• 약학회지
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• 제41권2호
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• pp.187-194
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• 1997

For the development of antifungal agents, modification of naftifine which exhibits significant antimycotic activity was performed by replacing the naphthalene ring of it to hete ro cyclic rings such as morpholine. benzothiazole, piperidine and pyridine derivatives. The synthesized compounds were tested in vitro antifungal activity against five different fungi with naftifine as a comparative antimycotic molecule. From the biological evaluation two compounds, (E)-N-(3-phenyl-2-propenyl)-N-(4-piperidinylmethyl)amine(3d) and (E)-N-(3-phenyl-2-propenyl)-N-(3-pyridylmethyl)amine(3f) showed relatively noticeable activity(MIC=50${\mu}g$/ml). On the other hand, the other compounds had no activity.

• Parasites, Hosts and Diseases
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• 제62권1호
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• pp.42-52
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• 2024

Antimalarial drugs are an urgently need and crucial tool in the campaign against malaria, which can threaten public health. In this study, we examined the cytotoxicity of the 9 antimalarial compounds chemically synthesized using SKM13-2HCl. Except for SKM13-2HCl, the 5 newly synthesized compounds had a 50% cytotoxic concentration (CC₅₀) >100 μM, indicating that they would be less cytotoxic than SKM13-2HCl. Among the 5 compounds, only SAM13-2HCl outperformed SKM13-2HCl for antimalarial activity, showing a 3- and 1.3-fold greater selective index (SI) (CC₅₀/IC₅₀) than SKM13-2HCl in vitro against both chloroquine-sensitive (3D7) and chloroquine -resistant (K1) Plasmodium falciparum strains, respectively. Thus, the presence of morpholine amide may help to effectively suppress human-infectious P. falciparum parasites. However, the antimalarial activity of SAM13-2HCl was inferior to that of the SKM13-2HCl template compound in the P. berghei NK65-infected mouse model, possibly because SAM13-2HCl had a lower polarity and less efficient pharmacokinetics than SKM13-2HCl. SAM13-2HCl was more toxic in the rodent model. Consequently, SAM13-2HCl containing morpholine was selected from screening a combination of pharmacologically significant structures as being the most effective in vitro against human-infectious P. falciparum but was less efficient in vivo in a P. berghei-infected animal model when compared with SKM13-2HCl. Therefore, SAM13-2HCl containing morpholine could be considered a promising compound to treat chloroquine-resistant P. falciparum infections, although further optimization is crucial to maintain antimalarial activity while reducing toxicity in animals.

• Bulletin of the Korean Chemical Society
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• 제21권3호
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• pp.339-341
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• 2000

• 대한의용생체공학회:의공학회지
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• 제13권2호
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• pp.147-154
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• 1992

Poly (glycolic aclu-co-glycine-L-lactic aclu) has been prepared by rlng opening polymerlzation. The monomer 6-methyl morpholine-2, 5-dlone was synthe-slzed by bromoproplonylation of 2 bromopropionyl bromide with glycine. Glycolide and 6-methyl morpholine-2, 5-dione have been used as starling materials for polydepsipeptides. The synthesized copolymers have been Identlrled by NMR and FT-lR spectrophotometer. The Tg value of poly(glycollc aclu-co glycine-L-tactic acld ) Is In creased with increasing mole fraction of 6-methylmorpholine-2, 5-dlone(60-$84^{\circ}C$). The glass trasltion temperature of poly(glycolic acid-co-glycine-L-lactic-acid) (62-$86^{\circ}C$) is lower than that of poly (L-lactic acrid-co-glycine-L-lactic acid ). The thermal degradation of poly( L-lactic acid-co- glycine-L-lactic acid ) Is decreased with increasing mole fraction of L-lactide. The thermal degrada pion of poly(glycolic acrid-co-91ycine-L-lactic aclu ) is increased with increasing mole Fraction of glycolide.

• 대한의용생체공학회:의공학회지
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• 제9권1호
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• pp.37-46
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• 1988

Synthetic biodegradable polymers are of great interest for biomedical applications such as surgical sutures and drug delivery systems. The copolymers of ${alpha}-amino$ acids and ${alpha}-hydroxy$ matrices having the required permeability for drugs. Poly (glycine.co-lactic acid) and poly (glycine-co-glycolic acid) have been synthesized by ring-opening polymerization. Morpholine-2, 5-diane, lactide, and glycolid have been used as starting materials for polydepsipeptides. The synthesized monomers and copoylmers have been identified by NMR and FT-lR spectrophotometer. The thermal properties and glass transition temperatures ($T_g$) of the copolymers have been measured by differential scanning calorimetry. The $T_g$ values of poly (glycine-co-lactic acid) and poly (glycine co.glycolic acid) are increased with increasing mole fraction of morpholine-2, 5-dione in the copolymers.

