排序方式: 共有13条查询结果,搜索用时 31 毫秒
1.
Warshakoon NC Wu S Boyer A Kawamoto R Sheville J Renock S Xu K Pokross M Zhou S Winter C Walter R Mekel M Evdokimov AG 《Bioorganic & medicinal chemistry letters》2006,16(21):5517-5522
A new series of potent 8-hydroxyquinolines was designed based on the newly resolved X-ray crystal structure of EGLN-1. Both alkyl and aryl 8-hydroxyquinoline-7-carboxyamides were good HIF-1alpha prolyl hydroxylase (EGLN) inhibitors. In subsequent VEGF induction assays, these exhibited potent VEGF activity. In addition, this class of compounds did show the ability to stabilize HIF-1alpha. 相似文献
2.
Warshakoon NC Sheville J Bhatt RT Ji W Mendez-Andino JL Meyers KM Kim N Wos JA Mitchell C Paris JL Pinney BB Reizes O Hu XE 《Bioorganic & medicinal chemistry letters》2006,16(19):5207-5211
A novel series of substituted quinoline analogs were designed and synthesized as potent and selective melanin concentrating hormone (MCH) antagonists. These analogs show potent (nM) activity (12a-k) with a moderate selectivity. Conversely, the conformationally constrained thienopyrimidinone analogs (18a-g) showed improved activity in MCH-1R and selectivity over 5HT2C. 相似文献
3.
P. K. Dileepa Chathuranga D. M. R. E. A. Dissanayake Namal Priyantha Sithy S. Iqbal 《Bioremediation Journal》2014,18(3):192-203
The potential of nonliving biomass of Hydrilla verticillata to adsorb Pb(II) from an aqueous solution containing very low concentrations of Pb(II) was determined in this study. Effects of shaking time, contact time, biosorbent dosage, pH of the medium, and initial Pb(II) concentration on metal-biosorbent interactions were studied through batch adsorption experiments. Maximum Pb(II) removal was obtained after 2 h of shaking. Adsorption capacity at the equilibrium increased with increasing initial Pb(II) concentration, whereas it decreased with increasing biosorbent dosage. The optimum pH of the biosorption was 4.0. Surface titrations showed that the surface of the biosorbent was positively charged at low pH and negatively charged at pH higher than 3.6. Fourier transform infrared (FT-IR) spectra of the biosorbent confirmed the involvement of hydroxyl and C?O of acylamide functional groups on the biosorbent surface in the Pb(II) binding process. Kinetic and equilibrium data showed that the adsorption process followed the pseudo-second-order kinetic model and both Langmuir and Freundlich isothermal models. The mean adsorption energy showed that the adsorption of Pb(II) was physical in nature. The monolayer adsorption capacity of Pb(II) was 125 mg g?1. The desorption of Pb(II) from the biosorbent by selected desorbing solutions were HNO3 > Na2CO3 > NaOH > NaNO3. 相似文献
4.
Kim N Meyers KM Mendez-Andino JL Warshakoon NC Ji W Wos JA Colson A Mitchell MC Davis JR Pinney BB Reizes O Hu XE 《Bioorganic & medicinal chemistry letters》2006,16(20):5445-5450
A substituted 4-aminopiperidine was identified as showing activity in an MCH assay from an HTS effort. Subsequent structural modification of the scaffold led to the identification of a number of active MCH antagonists. 3,5-Dimethoxy-N-(1-(naphthalen-2-ylmethyl)piperidin-4-yl)benzamide (5c) was among those with the highest binding affinity to the MCH receptor (K(i)=27nM), when variations were made at benzoyl and naphthylmethyl substitution sites from the initial HTS hit. Further optimization via piperidine ring contraction resulted in enhanced MCH activity in a 3-aminopyrrolidine series, where (R)-3,5-dimethoxy-N-(1-(naphthalen-2-ylmethyl)-pyrrolidin-3-yl)benzamide (10i) was found to be an excellent MCH antagonist (K(i)=7nM). 相似文献
5.
