• Archives of Pharmacal Research
• /
• 제20권6호
• /
• pp.597-601
• /
• 1997

An oxidimetric titrant, 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone in anhydrous acetic acid is used for the semimicro-determination of hydrazine hydrate, phenylhydrazine hydrochloride, isoniazid and iproniazid phosphate in pure forms as well as in some pharmaceutical preparations containing isoniazid and iproniazid phosphate. The end point was detected potentiometrically using a platinum-calomel combination electrode. The results obtained are compared statistically with those obtained by the official methods and they are in good agreement.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
• /
• pp.242.1-242.1
• /
• 2003

The nucleoside analogue, L-FMUS was synthesized from L-FMAU which has been shown to have significant antiviral activity against hepatitis B virus (HBV). It was prepared by two steps. First, 5'hydroxyl of L-FMAU was substituted by thioacetyl group using diisopropylazodicarboxylate(DIAD), Triphenyl phosphine(PPh3) and thioacetic acid in anhydrous THF. (omitted)

• Bulletin of the Korean Chemical Society
• /
• 제31권2호
• /
• pp.303-308
• /
• 2010

Pseudo-first-order rate constants ($k_{obsd}$) have been measured spectrophotometrically for nucleophilic substitution reactions of 4-nitrophenyl benzoate (5a), 4-nitrophenyl 4-methoxybenzoate (5b), and 4-nitrophenyl 4-hydroxybenzoate (5c) with alkali metal ethoxides, $EtO^-M^+$ ($M^+=Li^+$, $Na^+$ and $K^+$) in anhydrous ethanol (EtOH) at $25.0{\pm}0.1^{\circ}C$. The plots of $k_{obsd}$ vs. [$EtO^-M^+$] exhibit upward curvatures in all cases, indicating that $M^+$ ions catalyze the reactions and ionpaired $EtO^-M^+$ species are more reactive than dissociated $EtO^-$. Second-order rate constants for reactions with dissociated $EtO^-$ and ion-paired $EtO^-M^+$ (i.e., $k_{EtO^-}$ and $k_{EtO^-M^+}$, respectively) have been calculated from ion-pair treatment for the reactions of 5a and 5b. However, such ion-pair treatment has failed to determine $k_{EtO^-}$ and $k_{EtO^-M^+}$ values for the reactions of 5c. It has been concluded that reactions of 5a and 5b are catalyzed by one metal ion, which increases electrophilicity of the reaction center through coordination on the carbonyl oxygen. In contrast, reactions of 5c have been suggested to involve two metal ions, i.e., the one coordinated on the carbonyl oxygen increases the electrophilicity of the reaction center while the other one associated on the phenoxy oxygen decreases the charge repulsion between the anionic reagents (i.e., $EtO^-$ and deprotonated 5c). It has been found that the rate equation derived from the mechanism involving two metal ions fits nicely to the kinetic results obtained for the reactions of 5c.

• Bulletin of the Korean Chemical Society
• /
• 제32권6호
• /
• pp.1951-1956
• /
• 2011

A kinetic study is reported on nucleophilic substitution reactions of 4-nitrophenyl nicotinate 5 and isonicotinate 6 with alkali metal ethoxide EtOM (M = K, Na, and Li) in anhydrous ethanol at $25.0{\pm}0.1^{\circ}C$. Plots of pseudo-first-order rate constant $k_{obsd}$ vs. EtOM concentration exhibit upward curvature for the reactions of 5 and 6 with EtOK and EtONa but are almost linear for those with EtOLi. Dissection of $k_{obsd}$ into $k_{EtO^-}$ and $k_{EtOM}$ (i.e., the second-order rate constant for the reaction with dissociated $EtO^-$ and ion-paired EtOM, respectively) has shown that $k_{EtOK}$ ${\geq}$ $k_{EtONa}$ > $k_{EtO^-}$ but $k_{EtOLi}$ < $k_{EtO^-}$. It has been concluded that $K^+$ and $Na^+$ ions catalyze the reactions by increasing the electrophilicity of the carbonyl carbon atom through formation of a 4-membered cyclic transition state $TS_3$ or $TS_4$. However, $M^+$ ion catalysis has been found to be much less significant for the reactions of 5 and 6 than for the corresponding reactions of 4-nitrophenyl picolinate 4, which was reported to proceed through a 5-membered cyclic transition state $TS_2$. Although 5 and 6 are significantly more reactive than 4-nitrophenyl benzoate 3, the reactions of 5 and 6 result in smaller $k_{EtOK}/k_{EtO^-}$ ratios than those of 3. The electron-withdrawing ability of the nitrogen atom in the acyl moiety of 5 and 6 has been suggested to be responsible for the increase in reactivity and the decrease in the $k_{EtOK}/k_{EtO^-}$ ratio.

