• 대한화학회지
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• 제45권5호
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• pp.436-441
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• 2001

77K에서 mer-[Cr(dien)(glygly)]$ClO_4$의 방출 및 들뜬 상태 스펙트럼과 실온에서 적외선 및 가시선 스펙트럼을 측정하였다. 스핀-허용 및 스핀-금지에 해당하는 12개의 전자 전이의 성분을 배정하였다. 관측한 전이를 이용하여 Cr(Ⅲ) 착물에 배위된 원자의 결합성을 결정하기 위해서 리간드장 해석을 수행하였다. 이 연구에서 dien과 glygly 리간드의 아민 N 원자는 강한 $\sigma$-주개 특성을 갖는 반면에, glygly의 펩티드 N 원자는 Cr(Ⅲ) 이온에 약한 $\pi$-주개의 성질이 있음을 확인할 수 있었다.

• 대한화학회지
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• 제34권1호
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• pp.37-43
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• 1990

$D_{2d}$ 점군에 속하는 강결정장의 tetragonally 일그러진 사면체 3$d^9$전자계 착물의 바닥상태에 대한 리간드 궤도함수의 spin-orbit coupling과 중심 금속의 3d와 4p궤도함수의 intermixing이 미치는 영향에 대하여 중첩 섭동론을 사용하여 연구하였다. 단결정 $Cs_2CuCl_4$의 tetragonally 일그러진 $CuCl_4^{2-}$에 대한 d-d전이의 실험값을 사용한 LCAO-MO분석은 구리이온과 리간드 사이의 공유결합성은 Cu 4p orbital의 기여가 증가하므로서 급격히 감소하고 리간드 Cl 3p궤도함수의 spin-orbit coupling 상호작용에 의한 바닥상태의 에너지 준위 분리에 대한 효과는 $\Gamma_7(E)\;\to\;\Gamma_6(E)\; >\;\Gamma_7(B_2)\;\to\;\Gamma_6(E)\; >\;\Gamma_7(B_2)\;\to\;\Gamma_7(E)$의 순서로 감소하였다.

• Bulletin of the Korean Chemical Society
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• 제29권8호
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• pp.1499-1504
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• 2008

Pyrazine derivatives bind to b-RAF receptor which is important in cancer therapy. The ligand-receptor interactions have been studied by comparative molecular field analysis (CoMFA) and molecular docking methods. Applying conventional ligand-based alignment schemes for the whole set was not successful. However, QM and DFT results suggested that some ligands have electrostatic interaction while others have steric interactions. On the basis of these results, we divided the dataset into two subsets. Electrostatic effect was found to be important in one set while steric effect for the other. Best docking modes were obtained for each subset based on the available crystal structure. These receptor-guided CoMFA models propose an interesting possibility which is difficult to obtain otherwise. i.e., in one binding mode the electrostatic interaction plays a key role for one subset ($q^2$ = 0.46, $r^2$ = 0.98), while in another binding mode steric effect is important with another subset ($q^2$ = 0.43, $r^2$ = 0.74).

• 통합자연과학논문집
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• 제9권2호
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• pp.121-127
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• 2016

CXC chemokine receptor 2 (CXCR2) is a prominent chemokine receptor on neutrophils. The neutrophilic inflammation in the lung diseases is found to be largely regulated through CXCR2 receptor. Antagonist of CXCR2 may reduce the neutrophil chemotaxis and alter the inflammatory response. Hence, in the present study, ligand based Comparative molecular field analysis (CoMFA) was performed on a series of CXCR2 antagonist named pyrimidine-5-carbonitrile-6-alkyl derivatives. The optimum CoMFA model was obtained with statistically significant cross-validated coefficients ($q^2$) of 0.568 and conventional coefficients ($r^2$) of 0.975. The contour maps suggest the important structural modifications and this study can be used to guide the development of potent CXCR2 antagonist.

• 통합자연과학논문집
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• 제8권3호
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• pp.214-220
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• 2015

Cancer has emerged as one of the leading cause of deaths worldwide. A three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was performed on a series of quinazoline-based anticancer agents. Purpose of the study is to understand the structural basis for their inhibitory activity. Comparative molecular field analysis (CoMFA) technique was employed to develop 3D-QSAR model. Ligand-based alignment scheme was used to generate a reliable CoMFA model. The model produced statistically significant results with a cross-validated correlation coefficient ($q^2$) of 0.589 and a non-cross-validated correlation coefficient ($r^2$) of 0.928. Model was further validated by bootstrapping and progressive scrambling analysis. This study could assist in the design of novel and more potent anticancer agents.

