Structure-activity relationships of antibacterial 6,7- and 7,8-disubstituted 1-alkyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acids.

abstract：:To provide practical means for rapidly scanning the extensive experimental combinatorial chemistry libraries now available for high-throughput screening (HTS), it is essential to establish computational virtual ligand screening (VLS) techniques to rapidly identify out of a large library all active compounds against a ...

journal_title：Journal of medicinal chemistry

authors： Floriano WB,Vaidehi N,Zamanakos G,Goddard WA 3rd

更新日期：2004-01-01 00:00:00

abstract：:The use of deuteration in medicinal chemistry has exploded in the past years, and the FDA has recently approved the first deuterium-labeled drug. Precision deuteration goes beyond the pure and simple amelioration of the pharmacokinetic parameters of a drug and might provide an opportunity when facing problems in terms...

journal_title：Journal of medicinal chemistry

authors： Pirali T,Serafini M,Cargnin S,Genazzani AA

更新日期：2019-06-13 00:00:00

abstract：:Despite a myriad of available pharmacotherapies for the treatment of type 2 diabetes (T2D), challenges still exist in achieving glycemic control. Several novel glucose-lowering strategies are currently under clinical investigation, highlighting the need for more robust treatments. Previously, we have shown that suppre...

journal_title：Journal of medicinal chemistry

authors： Lin H,Sharabi K,Lin L,Ruiz C,Zhu D,Cameron MD,Novick SJ,Griffin PR,Puigserver P,Kamenecka TM

更新日期：2021-01-28 00:00:00

abstract：:There is compelling evidence that Bax channel activity stimulates cytochrome c release leading ultimately to cell death, which is a key event in ischemic injuries and neurodegenerative diseases. Here 3,6-dibromocarbazole piperazine derivatives of 2-propanol are described as the first small and potent modulators of the...

journal_title：Journal of medicinal chemistry

authors： Bombrun A,Gerber P,Casi G,Terradillos O,Antonsson B,Halazy S

更新日期：2003-10-09 00:00:00

abstract：:If no structural information about a particular target protein is available, methods of rational drug design try to superimpose putative ligands with a given reference, e.g., an endogenous ligand. The goal of such structural alignments is, on the one hand, to approximate the binding geometry and, on the other hand, to...

journal_title：Journal of medicinal chemistry

authors： Lemmen C,Lengauer T,Klebe G

更新日期：1998-11-05 00:00:00

abstract：:A variety of N-(aminoalkanoyl)-S-acylcysteamine and N,N'-bis(aminoalkanoyl)cystamine salt derivatives were synthesized. Toxicity and radioprotective activity (as the dose reduction factor DRF) were determined in vivo on mice and compared to WR 2721 and S-acetylcysteamine hydrochloride. One of the most interesting comp...

journal_title：Journal of medicinal chemistry

authors： Oiry J,Pue JY,Imbach JL,Fatome M,Sentenac-Roumanou H,Lion C

更新日期：1986-11-01 00:00:00

abstract：:Rexinoids are ligands for the retinoid X receptor (RXR) that have great promise for both the prevention and treatment of cancer and metabolic diseases. In this regard, synthetic, functional, and structural investigations into the structure-activity relationships of derivatives of the potent RXR agonist (E)-3-[3-(3,5,5...

journal_title：Journal of medicinal chemistry

authors： Pérez Santín E,Germain P,Quillard F,Khanwalkar H,Rodríguez-Barrios F,Gronemeyer H,de Lera AR,Bourguet W

更新日期：2009-05-28 00:00:00

abstract：:Eight novel single amino acid (6-11) and dipeptide (12, 13) tyrosine P-O esters of cyclic cidofovir ((S)-cHPMPC, 4) and its cyclic adenine analogue ((S)-cHPMPA, 3) were synthesized and evaluated as prodrugs. In vitro IC(50) values for the prodrugs (<0.1-50 μM) vs vaccinia, cowpox, human cytomegalovirus, and herpes sim...

journal_title：Journal of medicinal chemistry

authors： Zakharova VM,Serpi M,Krylov IS,Peterson LW,Breitenbach JM,Borysko KZ,Drach JC,Collins M,Hilfinger JM,Kashemirov BA,McKenna CE

