当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Identification of N-ethylmethylamine as a novel scaffold for inhibitors of soluble epoxide hydrolase by crystallographic fragment screening.

Identification of N-ethylmethylamine as a novel scaffold for inhibitors of soluble epoxide hydrolase by crystallographic fragment screening.

Abstract：

:Soluble epoxide hydrolase (sEH) is a potential target for the treatment of inflammation and hypertension. X-ray crystallographic fragment screening was used to identify fragment hits and their binding modes. Eight fragment hits were identified via soaking of sEH crystals with fragment cocktails, and the co-crystal structures of these hits were determined via individual soaking. Based on the binding mode, N-ethylmethylamine was identified as a promising scaffold that forms hydrogen bonds with the catalytic residues of sEH, Asp335, Tyr383, and Tyr466. Compounds containing this scaffold were selected from an in-house chemical library and assayed. Although the starting fragment had a weak inhibitory activity (IC50: 800μM), we identified potent inhibitors including 2-({[2-(adamantan-1-yl)ethyl]amino}methyl)phenol exhibiting the highest inhibitory activity (IC50: 0.51μM). This corresponded to a more than 1500-fold increase in inhibitory activity compared to the starting fragment. Co-crystal structures of the hit compounds demonstrate that the binding of N-ethylmethylamine to catalytic residues is similar to that of the starting fragment. We therefore consider crystallographic fragment screening to be appropriate for the identification of weak but promising fragment hits.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Amano Y,Tanabe E,Yamaguchi T

doi

10.1016/j.bmc.2015.03.083

subject

Has Abstract

pub_date

2015-05-15 00:00:00

pages

2310-7

issue

10

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(15)00279-5

journal_volume

23

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY文献大全
  • The discovery of UK-369003, a novel PDE5 inhibitor with the potential for oral bioavailability and dose-proportional pharmacokinetics.

    abstract：:This paper describes our recent efforts to design and synthesise potent and selective PDE5 inhibitors and the use of in vitro predictors of clearance, absorption and permeability to maximise the potential for dose-proportional pharmacokinetics and good oral bioavailability in man. Optimisation of the preclinical profi...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.10.022

    authors： Rawson DJ,Ballard S,Barber C,Barker L,Beaumont K,Bunnage M,Cole S,Corless M,Denton S,Ellis D,Floc'h M,Foster L,Gosset J,Holmwood F,Lane C,Leahy D,Mathias J,Maw G,Million W,Poinsard C,Price J,Russel R,Street S

    更新日期：2012-01-01 00:00:00

  • Synthesis and biological evaluation of 1,4-dihydropyridine calcium channel modulators having a diazen-1-ium-1,2-diolate nitric oxide donor moiety for the potential treatment of congestive heart failure.

    abstract：:A group of racemic 4-aryl(heteroaryl)-1,4-dihydro-2,6-dimethyl-3-nitropyridines possessing nitric oxide donor O(2)-acetoxymethyl-1-(N-ethyl-N-methylamino, or 4-ethylpiperazin-1-yl)diazen-1-ium-1,2-diolate, C-5 ester substituents were synthesized by coupling the respective 4-aryl(heteroaryl)-1,4-dihydro-2,6-dimethyl-3-...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2004.05.008

    authors： Velázquez C,Knaus EE

    更新日期：2004-07-15 00:00:00

  • Synthesis and evaluation of symmetric acyclic nucleoside bisphosphonates as inhibitors of the Plasmodium falciparum, Plasmodium vivax and human 6-oxopurine phosphoribosyltransferases and the antimalarial activity of their prodrugs.

    abstract：:Two new series of symmetric acyclic nucleoside bisphosphonates (ANbPs) have been synthesised as potential inhibitors of the Plasmodium falciparum (Pf) and vivax (Pv) 6-oxopurine phosphoribosyltransferases. The structural variability between these symmetric ANbPs lies in the number of atoms in the two acyclic linkers c...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2017.05.048

    authors： Špaček P,Keough DT,Chavchich M,Dračínský M,Janeba Z,Naesens L,Edstein MD,Guddat LW,Hocková D

    更新日期：2017-08-01 00:00:00

  • Design, synthesis and biological evaluation of novel 3,4,5-trisubstituted aminothiophenes as inhibitors of p53-MDM2 interaction. Part 2.