• 한국자기공명학회논문지
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• 제20권1호
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• pp.27-35
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• 2016

NMR spectrometer has been regarded as essential tool for structure elucidation in variable scientific field as like organic synthesis, natural product and macro protein research. Also NMR can be applied for defining dynamic behavior like ligand and receptor binding. One of advantage of research with NMR is that to be great confident to confirm structure and the measured sample could be recovered. Nevertheless NMR also has a weak points than other spectroscopic methods that require a lot of time for interpreting acquired spectrum and running time due to low sensitivity. For last two decade Bruker has developed hardware and software solution for overcome those weak points. In order to overcome low sensitivity Bruker introduced Cryo and Micro diameter probe head technology. And researcher can reduce the time for routine spectrum processing and interpretation works due to lots of introductions in software solutions for quantification, identification and statistics analysis. With four examples, this article describing those new hardware and software solutions in field of recent pharmaceutical research as follows. - New Horizons for NMR in the Biopharmaceutical Industry - The development and application of solid-state NMR spectroscopy (SSNMR) in pharmaceutical analysis - Assisted NMR Data Interpretation in Synthetic Chemistry - Complete Analysis of New Psychoactive Substances Using NMR.

• Applied Biological Chemistry
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• 제51권2호
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• pp.119-123
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• 2008

3-치환된 5,5'-diphenylimidazolidine-2,4-dione 유도체(1-22)들의 fatty acid amide hydrolase (FAAH) 저해활성에 관한 3차원적인 정량적 구조와 활성과의 관계(3D-QSARs)를 비교 분자장 분석(CoMFA)과 비교분자 유사성 지수분석(CoMFA) 방법으로 각각 검토하였다. CoMFA A1 모델과 CoMSIA 2F 모델 모두 상관성과 예측성이 양호하였다. 두 모델의 정보에 의한 등고도에 따라 설계된 X=I, Y=$N_2{^+}$-치환체(P1: $Pred.pI_{50}$=6.55)는 FAAH에 대하여 가장 높은 저해활성을 나타내었다.

• 통합자연과학논문집
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• 제4권4호
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• pp.266-272
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• 2011

Focal adhesion kinase (FAK) is a potential target for the treatment of primary cancers as well as prevention of tumor metastasis. To understand the structural and chemical features of FAK inhibitors, we report comparative molecular field analysis (CoMFA) for the series of 7H-pyrrolo(2,3-d)pyrimidines. The CoMFA models showed good correlation between the actual and predicted values for training set molecules. Our results indicated the ligand-based alignment has produced better statistical results for CoMFA ($q^2$ = 0.505, $r^2$ = 0.950). Both models were validated using test set compounds, and gave good predictive values of 0.537. The statistical parameters from the generated 3D-QSAR models were indicated that the data are well fitted and have high predictive ability. The contour map from 3D-QSAR models explains nicely the structure-activity relationships of FAK inhibitors and our results would give proper guidelines to further enhance the activity of novel inhibitors.

• 통합자연과학논문집
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• 제8권1호
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• pp.40-47
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• 2015

Glycogen synthase kinase 3 (GSK-3) is a serine/threonine protein kinase that has recently emerged as a promising target in drug discovery. It is involved in multiple cellular processes and associated with the pathogenesis of several diseases. A three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was performed on a series of GSK-3 inhibitors to understand the structural basis for inhibitory activity. Comparative molecular field analysis (CoMFA) method was used to derive 3D-QSAR models. A reliable CoMFA model was developed using ligand-based alignment scheme. The model produced statistically acceptable results with a cross-validated correlation coefficient ($q^2$) of 0.594 and a non-cross-validated correlation coefficient ($r^2$) of 0.943. Robustness of the model was checked by bootstrapping and progressive scrambling analysis. This study could assist in the design of novel compounds with enhanced GSK-3 inhibitory activity.

• Bulletin of the Korean Chemical Society
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• 제35권7호
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• pp.2065-2071
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• 2014

${\beta}$-Secretase (beta-amyloid converting enzyme 1 [BACE1]) is involved in the first and rate-limiting step of ${\beta}$-amyloid ($A{\beta}$) peptides production, which leads to the pathogenesis of Alzheimer's disease(AD). Therefore, inhibition of BACE1 activity has become an efficient approach for the treatment of AD. Ligand-based and docking-based 3D-quantitative structure-activity relationship (3D-QSAR) studies of acyl guanidine analogues were performed with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) to obtain insights for designing novel potent BACE1 inhibitors. We obtained highly reliable and predictive CoMSIA models with a cross-validated $q^2$ value of 0.725 and a predictive coefficient $r{^2}_{pred}$ value of 0.956. CoMSIA contour maps showed the structural requirements for potent activity. 3D-QSAR analysis suggested that an acyl guanidine and an amide group in the $R_6$ substituent would be important moieties for potent activity. Moreover, the introduction of small hydrophobic groups in the phenyl ring and hydrogen bond donor groups in 3,5-dichlorophenyl ring could increase biological activity.