New dibenzothiadiazepine derivatives with antidepressant activities.

abstract：:N(α)-Boc-l-Asp(OBn)-l-Lys(Z)-OtBu (reversin 121, 1), an inhibitor of the P-gp ABC transporter, was used to conceive compounds inhibiting the drug efflux occurring through the Hoechst 33342 and daunorubicin transport sites of P-gp, respectively H and R sites. Replacement of the aspartyl residue by trans-4-hydroxy-l-pro...

journal_title：Journal of medicinal chemistry

authors： Arnaud O,Koubeissi A,Ettouati L,Terreux R,Alamé G,Grenot C,Dumontet C,Di Pietro A,Paris J,Falson P

更新日期：2010-09-23 00:00:00

abstract：:Dual leucine zipper kinase (DLK, MAP3K12) is an essential driver of the neuronal stress response that regulates neurodegeneration in models of acute neuronal injury and chronic neurodegenerative diseases such as Alzheimer's, Parkinson's, and ALS. In this review, we provide an overview of DLK signaling mechanisms and d...

journal_title：Journal of medicinal chemistry

authors： Siu M,Sengupta Ghosh A,Lewcock JW

更新日期：2018-09-27 00:00:00

abstract：:N-Benzoyl-DL-phenylalanine (1) was found to possess hypoglycemic activity. A series of the analogues of compound 1 were prepared and evaluated for their blood glucose lowering activity. Both the steric effects of the phenylalanine moiety and the effects of variations in the acyl moiety were investigated. This study el...

journal_title：Journal of medicinal chemistry

authors： Shinkai H,Toi K,Kumashiro I,Seto Y,Fukuma M,Dan K,Toyoshima S

更新日期：1988-11-01 00:00:00

abstract：:New, racemic, tricyclic trioxane alcohol 3 was designed and synthesized as a structurally simple analog of clinically useful, tetracyclic, antimalarial artemisinin. A series of 20 ester and ether derivatives of alcohol 3 were prepared easily, without destruction of the essential trioxane system. Chemical structure-ant...

journal_title：Journal of medicinal chemistry

authors： Posner GH,Oh CH,Gerena L,Milhous WK

更新日期：1992-06-26 00:00:00

abstract：:The o-carboxylic acid substituted bisanilinopyrimidine 1 was identified as a potent hit (Aurora A IC(50) = 6.1 ± 1.0 nM) from in-house screening. Detailed structure-activity relationship (SAR) studies indicated that polar substituents at the para position of the B-ring are critical for potent activity. X-ray crystallo...

journal_title：Journal of medicinal chemistry

authors： Lawrence HR,Martin MP,Luo Y,Pireddu R,Yang H,Gevariya H,Ozcan S,Zhu JY,Kendig R,Rodriguez M,Elias R,Cheng JQ,Sebti SM,Schonbrunn E,Lawrence NJ

更新日期：2012-09-13 00:00:00

abstract：:We have identified a novel series of antidiabetic N-(2-benzoylphenyl)-L-tyrosine derivatives which are potent, selective PPARgamma agonists. Through the use of in vitro PPARgamma binding and functional assays (2S)-3-(4-(benzyloxy)phenyl)-2-((1-methyl-3-oxo-3-phenylpropenyl)+ ++amin o)propionic acid (2) was identified ...

journal_title：Journal of medicinal chemistry

authors： Henke BR,Blanchard SG,Brackeen MF,Brown KK,Cobb JE,Collins JL,Harrington WW Jr,Hashim MA,Hull-Ryde EA,Kaldor I,Kliewer SA,Lake DH,Leesnitzer LM,Lehmann JM,Lenhard JM,Orband-Miller LA,Miller JF,Mook RA Jr,Noble SA,Ol

更新日期：1998-12-03 00:00:00

abstract：:A new class of histamine analogues characterized by a 3, 3-diphenylpropyl substituent at the 2-position of the imidazole nucleus has been prepared outgoing from 4,4-diphenylbutyronitrile (4b) via cyclization of the corresponding methyl imidate 5b with 2-oxo-4-phthalimido-1-butyl acetate or 2-oxo-1,4-butandiol in liqui...

journal_title：Journal of medicinal chemistry

authors： Elz S,Kramer K,Pertz HH,Detert H,ter Laak AM,Kühne R,Schunack W

更新日期：2000-03-23 00:00:00

abstract：:A number of 7-amino and 7-acylamino substituted 4,4a-dihydro-5H-indeno[1,2-c]pyridazin-3-ones have been synthesized as rigid congeners of hypotensive 6-aryl-5-methyl-4,5-dihydro-3(2H)-pyridazinones and tested as antihypertensive, antithrombotic, antiulcer, and antiinflammatory agents. Unlike the previously described 7...

journal_title：Journal of medicinal chemistry

authors： Cignarella G,Barlocco D,Pinna GA,Loriga M,Tofanetti O,Germini M,Sala F

更新日期：1986-11-01 00:00:00

abstract：:A series of novel 2-[(4-phenylpiperazin-1-yl)methyl]imidazoazines and aza-analogues were prepared and screened at selected dopamine, serotonin, and adrenergic receptor subtypes. 2-Substituted imidazopyridines and pyridazines presented high affinities and selectivities for D4 dopamine receptors. Whereas functional expe...

