Tetramisole analogues as inhibitors of alkaline phosphatase, an enzyme involved in the resistance of neoplastic cells to 6-thiopurines.

abstract：:We have reported the preparation and anticancer evaluation of certain 4-anilinofuro[2,3-b]quinolines. However, drawbacks such as lack of selective cytotoxicity, poor oral bioavailability, and poor water solubility exhibited by these compounds prompted us to search for newer derivatives. Among them, (E)-1-(4-(furo[2,3-...

journal_title：Journal of medicinal chemistry

authors： Chen YW,Chen YL,Tseng CH,Liang CC,Yang CN,Yao YC,Lu PJ,Tzeng CC

更新日期：2011-07-14 00:00:00

abstract：:In an attempt to determine which conformational parameters are important for the biological activity of ovine corticotropin-releasing factor (oCRF), we have synthesized in significant amounts (50-200 mg) and characterized chemically, structurally (CD), and biologically, oCRF analogues with substitution of each amino a...

journal_title：Journal of medicinal chemistry

authors： Rivier J,Rivier C,Galyean R,Miranda A,Miller C,Craig AG,Yamamoto G,Brown M,Vale W

更新日期：1993-10-01 00:00:00

abstract：:Potent and selective inhibitors of Dyrk1B kinase were developed to explore the hypothesis, based on siRNA studies, that Dyrk1B may be a resistance mechanism in cells undergoing a stress response. ...

journal_title：Journal of medicinal chemistry

authors： Kettle JG,Ballard P,Bardelle C,Cockerill M,Colclough N,Critchlow SE,Debreczeni J,Fairley G,Fillery S,Graham MA,Goodwin L,Guichard S,Hudson K,Ward RA,Whittaker D

更新日期：2015-03-26 00:00:00

abstract：:A series of inhibitors of the malarial aspartic proteases Plm I and II have been synthesized with L-mannitol as precursor. These inhibitors are characterized by either a diacylhydrazine or a five-membered oxadiazole ring replacing backbone amide functionalities. Molecular dynamics simulations were applied in the desig...

journal_title：Journal of medicinal chemistry

authors： Ersmark K,Nervall M,Hamelink E,Janka LK,Clemente JC,Dunn BM,Blackman MJ,Samuelsson B,Aqvist J,Hallberg A

更新日期：2005-09-22 00:00:00

abstract：:A new series of N-aryl-N'-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)ureas bearing an alkoxycarbonylamino group at the 6-position were synthesized and examined as putative anticancer agents targeting sirtuins in glioma cells. On the basis of computational docking combined to in vitro sirtuin 1/2 inhibition assays, ...

journal_title：Journal of medicinal chemistry

authors： Schnekenburger M,Goffin E,Lee JY,Jang JY,Mazumder A,Ji S,Rogister B,Bouider N,Lefranc F,Miklos W,Mathieu V,de Tullio P,Kim KW,Dicato M,Berger W,Han BW,Kiss R,Pirotte B,Diederich M

更新日期：2017-06-08 00:00:00

abstract：:Undetected pan-assay interference compounds (PAINS) with false-positive activities in assays often propagate through medicinal chemistry programs and compromise their outcomes. Although a large number of PAINS have been classified, often on the basis of individual studies or chemical experience, little has been done s...

journal_title：Journal of medicinal chemistry

authors： Jasial S,Hu Y,Bajorath J

更新日期：2017-05-11 00:00:00

abstract：:The plant metabolite 3,4,5-tri-O-galloylquinic acid methyl ester (TGAME, compound 6) was synthesized, and its potential effect on calcium oxalate monohydrate (COM) crystal binding to the surface of Madin-Darby canine kidney cells type I (MDCKI) and crystal growth in a Drosophila melanogaster Malpighian tubule (MT) mod...

journal_title：Journal of medicinal chemistry

authors： Abd El-Salam M,Bastos JK,Han JJ,Previdi D,Coelho EB,Donate PM,Romero MF,Lieske J

更新日期：2018-02-22 00:00:00

abstract：:A series of substituted chromone-2-carboxylic acids was synthesized and tested as antagonists of SRS-A induced contractions of isolated guinea pig ileum. This work led to the discovery of sodium 7-[3-(4-acetyl-3hydroxy-2-propylphenoxy)-2-hydroxypropoxy]-4-oxo-8-propyl-4H-1-benzopyran-2-carboxylate (FPL 55712) which is...

journal_title：Journal of medicinal chemistry

authors： Appleton RA,Bantick JR,Chamberlain TR,Hardern DN,Lee TB,Pratt AD

更新日期：1977-03-01 00:00:00

abstract：:SHP-2, a nonreceptor protein tyrosine phosphatase encoded by the PTPN11 gene, mediates cell signaling by growth factors and cytokines via the RAS/MAP kinase pathway. Somatic mutations in PTPN11 gene account for approximately 18% of juvenile myelomonocytic leukemia (JMML) patients. Moreover, SHP-2 mutations leading to ...

journal_title：Journal of medicinal chemistry

authors： Geronikaki A,Eleftheriou P,Vicini P,Alam I,Dixit A,Saxena AK

更新日期：2008-09-11 00:00:00

abstract：:The synthesis of cis and trans isomers of N,N-N-trimethyl-2-phenoxycyclohexylammonium bromide, cis-N,N,-N-trimethyl-2(2',6'-xylyloxy)cyclohexylammonium bromide, and N,N-dimethyl-3-phenoxypiperidinium bromide is described. Their structures and conformations were determined by NMR and uv absorption spectroscopy, the min...

