Development of 1,4-benzodiazepine cholecystokinin type B antagonists.

abstract：:Melanin concentrating hormone (MCH) is involved in regulation of food intake and energy homeostasis. Antagonists of the MCH receptor are expected to affect food intake and weight gain, making MCH-R1 an attractive target for obesity treatment. Herein, we report the discovery of a novel, orally active series of MCH-R1 a...

journal_title：Journal of medicinal chemistry

authors： McBriar MD,Guzik H,Xu R,Paruchova J,Li S,Palani A,Clader JW,Greenlee WJ,Hawes BE,Kowalski TJ,O'Neill K,Spar B,Weig B

更新日期：2005-04-07 00:00:00

abstract：:Five series of pyrrolo[3,2-d]pyrimidines were synthesized and evaluated with respect to potency and selectivity toward multidrug resistance-associated protein 1 (MRP1, ABCC1). This transport protein is a major target to overcome multidrug resistance in cancer patients. We investigated differently substituted pyrrolopy...

journal_title：Journal of medicinal chemistry

authors： Schmitt SM,Stefan K,Wiese M

更新日期：2016-04-14 00:00:00

abstract：:The 18 kDa translocator protein (TSPO) is a mitochondrial protein whose basal density is altered in several diseases, with the result that the evaluation of its expression levels by means of molecular imaging techniques represents a promising diagnostic approach. Experimental procedures using a labeled ligand often ca...

journal_title：Journal of medicinal chemistry

authors： Taliani S,Da Pozzo E,Bellandi M,Bendinelli S,Pugliesi I,Simorini F,La Motta C,Salerno S,Marini AM,Da Settimo F,Cosimelli B,Greco G,Novellino E,Martini C

更新日期：2010-05-27 00:00:00

abstract：:The syntheses of three new cyclosporin A (CsA) analogues that contain novel MeBmt derivatives in the 1-position are described. The MeBmt analogue that contains an additional methyl group on C4, (2S,3R,6E)-4,4-dimethyl-3-hydroxy-2-(N-methylamino)-6-octenoic acid (MeBm2t), was synthesized in four steps beginning with th...

journal_title：Journal of medicinal chemistry

authors： Aebi JD,Deyo DT,Sun CQ,Guillaume D,Dunlap B,Rich DH

更新日期：1990-03-01 00:00:00

abstract：:Aminoglycosides (AGs) constitute a major family of potent and broad-spectrum antibiotics disturbing protein synthesis through binding to the A site of 16S rRNA. Decades of widespread clinical use of AGs strongly reduced their clinical efficacy through the selection of resistant bacteria. Recently, conjugation of lipop...

journal_title：Journal of medicinal chemistry

authors： Zimmermann L,Das I,Désiré J,Sautrey G,Barros R S V,El Khoury M,Mingeot-Leclercq MP,Décout JL

更新日期：2016-10-27 00:00:00

abstract：:The coordination complex cyclo-tetrakis[bis(1-phenyl-3-methyl-4-benzoylpyrazolon-5-ato++ +)mu-o xotitanium(IV)] has been synthesized and characterized with IR and NMR spectroscopies and X-ray diffraction. The core of this species consists of an eight-membered Ti-mu-oxo ring with alternate short-long Ti-O bond lengths....

journal_title：Journal of medicinal chemistry

authors： Caruso F,Rossi M,Tanski J,Sartori R,Sariego R,Moya S,Diez S,Navarrete E,Cingolani A,Marchetti F,Pettinari C

更新日期：2000-10-05 00:00:00

abstract：:The prevalence of multidrug resistance among clinically significant bacterial pathogens underscores a critical need for the development of new classes of antibiotics with novel mechanisms of action. Here we describe the synthesis and evaluation of a guanidinomethyl biaryl compound {1-((4'-(tert-butyl)-[1,1'-biphenyl]-...

journal_title：Journal of medicinal chemistry

authors： Kaul M,Parhi AK,Zhang Y,LaVoie EJ,Tuske S,Arnold E,Kerrigan JE,Pilch DS

更新日期：2012-11-26 00:00:00

abstract：:A series of (substituted amino)-1,2,4-benzothiadiazine 1-oxides has been synthesized and most members of the series have been shown to have blood pressure lowering effects in normotensive rabbits and in spontaneously hypertensive rats. The most active member of the series was 3-[4-(2-furoyl)-1-piperazinyl]-6,7-dimetho...

journal_title：Journal of medicinal chemistry

authors： Dillard RD,Yen TT,Stark P,Pavey DE

更新日期：1980-07-01 00:00:00

abstract：:A pharmacophore model, Hypo1, was built on the basis of 21 training-set indole compounds with varying levels of antiproliferative activity. Hypo1 possessed important chemical features required for the inhibitors and demonstrated good predictive ability for biological activity, with high correlation coefficients of 0.9...

journal_title：Journal of medicinal chemistry

authors： Chiang YK,Kuo CC,Wu YS,Chen CT,Coumar MS,Wu JS,Hsieh HP,Chang CY,Jseng HY,Wu MH,Leou JS,Song JS,Chang JY,Lyu PC,Chao YS,Wu SY