更新日期：2011-08-25 00:00:00

abstract：:Genetic mutations in the phosphatase PTPN11 (SHP2) are associated with childhood leukemias. These mutations cause hyperactivation of SHP2 due to the disruption of the autoinhibitory conformation. By targeting the activation-associated protein conformational change, we have identified an SHP2 inhibitor ( E)-1-(1-(5-(3-...

journal_title：Journal of medicinal chemistry

authors： Wu X,Xu G,Li X,Xu W,Li Q,Liu W,Kirby KA,Loh ML,Li J,Sarafianos SG,Qu CK

更新日期：2019-02-14 00:00:00

abstract：:A novel series of 3-heteroaryl-5,6-bis(aryl)-1-methyl-2-pyridones were developed with high affinity for the benzodiazepine (BZ) binding site of human gamma-aminobutyric acid (GABA(A)) receptor ion channels, low binding selectivity for alpha 2- and/or alpha 3- over alpha 1-containing GABA(A) receptor subtypes and high ...

journal_title：Journal of medicinal chemistry

authors： Collins I,Moyes C,Davey WB,Rowley M,Bromidge FA,Quirk K,Atack JR,McKernan RM,Thompson SA,Wafford K,Dawson GR,Pike A,Sohal B,Tsou NN,Ball RG,Castro JL

更新日期：2002-04-25 00:00:00

abstract：:The medicinal chemistry community has directed considerable efforts toward the discovery of selective inhibitors of interleukin-2 inducible T-cell kinase (ITK), given its role in T-cell signaling downstream of the T-cell receptor (TCR) and the implications of this target for inflammatory disorders such as asthma. We h...

journal_title：Journal of medicinal chemistry

authors： Burch JD,Barrett K,Chen Y,DeVoss J,Eigenbrot C,Goldsmith R,Ismaili MH,Lau K,Lin Z,Ortwine DF,Zarrin AA,McEwan PA,Barker JJ,Ellebrandt C,Kordt D,Stein DB,Wang X,Chen Y,Hu B,Xu X,Yuen PW,Zhang Y,Pei Z

更新日期：2015-05-14 00:00:00

abstract：:Several N-2 substituted 1-methyl-1-(4-tolylsulfonyl)hydrazines were synthesized and evaluated for antineoplastic activity against the L1210 leukemia and the B16 melanoma. The most active compound to emerge from this study, 2-(methylsulfonyl)-1-methyl-1-(4-tolylsulfonyl)hydrazine, produced maximum percent T/C values wi...

journal_title：Journal of medicinal chemistry

authors： Hrubiec RT,Shyam K,Cosby LA,Furubayashi R,Sartorelli AC

更新日期：1986-07-01 00:00:00

abstract：:Comparative molecular field analysis and comparative molecular similarity indices analysis were performed on 114 analogues of 1,2-diarylimidazole to optimize their cyclooxygenase-2 (COX-2) selective antiinflammatory activities. These studies produced models with high correlation coefficients and good predictive abilit...

journal_title：Journal of medicinal chemistry

authors： Desiraju GR,Gopalakrishnan B,Jetti RK,Nagaraju A,Raveendra D,Sarma JA,Sobhia ME,Thilagavathi R

更新日期：2002-10-24 00:00:00

abstract：:A series of novel chiral 7-(1-, 3-, 4-, and 6-methyl-[(1R,4R)-2,5- diazabicyclo[2.2.1]heptan-2-yl]-substituted naphthyridines has been prepared with the aim of obtaining good in vitro and in vivo antibacterial agents with a decrease of the pseudoallergic type reaction when compared to that observed with 7[(1R,4R)-2,5-...

journal_title：Journal of medicinal chemistry

authors： Remuzon P,Bouzard D,Guiol C,Jacquet JP

更新日期：1992-07-24 00:00:00

abstract：:A unique, dual-function, photoactivatable anticancer prodrug, RuEuL, has been tailored that features a ruthenium(II) complex linked to a cyclen-europium chelate via a π-conjugated bridge. Under irradiation at 488 nm, the dark-inactive prodrug undergoes photodissociation, releasing the DNA-damaging ruthenium species. U...

journal_title：Journal of medicinal chemistry

authors： Li H,Xie C,Lan R,Zha S,Chan CF,Wong WY,Ho KL,Chan BD,Luo Y,Zhang JX,Law GL,Tai WCS,Bünzli JG,Wong KL