• Journal of Pharmaceutical Investigation
• /
• 제40권1호
• /
• pp.15-21
• /
• 2010

Sibutramine is an orally administered centrally-acting antiobesity agent and inhibits both noradrenaline(norephinephirine) and serotonin(5-HT) reuptake. These effects are contributed by its active metabolites, M1 and M2. However, as the free base form of sibutramine is an oil form in room temperature, it had the problem of handling and stability. Thus, this drug should be used in the form of acid salt form in the pharmaceutical application. Unfortunately, anhydrous sibutramine hydrochloride is highly hygroscopic and unstable. In order to solve the hygroscopicity of the anhydrous salt form, another sibutramine acid salt form must be developed as a hydrate form. In this study. to overcome these problems, various of sibutramine acid salt forms were prepared with the pharmaceutically available salts such as maleate, esylate, mandelate, camsylate, besylate, salicylate, tartrate, isethionate and malate forms, and their physicochemical properties were investigated. Sibutramine malate was selected for excellent solubility and stability among the listed salt forms above. Its pharmacokinetic parameters were evaluated in rats comparing with sibutramine HCl, resulting in similar parameters. In vitro dissolution study of sibutramine malate-loaded capsule was performed comparison with commercial product ($Reductil^{(R)}$) in pH 1.2, pH 4.0, pH 6.8 and water medium. Our results indicated that there were no significant differences in their dissolution profiles were similar in all tested medium. Thus, sibutramine malate-loaded capsule should be a potential candiate due to its excellent solubility, good stability and biosimilar absorption.

• Bulletin of the Korean Chemical Society
• /
• 제29권1호
• /
• pp.117-121
• /
• 2008

Pseudo-first-order rate constants (kobsd) have been measured spectrophotometrically for nucleophilic substitution reactions of 5-nitro-8-quinolyl benzoate (5) with alkali metal ethoxides, EtO?M+ (M+ = Li+, Na+ and K+) in anhydrous ethanol (EtOH) at 25.0 0.1 C. The plots of kobsd vs. [EtO?M+] exhibit upward curvatures, while the corresponding plots for the reactions of 5 with EtO?Na+ and EtO?K+ in the presence of complexing agents, 15-crown-5-ether and 18-crown-6-ether are linear with rate retardation. The reactions of 5 with EtO?Na+ and EtO?Li+ result in significant rate enhancements on additions of Na+ClO4, indicating that the M+ ions behave as a catalyst. The dissociated EtO and ion-paired EtOM+ have been proposed to react with 5. The second-order rate constants for the reactions with EtO (kEtO) and EtOM+ (kEtOM+) have been calculated from ion-pairing treatments. The kEtO and kEtOM+ values decrease in the order kEtONa+ > kEtOK+ > kEtOLi+ > kEtO, indicating that ion-paired EtOM+ species are more reactive than the dissociated EtO ion, and Na+ ion exhibits the largest catalytic effect. The M+ ions in this study form stronger complex with the transition state than with the ground state. Coordination of the M+ ions with the O and N atoms in the leaving group of 5 has been suggested to be responsible for the catalytic effect shown by the alkali metal ions in this study.

• Bulletin of the Korean Chemical Society
• /
• 제31권9호
• /
• pp.2483-2487
• /
• 2010

Pseudo-first-order rate constants ($k_{obsd}$) were measured spectrophotometrically for nucleophilic substitution reactions of 4-nitrophenyl picolinate (6) with alkali metal ethoxides (EtOM, $M^+\;=\;K^+$, $Na^+$ and $Li^+$) in anhydrous ethanol at $25.0{\pm}0.1^{\circ}C$. The plot of $k_{obsd}$ vs. [EtOM] exhibits upward curvature regardless of the nature of $M^+$ ions. However, the plot for the reaction of 6 with EtOK is linear with significantly decreased $k_{obsd}$ values when 18-crown-6-ether (18C6, a complexing agent for $K^+$ ion) is added in the reaction medium. Dissection of $k_{obsd}$ into $k_{EtO^-}$ and $k_{EtOM}$ (i.e., the second-order rate constant for the reaction with dissociated $EtO^-$ and ion-paired EtOM, respectively) has revealed that ion-paired EtOM is 3~17 times more reactive than dissociated $EtO^-$. The reaction has been proposed to proceed through a 5-membered cyclic transition state, in which $M^+$ ion increases the electrophilicity of the reaction site. Interestingly, $Na^+$ ion exhibits the largest catalytic effect. The presence of a nitrogen atom in the pyridine moiety of 6 has been suggested to be responsible for the high $Na^+$ ion selectivity.

