• Bulletin of the Korean Chemical Society
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• 제7권3호
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• pp.201-204
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• 1986

Reduction of N-arylpyridinium compounds by $NaBH_4$ gave mixtures of the corresponding 1,2-dihydropyridine(major) and 1,4-dihydropyridine(minor), whereas similar reduction by $Na_2S_2O_4$ produced 1,4-dihydropyridines regioselectively. The proportion of 1,4-isomer in the product by $NaBH_4$ reduction appeared to increase with the electron-donating ability of N-aryl groups. When the N-aryl group is p-methylphenyl, p-ethylphenyl or p-methoxyphenyl, the 1,2-dihydropyridines in ethanol-water (4:1) solutions isomerized to the corresponding 1,4-dihydropyridines. N-(p-methylphenyl)-1,2-dihydropyridine and N-(p-ethylphenyl)-1,2-dihydropyridine in solid state also isomerized to the corresponding 1,4-dihydropyridines. The different behaviors of reduction among N-arylpyridiniums and isomerization of the reduction products depending on the substituent in N-aryl group were explained in terms of difference in the electronic effects of the substituents.

• Archives of Pharmacal Research
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• 제17권2호
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• pp.119-123
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• 1994

The synthesis of 3a, 3b, 7a fro Benzpthiazepinone and 1,4-dihyropyridine derivatives is described. Benzothiazepinone nad 1,4-dihydropyridine derivatives were prepared according to literature procedure. The key reactions involve esterification and amidation of benzothize-pinone nad 1,4-dihydropyridine derivatives.

• The Korean Journal of Physiology
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• 제22권2호
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• pp.207-218
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• 1988

Effects of 1, 4-dihydropyridine compounds, such as nifedipine, nisoldipine, nitrendipine, and nimodipine which were calcium antagonists on the normal and Ca-dependent, slow channel mediated action potentials in the guinea pig's papillary muscle were investigated. The glass microelectrode was impaled into a papillary muscle cell for measurements of potential changes with the simultaneous tracing of isometric contraction. The concentration of Ca antagonists were 1 mg/l (nifedipine and nisoldipine), 2 mg/l (nitrendipine and nimodipine), which showed the maximal inhibition of isometric contraction (above 90%) and simultaneous effects on the normal action potentials and only the halves of those concentrations were sufficient to observe the effects on the calcium action potentials. The data for analysis were only chosen when the microelectrode was maintained in a cell throughout the experiments. 1, 4-Dihydropyridine compounds decreased the action potential duration but did not affect the resting membrane potential, overshoot, and upstroke velocity of the normal action potentials with the decrease in the isometric contraction. And with the decrease in the area and amplitude of isometric contraction, the area, amplitude, upstroke velocity and duration of Ca action potential was decreased. But the differences in the effects of the Ca antagonists were not observed. Therefore it is inferred that the changes in normal and Ca action potential induced by the 1, 4-dihydropyridine compounds with a common chemical structure would be caused by the slow inward Ca-current, not by a fast Na-current.

• 대한화학회지
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• 제32권2호
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• pp.144-148
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• 1988

의약적으로 매우 유용한 1,4-디하히드로피리딘 3,5-디카르복실산 에스테르의 중간체인 1,4-디히드로피리딘 모노 유기산(V)을 알릴에스테르(IV)에 팔라듐 아세테이트 촉매를 사용하여 94%의 높은 수율로 얻었으며 이 중간체를 사용하여 2-(N-벤질-N-메틸아미노) 에틸메틸 2,6-디메틸-4-(3'-니트로페닐)-1,4-디히드로피리딘-3, 5-디카르복실산 에스테르(VII) 및 그 유도체들을 70~85%의 좋은 수율로 합성하였다.

• Archives of Pharmacal Research
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• 제18권1호
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• pp.27-30
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• 1995

The Hantzsh reaction of 7-hydroxy-8-methoxy-2-oxo-2H-benzopyran-6-carboxaldehyde (1) with ethyl acetoacetate and ammonia yields the dihydropyridine derivative 2 together with the pyridine derivative 3 and the eight membred ring derivative 4. Reaction of 1 with ethyl cyanoacetate and malononitrile gives the iminodicoumarin derivatives 5 and 6 respectiely. The latter compound was reacted with butan-2-one and acetophenone to produce the Michael adduct 71, b and the 2-aminopyridine derivatives 8a, b.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.252.3-252.3
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• 2003

An effective and convenient regioselective reduction of 5-benzylidene 2,4-thiazolidinedione derivatives to the corresponding 5-benzyl 2,4-thiazolidinedione derivatives has been accomplished using 3,5-dicarboethoxy-2,6-dimethyl-1,4-dihydropyridine (Hantzsch dihydropyridine ester: HEH) with silica gel as an acid catalyst in a good yield.

