A flexible approach to induced fit docking.

abstract：:Janus kinases (JAK1, JAK2, JAK3, and TYK2) are involved in the signaling of multiple cytokines important in cellular function. Blockade of the JAK-STAT pathway with a small molecule has been shown to provide therapeutic immunomodulation. Having identified JAK1 as a possible new target for arthritis at Galapagos, the c...

journal_title：Journal of medicinal chemistry

authors： Menet CJ,Fletcher SR,Van Lommen G,Geney R,Blanc J,Smits K,Jouannigot N,Deprez P,van der Aar EM,Clement-Lacroix P,Lepescheux L,Galien R,Vayssiere B,Nelles L,Christophe T,Brys R,Uhring M,Ciesielski F,Van Rompaey L

更新日期：2014-11-26 00:00:00

abstract：:The synthesis of a series of N-phosphonalkyl dipeptides 6 is described. Syntheses were devised that allowed the preparation of single diastereoisomers and the assignment of stereochemistry. The compounds were evaluated in vitro for their ability to inhibit the degradation of radiolabeled collagen by purified human lun...

journal_title：Journal of medicinal chemistry

authors： Bird J,De Mello RC,Harper GP,Hunter DJ,Karran EH,Markwell RE,Miles-Williams AJ,Rahman SS,Ward RW

更新日期：1994-01-07 00:00:00

abstract：:A computational approach for molecular design, PRO_LIGAND, has been developed within the PROMETHEUS molecular design and simulation system in order to provide a unified framework for the de novo generation of diverse molecules which are either similar or complementary to a specified target. In this instance, the targe...

journal_title：Journal of medicinal chemistry

authors： Waszkowycz B,Clark DE,Frenkel D,Li J,Murray CW,Robson B,Westhead DR

更新日期：1994-11-11 00:00:00

abstract：:Adrenomedullin (AM) is a peptide hormone implicated in blood pressure regulation and in the pathophysiology of several diseases such as hypertension, cancer, diabetes, and renal disorders, becoming an interesting new target for the development of drugs. In a recent high-throughput screening study, a positive modulator...

journal_title：Journal of medicinal chemistry

authors： García MA,Martín-Santamaría S,Cacho M,de la Llave FM,Julián M,Martínez A,de Pascual-Teresa B,Ramos A

更新日期：2005-06-16 00:00:00

abstract：:The EP(3) receptor on the platelet mediates prostaglandin E(2) potentiation of thrombogenic coagonists including collagen and adenosine diphosphate (ADP). A pharmacophore driven approach led to the identification of diverse peri-substituted heterocycles as potent and selective EP(3) receptor antagonists. A simultaneou...

journal_title：Journal of medicinal chemistry

authors： Singh J,Zeller W,Zhou N,Hategan G,Mishra RK,Polozov A,Yu P,Onua E,Zhang J,Ramírez JL,Sigthorsson G,Thorsteinnsdottir M,Kiselyov AS,Zembower DE,Andrésson T,Gurney ME

更新日期：2010-01-14 00:00:00

abstract：:Cathepsin B (CTB) is a cysteine protease believed to be an important therapeutic target or biomarker for several diseases including aggressive cancer, arthritis, and parasitic infections. The development of probes capable of assessing CTB activity in cell lysates, living cells, and animal models of disease are needed ...

journal_title：Journal of medicinal chemistry

authors： Chowdhury MA,Moya IA,Bhilocha S,McMillan CC,Vigliarolo BG,Zehbe I,Phenix CP

更新日期：2014-07-24 00:00:00

abstract：:The previous paper reported on the synthesis and pharmacological evaluation of N-(6-amino-3-pyridyl)-N'-bicycloalkyl-N"-cyanoguanidine derivatives, from among which three compounds were selected as potent potassium-channel openers. In the present study, selected compounds were tested for antagonism of potassium-induce...

journal_title：Journal of medicinal chemistry

authors： Eda M,Takemoto T,Ono S,Okada T,Kosaka K,Gohda M,Matzno S,Nakamura N,Fukaya C

