当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > 3-Amino-2-hydroxy-propionaldehyde and 3-amino-1-hydroxy-propan-2-one derivatives: new classes of aminopeptidase inhibitors.

3-Amino-2-hydroxy-propionaldehyde and 3-amino-1-hydroxy-propan-2-one derivatives: new classes of aminopeptidase inhibitors.

Abstract：

:3-Amino-2-hydroxy-propionaldehydes [H2NCH(R)CHOHCHO with R = H, i-Bu, CH2Ph] were designed as metallo-aminopeptidase inhibitors based on the metal active site chelation concept. These compounds were found to be micromolar inhibitors of aminopeptidase-M (AP-M, EC 3.4.11.2) with potencies similar to bestatin (Ki = 3.5 microM). Notably, compound 5a (R = H) is a selective inhibitor of AP-M (Ki = 7 microM) with respect to cytosolic leucine aminopeptidase (LAPc, EC 3.4.11.1) (Ki = 385 microM). However, due to their easy oligomerization, these compounds are low practical value. In contrast, the corresponding isomeric 3-amino-1-hydroxy-propan-2-one derivatives [H2NCH(R)COCH2OH with R = H, i-Bu, CH2Ph, i-Pr, CH2Biph] are well defined structures. These hydroxymethylketones also exhibit micromolar affinities on AP-M. Compound 6c (R = CH2Ph) was the most potent (Ki = 1 microM). Selectivity studies of 6a (R = H) and 6b (R=i-Bu) show a preference for AP-M. Compound 6a is moderately active on AP-M (Ki = 25 microM) and inactive on LAPc. This new class of inhibitors is proposed to bind as bidentates, analogous to hydroxamates.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Tarnus C,Rémy JM,d'Orchymont H

doi

10.1016/0968-0896(96)00115-0

subject

Has Abstract

pub_date

1996-08-01 00:00:00

pages

1287-97

issue

8

eissn

0968-0896

issn

1464-3391

pii

0968089696001150

journal_volume

4

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY文献大全
  • Synthesis and preliminary biological evaluation of O6-[4-(2-[18F]fluoroethoxymethyl)benzyl]guanine as a novel potential PET probe for the DNA repair protein O6-alkylguanine-DNA alkyltransferase in cancer chemotherapy.

    abstract：:A novel fluorine-18-labeled O6-benzylguanine (O6-BG) derivative, O6-[4-(2-[18F]fluoroethoxymethyl)benzyl]guanine (O6-[18F]FEMBG, [18F]1), has been synthesized for evaluation as a potential positron emission tomography (PET) probe for the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) in cancer chemother...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.05.061

    authors： Wang JQ,Kreklau EL,Bailey BJ,Erickson LC,Zheng QH

    更新日期：2005-10-15 00:00:00

  • A para-nitrophenol phosphonate probe labels distinct serine hydrolases of Arabidopsis.

    abstract：:Activity-based protein profiling represents a powerful methodology to probe the activity state of enzymes under various physiological conditions. Here we present the development of a para-nitrophenol phosphonate activity-based probe with structural similarities to the potent agrochemical paraoxon. We demonstrate that ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.06.041

    authors： Nickel S,Kaschani F,Colby T,van der Hoorn RA,Kaiser M

    更新日期：2012-01-15 00:00:00

  • Synthesis and antimicrobial evaluation of some new substituted purine derivatives.

    abstract：:A series of 8,9-disubstituted adenines (4, 5, 8), 6-substituted aminopurines (10-13) and 9-(p-fluorobenzyl/cyclopentyl)-6-substituted aminopurines (16, 17, 19-30) have been prepared and the antimicrobial activities of these compounds against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA, standard and cl...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.12.050

    authors： Tunçbilek M,Ateş-Alagöz Z,Altanlar N,Karayel A,Ozbey S

    更新日期：2009-02-15 00:00:00

  • Benzimidazole inhibitors from the Niclosamide chemotype inhibit Wnt/β-catenin signaling with selectivity over effects on ATP homeostasis.

