当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Exploring the binding mode of semicarbazide-sensitive amine oxidase/VAP-1: identification of novel substrates with insulin-like activity.

Exploring the binding mode of semicarbazide-sensitive amine oxidase/VAP-1: identification of novel substrates with insulin-like activity.

Abstract：

:We previously reported that substrates of semicarbazide-sensitive amine oxidase in combination with low concentrations of vanadate exert potent insulin-like effects. Here we performed homology modeling of the catalytic domain of mouse SSAO/VAP-1 and searched through chemical databases to identify novel SSAO substrates. The modeling of the catalytic domain revealed that aromatic residues Tyr384, Phe389, and Tyr394 define a pocket of stable size that may participate in the binding of apolar substrates. We identified a number of amines as substrates of human, rat, and mouse SSAO. The compounds PD0119035, 2,3-dimethoxy-benzylamine, and C-naphthalen-1-yl-methylamine showed high affinity as substrates of rat SSAO. C-Naphthalen-1-yl-methylamine was the only substrate that showed high affinity for human SSAO. C-Naphthalen-1-yl-methylamine and 4-aminomethyl-benzenesulfonamide showed the highest capacity to stimulate glucose transport in isolated rat adipocytes. The impact of these findings on the development of new treatments for diabetes is discussed.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Marti L,Abella A,De La Cruz X,García-Vicente S,Unzeta M,Carpéné C,Palacín M,Testar X,Orozco M,Zorzano A

doi

10.1021/jm0499211

keywords:

subject

Has Abstract

pub_date

2004-09-23 00:00:00

pages

4865-74

issue

20

eissn

0022-2623

issn

1520-4804

journal_volume

47

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Theoretical model-based equations for the linear free energy relationships of the biological activity of ionizable substances. 1. Equilibrium-controlled potency.

    abstract：:Because of the ambiguities of how to treat ionization in empirical equations which relate biological activity to partition coefficient by use of a (log P)2 term, a theoretical approach to the problem is proposed. Based on a simplified view of assays of potency following in vitro or continuous infusion administration o...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00230a012

    authors： Martin YC,Hackbarth JJ

    更新日期：1976-08-01 00:00:00

  • N'-(arylsulfonyl)pyrazoline-1-carboxamidines as novel, neutral 5-hydroxytryptamine 6 receptor (5-HT₆R) antagonists with unique structural features.

    abstract：:The 5-HT(6) receptor (5-HT(6)R) has been in the spotlight for several years regarding CNS-related diseases. We set out to discover novel, neutral 5-HT(6)R antagonists to improve off-target selectivity compared to basic amine-containing scaffolds dominating the field. High-throughput screening identified the N'-(sulfon...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm200466r

    authors： van Loevezijn A,Venhorst J,Iwema Bakker WI,de Korte CG,de Looff W,Verhoog S,van Wees JW,van Hoeve M,van de Woestijne RP,van der Neut MA,Borst AJ,van Dongen MJ,de Bruin NM,Keizer HG,Kruse CG

    更新日期：2011-10-27 00:00:00

  • 2-Aryl-3-methyloctahydrophenanthrene-2,3,7-triols as potent dissociated glucocorticoid receptor agonists.

    abstract：:A significant improvement in agonist activity of the previously described 2-aryloctahydrophenanthrene-2,3,7-triol series of dissociated glucocorticoid receptor agonists (DAGRs) was achieved by modifying the substitution at C3 from (S)-3-hydroxy to (R)-3-hydroxy-3-methyl. The IC50 of the prototype 13 in the efficacy as...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm501601b

    authors： Chantigny YA,Murray JC,Kleinman EF,Robinson RP,Plotkin MA,Reese MR,Buckbinder L,McNiff PA,Millham ML,Schaefer JF,Abramov YA,Bordner J

    更新日期：2015-03-26 00:00:00

  • Design of HIV-1 protease inhibitors active on multidrug-resistant virus.

    abstract：:On the basis of structural data gathered during our ongoing HIV-1 protease inhibitors program, from which our clinical candidate TMC114 9 was selected, we have discovered new series of fused heteroaromatic sulfonamides. The further extension into the P2' region was aimed at identifying new classes of compounds with an...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm049454n

    authors： Surleraux DL,de Kock HA,Verschueren WG,Pille GM,Maes LJ,Peeters A,Vendeville S,De Meyer S,Azijn H,Pauwels R,de Bethune MP,King NM,Prabu-Jeyabalan M,Schiffer CA,Wigerinck PB

