• YAKHAK HOEJI
• /
• v.34 no.4
• /
• pp.219-223
• /
• 1990

7,8-Dihydro-6,11-dihydroxy-9(10H)benzo(b)phenazinone was prepared from 1,2,3,4-tetra-hydrophenazine as a potential isostere of anthracyclinone. The attempts to functionalize at $C_9$ were not successful due to the unstability of the above ketone.

• Bulletin of the Korean Chemical Society
• /
• v.21 no.12
• /
• pp.1207-1212
• /
• 2000

The free energy simulation technique is used to evaluate the relative binding affinity of a set of hydroxyethylene isostere inhibitors of the HIV-1 protease. The binding reactions and an alchemical mutation construct the thermodynamic cycle, which reduces the free energy difference of the binding interactions into that of the alchemical processes. In the alchemical process, a methyl group is mutated into a hydrogen atom. Albeit the change is a small perturbation to the inhibitor-protease complex, it results in 25 fold difference in the binding constants. The simulation reproduces the experimentally measured binding affinities within 2% of the free energy difference. The protonation state of the catalytic aspartic acid residues is also investigated through the free energy simulations.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1994.04a
• /
• pp.219-219
• /
• 1994

고혈압 치료제의 하나로 사용되고 있는 Angiotensin Converting Enzymc (ACE) 억제제를 본 실험실에서 개발한 $\alpha$-hydroxy ketomethylene isostere를 핵심요소로 하여 합성하였다. 합성한 억제제 후보물질의 억제효과는 Rabbit Ling으로 부터 단리된 ACE를 사용하여 분광학적인 방법에 의해 결정되었다. 화합물 1은 우수한 억제효과를 나타내었다.

• YAKHAK HOEJI
• /
• v.37 no.1
• /
• pp.36-40
• /
• 1993

The 4-(2'-(N-(l-methyl-3'-carbamylphenyl)-n-propyl))aminoethyl)-l- hydroxy-2-pyridone which has isoelectronic and isosteric structural similarity with dobutamine without having the Catechol-O- Methyltransferase(COMT) vulnerable m-hydroxy group was synthesized via 12 synthetic steps.

• Korean Journal of Food Science and Technology
• /
• v.23 no.6
• /
• pp.656-660
• /
• 1991

Heats of moisture adsorption of the sunflower nutmeat products (ground nutmeat, meal, protein concentrate and protein isolate) were determined from their isosteres at temperatures 10, 20 and $30^{\circ}C$. The changes in the heat of adsorption with moisture level were analyzed by Hunter equation. The Hunter equation was valid for representing the relationship between the heat of adsorption and the moisture content for the sunflower nutmeat products, and the accuracy-of-fit increased as protein content of the materials increased. The heat of adsorption decreased as moisture content increased, but increased as protein content increased. The heats of adsorption were 11.8-10.6 kcal/mole for the ground nutmeat at 4-12% moisture (d.b.) and 12.4-11.0 kcal/mole for the protein isolate at 6-20% moisture (d.b.).

• Biomolecules & Therapeutics
• /
• v.2 no.2
• /
• pp.155-160
• /
• 1994

Human immunodeficiency virus type 1 (HIV-1) protease is essential for the replication of the virus and it is therefore an attractive target for antiviral drugs of HIV-1. Several dipeptide isosteres containing 2-isoxazoline or $\alpha$-hydroxy ketomethylene have been synthesized and their inhibitory effects on the HIV-1 protease examined. The enzymatically active HIV-1 protease was purified to homogeniety from E. coli transformed with a recombinant plasmid (pMAL-pro) containing the entire gene encoding the protease. The purified protease had the substrate specificity with Km value of 9.8$\mu$M when an undecapeptide His-Lys-Ala-Arg-Val-Leu-(p-nitro)Phe-Glu-Ala-Nle-Ser-amide was used as a substrate, and the products from the substrate after specific cleavage by HIV-1 protease were analyzed by HPLC. The synthetic compounds containing dipeptide isosteres showed specific inhibitory effects while a dipeptide isostere containing an isoxazoline ring inhibited the HIV-1 protease competitively with Ki value of 500 $\mu$M. Even if the inhibition effects of HIV-1 protease were not very high, these novel dipeptide isosteres can be used as key structural moieties for developing specific inhibitors of HIV-1 protease.

• YAKHAK HOEJI
• /
• v.39 no.5
• /
• pp.506-510
• /
• 1995

The 5-(2'-(N-(1-methyl-3'-carbamylphenyl)-n-propyl))aminoethyl)-8- hydroxy-4-methyl-carbostyril derivatives which have isoelectronic and isosteric structural similarity with dobutamine without having the Catechol-O-Methyltransferase (COMT) vulnerable m-hydroxy group were synthesized via 7 synthetic steps, and their stabilities in phosphate buffer solution(pH=7.4), human blood. 80% human plasma and 20% rat liver homogenate were determined in vitro condition.

• The Korean Journal of Pesticide Science
• /
• v.10 no.2
• /
• pp.69-75
• /
• 2006

For the development of new agrochemical fungicide 3-amino-2-phenylimino-1,3-thiazolines 2 were designed through the molecular modification based on isostere concept of 3-methyl-2-phenylimino-1,3-thiazolines 1 which showed antifungal activity against rice blast. All the compounds 2 were fit Lipinski rule and they had higher solubility in water than that of 1 by virtual calculation. We constructed 195 kinds of focused library of 3-amino-2-phenylimino-1,3-thiazolines through 6H-[1,3,4]thiadiazines (195 compounds) which synthesized from the reaction of thiourea 4 with $\gamma$-chloroacetoacetanilides 5.

• Journal of Integrative Natural Science
• /
• v.5 no.4
• /
• pp.229-232
• /
• 2012

The pharmaceutical industry has an ongoing need for new, safe medicines with genuine biomedical effects. Most of the candidate molecules are far from becomes a drug, because of their pharmacokinetic and pharmacodynamic properties. The introduction of bioisostere to improve properties of molecules and to obtain new class of compound is currently increased. Silicon substitution of carbon of existing drugs is an attractive strategy to search a new candidate with improved biological and physicochemical properties. The fundamental differences between carbon and silicon can lead to improved profile of the silicon containing candidate, and could be exploited to get further benefit in drug design process.

• Bulletin of the Korean Chemical Society
• /
• v.32 no.11
• /
• pp.4089-4091
• /
• 2011