• 생약학회지
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• 제30권2호
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• pp.145-150
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• 1999

To explain the theory of KIMI which is the theory of therapeutics in oriental medicine, monoamine oxidase(MAO) activities were measured in the brain and liver of mice which were orally administered oriental medicinal herbs which were classified into cold and hot drugs. Rheum palmatum, Anemarrhena asphodeloides, Gardenia jasminoides, Scutellaria baicalensis and Coptis japonica were considered as the cold drugs and Zingiber officinale, Aconitum carmichaeli, Asiasarum sieboldi, Evodia officinalis and Cinnamomum cassia were included in the hot drugs. The effects of cold and hot drugs on in vitro enzyme activities were measured and compared with the in vivo effects. Serotonin is important neurotransmetter involved in the control of body temperature. The MAO plays a central role in the metabolism of many neurotransmetter monoamines including serotonin. MAO is a flavoprotein found exclusively in the mitochondrial outer membrane, occuring in the MAO-A and MAO-B subtypes. MAO-A deaminates serotonin and noradrenaline, whereas MAO-B prefers phenylethylamine and benzylamine as substrates. Coptis japonica and Aconitum carmichaeli elevated the in vivo MAO activities and especialy, in vivo MAO-B activities were significantly increased. In vitro MAO-A activities were increased by hot drugs, whereas the in vitro MAO-B activities were inhibited. Cold drugs inhibited both enzyme activities in vitro.

• Bulletin of the Korean Chemical Society
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• 제24권2호
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• pp.193-196
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• 2003

Nucleophilic addition reactions of benzylamines $(XC_6H_4CH_2NH_2)$ to benzylidene Meldrum's acids (BMA; $YC_6H_4CH=C(COO)_2C(CH_3)_2$) have been investigated in acetonitrile at 20.0 ℃. The rates of addition are greatly enhanced due to the abnormally high acidity of Meldrum's acid. The magnitudes of the Hammett $({\rho}_X\;and\;{\rho}_Y)$ and Bronsted $({\rho}_X$)$ coefficients are rather small suggesting an early transition state. The sign and magnitude of the cross-interaction constant, ${\rho}_{XY}$ (= -0.33), and kinetic isotope effects $(k_H/k_D\;{\stackrel}{~}{=}\;1.5-1.7)$ involving deuterated benzylamine nucleophilies $(XC_6H_4CH_2ND_2)$ are indicative of hydrogen-bonded cyclic transition state. The activation parameters, ${\Delta}H^{\neq}\;{\stackrel}{~}{=}\;4\;kcal\;mol^{-1}\;and\;{\Delta}S^{\neq}\;{\stackrel}{~}{=}\;-37\;e.u.$, are also in line with the proposed mechanism.

• Bulletin of the Korean Chemical Society
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• 제18권3호
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• pp.274-280
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• 1997

The rates and stoichiometry of the reaction of gallane-trimethylamine with selected organic compounds containing representative functional groups were examined in tetrahydrofuran solution under standardized conditions (THF, 0 ℃). And its reducing characteristics were compared with those of aluminum hydride-triethylamine(AHTEA). The rate of hydrogen evolution from active hydrogen compounds varied considerably with the nature of the functional group and the structure of the hydrocarbon moiety. Alcohols, phenol, amines, thiols evolved hydrogen rapidly and quantitatively. Aldehydes and ketones were reduced moderately to the corresponding alcohols. Cinnamaldehyde was reduced to cinnamyl alcohol, which means that the conjugated double bond was not attacked by gallane-trimethylamine. Carboxylic acids, esters, and lactones were stable to the reagent under standard conditions. Acid chlorides also were rapidly reduced to the corresponding alcohols. Epoxides and halides were inert to the reagent. Caproamide and nitrile were stable to the reagent, whereas benzamide was rapidly reduced to benzylamine. Nitropropane, nitrobenzene and azoxybenzene were stable to the reagent, whereas azobenzene was reduced to 1,2-diphenylhydrazine. Oximes and pyridine N-oxide were reduced rapidly. Di-n-butyl disulfide and dimethyl sulfoxide were reduced only slowly, but diphenyl disulfide was reduced rapidly. Finally, sulfones and sulfonic acids were inert to the reagent under the reaction.

• Archives of Pharmacal Research
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• 제10권1호
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• pp.50-59
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• 1987

