Effect of structural change on acute toxicity and antiinflammatory activity in a series of imidazothiazoles and thiazolobenzimidazoles.

abstract：:Cyclin dependent kinases are a key family of kinases involved in cell cycle regulation and are an attractive target for cancer chemotherapy. The roles of four residues of the cyclin-dependent kinase active site in inhibitor selectivity were investigated by producing cyclin-dependent kinase 2 mutants bearing equivalent...

journal_title：Journal of medicinal chemistry

authors： Pratt DJ,Bentley J,Jewsbury P,Boyle FT,Endicott JA,Noble ME

更新日期：2006-09-07 00:00:00

abstract：:A series of quinolone and naphthyridine antibacterial agents possessing as the C7-heterocycle bicyclic 2,5-diazabicyclo[n.2.m]alkanes, where n = 2, 3 and m = 1, 2, and a series including 4-aminopiperidine and 3-amino-8-azabicyclo[3.2.1]octanes have been prepared and evaluated in vitro and in vivo for antibacterial act...

journal_title：Journal of medicinal chemistry

authors： Kiely JS,Hutt MP,Culbertson TP,Bucsh RA,Worth DF,Lesheski LE,Gogliotti RD,Sesnie JC,Solomon M,Mich TF

更新日期：1991-02-01 00:00:00

abstract：:Substitution at the ortho position of N-(3,4-dimethyl-5-isoxazolyl) benzenesulfonamide led to the identification of the biphenylsulfonamides as a novel series of endothelin-A (ETA) selective antagonists. Appropriate substitutions on the pendant phenyl ring led to improved binding as well as functional activity. A hydr...

journal_title：Journal of medicinal chemistry

authors： Murugesan N,Gu Z,Stein PD,Bisaha S,Spergel S,Girotra R,Lee VG,Lloyd J,Misra RN,Schmidt J,Mathur A,Stratton L,Kelly YF,Bird E,Waldron T,Liu EC,Zhang R,Lee H,Serafino R,Abboa-Offei B,Mathers P,Giancarli M,Seymou

更新日期：1998-12-17 00:00:00

abstract：:Starting from the lead isodaphnetin, a natural product inhibitor of DPP-4 discovered through a target fishing docking based approach, a series of novel 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine derivatives as potent DPP-4 inhibitors are rationally designed utilizing highly efficient 3D molecular similarity based...

journal_title：Journal of medicinal chemistry

authors： Li S,Xu H,Cui S,Wu F,Zhang Y,Su M,Gong Y,Qiu S,Jiao Q,Qin C,Shan J,Zhang M,Wang J,Yin Q,Xu M,Liu X,Wang R,Zhu L,Li J,Xu Y,Jiang H,Zhao Z,Li J,Li H

更新日期：2016-07-28 00:00:00

abstract：:N5-Acetyl-N5-hydroxy-L-ornithyl-N5-acetyl-N5-hydroxy-L-ornithyl-N5-acety l- N5-hydroxy-L-ornithine, the functionally instrumental component of the albomycins and ferrichromes, has been incorporated as a "carrier" substructure into both carbacephalosporin and oxamazin type beta-lactam antibiotics. The previously synthe...

journal_title：Journal of medicinal chemistry

authors： Dolence EK,Minnick AA,Lin CE,Miller MJ,Payne SM

更新日期：1991-03-01 00:00:00

abstract：:Some glycine, leucine and phenylalanine dipeptide derivatives of the transport inhibitory, tricycloaliphatic alpha-amino acid, adamantanine (1), have been synthesized using classical methods of peptide synthesis with the aim of improving the latter's bioavailability. Although test doses of glycyladamantanine and L-leu...

journal_title：Journal of medicinal chemistry

authors： Nagasawa HT,Elberling JA,Shirota FN

更新日期：1975-08-01 00:00:00

abstract：:It is well established that intramolecular hydrogen bonding and N-methylation play important roles in the passive permeability of cyclic peptides, but other structural features have been explored less intensively. Recent studies on the oral bioavailability of the cyclic heptapeptide sanguinamide A have raised the ques...

journal_title：Journal of medicinal chemistry

authors： Bockus AT,Schwochert JA,Pye CR,Townsend CE,Sok V,Bednarek MA,Lokey RS

更新日期：2015-09-24 00:00:00

abstract：:In humans, bitter taste is mediated by 25 TAS2Rs. Many compounds, including certain active pharmaceutical ingredients, excipients, and nutraceuticals, impart their bitter taste (or in part) through TAS2R8 activation. However, effective TAS2R8 blockers that can either suppress or reduce the bitterness of these compound...

journal_title：Journal of medicinal chemistry

authors： Fotsing JR,Darmohusodo V,Patron AP,Ching BW,Brady T,Arellano M,Chen Q,Davis TJ,Liu H,Servant G,Zhang L,Williams M,Saganich M,Ditschun T,Tachdjian C,Karanewsky DS

更新日期：2020-05-14 00:00:00

abstract：:The Mediterranean tunicate Stolonica socialis contains a new class of powerful cytotoxic acetogenins, generically named stolonoxides. In this paper, which also details the isolation and chemical characterization of a minor component (3a) of the tunicate extract, we report the potent inhibitory activity (IC(50) < 1 mic...