更新日期：1994-06-24 00:00:00

abstract：:Reaction of nitric oxide (NO) with L-proline in methanolic sodium methoxide yields a diazeniumdiolate product, C5H7N3O4Na2.CH3OH (PROLI/NO), that can be stabilized in basic solution but that dissociates to proline (1 mol) and NO (2 mol) with a half-life of only 1.8 s at pH 7.4 and 37 degrees C. This kinetic behavior h...

journal_title：Journal of medicinal chemistry

authors： Saavedra JE,Southan GJ,Davies KM,Lundell A,Markou C,Hanson SR,Adrie C,Hurford WE,Zapol WM,Keefer LK

更新日期：1996-10-25 00:00:00

abstract：:A new approach to generating information on ligand receptor interactions within the binding pocket of G protein-coupled receptors has been developed, called Biophysical Mapping (BPM). Starting from a stabilized receptor (StaR), minimally engineered for thermostability, additional single mutations are then added at pos...

journal_title：Journal of medicinal chemistry

authors： Zhukov A,Andrews SP,Errey JC,Robertson N,Tehan B,Mason JS,Marshall FH,Weir M,Congreve M

更新日期：2011-07-14 00:00:00

abstract：:Since their discovery over 5 decades ago, quinolone antibiotics have found enormous success as broad spectrum agents that exert their activity through dual inhibition of bacterial DNA gyrase and topoisomerase IV. Increasing rates of resistance, driven largely by target-based mutations in the GyrA/ParC quinolone resist...

journal_title：Journal of medicinal chemistry

authors： Skepper CK,Armstrong D,Balibar CJ,Bauer D,Bellamacina C,Benton BM,Bussiere D,De Pascale G,De Vicente J,Dean CR,Dhumale B,Fisher LM,Fuller J,Fulsunder M,Holder LM,Hu C,Kantariya B,Lapointe G,Leeds JA,Li X,Lu P,Lv

更新日期：2020-07-23 00:00:00

abstract：:A series of 2-substituted methyl 2,3-dihydroimidazo[1, 2-c]quinazolin-5(6H)-ones (4), 3-substituted methyl 2, 3-dihydroimidazo[1,2-c]quinazolin-5(6H)-ones (5), 3-substituted methyl 2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-ones (15a,b), 3-substituted methyl 2,3-dihydroimidazo[2,1-b]quinazolin-5(1H)-ones (16a,b), 3-su...

journal_title：Journal of medicinal chemistry

authors： Chern JW,Tao PL,Wang KC,Gutcait A,Liu SW,Yen MH,Chien SL,Rong JK

更新日期：1998-08-13 00:00:00

abstract：:N-Piperidinopropyl-galanthamine (2) and N-saccharinohexyl-galanthamine (3) were used to investigate interaction sites along the active site gorge of Torpedo californica actylcholinesterase (TcAChE). The crystal structure of TcAChE-2 solved at 2.3 A showed that the N-piperidinopropyl group in 2 is not stretched along t...

journal_title：Journal of medicinal chemistry

authors： Bartolucci C,Haller LA,Jordis U,Fels G,Lamba D

更新日期：2010-01-28 00:00:00

abstract：:A series of 7 alpha-methoxy-7 beta-amido-3-chloro-3-cephem-4-carboxylic acids was prepared and evaluated for biological activity. When compared with the parent 7-non-methoxy analogues, these new 7 alpha-methoxy-3-chloro cephalosporins displayed diminished antimicrobial activity. ...

journal_title：Journal of medicinal chemistry

authors： Pfeil-Doyle J,Kukolja S

更新日期：1988-10-01 00:00:00

abstract：:Cathepsin K is a major drug target for osteoporosis and related-bone disorders. Using a combination of virtual combinatorial chemistry, QSAR modeling, and molecular docking studies, a series of cathepsin K inhibitors based on N-(functionalized benzoyl)-homocycloleucyl-glycinonitrile scaffold was developed. In order to...

journal_title：Journal of medicinal chemistry

authors： Borišek J,Vizovišek M,Sosnowski P,Turk B,Turk D,Mohar B,Novič M

更新日期：2015-09-10 00:00:00

abstract：:Mono- and diphenylpyridazine ureido derivatives, structurally related to DuP 128, were synthesized and tested for their inhibitory activity against ACAT isolated from rat liver microsomes. Several compounds displayed ACAT inhibition in the micromolar range. The amino derivatives 4a-c were also tested against hACAT-1 a...

