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11.
Roland K. Robins Ganapathi R. Revankar Darrell E. O'Brien Robert H. Springer Thomas Novinson Anthony Albert Keitaro Senga Jon P. Miller David G. Streeter 《Journal of heterocyclic chemistry》1985,22(3):601-634
A number of new hypoxanthine analogs have been prepared as substrate inhibitors of xanthine oxidase. Most noteworthy inhibitory new hypoxanthine analogs are 3-(m-tolyl)pyrazolo[1,5-a]pyrimidin-7-one ( 47 ), ID50 0.06 μM and 3-phenylpyrazolo[1,5-a]pyrimidin-7-one ( 46 ), ID50 0.40 μM. 5-(p-Chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-one ( 63 ) and the corresponding 5-nitrophenyl derivative 64 exhibited an ID50 of 0.21 and 0.23 μM, respectively. 7-Phenylpyrazolo[1,5-a]-s-triazin-4-one ( 40 ) is shown to exhibit an ID50 of 0.047 μM. The structure-activity relationships of these new phenyl substituted hypoxanthine analogs are discussed and compared with the xanthine analogs 3-m-tolyl- and 3-phenyl-7-hydroxypyrazolo[1,5-a]pyrimidin-5-ones ( 90 ) and ( 91 ), previously reported from our laboratory to have ID50 of 0.025 and 0.038 μM, respectively. The presence of the phenyl and substitutedphenyl groups contribute directly to the substrate binding of these potent inhibitors. This work presents an updated study of structure-activity relationships and binding to xanthine oxidase. In view of the recent elucidation of the pterin cofactor and the proposed binding of this factor to the molybdenum ion in xanthine oxidase, a detailed mechanism of xanthine oxidase oxidation of hypoxanthine and xanthine is proposed. Three types of substrate binding are viewed for xanthine oxidase. The binding of xanthine to xanthine oxidase is termed Type I binding. The binding of hypoxanthine is termed Type II binding and the specific binding of alloxanthine is assigned as Type III binding. These three types of substrate binding are analyzed relative to the most potent compounds known to inhibit xanthine oxidase and these inhibitors have been classified as to the type of inhibitor binding most likely to be associated with specific enzyme inhibition. The structural requirements for each type of binding can be clearly seen to correlate with the inhibitory activity observed. The chemical syntheses of the new 3-phenyl- and 3-substituted phenylpyrazolo[1,5-a]pyrimidines with various substituents are reported. The syntheses of various 8-phenyl-2-substituted pyrazolo-[1,5-a]-s-triazines, certain s-triazolo[1,5-a]-s-triazines and s-triazolo[1,5-a]pyrimidine derivatives prepared in connection with the present study are also described. 相似文献
12.
Mavis M. Kadooka Mildred Y. Chang Hiroshi Fukami P.J. Scheuer Jon Clardy Barbara A. Solheim James P. Springer 《Tetrahedron》1976,32(8):919-924
From the bark of the endemic Hawaiian tree Sophora chrysophylla Seem. we have isolated two unprecedented quainolizidine alkaloids, mamanine (4) and pohakuline (5). Both bases are 1-hydroxymethylenequinolizidines which are linked at C-3 to α-pyridone or α-piperidone moieties. The alkaloids may be intermediates in a heretofore unknown biogenetic pathway of Sophora alkaloids. 相似文献
13.
Lynch CL Hale JJ Budhu RJ Gentry AL Finke PE Caldwell CG Mills SG MacCoss M Shen DM Chapman KT Malkowitz L Springer MS Gould SL DeMartino JA Siciliano SJ Cascieri MA Carella A Carver G Holmes K Schleif WA Danzeisen R Hazuda D Kessler J Lineberger J Miller M Emini E 《Organic letters》2003,5(14):2473-2475
[reaction: see text] A novel approach to alpha,alpha-disubstituted-beta-amino acids (beta(2,2)-amino acids) was employed in the synthesis of a series of 3-(pyrrolidin-1-yl)propionic acids possessing high affinity for the CCR5 receptor and potent anti-HIV activity. The rat pharmacokinetics for these new analogues featured higher bioavailabilities and lower rates of clearance as compared to cyclopentane 1. 相似文献
14.