更新日期：2017-11-09 00:00:00

abstract：:We previously reported the discovery of 4-[(Z)-(4-bromophenyl)(ethoxyimino)methyl]-1'-[(2,4-dimethyl-3-pyridinyl)carbonyl]-4'-methyl-1,4'-bipiperidine N-oxide 1 (SCH 351125) as an orally bioavailable human CCR5 antagonist for the treatment of HIV-1 infection. Herein, we describe in detail the discovery of 1 from our i...

journal_title：Journal of medicinal chemistry

authors： Palani A,Shapiro S,Josien H,Bara T,Clader JW,Greenlee WJ,Cox K,Strizki JM,Baroudy BM

更新日期：2002-07-04 00:00:00

abstract：:Fatty acid amide hydrolase (FAAH) degrades neuromodulating fatty acid amides including anandamide (endogenous cannabinoid agonist) and oleamide (sleep-inducing lipid) at their sites of action and is intimately involved in their regulation. Herein we report the discovery of a potent, selective, and efficacious class of...

journal_title：Journal of medicinal chemistry

authors： Boger DL,Miyauchi H,Du W,Hardouin C,Fecik RA,Cheng H,Hwang I,Hedrick MP,Leung D,Acevedo O,Guimarães CR,Jorgensen WL,Cravatt BF

更新日期：2005-03-24 00:00:00

abstract：:Ghrelin, a gut-derived orexigenic hormone, is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R). Centrally administered ghrelin has been shown to cause hunger and increase food intake in rodents. Inhibition of ghrelin actions with ghrelin antibody, peptidyl GHS-R antagonists, and antisense oligo...

journal_title：Journal of medicinal chemistry

authors： Serby MD,Zhao H,Szczepankiewicz BG,Kosogof C,Xin Z,Liu B,Liu M,Nelson LT,Kaszubska W,Falls HD,Schaefer V,Bush EN,Shapiro R,Droz BA,Knourek-Segel VE,Fey TA,Brune ME,Beno DW,Turner TM,Collins CA,Jacobson PB,Sham H

更新日期：2006-04-20 00:00:00

abstract：:A 2A adenosine receptor antagonists usually have bi- or tricyclic N aromatic systems with varying substitution patterns to achieve desired receptor affinity and selectivity. Using a pharmacophore model designed by overlap of nonxanthine type of previously known A 2A antagonists, we synthesized a new class of compounds...

journal_title：Journal of medicinal chemistry

authors： Mantri M,de Graaf O,van Veldhoven J,Göblyös A,von Frijtag Drabbe Künzel JK,Mulder-Krieger T,Link R,de Vries H,Beukers MW,Brussee J,Ijzerman AP

更新日期：2008-08-14 00:00:00

abstract：:Following erythrocyte invasion, malaria parasites export a catalogue of remodeling proteins into the infected cell that enable parasite development in the human host. Export is dependent on the activity of the aspartyl protease, plasmepsin V (PMV), which cleaves proteins within the Plasmodium export element (PEXEL; Rx...

journal_title：Journal of medicinal chemistry

authors： Sleebs BE,Gazdik M,O'Neill MT,Rajasekaran P,Lopaticki S,Lackovic K,Lowes K,Smith BJ,Cowman AF,Boddey JA

更新日期：2014-09-25 00:00:00

abstract：:Quadruplex-forming sequences are widely prevalent in human and other genomes, including bacterial ones. These sequences are over-represented in eukaryotic telomeres, promoters, and 5' untranslated regions. They can form quadruplex structures, which may be transient in many situations in normal cells since they can be ...

journal_title：Journal of medicinal chemistry

authors： Neidle S

更新日期：2016-07-14 00:00:00

abstract：:Little is known of the conformation of peptide hormones as they interact with their receptors for a number of reasons: peptide hormones are notoriously flexible in solution, their receptors are particularly complex, and there is strong evidence that receptor-ligand interaction leading to activation is a dynamic proces...

journal_title：Journal of medicinal chemistry

authors： Koerber SC,Rizo J,Struthers RS,Rivier JE

更新日期：2000-03-09 00:00:00

abstract：:Two new analogues derived from the platelet activating factor (PAF), containing glucosamine instead of the acetyl group, were synthesized, and their effect on the human keratinocyte cell line HaCaT was evaluated with respect to cytotoxicity, proliferation, adhesion, and migration. Starting with (R)-1,2-isopropylideneg...

