当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > CCK peptides with combined features of hexa- and tetrapeptide CCK-A agonists.

CCK peptides with combined features of hexa- and tetrapeptide CCK-A agonists.

Abstract：

:Selective CCK-A agonist activity has been reported to induce satiety in a variety of animals, including man, and thereby suggests a therapeutic role for CCK in the management of obesity. To date, three general classes of CCK-A agonists have been reported, the full-length, sulfated hepta- and hexapeptides, a series of tetrapeptides, and most recently a series of benzodiazepines. The SAR of the hexa- and tetrapeptide classes suggests that the Hpa(SO(3)H) and Tac groups may not interact at the CCK-A receptor in the same location. However, the C-terminal dipeptide part of the hexapeptides and tetrapeptides appear to interact at the CCK-A receptor in a similar manner. Compound 7 (Hpa-Nle-Gly-Trp-Lys(Tac)-Asp-MePhe-NH(2)) derived from combining the features of the hexapeptides and the tetrapeptides has subnanomolar affinity and 3500-fold selectivity for CCK-A receptors. Compound 7 administered intraperitoneally produces potent, long-lasting reduction in food intake in rats and a corresponding weight loss when administered over nine consecutive days.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Pierson ME,Comstock JM,Simmons RD,Julien R,Kaiser F,Rosamond JD

doi

10.1021/jm990252e

keywords:

subject

Has Abstract

pub_date

2000-06-15 00:00:00

pages

2350-5

issue

12

eissn

0022-2623

issn

1520-4804

pii

jm990252e

journal_volume

43

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Phosphorus-nitrogen compounds. 22. Synthesis and antitumor activity of arylsulfonylhydrazone analogues.

    abstract：:A series of pyridine-2-carboxaldehyde N-oxide and pyridine-2-carboxaldehyde (thio)phosphoric hydrazones and two cupric chelates was synthesized. The hydrazones, chelates, and combinations of hydrazones and cupric chloride were tested against mice bearing P388 lymphocytic leukemia, Sarcoma 180, or Ehrlich carcinoma asc...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00209a011

    authors： Cates LA,Good DJ,Jones GS,Lemke TL

    更新日期：1978-11-01 00:00:00

  • Discovery of potent and highly selective thienopyridine Janus kinase 2 inhibitors.

    abstract：:Developing Janus kinase 2 (Jak2) inhibitors has become a significant focus for small molecule drug discovery programs in recent years due to the identification of a Jak2 gain-of-function mutation in the majority of patients with myeloproliferative disorders (MPD). Here, we describe the discovery of a thienopyridine se...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm200911r

    authors： Schenkel LB,Huang X,Cheng A,Deak HL,Doherty E,Emkey R,Gu Y,Gunaydin H,Kim JL,Lee J,Loberg R,Olivieri P,Pistillo J,Tang J,Wan Q,Wang HL,Wang SW,Wells MC,Wu B,Yu V,Liu L,Geuns-Meyer S

    更新日期：2011-12-22 00:00:00

  • Discovery of potent and selective pyrazolopyrimidine janus kinase 2 inhibitors.

    abstract：:The discovery of somatic Jak2 mutations in patients with chronic myeloproliferative neoplasms has led to significant interest in discovering selective Jak2 inhibitors for use in treating these disorders. A high-throughput screening effort identified the pyrazolo[1,5-a]pyrimidine scaffold as a potent inhibitor of Jak2....

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm3012239

    authors： Hanan EJ,van Abbema A,Barrett K,Blair WS,Blaney J,Chang C,Eigenbrot C,Flynn S,Gibbons P,Hurley CA,Kenny JR,Kulagowski J,Lee L,Magnuson SR,Morris C,Murray J,Pastor RM,Rawson T,Siu M,Ultsch M,Zhou A,Sampath D,Ly

    更新日期：2012-11-26 00:00:00

  • The Race to Bash NASH: Emerging Targets and Drug Development in a Complex Liver Disease.

    abstract：:Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD) characterized by liver steatosis, inflammation, and hepatocellular damage. NASH is a serious condition that can progress to cirrhosis, liver failure, and hepatocellular carcinoma. The association of NASH with obesity, type...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1021/acs.jmedchem.9b01701

    authors： Romero FA,Jones CT,Xu Y,Fenaux M,Halcomb RL

    更新日期：2020-05-28 00:00:00

  • Dose Predictions for Drug Design.