    更新日期：2005-03-24 00:00:00

  • Discovery of novel 2-aryl-4-benzoyl-imidazoles targeting the colchicines binding site in tubulin as potential anticancer agents.

    abstract：:A series of 2-aryl-4-benzoyl-imidazoles (ABI) was synthesized as a result of structural modifications based on the previous set of 2-aryl-imidazole-4-carboxylic amide (AICA) derivatives and 4-substituted methoxylbenzoyl-aryl-thiazoles (SMART). The average IC(50) of the most active compound (5da) was 15.7 nM. ABI analo...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm100884b

    authors： Chen J,Wang Z,Li CM,Lu Y,Vaddady PK,Meibohm B,Dalton JT,Miller DD,Li W

    更新日期：2010-10-28 00:00:00

  • How Frequently Are Pan-Assay Interference Compounds Active? Large-Scale Analysis of Screening Data Reveals Diverse Activity Profiles, Low Global Hit Frequency, and Many Consistently Inactive Compounds.

    abstract：:Undetected pan-assay interference compounds (PAINS) with false-positive activities in assays often propagate through medicinal chemistry programs and compromise their outcomes. Although a large number of PAINS have been classified, often on the basis of individual studies or chemical experience, little has been done s...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.7b00154

    authors： Jasial S,Hu Y,Bajorath J

    更新日期：2017-05-11 00:00:00

  • 6- and 7-substituted 2-[2'-(dimethylamino)ethyl]-1,2-dihydro-3H-dibenz[de,h] isoquinoline-1,3-diones: synthesis, nucleophilic displacements, antitumor activity, and quantitative structure-activity relationships.

    abstract：:New 2-[2'-(dimethylamino)ethyl]-3H-dibenz[de,h]isoquinoline-1,3-diones with substituents at the 6- and 7-positions were prepared. Nucleophilic aromatic displacement was a key reaction in the syntheses. Ten of the new compounds were more potent than the unsubstituted compound, azonafide, in a panel of tumor cells inclu...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm950742g

    authors： Sami SM,Dorr RT,Sòlyom AM,Alberts DS,Iyengar BS,Remers WA

    更新日期：1996-04-12 00:00:00

  • Structure-Based Design of 5-Methylpyrimidopyridone Derivatives as New Wild-Type Sparing Inhibitors of the Epidermal Growth Factor Receptor Triple Mutant (EGFRL858R/T790M/C797S).

    abstract：:Tertiary EGFRC797S mutation induced resistance against osimertinib (1) is an emerging "unmet clinical need" for non-small-cell lung cancer (NSCLC) patients. A series of 5-methylpyrimidopyridone derivatives were designed and synthesized as new selective EGFRL858R/T790M/C797S inhibitors. A representative compound, 8r-B,...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b00576

    authors： Shen J,Zhang T,Zhu SJ,Sun M,Tong L,Lai M,Zhang R,Xu W,Wu R,Ding J,Yun CH,Xie H,Lu X,Ding K

    更新日期：2019-08-08 00:00:00

  • Design, synthesis, and biochemical evaluation of phosphonate and phosphonamidate analogs of glutathionylspermidine as inhibitors of glutathionylspermidine synthetase/amidase from Escherichia coli.

    abstract：:Three phosphapeptides designed to mimic two distinct tetrahedral intermediates formed during either the synthesis or hydrolysis of glutathionylspermidine (Gsp) were synthesized and evaluated as inhibitors of the bifunctional enzyme Gsp synthetase/amidase. While the polyamine-containing phosphapeptides were determined ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm970414b

    authors： Chen S,Lin CH,Kwon DS,Walsh CT,Coward JK

    更新日期：1997-11-07 00:00:00

  • Imidazolopiperazines: lead optimization of the second-generation antimalarial agents.

    abstract：:On the basis of the initial success of optimization of a novel series of imidazolopiperazines, a second generation of compounds involving changes in the core piperazine ring was synthesized to improve antimalarial properties. These changes were carried out to further improve the potency and metabolic stability of the ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm300041e

    authors： Nagle A,Wu T,Kuhen K,Gagaring K,Borboa R,Francek C,Chen Z,Plouffe D,Lin X,Caldwell C,Ek J,Skolnik S,Liu F,Wang J,Chang J,Li C,Liu B,Hollenbeck T,Tuntland T,Isbell J,Chuan T,Alper PB,Fischli C,Brun R,Lakshm

