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새로운 Quinolone 항균제 개발 연구

  • 함원훈
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1993.04a
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    • pp.118-118
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    • 1993
  • 퀴놀론 모핵의 합성은 기존에 알려진 합성 방법인 Could-Jacobs방법과 Bayer방법에 의해서 Intermediate로 사용된 7-chloro-1-ethyl-6-fluoro-1, 4-dihydro-4-oxoquinoline-3-carboxylic acid와 1-cyclopropyl-7-chloro-6-Fluoro-1,4-dihydro-4-oxoquinolne-3-carboxylic acid를 합성하였다. Heteroaromatic tin compound는 furan, thiophene, 3-bromopyridine, 2-fluoropyridine에 n-BuLi을 사용하여 metallation 한후 electrophile로 tributyltin chloride를 사용하여 2-tributylstannofuran, 2-tributylst-annothiophene, 3-tributylstannopyridine, 2- fluoro-2-tributylstannop-yridine을 합성할 수 있었다. 이상의 Intermediate와 tin compounds를 p-alladium 촉매하에서 반응시켜 1-ethyl-7-(2-furanyl)-6-fluoro-1,4-dihy-dro-4-oxo-3-quinoline-carboxylic acid (compound 3), 1-ethyl-7-(2-th-iophenyl)-6-fluoro-1,4-dihydro-4-oxo-3-quinol in carboxylic acid(compound 5), 1-ethyl-7-(3-pyridinyl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid (compound 7), 1-ethyl-7-(2-fluoro-3-pyrid-nyl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid (compound 9), 1-cyclopropyl-7-(2-furanyl) -6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid (compound 4), 1-cyclopropyl-7-(2-thiophenyl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid (compound 6) ,1-cyclopropyl-7-(3-pyridinyl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid (compound 8), 1-cyclopropyl-7-(2-fluoro-3-pyridinyl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid (compound 10)를 합성하였다.

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Degenerate Weakly (k1, k2)-Quasiregular Mappings

  • Gao, Hongya;Tian, Dazeng;Sun, Lanxiang;Chu, Yuming
    • Kyungpook Mathematical Journal
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    • v.51 no.1
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    • pp.59-68
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    • 2011
  • In this paper, we first give the definition of degenerate weakly ($k_1$, $k_2$-quasiregular mappings by using the technique of exterior power and exterior differential forms, and then, by using Hodge decomposition and Reverse H$\"{o}$lder inequality, we obtain the higher integrability result: for any $q_1$ satisfying 0 < $k_1({n \atop l})^{3/2}n^{l/2}\;{\times}\;2^{n+1}l\;{\times}\;100^{n^2}\;\[2^l(2^{n+3l}+1)\]\;(l-q_1)$ < 1 there exists an integrable exponent $p_1$ = $p_1$(n, l, $k_1$, $k_2$) > l, such that every degenerate weakly ($k_1$, $k_2$)-quasiregular mapping f ${\in}$ $W_{loc}^{1,q_1}$ (${\Omega}$, $R^n$) belongs to $W_{loc}^{1,p_1}$ (${\Omega}$, $R^m$), that is, f is a degenerate ($k_1$, $k_2$)-quasiregular mapping in the usual sense.

Synthesis and Cobalt-Complexes of 1,2,3,4,5,6-Hexaalkyl-1,4-dibora-2-cyclohexene (1,2,3,4,5,6-Hexaalkyl-1,4-dibora-2-cyclohexene의 생성과 착물 생성)

  • Uhm, Jae-Koouk;An, Hee-Won
    • Journal of the Korean Chemical Society
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    • v.41 no.11
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    • pp.586-589
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    • 1997
  • 1,2,3,4,5,6-Hexaalkyl-1,4-dibora-2-cyclohexene was not produced by the general preparation method in our laboratory because of difficulties in the preparation of $B_2Cl_4.$ 2,3-Dietyl-1,4,5,6-tetramethyl-1,4-dibora-2-cyclohexene, 2 was synthesized by the reduction-oxidation reaction of potassium and methyliodide from 1,4-dimethyl-2,3-diethyl-1,4-dibora-2-cyclohexene, 1 as a substrate. Cobalt sandwich-complexes, 6, 7 and 8 were synthesized by the reaction of 2,3-diethyl-1,4,5,6-tetramethyl-1,4-dibora-2-cyclohexene with $({\eta}5-C_5H_5Co(C_2H_4)_2.$.