    abstract：:Five series of novel 3,4,5-trisubstituted aminothiophene derivatives and analogs were designed and synthesized based on our previous studies. All target compounds were evaluated for their p53-MDM2 binding inhibitory activities and anti-proliferation activities against A549 and PC3 tumor cell lines. Twelve compounds di...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2013.03.070

    authors： Wang W,Lv D,Qiu N,Zhang L,Hu C,Hu Y

    更新日期：2013-06-01 00:00:00

  • Synthesis and pharmacological characterization of functionalized 2-pyridones structurally related to the cardiotonic agent milrinone.

    abstract：:A new class of cardiotonic agents characterized by a 2-pyridone structure was synthesized. Appropriate sym-2-dimethylaminomethylene-1,3-diones reacted with methylcyanoacetate to afford the desired compounds. These derivatives were evaluated for their ability in inducing cardiotonic response on guinea pig isolated myoc...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(03)00528-5

    authors： Fossa P,Menozzi G,Dorigo P,Floreani M,Mosti L

    更新日期：2003-11-03 00:00:00

  • Synthesis, nicotinic acetylcholine receptor binding, in vitro and in vivo pharmacology properties of 3'-(substituted pyridinyl)-deschloroepibatidine analogs.

    abstract：:Over the last several years we have synthesized and studied the in vitro and in vivo nAChR pharmacological properties of epibatidine (4) analogs. In this study we report the synthesis, nAChR in vitro and in vivo pharmacological properties of 3'-(substituted pyridinyl)-deschloroepibatidine analogs (5a-e and 6a-e). All ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2015.07.021

    authors： Ondachi PW,Ye Z,Castro AH,Luetje CW,Damaj MI,Mascarella SW,Navarro HA,Carroll FI

    更新日期：2015-09-01 00:00:00

  • Novel dimeric aryldiketo containing inhibitors of HIV-1 integrase: effects of the phenyl substituent and the linker orientation.

    abstract：:Aryl diketoacids (ADK) and their bioisosteres are among the most promising HIV-1 integrase (IN) inhibitors. Previously, we designed a series of ADK dimers as a new class of IN inhibitors that were hypothesized to target two divalent metal ions on the active site of IN. Herein we present a further structure-activity re...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.07.008

    authors： Zeng LF,Jiang XH,Sanchez T,Zhang HS,Dayam R,Neamati N,Long YQ

    更新日期：2008-08-15 00:00:00

  • New derivatives of silybin and 2,3-dehydrosilybin and their cytotoxic and P-glycoprotein modulatory activity.

    abstract：:Large series of O-alkyl derivatives (methyl and benzyl) of silybin and 2,3-dehydrosilybin was prepared. Selective alkylation of the silybin molecule was systematically investigated. For the first time we present here, for example, preparation of 19-nor-2,3-dehydrosilybin. All prepared silybin/2,3-dehydrosilybin deriva...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.01.035

    authors： Dzubák P,Hajdúch M,Gazák R,Svobodová A,Psotová J,Walterová D,Sedmera P,Kren V

    更新日期：2006-06-01 00:00:00

  • N-Methylthio beta-lactam antibacterials: effects of the C3/C4 ring substituents on anti-MRSA activity.

    abstract：:N-Thiolated beta-lactams are a new family of antibacterials that inhibit the growth of Staphylococcus bacteria. Unlike other beta-lactam drugs, these compounds retain their full antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) strains and operate through a different mode of action. The...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.08.011

    authors： Turos E,Coates C,Shim JY,Wang Y,Leslie JM,Long TE,Reddy GS,Ortiz A,Culbreath M,Dickey S,Lim DV,Alonso E,Gonzalez J

    更新日期：2005-12-01 00:00:00

  • Design, synthesis, conformational analysis, and biological studies of urotensin-II lactam analogues.

    abstract：:Human urotensin II (hU-II; H-Glu-Thr-Pro-Asp-cyclo[Cys-Phe-Trp-Lys-Tyr-Cys]-Val-OH) is a disulfide bridged undecapeptide recently identified as the ligand of an orphan G protein-coupled receptor. hU-II has been described as the most potent vasoconstrictor compound identified to date. With the aim of replacing the disu...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(02)00372-3

    authors： Grieco P,Carotenuto A,Patacchini R,Maggi CA,Novellino E,Rovero P

    更新日期：2002-12-01 00:00:00

  • Competitive antagonism of insect GABA receptors by 4-substituted 5-(4-piperidyl)-3-isothiazolols.