    更新日期：2012-05-10 00:00:00

  • Intramolecular hydrogen bonding in medicinal chemistry.

    abstract：:The formation of intramolecular hydrogen bonds has a very pronounced effect on molecular structure and properties. We study both aspects in detail with the aim of enabling a more rational use of this class of interactions in medicinal chemistry. On the basis of exhaustive searches in crystal structure databases, we de...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm100087s

    authors： Kuhn B,Mohr P,Stahl M

    更新日期：2010-03-25 00:00:00

  • Development of Orally Efficacious Allosteric Inhibitors of TNFα via Fragment-Based Drug Design.

    abstract：:Tumor necrosis factor α (TNFα) is a soluble cytokine that is directly involved in systemic inflammation through the regulation of the intracellular NF-κB and MAPK signaling pathways. The development of biologic drugs that inhibit TNFα has led to improved clinical outcomes for patients with rheumatoid arthritis and oth...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.0c01280

    authors： Dietrich JD,Longenecker KL,Wilson NS,Goess C,Panchal SC,Swann SL,Petros AM,Hobson AD,Ihle D,Song D,Richardson P,Comess KM,Cox PB,Dombrowski A,Sarris K,Donnelly-Roberts DL,Duignan DB,Gomtsyan A,Jung P,Krueger AC,Ma

    更新日期：2021-01-14 00:00:00

  • 3 alpha-Hydroxy-3 beta-(phenylethynyl)-5 beta-pregnan-20-ones: synthesis and pharmacological activity of neuroactive steroids with high affinity for GABAA receptors.

    abstract：:Neuroactive steroids that allosterically modulate GABAA receptors have potential uses as anticonvulsants, anxiolytics, and sedative-hypnotic agents. Recently, a series of pregnanes substituted with simple alkyl groups at the 3 beta-position were synthesized and found to be active in vitro. The present report describes...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm9605344

    authors： Upasani RB,Yang KC,Acosta-Burruel M,Konkoy CS,McLellan JA,Woodward RM,Lan NC,Carter RB,Hawkinson JE

    更新日期：1997-01-03 00:00:00

  • Synthesis and in vivo antitumor activity of 2-amino-9H-purine-6-sulfenamide, -sulfinamide, and -sulfonamide and related purine ribonucleosides.

    abstract：:A number of 6-sulfenamide, 6-sulfinamide, and 6-sulfonamide derivatives of 2-aminopurine and certain related purine ribonucleosides have been synthesized and evaluated for antileukemic activity in mice. Amination of 6-mercaptopurine ribonucleoside (7a) and 6-thioguanosine (7b) with chloramine solution gave 9-beta-D-ri...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00163a020

    authors： Revankar GR,Hanna NB,Imamura N,Lewis AF,Larson SB,Finch RA,Avery TL,Robins RK

    更新日期：1990-01-01 00:00:00

  • Synthesis and biological evaluation of a novel series of furans: ligands selective for estrogen receptor alpha.

    abstract：:A variety of nonsteroidal systems can function as ligands for the estrogen receptor (ER), in some cases showing selectivity for one of the two ER subtypes, ER alpha or ER beta. We have prepared a series of heterocycle-based (furans, thiophenes, and pyrroles) ligands for the estrogen receptor and assessed their behavio...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm010211u

    authors： Mortensen DS,Rodriguez AL,Carlson KE,Sun J,Katzenellenbogen BS,Katzenellenbogen JA

    更新日期：2001-11-08 00:00:00

  • Design, Multicomponent Synthesis, and Anticancer Activity of a Focused Histone Deacetylase (HDAC) Inhibitor Library with Peptoid-Based Cap Groups.

    abstract：:In this work, we report the multicomponent synthesis of a focused histone deacetylase (HDAC) inhibitor library with peptoid-based cap groups and different zinc-binding groups. All synthesized compounds were tested in a cellular HDAC inhibition assay and an MTT assay for cytotoxicity. On the basis of their noteworthy a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.7b00197

    authors： Krieger V,Hamacher A,Gertzen CGW,Senger J,Zwinderman MRH,Marek M,Romier C,Dekker FJ,Kurz T,Jung M,Gohlke H,Kassack MU,Hansen FK

    更新日期：2017-07-13 00:00:00

  • Stereochemical requirements for cannabinoid activity.

