geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

N-substituted oxopyrimidines and nucleosides: structure-activity relationship for hypnotic activity as central nervous system depressant


, : N-substituted oxopyrimidines and nucleosides: structure-activity relationship for hypnotic activity as central nervous system depressant. Journal of Medicinal Chemistry 30(12): 2227-2231

N3-Benzyluridine (3-(phenylmethyl)-1-beta-D-ribofuranosyluracil) (1f) and its related compounds were synthesized and evaluated for hypnotic activity as central depressants. The primary structural modification has been carried out at the N3 position of the pyrimidine ring in uridine. N3-Benzyl-substituted uridine exhibited hypnotic activity as well as pentobarbital (PB) induced sleep effect on mice when administered by intracerebroventricular (icv) injection. From this result, the secondary modification was performed, namely, converting the benzyl group into a benzyl analogous group. These compounds also showed hypnotic activity, but their intensities were varied. Thirdly, changing the sugar moiety was investigated; however, it was found to be necessary for hypnotic activity. In general, introduction of benzyl analogous groups at the N3 position of uridine increased the hypnotic activity, and modification of the sugar moiety decreased the activity. Intravenous (iv) administration failed to indicate hypnotic activity in most of the compounds tested. However, modified sugars such as 2',3',5'-tri-O-methyl or -acetyl derivatives of 1f elicited hypnotic activity by iv injection. The majority of compounds were found to show potentiation of the PB-induced sleep, and their effects were in parallel with the hypnotic activity. The result clearly indicates that the benzyl group and beta-D-ribofuranosyl, at the N3 and N1 positions, respectively, are necessary for hypnotic activity. The critical portion of the chemical structure for both effects appears to be the uridine moiety.

US$29.90

PMID: 3681892


Other references

Jakobsen, H.; Adarna, B.C.; Schulz, D.; Rappuoli, R.; Jonsdottir, I., 2000: LT-mutants enhance predominantly the IgG2a antibody response to pneumococcal conjugate vaccine to mimick the natural response to encapsulated bacteria. Scandinavian Journal of Immunology 52(4): 423-424, October

Price, D.W.; Goodman, G.S., 1990: Visiting the wizard: children's memory for a recurring event. The development of children's scripts for a recurring event was examined. 24 girls.sbd.2.5, 4, and 5.5 years of age.sbd.repeatedly experienced an initially novel episode (a trip to the "wizard's room") in a laboratory setting....

Fudala, R.; Rich, R.; Mukerjee, A.; Ranjan, A.P.; Vishwanatha, J.K.; Kurdowska, A.K.; Gryczynski, Z.; Borejdo, J.; Gryczynski, I., 2015: Fluorescence detection of MMP-9. II. Ratiometric FRET-based sensing with dually labeled specific peptide. In our previous paper we showed that the MMP-9 enzyme recognizes a specific peptide sequence, Lys-Gly- Pro-Arg-Ser-Leu-Ser-Gly-Lys, and cleaves the peptide into two parts [1]. In this study, the peptide is labeled with two dyes, carboxyfluorescein...

Routh, J.I., 1951: Paper chromatography of acetylsalicylic acid and its metabolites. Fed Proc: 232

Sergeant, G.P.; Hollywood, M.A.; Mccloskey, K.D.; Thornbury, K.D.; Mchale, N.G., 2000: Specialised pacemaking cells in the rabbit urethra. 1. Collagenase dispersal of strips of rabbit urethra yielded, in addition to normal spindle-shaped smooth muscle cells, a small proportion of branched cells which resembled the interstitial cells of Cajal dispersed from canine colon. These were cl...

Ozbeyaz, C.; Yagci, T.; Bagci, C.; Alpan, O., 1997: Commercial crossbreeding of Jersey cows for beef production using Brangus, Limousin and Simmental sires. II. Fattening, slaughtering and carcass characteristics. Ten Brangus x Jersey (F1), 21 Simmental x Jersey (F1) and 28 Limousin x Jersey (F1) crossbreds were studied at a state farm in Turkey. For the 3 crossbred types respectively, overall daily weight gain during the 510-day fattening period averaged 0...

Yang, C.M.ng, B.C.en, M.L.u, X.H.a, Y.N., Z., 2006: Laser-light-scattering study of structure and dynamics of waxy corn amylopectin in dilute aqueous solution. The average molecular weight, gyration radius (Rg), second virial coefficient (A2) and fractal dimension (df) of waxy corn amylopectin in aqueous solution were characterized by static light scattering. The results indicated that the single waxy co...

Liang, Q.; Richardson, T., 1992: A simple and rapid method for screening transformant yeast colonies using PCR. A simple and rapid procedure for screening transformant yeast colonies is described. In this method, a trace amount of plasmid DNA is isolated from a small amount of yeast cell mass; then, the presence of the exogenous DNA in each yeast colony is...

Malyshev N.A.; Maidl T.V.; Pimenov B.A.; Moreyn V.E., 1992: Lithologic criteria of forecasting reservoirs and caps in Ordovician-Lower Devonian sediments of northeastern Timan-Pechora province. Pages 84-89 1992

Grau, I., 1982: Possibilities of using ear culture for pollination control and effective greenhouse utilization. Hydroponic cultivation of detached ear-bearing stems resulted in ears with between 12 and 42 viable grains (percentage germination ranged from 85 to 98%) with a 1000-grain weight of up to 42 g. It is suggested that the technique represents an effi...