当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Achieving structural diversity using the perpendicular conformation of alpha-substituted phenylcyclopropanes to mimic the bioactive conformation of ortho-substituted biphenyl P4 moieties: discovery of novel, highly potent inhibitors of Factor Xa.

Achieving structural diversity using the perpendicular conformation of alpha-substituted phenylcyclopropanes to mimic the bioactive conformation of ortho-substituted biphenyl P4 moieties: discovery of novel, highly potent inhibitors of Factor Xa.

Abstract：

:Ortho-substituted biphenyl moieties are widely used in drug design. We herein report a successful use of the perpendicular conformation of the alpha-substituted phenylcyclopropyl groups to mimic the aplanar, biologically active conformation of the ortho-substituted biphenyl moieties to achieve structural diversity. This is exemplified by the design and synthesis of a series of highly potent pyrazole bicyclic-based Factor Xa (FXa) inhibitors bearing alpha-substituted phenylcyclopropyl P4 moieties. The designed perpendicular conformation was confirmed by the X-ray structure of FXa-bound compound 2r. The potential structural basis for the high FXa potency in the phenylcyclopropyl P4 analogs and their improved FXa inhibitory activities compared with the biphenyl P4 counterparts are discussed.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Qiao JX,Cheney DL,Alexander RS,Smallwood AM,King SR,He K,Rendina AR,Luettgen JM,Knabb RM,Wexler RR,Lam PY

doi

10.1016/j.bmcl.2008.05.095

subject

Has Abstract

pub_date

2008-07-15 00:00:00

pages

4118-23

issue

14

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(08)00604-5

journal_volume

18

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • Opioids and efflux transporters. Part 4: influence of N-substitution on P-glycoprotein substrate activity of noroxymorphone analogues.

    abstract：:The efflux transporter protein P-glycoprotein (P-gp) is capable of affecting the central distribution of diverse neurotherapeutics, including opioid analgesics, through their active removal from the brain. P-gp located at the blood brain barrier has been implicated in the development of tolerance to opioids and demons...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.05.033

    authors： Metcalf MD,Rosicky AD,Hassan HE,Eddington ND,Coop A,Cunningham CW,Mercer SL

    更新日期：2014-08-01 00:00:00

  • Potent hFPRL1 (ALXR) agonists as potential anti-inflammatory agents.

    abstract：:We report the discovery of potent agonists for the human formyl-peptide-like 1 receptor (hFPRL1). These compounds did not act at a closely related receptor denoted human formyl peptide receptor (hFPR) up to 10 microM concentration. Recent studies have indicated that agonizing this receptor may promote resolution of in...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.04.068

    authors： Bürli RW,Xu H,Zou X,Muller K,Golden J,Frohn M,Adlam M,Plant MH,Wong M,McElvain M,Regal K,Viswanadhan VN,Tagari P,Hungate R

    更新日期：2006-07-15 00:00:00

  • Transformation of 8-prenylnaringenin by Absidia coerulea and Beauveria bassiana.

    abstract：:Beauveria bassiana AM278 and Absidia coerulea AM93 converted 8-prenylnaringenin (1) into two glycoside derivatives (7-O-β-D-glucopyranoside) (2) and 7-O-β-D-4'''-O-methylglucopyranoside) (3) in high yields in processes conducted in Saboraud medium. 8-Prenylnaringenin 7-O-β-D-4'''-O-methylglucopyranoside (3) is a new c...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.08.060

    authors： Bartmańska A,Tronina T,Huszcza E

    更新日期：2012-10-15 00:00:00

  • Highly potent growth hormone secretagogues: hybrids of NN703 and ipamorelin.

    abstract：:A series of NN703 analogues with lysine mimetics combined with naphthyl- or biphenylalanine in the core has been prepared and tested in vitro in a rat pituitary cell based assay and subsequently in vivo in pigs in a single dose at 50 nmol/kg. Re-introduction of certain pharmacophores in the C-terminal of NN703, which ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00345-6

    authors： Hansen TK,Ankersen M,Raun K,Hansen BS

    更新日期：2001-07-23 00:00:00

  • Synthesis and biological activities of NB-506 analogues: Effects of the positions of two hydroxyl groups at the indole rings.