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Synthesis of Dipeptides Containing Aminobenzylphosphonic Acid (Aminobenzylphosphonic Acid 를 포함하는 Peptide의 합성에 관한 연구)

  • Rho Man Khyun;Hong Suck In;Kim Yong Joon
    • Journal of the Korean Chemical Society
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    • v.19 no.3
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    • pp.169-173
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    • 1975
  • Ten previously unreported dipeptides ontaining aminobenzylphosphonic acid were prepared by carbodiimide method. These are; Glycyl-dl-1-aminobenzylphosphonic acid, alanyl-dl-1-aminobenzylphosphonic acid, L-alanyl-dl-1-aminobenzylphosphonic acid, N-phthalyl-L-phenylalanyl-dl-1-aminobenzylphosphonic acid diethyl ester, N-carbobenzoxyglycyl-dl-1-aminobenzylphosphonic acid diethyl ester, N-carbobenzoxyalanyl-dl-1-aminobenzylphosphonic acid diethyl ester, N-carbobenzoxy-L-alanyl-dl-1-aminobenzylphosphonic acid diethyl ester, glycyl-dl-1-aminobenzylphosphonic acid diethyl ester hydrobromide, alanyl-dl-1-aminobenzylphosphonic acid diethyl ester hydrobromide and L-alanyl-dl-1-aminobenzylphosphonic acid diethyl ester hydrobromide. The first six compounds were characterized, and the last four compounds were obtained in the crude state.

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Synthesis of Nucleophilic Adducts of Thiols (Ⅰ). Addition of Cysteine to $\beta$-Nitrostyrene Derivatives

  • Kim, Tae-Rin;Choi, Sung-Yong
    • Bulletin of the Korean Chemical Society
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    • v.2 no.4
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    • pp.125-129
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    • 1981
  • The addition reactions of cysteine without blocking amino and carboxyl groups to substituted and unsubstituted ${\beta}$-nitro-styrene derivatives were investigated. ${\beta}$-Nitrostyrene(1a), p-methyl-${\beta}$-nitrostyrene(1b), 3,4,5-trimethoxy-$[\beta}$ -nitrostyrene(1c), $[\varpi}$-3,4-methylenedioxy-${\beta}$ -nitrostyrene(1d), o-, m- and p-chloro-${\beta}$ -nitrostyrene (1e, 1f, 1g) and o-, m- and p-methoxy-${\beta}$-nitrostyrene (1h, 1i, 1j) easily undergo addition reactions with cysteine to form S-(2-nitro-1-phenylethyl)-L-cysteine(3a), S-[2-nitro-1-(p-methyl)phenyl-ethyl]-L-cysteine(3b), S-[2-nitro-1-(3',4',5'-trimethoxy) phenylethyl]-L-cysteine(3c), S-[2-nitro-1-($[\vatpi}$ -3',4'-methylenedioxy)phenylethyl]-L-cysteine(3d), S-[2-nitro-1-(o-chloro)phenylethyl]-L-cysteine(3e), S-[2-nitro-1-(m-chloro)-phenylethyl]-L-cysteine(3f), S-[2-nitro-1-(p-chloro)phenylethyl]-L-cysteine(3g), S-[2-nitro-1-(o-methoxy)phenylethyl]-L-cysteine(3h), S-[2-nitro-1-(m-methoxy)phenylethyl]-L-cysteine(3i) and S-[2-nitro-1-(p-methoxy)phenylethyl]-L-cysteine(3j), respectively. The structure of adducts were confirmed by means of UV-spectrum, IR-spectrum, molecular weight measurement and elemental analysis. The various factors effecting the yield of cysteine adducts to ${\beta}$-nitrostyrene derivatives were also studied.

