Imidazoline Derivatives Research Articles

Thermal study of four irradiated imidazoline derivatives in solid state

Four imidazoline derivatives: antazoline (AN), naphazoline (NN), tymazoline (TM), xylometazoline (XM), in the form of hydrochlorides in solid phase have been subjected to high energy e-beam irradiation from an accelerator (~10 MeV) at a dose varied from 25 to 200 kGy. The effects of the irradiation have been assessed by DSC, X-ray diffraction, FTIR, EPR and TLC. The standard sterilisation dose of 25 kGy has been found to produce changes in the properties of one derivative (XM), two other ones (AN and TM) have been found sensitive to doses >100 kGy, whereas NN has been resistant to irradiation in the whole range studied (25–200 kGy). EPR results indicated that the changes taking place in the therapeutic substances studied are related to radical formation. The irradiation induced changes in colour, a decrease or increase in the melting point, changes in the XRD pattern, small changes in the shape of FTIR peaks and the presence of radiolysis products. The XM compounds cannot be sterilised by irradiation because of the radiation induced changes in its physico-chemical properties.

Imidazole and Imidazoline Derivatives as N‐Donor Ligands for Palladium‐Catalyzed Mizoroki–Heck Reaction

AbstractImidazole and imidazoline (dihydroimidazole) derivatives can serve as efficient and simple ligands for the palladium‐catalyzed Mizoroki–Heck reaction. Among the imidazole and imidazoline derivatives in our investigations, the 2‐methylimidazoline‐palladium(II) chloride complex exhibited the highest catalytic activity.

Drug facilitated sexual assault using an over-the-counter ocular solution containing tetrahydrozoline (Visine ®)

Drug facilitated sexual assault (DFSA) has been defined as sexual activity occurring where consent is invalid or absent due to the effects of drugs and or alcohol. We report the use of a commonly available over-the-counter drug to induce an obtunded compliant victim with no memory of the period during the sexual assault. An adult male repeatedly used tetrahydrozoline to induce a comatose state in an adult female and four female children for the purposes of sexual assault. It may be warranted to include imidazoline derivatives in the testing for cases of DFSA.

Imidazoline and Its Derivatives : An Overview

Imidazoline derivatives, a class of novel cationic surfactants are presently gaining importance in global detergent market due to their wide range of applications. These are extensively used mainly as fabric softeners and antistatic agents. The present communication reviews the preparation, reaction scheme, reaction rates and properties of imidazoline derivatives. The analysis of imidazoline derivatives, its mode of action, their biodegradation and various applications have also been discussed.

Investigation on imidazoline amide adsorption and electrochemical behaviour of coupled steels

The adsorption behaviour of imidazoline derivative as a cationic inhibitor on the galvanic electrode has been investigated by electrochemical methods, Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). The galvanic electrode was prepared by coupling N80 carbon steel and S31803 stainless steel, and all experiments were performed in NaCl solution in the presence or absence of the inhibitor. Electrochemical experiments reveal stainless steel and carbon steel carry positive and negative excess charges in NaCl solution. For the galvanic electrode, positive and negative charges are carried on the carbon steel side and stainless steel side respectively, and the inhibitor is a type of cathodic inhibitor for galvanic corrosion. Fourier transform infrared spectroscopy and AFM were used to analyse the protective layer formed on the electrodes, a weaker adsorbability of the inhibitor on the anode (carbon steel side) of the galvanic electrode was measured. Results show the protective layer formed on the single carbon steel electrode is compact. In the case of coupling carbon steel and stainless steel, the adsorption film on the anode (carbon steel side) of galvanic electrode (GE) is not intact but defective. A major cause of failure of inhibiting galvanic corrosion is proposed based on the results obtained from electrochemical methods, FTIR and AFM.