    abstract：:In the course of a study of 6-N-amino-substituted analogues of NB-506 (1), a more potent anticancer drug, J-109,404 (2), in which the formyl group of NB-506 was replaced with a 1,3-dihydroxypropane group, was reported. A study of further modification in the positions of two hydroxyl groups at the indole rings of 2 res...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00595-8

    authors： Ohkubo M,Nishimura T,Honma T,Nishimura I,Ito S,Yoshinari T,Suda HA,Morishima H,Nishimura S

    更新日期：1999-12-06 00:00:00

  • Highly potent and long-acting trimeric and tetrameric inhibitors of influenza virus neuraminidase.

    abstract：:A set of trimeric and tetrameric derivatives 6-11 of the influenza virus neuraminidase inhibitor zanamivir 1 have been synthesized by coupling a common monomeric zanamivir derivative 3 onto various multimeric carboxylic acid core groups. These discrete multimeric compounds are all significantly more antiviral than zan...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.09.102

    authors： Watson KG,Cameron R,Fenton RJ,Gower D,Hamilton S,Jin B,Krippner GY,Luttick A,McConnell D,MacDonald SJ,Mason AM,Nguyen V,Tucker SP,Wu WY

    更新日期：2004-03-22 00:00:00

  • Thiophene-based vitronectin receptor antagonists.

    abstract：:A series of alpha(v)beta(3) antagonists based on a thiophene scaffold were synthesized via two routes and evaluated for in vitro biological activity. We have identified several structurally similar antagonists with different selectivities towards alpha(IIb)beta(3), alpha(v)beta(5) and alpha(5)beta(1) at the cellular l...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00942-3

    authors： Bubenik M,Meerovitch K,Bergeron F,Attardo G,Chan L

    更新日期：2003-02-10 00:00:00

  • Discovery of 4-aminomethylphenylacetic acids as γ-secretase modulators via a scaffold design approach.

    abstract：:Starting from literature examples of nonsteroidal anti-inflammatory drugs (NSAIDs)-type carboxylic acid γ-secretase modulators (GSMs) and using a scaffold design approach, we identified 4-aminomethylphenylacetic acid 4 with a desirable γ-secretase modulation profile. Scaffold optimization led to the discovery of a nov...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.10.047

    authors： Xin Z,Peng H,Zhang A,Talreja T,Kumaravel G,Xu L,Rohde E,Jung MY,Shackett MN,Kocisko D,Chollate S,Dunah AW,Snodgrass-Belt PA,Arnold HM,Taveras AG,Rhodes KJ,Scannevin RH

    更新日期：2011-12-15 00:00:00

  • Substituted aminobenzimidazole pyrimidines as cyclin-dependent kinase inhibitors.

    abstract：:A series of aminobenzimidazole-substituted pyrimidines were synthesized and evaluated for biochemical activity against CDK1. A high-speed parallel synthesis approach enabled the identification of a potent lead series having improved potency in the CDK1 assay (IC(50)<10nM). Cell cycle analysis showed that the compounds...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.02.076

    authors： Verma S,Nagarathnam D,Shao J,Zhang L,Zhao J,Wang Y,Li T,Mull E,Enyedy I,Wang C,Zhu Q,Altieri M,Jordan J,Dang TT,Reddy S

    更新日期：2005-04-15 00:00:00

  • Two new secondary metabolites isolated from Avena sativa L. (Oat) seedlings and their effects on osteoblast differentiation.

    abstract：:Seedlings of natural crops are valuable sources of pharmacologically active phytochemicals. In this study, we aimed to identify new active secondary metabolites in Avena sativa L. (oat) seedlings. Two new compounds, avenafuranol (1) and diosgenoside (2), along with eight known compounds (3-10) were isolated from the A...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127250

    authors： Woo SY,Lee KS,Shin HL,Kim SH,Lee MJ,Young Kim H,Ham H,Lee DJ,Choi SW,Seo WD

    更新日期：2020-07-15 00:00:00

  • Synthesis and evaluation of vancomycin and vancomycin aglycon analogues that bear modifications in the residue 3 asparagine.