journal_title：Journal of medicinal chemistry

authors： Gelain A,Bettinelli I,Barlocco D,Kwon BM,Jeong TS,Cho KH,Toma L

更新日期：2005-12-01 00:00:00

abstract：:Pyroptosis is a caspase-1-dependent pro-inflammatory form of programmed cell death implicated in the pathogenesis of autoinflammatory diseases as well as in disorders characterized by excessive cell death and inflammation. Activation of NLRP3 inflammasome is a key event in the pyroptotic cascade. In this study, we des...

journal_title：Journal of medicinal chemistry

authors： Cocco M,Garella D,Di Stilo A,Borretto E,Stevanato L,Giorgis M,Marini E,Fantozzi R,Miglio G,Bertinaria M

更新日期：2014-12-26 00:00:00

abstract：:A three-dimensional model of the AT1 receptor was constructed by means of a homology modeling procedure, using the X-ray structure of bovine rhodopsin as the initial template and taking into account the available site-directed mutagenesis data. The docking of losartan and its active metabolite EXP3174, followed by 1 n...

journal_title：Journal of medicinal chemistry

authors： Tuccinardi T,Calderone V,Rapposelli S,Martinelli A

更新日期：2006-07-13 00:00:00

abstract：:The preparation of stable complexes between the N7-[2-(2-pyridyl)ethyl] and N7-(2-piperazinylethyl) derivatives of mitomycin C and metal ions such as Cu(II), Zn(II), and Pt(II) was accomplished. Mitomycin C did not form stable complexes, but it rearranged to a mitosene capable of complex formation. Some of these compl...

journal_title：Journal of medicinal chemistry

authors： Iyengar BS,Takahashi T,Remers WA,Bradner WT

更新日期：1986-01-01 00:00:00

abstract：:A series of 2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-ones were synthesized and evaluated for anticonvulsant activity in DBA/2 mice against sound-induced seizures and in rats against maximal electroshock-induced seizures. Most of the derivatives showed an anticonvulsant effect better than that of valproate, ...

journal_title：Journal of medicinal chemistry

authors： Chimirri A,De Sarro A,De Sarro G,Grasso S,Trimarchi GR,Zappalà M

更新日期：1989-01-01 00:00:00

abstract：:C-terminally truncated fragments of human alpha-calcitonin gene-related peptide (h-alpha-CGRP) were tested for their ability to stimulate amylase secretion from pancreatic acinar cells and relax precontracted mesenteric arteries. h-alpha-CGRP, h-alpha-CGRP (1-36), h-alpha-CGRP (1-35), and h-alpha-CGRP (1-34) were made...

journal_title：Journal of medicinal chemistry

authors： Smith DD,Li J,Wang Q,Murphy RF,Adrian TE,Elias Y,Bockman CS,Abel PW

更新日期：1993-08-20 00:00:00

abstract：:We report the syntheses of first-generation derivatives of isothiazolopyridones and their in vitro evaluation as antibacterial agents. These compounds, containing a novel heterocyclic nucleus composed of an isothiazolone fused to a quinolizin-4-one (at C-2 and C-3 of the quinolizin-4-one), were prepared using a sequen...

journal_title：Journal of medicinal chemistry

authors： Wiles JA,Hashimoto A,Thanassi JA,Cheng J,Incarvito CD,Deshpande M,Pucci MJ,Bradbury BJ

更新日期：2006-01-12 00:00:00

abstract：:A group of oligopeptides has been synthesized that are structurally related to the natural antiviral antitumor agents netropsin and distamycin but which bear alkylating functions. Cytostatic activity against both human and murine tumor cell lines as well as their in vitro activity against a range of viruses is reporte...

journal_title：Journal of medicinal chemistry

authors： Krowicki K,Balzarini J,De Clercq E,Newman RA,Lown JW

更新日期：1988-02-01 00:00:00

abstract：:New efficient antifungal agents are urgently needed to treat drug-resistant fungal infections. Here, we designed and synthesized a series of cationic xanthone amphiphilics as antifungal agents from natural α-mangostin to combat fungal resistance. The attachment of cationic residues on the xanthone scaffold of α-mangos...

