calcium channel agonist provides better and safer compounds particularly in patients with compromised cardiac contractility. In the present study, dual cardioselective Ca(2+) channel agonists / vascular selective smooth muscle Ca(2+) channel antagonists as third generation of DHP drugs were synthesized by a reported method. Methods: Synthetic procedure involved condensation of isopropyl-3-aminocrotonate with nitroacetone and 1-methyl-5-nitroimidazole2-carboxaldehyde and condensation of alkylacetoacetates with 3-aminocrotonitryl and 1-methyl-5-nitro-1H-imidazole-2carbaldehyde for the preparation of 1,4-Dihydo-2,6-dimethyl-3-nitro and cyano-4-(1-methyl-5-nitro-1H-imidazol-2-yl)-5-pyridinecarboxylates, respectively. The in vitro effects of the synthesized compounds were evaluated on longitudal Smooth Muscle (GPILSM) and Guinea Pig Left Atrium (GPLA) preparations and finally, their conformations and structure-activity relationships were assessed. Results and major conclusion: All compounds showed calcium channel antagonist activity on isolated guinea pig ileum and some of them showed calcium channel agonist effects (or positive inotropic effect instead of calcium channel agonist effect) on isolated guinea-pig left atrium. QSAR and conformational analyses showed that conformation and charge of aryl substituents at C4 position have a main role in antagonistic activity while carbonyl group at C(5) position plays an important role in agonistic effects

Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ2 (PPARγ-2) gene is associated with greater insulin sensitivity and decreased risk of type 2 diabetes in an Iranian population

Background: The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ2 (PPARγ-2) gene has been variably associated with insulin resistance, obesity and type 2 diabetes in several populations. However, this association has not been studied in Iranian subjects and we hypothesized that this variation might be associated with insulin resistance, type 2 diabetes and related metabolic traits in this population. Methods: The Pro12Ala genotypes were determined by PCR-restriction fragment length polymorphism in 696 unrelated subjects including 412 non-diabetic controls and 284 type 2 diabetic patients. Results: The frequency of the Ala allele was 9.4 and 5.9 in controls and type 2 diabetic subjects, respectively adjusted odds ratio (OR) 0.457, p=0.005. The Ala allele did not show a significant effect on anthropometric and biochemical parameters in the type 2 diabetic group, whereas in non-diabetic subjects, carriers of the Ala allele had significantly lower fasting insulin (p=0.007) and homeostasis model assessment of insulin resistance (HOMA-IR) (p=0.009) levels compared to Pro/Pro subjects. Multivariate logistic regression analysis showed that Pro12Ala polymorphism was an independent determinant of type 2 diabetes in this population. Conclusions: Our results for a sample of Iranian type 2 diabetes cases and controls provide evidence that the Pro/Ala genotype of the PPARγ-2 gene is associated with insulin sensitivity and may also have protective role against type 2 diabetes. ©2007 by Walter de Gruyter

Enhancement of electrical characteristics of a-ZTO TFTs based on channel layers produced with alternating precursor concentration

The enhancement in electrical characteristics of the thin film transistors (TFTs) based on the mixed-stacked amorphous zinc tin oxide (a-ZTO) with an alternating precursor concentration is reported. The channel layers were deposited via sol-gel on oxidised p-Si. The source/drain ohmic contacts were prepared on the ZTO layer, constructing the bottom-gate TFTs. In this investigation, the TFTs with the following three channel layers were fabricated, and their characteristics were compared; (i) four layers produced from 0.05 M precursor solution, (ii) four layers produced from 0.2 M precursor solution, and (iii) four layers with alternating 0.05 and 0.2 M precursor solutions. It was found that the mobility (5.3 cm2/V s) of the TFT fabricated with the channel layers with alternating precursor concentration was higher than those with single concentration. Although the mechanism for this mobility enhancement is still being further analysed, it was conjectured that alternating precursor concentration might have reduced the trap density in the transistor channel and/or ZTO/SiO2 interfaces.Scopu

Electrical characteristics and density of states of thin-film transistors based on sol-gel derived ZnO channel layers with different annealing temperatures

We report on the fabrication and electrical characterization of bottom gate thin-film transistors (TFTs) based on a sol-gel derived ZnO channel layer. The effect of annealing of ZnO active channel layers on the electrical characteristics of the ZnO TFTs was systematically investigated. Photoluminescence (PL) spectra indicate that the crystal quality of the ZnO improves with increasing annealing temperature. Both the device turn-on voltage (Von) and threshold voltage (VT) shift to a positive voltage with increasing annealing temperature. As the annealing temperature is increased, both the subthreshold slope and the interfacial defect density (Dit) decrease. The field effect mobility (?FET) increases with annealing temperature, peaking at 800 �C and decreases upon further temperature increase. An improvement in transfer and output characteristics was observed with increasing annealing temperature. However, when the annealing temperature reaches 900 �C, the TFTs demonstrate a large degradation in both transfer and output characteristics, which is possibly produced by non-continuous coverage of the film. By using the temperature-dependent field effect measurements, the localized sub-gap density of states (DOSs) for ZnO TFTs with different annealing temperatures were determined. The DOSs for the subthreshold regime decrease with increasing annealing temperature from 600 �C to 800 �C and no substantial change was observed with further temperature increase to 900 �C. - 2017 Author(s).The project was funded by AU-IGP. Park would like to thank Walter Professorship for partial support of this project