PEG mediated synthesis and pharmacological evaluation of some fluoro substituted pyrazoline derivatives as antiinflammatory and analgesic agents

A new series of fluoro substituted pyrazoline derivatives 5a–g and 6a–g were synthesized in good to excellent yield from the corresponding pyrazole chalcones, 4a–g, by using polyethylene glycol-400 (PEG-400) as an alternative reaction medium. The newly synthesized compounds were characterized and screened for their in vivo antiinflammatory and analgesic activity. Compounds 5g and 6g were found to be more potent than standard drug Diclofenac and six other compounds 5b, 5c, 5f, 6b, 6c and 6f showed significant antiinflammatory activity as compared to standard drug. Compounds 5c, 5d, 5e, 5f, 6c, 6d, 6e and 6f showed significant analgesic activity as compared to standard drug Aspirin.     

The synthesis of -xylo-hexos-4-ulose and some derivatives

D-xylo-Hexos-4-ulose has been synthesised, characterised chromatographically, and methyl α- -xylo-hexopyranosid-4-ulose has been shown to be stable in neutral aqueous solution, contrary to a previous report. Glycosyl phosphate derivatives are also reported.     

Evolution of sucrose synthesis

Cyanobacteria and proteobacteria (purple bacteria) are the only prokaryotes known to synthesize sucrose (Suc). Suc-P synthase, Suc-phosphatase (SPP), and Suc synthase activities have previously been detected in several cyanobacteria, and genes coding for Suc-P synthase (sps) and Suc synthase (sus) have been cloned from Synechocystis sp. PCC 6803 and Anabaena (Nostoc) spp., respectively. An open reading frame in the Synechocystis genome encodes a predicted 27-kD polypeptide that shows homology to the maize (Zea mays) SPP. Heterologous expression of this putative spp gene in Escherichia coli, reported here, confirmed that this open reading frame encodes a functional SPP enzyme. The Synechocystis SPP is highly specific for Suc-6(F)-P (K(m) = 7.5 microM) and is Mg(2+) dependent (K(a) = 70 microM), with a specific activity of 46 micromol min(-1) mg(-1) protein. Like the maize SPP, the Synechocystis SPP belongs to the haloacid dehalogenase superfamily of phosphatases/hydrolases. Searches of sequenced microbial genomes revealed homologs of the Synechocystis sps gene in several other cyanobacteria (Nostoc punctiforme, Prochlorococcus marinus strains MED4 and MIT9313, and Synechococcus sp. WH8012), and in three proteobacteria (Acidithiobacillus ferrooxidans, Magnetococcus sp. MC1, and Nitrosomonas europaea). Homologs of the Synechocystis spp gene were found in Magnetococcus sp. MC1 and N. punctiforme, and of the Anabaena sus gene in N. punctiforme and N. europaea. From analysis of these sequences, it is suggested that Suc synthesis originated in the proteobacteria or a common ancestor of the proteobacteria and cyanobacteria.     

The synthesis of some cholest-7-en-6-one derivatives related to ecdysones

Cholest-7-en-6-one, 14α-hydroxycholest-7-en-6-one, 2β, 3β,5α-trihydroxycholest-7-en-6-one and ten other related compounds have been synthesized by efficient routes from cholesterol. The named compounds possess some of the characteristics of the insect moulting hormones, ecdysones.     

Design, synthesis and antimuscarinic activity of some imidazolium derivatives

A series of imidazolium salt derivatives was prepared as part of a search for subtype-selective antimuscarinic agents. On the basis of measurements of the antimuscarinic activity and subtype-selectivity for M2 and M3 muscarinic receptors, the structure-activity relationships of these compounds are discussed.     

Regioselective synthesis and antitumor screening of some novel N-phenylpyrazole derivatives

The versatile, hitherto unreported 4-acetyl-5-methyl-1-phenyl-3-phenylcarbamoyl-1H-pyrazole (3) was prepared via the reaction of 2-(2-phenylhydrazono)-2-chloro-N-phenylacetamide with pentan-2,4-dione in the presence of sodium ethoxide. Reaction of 3 with dimethylformamide-dimethylacetal (DMF-DMA) furnished the corresponding 4-[(E)-3-(dimethylamino)acryloyl]-5-methyl-1-phenyl-3-phenylcarbamoyl-1H-pyrazole (5). The latter product underwent regioselective 1,3-dipolar cycloaddition with some nitrilimines to afford the non-isolable dihydropyrazole intermediates which then lose dimethylamine yielding the corresponding pyrazole derivatives. The preliminary screening for the antitumor activity of all newly synthesized compounds was carried out against Ehrlich Ascites Carcinoma tumor cells.     