Static pressure usually increases the transition temperatures of polymers by decreasing their free volume. If the pressurizing medium is soluble in the polymer matrix, the opposing effect of increasing the free volume is possible. Those shifts of transition temperatures were monitored with a medium-pressure Differential Scanning Calorimetry (DSC) device. The influences of sorbed and surrounding gas molecules are demonstrated by changes occurring in the transition temperature regions. The results show the severe plasticizing effect of CO2 on poly(p-phenylene sulphide) (PPS). The glass transition temperature TG and the temperature of crystallization TC are influenced by sorbed gas molecules. They decrease due to sorbed CO2 molecules. Glass transition is lowered, but is difficult to interpret, as relaxation phenomena which diminish with increasing pressure occur during DSC runs. In crystallites no gas solution is usually possible, so that the melting point of PPS is mainly affected by influences other than plasticization. 相似文献
15.
Alejandro J. González Fá Isabella Cerutti Valeria Springer Stefano Girotti María E. Centurión María S. Di Nezio Marcelo F. Pistonesi 《Chromatographia》2017,80(9):1459-1466
The development of methodologies for the characterization of silver nanoparticles (AgNPs) synthesized using natural products has received increasing attention, especially to monitoring its stability and size for further application. In this paper, a capillary electrophoretic (CE) method is presented for characterization of AgNPs synthesized using honey or glucose as reducing agents. A simple electrolyte solution composed of 20 mM sodium borate and 20 mM sodium dodecylsulfate (SDS) at pH 8.5 was used for separation of AgNPs within a short analysis time (<12 min). The obtained results were compared with the traditional characterization techniques, such as transmission electron microscopy (TEM) and dynamic light scattering (DLS), showing satisfactory correlation in terms of size distribution. In addition, valuable information about electrophoretic mobility and zeta potential values of AgNPs was obtained by applying the CE-UV/Vis method. Thus, the proposed methodology represents a straightforward tool for the fast and cost-effective characterization of AgNPs within a single analysis, employing minimal amounts of reagents and samples. 相似文献
16.
Ferroelectric liquid-crystalline side chain polymers containing polyacrylate or polysiloxane main chains, a mesogenic unit of three aromatic cores and chiral end groups were synthesized and characterized by D.S.C., optical microscopy, and X-ray diffraction. Polyacrylates with a flexible spacer of eleven methylene groups exhibit fast bistable switching in oriented samples (2 to 4μm cells) with response times of some ms at low D.C. voltages, making these polymers interesting for the fabrication of electrooptical devices. Somewhat longer response times were found for the first switchable polysiloxanes. In this case some problems in obtaining well orientated samples have to be solved. 相似文献
17.
18.
The symmetric varieties considered in this paper are the quotientsG/H, whereG is an adjoint semi-simple group over a fieldk of characteristic 2, andH is the fixed point group of an involutorial automorphism ofG which is defined overk. In the casek=C, De Concini and Procesi (1983) constructed a wonderful compactification ofG/H. We prove the existence of such a compactification for arbitraryk. We also prove cohomology vanishing results for line bundles on the compactification.
Dedicated to the memory of C. Chevalley 相似文献
19.
Liquid crystalline side group polymers with azo-chromophores and fluorinated tails of varying length
Ralf Ruhmann Thomas Thiele Dietmar Wolff Dietrich Prescher Jü rgen Springer 《Liquid crystals》1996,21(3):307-312
A series of side group liquid crystalline polymethacrylates with 4'-(1H,1H-perfluoroalkoxy)-azobenzene mesogenic units was synthesized and characterized by differential scanning calorimetry, polarizing optical microscopy and X-ray diffraction methods depending on the tail length. The phase behaviour is discussed as a function of the length of the tail groups. Very high clearing temperatures up to 290°C were observed for the polymers with long tail groups. 相似文献
20.
With a high pressure gas target muonic F and S X-ray intensities in SF6 and H2+SF6 have been measured. It was found that the distribution of muons between sulphur and fluorine is not at all equal to the ratio of the atomic numbers Z. 相似文献