Tricyclic Imidazoline Derivatives as Potent and Selective Adenosine A1 Receptor Antagonists

Novel tricyclic imidazoline antagonists of the adenosine A1 receptor are described. For key compounds, the selectivity level over other adenosine receptor subtypes is examined along with their in vivo effects in a rat diuresis model. Compound 14, the (R)-isomer of 7,8-dihydro-8-ethyl-2-(4-bicyclo[2.2.2]octan-1-ol)-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one, is a particularly potent adenosine A1 receptor antagonist with good selectivity over the other three adenosine receptor subtypes: A1 (human) Ki=22 nM; A2A (human) Ki=4400 nM; A2B (human) Ki=580 nM; A3 (human) Ki>or=10,000 nM. Imidazoline 14 is a competitive adenosine A1 receptor antagonist with a pA2 value of 8.88 and is highly soluble in water (>100 mg/mL). In addition, it has an oral bioavailability of 84% and an oral half-life of 3.8 h in rats. When orally administered in a rat diuresis model, compound 14 promoted sodium excretion (ED50=0.01 mg/kg). This level of efficacy is comparable to that of BG9928, a selective adenosine A1 receptor antagonist that is currently in clinical trials as a treatment for congestive heart failure. Additional modifications to 14 also showed that the bridgehead hydroxyl group could be replaced with a propionic acid (compound 36) without a significant loss in binding affinity or in vivo activity.

N, N‘ (4,5-Dihydro-1H-imidazol-2-yl)3-aza-1, 10-decane-diamine and N, N’(4,5-dihydro-1H-imidazol-2-yl)3-aza-1, 10-dodecane-diamine antagonize cell proliferation as selective ligands towards topoisomerase II

New alkyl imidazoline derivatives have been synthesized as potential anti-cancer agents. The anti-proliferative activity of these compounds, evaluated against representative human haematological and solid neoplastic cell lines, showed that N, N'-di (4,5-dihydro-1H-imidazol-2-yl)3-aza-1,10-decane-diamine (8) and N, N'-di (4,5-dihydro-1H-imidazol-2-yl)3-aza-1,10-dodecane-diamine (9) were the most active compounds; in fact, they inhibited the cell proliferation at submicromolar concentrations. In enzyme assays, compound 9 turned out to be an inhibitor of topoisomerase II at concentrations comparable with those of the reference topoisomerase II inhibitor, etoposide.

Design and synthesis of novel imidazoline derivatives with potent antihyperglycemic activity in a rat model of type 2 diabetes

Imidazoline derivatives have been reported to show antihyperglycemic activity in vivo. In the present study, we first showed that there was no correlation between the in vivo antidiabetic activity and the in vitro affinities for the I 1/ I 2 binding sites for several substituted aryl imidazolines. Among these compounds, 2-(α-cyclohexyl-benzyl)-4,5-dihydro-1 H-imidazole 2 exhibited potent antihyperglycemic properties. It was then chosen as lead compound. Thirty-six new derivatives were synthesized by replacing the cyclohexyl/benzyl group by various cyclic systems or the imidazoline ring by isosteric heterocycles. These compounds were evaluated in vivo for their antihyperglycemic activity using an oral glucose tolerance test (OGTT) in a rat model of type-2 diabetes obtained by giving a single intravenous (iv) injection of a low dose of streptozotocin to rats (STZ rats) and in normal rats. Nine compounds with an imidazoline moiety, possibly substituted by a methyl group, had a potent effect on the glucose tolerance in normal or STZ-diabetic rats, after an oral (po) administration of the test compound at a dose of 30 or 10 mg kg −1, without any hypoglycemia. Replacement of the imidazoline ring by isosteric heterocycles resulted in a total loss of activity.

Computational simulations of the molecular structure and corrosion properties of amidoethyl, aminoethyl and hydroxyethyl imidazolines inhibitors

To proof the corrosion efficiency of hydroxyethyl, aminoethyl and amidoethyl imidazolines, they were evaluated by linear polarization resistance and polarization curves in deaerated 3% NaCl + Diesel + inhibitors saturated with CO 2 at 50 °C. The most efficient inhibitor was the amido ethyl imidazoline, with an efficiency of 97.88% whereas the least efficient was the hydroxyethyl imidazoline, with an efficiency of 88.8%. A theoretical study of the corrosion inhibition efficiency of these imidazoline derivatives, was carried out using density functional theory (DFT). The computational calculations were used to obtain information about their molecular structure and those properties related with the inhibition efficiency of these inhibitors. The obtained correlations and theoretical conclusions agree well with the experimental results.

