Radiosynthesis and Preclinical Evaluation of an α-Adrenoceptor Tracer Candidate, 6-[F]Fluoro-marsanidine.

Purpose: The α-adrenoceptors mediate many effects of norepinephrine and epinephrine, and participate in the regulation of neuronal, endocrine, cardiovascular, vegetative, and metabolic functions. Of the three receptor subtypes, only α and α are found in the brain in significant amounts. Subtype-selective positron emission tomography (PET) imaging of α-adrenoceptors has been limited to the α subtype.

COMPARISON OF THE EFFECTS OF MARSANIDINE DERIVATIVES ON RAT CARDIOVASCULAR SYSTEM.

Since clonidine was introduced in clinical practice, attempts are still made to obtain substances capable of centrally controlling blood pressure, however with pharmacological profile better than currently avail- able, such as moxonidine and rilmenidine. Recently synthesized indazole derivatives exert promising action on blood pressure and heart rate in Wistar rats. In the present study, our aim was to check which of tested substituted compound exerts the best effect on basic circulatory parameters.

1-[(Imidazolidin-2-yl)imino]-1H-indoles as new hypotensive agents: synthesis and in vitro and in vivo biological studies.

A series of 1-[(imidazolidin-2-yl)imino]-1H-indole analogues of hypotensive α -AR agonists, 1-[(imidazolidin-2-yl)imino]-1H-indazoles, was synthesized and tested in vitro for their activities at α - and α -adrenoceptors as well as imidazoline I and I receptors. The most active 1-[(imidazolidin-2-yl)imino]-1H-indoles displayed high or moderate affinities for α - and α -adrenoceptors and substantial selectivity for α -adrenoceptors over imidazoline-I binding sites. The in vivo cardiovascular properties of indole derivatives 3 revealed that substitution at C-7 position of the indole ring may result in compounds with high cardiovascular activity.

Transfer of SAR information from hypotensive indazole to indole derivatives acting at α-adrenergic receptors: In vitro and in vivo studies.

In a search for novel antihypertensive drugs we applied scaffold hopping from the previously described α1-adrenergic receptor antagonists, 1-[(imidazolin-2-yl)methyl]indazoles. The aim was to investigate whether the α-adrenergic properties of the indazole core were transferable to the indole core. The newly obtained 1-[(imidazolin-2-yl)methyl]indole analogues were screened in vitro for their binding affinities for α1-and α2-adrenoceptors, which allowed the identification of the target-based SAR transfer (T_SAR transfer) as well as structure-based SAR transfer (S_SAR transfer) events.

1-[(IMIDAZOLIN-2-YL)AMINO]INDOLINE AND 1-[(IMIDAZOLIN-2 YL)AMINO] 1,2,3,4-TETRAHYDROQUINOLINE DERIVATIVES: NEW INSIGHTS INTO THEIR CIRCULATORY ACTIVITIES.

N-[(Imidazolin-2-yl)amino]indolines and N-[(imidazolin-2-yl)amino]-1,2,3,4-tetrahydroquinolines, previously described in patent literature as hypertensive agents, were synthesized and tested in viny for their affinities to α1- and α2-adrenoceptors as well as imidazoline I, and I2 receptors. The compounds most potent at either α1- or α2-adrenoceptors were administered intravenously to normotensive Wistar rats to determine their effects on mean arterial blood pressure and heart rate. Upon intravenous administration at dose of 0.

The effect of 7-fluoro-marsanidine, a novel α2-adrenoceptor agonist, on extracellular noradrenaline in rat frontal cortex: a microdialysis study.

Previous in vitro binding studies identified a 7-fluoro derivative of marsanidine, a partial α2-adrenoceptor (α2-AR) agonist, to display high affinity and selectivity for α2-AR over α1-AR, imidazoline-1 and imidazoline-2 binding sites. In the present study 7-fluoro-marsanidine is further characterised in vivo to investigate its pharmacological effects on extracellular noradrenaline (NA) levels at frontal cortex in conscious freely moving rats using the technique of in vivo brain microdialysis. Peripheral administration of 7-fluoro-marsanidine via intraperitoneal (i.

Fluorinated analogues of marsanidine, a highly α2-AR/imidazoline I1 binding site-selective hypotensive agent. Synthesis and biological activities.

The aim of these studies was to establish the influence of fluorination of the indazole ring on the pharmacological properties of two selective α2-adrenoceptor (α2-AR) agonists: 1-[(imidazolidin-2-yl)imino]-1H-indazole (marsanidine, A) and its methylene analogue 1-[(4,5-dihydro-1H-imidazol-2-yl)methyl]-1H-indazole (B). Introduction of fluorine into the indazole ring of A and B reduced both binding affinity and α2-AR/I1 imidazoline binding site selectivity. The most α2-AR-selective ligands were 6-fluoro-1-[(imidazolidin-2-yl)imino]-1H-indazole (6c) and 7-fluoro-1-[(imidazolidin-2-yl)imino]-1H-indazole (6d).

Induction of apoptosis in HL-60 cells through the ROS-mediated mitochondrial pathway by ramentaceone from Drosera aliciae.

Ramentaceone (1) is a naphthoquinone constituent of Drosera aliciae that exhibits potent cytotoxic activity against various tumor cell lines. However, its molecular mechanism of cell death induction has still not been determined. The present study demonstrates that 1 induces apoptosis in human leukemia HL-60 cells.

5-Methyl-3,6,7,8a-tetra-hydro-2H-diimidazo[1,2-c:1',2'-e]pyrido[1,2-a][1,3,5]triazin-5-ium iodide.

The structure of the title compound, C(12)H(16)N(5) (+)·I(-), shows that the methyl-ation reaction with CH(3)I occurred at the imine N atom at position 5 of the 3,6,7,8a-tetra-hydro-2H-diimidazo[1,2-c:1',2'-e]pyrido[1,2-a][1,3,5]triazine system. In the cation, the sp(3)-hybridized C atom belonging to the fused dihydro-pyrine and dihydro-1,3,5-triazine rings deviates by 0.514 (3) Å from the best plane defined by the remaining cationic non-H atoms.

The guard cell as a single-cell model towards understanding drought tolerance and abscisic acid action.

Stomatal guard cells are functionally specialized epidermal cells usually arranged in pairs surrounding a pore. Changes in ion fluxes, and more specifically osmolytes, within the guard cells drive opening/closing of the pore, allowing gas exchange while limiting water loss through evapo-transpiration. Adjustments of the pore aperture to optimize these conflicting needs are thus centrally important for land plants to survive, especially with the rise in CO(2) associated with global warming and increasing water scarcity this century.

An update on abscisic acid signaling in plants and more..

The mode of abscisic acid (ABA) action, and its relations to drought adaptive responses in particular, has been a captivating area of plant hormone research for much over a decade. The hormone triggers stomatal closure to limit water loss through transpiration, as well as mobilizes a battery of genes that presumably serve to protect the cells from the ensuing oxidative damage in prolonged stress. The signaling network orchestrating these various responses is, however, highly complex.