    abstract：:The synthesis and biological evaluation of a set of residue 3 analogues of vancomycin and its aglycon are described. These investigations follow from the promising biological activity of a protected and synthetically modified vancomycin aglycon analogue in which the asparagine side chain was modified to possess a nitr...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00130-0

    authors： McAtee JJ,Castle SL,Jin Q,Boger DL

    更新日期：2002-05-06 00:00:00

  • P4 capped amides and lactams as HCV NS3 protease inhibitors with improved potency and DMPK profile.

    abstract：:SAR studies on the extension of P3 unit of Boceprevir (1, SCH 503034) with amides and lactams and their synthesis is described. Extensive SAR studies resulted in the identification of 36 bearing 4, 4-dimethyl lactam as the new P4 cap unit with improved potency (K(i)( *)=15nM, EC 90=70nM) and pharmacokinetic properties...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.11.094

    authors： Nair LG,Sannigrahi M,Bogen S,Pinto P,Chen KX,Prongay A,Tong X,Cheng KC,Girijavallabhan V,George Njoroge F

    更新日期：2010-01-15 00:00:00

  • Enediynes: Exploration of microbial genomics to discover new anticancer drug leads.

    abstract：:The enediyne natural products have been explored for their phenomenal cytotoxicity. The development of enediynes into anticancer drugs has been successfully achieved through the utilization of polymer- and antibody-drug conjugates (ADCs) as drug delivery systems. An increasing inventory of enediynes would benefit curr...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章,评审

    doi：10.1016/j.bmcl.2014.11.019

    authors： Shen B,Hindra,Yan X,Huang T,Ge H,Yang D,Teng Q,Rudolf JD,Lohman JR

    更新日期：2015-01-01 00:00:00

  • Synthesis of glycosyl phosphoramidates: novel isosteric analogues of glycosyl phosphates.

    abstract：:Several newer isosteric analogues of glycosyl phosphates, namely of glycosyl phosphoramidates, were synthesized in good yields using Staudinger reaction of their corresponding azides with trimethyl phosphite followed by de-O-acetylation. The structure and conformation of the fully protected analogue synthesized, namel...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00469-3

    authors： Kannan T,Vinodhkumar S,Varghese B,Loganathan D

    更新日期：2001-09-17 00:00:00

  • Discovery of novel sphingosine kinase-1 inhibitors. Part 2.

    abstract：:Building on our initial work, we have identified additional novel inhibitors of sphingosine kinase-1 (SK1). These new analogs address the shortcomings found in our previously reported compounds. Inhibitors 51 and 54 demonstrated oral bioavailability in a rat PK study. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.06.019

    authors： Xiang Y,Hirth B,Kane JL Jr,Liao J,Noson KD,Yee C,Asmussen G,Fitzgerald M,Klaus C,Booker M

    更新日期：2010-08-01 00:00:00

  • Synthesis and pharmacology of modified amidine isoxazoline glycoprotein IIb/IIIa receptor antagonists.

    abstract：:Selective antagonism of the platelet GPIIb/IIIa receptor represents an attractive mechanism for the prevention and treatment of a number of thrombotic disease states. The antiplatelet activity of the oral GPIIb/IIIa receptor antagonists DMP 754 and DMP 802 have been disclosed. In this paper, the synthesis and biologic...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00406-1

    authors： Sielecki TM,Liu J,Mousa SA,Racanelli AL,Hausner EA,Wexler RR,Olson RE

    更新日期：2001-08-20 00:00:00

  • Pharmacokinetics and metabolism studies on (3-tert-butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy) pyrazolo[1,5-d][1,2,4]triazine, a functionally selective GABA(A) alpha5 inverse agonist for cognitive dysfunction.

    abstract：:(3-tert-Butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)pyrazolo[1,5-d][1,2,4]triazine (1) was recently identified as a functionally selective, inverse agonist at the benzodiazepine site of GABA(A) alpha5 receptors and enhances performance in animal models of cognition. The routes of metabolis...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.11.012

    authors： Jones P,Atack JR,Braun MP,Cato BP,Chambers MS,O'Connor D,Cook SM,Hobbs SC,Maxey R,Szekeres HJ,Szeto N,Wafford KA,MacLeod AM

    更新日期：2006-02-15 00:00:00

  • Synthesis and anthelmintic activity of cyclohexadepsipeptides with (S,S,S,R,S,R)-configuration.