Evidence against α2‐adrenoceptors mediating relaxation in rat thoracic aortae: α2‐agonists relaxation depends on interaction with α1‐adrenoceptors

In rat aorta, the presence of functional alpha(2)-adrenoceptors (alpha(2)-AR) was investigated in ring preparations preconstricted with alpha(1)-adrenergic and non- alpha(1)-adrenergic agonists. Particularly, the hypothetical interference of alpha(2)-AR agonists with alpha(1)-AR-mediated vasoconstriction was evaluated. Relaxant and contractile responses to alpha(2)-AR agonists were obtained. In endothelium-intact and endothelium-denuded aortic rings preconstricted with phenylephrine (1 x 10(-6) m), the imidazoline derivatives, clonidine and UK14304, induced relaxations with similar order of potencies (-log EC(50)) and maxima relaxant effects respectively. Pretreatment with the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) had no effect on the relaxant responses to clonidine and UK14304. In phenylephrine-constricted rings with endothelium, relaxations to clonidine and UK 14304 were not antagonized by the selective alpha(2)-AR antagonist, rauwolscine (< or =1 x 10(-6) m). Clonidine and UK 14304 induced only contractions on endothelium-intact and endothelium-denuded aortic rings contracted with prostaglandin F(2alpha) (3 x 10(-7) m). Moreover, clonidine and UK 14304-induced relaxation of endothelium-denuded arteries precontracted with methoxamine but not with serotonin. Finally, the concentration-contraction curves to clonidine and UK 14304 in endothelium-denuded aortic rings were significantly shifted to the right by the alpha(1D)-AR selective antagonist, BMY 7378, and rauwolscine. The pA(2) and pK(B) values for BMY 7378 and rauwolscine, respectively, against endothelium-independent actions of clonidine and UK 14304 were characteristic of an effect on the alpha(1D)-AR. The other selective alpha(2)-AR agonist tested BHT 933 (an azepine derivative), lacks considerable relaxant and contractile effects in rat aorta. The results provide no evidence for the presence of functional alpha(2)-AR in rat aorta. Respectively, the relaxant and contractile effects of the imidazoline derivatives, clonidine and UK 14304, may be due to an adjustable (in relation to the agonist-dependent active state of the alpha(1)-AR), inhibitory and excitatory, interaction with alpha(1)-ARs.

Adsorption behavior and synergistic mechanism of a cationic inhibitor and KI on the galvanic electrode

The synergistic effect between KI and imidazoline derivative as a cationic inhibitor for inhibiting galvanic corrosion has been investigated by using electrochemical methods, atomic force microscopy and Fourier transform infrared (FTIR) spectroscopy. A galvanic electrode was prepared by coupling N80 carbon steel and S31803 stainless steel, and all experiments were performed in NaCl solution in the presence or absence of imidazoline derivative (MAD) and KI. Zero charge potential experiments reveal carbon steel and stainless steel carry positive and negative excess charges in NaCl solution, respectively, and stainless steel carries negative excess charge in NaCl solution with KI. Polarization curves and galvanic current measurements suggest that, for the galvanic corrosion, both MAD and KI are mainly cathodic type inhibitors, and a synergistic effect exists between KI and MAD. FTIR and AFM were used to analyze the inhibitor film formed on the surface of the electrodes. Results show that in the presence of KI, compared with that in the absence of KI, the inhibitor film on the anode of galvanic electrodes (GE) is more compact, and the adsorbability of the inhibitor on the surface of carbon steel is strengthened. A suitable mechanism of corrosion inhibition is proposed based on the results obtained from electrochemical measurements, AFM and FTIR. It is found that the anion I − can change the distribution of excess charge on the surface of galvanic electrode, thus helps the inhibitor to adsorb on both the cathodic area and the anodic area.

