• Archives of Pharmacal Research
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• 제18권6호
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• pp.440-448
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• 1995

Fitty two flavones were synthesized from polyoxygenated dibenzoylmethanes which were obtained by a modified Baker-Venkatarman rearrangement, of 2-benzoyl oxyacetophenones. The following flavones among them showed good cytotoxic activities against L1210 and HL60 cells ; 2'-benzoyloxy-5,7-dimethoxyflavone $(8.2{\mu}g/ml,{\;}5.0 {\mu}g/ml)$, 2'-benzyloxy-5,7,8-trimethoxyflavone $(5,9 {\mu}g/ml,{\;}11.0{\mu}g/ml,{\;}2.7{\mu}g/ml)$, 2'-hydroxy-5,7,8-trimethoxyflavone $(9.8{\mu}/ml,{\;}6.2{\mu}g/ml)$, 2'-benzyloxy-5-hydroxyflavone $(5.2 {\mu}g/ml,{\;}3.6{\mu}g/ml)$, and 5,2'-dihydroxyflavone $(5.1{\mu}g/ml,{\;}4.0{\mu}g/ml)$. Presence of 5-methoxy group potentiated the cytotoxic activity, while the existence of 7-methoxy group decreased the activity. 5-Hydroxy or methoxy activates 4-carbonyl group, while 7-methoxy group deactivates the acrbonyl group. From these observation it was concluded that the activation of carbonyl group at C-4 of a flavone is important for the enahncement of the cytotoxic activity. The presence of both 5-hydroxy and 2-benzyloxy-or 2-hydroxy group enhanced the antitumor activity; 2'-benzyloxy-5-hydroxy-7-methoxyflaone 9T/C=144%), 5.2'-dihydroxy-7-methoxyflavone (T/C=132%) and 5,2'-dihydroxy-6,78,6' trtramethoxyflvone (T/C = 172%) 2'hexanolytion of 5,2'-dihydroxy-flavones did not improve the natitumor activity; 2' hexanoyloxy-5-hydroxy-7-methoxyflavone showed T/C = 132%, about the same as that of 5,2'-dihydroxy-7-methoxyflvone (T/C=130%)

• 약학회지
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• 제54권4호
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• pp.288-294
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• 2010

Three dimensional quantitative-structure relationships (3D-QSARs) models between structures of phenoxy, phenylthio or benzyloxy substituted quinolone analogues and their antitrypanosomal activity against Chagas disease (Trypanosoma cruzi) were derived and discussed quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. The optimized CoMFA 1 model ($q^2$=0.528 and $r^2$=0.964) showed the best statistical results. According to the optimized CoMFA 1 model, the antitrypanosomal activities were dependent on the steric (60.0%) and electrostatic (36.2%) factors of quinolone derivatives. From the contour maps, it is predicted that the activity will be increased when sterically favored groups were located in $R_4$ and $R_5$ position and sterically disfavored groups were located in $R_2$ position. Also, the positively charged groups on $R_2$ would be able to increase the antitrypanosomal activities.

• 폴리머
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• 제34권4호
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• pp.381-385
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• 2010

Poly(lactic acid)계 고분자의 기능화를 목적으로 곁사슬에 아미노기를 도입한 지방족 폴리에스테르를 합성하 고자 하며, N-$\varepsilon$-benzyloxy-carbonyl-L-lysine을 출발물질로 한 디에스테르 단량체 3-[(benzyloxycarbonylamino) butyl]-1,4-dioxane-2,5-dione(BABD)를 합성하였다. BABD와 L-lactide와의 공중합의 결과, PLLA 사슬에 BABD단위가 도입된 것이 확인되었으며 공중합체의 조성은 단량체의 첨가량에 따라 제어가 가능함을 알 수 있었다. 얻어진 폴리머는 $M_n$=3300 정도로 낮은 중합도를 나타내었으나 단량체의 정제 및 중합시 간의 검토에 의해 고분자량체의 생성이 가능함을 확인하였다. 곁사슬에 아미노기를 도입함에 의해 얻어진 폴리머는 친수성의 향상, 아미노기에 대한 화학수식 등에 의해 기능성의 부여가 기대된다.

• Archives of Pharmacal Research
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• 제29권11호
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• pp.969-976
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• 2006

Novel chalcones were found as potent inhibitors of interleukin-5 (II-5). 1-(6-Benzyloxy-2-hydroxyphenyl)-3-(4-hydroxyphenyl)propenone (2a, 78.8% inhibition at $50\;{\mu}M,\;IC_{50}=25.3\;{\mu}M$) was initially identified as a potent inhibitor of IL-5. This activity is comparable to that of budesonide or sophoricoside (1a). The benzyloxy group appears to be critical for the enhancement of the IL-5 inhibitory activity. To identify the role of this hydrophobic moiety, cyclohexyloxy (2d), cyclohexylmethoxy (2c), cyclohexylethoxy (2e), cyclohexylpropoxy (2f), 2-methylpropoxy (2g), 3-methylbutoxy (2h), 4-methylpentoxy (2i), and 2-ethylbutoxy (2j) analogs were prepared and tested for their effects on IL-5 bioactivity. Compounds 2c ($IC_{50}=12.6\;{\mu}M$), 2d ($IC_{50}=12.2\;{\mu}M$), and 2i ($IC_{50}=12.3\;{\mu}M$) exhibited the most potent activity. Considering the cLog P values of 2, the alkoxy group contributes to the cell permeability of 2 for the enhancement of activity, rather than playing a role in ligand motif binding to the receptor. The optimum alkoxy group in ring A of 2 should be one that provides the cLog P of 2 in the range of 4.22 to 4.67.