Aonuma H Suzuki M Iseki H Perera N Nelson B Igarashi I Yagi T Kanuka H Fukumoto S 《Biochemical and biophysical research communications》2008,376(4):671-676
With an aim to develop a quick and simple method to survey pathogen-transmitting vectors, LAMP (loop-mediated isothermal amplification) was applied to the identification of Plasmodium-carrying mosquitoes, specifically a Plasmodium-transmitting experimental model using rodent malaria parasite (Plasmodium berghei) and anopheline mosquitoes (Anopheles stephensi). The detection sensitivity limit of the LAMP reaction amplifying the SPECT2 gene was determined to be 1 × 102 purified Plasmodium parasites, estimated to be sufficient for reliable identification of infectious mosquitoes. The robustness of the LAMP reaction was revealed by its ability to detect both Plasmodium oocysts and sporozoites from an “all-in-one” template using whole mosquito bodies. Moreover, LAMP successfully identified an infectious mosquito carrying just a single oocyst in its midgut, a level that can be easily overlooked in conventional microscopic analysis. These observations suggest that LAMP is more reliable and useful for routine diagnosis of vector mosquitoes in regions where vector-borne diseases such as malaria are endemic. 相似文献
6.
Tong Li Prasad KDV Yarlagadda Adekunle Oloyede Namal Thibbotuwawa YuanTong Gu 《Molecular & cellular biomechanics : MCB》2015,12(1):17-35
Living cells are the functional unit of organs that controls reactions to their exterior. However, the mechanics of living cells can be difficult to characterize due to the crypticity of their microscale structures and associated dynamic cellular processes. Fortunately, multiscale modelling provides a powerful simulation tool that can be used to study the mechanical properties of these soft hierarchical, biological systems. This paper reviews recent developments in hierarchical multiscale modeling technique that aimed at understanding cytoskeleton mechanics. Discussions are expanded with respects to cytoskeletal components including: intermediate filaments, microtubules and microfilament networks. The mechanical performance of difference cytoskeleton components are discussed with respect to their structural and material properties. Explicit granular simulation methods are adopted with different coarse-grained strategies for these cytoskeleton components and the simulation details are introduced in this review. 相似文献
7.
Design and synthesis of substituted pyridine derivatives as HIF-1alpha prolyl hydroxylase inhibitors
Warshakoon NC Wu S Boyer A Kawamoto R Sheville J Bhatt RT Renock S Xu K Pokross M Zhou S Walter R Mekel M Evdokimov AG East S 《Bioorganic & medicinal chemistry letters》2006,16(21):5616-5620
Structure-guided de novo drug design led to the identification of a novel series of substituted pyridine derivatives as HIF-1alpha prolyl hydroxylase inhibitors. Pyridine carboxyamide derivatives bearing a substituted aryl group at the 5-position of the pyridine ring show appreciable activity, while constraining the side chain by placing a pyrazole carboxylic acid generated a potent lead series with consistent activity against EGLN-1. 相似文献
8.
Warshakoon NC Wu S Boyer A Kawamoto R Sheville J Renock S Xu K Pokross M Evdokimov AG Walter R Mekel M 《Bioorganic & medicinal chemistry letters》2006,16(21):5598-5601
Utilizing modeling information from a recently resolved structure of human HIF-1alpha prolyl hydroxylase (EGLN1) and structure-based design, a novel series of imidazo[1,2-a]pyridine derivatives was prepared. The activity of these compounds was determined in a human EGLN1 assay and a limited SAR was developed. 相似文献
9.
Warshakoon NC Wu S Boyer A Kawamoto R Renock S Xu K Pokross M Evdokimov AG Zhou S Winter C Walter R Mekel M 《Bioorganic & medicinal chemistry letters》2006,16(21):5687-5690
Recently resolved X-ray crystal structure of HIF-1alpha prolyl hydroxylase was used to design and develop a novel series of pyrazolopyridines as potent HIF-1alpha prolyl hydroxylase inhibitors. The activity of these compounds was determined in a human EGLN-1 assay. Structure-based design aided in optimizing the potency of the initial lead (2, IC(50) of 11 microM) to a potent (11l, 190 nM) EGLN-1 inhibitor. Several of these analogs were potent VEGF inducers in a cell-based assay. These pyrazolopyridines were also effective in stabilizing HIF-1alpha. 相似文献
10.
Meyers KM Méndez-Andino JL Colson AO Warshakoon NC Wos JA Mitchell MC Hodge KM Howard JM Ackley DC Holbert JK Mittelstadt SW Dowty ME Obringer CM Reizes O Hu XE 《Bioorganic & medicinal chemistry letters》2007,17(3):819-822
A direct correlation between hERG binding and QTc prolongation was established for a series of aminomethyl tetrahydronaphthalene ketopiperazine MCH-R1 antagonists. Compounds within this class with greater selectivity over hERG were developed. Compound 4h proved to have the best profile, with MCH-R1 Ki = 16 nm and hERG IC50 = 25 microM. 相似文献