    abstract：:γ-Aminobutyric acid (GABA) receptors are important targets of parasiticides/insecticides. Several 4-substituted analogs of the partial GABAA receptor agonist 5-(4-piperidyl)-3-isothiazolol (Thio-4-PIOL) were synthesized and examined for their antagonism of insect GABA receptors expressed in Drosophila S2 cells or Xeno...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.07.021

    authors： Liu G,Furuta K,Nakajima H,Ozoe F,Ozoe Y

    更新日期：2014-09-01 00:00:00

  • Comparative reactivity analysis of small-molecule thiol surrogates.

    abstract：:Targeted covalent inhibitors represent an increasingly popular approach to modulate challenging drug targets. Since covalent and non-covalent interactions are both contributing to the affinity of these compounds, evaluation of their reactivity is a key-step to find feasible warheads. There are well-established HPLC- a...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2020.115357

    authors： Petri L,Ábrányi-Balogh P,Varga PR,Imre T,Keserű GM

    更新日期：2020-04-01 00:00:00

  • Evaluation of fosmidomycin analogs as inhibitors of the Synechocystis sp. PCC6803 1-deoxy-D-xylulose 5-phosphate reductoisomerase.

    abstract：:Analogs of the antibiotic fosmidomycin, an inhibitor of the methylerythritol phosphate pathway to isoprenoids, were synthesized and evaluated against the recombinant Synechocystis sp. PCC6803 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR). Fosfoxacin, the phosphate analog of fosmidomycin, and its acetyl congene...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.11.012

    authors： Woo YH,Fernandes RP,Proteau PJ

    更新日期：2006-04-01 00:00:00

  • Pharmacophore-based discovery of FXR-agonists. Part II: identification of bioactive triterpenes from Ganoderma lucidum.

    abstract：:The farnesoid X receptor (FXR) belonging to the metabolic subfamily of nuclear receptors is a ligand-induced transcriptional activator. Its central function is the physiological maintenance of bile acid homeostasis including the regulation of glucose and lipid metabolism. Accessible structural information about its li...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.09.039

    authors： Grienke U,Mihály-Bison J,Schuster D,Afonyushkin T,Binder M,Guan SH,Cheng CR,Wolber G,Stuppner H,Guo DA,Bochkov VN,Rollinger JM

    更新日期：2011-11-15 00:00:00

  • Muscarinic subtypes profile modulation within a series of new antagonists, bridged bicyclic derivatives of 2,2-diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine.

    abstract：:A set of new muscarinic antagonists, bridged bicyclic derivatives of 2,2-diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine (1), was synthesized and tested to evaluate their affinity and selectivity for M(1), M(2), M(3) and M(4) receptor subtypes. The conformational constraint of 1 in a bicyclic structure, and the varia...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(03)00431-0

    authors： Piergentili A,Gentili F,Ghelfi F,Marucci G,Pigini M,Quaglia W,Giannella M

    更新日期：2003-09-01 00:00:00

  • Design and synthesis of novel pyrimido[5,4-d]pyrimidine derivatives as GPR119 agonist for treatment of type 2 diabetes.

    abstract：:We described the discovery and optimization of a novel series of pyrimidopyrimidine derivatives as G-protein coupled receptor 119 (GPR119) agonists against type 2 diabetes. Most designed compounds displayed significant GPR119 agonistic activities. Optimized analogues 15a and 21e exhibited highly potent agonistic activ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2018.06.035

    authors： Fang Y,Xu J,Li Z,Yang Z,Xiong L,Jin Y,Wang Q,Xie S,Zhu W,Chang S

    更新日期：2018-08-07 00:00:00

  • Synthesis and antiviral evaluation of 2-amino-6-carbamoylpurine dioxolane nucleoside derivatives and their phosphoramidates prodrugs.

