• YAKHAK HOEJI
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• v.38 no.2
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• pp.140-148
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• 1994

${\beta}-Lactamase$ stability, chemotherapeutic activity, and pharmacokinetics of 7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyridyl)piperazinyl]thiocarbonylthiomethyl-3-cephem-4-carboxylic acid(CEN1), 7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyrimidyl)piperazinyl]thiocarbonylthiomethyl-3-cephem-4-carboxylic acid(CEN2), pivaloyloxymethyl-7-[(Z)-2-(2-aminothizaole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyridyl)piperazinyl]thiocarbonyl-thiomethyl-3-cephem-4-carboxylate(CEN1P), and pivaloyloxymethyl-7-{(Z)--2-(2-aminothizaole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyridyl)piperazinyl]thiocarbonyl-thiomethyl-3-cephem-4-carboxylate(CEN2P) were examined. CEN1, CEN2, CEN1P, and CEN2P were very stable to the ${\beta}-lactamase$ obtained from three strains(Enterobacter cloacae P99, Escherichia coli TEM, and Citrobacter freundii). Chemotherapeutic activities$(ED_{50})$ of CEN2 and CEN2P against experimental systemic infections due to Streptococcus pyogenes 77A and Escherichia coli 078 were superior to those of CEN1 and CEN1P, respectively. The $ED_{50}$ values of CEN1, CEN2 were 5.82 mg/kg, 0.89 mg/kg(s.c., S. pyogenes 77A) while those of CEN1P, CEN2P were 14.56mg/kg, 6.40mg/kg(p.o., S. pyogenes 77A), respectively. The pharmacokinetics of CEN1, CEN2, CEN1P, and CEN2P were investigated in mice and rats. In mice, peak blood levels of $1.25\;{\mu}g/ml$ were recorded within 20 min after oral administration of a single dose equivalent to 40 mg/kg CEN1P. Cmax of CEN1P was much higher than that of CEN1 in mice and rats. Oral absorption of CEN2P was much higher than that of CEN2.

• Bulletin of the Korean Chemical Society
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• v.11 no.4
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• pp.323-327
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• 1990

The synthesis and some biological properties of $7{\beta} $-[2-(Z)-(2-aminothiazole-4-yl)-2-(N-substitutedcar bonyl)ethoxyiminoacetamido]-3-vinyl-3-cephem-4- carboxylic acid are described. The effect of substituents on the carbamoly group in the 7-side chain were investigated in order to improve antibacterial activities. Two of these new orally active $7{\beta} $-lactam derivatives showed wide expanded antimicrobial activities against Gram-positive and Gram-negative bacteria, including Pseudomonas aeruginosa, as well as good stability to $7{\beta} $ -lactamases.

• YAKHAK HOEJI
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• v.52 no.1
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• pp.20-26
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• 2008

2-Aminothiazole ring as a bioisoster of catechol in dopamine has provided with good oral availability and lipophilic property. Selenium was reported to have an improved antioxidant ability and to reduce the loss of dopamine. 2-Aminoindan, is a rigid form of dopamine, was evaluated as a dopamine agonist with low neurotoxocity. In order to develop a novel dopamine agonist, we tried to synthesize the selenazoloaminoindan derivative that is a hybrid structure of aminoindan and aminoselenazole instead of aminothiazole. 2-Indanone-2-oxime was reduced with $TiCl_4$ and $NaBH_4$ to form 2-aminoindan, which was reacted with propionyl chloride to give 2-N-n-propionylaminoindan (2). Compound 2 was reduced with $TiCl_4$ and $NaBH_4$ to afford 2-N-n-propylaminoindan (3) and it was nitrated and reduced to form 5-amino-2-N-n-propylaminoindan (5), which was reacted with KSeCN, $Br_2$, and glacial acetic acid to give 4,6-dibromo-5- amino-2-N-n-propylaminoindan (7) instead of selenazole ring formation. Otherwise, compound 2 was nitrated and hydrogenated to form 5-amino-2-N-n-propionylaminoindan (9), which was treated with KSeCN, $Br_2$, and glacial acetic acid to give 4,6-dibromo-5-amino-2-N-n-propionylaminoindan (10). Compound 9 was cyc1ized with KSeCN and glacial acetic acid in the absence of $Br_2$ to give 6-amino-2-N-(n-propionylamino)selenazolo[4,5-f]indan (11).