    abstract：:The Wnt signaling pathway plays a key role in organ and tissue homeostasis, and when dysregulated, can become a major underlying mechanism of disease, particularly cancer. We reported previously that the anthelmintic drug Niclosamide inhibits Wnt/β-catenin signaling and suppresses colon cancer cell growth in vitro and...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2017.01.046

    authors： Mook RA Jr,Ren XR,Wang J,Piao H,Barak LS,Kim Lyerly H,Chen W

    更新日期：2017-03-15 00:00:00

  • The influence of hydroquinone on tyrosinase kinetics.

    abstract：:In vitro studies, using combined spectrophotometry and oximetry together with hplc/ms examination of the products of tyrosinase action demonstrate that hydroquinone is not a primary substrate for the enzyme but is vicariously oxidised by a redox exchange mechanism in the presence of either catechol, L-3,4-dihydroxyphe...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.05.041

    authors： Stratford MR,Ramsden CA,Riley PA

    更新日期：2012-07-15 00:00:00

  • Total syntheses of three copper (II) tetracarboranylphenylporphyrins containing 40 or 80 boron atoms and their biological properties in EMT-6 tumor-bearing mice.

    abstract：:Three carboranyltetraphenylporphyrins containing 40 or 80 boron atoms were synthesized and evaluated for their biodistribution and toxicity in EMT-6 tumor-bearing mice. Copper (II) meso-5,10,15,20-tetrakis[3-methoxy-4-(o-carboranylmethoxy)phenyl]porphyrin, 6, and copper (II) meso-5,10,15,20-tetrakis[3-hydroxy-4-(o-car...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.04.010

    authors： Wu H,Micca PL,Makar MS,Miura M

    更新日期：2006-08-01 00:00:00

  • A novel 3-arylethynyl-substituted pyrido[2,3,-b]pyrazine derivatives and pharmacophore model as Wnt2/β-catenin pathway inhibitors in non-small-cell lung cancer cell lines.

    abstract：:We developed Wnt/β-catenin inhibitors by identifying 13 number of 3-arylethynyl-substituted pyrido[2,3,-b]pyrazine derivatives that were able to inhibit the Wnt/β-catenin signal pathway and cancer cell proliferation. In the optimization process, a series of 2,3,6-trisubstituted pyrido[2,3,-b]pyrazine core skeletons sh...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.07.028

    authors： Gong YD,Dong MS,Lee SB,Kim N,Bae MS,Kang NS

    更新日期：2011-09-15 00:00:00

  • Piperazines as nootropic agents: New derivatives of the potent cognition-enhancer DM235 carrying hydrophilic substituents.

    abstract：:The piperazine ring of the potent nootropic drug DM235 has been decorated with H-bond donor and acceptor groups (CH2OH, CH2OMe, CH2OCOMe, COOEt); the aim was to insert new functional groups, suitable for further chemical manipulation. The influence of these modifications on nootropic activity was assessed by means of ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2017.02.019

    authors： Martino MV,Guandalini L,Di Cesare Mannelli L,Menicatti M,Bartolucci G,Dei S,Manetti D,Teodori E,Ghelardini C,Romanelli MN

    更新日期：2017-03-15 00:00:00

  • Tannic acid inhibited norovirus binding to HBGA receptors, a study of 50 Chinese medicinal herbs.

    abstract：:Noroviruses (NoVs) are the leading cause of viral acute gastroenteritis affecting people of all ages worldwide. The disease is difficult to control due to its widespread nature and lack of an antiviral or vaccine. NoV infection relies on the interaction of the viruses with histo-blood group antigens (HBGAs) as host re...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.11.040

    authors： Zhang XF,Dai YC,Zhong W,Tan M,Lv ZP,Zhou YC,Jiang X

    更新日期：2012-02-15 00:00:00

  • Synthesis and antibacterial activity of novel 4-pyrrolidinylthio carbapenems Part IV. 2-Alkyl substituents containing cationic heteroaromatics linked via a C-C bond.

    abstract：:The synthesis and biological activity of a novel series of 2-alkyl-4-pyrrolidinylthio-beta-methylcarbapenems containing a variety of cationic heteroaromatic substituents linked via a C-C bond is described. As a result of these studies, we selected FR21818 (In) as a candidate compound for development. FR21818 exhibited...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(00)00314-x

    authors： Zam HA,Barrett D,Tanaka A,Sasaki H,Matsuda K,Sakurai M,Terasawa T,Shirai F,Chiba T,Matsumoto Y,Tawara S