(E)-2-Phenylcyclopropylamine ((E)-TCP), (Z)-2-Phenylacyclopropylamine ((Z)-TCP), (E)-1-methyl-2-phenylcyclopropylamine ((E)-MTCP), and (Z)-1-methyl-2-phenylcyclopropylamine ((Z)-MTCP) were synthesized and used to determine to what extent 1-methylsubstitution and stereochemistry of 2-phenycyclopropylamines affect inhibition of monoamine oxidase (MAO). Inhibition of rat brain mitochondrial MAO-A and B by the compounds were measured using serotonin and benzylamine as the substrate, respectively and $IC_{50}$ values obtianed with 95% confidence limits by the method of computation. For the inhibition of MAO-A, (E)-MTPC ($IC_{50}$ = 6.2 * $10^{-8}$M) was found to be 37 times more potent than (Z)-MTCP ($IC_{50}$ = 7.8 * $10^{-8}$M), was 7 times more potent than (Z)-MTCP($IC_{50}$= 4.7 * $10^{-7}$M) and (E)-TCP($IC_{50}$ =7.8 * $10^{-8}$M),0.6 times as potent as (Z)- TCP ($IC_{50}$ = 4.4 * $10^{-8}$M). The results suggested that while without 1-methyl group, potency of a (Z)-isomer was comparable to that of (E)-isomer, the methyl group in its (Z)-position was very unfavorable to the inhibition of MAO and that in its (E)-position, the methyl group contributed positively to the potency as found by the fact that (E)-MTCP was 1-5 times more potent than (E)-TCP. In view of the selective inhibition of MAO-A- or B over MAO-A and 1-methyl substitution as well as the stereochemical factors did not significantly influence the selectivity.

• Bulletin of the Korean Chemical Society
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• 제32권5호
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• pp.1625-1629
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• 2011

Kinetic studies of the reactions of O,O-diphenyl Z-S-aryl phosphorothioates with X-benzylamines have been carried out in dimethyl sulfoxide at 55.0 $^{\circ}C$. The Hammett (log $k_2$ vs ${\sigma}_X$) and Bronsted [log $k_2$ vs $pK_a(X)$] plots for substituent X variations in the nucleophiles are biphasic concave downwards with a maximum point at X = H, and the unusual positive ${\rho}_X$ and negative ${\beta}_X$ values are obtained for the strongly basic benzylamines. The sign of the cross-interaction constant (${\rho}_{XZ}$) is negative for both the strongly and weakly basic nucleophiles. Greater magnitude of ${\rho}_{XZ}$ value is observed with the weakly basic nucleophiles (${\rho}_{XZ}$ = -2.35) compared to with the strongly basic nucleophiles (${\rho}_{XZ}$ = -0.03). The deuterium kinetic isotope effects ($k_H/k_D$) involving deuterated benzylamines [$XC_6H_4CH_2ND_2$] are primary normal ($k_H/k_D$ > 1). The proposed mechanism is a concerted $S_N2$ involving a frontside nucleophilic attack with a hydrogen bonded, four-center-type transition state for both the strongly and weakly basic nucleophiles. The unusual positive ${\rho}_X$ and negative ${\beta}_X$ values with the strongly basic benzylamines are rationalized by through-space interaction between the ${\pi}$-clouds of the electron-rich phenyl ring of benzylamine and the phenyl ring of the leaving group thiophenoxide.

• Bulletin of the Korean Chemical Society
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• 제34권7호
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• pp.2125-2130
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• 2013

A new nickel(II) complex $[NiL^1]^{2+}$ ($L^1$ = 1-(2-aminoethyl)-3-(N-{2-aminoethyl}aminomethyl-1,3-diazacyclohexane) containing one 1,3-diazacyclohexane ring has been prepared selectively by the metal-template condensation of formaldehyde with N-(2-aminoethyl)-1,3-propanediamine and ethylenediamine at room temperature. The complex reacts with nitroethane and formaldehyde to yield the pentaaza macrocyclic complex $[NiL^2]^{2+}$ ($L^2$ = 8-methyl-8-nitro-1,3,6,10,13-pentaazabicyclo[13.3.1]heptadecane) bearing one C-$NO_2$ pendant arm. The reduction of $[NiL^2]^{2+}$ by using Zn/HCl produces $[NiL^3(H_2O)]^{2+}$ ($L^3$ = 8-amino-8-methyl-1,3,6,10,13-pentaazabicyclo[13.3.1]heptadecane) bearing one coordinated C-$NH_2$ pendant arm that is readily protonated in acid solutions. The hexaaza macrocyclic complex $[NiL^4]^{2+}$ ($L^4$ = 8-phenylmethyl-8-nitro-1,3,6,8,10,13-hexaazabicyclo[13.3.1]heptadecane) bearing one N-$CH_2C_6H_5$ pendant arm has also been prepared by the reaction of $[NiL^1]^{2+}$ with benzylamine and formaldehyde. The nickel(II) complexes of $L^1$, $L^2$, and $L^4$ have square-planar coordination geometry in the solid states and in nitromethane. However, they exist as equilibrium mixtures of the square-planar $[NiL]^{2+}$ (L = $L^1$, $L^2$, or $L^4$) and octahedral $[NiL(S)_2]^{2+}$ species in various coordinating solvents (S); the proportion of the octahedral species $[NiL(S)_2]^{2+}$ is strongly influenced by the ligand structure and the nature of the solvent. Synthesis, spectra, and chemical properties of the nickel(II) complexes of $L^1-L^4$ are described.