• Fibers and Polymers
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• v.3 no.1
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• pp.43-48
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• 2002

A series of monoazo disperse dyes based on 2-amino-4-phenylthiazole was prepared using various N,N-dialkvlaniline derivatives as the coupling component. The dyes were characterized by IR spectral studies, visible absorption spectroscopy and elemental analysis. The dyeing performance of these dyes was assessed on cellulose triacetate and nylon fibers. These dyes were found to give a wide range of colour shades varying from bright red to royal blue with very good depth, brightness and levelness on fibers. The dyed fibers showed good to very good light fastness and very good to excellent fastness to washing, perspiration, rubbing and sublimation. The dyebath exhaustion and fixation on the fibers were found to be very good.

• YAKHAK HOEJI
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• v.43 no.3
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• pp.306-315
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• 1999

To develop new cephalosporin antibiotics with improved antibacterial activities, a series of 7$\beta$-[2-(2-aminothiazol-4-y)-(Z)-2-(1-carboxy-1-methylethoxyimino)acetamido] -3-[5-(heterocycle)thiomethylpy-rrolidin-3-ylthio]methyl-3-cephem-4-carboxylic acid (14~18) having aminothiazol carboxymethylethoxy-imino group on the C-7 position and (heterocycle) thiomethyl pyrrolidinthiomethyl group on the C-3 position of the cephem ring were synthesized. These compounds were tested for antimicrobial activity in vitro against Gram(+) and Gram(-) bacteria. Compounds 15 and 16 showed remarkable antibacterial activity against Salmonella typhimurium TV119 and Alcalienes faecalis KCTC1004, but most of compounds showed lower activity than cefotaxime.

• YAKHAK HOEJI
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• v.52 no.6
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• pp.488-493
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• 2008

2-Aminothiazole ring as a bioisoster of catechol in dopamine has provided with good oral availability and lipophilic property. 2-Aminoindan, is a rigid form of dopamine, was evaluated as a dopamine D3 agonist with low neurotoxicity. Dopamine D3 agonist was evaluated as selective for the treatment of Parkinson's disease. In order to develop a novel dopamine D3 agonist, we tried to synthesize the aminothiazoloindenoxazine derivative that is a hybrid structure of aminoindenoxazine and thiazole ring. cis-2-Amino-1-indanol (2) was synthesized from 1,2-indandione-2-oxime by catalytic hydrogenation and it was treated with chloroacetyl chloride and NaH in benzene solution to give (${\pm}$)-cis-4,4a,5,9b-tetrahydroindeno[1,2-b][1,4]oxazin-3(2H)-one (6). Nitration of 6 by the mixed acid gave 8-nitro compound (7) and the carbonyl group of 7 was reduced with $LiAlH_4$ to afford compound (8). 8 was reduced to form (${\pm}$)-cis-8-amino-2,3,4,4a,5,9b-hexahydroindeno[1,2-b][1,4]oxazine (9) and finally it was cyclized with KSCN in glacial acetic acid to yield (${\pm}$)-cis-8-amino-2,3,4,4a,5,10b-hexahydrothiazolo[4,5-f]indeno[1,2-b][1,4]oxazine (10).

• YAKHAK HOEJI
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• v.44 no.2
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• pp.155-161
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• 2000

New cephalosporin antibiotics , 3-[(4-carboxy-5-ethylthioisothiazol-3-yl)oxymethyl]-7-[(1H-tetra-zol-1-yl)acetamido]-3-cephem-4-carboxylic acid 2, 3-[(4-carboxy-5-ethylthioisothiazol-3-yl) oxymethyl]-7-[(2-aminothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid 3, 3-[(4-carb oxy-5-ethylthioisothiazol-3-yl)-oxymethyl]-7-[5-(ethylthio-3-hydroxyisothiazol-4-yl)carboxamido]-3-cephem-4-carboxylic acid 4, 3-[(4-car-boxy-5-ethylthioisothiazo1-3-yl)oxymethy1]-7-[(Z)-2-(fur-2-yl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylic acid 5, 7-[(Z)-2-(2-aminothiazol-4-yl)-2-[(alkoxyimino)acetamido]-3-[(4-carboxy-5-ethylthioisothiazol-3-yl)oxymethyl]-3-cephem-4-carboxylic acid 6-8 were synthesized. Antibacterial activities and structure-activity relationships of these new cephalosporin derivatives were examined. Among them, 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-[(4-carboxy-5-ethylthylth-ioisothiazol-3-yl)oxymethyl]-3-cephem-4-carboxylic acid 7 exhibited good antibacterial activities compared to cefotaxime and ceftriaxone.