    abstract：:Several pairs of cannabinoid isomers were synthesized and tested for psychotropic activity in rhesus monkeys. Two regularities were observed: (a) In the absence of the other substituents, the equatorial stereochemistry of the substituent at C-1 determines activity. (b) Two groups of THC-type cannabinoids which differ ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00184a002

    authors： Mechoulam R,Lander N,Varkony TH,Kimmel I,Becker O,Ben-Zvi Z,Edery H,Porath G

    更新日期：1980-10-01 00:00:00

  • Discovery of Potent and Orally Bioavailable GPR40 Full Agonists Bearing Thiophen-2-ylpropanoic Acid Scaffold.

    abstract：:The free fatty acid receptor GPR40 is predominantly expressed in pancreatic β-cells and enhances insulin secretion in a glucose dependent manner. Therefore, GPR40 agonists are possible novel insulin secretagogues with reduced or no risk of hypoglycemia for the treatment of type 2 diabetes mellitus (T2DM). Chemically a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b01357

    authors： Li H,Huang Q,Chen C,Xu B,Wang HY,Long YQ

    更新日期：2017-04-13 00:00:00

  • 5,5'-substituted indirubin-3'-oxime derivatives as potent cyclin-dependent kinase inhibitors with anticancer activity.

    abstract：:To enhance the ability of indirubin derivatives to inhibit CDK2/cyclin E, a target of anticancer agents, we designed and synthesized a new series of indirubin-3'-oxime derivatives with combined substitutions at the 5 and 5' positions. A molecular docking study predicted the binding of derivatives with OH or halogen su...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm100080z

    authors： Choi SJ,Lee JE,Jeong SY,Im I,Lee SD,Lee EJ,Lee SK,Kwon SM,Ahn SG,Yoon JH,Han SY,Kim JI,Kim YC

    更新日期：2010-05-13 00:00:00

  • Novel synthesis, cytotoxic evaluation, and structure-activity relationship studies of a series of alpha-alkylidene-gamma-lactones and lactams.

    abstract：:5-Alkyl- and 5-arylalkyl-3-methylenedihydrofuran-2-ones 13a-e, 3-alkylidenedihydrofuran-2-ones 18a-c, and 3-methylenepyrrolidin-2-ones 16a-e were synthesized utilizing ethyl 2-diethoxyphosphoryl-4-nitroalkanoates 9a-e as common intermediates. All obtained compounds were tested against L-1210, HL-60, and NALM-6 leukemi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm048970a

    authors： Janecki T,Błaszczyk E,Studzian K,Janecka A,Krajewska U,Rózalski M

    更新日期：2005-05-19 00:00:00

  • 5,6-Cis-penems: broad-spectrum anti-methicillin-resistant Staphylococcus aureus beta-lactam antibiotics.

    abstract：:5,6-cis-Penem derivatives have been synthesized and evaluated as anti-MRSA antibiotics. The cis-penems 5 and 6 showed potent activities against not only MRSA but also a wide variety of bacteria including beta-lactamase-producing microorganisms. These compounds were designed to have high affinity to the penicillin-bind...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm9703348

    authors： Ishiguro M,Tanaka R,Namikawa K,Nasu T,Inoue H,Nakatsuka T,Oyama Y,Imajo S

    更新日期：1997-07-04 00:00:00

  • Dicarba analogues of the cyclic enkephalin peptides H-Tyr-c[D-Cys-Gly-Phe-D(or L)-Cys]NH(2) retain high opioid activity.

    abstract：:Dicarba analogues of the cyclic opioid peptides H-Tyr-c[d-Cys-Gly-Phe-d(or l)-Cys]NH2 were synthesized on solid phase by substituting allylglycines for the cysteines and cyclization by ring-closing metathesis between the side chains of the allylglycine residues. Mixtures of cis and trans isomers of the resulting olefi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm061294n

    authors： Berezowska I,Chung NN,Lemieux C,Wilkes BC,Schiller PW

    更新日期：2007-03-22 00:00:00

  • Synthesis and in vitro evaluation of N-substituted maleimide derivatives as selective monoglyceride lipase inhibitors.

    abstract：:The endocannabinoid 2-arachidonoylglycerol (2-AG) plays a major role in many physiological processes, and its action is quickly terminated via enzymatic hydrolysis catalyzed by monoglyceride lipase (MGL). Regulating its endogenous level could offer therapeutic opportunities; however, few selective MGL inhibitors have ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm900461w

    authors： Matuszak N,Muccioli GG,Labar G,Lambert DM

    更新日期：2009-12-10 00:00:00

  • Dermorphin and deltorphin glycosylated analogues: synthesis and antinociceptive activity after systemic administration.

