Synthesis of novel 5H‐Pyrimido[5,4‐b]mdole‐(1H,3H)2,4‐diones as potential ligands for the cloned α1‐adrenoceptor subtypes

A new series of 3‐[ω‐[4‐(4‐substituted phenyl)piperazin‐1‐yl]alkyl]‐5H‐pyrimido[5,4‐b]indole‐(1H,3H)‐2,4‐diones ( 3–10 and 12–13 ) were synthesized from the N‐(2‐chloroethyl)‐N'‐[3‐(2‐ethoxycarbonyl)indolyl] urea ( 1 ) or the N‐(3‐chloropropyl)‐N'‐[3‐(2‐ethoxycarbonyl)indolyl] urea ( 2 ) and a number of 1‐(4‐substi‐tuted‐phenyl)piperazines. 3‐[2‐[4‐(4‐Aminophenyl)piperazin‐1‐yl]ethyl]‐5H‐pyrimido[5,4‐b]indole‐(1H,3H)2,4‐dione ( 14 ) was obtained by reduction of the parent nitro compound 8 . The obtained 5H‐pyrimido[5,4‐b]indole‐(1H,3H)2,4‐dione derivatives were tested towards cloned α_1A, α_1B and α_1D adrenergic receptors subtypes in binding assays. Some compounds showed good affinity and selectivity for the α_1D‐adrenoceptor subtype.     

Spectral and Electrical Properties of a Medium Pressure,Low-Power,RF-Generated Postdischarge Nitrogen Plasma Jet

A method for obtaining a medium pressure (p ～ 1 torr), low power (< 100 W), RF-generated plasma jet, suitable for chemical kinetics studies and technological applications is described. Though various supply gases can be used to create the plasma jet, only results on the properties of a nitrogen jet are given in this paper with an emphasis on some spectral and electrical characteristics. The emission spectra of the nitrogen jet are discussed and spatial distributions of the relative concentration of nitrogen or radical impurities emitting species such as N₂(C³Π_u, v' = 0), NH(A³Π_g, v'=0) in the bulk of the postdischarge plasma are calculated from the intensity of their vibrational bands. Electrical space resolved double probe measurements and the spatial distributions of the electron density and temperature in the plasma jet are also presented. Possible applications are shortly discussed.     

A polynomial case of the parsimony haplotyping problem

The parsimony haplotyping problem was shown to be NP-hard when each genotype had k?3ambiguous positions, while the case for k?2 was open. In this paper, we show that the case for k?2 is polynomial, and we give approximation and FPT algorithms for the general case of k?0 ambiguous positions.     

Thermal behaviour of <Emphasis Type="Italic">sym</Emphasis>-octahydroacridines and their corresponding N(10)-oxides

We present and discuss results on the thermal behaviour of 1,2,3,4,5,6,7,8-octahydroacridine (OHA), together with six 9-substituted congeners, i.e. R = –Br, –OCH₃, –NH₂, –NO₂, –OH, and furyl (–C₄H₃O), and their corresponding N(10)-oxides, under nitrogen atmosphere and with alumina as reference, at a heating rate of 5 °C min^?1 from room temperature to 300 °C. Chromatography has been carried out on aluminium sheets, with aluminium oxide 60 F254 neutral (Merck). Melting effects are observed for almost all compounds in their corresponding curves, precisely determined by using a Boetius apparatus. Homolysis of the carbon-substituent bond occurs in most cases, a phenomenon which is consistent with the values of the bond dissociation energy. For all compounds, except for hydroxyl congeners, thermal decomposition started with an endothermic peak. Octahydroacridines readily decompose into volatile products, an effect which correlates with their low melting points, while little amounts of residue remain in place of the aromatic amines compared to the N(10)-oxides. The presence of N–O bonds greatly influences the thermal stability of the compound, in the sense of increasing it compared with the parent amine. Quantitative studies of the decomposition products reveal that the melting points, the 9-position substituent, and N–O bond all play an important role upon the thermal behaviour. Mechanistic/kinetic pathways are also proposed as such results are important in further designing laser processing protocols, i.e. matrix-assisted pulsed laser evaporation (MAPLE) or laser-induced forward transfer (LIFT), for thin film deposition and/or device printing.     

Neuraminic Acid Derivatives as Anti-Influenza Drugs

Influenza types A and B both cause serious disease in man; vaccines are in use but must be reformulated each year in response to antigenic variation and are frequently ineffective against new influenza variants. Influenza viruses are enveloped RNA viruses which contain two major surface glycoproteins: hemagglutinin (HA) and neuraminidase (NA, EC 3.2.1.18). These proteins are essential for infection and offer potential targets for antiviral drug development. Based upon the knowledge of the most important steps of the whole interaction between virus and host cell, the main purpose of our research was to find a sialic acid analogue for increasing the affinity of the sialic acid cell receptor analogue to the principal binding site of HA. A series of sialic acid analogues were prepared and their structures were designed with the goal to have molecules able to saturate the HA receptor and thereby be potentially useful as anti-influenza drugs.     

A capillary-based amperometric flow immunoassay for 2,4,6-trichlorophenol

This paper describes the development of two different capillary-based heterogeneous competitive flow immunoassay formats (capillary flow injection immunoassay (CFIIA) and capillary sequential injection immunoassay (CSIIA)) for the determination of 2,4,6-trichlorophenol (2,4,6-TCP). The assays are based on the competition between the analyte and an analyte derivative labelled with the enzyme beta-galactosidase, for an anti-TCP antibody, followed by the injection of the mixture at equilibrium into a flow stream, where separation between the fractions bound and unbound to the antibody is performed in a glass capillary containing immobilised protein A. The antibody-tracer fraction retained inside the protein A capillary was measured by injection of 4-aminophenyl- beta- D-galactoside (4-APG), followed by amperometric detection of the enzymatically generated 4-aminophenol (4-AP), leading to a negative correlation between the signal and the analyte concentration.The two immunoassay formats were compared in terms of sensitivity and speed, giving IC(50) values of 1.41+/-0.03 and 1.64+/-0.07 micro g L(-1), detection limits of 0.2 and 0.4 micro g L(-1), and sample throughputs of 6 and 4 h(-1) for the CFIIA and CSIIA system, respectively.The influence of different interfering chlorophenolic compounds in the assay was minor, with only one exception (i.e. 2,4-dichlorophenol). In addition, different water matrices were tested (surface, tap, and rain water), showing that the matrix influence was negligible, except for rainwater, which resulted in a 30% increase in sensitivity. As a conclusion, the assay is suitable for the fast screening of TCP present at low concentration levels in water samples.     

Stereoselective synthesis of new bicyclic N,O-iso-homonucleoside analogues

The synthesis of two new bicyclic nucleoside analogues is reported. These compounds are iso-homonucleoside and are synthesised through a 1,3-dipolar cycloaddition of an enantiopure cyclic nitrone to protected allyl acohol and subsequent introduction of thymine by a Mitsunobu reaction.