Synthesis of arabinofuranosyl derivatives of 3-deazaguanine.

abstract：:A series of esters of 6beta-hydroxynortropane and the N-methyl analogue 6beta-tropanol were synthesized and screened versus binding of an antagonist (quinuclidinyl benzilate) and an agonist (oxotremorine-M) at sites on human m(1)-, m(2)-, m(3)-, and m(4)-muscarinic receptors in transfected cell membranes and on native...

journal_title：Journal of medicinal chemistry

authors： Daly JW,Gupta TH,Padgett WL,Pei XF

更新日期：2000-06-29 00:00:00

abstract：:Modern rational drug design not only deals with the search for ligands binding to interesting and promising validated targets but also aims to identify the function and ligands of yet uncharacterized proteins having impact on different diseases. Additionally, it contributes to the design of inhibitors with distinct se...

journal_title：Journal of medicinal chemistry

authors： Ehrt C,Brinkjost T,Koch O

更新日期：2016-05-12 00:00:00

abstract：:We present Fleksy, a new approach to consider both ligand and receptor flexibility in small molecule docking. Pivotal to our method is the use of a receptor ensemble to describe protein flexibility. To construct these ensembles, we use a backbone-dependent rotamer library and implement the concept of interaction sampl...

journal_title：Journal of medicinal chemistry

authors： Nabuurs SB,Wagener M,de Vlieg J

更新日期：2007-12-27 00:00:00

abstract：:MMP-12 plays a significant role in airway inflammation and remodeling. Increased expression and production of MMP-12 have been observed in the lungs of asthmatic patients. Compound 27 was identified as a potent and selective MMP-12 inhibitor possessing good physicochemical properties. In pharmacological studies, the c...

journal_title：Journal of medicinal chemistry

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

更新日期：2009-09-10 00:00:00

abstract：:A high-throughput screen at 100 microM inhibitor concentration for the BACE-1 enzyme revealed a novel spiropiperidine iminohydantoin aspartyl protease inhibitor template. An X-ray cocrystal structure with BACE-1 revealed a novel mode of binding whereby the inhibitor interacts with the catalytic aspartates via bridging...

journal_title：Journal of medicinal chemistry

authors： Barrow JC,Stauffer SR,Rittle KE,Ngo PL,Yang Z,Selnick HG,Graham SL,Munshi S,McGaughey GB,Holloway MK,Simon AJ,Price EA,Sankaranarayanan S,Colussi D,Tugusheva K,Lai MT,Espeseth AS,Xu M,Huang Q,Wolfe A,Pietrak B,Z

更新日期：2008-10-23 00:00:00

abstract：:In our ongoing program aimed at the design, synthesis, and biological evaluation of novel gem-difluoromethylenated glycosidase inhibitors, gem-4,4-difluoromethylenated iminosugars (5-9) were synthesized. The biological evaluation of these synthetic iminosugars showed that the gem-difluoromethylenyl group generally red...

journal_title：Journal of medicinal chemistry

authors： Wang RW,Qiu XL,Bols M,Ortega-Caballero F,Qing FL

更新日期：2006-05-18 00:00:00

abstract：:Natural product rakicidin A induces cell death in TKI-resistant chronic myelogenous leukemia (CML) cells. Therefore, 14 rakicidin A analogues were synthesized via a highly efficient combinatorial strategy and were evaluated against CML cell lines. The conjugated diene moiety was found to be crucial for the anti-CML ac...

journal_title：Journal of medicinal chemistry

authors： Sang F,Ding Y,Wang J,Sun B,Sun J,Geng Y,Zhang Z,Ding K,Wu LL,Liu JW,Bai C,Yang G,Zhang Q,Li LY,Chen Y

更新日期：2016-02-11 00:00:00

abstract：:The Rho kinases (ROCK1 and ROCK2) are highly homologous serine/threonine kinases that act on substrates associated with cellular motility, morphology, and contraction and are of therapeutic interest in diseases associated with cellular migration and contraction, such as hypertension, glaucoma, and erectile dysfunction...