• 약학회지
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• 제32권3호
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• pp.157-163
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• 1988

4-Aryl-1, 4-dihydropyridines(DHP) derived from Hantsch type condensation of aromatic aldehydes with aminocrotonates and acetoacetic esters are studied as calcium channel blocking drugs. New DHP derivatives containing alkenyl ester show fairly good cardiovascular activity in mice. Preparation of the DHP derivatives and their major biological activity are presented along with their physical data.

• 약학회지
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• 제33권3호
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• pp.167-174
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• 1989

KR-1008 and KR-30006 are 1,4-dihydropyridine derivatives, new vasodilatory calcium antagonists from KRICT. Calcium antagonistic properties of the compounds were studied in the isolated heart (Langendorff preparation), pulmonary artery (vasodilation), and in the papillary muscle (negative inotropic effect) of the guinea pig. Antihypertensive effect were also investigated after i.v. or oral administration in the SHR (spontaneously hypertensive rat). They produced a sigificant inhibition of Ca-induced contraction in the guinea pig pulmonary artery at the concentrations of above $10^{-8}M$. The negative inotropic effect of the electrically stimulated papillary muscle appeared from the concentration of $10^{-6}M$, which is about hundred times higer than the concentration of vasodilation effect. Left ventricular pressure also decreased from the concentration of $3\;{\times}\;10^{-6}M$ in KR-1008 and KR-3006 in the Langendorff heart preparations. Coronary flow rate increased from $10^{-6}M$ in KR-1008 and nicardipine and appeared no change in KR-30006. The antihypertensive effect of KR-1008 (EC 20: $2.9\;{\mu}g/kg$) was potent more than nicardipine (EC 20: $3.4\;{\mu}g/kg$) and than Kr-30006 (EC 20: $6.8\;{\mu}g/kg$) was, after i.v. bolus injection in the anesthetized SHR. The antihypertensive effect in the conscious SHR appeared 30 minutes after oral administration of 10 mg/kg and persisted 4 hrs in KR-1008 and 12 hrs in KR-30006. Heart rate tended to increase for 0.5-1 hr after oral administration of the test compounds.

• Bulletin of the Korean Chemical Society
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• 제8권3호
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• pp.168-170
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• 1987

The reaction between 1-benzyl-3-carbamoyl-1,4-dihydropyridine (BNAH) 1 and various 1-arylpyridinium salts 2, and the reaction between 1-(4-methylphenyl)-1,4-dihydropyridine 4b and 1-aryl-3-carbamoylpyridinium (1-arylnicotinamide) salts 5 were carried out. The extents of reaction in equilibrium were estimated by nmr integration data. The equilibrium constants for the reactions, K, and the standard Gibbs free energy changes for the reduction of the pyridinium salts to the corresponding 1,4-dihydropyridines ${\Delta}G^{\circ}'$ were evaluated. The Hammett plot of log K for the reaction between 1 and 2, and ${\Delta}G^{\circ}'$ against ${\sigma}_p$ of the substituents in 1-aryl moiety shows linear correlation with the reaction constant ${\rho}$ of 9.4 (for log K vs ${\sigma}_p$) and -54.5 KJ/mole (for ${\Delta}G^{\circ}'$ vs ${\sigma}_p$). It was found that 1-aryl-1,4-dihydropyridines have much higher reducing power than the corresponding 1-aryl-1,4-dihydronicotinamides, and the power is affected greatly by the electron-withdrawing ability of the substituents in aryl group. The reactions were utilized for preparation of 1,4-dihydropyridines bearing highly electron-withdrawing groups such as 4-nitrophenyl and 2,4-dinitrophenyl, which could not be obtained by conventional dithionite reduction of the corresponding pyridinium salts due to the base-labile nature of the salts.

• 분석과학
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• 제7권2호
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• pp.187-191
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• 1994

Pyridine과 $^tBuLi$의 반응생성물과 $Me_3SiCl$의 반응에 의해 반응성이 매우 큰 반응 중간체 1,2-dihydropyridine 유도체 (2)를 낮은 온도의 비극성 용매 속에서 합성하여 분리하였으며 SPINX3을 이용한 $^1H-NMR$ 미세 구조 분석에 의해 반응생성물 (2)의 구조를 확인하였다. $^1H-NMR$ spectrum에서 화학적 이동상수와 NH, 그리고 4개의 aromatic CH proton의 coupling에 관한 정보를 분석하였으며, 이 화합물의 형성반응에 의한 반응형성물 3과 4의 합성에 의해 확인하였다.