    更新日期：2001-04-01 00:00:00

  • Multi-receptor drug design: Haloperidol as a scaffold for the design and synthesis of atypical antipsychotic agents.

    abstract：:Using haloperidol as a scaffold, new agents were designed to investigate the structural contributions of various groups to binding at CNS receptors associated with atypical antipsychotic pharmacology. It is clear that each pharmacophoric group, the butyrophenone, the piperidine and the 4-chlorophenyl moieties contribu...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.12.019

    authors： Peprah K,Zhu XY,Eyunni SV,Setola V,Roth BL,Ablordeppey SY

    更新日期：2012-02-01 00:00:00

  • Identification and characterisation of 2-aminopyridine inhibitors of checkpoint kinase 2.

    abstract：:5-(Hetero)aryl-3-(4-carboxamidophenyl)-2-aminopyridine inhibitors of CHK2 were identified from high throughput screening of a kinase-focussed compound library. Rapid exploration of the hits through straightforward chemistry established structure-activity relationships and a proposed ATP-competitive binding mode which ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.11.058

    authors： Hilton S,Naud S,Caldwell JJ,Boxall K,Burns S,Anderson VE,Antoni L,Allen CE,Pearl LH,Oliver AW,Wynne Aherne G,Garrett MD,Collins I

    更新日期：2010-01-15 00:00:00

  • New acridone-4-carboxylic acid derivatives as potential inhibitors of hepatitis C virus infection.

    abstract：:A new class of compounds--acridone derivatives--was tested using the direct fluorometric helicase activity assay to determine the inhibitory properties of the derivatives towards the NS3 helicase of Hepatitis C virus (HCV). The compounds were also tested as putative transcription inhibitors of in vitro transcription b...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.08.074

    authors： Stankiewicz-Drogon A,Palchykovska LG,Kostina VG,Alexeeva IV,Shved AD,Boguszewska-Chachulska AM

    更新日期：2008-10-01 00:00:00

  • Design, synthesis, biological evaluation and docking studies of pterostilbene analogs inside PPARalpha.

    abstract：:Pterostilbene, a naturally occurring analog of resveratrol, has previously shown PPARalpha activation in H4IIEC3 cells and was found to decrease cholesterol levels in animals. In this study, analogs of pterostilbene were synthesized and their ability to activate PPARalpha was investigated. Among analogs that was synth...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.01.051

    authors： Mizuno CS,Ma G,Khan S,Patny A,Avery MA,Rimando AM

    更新日期：2008-04-01 00:00:00

  • 4-Aminophenyl acetamides and propanamides as potent transient receptor potential vanilloid 1 (TRPV1) ligands.

    abstract：:A series of 2-(3,5-substituted 4-aminophenyl)acetamide and propanamide derivatives were investigated as human TRPV1 antagonists. The analysis of the structure-activity relationship indicated that 2-(3,5-dihalo 4-aminophenyl)acetamide analogues displayed excellent antagonism of hTRPV1 activation by capsaicin and showed...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2018.07.040

    authors： Kim C,Ann J,Lee S,Kim E,Choi S,Blumberg PM,Frank-Foltyn R,Bahrenberg G,Stockhausen H,Christoph T,Lee J

    更新日期：2018-08-15 00:00:00

  • Synthesis, molecular docking and biological evaluation of N,N-disubstituted 2-aminothiazolines as a new class of butyrylcholinesterase and carboxylesterase inhibitors.

    abstract：:A series of 31 N,N-disubstituted 2-amino-5-halomethyl-2-thiazolines was designed, synthesized, and evaluated for inhibitory potential against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and carboxylesterase (CaE). The compounds did not inhibit AChE; the most active compounds inhibited BChE and CaE with I...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2016.01.031

    authors： Makhaeva GF,Boltneva NP,Lushchekina SV,Serebryakova OG,Stupina TS,Terentiev AA,Serkov IV,Proshin AN,Bachurin SO,Richardson RJ