    abstract：:The (S,S,S,R,S,R)-configurated cyclohexadepsipeptides (CHDPs) represent novel enniatin derivatives with strong in vivo activity against the parasitic nematode Haemonchus contortus Rudolphi in sheep. 2D NMR spectroscopic analysis revealed for the major conformation the asymmetric conformer, containing a cis-amide bond ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(03)00688-7

    authors： Jeschke P,Benet-Buchholz J,Harder A,Etzel W,Schindler M,Thielking G

    更新日期：2003-10-06 00:00:00

  • Discovery of potent and selective matrix metalloprotease 12 inhibitors for the potential treatment of chronic obstructive pulmonary disease (COPD).

    abstract：:Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease associated with irreversible progressive airflow limitation. Matrix metalloproteinase-12 (MMP-12) has been characterized to be one of the major proteolytic enzymes to induce airway remodeling, destruction of elastin and the aberrant remodelin...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.11.046

    authors： Wu Y,Li J,Wu J,Morgan P,Xu X,Rancati F,Vallese S,Raveglia L,Hotchandani R,Fuller N,Bard J,Cunningham K,Fish S,Krykbaev R,Tam S,Goldman SJ,Williams C,Mansour TS,Saiah E,Sypek J,Li W

    更新日期：2012-01-01 00:00:00

  • A series of thiazole derivatives bearing thiazolidin-4-one as non-competitive ADAMTS-5 (aggrecanase-2) inhibitors.

    abstract：:A series of thiazole bearing thiazolidin-4-one was discovered via high-throughput screening as non-competitive inhibitors of ADAMTS-5. Compound 31 appeared to give the best ADAMTS-5 inhibition and good selectivity over other metalloproteases. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.01.121

    authors： Atobe M,Maekawara N,Ishiguro N,Sogame S,Suenaga Y,Kawanishi M,Suzuki H,Jinno N,Tanaka E,Miyoshi S

    更新日期：2013-04-01 00:00:00

  • The synthesis and selective IL-2 inhibitory activity of bis piperazine-phenol Mannich adducts.

    abstract：:Novel phenol bis-Mannich adducts were identified as IL-2 expression inhibitors in a T cell proliferation screening assay. Analogues of the lead compound were prepared through parallel synthesis and a highly selective IL-2 inhibitor was discovered that provided a suitable compound for further optimization. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00011-2

    authors： Geng B,Fleming PR,Umlauf S,Lin A,Pallai PV

    更新日期：2002-03-11 00:00:00

  • Design and synthesis of triazolopyrimidine acylsulfonamides as novel anti-mycobacterial leads acting through inhibition of acetohydroxyacid synthase.

    abstract：:Novel triazolopyrimidine acylsulfonamides class of antimycobacterial agents, which are mycobacterial acetohydroxyacid synthase (AHAS) inhibitors were designed by hybridization of known AHAS inhibitors such as sulfonyl urea and triazolopyrimidine sulfonamides. This Letter describes the synthesis and SAR studies of this...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.02.054

    authors： Patil V,Kale M,Raichurkar A,Bhaskar B,Prahlad D,Balganesh M,Nandan S,Shahul Hameed P

    更新日期：2014-05-01 00:00:00

  • Nav1.7 inhibitors for the treatment of chronic pain.

    abstract：:The voltage gated sodium channel Nav1.7 plays an essential role in the transmission of pain signals. Strong human genetic validation has motivated extensive efforts to discover potent, selective, and efficacious Nav1.7 inhibitors for the treatment of chronic pain. This digest will introduce the structure and function ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章,评审

    doi：10.1016/j.bmcl.2018.08.007

    authors： McKerrall SJ,Sutherlin DP

    更新日期：2018-10-15 00:00:00

  • Structure-based design, synthesis and structure-activity relationships of dibenzosuberyl- and benzoate-substituted tropines as ligands for acetylcholine-binding protein.