journal_title：Journal of medicinal chemistry

authors： Fontana A,Cimino G,Gavagnin M,González MC,Estornell E

更新日期：2001-07-05 00:00:00

abstract：:A series of 3-fluoromethyl-1,2,3,4-tetrahydroisoquinolines (3-fluoromethyl-THIQs) was proposed, and their phenylethanolamine N-methyltransferase (PNMT) and alpha(2)-adrenoceptor affinities were predicted through the use of comparative molecular field analysis (CoMFA) models. These compounds were synthesized and evalua...

journal_title：Journal of medicinal chemistry

authors： Grunewald GL,Caldwell TM,Li Q,Slavica M,Criscione KR,Borchardt RT,Wang W

更新日期：1999-09-09 00:00:00

abstract：:A series of analogues of the analgesic dipeptide derivative H-Lys-Trp(NPS)-OMe has been designed to determine the influence of the (2-nitrophenyl)sulfenyl (NPS) moiety on the activity. The syntheses and antinociceptive effects of these analogues of general formula H-Lys-Trp(R)-OMe [R = phenylsulfenyl (PS) (9); R = (2-...

journal_title：Journal of medicinal chemistry

authors： Garcia-López MT,González-Muñiz R,Molinero MT,Naranjo JR,Del Rio J

更新日期：1987-09-01 00:00:00

abstract：:We previously reported that [[N-[3beta-hydroxyllup-20(29)-en-28-oyl]-7-aminoheptyl]carbamoyl]methane (A43D, 4) was a potent HIV-1 entry inhibitor. However, 4 was inactive against HIV-2 virus, suggesting the structural requirements for targeting these two retroviruses are different. In this study, a series of new betul...

journal_title：Journal of medicinal chemistry

authors： Dang Z,Lai W,Qian K,Ho P,Lee KH,Chen CH,Huang L

更新日期：2009-12-10 00:00:00

abstract：:Four 11-(1-piperazinyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepines were prepared and evaluated as central nervous system agents. All were active psychotropic agents as determined by animal screening tests. The most interesting compound, 11-(1-piperazinyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine, showed dual activity as an ant...

journal_title：Journal of medicinal chemistry

authors： Wright WB Jr,Greenblatt EN,Day IP,Quinones NQ,Hardy RA Jr

更新日期：1980-04-01 00:00:00

abstract：:In an attempt to rationalize the inability of phenolic benzocycloheptenylamines to activate dopamine (DA) D2 receptors, we have studied the conformational preferences and topography of 6,7,8,9-tetrahydro-1-hydroxy-N,N-dipropyl-5H-benzocyclohepten-6-++ +ylamine (1). Preferred conformations of 1 have been defined by use...

journal_title：Journal of medicinal chemistry

authors： Karlén A,Helander A,Kenne L,Hacksell U

更新日期：1989-04-01 00:00:00

abstract：:The 3C-like proteinase (3CL(pro)) of severe acute respiratory syndrome (SARS) coronavirus is a key target for structure-based drug design against this viral infection. The enzyme recognizes peptide substrates with a glutamine residue at the P1 site. A series of keto-glutamine analogues with a phthalhydrazido group at ...

journal_title：Journal of medicinal chemistry

authors： Jain RP,Pettersson HI,Zhang J,Aull KD,Fortin PD,Huitema C,Eltis LD,Parrish JC,James MN,Wishart DS,Vederas JC

更新日期：2004-12-02 00:00:00

abstract：:A series of imidazo[1,2-b]thiazole derivatives is shown to activate the NAD(+)-dependent deacetylase SIRT1, a potential new therapeutic target to treat various metabolic disorders. This series of compounds was derived from a high throughput screening hit bearing an oxazolopyridine core. Water-solubilizing groups could...

journal_title：Journal of medicinal chemistry

authors： Vu CB,Bemis JE,Disch JS,Ng PY,Nunes JJ,Milne JC,Carney DP,Lynch AV,Smith JJ,Lavu S,Lambert PD,Gagne DJ,Jirousek MR,Schenk S,Olefsky JM,Perni RB

更新日期：2009-03-12 00:00:00

abstract：:Building on insights gained from the discovery of the antimalarial ozonide arterolane (OZ277), we now describe the structure-activity relationship (SAR) of the antimalarial ozonide artefenomel (OZ439). Primary and secondary amino ozonides had higher metabolic stabilities than tertiary amino ozonides, consistent with t...

journal_title：Journal of medicinal chemistry

authors： Dong Y,Wang X,Kamaraj S,Bulbule VJ,Chiu FC,Chollet J,Dhanasekaran M,Hein CD,Papastogiannidis P,Morizzi J,Shackleford DM,Barker H,Ryan E,Scheurer C,Tang Y,Zhao Q,Zhou L,White KL,Urwyler H,Charman WN,Matile H,Witt