    更新日期：2016-03-01 00:00:00

  • Dual inhibitors of inosine monophosphate dehydrogenase and histone deacetylase based on a cinnamic hydroxamic acid core structure.

    abstract：:Small molecules that act on multiple biological targets have been proposed to combat the drug resistance commonly observed for cancer chemotherapy. By combining the structural features of known inhibitors of inosine monophosphate dehydrogense (IMPDH) and histone deacetylase (HDAC), dual inhibitors of IMPDH and HDAC ba...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.06.081

    authors： Chen L,Petrelli R,Gao G,Wilson DJ,McLean GT,Jayaram HN,Sham YY,Pankiewicz KW

    更新日期：2010-08-15 00:00:00

  • HSP90-like artificial chaperone activity based on indole beta-cyclodextrin.

    abstract：:Indole beta-cyclodextrin (beta-1) was found to be able to prevent aggregation of citrate synthase (CS) on heating condition. As a result, beta-1 showed anti-CS aggregation in this system by regulating in early stage. The depression mechanism of beta-1 for aggregation of CS is as follows: the beta-1 formed a complex wi...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.12.040

    authors： Toda M,Itoh H,Kondo Y,Hamada F

    更新日期：2007-03-01 00:00:00

  • 4-Fluoro-N-butylphenylacetamide (H6) inhibits cell growth via cell-cycle arrest and apoptosis in human cervical cancer cells.

    abstract：:Phenylacetate induced tumor cytostasis and differentiation. The chemotherapeutic function of the compound in lung cancer has been previously reported, however, whether or not phenylacetate performs other activities is not known. In this study, the potential usage of synthetic phenylacetate derivatives, 4-fluoro-N-buty...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.11.028

    authors： Liu CH,Huang LJ,Kuo SC,Lee TH,Tsai KJ,Chan HC

    更新日期：2009-01-01 00:00:00

  • Design, synthesis and biological evaluation of novel 6-phenyl-1,3a,4,10b-tetrahydro-2H-benzo[c]thiazolo[4,5-e]azepin-2-one derivatives as potential BRD4 inhibitors.

    abstract：:Bromodomain-containing protein 4 (BRD4) is a key epigenetic regulator in cancer, and inhibitors targeting BRD4 exhibit great anticancer activity. By replacing the methyltriazole ring of the BRD4 inhibitor I-BET-762 with an N-methylthiazolidone heterocyclic ring, fifteen novel BRD4 inhibitors were designed and synthesi...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2020.115601

    authors： Li Q,Li J,Cai Y,Zou Y,Chen B,Zou F,Mo J,Han T,Guo W,Huang W,Qiu Q,Qian H

    更新日期：2020-08-01 00:00:00

  • Borrelidins F-I, cytotoxic and cell migration inhibiting agents from mangrove-derived Streptomyces rochei SCSIO ZJ89.

    abstract：:Borrelidin A (1) is produced by several species of Streptomyces and within its bioactive scaffold, the vinylic nitrile moiety is essential for activity. We report herein newly discovered members of the borrelidin family, borrelidin F (2), borrelidin G (3), borrelidin H (4) and borrelidin I (5); all were isolated from ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2018.01.010

    authors： Sun J,Shao J,Sun C,Song Y,Li Q,Lu L,Hu Y,Gui C,Zhang H,Ju J

    更新日期：2018-05-01 00:00:00

  • Substituted indolin-2-ones as p90 ribosomal S6 protein kinase 2 (RSK2) inhibitors: Molecular docking simulation and structure-activity relationship analysis.

    abstract：:A series of novel indolin-2-ones inhibitors against p90 ribosomal S6 protein kinase 2 (RSK2) were designed and synthesized and their structure-activity relationship (SAR) was studied. The most potent inhibitor, compound 3s, exhibited potent inhibition against RSK2 with an IC50 value of 0.5 μM and presented a satisfact...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2013.01.047

    authors： Zhong Y,Xue M,Zhao X,Yuan J,Liu X,Huang J,Zhao Z,Li H,Xu Y

    更新日期：2013-04-01 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

  • Tyrosinase inhibitory activity of a 6-isoprenoid-substituted flavanone isolated from Dalea elegans.