journal_title：Journal of medicinal chemistry

authors： Green J,Cao J,Bandarage UK,Gao H,Court J,Marhefka C,Jacobs M,Taslimi P,Newsome D,Nakayama T,Shah S,Rodems S

更新日期：2015-06-25 00:00:00

abstract：:Two prototype N-methyl-4-thio-substituted cyclophosphamide (CP) derivatives (5 and 6), prodrugs of 4-hydroxycyclophosphamide (4-HO-CP), were designed to undergo oxidative N-demethylation to release the active alkylating agent. These prodrugs were chemically stable until oxidatively N-demethylated in the presence of he...

journal_title：Journal of medicinal chemistry

authors： Moon KY,Shirota FN,Baturay N,Kwon CH

更新日期：1995-03-03 00:00:00

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

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

更新日期：1975-07-01 00:00:00

abstract：:Three derivatives of angelicin (1) [4'-methyl-, 4,4'-dimethyl-, and 4',5-dimethylangelicin (2a-c)] have been prepared with the aim of obtaining new agents for the photochemotherapy of psoriasis. These compounds form a complex in the dark with DNA that shows an affinity for the macromolecule higher than that of the par...

journal_title：Journal of medicinal chemistry

authors： Dall'Acqua F,Vedaldi D,Bordin F,Baccichetti F,Carlassare F,Tamaro M,Rodighiero P,Pastorini G,Guiotto A,Recchia G,Cristofolini M

更新日期：1983-06-01 00:00:00

abstract：:Analogues of the previously reported potent cytotoxic spiro[(dihydropyrazine-2,5-dione)-6,3'-(2',3'-dihydrothieno[2,3-b]naphtho-4',9'-dione)] derivatives (3, 3') were prepared to explore new structural requirements at the diketopiperazine domain for the cytotoxic activity. The in vitro activity was evaluated against t...

journal_title：Journal of medicinal chemistry

authors： Gomez-Monterrey I,Campiglia P,Carotenuto A,Stiuso P,Bertamino A,Sala M,Aquino C,Grieco P,Morello S,Pinto A,Ianelli P,Novellino E

更新日期：2008-05-22 00:00:00

abstract：:We have previously reported that rhodacyanine dyes, such as 1 and 2, exhibited a potent inhibitory effect on the growth of several tumor cells and that 4-oxothiazolidine (rhodanine) was an essential moiety for antitumor activity. On the basis of our foregoing work, two types of rhodacyanine dyes, which categorized int...

journal_title：Journal of medicinal chemistry

authors： Kawakami M,Koya K,Ukai T,Tatsuta N,Ikegawa A,Ogawa K,Shishido T,Chen LB

更新日期：1998-01-01 00:00:00

abstract：:Ligand-induced stabilization of G-quadruplex structures formed by the human telomeric DNA is an active area of research. The compounds which stabilize the G-quadruplexes often lead to telomerase inhibition. Herein we present the results of interaction of new monomeric and dimeric ligands having 1,3-phenylene-bis(piper...

journal_title：Journal of medicinal chemistry

authors： Jain AK,Paul A,Maji B,Muniyappa K,Bhattacharya S

更新日期：2012-04-12 00:00:00

abstract：:A novel series of optically active 2,6-disubstituted alkylphenols with improved anesthetic profiles compared to widely used propofol were synthesized. The incorporation of the cyclopropyl group not only increased the steric effect but also introduced stereoselective effects over their anesthetic properties. Compounds ...

journal_title：Journal of medicinal chemistry

authors： Qin L,Ren L,Wan S,Liu G,Luo X,Liu Z,Li F,Yu Y,Liu J,Wei Y

更新日期：2017-05-11 00:00:00

abstract：:Computational ADME (absorption, distribution, metabolism, and excretion) models may be used early in the drug discovery process in order to flag drug candidates with potentially problematic ADME profiles. We report the development, validation, and application of quantitative structure-property relationship (QSPR) mode...