• 약학회지
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• 제50권5호
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• pp.326-331
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• 2006

We designed and synthesized new benzylpiperidinyl ether derivatives as beta-amyloid aggregation inhibitors for the development of novel anti-Alzheimer's disease agents. As starting material, 4-hydroxypiperidine was used. For protection of the amine group in piperidine (2), di-tert-butyl dicarbonate was reacted with 4-hydroxypiperidine in the presence of triethylamine. For introduction of benzyl group, benzylbromide was treated with compound 2 in dioxane. After deprotection of Boc group on amine in compound 3, ester (5) was synthesized by addition of ethyl-4-chlorobutyrate. The alcohol 6 was synthesized by hydride reduction of 5 using $LiAlH_4$. To obtain final products (7-14), the alcohol 6 was condensed with each of substituted benzoic acids. To screen beta-amyloid aggregation inhibition of the products, thioflavinT assay was performed using $A{\beta}1-42\;at\;37^{\circ}C$ for 26 h incubation, in vitro. From the result of screening, compound 8, 9, 11 and 12 showed effective activity about $65{\sim}85\;{\mu}M\;as\;IC_{50}$ value. Among the prepared compounds, 4-[4-(benzyloxy)piperidino]butyl-4-chlorobenzoate (8) was the most effective inhibitor having $IC_{50}\;of\;65.4{\mu}M$.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.4075-4079
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• 2012

Benzimidazoles 1-4 were obtained using modified synthesis methods and studied for their ability to inhibit cell proliferation of colon cancer cell HCT-116 and breast cancer cell MCF-7 using MTT assays. In the HCT-116 cell line, benzimidazole 2 was found to have an $IC_{50}$ value of $16.2{\pm}3.85{\mu}g/mL$ and benzimidazole 1 a value of $28.5{\pm}2.91{\mu}g/mL$, while that for benzimidazole 4 was $24.08{\pm}0.31{\mu}g/mL$. In the MCF-7 cell line, benzimidazole 4 had an $IC_{50}$ value of $8.86{\pm}1.10{\mu}g/mL$, benzimidazole 2 a value of $30.29{\pm}6.39{\mu}g/mL$, and benzimidazole 1 a value of $31.2{\pm}4.49{\mu}g/mL$. Benzimidazole 3 exerted no cytotoxity in either of the cell lines, with $IC_{50}$ values $>50{\mu}g/mL$. The results suggest that benzimidazoles derivatives may have chemotherapeutic potential for treatment of both colon and breast cancers.

• Nuclear Medicine and Molecular Imaging
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• 제41권4호
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• pp.326-334
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• 2007

에스트로젠 수용체 양성 유방암에서 과발현되는 에스트로젠 수용체는 $[^{18}F]FES$와 같은 $^{18}F$이 표지된 스테로이드계 에스트로젠 수용체 리간드를 사용하여 양전자방출단층촬영기로 영상을 얻을 수 있다. 반감기가 12.7시간인 $^{64}Cu$에 비해 1.8시간인 $^{18}F$은 반감기가 짧고, $^{64}Cu$로 표지 하는 경우보다 수율이 낮은 단점이 있다. 사이클렌은 구리, 인듐, 갈륨, 가돌리륨 등과 같은 금속과 안정한 착물을 형성한다. 이를 근거로 2개의 페놀 하이드록시 그룹을 가지고 있는 사이클렌을 기본구조로 한 구리 착물을 합성하였다. 재료 및 방법 : 1,7 위치에 보호기를 가지고 있는 1,7-bis(benzyloxy-carbonyl)-cyclen은 기존에 알려진 방법에 따라 합성 되어졌다. 여기에 4,10 위치에 2개의 4-benzyloxybenzyl groups을 도입한 후, Pd/C상에서의 수소화 반응으로 benzyloxycarbonyl과 benzyl groups이 모두 제거됨으로써 1,7-bis(4-hydroxybenzyl)-cyclen (1)을 성공적으로 합성할 수 있었다. 결과: 우리가 합성한 물질 1은 $^1H,\;^{13}C-NMR$ 그리고 질량분석기로 만들어졌는지 여부를 확인하였다. 이 물질들은 구리 이온과 반응하여 $[Cu(1)]^{2+}2(ClO_4)^-$와 $[Cu(1)Cl]^+Cl^-$를 형성하였고, 고분해능 FAB 질량분석기로 확인하였다. 결론: 우리는 질소원자에 trans 방향으로 2개의 페놀 그룹을 가지고 있는 cyclen 유도체를 합성하는데 성공하였고, 구리이온과 반응하여 각각 전체 전하가 +2그리고 +1인 구리 착물을 합성하였으며, 이들은 에스트로젠 수용체의 영상화를 위한 PET 추적자로 쓰일 수 있는 가능성이 있다.