    abstract：:The synthesis of 9-(β-d-1,3-dioxolan-4-yl)2,6-diaminopurine nucleoside phosphoramidate prodrugs as well as various 2-amino-6-carbamoylpurine dioxolane derivatives and their phosphoramidates prodrugs is reported. Their ability to block HIV and HBV replication along with their cytotoxicity toward HepG2, human lymphocyte...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.10.003

    authors： Cho JH,Bondana L,Detorio MA,Montero C,Bassit LC,Amblard F,Coats SJ,Schinazi RF

    更新日期：2014-12-01 00:00:00

  • Synthesis, biological evaluation, and molecular docking of N-{3-[3-(9-methyl-9H-carbazol-3-yl)-acryloyl]-phenyl}-benzamide/amide derivatives as xanthine oxidase and tyrosinase inhibitors.

    abstract：:Claisen-Schmidt condensation of 3-formyl-9-methylcarbazole with various amides of 3-aminoacetophenone afforded N-{3-[3-(9-methyl-9H-carbazol-3-yl)-acryloyl]-phenyl}-benzamide/amide derivatives. All compounds were investigated for their in vitro xanthine oxidase (XO), tyrosinase and melanin production inhibitory activi...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.07.001

    authors： Bandgar BP,Adsul LK,Chavan HV,Shringare SN,Korbad BL,Jalde SS,Lonikar SV,Nile SH,Shirfule AL

    更新日期：2012-09-15 00:00:00

  • Bis(N-amidinohydrazones) and N-(amidino)-N'-aryl-bishydrazones: New classes of antibacterial/antifungal agents.

    abstract：:The emergence of multidrug-resistant bacterial and fungal strains poses a threat to human health that requires the design and synthesis of new classes of antimicrobial agents. We evaluated bis(N-amidinohydrazones) and N-(amidino)-N'-aryl-bishydrazones for their antibacterial and antifungal activities against panels of...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2016.10.009

    authors： Shrestha SK,Kril LM,Green KD,Kwiatkowski S,Sviripa VM,Nickell JR,Dwoskin LP,Watt DS,Garneau-Tsodikova S

    更新日期：2017-01-01 00:00:00

  • Efficient one-pot synthesis of biologically active polysubstituted aromatic amines.

    abstract：:An efficient and modular one-pot synthesis of polysubstituted aromatic amines by a mild reductive amination procedure is described and the biological potential of these nitrogen-centered compounds is demonstrated by growth inhibition of murine connective tissue cells and microscopy-based morphological studies. ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2007.08.048

    authors： Menche D,Arikan F,Li J,Rudolph S,Sasse F

    更新日期：2007-12-01 00:00:00

  • Identification of 2-mercaptohexanoic acids as dual inhibitors of 5-lipoxygenase and microsomal prostaglandin E₂ synthase-1.

    abstract：:5-Lipoxygenase (5-LO) and microsomal prostaglandin E₂ synthase (mPGES)-1 are key enzymes in the biosynthesis of leukotrienes and prostaglandin (PG)E₂, respectively, and are considered as valuable targets for the treatment of inflammatory diseases. Here, we present the identification of 2-mercaptohexanoic acid derivati...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.04.034

    authors： Greiner C,Zettl H,Koeberle A,Pergola C,Northoff H,Schubert-Zsilavecz M,Werz O

    更新日期：2011-06-01 00:00:00

  • Tryptophan-based fluorophores for studying protein conformational changes.

    abstract：:With the continuing interest in deciphering the interplay between protein function and conformational changes, small fluorescence probes will be especially useful for tracking changes in the crowded protein interior space. Presently, we describe the potential utility of six unnatural amino acid fluorescence donors str...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.09.015

    authors： Talukder P,Chen S,Liu CT,Baldwin EA,Benkovic SJ,Hecht SM

    更新日期：2014-11-01 00:00:00

  • RO4383596, an orally active KDR, FGFR, and PDGFR inhibitor: synthesis and biological evaluation.

    abstract：:(+/-)-1-(anti-3-Hydroxy-cyclopentyl)-3-(4-methoxy-phenyl)-7-phenylamino-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one (RO4383596) is a potent and selective inhibitor of the pro-angiogenic receptor tyrosine kinases KDR, FGFR, and PDGFR. This agent has an excellent pharmacokinetic profile and is highly efficacious in ro...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.05.012

    authors： McDermott LA,Simcox M,Higgins B,Nevins T,Kolinsky K,Smith M,Yang H,Li JK,Chen Y,Ke J,Mallalieu N,Egan T,Kolis S,Railkar A,Gerber L,Luk KC

