IY-80843, N[2-(2-methoxyphenyl)ethyl]-N'-[4-(lmidazole-4-yl)phenyl] formamidine, is a new potent $H_2-receptor$ anagonist. The potential secondary pharmacologic effects of this agent, on the central nervous and cardiovascular systems were studied. IY-80843 caused ptosis, suppression of locomotion, hypotehrmia, prolongation of sleeping time and hypotensive effects in mice, rats and dogs. These results suggest that IY-80843 affects the funcition of the central nervous and cardiovascular systems in a dose-dependent manner.

Biodegradability of poly $Poly({\gamma}-benzyl L-Glutamate)/poly(ethylene oxide)/Poly({\gamma}-benzyl L-Glutamate)$ block copolymer (GEG) having different content of poly(ethylene oxide) (PEO) were examined using magnetite as a tracer in mice. GEG microspheres containing magnetite were injected into mice through tail vein. Biodegradability and tissue distribution of microspheres were examined by analyzing the amount of magnetite in the microspheres recollected from mice organs after specific time interval. The results showed that GEG microsphere of high content of PEO was degraded more rapidly than those of low content of PEO in the mice organs.

It is essential to clone the preptide transporter in order to obtain better understanding of its molecular structure, regulation, and substrate specificity. Characteristics of an endogenous peptide transporter in oocytes were studied along with expression of an exogenous protor/peptide cotransporter from rabbit intestine. And further efforts toward cloning the transporter were performed. The presence of an endogenous peptide transporter was detected in Xenopus laevis oocytes by measuring the uptake of $0.25/{mu}M(10{\;}{\mu}Ci/ml)[^3H]$-glycylsarcosine (Gly-Sar) at pH 5.5 with or without inhibitors. Yptake of Gly-Sae in oocytes was significantly inhibited by $25{\mu}M$ glycine nd sarcosine. This result suggests that a selective transporter is involved in the endogneous uptake of dipeptides. Collagenase treatment of oocytes used to strip oocytes from ovarian follicles did not affect the Gly-Sar uptake. Changing pH from 5.5 to 7.5 did not affect the Gly-Sae uptake significantly, suggesting no depedence of the endogenous transporter on a transmembrane proton gradient. An exogenous $H^+/pep-tide$ contransported was expressed after microinjection of polyadenylated messenger ribonucleic acid $[poly(A)^+ -mRNA]$ obtained from rabbit small intestine. The Gly-Sar uptake in mRNA-injected oocytes was 9 times thigher than that in water-injected oocyltes. Thus, frog occytes can be utilized fro expression cloning of the genes encoding intestinal $H^+$peptide contransporters. Size fractionation of mRNA was successfully obtained using this technique.

Poly(ethylene glycol)(PEG) macrocers teminated with acrylate groups and semi-interpenetrating polymer networks (IPNs) composed of poly-.epsilon.-capolactone(PCL) and PEG macromer were syntheswized with the aim of obtaining a bioerodible hydrogel that could be used to release drugs for implantable delivery system. Polymerization of PEG macromer resulted in the formation of cross-linked gels due to the multifunctionality of macromer. Non-crosslinked PCL chains were interpenetrated into the cross-linked three-dimensions networks of PEG. The IPNs, largw drug loading lower concentration of PEG macromer in the IPNs concentration and the higher molecular weight of PEG macromer. Also, 5-FU was more fast released than hydrocortisone to the increased water solubility.