更新日期：2009-07-23 00:00:00

abstract：:Protein kinase C (PKC) is a widely studied molecular target for the treatment of cancer and other diseases. We have approached the issue of modifying PKC function by targeting the C1 domain in the regulatory region of the enzyme. Using the X-ray crystal structure of the PKC delta C1b domain, we have discovered conveni...

journal_title：Journal of medicinal chemistry

authors： Boije af Gennäs G,Talman V,Aitio O,Ekokoski E,Finel M,Tuominen RK,Yli-Kauhaluoma J

更新日期：2009-07-09 00:00:00

abstract：:A series of dithiocarbamates were prepared by reaction of primary/secondary amines with carbon disulfide in the presence of bases. These compounds were tested for the inhibition of four human (h) isoforms of the zinc enzyme carbonic anhydrase, CA (EC 4.2.1.1), hCA I, II, IX, and XII, involved in pathologies such as gl...

journal_title：Journal of medicinal chemistry

authors： Carta F,Aggarwal M,Maresca A,Scozzafava A,McKenna R,Masini E,Supuran CT

更新日期：2012-02-23 00:00:00

abstract：:Antimicrobial resistance (AMR) represents a hot topic in drug discovery. Besides the identification of new antibiotics, the use of nonantibiotic molecules to block resistance mechanisms is a powerful alternative. Bacterial efflux pumps exert an early step in AMR development by allowing bacteria to grow at subinhibitor...

journal_title：Journal of medicinal chemistry

authors： Felicetti T,Cannalire R,Pietrella D,Latacz G,Lubelska A,Manfroni G,Barreca ML,Massari S,Tabarrini O,Kieć-Kononowicz K,Schindler BD,Kaatz GW,Cecchetti V,Sabatini S

更新日期：2018-09-13 00:00:00

abstract：:Re-examination of the design of the cyclic urea class of HIV protease (HIVPR) inhibitors suggests a general approach to designing novel nonpeptide cyclic HIVPR inhibitors. This process involves the inversion of the stereochemical centers of the core transition-state isostere of the linear HIVPR inhibitors and cyclizat...

journal_title：Journal of medicinal chemistry

authors： De Lucca GV,Liang J,Aldrich PE,Calabrese J,Cordova B,Klabe RM,Rayner MM,Chang CH

更新日期：1997-05-23 00:00:00

abstract：:HP-236 (3-[4-[4-(6-Fluorobenzo[b]thien-3-yl)-1-piperazinyl]butyl]-2,5,5- trimethyl-4-thiazolidinone maleate; P-9236) (54) displayed a pharmacological profile indicative of potential atypical antipsychotic activity. A series of piperazinyl butyl thiazolidinones structurally related to this compound were prepared and ev...

journal_title：Journal of medicinal chemistry

authors： Hrib NJ,Jurcak JG,Bregna DE,Burgher KL,Hartman HB,Kafka S,Kerman LL,Kongsamut S,Roehr JE,Szewczak MR,Woods-Kettelberger AT,Corbett R

更新日期：1996-09-27 00:00:00

abstract：:Tocotrienols are farnesylated benzopyran natural products that exhibit hypocholesterolemic activity in vitro and in vivo. The mechanism of their hypolipidemic action involves posttranscriptional suppression of HMG-CoA reductase by a process distinct from other known inhibitors of cholesterol biosynthesis. An efficient...

journal_title：Journal of medicinal chemistry

authors： Pearce BC,Parker RA,Deason ME,Qureshi AA,Wright JJ

更新日期：1992-10-02 00:00:00

abstract：:In order to find a new class of anti-Helicobacter pylori (H. pylori) agents, a series of 4-[(3-acetamido)phenyl]-2-(substituted guanidino)thiazoles and some structurally rigid analoges were synthesized and evaluated for antimicrobial activity against H. pylori. Among the compounds obtained, high anti-H. pyrori activit...

journal_title：Journal of medicinal chemistry

authors： Katsura Y,Tomishi T,Inoue Y,Sakane K,Matsumoto Y,Morinaga C,Ishikawa H,Takasugi H

更新日期：2000-08-24 00:00:00

abstract：:A series of novel triazol-3-ones have been synthesized, and their in vitro and in vivo antifungal properties are reported. Compound 68 (itraconazole), which displays a pronounced oral activity against vaginal candidosis in rats and against microsporosis in guinea pigs, has been selected for clinical evaluation. ...

journal_title：Journal of medicinal chemistry

authors： Heeres J,Backx LJ,Van Cutsem J

更新日期：1984-07-01 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：:Selenosemicarbazones show marked antitumor activity. However, their mechanism of action remains unknown. We examined the medicinal chemistry of the selenosemicarbazone, 2-acetylpyridine 4,4-dimethyl-3-selenosemicarbazone (Ap44mSe), and its iron and copper complexes to elucidate its mechanisms of action. Ap44mSe demons...

journal_title：Journal of medicinal chemistry

authors： Al-Eisawi Z,Stefani C,Jansson PJ,Arvind A,Sharpe PC,Basha MT,Iskander GM,Kumar N,Kovacevic Z,Lane DJ,Sahni S,Bernhardt PV,Richardson DR,Kalinowski DS