• Bulletin of the Korean Chemical Society
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• 제23권2호
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• pp.201-204
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• 2002

The rates of the aminolysis of S-phenyl substituted-acetate series $(RC(=O)SC_6H_4Z$, with R=Me, Et, i-Pr, t-Bu and Bn) with benzylamines $(XC_6H_4CH_2NH_2)$ are not correlated simply with the Taft's polar $({\sigma}^{\ast})$ and/or steric effect constants $(E_s)$ of the substituents due to abnormally enhanced rate of the substrate with R=Et. Furthermore, the cross-interaction constant, ${\rho}x_z$ , is the largest with R=Et. These anomalous behaviors can only be explained by invoking the vicinal bond $({\sigma})$-antibond $({\sigma}^{\ast})$ charge transfer interaction between C-$C{\alpha}$ and C-S bonds. In the tetrahedral zwitterionic intermediate, $T^{\pm}$ , formed with R=Et the vicinal ${\sigma}_{c-c}-{\sigma}^{\ast}_{c-s}$ delocalization is the strongest with an optimum antiperiplanar arrangement and a narrow energy gap, ${\Delta}{\varepsilon}={\varepsilon}_{{\sigma}^{\ast}}-{\varepsilon}_{\sigma}$. Due to this charge transfer interaction, the stability of the intermediate increases (with the concomitant increase in the equilibrium constant K (= $k_a/k_{-a}$)) and also the leaving ability of the thiophenolate leaving group increases (and hence $k_b$ increases) so that the overall rate, $k_n\;=\;Kk_b$, is strongly enhanced. Theoretical support is provided by the natural bond orbital (NBO) analyses at the B3LYP/6-31+$G^{\ast}$ level. The anomaly exhibited by R=Et attests to the stepwise reaction mechanism in which the leaving group departure is rate limiting.

• 공업화학
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• 제3권2호
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• pp.318-326
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• 1992

분자량 350~360을 가진 비스페놀형 에폭시 수지(DER 331)를 전체 에폭시 성분 중 50% 이내의 범위에서 분자량 1,000~1,600을 가진 비스페놀형 에폭시수지(DER 662, 664) 및 분자량 800~1,000을 가진 노블락형 에폭시수지(DEN 439)와 혼합 사용하여 합성한 비닐에스테르수지의 액상 및 경화물성을 연구하였다. 희석점도는 분자량과 용해성의 영향을 받았으며 저분자량의 함량이 늘어날수록 낮아졌다. 경화시간은 MAA의 양에 영향을 받았으며 저분자량의 함량이 늘어날수록 비스페놀형은 빨라졌고 노블락형은 변화를 보이지 않았다. 경도와 신율은 분자구조의 영향을 받았으며 저분자량의 함량이 늘어날수록 떨어졌다. 굴곡강도와 인장강도는 DER 331 함량 30~40%에서 가장 우수했다.

• Archives of Pharmacal Research
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• 제11권1호
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• pp.33-40
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• 1988

Two new nitro analogs of tranylcypromine, (E)-2-(p-nitrophenyl)cyclopropylamine ((E)-p-NTCP) and (E)-2-(m-nitrophenyl)cyclopropylamine ((E)-m-NTCP) were synthesized in order to examine the effect of aromatic nitro substitution on the MAO-inhibitory activity of 2-phenylcyclopropylamines. The compounds were obtained by treating t-butyl (E)-2-(p-nitrophenyl) cyclopropanecarbamate and t-butyl (E)-2-(m-nitrophenyl)cyclopropanecarbamate with p-toluenesulfonic acid in $CH_3$CN. Inhibitions of rat brain mitochondrial MAO-A and B by the compounds were examined using serotonin and benzylamine as the substrate at both in vitro and ex vivo levels. It was found from in vitro measurements that (E)-p-NTCP at $6.0{\times}10^{-5}M$ elicited merely 22.5% inhibition against MAO-B without any effect on MAO-A. In contrast, (E)-m-NTCP showed fair degrees of inhibitions of MAO-A and B with $IC_{50}$ values, $2.5{\times}10^{-7}M\;and\;1.4{\times}10^{-6}M$, respectively. It was also noted from (E)-m-NTCP that m-nitro substitution caused a shift of selectivity of the inhibition toward MAO-A. According to ex vivo measurements at 1.5, 3, 6, and 12 hr following the administration of a dose of 0.015 mmol/kg, i.p. to the rats, the inhibition percents of MAO-A by (E)-m-NTCP were 58.6, 63.7 63.6, and 46.6%, slightly lower than those observed by tranylcypromine. Whereas, (E)-m-NTCP at the same dose level did not show significant inhibitions against both MAO-A and MAO-B. Possible reasons for the difference in potencies between (E)-m-NTCP and (E)-p-NTCP were sought in relation to differing electron withdrawing effects of m- and p-substituents which will influence electron density of the side chain amino functions and the partitions.

• 한국미생물·생명공학회지
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• 제1권1호
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• pp.51-57
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• 1973

(1) 2,2'-Methylene bis (3,4,6-trichloroacetoxy benzene)을 모체화합물로 하여 Mannich반응에 의해 11종의 새로운 화합물을 합성했다. (2) 합성화합물중 R위치에 (구조식 들어감) 기를 가진 유도체가 효모보다 세균에 대해 비교적 강한 항균력을 나타냈다.