更新日期：2017-04-13 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：:n-Octyl, n-dodecyl, and n-hexadecyl alpha- and gamma-esters of methotrexate (MTX) were compared with the previously described alpha- and gamma-n-butyl esters and with MTX as inhibitors of dihydrofolate reductase (DHFR) and human leukemic lymphoblasts (CEM cells) in culture. The overall order of activity in both test s...

journal_title：Journal of medicinal chemistry

authors： Rosowsky A,Forsch RA,Yu CS,Lazarus H,Beardsley GP

更新日期：1984-05-01 00:00:00

abstract：:Using easily accessible keto-trioxanes 7a-g as the starting materials, a series of new variously functionalized 1,2,4-trioxanes 10-36 have been prepared and evaluated for antimalarial activity against multi-drug-resistant Plasmodium yoelii nigeriensis in mice in the dose range of 24 mg/kg x 4 days to 96 mg/kg x 4 days...

journal_title：Journal of medicinal chemistry

authors： Singh C,Malik H,Puri SK

更新日期：2006-05-04 00:00:00

abstract：:We report the results of a three-dimensional quantitative structure-activity relationship (3D-QSAR) and pharmacophore modeling investigation of the interaction of the enzyme 3-phosphoglycerate kinase (PGK) with aryl and alkyl bisphosphonates. For the human enzyme, the IC50 values are predicted within a factor of 2 ove...

journal_title：Journal of medicinal chemistry

authors： Kotsikorou E,Sahota G,Oldfield E

更新日期：2006-11-16 00:00:00

abstract：:We report on the design, synthesis, and evaluation of a series of furanyl-salicyl-nitroxide derivatives as effective chemical probes for second-site screening against phosphotyrosine phosphatases (PTPs) using NMR-based techniques. The compounds have been tested against a panel of PTPs to assess their ability to inhibi...

journal_title：Journal of medicinal chemistry

authors： Vazquez J,Tautz L,Ryan JJ,Vuori K,Mustelin T,Pellecchia M

更新日期：2007-05-03 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：:Novel quinazolin-4-one derivatives containing a hydroxamic acid moiety were designed and synthesized. All compounds were subjected to histone deacetylase (HDAC) enzymatic assays to identify selective HDAC6 inhibitors with nanomolar IC50 values. (E)-3-(2-Ethyl-7-fluoro-4-oxo-3-phenethyl-3,4-dihydroquinazolin-6-yl)-N-hy...

journal_title：Journal of medicinal chemistry

authors： Yu CW,Chang PT,Hsin LW,Chern JW

更新日期：2013-09-12 00:00:00

abstract：:The effects of 3-position substitution of 9-aminomethyl-9,10-dihydroanthracene (AMDA) on 5-HT 2A receptor affinity were determined and compared to a parallel series of DOB-like 1-(2,5-dimethoxyphenyl)-2-aminopropanes substituted at the 4-position. The results were interpreted within the context of 5-HT 2A receptor mod...

journal_title：Journal of medicinal chemistry

authors： Runyon SP,Mosier PD,Roth BL,Glennon RA,Westkaemper RB

更新日期：2008-11-13 00:00:00

abstract：:To evaluate nonaromatic catechol bioisosteres, the conformationally restrained enynes 1 and enediynes 2 were synthesized via palladium-catalyzed coupling as the key reaction step. Subsequent receptor binding studies at the dopamine receptor subtypes D(1), D(2 long), D(2 short), D(3), and D(4) showed highly interesting...

journal_title：Journal of medicinal chemistry

authors： Hübner H,Haubmann C,Utz W,Gmeiner P

更新日期：2000-02-24 00:00:00

abstract：:Synthesis and identification of novel phenylalkyl isoselenocyanates (ISCs), isosteric selenium analogues of naturally occurring phenylalkyl isothiocyanates (ITCs), as effective cytotoxic and antitumor agents are described. The structure-activity relationship comparison of ISCs with ITCs and effect of the increasing al...

journal_title：Journal of medicinal chemistry

authors： Sharma AK,Sharma A,Desai D,Madhunapantula SV,Huh SJ,Robertson GP,Amin S

更新日期：2008-12-25 00:00:00

abstract：:The binding affinities at rat A1, A2a, and A3 adenosine receptors of a wide range of derivatives of adenosine have been determined. Sites of modification include the purine moiety (1-, 3-, and 7-deaza; halo, alkyne, and amino substitutions at the 2- and 8-positions; and N6-CH2-ring, -hydrazino, and -hydroxylamino) and...

journal_title：Journal of medicinal chemistry

authors： Siddiqi SM,Jacobson KA,Esker JL,Olah ME,Ji XD,Melman N,Tiwari KN,Secrist JA 3rd,Schneller SW,Cristalli G

更新日期：1995-03-31 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：:The cytotoxicities and DNA cross-linking abilities of several alkyl-substituted diaziridinylquinones have been investigated. The cytotoxicities were determined in DT-diaphorase-rich (H460 and HT29) and -deficient (H596 and BE) cell lines. It was shown that the cytotoxicities in these cell lines correlated with the rel...

journal_title：Journal of medicinal chemistry

authors： Hargreaves RH,O'Hare CC,Hartley JA,Ross D,Butler J

更新日期：1999-06-17 00:00:00