• Biomolecules & Therapeutics
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• v.9 no.2
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• pp.69-78
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• 2001

Cyclooxygenase (COX) is an enzyme, which catalyzes the production of prostaglandins from arachi-donic acid and exists in two isoforms (COX-1 and COX-2). COX-1 is involved in the maintenance of physiological functions such as platelet aggregation, cytoprotection in the stomach and maintenance of normal kidney function. COX-2 is induced significantly in vivo under inflammatory conditions. COX-1 and COX-2 serve different physiological and pathological functions. All commercially available nonsteroidal antiinflammatory drugs (NSAIDS) are inhibitors of both COX-1 and COX-2. Therefore, selective inhibitors of COX-2 may be effective antiinflammatory agents without the ulcerogenic effects associated with current NSAms. Since the mid 1990s, a number of reports have been appeared on the preparation and biological activity of selective COX-2 inhibitors. Recently celecoxib, and rofecoxib, the representative COX-2 inhibitors, are introduced in the drug market. In this paper the relationship of structure-activity for selective COX-2 inhibitors is reviewed.

• YAKHAK HOEJI
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• v.57 no.6
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• pp.426-431
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• 2013

In our previous studies, 6-hydroxy-7-methoxychroman-2-carboxylic acid N-phenylamide (KL-1156) was identified as a good inhibitor of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activation. In continuation of our study, we describe the structure-activity relationship of chroman derivatives containing N-arylalkyl groups and their NF-${\kappa}B$ inhibitory activities. In addition, inhibitory effects of cell proliferation are evaluated against human cancer cell lines (NCI-H23 and PC-3). The most active compounds 3i and 3j contained diphenylethyl and diphenylpropyl side chain on amide nitrogen.

• Archives of Pharmacal Research
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• v.26 no.9
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• pp.686-696
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• 2003

Ethyl (coumarin-4-oxy)acetate 1 was prepared through the reaction of 4-hydroxycoumarin with ethyl bromoacetate. Compound 1 was allowed to react with hydrazine hydrate to produce coumarin-4-oxyacetic hydrazide 2. The synthesis of N-(arylidene and alkylidene)-coumarin-4-oxyacetic hydrazones 3-20 was performed. The preparation of 2-substituted-3-[(coumarin-4-oxy) acetamido]thiazolidinones 21-26 and 2-[(coumarin-4-oxy )methyl]-4-acetyl-5-substituted-$\Delta^2$-1,3,4-oxadiazolines 27-33 was performed by the reaction of the hydrazones 3, 4, 7, 9, 12, 14 with mercaptoacetic acid and the hydrazones 3, 4, 5, 7, 12, 15, 16 with acetic anhydride, respectively. The antiviral activities, cytotoxicities and structure-activity relationship (SAR) towards different microorganisms of the prepared compounds were studied.

• Applied Biological Chemistry
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• v.38 no.6
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• pp.570-576
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• 1995

The new sixteen herbicidal N-2-(1-hydroxy-2-fluoroethyl)-6-substituted(X)-benzenesulfonyl-N'-4,6-dimethoxypyrimidinyl-2-yl urea derivatives(S) were synthesized and thier herbicidal activities$(pI_{50})$ in vivo against rice(Orysa Sativa L.), Barnyard grass(Echninochloa orizicola) and Bulrush(Scirpus juncoides) were measured by the pot test under paddy conditions. The structure activity relationship(SAR) were studied using the physicochemical parameters of ortho-substituents(X) and hydrolysis rate constant(logk) and herbicidal activities by the multiple regression technique. The SAR suggested that the herbicidal activities were more dependant on the hydrolysis rate constant(logk>0) than the steric constants $(Es, small width($B_4$) and length($L_1$). Among them, halogens(2 & 5), methyl(15) and non(H) substituent(1) showed higher herbicidal activity for weeds which was not tolerent to rise and weeds. The herbicidal activity was increased and the persistency in aqueous solution was decreased by electron donating(${\sigma}0<0$) groups as ortho-substituent(X). From the relationship equation between herbicidal activity and hydrolysis rate constant, it was assumed that the both reactions would be proceeds with similar process. And the conditions on the ortho substituents to show higher herbicidal activity and the persistency in aqueous solution were also discussed.

• Bulletin of the Korean Chemical Society
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• v.24 no.6
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• pp.731-732
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• 2003

Mutagen X (MX), 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone is one of the most potent directing acting mutagen ever tested in SAL TA100 assay. Although MX analogues have been synthesized, tested for mutagenicity and modeled by structure-activity relationship (SAR) methods, the mechanism of interaction of these compounds with DNA to produce their remarkable mutagenic potency remains unresolved. MX exists as an equilibrium mixture of both ring and open form in water. This equilibrium is very fast for Ames test. Because the mixture is not separable by experimental methods, it is not clear which one is really responsible for the observed mutagenicity. There have been many debates that which one is really responsible for the observed mutagenicity. We used ab initio methods for the MX analogues. It seems both ring and open form could react with DNA bases as electrophiles. However, every open form has consistently lower LUMO energy than corresponding ring form. It is reasonable to assume that the major reaction will go through via open form for MX analogues. This suggest that the open form is more likely really mutagenic.