journal_title：Journal of medicinal chemistry

authors： Lin S,Sin WLW,Koh JJ,Lim F,Wang L,Cao D,Beuerman RW,Ren L,Liu S

更新日期：2017-12-28 00:00:00

abstract：:The synthesis of new meridianin derivatives is described. The indolic ring system was substituted at the C-4 to C-7 positions either by a bromine atom or by nitro or amino groups. Additionally, an iodine atom or various aryl groups were introduced at the C-5 position of the 2-aminopyrimidine ring. These compounds as w...

journal_title：Journal of medicinal chemistry

authors： Giraud F,Alves G,Debiton E,Nauton L,Théry V,Durieu E,Ferandin Y,Lozach O,Meijer L,Anizon F,Pereira E,Moreau P

更新日期：2011-07-14 00:00:00

abstract：:We present the first report of the application of the dipeptidyl peptidase IV (DPPIV/CD26) based prodrug approach to hydroxy-containing drug derivatives. In particular, we applied this strategy to the highly lipophilic antiviral drug family of bicyclic furanopyrimidine nucleoside analogues (BCNA) in order to improve t...

journal_title：Journal of medicinal chemistry

authors： Diez-Torrubia A,Balzarini J,Andrei G,Snoeck R,De Meester I,Camarasa MJ,Velázquez S

更新日期：2011-03-24 00:00:00

abstract：:Attempts to directly drug the important oncogene KRAS have met with limited success despite numerous efforts across industry and academia. The KRASG12C mutant represents an "Achilles heel" and has recently yielded to covalent targeting with small molecules that bind the mutant cysteine and create an allosteric pocket ...

journal_title：Journal of medicinal chemistry

authors： Kettle JG,Bagal SK,Bickerton S,Bodnarchuk MS,Breed J,Carbajo RJ,Cassar DJ,Chakraborty A,Cosulich S,Cumming I,Davies M,Eatherton A,Evans L,Feron L,Fillery S,Gleave ES,Goldberg FW,Harlfinger S,Hanson L,Howard M,Howe

更新日期：2020-05-14 00:00:00

abstract：:A series of thymidylate synthetase inhibitors was synthesized, some of which were potential irreversible inhibitors. 5-Formyl-2'-deoxyuridine (9) and its dithiolane derivative 11 were prepared by condensation of the bis(trimethylsilyl) derivative of 5-formyluracil dimethyl acetal and the protected chloro sugar followe...

journal_title：Journal of medicinal chemistry

authors： Kampf A,Pillar CJ,Woodford WJ,Mertes MP

更新日期：1976-07-01 00:00:00

abstract：:Glucose-dependent insulinotropic polypeptide (GIP) is a physiological insulin releasing peptide. We have developed two novel fatty acid derivatized GIP analogues, which bind to serum albumin and demonstrate enhanced duration of action in vivo. GIP(Lys(16)PAL) and GIP(Lys(37)PAL) were resistant to dipeptidyl peptidase ...

journal_title：Journal of medicinal chemistry

authors： Irwin N,O'Harte FP,Gault VA,Green BD,Greer B,Harriott P,Bailey CJ,Flatt PR

更新日期：2006-02-09 00:00:00

abstract：:Water-ligand observed via gradient spectroscopy (WaterLOGSY) represents a powerful method for primary NMR screening in the identification of compounds interacting with macromolecules, including proteins and DNA or RNA fragments. The method is useful for the detection of compounds binding to a receptor with binding aff...

journal_title：Journal of medicinal chemistry

authors： Dalvit C,Fasolini M,Flocco M,Knapp S,Pevarello P,Veronesi M

更新日期：2002-06-06 00:00:00

abstract：:In the present study, the synthesis of the 5.5.6. and 5.6.5. spiro bicyclic lactam PLG peptidomimetics, compounds 3 and 4, respectively, was undertaken. These peptidomimetics were designed to examine the following: (1) the effect that changing the size of the thiazolidine and lactam ring systems would have on the abil...

journal_title：Journal of medicinal chemistry

authors： Khalil EM,Ojala WH,Pradhan A,Nair VD,Gleason WB,Mishra RK,Johnson RL

更新日期：1999-02-25 00:00:00