journal_title：Journal of medicinal chemistry

authors： Shen M,Xiao Y,Golbraikh A,Gombar VK,Tropsha A

更新日期：2003-07-03 00:00:00

abstract：:The effect of substitution of the pyrrolo- and indolo-N atoms in tetrahydronaltrindole (TNTI), tetrahydrooxymorphindole (TOMI), and 17-cyclopropylmethyl-3,14-dihydroxy-4,5-epoxy-4'-phenyl-6,7:2',3'-pyrrolomorphinan (4) is reported. In opioid functional assays 4 were potent deltaopioid receptor (DOR) antagonists while ...

journal_title：Journal of medicinal chemistry

authors： Srivastava SK,Shefali S,Miller CN,Aceto MD,Traynor JR,Lewis JW,Husbands SM

更新日期：2004-12-16 00:00:00

abstract：:A new goup of acridone derivatives, obtained by reaction of acridone-4-carboxylic acid derivatives with aromatic amines, was tested to determine the inhibitory properties toward the NS3 helicase of hepatitis C virus (HCV). Six compounds inhibited the NS3 helicase at low concentrations (IC(50) from 1.5 to 20 microM). T...

journal_title：Journal of medicinal chemistry

authors： Stankiewicz-Drogoń A,Dörner B,Erker T,Boguszewska-Chachulska AM

更新日期：2010-04-22 00:00:00

abstract：:A new series of quinazolinone derivatives was synthesized and evaluated as nonimidazole H 3 receptor inverse agonists. 2-Methyl-3-(4-[[3-(1-pyrrolidinyl)propyl]oxy]phenyl)-5-(trifluoromethyl)-4(3 H)-quinazolinone ( 1) was identified as a promising derivative for further evaluation following optimization of key paramet...

journal_title：Journal of medicinal chemistry

authors： Nagase T,Mizutani T,Ishikawa S,Sekino E,Sasaki T,Fujimura T,Ito S,Mitobe Y,Miyamoto Y,Yoshimoto R,Tanaka T,Ishihara A,Takenaga N,Tokita S,Fukami T,Sato N

更新日期：2008-08-14 00:00:00

abstract：:Electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) have been used for the first time to study the interaction of human alpha-thrombin with methyl 3-(2-methyl-1-oxopropoxy)[1]benzothieno[3,2-b]furan-2-carbox ylate (LY806303; 1), a potent and selective inhibitor whose mechanism of ac...

journal_title：Journal of medicinal chemistry

authors： Sall DJ,Kaiser RE Jr

更新日期：1993-08-06 00:00:00

abstract：:Tumor suppressor protein, p53, is an intracellular protein that is critical within the biochemical cascade that leads to cell death via apoptosis. Recent studies identified the tetrahydrobenzothiazole analogue, pifithrin-alpha (2), as a p53 inhibitor that was effective in protecting neuronal cells against a variety of...

journal_title：Journal of medicinal chemistry

authors： Zhu X,Yu QS,Cutler RG,Culmsee CW,Holloway HW,Lahiri DK,Mattson MP,Greig NH

更新日期：2002-11-07 00:00:00

abstract：:The understanding of the physiological role of the G-protein coupled serotonin 5-HT(7) receptor is largely rudimentary. Therefore, selective and potent pharmacological tools will add to the understanding of serotonergic effects mediated through this receptor. In this report, we describe two compound classes, chromans ...

journal_title：Journal of medicinal chemistry

authors： Holmberg P,Sohn D,Leideborg R,Caldirola P,Zlatoidsky P,Hanson S,Mohell N,Rosqvist S,Nordvall G,Johansson AM,Johansson R

更新日期：2004-07-29 00:00:00

abstract：:Several new 1-substituted 3,5-dimethylpyrazoles were prepared for testing as hypoglycemic agents. A number of these containing para-substituted 1-carbonylphenylurea and para-substituted 1-carbamoylbenzenesulfonylurea derivatives were found to possess potent hypoglycemic activity. ...