EBP1 regulates Suv39H1 stability via the ubiquitin-proteasome system in neural development

  • Kim, Byeong-Seong;Ko, Hyo Rim;Hwang, Inwoo;Cho, Sung-Woo;Ahn, Jee-Yin
    • BMB Reports
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    • v.54 no.8
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    • pp.413-418
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    • 2021
  • ErbB3-binding protein 1 (EBP1) is a multifunctional protein associated with neural development. Loss of Ebp1 leads to upregulation of the gene silencing unit suppressor of variegation 3-9 homolog 1 (Suv39H1)/DNA (cytosine 5)-methyltransferase (DNMT1). EBP1 directly binds to the promoter region of DNMT1, repressing DNA methylation, and hence, promoting neural development. In the current study, we showed that EBP1 suppresses histone methyltransferase activity of Suv39H1 by promoting ubiquitin-proteasome system (UPS)-dependent degradation of Suv39H1. In addition, we showed that EBP1 directly interacts with Suv39H1, and this interaction is required for recruiting the E3 ligase MDM2 for Suv39H1 degradation. Thus, our findings suggest that EBP1 regulates UPS-dependent degradation of Suv39H1 to govern proper heterochromatin assembly during neural development.

On the comparison of mean object size in M/G/1/PS model and M/BP/1 model for web service

  • Lee, Yongjin
    • International Journal of Internet, Broadcasting and Communication
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    • v.14 no.3
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    • pp.1-7
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    • 2022
  • This paper aims to compare the mean object size of M/G/1/PS model with that of M/BP/1 model used in the web service. The mean object size is one of important measure to control and manage web service economically. M/G/1/PS model utilizes the processor sharing in which CPU rotates in round-robin order giving time quantum to multiple tasks. M/BP/1 model uses the Bounded Pareto distribution to describe the web service according to file size. We may infer that the mean waiting latencies of M/G/1/PS and M/BP/1 model are equal to the mean waiting latency of the deterministic model using the round robin scheduling with the time quantum. Based on the inference, we can find the mean object size of M/G/1/PS model and M/BP/1 model, respectively. Numerical experiments show that when the system load is smaller than the medium, the mean object sizes of the M/G/1/PS model and the M/BP/1 model become the same. In particular, when the shaping parameter is 1.5 and the lower and upper bound of the file size is small in the M/BP/1 model, the mean object sizes of M/G/1/PS model and M/BP/1 model are the same. These results confirm that it is beneficial to use a small file size in a web service.

Dikkopf-1 promotes matrix mineralization of osteoblasts by regulating Ca+-CAMK2A- CREB1 pathway

  • Hyosun, Park;Sungsin, Jo;Mi-Ae, Jang;Sung Hoon, Choi;Tae-Hwan, Kim
    • BMB Reports
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    • v.55 no.12
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    • pp.627-632
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    • 2022
  • Dickkopf-1 (DKK1) is a secreted protein that acts as an antagonist of the canonical WNT/β-catenin pathway, which regulates osteoblast differentiation. However, the role of DKK1 on osteoblast differentiation has not yet been fully clarified. Here, we investigate the functional role of DKK1 on osteoblast differentiation. Primary osteoprogenitor cells were isolated from human spinal bone tissues. To examine the role of DKK1 in osteoblast differentiation, we manipulated the expression of DKK1, and the cells were differentiated into mature osteoblasts. DKK1 overexpression in osteoprogenitor cells promoted matrix mineralization of osteoblast differentiation but did not promote matrix maturation. DKK1 increased Ca+ influx and activation of the Ca+/calmodulin-dependent protein kinase II Alpha (CAMK2A)-cAMP response element-binding protein 1 (CREB1) and increased translocation of p-CREB1 into the nucleus. In contrast, stable DKK1 knockdown in human osteosarcoma cell line SaOS2 exhibited reduced nuclear translocation of p-CREB1 and matrix mineralization. Overall, we suggest that manipulating DKK1 regulates the matrix mineralization of osteoblasts by Ca+-CAMK2A-CREB1, and DKK1 is a crucial gene for bone mineralization of osteoblasts.