The synthesis of chlorodeoxyhexofuranoid derivatives

The reaction of 1,2-O-isopropylidene-α- d-glucofuranose with sulfuryl chloride at 0° and at 50° afforded 6-chloro-6-deoxy-1,2-O-isopropylidene-α- d-glucofuranose 3,5-bis(chlorosulfate) ( 3) and 5,6-dichloro-5,6-dideoxy-1,2-O-isopropylidene-β- l-idofuranose 3-chlorosulfate ( 7, not characterised), respectively. Dechlorosulfation of 3 afforded the hydroxy derivative, whereas treatment of 3 with pyridine gave the 3,5-(cyclic sulfate). Dechlorosulfation of 7 afforded 5,6-dichloro-5,6-dideoxy-1,2-O-isopropylidene-β- l-idofuranose which, on acid hydrolysis, was converted into 3,6-anhydro-5-chloro-5-deoxy- l-idofuranose. 5-Chloro-5-deoxy-α- l-idofuranosidurono-6,3-lactone and 5-chloro-5-deoxy-β- l-idofuranurono-6,3-lactone derivatives were also prepared.     

The fluorescence of some biphenyl derivatives

1. The variation with pH of the excitation and fluorescence wavelengths and fluorescence intensity of several hydroxy- and amino-biphenyls has been investigated with a view to using the data for the determination of hydroxybiphenyls in biological material. 2. 2- and 3-Hydroxy-, 2,2'-dihydroxy-, and 2-, 3- and 4-amino-biphenyl exhibited excited-state ionization. 4-Hydroxy- and 4,4'-dihydroxybiphenyl did not, and showed normal fluorescence changes with pH. 3. Biphenyl and 2- and 4-methoxybiphenyl showed no changes in fluorescence in the range pH0-14. 4. 4,4'-Dihydroxybiphenyl showed fluorescent peaks corresponding to the un-ionized form, the monoanion and dianion at the appropriate pH values, but 2,2'-dihydroxybiphenyl showed fluorescent peaks corresponding to the un-ionized form and the monoanion only, suggesting that it did not form a dianion. 5. 3- and 4-Nitrobiphenyl were non-fluorescent. 6. These results are discussed.     

In vitro and in vivo inhibition of sucrose synthesis by sucrose

The inhibitory effects of sucrose on rates of sucrose synthesis by sucrose phosphate synthase (SPS) from the maize scutellum and on net rates of sucrose production in maize scutellum slices from added glucose or fructose were studied. Scutellum extracts were prepared by freezing and thawing scutellum slices in buffer. The extracts contained SPS and sucrose phosphate phosphatase, but were free of sucrose synthase. SPS activity was calculated from measurement of UDP formation in the presence of UDPG, fructose-6-P and sucrose. The ranges of metabolite concentrations used were those estimated to be in scutellum slices after incubation in water or fructose for periods up to 5 hr. UDPG and fructose-6-P also were added at concentrations that saturated SPS. At saturating substrate levels, sucrose inhibition of SPS was less than that when tissue levels of substrates were used. With tissue levels of substrates and sucrose concentrations up to ca 166 mM, sucrose inhibitions of sucrose synthesis in vitro by SPS were similar to those observed in vivo. However, as the sucrose concentration rose above 166 mM, SPS activity was not inhibited further, whereas there was a further sharp decline in sucrose production by the slices. It is concluded that sucrose synthesis in vivo is controlled by sucrose inhibition of SPS over a considerable range of internal sucrose concentrations.     

Design,synthesis and cardiovascular evaluation of some aminoisopropanoloxy derivatives of xanthone

A series of aminoisopropanoloxy derivatives of xanthone has been synthesized and their pharmacological properties regarding the cardiovascular system has been evaluated. Radioligand binding and functional studies in isolated organs revealed that title compounds present high affinity and antagonistic potency for α₁-(compound 2 and 8), β-(compounds 1, 3, 4, 7), α₁/β-(compounds 5 and 6) adrenoceptors. Furthermore, compound 7, the structural analogue of verapamil, possesses calcium entry blocking activity. The title compounds showed hypotensive and antiarrhythmic properties due to their adrenoceptor blocking effect. Moreover, they did not affect QRS and QT intervals, and they did not have proarrhythmic potential at tested doses. In addition they exerted anti-aggregation effect. The results of this study suggest that new compounds with multidirectional activity in cardiovascular system might be found in the group of xanthone derivatives.