The solubility and dissolution rate of naproxen (NPX) complexed with 2-hydroxypropyl-.betha.-cyc-lodextrin (2-HP.betha.CD) using coprecipitation, evaporation, freeze-drying and kneading method were investigated. Solubility of NPX linearly increased (correlation cefficient, 0.995) as $2-HP\betaCD$ concentraction increased, resutling in $A_l$ type phase solubility curve. Inclusion complexes prepared by four different methods were compared by different methods were compared by dfferential scanning calorimetry(DSC). The NPX showed sharp endothemic peak around $156^{\circ}C$ but inclusion complexes by evaporation, freeze-drying and kneading method showed very broad peak without distinct phase transtion temperature. In contrast, inclusion complex prepared by coprecipitation method resulted in detectable peak around $156^{\circ}C$ which is similar to NPX, suggesting incoplete formation of indusion co plex. Dissolution rate of inclusion complexes prepared by evaporation, frezz-drying and kneding except coprecipitation method was largely enhanced in the simultaed gastric and intestinal fluid when compared to NPX powder and commercial $NA-XEN^\registered$tablet. However, about 65% of NPX in gstric fluid. in case of inclusion complex prepared by coprecipitation method, formation of inclusion complex appeared to be incoplete, resulting in no marked enhancement of dissolution rate. From these findings, inclusion complexes of poorly water-soluble NPX with $2-HP\betaCD$ were useful to increase soubility and dissolution rate, resting in enhancement of bioavailability and minimization of gastrointestinal toxicity of drug upon oral administration of inclusion complex.

The Hantzsh reaction of 7-hydroxy-8-methoxy-2-oxo-2H-benzopyran-6-carboxaldehyde (1) with ethyl acetoacetate and ammonia yields the dihydropyridine derivative 2 together with the pyridine derivative 3 and the eight membred ring derivative 4. Reaction of 1 with ethyl cyanoacetate and malononitrile gives the iminodicoumarin derivatives 5 and 6 respectiely. The latter compound was reacted with butan-2-one and acetophenone to produce the Michael adduct 71, b and the 2-aminopyridine derivatives 8a, b.

S. pneumoniae (pneumococcus) gene cloning and library construction in E. coli multicopy plasmid has been hampered, in part, by instability problems. In this study, stability of pneumococcus gene library in cosmid vector and pACYC184 was examined. Pneumococcus library in the cosmid vector pHC79 was extermely unstable that most of the recobinant clones were degenerated rapidly. Only 2 out 849 clones were stable and had appropriate insert size. Pneumococcus library in pACYC184 was also so unstable that the pneumococcal inserg and/or part of the vector were deleted. However, the instability problems seemed to be resolved when transcription teminator plasmid was employed for pneumococcus library construction.

melandrin exhibited an analgesic activity as assessed by inhibition of writhing syndromein mice and by pressure method of inflamed paws of arts and inflamed tails of mmice, and showed a hypothermic effect. However, no anti-inflammatory activity was shown.

The linkage pattem of two side chains i.e., a isopentenyl and a lavandulyl group in kushenol M(I), a flavonoid from Sophora flavescens was established by the aid of 2-D NMR techniques, especially DEPT, ${13}C-^1H$ COSY and COLOC experiments. Thus, I was unequivocally determined as (2R, 3R)-5, 7, 2', 4'-tetrahydroxy-6-isopentenyl-8-lavandulyflavanonol.

The synthesis of osme quinoxaline derivatives containing indoline-2, 3-dione or thiazolidlinone residue is described. The synthesized derivatives were sureened in vitro for their growth inhibitory activity against six species of bacteria, viz. Staphylococcus aureus, Streptococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens and Mycobacterium semegmatils. Most of the compounds exhibited antimicrobial activity especially those having indoline-2, 3-dione moiety.

The $^1H NMR singls of three 6{\alpha}-bromopenicillanates$ have been assigned and the Nuclear Overthauser Effect(NOE) study of these compounds was undertaken.

A facile convenient syntheses of the titled compounds, via reacting the precusor 2-amino-2-(pentane-2, 4-dion-3-yithio)-6-phenylpyrimidine-5-carbonitrile (1) with nitrogen nucleophiles and with the carbanions of some active methylene compounds, is reported. Chemical and spectroscopic evidence of the newly syntheised compounds are described.

The effect of ceruloplasmin or copper ion on hepatic xanthine oxidase activity and type conversion was investigated using rat liver in vitro. It was observed that ceruloplasmin increased xanthine oxidase type conversion depending on duration of its storage. Xanthine oxidase (type O) activity and type conversion in incubation mixture was increased by the addition of heated celuroplasmin in a temperature dependent manner. The type conversioin of xanthine oxidase induced by heated ceruloplasmin was retumed to normal by the tratment with DTT or penicillamine. The effect of copper ion on type conversion of xanthine oxidase was similar to that of heated ceruloplasmin.