Fluorescence detection of Al(III) using derivatives of oxazoline and imidazoline

Coordination ability of Al(III) towards 2-(4,5-dihydro-1,3-oxazol-2-yl)phenol ( 1) and 2-(4,5-dihydro-1,3-imidazol-2-yl)phenol ( 2) was studied added to the determination of the stoichiometry of the adducts formed in solution. The fluorogenic sensor character, that means efficiency and selectivity, of the two studied molecules was then quantified.

The Inhibition Synergistic Effect Between Imidazoline Derivative and Thiourea

The Inhibition Synergistic Effect Between Imidazoline Derivative and Thiourea

Corrosion inhibition approach of oil production systems in offshore oilfields

AbstractSynthesis and modification of imidazoline were carried out based on review of the corrosion inhibitor development and application for oilfields. A series of imidazoline compounds were synthesised through the solvent dewatering and vacuum dewatering methods. After reaction of imidazoline with ethane oxide, the produced compound was used to react with halogen hydrocarbon and polyphosphoric acid respectively. Finally an agent with performance of corrosion‐inhibition, sterilisation and anti‐scaling was obtained. The structures of the compounds were characterised by the Fourier transformation infrared spectrum. The relationships between corrosion inhibition effectiveness of the compounds and their structures were investigated so as to determine the structure of a novel corrosion inhibitor. The selected corrosion inhibitor was evaluated by a series of experiments to understand the characteristics of imidazoline derivative and some major factors associated with oil production in the oilfields of China. The experimental results showed that this corrosion inhibitor has outstanding performance of corrosion inhibition and sterilization, and is suitable for corrosion inhibition of the oil abstraction systems with high water‐content in the offshore oilfields.

2-(Anilino)imidazolines and 2-(benzyl)imidazoline derivatives as h5-HT 1D serotonin receptor ligands

2-(Anilino)imidazolines were identified as novel human 5-HT 1D receptor ligands, but offered no particular advantage over previously reported 2-(benzyl)imidazolines. Pharmacokinetic and functional data were obtained for selected 2-(benzyl)imidazoline derivatives.

Flow injection analysis of oxymetazoline hydrochloride with inhibited chemiluminescent detection

A rapid and sensitive chemiluminescence method for the quantitation of oxymetazoline hydrochloride in pharmaceutical formulations has been developed. Oxymetazoline hydrochloride inhibits strongly the chemiluminescence from the oxidation of luminol in alkaline medium. Based on this effect, a simple method is proposed for the determination of this imidazoline derivative by flow injection analysis employing chemiluminescence detection. The optimization of the experimental and instrumental variables such as, selection of the oxidant, concentration of reagents, flow rates, injection volume, etc., has been carried out using the proposed flow injection manifold. The performance characteristics have been established, showing a wide linear response in the range of 1.88–200 ng/ml and a detection limit of 1.21 ng/ml. This is the first chemiluminescent method for the determination of oxymetazoline which has been satisfactorily applied to the analysis of the drug in intranasal pharmaceutical formulations.

Neue 3-Imidazolin-1-oxyl-Radikale mit pyridyl und chinolylhaltigen 4-(2-Aminovinyl)-Substituenten und Palladium, Platin und Ruthenium-Komplexe mit diesen 4-Amino-1-azadien-Liganden / New 3-Imidazoline-1-oxyl Radicals with Pyridyl and Quinolyl Containing 4-(2-Aminovinyl) Substituents and Palladium, Platinum and Ruthenium Complexes of these 4-Amino-1-aza-diene Ligands

The addition of pyridyl and quinolyl nitriles to the 4-lithium salt of 1-hydroxy-2.2.4.5.5- pentamethyl-3-imidazoline with a silyl protected OH group affords 4-aminovinyl substituted imidazoline derivatives 3, 6, 9, 12, and 15 which can be converted into the corresponding nitroxide radicals 5, 8, 11, 14 and 17. The 4-amino-1-azadiene residues of these imidazoline nitroxides form a series of chelates of palladium (22 - 26, 29 - 32) and with ruthenium half sandwich complexes (33 - 36). Coordination of the pyridine or quinoline N atom has been observed in mononuclear (19 - 21) and trinuclear (27, 28) palladium complexes and the structure of 19 was determined by X-ray diffraction.