A Study of Total Medical Cost and Hospitalization Risk of Patients with Schizophrenia and Type 1 Diabetes Mellitus (제1형 당뇨병을 동반한 조현병 환자의 총 의료비용 및 입원 위험)

  • Lee, Sang-Uk;Kim, You-Seok
    • Korean Journal of Schizophrenia Research
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    • v.22 no.1
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    • pp.8-13
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    • 2019
  • Objectives: The aim of this study was to explore the prevalence of type 1 diabetes in patients with schizophrenia and their total medical costs and risk of hospitalization. Methods: This study used Health Insurance Review and Assessment Service data in Korea. To examine total medical costs and risk of hospitalization, we selected 1,510 subjects with schizophrenia (half with and half without type 1 diabetes) that were 1:1 matched via propensity score matching. In health care system perspective, total medical costs included out-of-pocket and insurer's costs. Logistic regression models were used to examine the risk of hospitalization. Results: The prevalence of type 1 diabetes in patients with schizophrenia was 3.87 per 1,000 person year. Among patients with schizophrenia, the amount of total average medical costs and hospitalization costs in patients with type 1 diabetes was 1.49 and 1.59 times higher than those in patients without it, respectively. The odds of hospitalization were higher among patients with type 1 diabetes compared with those without it (odds ratio, OR=1.97 ; 95% CI 1.60-2.43). Conclusion: This study showed that medical costs and risk of hospitalization were higher in schizophrenia patients with type 1 diabetes. Therefore, these individuals may require specific care programs.

Allyl-isothiocyanate Content and Physiological Responses of Wasabia japonica Matusum as Affected by Different EC Levels in Hydroponics (고추냉이 수경재배시 배양액의 EC 수준이 Allyl-isothiocyanate 함량과 생리적 반응에 미치는 영향)

  • Choi, Ki-Young;Lee, Yong-Beom;Cho, Young-Yeol
    • Horticultural Science & Technology
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    • v.29 no.4
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    • pp.311-316
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    • 2011
  • This study aimed to determine the effect of EC (electrical conductivity) levels of nutrient solution in hydroponic culture on allyl-isothiocyanate (AITC) content within plant tissues, Vitamin C content and physiological responses in wasabi plant (Wasabia japonica M. 'Darma'). The 'Darma' was grown for 5 weeks with a deep flow technique (DFT) system controlled at 5 different EC levels, including 0.5, 1, 2, 3, and $5dS{\cdot}m^{-1}$. In result, the highest total content of AITC showed at EC level 5 and $3dS{\cdot}m^{-1}$ for 1 or 5- week, respectively. The total content of AITC increased about 1.2-1.4 times when the plants were grown in the EC levels between 0.5 and $2dS{\cdot}m^{-1}$, whereas the content decreased about 6 and 56 % in the EC level 3 and $5dS{\cdot}m^{-1}$, respectively. The content of AITC was relatively higher in petiole tissue, about 53 %, taken from 1 week-grown plants when the EC was controlled between 0.5 and $2dS{\cdot}m^{-1}$. Root tissue also had relatively higher content of AITC, about 45.1 %, when the EC was controlled at 3 and $5dS{\cdot}m^{-1}$. However, a 5-fold decrease in the AITC content was found in blade tissue and a 6.8-fold decrease in root when the EC was controlled at $5dS{\cdot}m^{-1}$ for 5 weeks. There was no significant difference in the vitamin C content in 1-week grown leaf tissues under the different EC level treatments; but, the content increased about 27% in 5-week grown plants at the EC level between 0.5 and $2dS{\cdot}m^{-1}$, compared to the 1 week-grown leaf tissue. Electrolyte leakage of leaf tissue taken from 3-week grown plant was 3-fold higher at the EC level $5dS{\cdot}m^{-1}$, compared to the EC level between 0.5 and $2dS{\cdot}m^{-1}$. Chlorophyll content, photosynthesis rate and transpiration rate were decreased when the EC was controlled at higher than $2dS{\cdot}m^{-1}$. Leaf water content, specific leaf area and growth were decreased when the EC was controlled at $5dS{\cdot}m^{-1}$ for 5 weeks. All the integrated results in this study suggest that the EC level of nutrient solution should be maintained at lower than $3dS{\cdot}m^{-1}$ in order to improve nutritional value and quantity required for hydroponically grown wasabi as functional vegetable.