journal_title：Journal of medicinal chemistry

authors： Bartolmäs T,Heyn T,Mickeleit M,Fischer A,Reutter W,Danker K

更新日期：2005-10-20 00:00:00

abstract：:We synthesized two series (7a-i and 8a-i) of 2,3,5-substituted [1,2,4]-thiadiazole analogues of SCH-202676 (7a, 2,3-diphenyl-5-N-methylimino-2H-[1,2,4]-thiadiazole) with emphasis on the N-imino substituent. Compounds 7a-g,i and 8a-g at a final concentration of 1 microM significantly inhibited [(3)H]CCPA (2-chloro-N(6)...

journal_title：Journal of medicinal chemistry

authors： Göblyös A,de Vries H,Brussee J,Ijzerman AP

更新日期：2005-02-24 00:00:00

abstract：:By use of standard cuprate methodology, a series of 18-cycloalkyl analogues of enisoprost was prepared in an effort to impede omega chain metabolism and prolong duration of gastric antisecretory activity. An initial product of omega chain oxidation, the C-20 hydroxy analogue, was also synthesized for pharmacological c...

journal_title：Journal of medicinal chemistry

authors： Collins PW,Gasiecki AF,Perkins WE,Gullikson GW,Jones PH,Bauer RF

更新日期：1989-05-01 00:00:00

abstract：:Ionotropic glutamate receptors (iGluRs) constitute a family of ligand-gated ion channels that are essential for mediating fast synaptic transmission in the central nervous system. This study presents a high-resolution X-ray structure of the competitive antagonist (S)-2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-4-isox...

journal_title：Journal of medicinal chemistry

authors： Hogner A,Greenwood JR,Liljefors T,Lunn ML,Egebjerg J,Larsen IK,Gouaux E,Kastrup JS

更新日期：2003-01-16 00:00:00

abstract：:A series of both aliphatic and aromatic amides and aromatic amidines derived from 2-amino-1,10-phenanthroline (3) according to the Topliss scheme were synthesized and subsequently tested for antimycoplasmal potency. Although the compounds themselves showed no activity, in the presence of a nontoxic copper concentratio...

journal_title：Journal of medicinal chemistry

authors： de Zwart MA,Bastiaans HM,van der Goot H,Timmerman H

更新日期：1991-03-01 00:00:00

abstract：:Peptidoaminobenzophenones (1), terminal N-substituted peptidoaminobenzophenones (14), and acylglycylaminobenzophenones (16) were prepared as a novel series of ring-opened derivatives of 1,4-benzodiazepine. Z-Gly- and Z-Ala-N-methylaminobenzophenones (4) were treated with HBr-HOAc to give Gly- and Ala-N-methylaminobenz...

journal_title：Journal of medicinal chemistry

authors： Hirai K,Ishiba T,Sugimoto H,Fujishita T,Tsukinoki Y,Hirose K

更新日期：1981-01-01 00:00:00

abstract：:Alpha-galactoglycosphingolipids (alpha-GalGSLs) are unique immunostimulatory glycosphingolipids from marine sponges. Analysis of the glycosphingolipid composition of the marine sponge Axinella damicornis revealed the presence of a new alpha-GalGSL, damicoside (3a), which is the first alpha-GalGSL with a glycosylated g...

journal_title：Journal of medicinal chemistry

authors： Costantino V,D'Esposito M,Fattorusso E,Mangoni A,Basilico N,Parapini S,Taramelli D

更新日期：2005-11-17 00:00:00

abstract：:A conformationally defined retinoic acid analog (1) which contains a dimethylene bridge to maintain the 6-s-trans orientation for two terminal double bonds in the polyene chain was synthesized. A Reformatsky reaction was utilized to extend the polyene chain of the starting enone, which provided exclusively the 9Z-conf...

journal_title：Journal of medicinal chemistry

authors： Vaezi MF,Alam M,Sani BP,Rogers TS,Simpson-Herren L,Wille JJ,Hill DL,Doran TI,Brouillette WJ,Muccio DD

更新日期：1994-12-23 00:00:00