• Bulletin of the Korean Chemical Society
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• 제28권8호
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• pp.1353-1357
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• 2007

Second-order rate constants (kN) have been determined spectrophotometrically for reactions of Y-substituted phenyl 2-furoates (1a-h) with piperidine and morpholine in 80 mol % H2O/20 mol % DMSO at 25.0 ± 0.1 oC. The Brønsted-type plot exhibits a downward curvature for the reactions with strongly basic piperidine but is linear for the reactions with weakly basic morpholine. The slope of the curved Brønsted-type plot changes from -1.25 to ?0.28 as the pKa of the conjugate acid of the leaving aryloxides decreases. The pKa at the center of the Brønsted curvature, defined as pKa°, was determined to be 6.4. The aminolysis of 1a-h has been concluded to proceed through a stepwise mechanism on the basis of the curved Brønsted-type plot. The reactions of Ysubstituted phenyl cinnamates (2a-g) with piperidine resulted in a curved Brønsted-type plot with a pKa° values of 6.4. However, the curved Brønsted-type plot has been suggested to be not due to a change in the RDS but due to a normal Hammond effect of a concerted mechanism, since the Brønsted-type plot for the corresponding reactions with morpholine results in also a curved Brønsted-type plot with a pKa° values of 6.1. The furoates with a basic leaving group (i.e., 1b-g) are less reactive than the corresponding cinnamates (i.e., 2b-g). The k2/ k-1 ratios for the reactions of 1b-h are much smaller than unity, which has been suggested to be responsible for their low reactivity.

• 대한화학회지
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• 제54권1호
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• pp.49-54
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• 2010

무수탄산칼륨 존재 하에서 2-chloro-N-(4,6-diarylpyrimidin-2-yl)acetamides 25-33를 모르포린과 축합 반응시켜서 2-morpholino-N-(4,6-diarylpyrimidin-2yl)acetamides 34-42 화합물들을 합성하였다. 합성된 화합물들의 녹는점, 원소분석, MS, FT-IR, $^1H$- & $^{13}C$-NMR로 화학적인 구조를 규명되었다.

• 대한화학회지
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• 제51권3호
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• pp.244-250
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• 2007

항암작용이 기대되는 일련의 새로운 6-allylthio-3-aminopyridazine 유도체를 allylthiolation, amination을 이용하여 합성하였다. 피리다진 핵은 hydrazine monohydrate와 maleic anhydride의 축합반응으로 제조하였다. 3,6- Dichloropyridazine은 3,6-dihydroxypyridazine을 POCl3에 가하여 합성하였다. 6-Allythio-3-chloropyridazine은 3,6- dichloropyridazine에 allylmercaptan과 sodium hydroxide을 이용하여 얻었다. Morpholine, piperazine, pyrazole, imidazole, pyrrolidine, piperidine, perhydroazepine 및 perhydroazocine와 같은 질소 친핵체를 갖는 hetero환을 피리 다진 환의 3번 위치에 도입시켜 6-allylthio-3-aminopyridazine 합성하였다. 이 과정은 아민 친핵체의 친핵성 치환반응 으로 n-buthanol에서 NH4Cl를 가하고 24~48시간 동안 환류시켜 진행하였다.

• Bulletin of the Korean Chemical Society
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• 제29권3호
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• pp.585-589
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• 2008

Second-order rate constants (kN) have been measured for reactions of Y-substituted phenyl 2-thiophenecarboxylates (6a-h) with morpholine and piperidine in 80 mol % H2O/20 mol % DMSO at 25.0 0.1 oC. The Brnsted-type plot for the reactions of 6a-h with morpholine is linear with b lg = 1.29, indicating that the reactions proceed through a tetrahedral zwitterionic intermediate (T?). On the other hand, the Brnsted-type plot for the reactions of 6a-h with piperidine exhibits a downward curvature, implying that a change in the rate-determining step occurs on changing the substituent Y in the leaving group. Dissection of kN into microscopic rate constants (i.e., k1 and k2/k1 ratio) has revealed that k1 is smaller for the reactions of 6a-h than for those of Y-substituted phenyl 2-furoates (5a-h), while the k2/k1 ratio is almost the same for the reactions of 5a-h and 6a-h. It is also reported that modification of the nonleaving group from the furoyl (5a-h) to the thiophenecarbonyl (6a-h) does not influence pKao (defined as the pKa at the center of the Brnsted curvature) as well as the k2/k1 ratio.

• Bulletin of the Korean Chemical Society
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• 제30권12호
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• pp.2909-2912
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• 2009

The amines studied in this study are less reactive toward ethyl propiolate (3) in MeCN than in H$_2$O although they are 7 to 9 pK$_a$ units more basic in the aprotic solvent. The reactivity of morpholine and deuterated morpholine toward 3 is found to be identical, indicating that proton transfer occurs after rate-determining step (RDS). The fact that kinetic isotope effect is absent excludes a stepwise mechanism in which proton transfer occurs in RDS as well as a concerted mechanism in which nucleophilic attack and proton transfer occur concertedly through a 4-membered cyclic transition state (TS). Thus, the reactions have been concluded to proceed through a stepwise mechanism in which proton transfer occurs after RDS. Brønsted-type plots are linear with small ${\beta}_{nuc}$ values, i.e., ${\beta}_{nuc}$ = 0.29 in H$_2$O and ${\beta}_{nuc}$ = 0.51 in MeCN, indicating that bond formation is not advanced significantly in RDS. The small ${\beta}_{nuc}$ value also supports the conclusion drawn from the study of kinetic isotope effect.