    abstract：:To aid the pharmaceutical and cosmetic industry in the development of alternatives to prevent melanin-related hyperpigmentation disorders, the plant Dalea elegans was submitted to fractionation with the aim of obtaining its anti-tyrosinase principle. Bioguided fractionation of D. elegans led to the isolation of 5,2',4...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.04.025

    authors： Chiari ME,Vera DM,Palacios SM,Carpinella MC

    更新日期：2011-06-01 00:00:00

  • Synthesis and evaluation of novel amide amino-β-lactam derivatives as cholesterol absorption inhibitors.

    abstract：:The β-lactam cholesterol absorption inhibitor ezetimibe is so far the only representative of this class of compounds on the market today. The goal of this work was to synthesize new amide ezetimibe analogs from trans-3-amino-(3R,4R)-β-lactam and to test their cytotoxicity and activity as cholesterol absorption inhibit...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2015.03.067

    authors： Dražić T,Sachdev V,Leopold C,Patankar JV,Malnar M,Hećimović S,Levak-Frank S,Habuš I,Kratky D

    更新日期：2015-05-15 00:00:00

  • The splicing modulator sulfonamide indisulam reduces AR-V7 in prostate cancer cells.

    abstract：:Alternative splicing of the androgen receptor (AR) is frequently observed in castration resistant prostate cancer (CRPC). One AR isoform, the AR-V7 splice variant, is a constitutively active transcription factor which lacks a ligand binding domain and is therefore undruggable. AR-V7 expression correlates with resistan...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2020.115712

    authors： Melnyk JE,Steri V,Nguyen HG,Hann B,Feng FY,Shokat KM

    更新日期：2020-10-15 00:00:00

  • Generation of hazardous methyl azide and its application to synthesis of a key-intermediate of picarbutrazox, a new potent pesticide in flow.

    abstract：:Generation and reactions of methyl azide (MeN3) were successfully performed by using a flow reactor system, demonstrating that the flow method serves as a safe method for handling hazardous explosive methyl azide. The reaction of NaN3 and Me2SO4 in a flow reactor gave a MeN3 solution, which was used for Huisgen reacti...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2017.07.005

    authors： Ichinari D,Nagaki A,Yoshida JI

    更新日期：2017-12-01 00:00:00

  • Quinazolindione derivatives as potent 5-HT3A receptor antagonists.

    abstract：:5-HT(3A) receptor antagonists have been used mainly for the treatment of nausea and vomiting. These days, the antagonists are of special interest due to their therapeutic potential to treat other diseases such as depression, psychotic disorder, drug abuse, and irritable bowel syndrome. To discover novel 5-HT(3A) recep...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.04.029

    authors： Lee BH,Choi MJ,Jo MN,Seo HJ,Nah SY,Cho YS,Nam G,Pae AN,Rhim H,Choo H

    更新日期：2009-07-01 00:00:00

  • STD-NMR studies of two acceptor substrates of GlfT2, a galactofuranosyltransferase from Mycobacterium tuberculosis: epitope mapping studies.

    abstract：:The major structural component of the mycobacterial cell wall, the mycolyl-arabinogalactan-peptidoglycan complex, possesses a galactan core composed of approximately 30 galactofuranosyl (Galf) resides attached via alternating beta-(1-->6) and beta-(1-->5) linkages. Recent studies have shown that the entire galactan is...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.05.069

    authors： Szczepina MG,Zheng RB,Completo GC,Lowary TL,Pinto BM

    更新日期：2010-07-15 00:00:00

  • Synthesis, biological activities and pharmacokinetic properties of new fluorinated derivatives of selective PDE4D inhibitors.

    abstract：:A new series of selective PDE4D inhibitors has been designed and synthesized by replacing 3-methoxy group with 3-difluoromethoxy isoster moiety in our previously reported cathecolic structures. All compounds showed a good PDE4D3 inhibitory activity, most of them being inactive toward other PDE4 isoforms (PDE4A4, PDE4B...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2015.04.027

    authors： Brullo C,Massa M,Villa C,Ricciarelli R,Rivera D,Pronzato MA,Fedele E,Barocelli E,Bertoni S,Flammini L,Bruno O

    更新日期：2015-07-01 00:00:00