    abstract：:The efficacious dose of a drug is perhaps the most holistic metric reflecting its therapeutic potential. Dose is predicted at many stages in drug discovery and development. Prior to the 1990s, dose prediction was limited to the drug "working" at a reasonable dose and dose regimen in an animal model. Through the early ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b01365

    authors： Maurer TS,Smith D,Beaumont K,Di L

    更新日期：2020-06-25 00:00:00

  • Nidufexor (LMB763), a Novel FXR Modulator for the Treatment of Nonalcoholic Steatohepatitis.

    abstract：:Farnesoid X receptor (FXR) agonists are emerging as important potential therapeutics for the treatment of nonalcoholic steatohepatitis (NASH) patients, as they exert positive effects on multiple aspects of the disease. FXR agonists reduce lipid accumulation in the liver, hepatocellular inflammation, hepatic injury, an...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b01621

    authors： Chianelli D,Rucker PV,Roland J,Tully DC,Nelson J,Liu X,Bursulaya B,Hernandez ED,Wu J,Prashad M,Schlama T,Liu Y,Chu A,Schmeits J,Huang DJ,Hill R,Bao D,Zoll J,Kim Y,Groessl T,McNamara P,Liu B,Richmond W,Sancho

    更新日期：2020-04-23 00:00:00

  • Synthesis of N-{4-[(2,4-diamino-5-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)thio]benzoyl}-L-glutamic acid and N-{4-[(2-amino-4-oxo-5-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)thio]benzoyl}-L-glutamic acid as dual inhibitors of dihydrofol

    abstract：:Two novel classical antifolates N-{4-[(2,4-diamino-5-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)thio]benzoyl}-L-glutamic acid 3 and N-{4-[(2-amino-4-oxo-5-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)thio]benzoyl}-L-glutamic acid 4 were designed, synthesized, and evaluated as antitumor agents. Compounds ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm058234m

    authors： Gangjee A,Lin X,Kisliuk RL,McGuire JJ

    更新日期：2005-11-17 00:00:00

  • Synthesis, structure-activity relationships, and in vivo evaluations of substituted di-tert-butylphenols as a novel class of potent, selective, and orally active cyclooxygenase-2 inhibitors. 2. 1,3,4- and 1,2,4-thiadiazole series.

    abstract：:Two isoforms of the cyclooxygenase (COX) enzyme have been identified: COX-1, which is expressed constitutively, and COX-2, which is induced in inflammation. Recently, it has been shown that selective COX-2 inhibitors have antiinflammatory activity and lack the GI side effects typically associated with NSAIDs. Initial ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm980570y

    authors： Song Y,Connor DT,Sercel AD,Sorenson RJ,Doubleday R,Unangst PC,Roth BD,Beylin VG,Gilbertsen RB,Chan K,Schrier DJ,Guglietta A,Bornemeier DA,Dyer RD

    更新日期：1999-04-08 00:00:00

  • Synthesis, antifertility activity, and protein binding affinity of 7(8 leads to 11 alpha)abeo steroids.

    abstract：:A series of 7(8 leads to 11 alpha)abeo steroids was synthesized by a modification of the previously described total synthesis of this class of compounds and evaluated for biological activity. In general, there was a marked reduction in the relative binding affinities of these compounds for the rabbit uterus estrogen a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00214a017

    authors： Wani MC,Rector DH,White DH,Pitt CG,Kimmel GL

    更新日期：1977-04-01 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

  • Synthesis and evaluation of melphalan-containing N,N-dialkylenkephalin analogues as irreversible antagonists of the delta opioid receptor.

    abstract：:N,N-Dialkylated leucine enkephalin analogues containing melphalan (Mel) in place of Phe4 were synthesized as potentially irreversible antagonists of the delta opioid receptor. These compounds, along with the corresponding Phe4 peptides, were tested for both agonist and antagonist activity in the GPI and MVD smooth mus...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00392a025

    authors： Lovett JA,Portoghese PS

    更新日期：1987-09-01 00:00:00

  • Derivatives of the triazoloquinazoline adenosine antagonist (CGS15943) are selective for the human A3 receptor subtype.