• Bulletin of the Korean Chemical Society
• /
• 제35권8호
• /
• pp.2438-2442
• /
• 2014

A kinetic study is reported for $S_NAr$ reaction of 1-fluoro-2,4-dinitrobenzene (5a) and 1-chloro-2,4-dinitrobenzene (5b) with alkali-metal ethoxides (EtOM, M = Li, Na, K and 18-crown-6-ether complexed K) in anhydrous ethanol. The second-order rate constant increases in the order $k_{EtOLi}$ < $k_{EtO^-}$ < $k_{EtONa}$ < $k_{EtOK}$ < $k_{EtOK/18C6}$ for the reaction of 5a and $k_{EtOLi}$ < $k_{EtONa}$ < $k_{EtO^-$ < $k_{EtOK}$ < $k_{EtOK/18C6}$ for that of 5b. This indicates that $M^+$ ion behaves as a catalyst or an inhibitor depending on the size of $M^+$ ion and the nature of the leaving group ($F^-$ vs. $Cl^-$). Substrate 5a is more reactive than 5b, although the $F^-$ in 5a is ca. $10pK_a$ units more basic than the $Cl^-$ in 5b, indicating that the reaction proceeds through a Meisenheimer complex in which expulsion of the leaving group occurs after the rate-determining step (RDS). $M^+$ ion would catalyze the reaction by increasing either the nucleofugality of the leaving group through a four-membered cyclic transition state or the electrophilicity of the reaction center through a ${\pi}$-complex. However, the enhanced nucleofugality would be ineffective for the current reaction, since expulsion of the leaving group occurs after the RDS. Thus, it has been concluded that $M^+$ ion catalyzes the reaction by increasing the electrophilicity of the reaction center through a ${\pi}$-complex between $M^+$ ion and the ${\pi}$-electrons in the benzene ring.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권14호
• /
• pp.5799-5804
• /
• 2014

Background: Radiofrequency ablation (RFA) is the most widely used and studied method internationally for the local treatment of liver tumors. However, the extension of coagulation necrosis in one RFA procedure is limited and incomplete coverage of the damaged area can lead to a high local recurrence rate. Objective: In this study, we compared the effects of different solutions in enhancing hepatic radiofrequency by establishing a rabbit VX2 liver cancer model. We also determined the optimal solution to maximise effects on the extent of RFA-induced coagulation necrosis. Methods: Thirty VX2 tumor rabbits were randomly assigned to five groups: group A, RFA alone; group B, RFA with anhydrous ethanol injection; group C, RFA with 5% hypertonic saline injection; group D, RFA with lidocaine injection; and group E, RFA with a mixed solution. Routine ultrasound examinations and contrast-enhanced ultrasound (CEUS) of the ablation areas were performed after RFA. Then, we measured the major axis and transverse diameter and compared the areas of coagulation necrosis induced by RFA. Results: The mean ablation area range increased in groups B, C and especially E, and the scopes were greater compared with group A. Preoperative application of anhydrous ethanol, hypertonic saline, lidocaine and the mixed solution (groups B, C, D and E, respectively) resulted in larger coagulation necrosis areas than in group A (p<0.05). Among the groups, the coagulation necrosis areas in group E was largest, and the difference was statistically significant compared with other groups (p<0.05). Pathological findings were consistent with imaging results. Conclusions: A mixture of dehydrated alcohol, hypertonic saline and lidocaine injected with RFA increases the extent of coagulation necrosis in the liver with a single application, and the mixed solution is more effective than any other injection alone.

• 센서학회지
• /
• 제7권1호
• /
• pp.73-82
• /
• 1998

실리콘 표면 미세가공에 있어서, 새로 개발된 HF 기상식각 공정은 미소구조체들을 띄우는데 매우 효과적임을 입증하였다. 무수 불화수소와 메탄올을 이용한 기상식각 시스템에 대한 기능 및 특성을 기술하였고, 실리콘 미세구조체룰 띄우기 위한 회생층 산화막들의 선택적 식각특성이 고찰되었다. 구조체층으로는 인이 주입된 다결정실리콘이나 SOI 기판의 단결정실리콘을 사용하였다. 회생층으로는 TEOS 산화막, 열산화막, 저온산화막을 사용하였다. 기존 습식식각과 비교해 볼 때, 공정에 기인된 고착현강이나 잔류물질이 없는 미세구조체를 성공적으로 제작하였다.