更新日期：2016-01-14 00:00:00

abstract：:A series of coumarins and the corresponding 2-thioxocoumarines were prepared and tested for their inhibition profiles against four physiologically relevant human carbonic anhydrases (hCAs, EC 4.2.1.1), isoforms hCA I, II, IX, and XII. The X-ray crystal structure of 6-hydroxy-2-thioxocoumarin bound to hCA II revealed a...

journal_title：Journal of medicinal chemistry

authors： Ferraroni M,Carta F,Scozzafava A,Supuran CT

更新日期：2016-01-14 00:00:00

abstract：:A series of 6-substituted purinyl alkoxycarbonyl amino acids were synthesized and evaluated for their ability to stimulate cytotoxic T lymphocytes (CTLs) and the mixed lymphocyte reaction (MLR). A few of these compounds, in particular [[5-[6-(N,N-dimethylamino)purin-9-yl]pentoxy]-carbonyl]D-arginine (BCH-1393, 4a), di...

journal_title：Journal of medicinal chemistry

authors： Zacharie B,Gagnon L,Attardo G,Connolly TP,St-Denis Y,Penney CL

更新日期：1997-08-29 00:00:00

abstract：:Glucuronidation and transporter-mediated efflux into bile are important in the elimination of xeno- and endobiotics, including the natural biladienone pigment bilirubin. The mechanisms of these processes and the structural factors that dictate whether cholephilic compounds are excreted directly in bile or require prio...

journal_title：Journal of medicinal chemistry

authors： McDonagh AF,Lightner DA

更新日期：2007-02-08 00:00:00

abstract：:A focused library approach identifying novel leads to develop a potent ORL1 antagonist is described. Beginning from a compound identified by random screening, an exploratory library that exhibited a diverse display of pharmacophores was designed. After evaluating ORL1 antagonistic activity, a highly focused library wa...

journal_title：Journal of medicinal chemistry

authors： Goto Y,Arai-Otsuki S,Tachibana Y,Ichikawa D,Ozaki S,Takahashi H,Iwasawa Y,Okamoto O,Okuda S,Ohta H,Sagara T

更新日期：2006-02-09 00:00:00

abstract：:Selective inhibition of neuronal nitric oxide synthase (nNOS) has been shown to prevent brain injury and is important for the treatment of various neurodegenerative disorders. This study shows that not only greater inhibitory potency and isozyme selectivity but more druglike properties can be achieved by fragment hopp...

journal_title：Journal of medicinal chemistry

authors： Ji H,Li H,Martásek P,Roman LJ,Poulos TL,Silverman RB

更新日期：2009-02-12 00:00:00

abstract：:Inhibition of histone deacetylase (HDAC) results in growth arrest, differentiation, and apoptosis in nearly all tumor cell lines, promoting HDACs as promising targets for antitumor therapy. In our previous study we developed a novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as HDAC inhibit...

journal_title：Journal of medicinal chemistry

authors： Zhang Y,Feng J,Jia Y,Wang X,Zhang L,Liu C,Fang H,Xu W

更新日期：2011-04-28 00:00:00

abstract：:Fragment-based lead discovery has over the years matured into an attractive alternative to high-throughput screening (HTS) for lead generation. Several techniques for screening libraries of typically 10(3)-10(4) fragments have been reported. In this work, the practical success rates that can be expected from the scree...

journal_title：Journal of medicinal chemistry

authors： Makara GM

更新日期：2007-07-12 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：:The binding structures of 11 human oxidosqualene cyclase inhibitors designed as cholesterol-lowering agents were determined for the squalene-hopene cyclase from Alicyclobacillus acidocaldarius, which is the only structurally known homologue of the human enzyme. The complexes were produced by cocrystallization, and the...

journal_title：Journal of medicinal chemistry

authors： Lenhart A,Reinert DJ,Aebi JD,Dehmlow H,Morand OH,Schulz GE

更新日期：2003-05-22 00:00:00

abstract：:Targeting of DNA secondary structures, such as G-quadruplexes, is now considered an appealing opportunity for drug intervention in anticancer therapy. So far, efforts made in the discovery of chemotypes able to target G-quadruplexes mainly succeeded in the identification of a number of polyaromatic compounds featuring...

journal_title：Journal of medicinal chemistry

authors： Cosconati S,Rizzo A,Trotta R,Pagano B,Iachettini S,De Tito S,Lauri I,Fotticchia I,Giustiniano M,Marinelli L,Giancola C,Novellino E,Biroccio A,Randazzo A

更新日期：2012-11-26 00:00:00

abstract：:Ruthenium polypyridyl complexes show great promise as new photodynamic therapy (PDT) agents. However, a lack of detailed understanding of their mode of action in cells poses a challenge to their development. We have designed a new Ru(II) PDT candidate that efficiently enters cells by incorporation of the lipophilic ar...

journal_title：Journal of medicinal chemistry

authors： Cloonan SM,Elmes RB,Erby M,Bright SA,Poynton FE,Nolan DE,Quinn SJ,Gunnlaugsson T,Williams DC

更新日期：2015-06-11 00:00:00