journal_title：Journal of medicinal chemistry

authors： Soliman R,Darwish SA

更新日期：1983-11-01 00:00:00

abstract：:Uridine (Urd) is a promising biochemical modulator to reduce host toxicity caused by 5-fluorouracil (5-FU) without impairing its antitumor activity. Elevated doses of Urd are required to achieve a protective effect against 5-FU toxicity, but exogenous administration of Urd is not well-tolerated. Selective inhibitors o...

journal_title：Journal of medicinal chemistry

authors： Renck D,Machado P,Souto AA,Rosado LA,Erig T,Campos MM,Farias CB,Roesler R,Timmers LF,de Souza ON,Santos DS,Basso LA

更新日期：2013-11-14 00:00:00

abstract：:Fifteen anthracene-9,10-dione ("anthraquinone") derivatives with (omega-aminoalkyl)carboxamido substituents at the 1-, 2-, 1,4-, or 2, 6-ring positions were tested for bacterial mutagenicity in reverse-mutation assays using Salmonella typhimurium frameshift strains TA1538, TA98, and TA97a, in the presence and absence ...

journal_title：Journal of medicinal chemistry

authors： Venitt S,Crofton-Sleigh C,Agbandje M,Jenkins TC,Neidle S

更新日期：1998-09-10 00:00:00

abstract：:An endogenous heptadecapeptide, nociceptin/orphanin FQ (N/OFQ), and a G-protein-coupled receptor, N/OFQ peptide (NOP) receptor [or opioid-receptor-like-1 (ORL1) receptor], have been described in terms of its structure, distribution, and pharmacology. Thus, the N/OFQ and NOP receptor are located in the central nervous ...

journal_title：Journal of medicinal chemistry

authors： Hayashi S,Hirao A,Imai A,Nakamura H,Murata Y,Ohashi K,Nakata E

更新日期：2009-02-12 00:00:00

abstract：:Bioconjugates composed of chlorotoxin and near-infrared fluorescent (NIRF) moieties are being advanced toward human clinical trials as intraoperative imaging agents that will enable surgeons to visualize small foci of cancer. In previous studies, the NIRF molecules were conjugated to chlorotoxin, which results in a mi...

journal_title：Journal of medicinal chemistry

authors： Akcan M,Stroud MR,Hansen SJ,Clark RJ,Daly NL,Craik DJ,Olson JM

更新日期：2011-02-10 00:00:00

abstract：:Edelfosine (ET-18-OCH3), a synthetic antitumor ether lipid, is taken up by malignant but not by normal cells, triggering apoptosis in a large variety of human tumor cells. The synthesis of the first fluorescent edelfosine analogue (6), with apoptotic activity comparable to that of the parent drug, is described. Fluore...

journal_title：Journal of medicinal chemistry

authors： Quesada E,Delgado J,Gajate C,Mollinedo F,Acuña AU,Amat-Guerri F

更新日期：2004-10-21 00:00:00

abstract：:A series of new spiroglumide amido acid derivatives was synthesized and evaluated for their ability to inhibit the binding of cholecystokinin (CCK) to guinea pig brain cortex (CCKB receptors) and peripheral rat pancreatic acini (CCKA receptors), as well as to inhibit in vitro the gastrin-induced Ca2+ increase in rabbi...

journal_title：Journal of medicinal chemistry

authors： Makovec F,Peris W,Frigerio S,Giovanetti R,Letari O,Mennuni L,Revel L

更新日期：1996-01-05 00:00:00

abstract：:This study aims to identify inhibitors that bind at the interface of HIV-1 integrase (IN) and human LEDGF/p75, which represents a novel target for anti-HIV therapy. To date, only a few such inhibitors have been reported. Here structure-based virtual screening was performed to search for the inhibitors from an in-house...

journal_title：Journal of medicinal chemistry

authors： Hu G,Li X,Zhang X,Li Y,Ma L,Yang LM,Liu G,Li W,Huang J,Shen X,Hu L,Zheng YT,Tang Y

更新日期：2012-11-26 00:00:00