    abstract：:In the present paper we describe the synthesis of some dermorphin and deltorphin analogues beta-O- and alpha-C-glycosylated on the C-terminal amino acid residue and report their opioid receptor affinity and selectivity as well as their analgesic potency after subcutaneous injection in mice. ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm9810699

    authors： Negri L,Lattanzi R,Tabacco F,Orrù L,Severini C,Scolaro B,Rocchi R

    更新日期：1999-02-11 00:00:00

  • Synthesis and biological activity of potential antimetabolites of L-fucose.

    abstract：:6-Substituted 6-deoxy-L-galactose (L-fucose) derivatives were synthesized as potential antimetabolites of L-fucose. The cytotoxic effects of these compounds were evaluated on P388 leukemia cells in culture. The L-fucose analogues which showed the most potent growth inhibition were the sulfonyl ester, bromo, and iodo d...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00194a017

    authors： May JA Jr,Sartorelli AC

    更新日期：1979-08-01 00:00:00

  • beta-Carbolines as benzodiazepine receptor ligands. 1. Synthesis and benzodiazepine receptor interaction of esters of beta-carboline-3-carboxylic acid.

    abstract：:Several esters of beta-carboline-3-carboxylic acid were synthesized and tested in respect to their affinity for the benzodiazepine receptor in bovine cortex membranes. Out of these derivatives, the methyl, ethyl, and n-propyl ester were clearly the most potent, while the n-butyl, benzyl, and 3-pyridylmethyl ester were...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00358a008

    authors： Lippke KP,Schunack WG,Wenning W,Müller WE

    更新日期：1983-04-01 00:00:00

  • Cholecystokinin antagonists: (R)-tryptophan-based hybrid antagonists of high affinity and selectivity for CCK-A receptors.

    abstract：:The intriguing structural similarities of glutamic acid based cholecystokinin (CCK) antagonists (A-64718 and A-65186) and the benzodiazepine CCK antagonist MK-329 (L-364,718) have been reported. Efforts to include the weak CCK antagonist benzotript into this construct utilizing a similar approach have resulted in a no...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00116a002

    authors： Kerwin JF Jr,Wagenaar F,Kopecka H,Lin CW,Miller T,Witte D,Stashko M,Nadzan AM

    更新日期：1991-12-01 00:00:00

  • A Smart Europium-Ruthenium Complex as Anticancer Prodrug: Controllable Drug Release and Real-Time Monitoring under Different Light Excitations.

    abstract：:A unique, dual-function, photoactivatable anticancer prodrug, RuEuL, has been tailored that features a ruthenium(II) complex linked to a cyclen-europium chelate via a π-conjugated bridge. Under irradiation at 488 nm, the dark-inactive prodrug undergoes photodissociation, releasing the DNA-damaging ruthenium species. U...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.7b01162

    authors： Li H,Xie C,Lan R,Zha S,Chan CF,Wong WY,Ho KL,Chan BD,Luo Y,Zhang JX,Law GL,Tai WCS,Bünzli JG,Wong KL

    更新日期：2017-11-09 00:00:00

  • Synthesis, characterization, and anti-human immunodeficiency virus activity of water-soluble salts of polyoxotungstate anions with covalently attached organic groups.

    abstract：:The cesium and tetramethylammonium (TMA) salts of polyoxotungstate anions with covalently attached organosilyl groups of formula [(RSi)2O]SiW11O39(4-), where R = CH2CH2COCH3, (CH2)3CN, and CH==CH2 (1-R, cesium salt, unless otherwise noted) have been prepared, purified, and spectroscopically characterized. The water so...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00085a008

    authors： Weeks MS,Hill CL,Schinazi RF

    更新日期：1992-04-03 00:00:00

  • Development of novel potent orally bioavailable oseltamivir derivatives active against resistant influenza A.

    abstract：:With the emergence of oseltamivir-resistant influenza viruses and in view of a highly pathogenic flu pandemic, it is important to develop new anti-influenza agents. Here, the development of neuraminidase (NA) inhibitors that were designed to overcome resistance mechanisms along with unfavorable pharmacokinetic (PK) pr...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm401492x

    authors： Schade D,Kotthaus J,Riebling L,Kotthaus J,Müller-Fielitz H,Raasch W,Koch O,Seidel N,Schmidtke M,Clement B

    更新日期：2014-02-13 00:00:00