    更新日期：2005-08-15 00:00:00

  • Luciferase-based HMG-CoA reductase degradation assay for activity and selectivity profiling of oxy(lano)sterols.

    abstract：:HMG-CoA reductase (HMGCR) is the rate-limiting enzyme in the cholesterol biosynthetic pathway, and is the target of cholesterol-lowering drugs, statins. Previous studies have demonstrated that the enzyme activity is regulated by sterol-induced degradation in addition to transcriptional regulation through sterol-regula...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2019.115298

    authors： Sagimori I,Yoshioka H,Hashimoto Y,Ohgane K

    更新日期：2020-02-01 00:00:00

  • Hydroxy- or methoxy-substituted benzaldoximes and benzaldehyde-O-alkyloximes as tyrosinase inhibitors.

    abstract：:Several benzaldoximes, benzaldehyde-O-ethyloximes, and acetophenonoximes were synthesized and evaluated as tyrosinase inhibitors by an assay based on tyrosinase catalyzed L-DOPA oxidation. Whereas benzaldoxime itself is only a weak inhibitor, its derivatives with one or two hydroxy or methoxy moieties in para and meta...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(01)00084-0

    authors： Ley JP,Bertram HJ

    更新日期：2001-07-01 00:00:00

  • Synthesis and insecticidal activity studies of novel phenylpyrazole derivatives containing arylimine or carbimidate moiety.

    abstract：:Phenylpyrazole insecticides are successful for crop protection and public hygiene by blocking gamma-aminobutyric acid (GABA)-gated chloride channels and glutamate-gated chloride (GluCl) channels. A series of novel phenylpyrazoles containing arylimine or 1-methoxyaryl groups were designed and synthesized. The addition ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2019.115092

    authors： Zhao Q,Sun R,Liu Y,Chen P,Li Y,Yang S,Wang Q

    更新日期：2019-11-01 00:00:00

  • The search for potent, small molecule NNRTIs: A review.

    abstract：:AIDS has become the leading pandemic disease, and is the cause of death worldwide. Presently, HAART treatment, a combination of reverse transcriptase (RT) and protease inhibitors is also unsuccessful due to the virus getting resistant to the drugs because of mutational changes. Two types of RT inhibitors exist namely ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.bmc.2009.06.060

    authors： Prajapati DG,Ramajayam R,Yadav MR,Giridhar R

    更新日期：2009-08-15 00:00:00

  • Synthesis and biological evaluation of novel pyrazolyl-2,4-thiazolidinediones as anti-inflammatory and neuroprotective agents.

    abstract：:Novel pyrazolyl-2,4-thiazolidinediones were prepared via the reaction of appropriate pyrazolecarboxaldehydes with 2,4-thiazolidinediones and substituted benzyl-2,4-thiazolidinediones. The resultant compounds were first evaluated for their anti-inflammatory and neuroprotective properties in vitro. The active compounds ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.01.021

    authors： Youssef AM,White MS,Villanueva EB,El-Ashmawy IM,Klegeris A

    更新日期：2010-03-01 00:00:00

  • Chemoenzymatic synthesis and lectin recognition of a selectively fluorinated glycoprotein.

    abstract：:A chemoenzymatic glycosylation remodeling method for the synthesis of selectively fluorinated glycoproteins is described. The method consists of chemical synthesis of a fluoroglycan oxazoline and its use as donor substrate for endoglycosidase (ENGase)-catalyzed transglycosylation to a GlcNAc-protein to form a homogene...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2013.03.009

    authors： Orwenyo J,Huang W,Wang LX

    更新日期：2013-08-15 00:00:00

  • Acetylcholinesterase inhibitors from the toadstool Cortinarius infractus.

    abstract：:Inhibition of acetylcholinesterase (AChE) and therefore prevention of acetylcholine degradation is one of the most accepted therapy opportunities for Alzheimer s disease (AD), today. Due to lack of selectivity of AChE inhibitor drugs on the market, AD-patients suffer from side effects like nausea or vomiting. In the p...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.01.074

    authors： Geissler T,Brandt W,Porzel A,Schlenzig D,Kehlen A,Wessjohann L,Arnold N

    更新日期：2010-03-15 00:00:00