Course and therapy of intoxication with imidazoline derivate naphazoline

Objective: Imidazoline derivatives like naphazoline have a firm place in diagnostics and therapy of otorhinolaryngology because of their vasoconstrictive and decongestive properties. Their alpha-adrenergic potential could induce not only local but also systemic side effects like hypertension and tachycardia which can increase a life-threatening intoxication. Signs of imidazoline intoxication are excessive systolic and diastolic hypertension and hypotension, bradycardia with arrthyhmia, respiratory depression, excitation or severe CNS depression. Patients: The typical course of an intoxication and its sufficient therapy is reported by means of two cases of intraoperative application of naphazoline for hemostasis. Results: In case of overdosage or intoxication, symptomatic drug therapy with intravenous administration of 5 mg phentolamine for adults and 1 mg phentolamine for infants has to be done. Phentolamine, an alpha-adrenoceptor antagonist, acting against peripheral and central side effects has to be used because no specific antidote is available. Conclusions: Especially pediatric otorhinolaryngologists have to know about symptoms and therapy of an intoxication after application of naphazoline. Particularly with children, a narrow therapeutic to toxic window can be observed in this frequently used drug.

Characteristics of Clonidine Responders in Childhood PTSD: Its Possible Use in Acute Trauma

Clonidine (CLD) is an imidazoline derivative and α2 adrenergic agonist with anxiolytic properties. It acts at the level of the locus ceruleus via stimulation of presynaptic autoreceptors, reducing sympathetic outflow. Originally introduced perhaps 20 years ago, it was employed as a weak vasodilator in the treatment of hypertension, though it was quickly supplanted by more effective agents, and relegated to the sidelines. It is still prescribed for treatment of peri–menopausal hot flashes, due to its apparent capacity to vaso–stabilize. Applications to child psychiatry did not appear before 1990, when it received some mention in the research literature, albeit as a ‘nonspecific’ application to a variety of psychopathological conditions. At present, its most widely–acclaimed indication is as an adjunct to treatment for Attention–Deficit Hyperactivity Disorder (ADHD), mainly for its properties in promoting sleep, either for primary parasomnias or those induced by stimulant treatment. There have been only sporadic citations in the research literature to clonidine’s utility in the treatment of Posttraumatic Stress Disorder (PTSD). Research into its capacity to ameliorate post–traumatic features was slowed by reports of its mediocre effects upon chronic PTSD, and its application to adults, as opposed to children. Several interesting reports however, yielded tantalizing glimpses into its potential for special application to childhood PTSD. Notably, in studies of non–specific anxiety, growth hormone (GH) response was found not to be blunted by CLD challenge—the opposite effect to that observed in adults—which led authors to speculate that adrenergic post–synaptic down regulation is not a feature of childhood anxiety, and further, that early intervention might prevent the development of down–regulation, which itself may be persistent. This would seem to suggest the possibility of a “window of opportunity” for pharmacologic treatment following traumatic exposure, in which noradrenergic outflow, prompted by exaggerated threat-estimate’s maximal, yet permanent changes in the form of persistent perhaps permanent down regulation of receptors has not yet occurred.

Evidence for nonadrenoceptor responses to imidazoline derivatives in the porcine isolated rectal artery.

High concentrations of phentolamine, efaroxan, and idazoxan were found to produce nonadrenoceptor contractions of the porcine isolated rectal artery previously exposed to U46619 and forskolin. These responses were insensitive to the putative imidazoline I(3) receptor antagonist KU-14R, unlike those previously reported in this preparation for oxymetazoline. The pharmacologic nature of this response and the obligate requirement for preconstriction suggests that these imidazoline derivatives modulate ion channel function through a novel nonadrenergic site.