journal_title：Journal of medicinal chemistry

authors： Enguehard-Gueiffier C,Hübner H,El Hakmaoui A,Allouchi H,Gmeiner P,Argiolas A,Melis MR,Gueiffier A

更新日期：2006-06-29 00:00:00

abstract：:Dipeptidyl peptidase IV (DPP-IV) inhibition has the potential to become a valuable therapy for type 2 diabetes. The synthesis and structure-activity relationship of a new DPP-IV inhibitor class, N-substituted-glycyl-2-cyanopyrrolidines, are described as well as the path that led from clinical development compound 1-[2...

journal_title：Journal of medicinal chemistry

authors： Villhauer EB,Brinkman JA,Naderi GB,Burkey BF,Dunning BE,Prasad K,Mangold BL,Russell ME,Hughes TE

更新日期：2003-06-19 00:00:00

abstract：:Mycobacterium abscessus (Mab) is a rapidly growing species of multidrug-resistant nontuberculous mycobacteria that has emerged as a growing threat to individuals with cystic fibrosis and other pre-existing chronic lung diseases. Mab pulmonary infections are difficult, or sometimes impossible, to treat and result in ac...

journal_title：Journal of medicinal chemistry

authors： Whitehouse AJ,Thomas SE,Brown KP,Fanourakis A,Chan DS,Libardo MDJ,Mendes V,Boshoff HIM,Floto RA,Abell C,Blundell TL,Coyne AG

更新日期：2019-08-08 00:00:00

abstract：:6,6,8-Triethyldesmosdumotin B (2) was discovered as a MDR-selective flavonoid with significant in vitro anticancer activity against a multidrug resistant (MDR) cell line (KB-VIN) but without activity against the parent cells (KB). Additional 2 analogues were synthesized and evaluated to determine the effect of B-ring ...

journal_title：Journal of medicinal chemistry

authors： Nakagawa-Goto K,Chang PC,Lai CY,Hung HY,Chen TH,Wu PC,Zhu H,Sedykh A,Bastow KF,Lee KH

更新日期：2010-09-23 00:00:00

abstract：:MTH1 is a member of the nudix phosphohydrolase superfamily of enzymes, and it is involved in nucleotide pool homeostasis. The protein exerts its scavenging action by hydrolyzing oxidized nucleotides, thus avoiding their misincorporation into replicating DNA. Recent reports have validated its inhibition as a potential ...

journal_title：Journal of medicinal chemistry

authors： Papeo G

更新日期：2016-03-24 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：:Aldehyde dehydrogenase (ALDH) activity is commonly used as a marker to identify cancer stem-like cells. The three ALDH1A isoforms have all been individually implicated in cancer stem-like cells and in chemoresistance; however, which isoform is preferentially expressed varies between cell lines. We sought to explore th...

journal_title：Journal of medicinal chemistry

authors： Huddle BC,Grimley E,Buchman CD,Chtcherbinine M,Debnath B,Mehta P,Yang K,Morgan CA,Li S,Felton J,Sun D,Mehta G,Neamati N,Buckanovich RJ,Hurley TD,Larsen SD

更新日期：2018-10-11 00:00:00

abstract：:G-Quadruplexes, noncanonical nucleic acid structures, act as silencers in the promoter regions of human genes; putative G-quadruplex forming sequences are also present in promoters of other mammals, yeasts, and prokaryotes. Here we show that also the HIV-1 LTR promoter exploits G-quadruplex-mediated transcriptional re...

journal_title：Journal of medicinal chemistry

authors： Perrone R,Nadai M,Frasson I,Poe JA,Butovskaya E,Smithgall TE,Palumbo M,Palù G,Richter SN

更新日期：2013-08-22 00:00:00

abstract：:The synthesis and the biological and pharmacological evaluation of several 14-phenylpropoxy analogues of 14-methoxymetopon are described. Most of the new compounds were nonselective and exhibited binding affinities in the subnanomolar or low nanomolar range at opioid receptors mu, kappa, delta), with 14-phenylpropoxym...

journal_title：Journal of medicinal chemistry

authors： Schütz J,Spetea M,Koch M,Aceto MD,Harris LS,Coop A,Schmidhammer H

更新日期：2003-09-11 00:00:00

abstract：:Changes in expression and dysfunctional signaling of TrkA/B/C receptors and oncogenic Trk fusion proteins are found in neurological diseases and cancers. Here, we describe the development of a first 18F-labeled optimized lead suitable for in vivo imaging of Trk, [18F]TRACK, which is radiosynthesized with ease from a n...

journal_title：Journal of medicinal chemistry

authors： Bernard-Gauthier V,Mossine AV,Mahringer A,Aliaga A,Bailey JJ,Shao X,Stauff J,Arteaga J,Sherman P,Grand'Maison M,Rochon PL,Wängler B,Wängler C,Bartenstein P,Kostikov A,Kaplan DR,Fricker G,Rosa-Neto P,Scott PJH,Schirr