• YAKHAK HOEJI
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• v.42 no.4
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• pp.364-369
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• 1998

New cephalosporin antibiotics. 7-[(1H-tetrazolyl)acetamidol]-3-[(4-carboxy-3-hydroxyisothiazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid trisodium salt 2,7-[(5-ethylthio-3-hydroxyisothiazol-4-yl)carbox-amidol-3-[(4-carboxy-3-hydroxyisothiazo1-5-yl)thiomethyl)-3-cephem-4-carboxylic acid 3,7-[(2-aminothiazol-4-yl)acetamido]-3-[(4-carboxy-3-hydroxyisothiazol-5-yl]thiomethyl]-3-cephem-4-caboxylic acid 4,7-[(Z)-2-(2-aminothiazol-4-yl)-2-(alkoxyimino)acetamido)-3-[(4-carboxy-3-hydroxyisothiazol-5-yl)thiomethyl)-3-cephem-4-carboxylic acid 5-9 were synthesized. Antibacterial activities of these new cephalosporin derivatives and the relationship between their structures and activities were examined. Among them, 7-((Z)-2-(2-aminothiazol-4-yl)-2-(carboxymethoxyimino)acetamido)-3-[(4-carboxy-3-hydroxyisothiazol-5-yl)thiomethyl)-3-cephem-4-carboxylic acid 8 and 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(l-carboxy-1-methylethoxyimino)acetamido]-3-[(4-carboxy-3-hydroxyisothiazol-5-yl)thiomethyl)-3-cephem-4-carboxylic acid 9 exhibited good antibacterial activities compared with those of cefotaxime and ceftriaxone.

• Applied Biological Chemistry
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• v.40 no.2
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• pp.157-162
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• 1997

A novel compound, named YH-487, was synthesized by attaching the thiol and aminothiazole residue to $C_3$ and $C_7$ position of 7-aminocephalosporanic acid (7-ACA). The therapeutic efficacy on infected animals, pharmacokinetics in vivo and the effect on intestinal microflora of YH-487 were examined. The pharmacokinetics of YH-487 were similar to that of cefotaxime, a third generation ${\beta}-lactam$ antibiotics, in rat. Upon in vivo administration, YH-487 was predominantly delivered to kidney, and mostly excreted through kidney without making any metabolites. The therapeutic efficacy of YH-487 to animal infected with E. coli was three times and twenty times higher than that of cefotaxime and cefotiam, respectively, In vivo administration of YH-487 to Sprague-Dawley rats significantly decreased the population of intestinal gram negative species such as Enterobacteria and Barteroides. However, no significant changes were obseved in gram positive species such as Lactobacillus, Bifidobacteria and Staphylococcus. In addition, continuous administration of YH-487 did not increase the possibility to induce resistant strains in intestinal microflora.

• The Korean Journal of Pesticide Science
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• v.10 no.4
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• pp.249-261
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• 2006

Fifty compounds such as ester, sulfonyl ester, carbamate, ether and phosphoyl ester derivatives of 4-isopropyl-3-methylphenol(I) and 5-isopropyl-3-methylphenol(II) were synthesized. These derivatives were identified by IR, GC/MS and $^1H$-NMR spectra. Their in vitro antifungal activities were tested against 10 plant pathogenic fungi. Among them, several compounds showed potent in vitro antifungal activity. The selected compounds showing potent in vitro antifungal activity were tested for their in vivo antifungal activities against 5 plant diseases such as rice blast, rice sheath blast, cucumber anthracnose, cucumber gray mold and tomato late blight. As a result, 4-isopropyl-3-methylphenyl(2-amino-thiazole-4-yl)methoxyiminoacetate(I-7a) showed a potent in vivo antifungal activity against rice blast. Both methyl (4-isopropyl-3-methylphenoxy)acetate(I-4d) and methyl (5-isopropyl-3-methylphenoxy)acetate(II-4d) effectively inhibited the development of cucumber gray mold.