    abstract：:The adenosine antagonist 9-chloro-2-(2-furanyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine (CGS15943) binds to human A3 receptors with high affinity (Ki = 14 nM), while it lacks affinity at rat A3 receptors. Acylated derivatives of the 5-amino group and other modifications were prepared in an effort to provide A3 subtype...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm960482i

    authors： Kim YC,Ji XD,Jacobson KA

    更新日期：1996-10-11 00:00:00

  • Quantitative correlations between albumin binding constants and chromatographic Rm values of phenothiazine derivatives.

    abstract：:The binding constants of 15 phenothiazine derivatives to bovine serum albumin were obtained by a circular dichroic probe technique; The lipophilicity of the drugs, measured by a reversed-phase thin-layer technique using oleyl alcohol and methanol-water mixtures as the solvents, is expressed as RMw. The binding constan...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00213a022

    authors： Hulshoff A,Perrin JH

    更新日期：1977-03-01 00:00:00

  • Drugs derived from cannabinoids. 2. Basic esters of nitrogen and carbocyclic analogs.

    abstract：:Various basic esters of nitrogen (2) and carbocyclic (3 and 4) analogs of cannabinoids were synthesized using dicyclohexylcarbodiimide in methylene chloride. The compounds in the three series werw studied in selected pharmacological tests in mice, rats, dogs, and cats. It was shown that making the basic ester from the...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00226a002

    authors： Razdan RK,Terris BZ,Pars HG,Plotnikoff NP,Dodge PW,Dren AT,Kyncl J,Somani P

    更新日期：1976-04-01 00:00:00

  • Synthesis, DNA cross-linking activity, and cytotoxicity of dimeric mitomycins.

    abstract：:Dimeric DNA cross-linking compounds have emerged as important new antitumor agents. We report the synthesis and biochemical evaluation of a select set of dimeric mitomycins in which the two mitomycin units are tethered at either the mitomycin C(7) amino or the aziridine N(1a) positions. Significantly, mitomycin C (1) ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm010090y

    authors： Na Y,Li VS,Nakanishi Y,Bastow KF,Kohn H

    更新日期：2001-10-11 00:00:00

  • A novel approach of water-soluble paclitaxel prodrug with no auxiliary and no byproduct: design and synthesis of isotaxel.

    abstract：:A novel water-soluble paclitaxel prodrug, isotaxel 2, that realizes a higher water-solubility and the formation of paclitaxel through a simple pH-dependent chemical mechanism via the O-N acyl migration was synthesized and showed promising results in water-solubility and kinetics. This prodrug, a 2'-O-benzoyl isoform o...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm034112n

    authors： Hayashi Y,Skwarczynski M,Hamada Y,Sohma Y,Kimura T,Kiso Y

    更新日期：2003-08-28 00:00:00

  • Novel tetralone-derived retinoic acid metabolism blocking agents: synthesis and in vitro evaluation with liver microsomal and MCF-7 CYP26A1 cell assays.

    abstract：:The potent inhibitory activity of novel 2-benzyltetralone and 2-benzylidenetetralone derivatives vs liver microsomal retinoic acid metabolizing enzymes and a MCF-7 CYP26A1 cell assay is described. In the liver microsomal assay, the 2-biphenylmethyl-6-hydroxytetralone derivatives 16a and 16b were found to be potent inh...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0501681

    authors： Yee SW,Jarno L,Gomaa MS,Elford C,Ooi LL,Coogan MP,McClelland R,Nicholson RI,Evans BA,Brancale A,Simons C

    更新日期：2005-11-17 00:00:00

  • Fluorinated conformationally restricted gamma-aminobutyric acid aminotransferase inhibitors.

    abstract：:On the basis of the structures of several potent inhibitor molecules for gamma-aminobutryric acid aminotransferase (GABA-AT) that were previously reported, six modified fluorine-containing conformationally restricted analogues were designed, synthesized, and tested as GABA-AT inhibitors. The syntheses of all six molec...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0608715

    authors： Lu H,Silverman RB

    更新日期：2006-12-14 00:00:00

  • Synthesis of 1-(3,4-dihydroxy-5-nitrophenyl)-2-phenyl-ethanone and derivatives as potent and long-acting peripheral inhibitors of catechol-O-methyltransferase.