• Archives of Pharmacal Research
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• v.22 no.2
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• pp.202-207
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• 1999

New series of catechol ether type derivatives 5, 6 have been synthesized and applied to biological tests. Even though it is ap preliminary data, some of our target molecules show the promising result against PDE IV inhibition. SAR and biological studies with studies with synthetic compounds will be discussed in detail.

• Applied Biological Chemistry
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• v.37 no.4
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• pp.287-294
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• 1994

New 3-phenyl-1-(2-furyl)propenones, 1 and 3-phenyl-1-(2-furyl)-3-thiophenyl-propanone, 2 derivatives were synthesized, and their fungicidal activities in vitro against Botrytis cineria (BC), Valsa ceratosperma (VC), Scelerotium cepivorum (SC) and Phytophthora capsici (PC) were investigated using a generalized structure-activity relationship (SAR). The activity of 1 was superior to those of 2, and nonsubstituent, 1a and chloro group substituent, 1d of E (Syn) conformer were the most effective $(EC_{50}=10{\sim}12\;ppm)$ compound to BC. Antifungal activities were able to predict to depend essentially on the ${\beta}$ carbon and their positive charge from the results that the good correlation $(r^2=0.90)$ was observed between hydrolysis rate constant (logk) of 1 and the electronic parameter $({\sigma})$ of X-substituent on the ${\beta}-phenyl$ ring.

• Bulletin of the Korean Chemical Society
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• v.28 no.12
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• pp.2235-2240
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• 2007

3-Aryloxy methyl-4-(N-pyrazin-2'yl carboxamido)-5-mercapto-1,2,4-triazoles (3a1-a14) were prepared starting from potassium dithio carbazinates (2a1-a14). These triazoles were then employed in the synthesis of 3-aryloxy methyl-4-(N-pyrazin-2'yl carboxamido)-5-hydrazino-1,2,4-triazoles (4a1-a14). All the newly synthesized compounds were characterized by analytical, IR, NMR spectral studies. The compounds were screened for their antibacterial, antifungal, anti-inflammatory and analgesic properties. Most of the compounds have shown significant antifungal activity while few have shown excellent anti-inflammatory and analgesic activity. An attempt is made to study the structure activity relationship (SAR).

• Applied Biological Chemistry
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• v.43 no.1
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• pp.52-56
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• 2000

The influence of the 2-(4-(6-chloro-2-benzoxazolyloxy)phenoxy)-N-phenyl- propionamide derivatives on the herbicide activities against rice plant with pre-emergence and post-emergence in down land were examined and the structure activity relationship (SAR) were analyzed by Free-Wilson and Hansch method. In pre-emergence, the SAR approach is shown that the optimal, $({\pi})_{opt}=0.91$, hydrophobicity with electron donating effect of the ortho substituted mono substituents and 2,3,4-substituted three substituents were found to be contribute the herbicidal activity. Whereas, in post-emergence, the optimal, ({\pi})_{opt}=0.50$, hydrophobicity with electron withdrawing effect of meta substituted mono subsituents and 2,3-substituted two substituents were found to be contribute the herbicide activity. The herbicide activities with post-emergence more increase than that of pre-emergence. It is assumed from the SAR equations that the 2-methyl-3-methoxy-4-cyano group substituent is selected as the most lowest herbicide activity against rice plant with post-emergence in green house. The hydrolysis reaction was proceeded through nucleophilic addition-elimination (Ad_{Nu-E})$ with the orbital control between LUMO of substrate and HOMO of water molecule. And molecular electrostatic potential (MEP) of none (H) substituent was discussed.

• YAKHAK HOEJI
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• v.56 no.3
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• pp.186-190
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• 2012

Nuclear factor-${\kappa}B$ (NF-${\kappa}B$) has been considered as one of the major targets for therapeutic agents of diverse human diseases. In the previous studies, 6-hydroxy-7-methoxychroman-2-carboxylic acid N-phenylamide (KL-1156) and chroman-2-carboxylic acid N-(4-chlorophenyl)amide were identified as good inhibitors of NF-${\kappa}B$ activation. In this continuous study, we describe the synthesis and NF-${\kappa}B$ inhibitory activities of chroman derivatives containing N-heteroaryl groups for exploration of SAR (structure-activity relationship). In addition, inhibitory effects of cell proliferation are evaluated against human cancer cell lines (NCI-H23 and PC-3).