更新日期：2018-02-22 00:00:00

abstract：:The potency of second generation antisense oligonucleotides (ASOs) in animals was increased 3- to 5 -fold (ED(50) approximately 2-5 mg/kg) without producing hepatotoxicity, by reducing ASO length (20-mer to 14-mer) and by employing novel nucleoside modifications that combine structural elements of 2'-O-methoxyethyl re...

journal_title：Journal of medicinal chemistry

authors： Seth PP,Siwkowski A,Allerson CR,Vasquez G,Lee S,Prakash TP,Wancewicz EV,Witchell D,Swayze EE

更新日期：2009-01-08 00:00:00

abstract：:Analogues of 9-oxo-9H-xanthene-4-acetic acid (XAA) bearing small, lipophilic 5-substituents are among the most dose-potent compounds yet reported with the capability of causing hemorrhagic necrosis of implanted colon 38 tumors in mice. To further extend structure-activity relationships among this class of compound, a ...

journal_title：Journal of medicinal chemistry

authors： Rewcastle GW,Atwell GJ,Li ZA,Baguley BC,Denny WA

更新日期：1991-01-01 00:00:00

abstract：:The ruthenium complex, trans-[Ru(Bz)(NH 3) 4SO 2](CF 3SO 3) 2 1, Bz = benznidazole ( N-benzyl-2-(2-nitro-1 H-imidazol-1-yl)acetamide), is more hydrosoluble and more active (IC 50try/1 h = 79 +/- 3 microM) than free benznidazole 2 (IC 50try/1 h > 1 mM). 1 also exhibits low acute toxicity in vitro (IC 50macrophages > 1 ...

journal_title：Journal of medicinal chemistry

authors： Nogueira Silva JJ,Pavanelli WR,Gutierrez FR,Alves Lima FC,Ferreira da Silva AB,Santana Silva J,Wagner Franco D

更新日期：2008-07-24 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：:Human G93A-superoxide dismutase-1 (G93AhSOD1) mutation causes amyotrophic lateral sclerosis (ALS) in rodents and humans. Recent observations indicate gain of interaction of G93AhSOD1 with cytosolic malate dehydrogenase (MDH1) and subsequent impairment in the malate aspartate shuttle which is vital to neurons. Using fl...

journal_title：Journal of medicinal chemistry

authors： Mali Y,Zisapel N

更新日期：2009-09-10 00:00:00

abstract：:A codrug of the anti-Alzheimer drug tacrine and the natural product silibinin was synthesized. The codrug's biological and pharmacological properties were compared to an equimolar mixture of the components. The compound showed potent acetyl- and butyrylcholinesterase inhibition. In a cellular hepatotoxicity model, ana...

journal_title：Journal of medicinal chemistry

authors： Chen X,Zenger K,Lupp A,Kling B,Heilmann J,Fleck C,Kraus B,Decker M

更新日期：2012-06-14 00:00:00

abstract：:Metastin/kisspeptin is an endogenous ligand of KISS1 Receptor (KISS1R). Metastin and KISS1R are suggested to play crucial roles in regulating the secretion of gonadotropin-releasing hormone (GnRH), and continuous administration of metastin derivatives attenuated the plasma testosterone levels in male rats. Our optimiz...

journal_title：Journal of medicinal chemistry

authors： Nishizawa N,Takatsu Y,Kumano S,Kiba A,Ban J,Tsutsumi S,Matsui H,Matsumoto SI,Yamaguchi M,Ikeda Y,Kusaka M,Ohtaki T,Itoh F,Asami T

更新日期：2016-10-13 00:00:00

abstract：:A series of N-alkyl-3-[m-(trifluoromethyl)phenyl]-5-hydroxy-2-pyrrolidinones and N-alkyl-3-(trifluoromethyl)-cinnamamides were prepared and screened in a series of tests designed to detect potential sleep inducers. The more active members of the series were evaluated for their ability to induce sleep in Cebus monkeys....

journal_title：Journal of medicinal chemistry

authors： Houlihan WJ,Gogerty JH,Ryan EA,Schmitt G

更新日期：1985-01-01 00:00:00

abstract：:The sea anemone peptide APETx2 is a potent and selective blocker of acid-sensing ion channel 3 (ASIC3). APETx2 is analgesic in a variety of rodent pain models, but the lack of knowledge of its pharmacophore and binding site on ASIC3 has impeded development of improved analogues. Here we present a detailed structure-ac...

journal_title：Journal of medicinal chemistry

authors： Jensen JE,Cristofori-Armstrong B,Anangi R,Rosengren KJ,Lau CH,Mobli M,Brust A,Alewood PF,King GF,Rash LD

更新日期：2014-11-13 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：: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：:Four chiral congeners of arachidonylethanolamide (anandamide) have been synthesized and evaluated for (a) their ability to bind to the cannabinoid receptor in rat forebrain membranes and (b) their pharmacological potency as measured by the compounds' ability to inhibit electrically-evoked contractions of the mouse vas...

journal_title：Journal of medicinal chemistry

authors： Abadji V,Lin S,Taha G,Griffin G,Stevenson LA,Pertwee RG,Makriyannis A

更新日期：1994-06-10 00:00:00