    abstract：:A homologous series of novel nitro-catechol structures (7a-7e) were synthesized and tested as inhibitors of the enzyme catechol-O-methyltransferase (COMT). Increasing chain length was found to have significant impact on both brain penetration and duration of COMT inhibition in the rat. Of this series, compound 7b (1-(...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0109964

    authors： Learmonth DA,Vieira-Coelho MA,Benes J,Alves PC,Borges N,Freitas AP,da-Silva PS

    更新日期：2002-01-31 00:00:00

  • 1,3-Dialkyl-8-(p-sulfophenyl)xanthines: potent water-soluble antagonists for A1- and A2-adenosine receptors.

    abstract：:A series of 8-(substituted phenyl) derivatives of theophylline and other 1,3-dialkylxanthines were evaluated for potency and selectivity as antagonists at A1- and A2-adenosine receptors in brain tissue. Theophylline has a similar potency (Ki = 14 microM) at both A1 and A2 receptors. 8-Phenyltheophylline is 25-35-fold ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00382a018

    authors： Daly JW,Padgett W,Shamim MT,Butts-Lamb P,Waters J

    更新日期：1985-04-01 00:00:00

  • Sterols as anticancer agents: synthesis of ring-B oxygenated steroids, cytotoxic profile, and comprehensive SAR analysis.

    abstract：:The cytotoxicity of oxysterols was systematically studied in tumor and normal cells. Synthetic strategies to prepare this library included oxidations at ring B and a new method to yield 6β-hemiphthalates directly from Δ(5)-steroids. Most oxysterols were cytotoxic and showed selectivity toward cancer cells, LAMA-84 cel...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm1007769

    authors： Carvalho JF,Silva MM,Moreira JN,Simões S,Sá e Melo ML

    更新日期：2010-11-11 00:00:00

  • Investigation into the P3 binding domain of m-calpain using photoswitchable diazo- and triazene-dipeptide aldehydes: new anticataract agents.

    abstract：:The photoswitchable N-terminal diazo and triazene-dipeptide aldehydes 8a-d, 10a,b, and 17a,b present predominantly as the (E)-isomer, which purportedly binds deep in the S3 pocket of calpain. All compounds are potent inhibitors of m-calpain, with 8b being the most active (IC50 of 35 nM). The diazo-containing inhibitor...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm061455n

    authors： Abell AD,Jones MA,Neffe AT,Aitken SG,Cain TP,Payne RJ,McNabb SB,Coxon JM,Stuart BG,Pearson D,Lee HY,Morton JD

    更新日期：2007-06-14 00:00:00

  • Novel synthesis of the hexahydroimidazo[1,5b]isoquinoline scaffold: application to the synthesis of glucocorticoid receptor modulators.

    abstract：:The first stereoselective synthesis of the hexahydroimidazo[1,5b]isoquinoline (HHII) scaffold as a surrogate for the steroidal A-B ring system is described. The structure-activity relationships of the analogs derived from this scaffold show that the basic imidazole moiety is tolerated by the glucocorticoid receptor (G...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm901551w

    authors： Xiao HY,Wu DR,Malley MF,Gougoutas JZ,Habte SF,Cunningham MD,Somerville JE,Dodd JH,Barrish JC,Nadler SG,Dhar TG

    更新日期：2010-02-11 00:00:00

  • Synthesis, cytostatic, antimicrobial, and anti-HCV activity of 6-substituted 7-(het)aryl-7-deazapurine ribonucleosides.

    abstract：:A series of 80 7-(het)aryl- and 7-ethynyl-7-deazapurine ribonucleosides bearing a methoxy, methylsulfanyl, methylamino, dimethylamino, methyl, or oxo group at position 6, or 2,6-disubstituted derivatives bearing a methyl or amino group at position 2, were prepared, and the biological activity of the compounds was stud...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm4018948

    authors： Nauš P,Caletková O,Konečný P,Džubák P,Bogdanová K,Kolář M,Vrbková J,Slavětínská L,Tloušt'ová E,Perlíková P,Hajdúch M,Hocek M