    abstract：:Using structure-based optimization procedures on in silico hits, dibenzosuberyl- and benzoate substituted tropines were designed as ligands for acetylcholine-binding protein (AChBP). This protein is a homolog to the ligand binding domain of the nicotinic acetylcholine receptor (nAChR). Distinct SAR is observed between...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.12.008

    authors： Edink E,Akdemir A,Jansen C,van Elk R,Zuiderveld O,de Kanter FJ,van Muijlwijk-Koezen JE,Smit AB,Leurs R,de Esch IJ

    更新日期：2012-02-01 00:00:00

  • Dimeric unnatural polyproline-rich peptides with enhanced antibacterial activity.

    abstract：:We report a dimerization strategy to enhance the antibacterial potency of an otherwise weak cationic amphiphilic polyproline helical (CAPH) peptide. Overall, the dimeric CAPHs were more active against Escherichia coli and Staphylococcus aureus than the monomeric counterpart, reaching up to a 60-fold increase in potenc...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.12.023

    authors： Hernandez-Gordillo V,Geisler I,Chmielewski J

    更新日期：2014-01-15 00:00:00

  • Polar substitutions in the benzenesulfonamide ring of celecoxib afford a potent 1,5-diarylpyrazole class of COX-2 inhibitors.

    abstract：:Several chemical modifications in the N(1)-benzenesulfonamide ring of celecoxib are presented. The series with a hydroxymethyl group adjacent to the sulfonamide was found to be the most potent modification that yielded many compounds selectively active against COX-2 enzyme in vitro. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.10.027

    authors： Singh SK,Reddy PG,Rao KS,Lohray BB,Misra P,Rajjak SA,Rao YK,Venkateswarlu A

    更新日期：2004-01-19 00:00:00

  • Synthesis, molecular docking and evaluation of thiazolyl-pyrazoline derivatives as EGFR TK inhibitors and potential anticancer agents.

    abstract：:Fourty-two thiazolyl-pyrazoline derivatives were synthesized to screen for their EGFR kinase inhibitory activity. Compound 4-(4-chlorophenyl)-2-(3-(3,4-dimethylphenyl)-5-p-tolyl-4,5-dihydro-1H-pyrazol-1-yl)thiazole (11) displayed the most potent EGFR TK inhibitory activity with IC(50) of 0.06 μM, which was comparable ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.07.010

    authors： Lv PC,Li DD,Li QS,Lu X,Xiao ZP,Zhu HL

    更新日期：2011-09-15 00:00:00

  • An inhibitor-like binding mode of a carbonic anhydrase activator within the active site of isoform II.

    abstract：:The 2,4,6-trimethylpyridinium derivative of histamine is an effective activator of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). However, unlike other CA activators, which bind at the entrance of the active site cavity, an X-ray crystal structure of hCA II in complex with the 1-[2-(1H-imidazol-4-yl)-ethyl]-2,4,...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.10.045

    authors： Dave K,Ilies MA,Scozzafava A,Temperini C,Vullo D,Supuran CT

    更新日期：2011-05-01 00:00:00

  • 1-Aryl-tetrahydroisoquinoline analogs as active anti-HIV agents in vitro.

    abstract：:A series of 1-aryl-6,7-dihydroxyl(methoxy)-1,2,3,4-tetrahydroisoquinolines (compounds 1-36) were synthesized via Pictet-Spengler cyclization. All the synthesized compounds were assayed for activities against HIV-1(IIIB) in C8166 cell cultures by MTT method for the first time. The results of the anti-HIV screening reve...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.02.040

    authors： Cheng P,Huang N,Jiang ZY,Zhang Q,Zheng YT,Chen JJ,Zhang XM,Ma YB

    更新日期：2008-04-01 00:00:00

  • Synthesis and preliminary pharmacological evaluation of N-2-(4-(4-(2-substitutedthiazol-4-yl) piperazin-1-yl)-2-oxoethyl)acetamides as novel atypical antipsychotic agents.

    abstract：:A series of N-2-(4-(4-(2-substitutedthiazol-4-yl) piperazin-1-yl)-2-oxoethyl)acetamides were synthesized in an effort to prepare novel atypical antipsychotic agents. The compounds were synthesized by either microwave irradiation technique or by conventional synthesis and were characterized by spectral data (IR, (1)H N...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.10.035

    authors： Sekhar KV,Rao VS,Devambatla RKV,Kumar MM

    更新日期：2008-12-01 00:00:00