    更新日期：2014-02-13 00:00:00

  • Discovery and Structure-Activity Relationships of Nociceptin Receptor Partial Agonists That Afford Symptom Ablation in Parkinson's Disease Models.

    abstract：:A novel series of C(3)-substituted piperdinylindoles were developed as nociceptin opioid receptor (NOP) partial agonists to explore a pharmacological hypothesis that NOP partial agonists would afford a dual pharmacological action of attenuating Parkinson's disease (PD) motor symptoms and development of levodopa-induce...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b02134

    authors： Kamakolanu UG,Meyer ME,Yasuda D,Polgar WE,Marti M,Mercatelli D,Pisanò CA,Brugnoli A,Morari M,Zaveri NT

    更新日期：2020-03-12 00:00:00

  • Analgesics. 3. Selected 1-substituted and 1,3-disubstituted 5-propionoxy-5-(1-phenylethyl)barbituric acids.

    abstract：:Several 1,3-disubstituted and 1-substituted derivatives of 5-propionoxy-5-(1-phenylethyl)barbituric acid were synthesized and evaluated for analgesic activity. Three of these compounds, 1,3-bis(methoxymethyl)-5-propionoxy-5-(1-phenylethyl)barbituric acid (2), 1,3-dimethyl-5-propionoxy-5-(1-phenylethyl)barbituric acid...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00241a010

    authors： Vida JA,Samour CM,O'Dea MH,Reinhard JF

    更新日期：1975-07-01 00:00:00

  • Antileishmanial pyrazolopyridine derivatives: synthesis and structure-activity relationship analysis.

    abstract：:Three series of 4-anilino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic esters were synthesized as part of a program to study potential anti-Leishmania drugs. These compounds were obtained by a condensation reaction of 4-chloro-1H-pyrazolo[3,4-b]pyridine with several aniline derivatives. Some of them were also obtained by a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0401006

    authors： de Mello H,Echevarria A,Bernardino AM,Canto-Cavalheiro M,Leon LL

    更新日期：2004-10-21 00:00:00

  • Piperazinylquinoxalines with central serotoninmimetic activity.

    abstract：:Regioselective syntheses of substituted 2-chloroquinoxalines and derived 2-(1-piperazinyl)quinoxalines are described. Selectivity in regards to serotonin reuptake blocking and serotoninmimetic activities of the piperazinylquinoxalines is reported. In general, introduction of a 6-substituent into the piperazinylquinoxa...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00133a019

    authors： Lumma WC Jr,Hartman RD,Saari WS,Engelhardt EL,Lotti VJ,Stone CA

    更新日期：1981-01-01 00:00:00

  • Synthesis and antitumor activity of 7- and 9-(6'-deoxy-alpha-L-talofuranosyl) hypoxanthine and 9-(6'-deoxy-alpha-L-talofuranosyl)-6-thiopurine.

    abstract：:Reaction of 6-deoxy-2,3,5-tris-O-(p-nitrobenzoyl)-L-talofuranosyl bromide (1) with the trimethylsilyl derivative of hypoxanthine, followed by removal of blocking groups, afforded 9- (6) and 7-(6'-deoxy-alpha-L-talofuranosyl)hypoxanthine (7). A study of the published optical rotations and circular dichroic (CD) spectra...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00364a032

    authors： Nelson V,El Khadem HS

    更新日期：1983-10-01 00:00:00

  • Discovery of Nanomolar Dengue and West Nile Virus Protease Inhibitors Containing a 4-Benzyloxyphenylglycine Residue.

    abstract：:The dengue virus (DENV) and West Nile Virus (WNV) NS2B-NS3 proteases are attractive targets for the development of dual-acting therapeutics against these arboviral pathogens. We present the synthesis and extensive biological evaluation of inhibitors that contain benzyl ethers of 4-hydroxyphenylglycine as non-natural p...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.5b01441

    authors： Behnam MA,Graf D,Bartenschlager R,Zlotos DP,Klein CD

    更新日期：2015-12-10 00:00:00