journal_title：Journal of medicinal chemistry

authors： Clark ER,Hughes IE,Smith CF

更新日期：1976-05-01 00:00:00

abstract：:A series of derivatives of the antimycobacterial natural product pyridomycin have been prepared with the C2 side chain attached to the macrocyclic core structure by a C-C single bond, in place of the synthetically more demanding enol ester double bond found in the natural product. Hydrophobic C2 substituents of suffic...

journal_title：Journal of medicinal chemistry

authors： Kienle M,Eisenring P,Stoessel B,Horlacher OP,Hasler S,van Colen G,Hartkoorn RC,Vocat A,Cole ST,Altmann KH

更新日期：2020-02-13 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：:A series of substituted 3-aryl- and hydroxy-3-aryloctahydropyrido[2,1-c][1,4]oxazines has been synthesized for purposes of investigating potentially useful CNS pharmacological actions of this novel heterocyclic system. The preferred conformation of the bicyclic system of the parent compounds, 1 and 2, has been shown t...

journal_title：Journal of medicinal chemistry

authors： Rankin GO,Riley TN,Murphy JC

更新日期：1978-05-01 00:00:00

abstract：:We synthesized 5-substituted pyrrolo[2,3-d]pyrimidine antifolates (compounds 5-10) with one-to-six bridge carbons and a benozyl ring in the side chain as antitumor agents. Compound 8 with a 4-carbon bridge was the most active analogue and potently inhibited proliferation of folate receptor (FR) α-expressing Chinese ha...

journal_title：Journal of medicinal chemistry

authors： Mitchell-Ryan S,Wang Y,Raghavan S,Ravindra MP,Hales E,Orr S,Cherian C,Hou Z,Matherly LH,Gangjee A

更新日期：2013-12-27 00:00:00

abstract：:The structural features of a new class of non-nucleoside HIV-1 reverse transcriptase inhibitors (3) are presented. Comparison of the structural and electronic properties with those of TIBO (1) and Nevirapine (2) yields a common three-dimensional model. This model permits the improvement of the lead compound 3 by chemi...

journal_title：Journal of medicinal chemistry

authors： Schäfer W,Friebe WG,Leinert H,Mertens A,Poll T,von der Saal W,Zilch H,Nuber B,Ziegler ML

更新日期：1993-03-19 00:00:00

abstract：:The bromodomain and extra-terminal domain (BET) family of proteins bind acetylated lysine residues on histone proteins. The four BET bromodomains-BRD2, BRD3, BRD4, and BRDT-each contain two bromodomain modules. BET bromodomain inhibition is a potential therapy for various cancers and immunoinflammatory diseases, but f...

journal_title：Journal of medicinal chemistry

authors： Law RP,Atkinson SJ,Bamborough P,Chung CW,Demont EH,Gordon LJ,Lindon M,Prinjha RK,Watson AJB,Hirst DJ

更新日期：2018-05-24 00:00:00

abstract：:TYK2 is an emerging drug target for various human autoimmune diseases. However, discovery of selective TYK2 inhibitor over other JAK family members (i.e., JAK1, 2, 3) by targeting the catalytically active site (Janus Homologue 1 (JH1) domain) is challenging. This Viewpoint discusses the discovery of a series of N-meth...

journal_title：Journal of medicinal chemistry

authors： Chang Y,Xu S,Ding K

更新日期：2019-10-24 00:00:00

abstract：:A series of α-ketooxazoles containing conformational constraints in the C2 acyl side chain of 2 (OL-135) were examined as inhibitors of fatty acid amide hydrolase (FAAH). Only one of the two possible enantiomers displayed potent FAAH inhibition (S vs R enantiomer), and their potency is comparable or improved relative ...

journal_title：Journal of medicinal chemistry

authors： Ezzili C,Mileni M,McGlinchey N,Long JZ,Kinsey SG,Hochstatter DG,Stevens RC,Lichtman AH,Cravatt BF,Bilsky EJ,Boger DL

更新日期：2011-04-28 00:00:00

abstract：:A series of N2-[(acylamino)alkyl]-6,7-dimethoxy-2,4-quinazolinediamines was synthesized as potential alpha 1-adrenoceptor antagonists. When administered to spontaneously hypertensive rats at 10 mg/kg po, a number of propanediamine derivatives showed good antihypertensive activity, whereas the ethanediamine derivatives...

journal_title：Journal of medicinal chemistry

authors： Manoury PM,Binet JL,Dumas AP,Lefèvre-Borg F,Cavero I

更新日期：1986-01-01 00:00:00

abstract：:A series of 4(6)- and 5-phenyl-substituted 2-amino- and 2-[(alkoxycarbonyl)amino]-1,4,5,6-tetrahydropyrimidines were prepared and evaluated for central nervous system (CNS) effects in animal models. Several 5-phenyl-substituted compounds possessed potent antidepressant activity and all compounds in this series were de...

journal_title：Journal of medicinal chemistry

authors： Weinhardt K,Wallach MB,Marx M

更新日期：1985-06-01 00:00:00

abstract：:K-Ras is one of the most frequently mutated signal transducing human oncogenes. Ras signaling activity requires correct cellular localization of the GTPase. The spatial organization of K-Ras is controlled by the prenyl binding protein PDEδ, which enhances Ras diffusion in the cytosol. Inhibition of the Ras-PDEδ intera...

journal_title：Journal of medicinal chemistry

authors： Zimmermann G,Schultz-Fademrecht C,Küchler P,Murarka S,Ismail S,Triola G,Nussbaumer P,Wittinghofer A,Waldmann H

更新日期：2014-06-26 00:00:00

abstract：:The prevalence of neurotensin receptor (NTR) in several human tumors makes it an attractive target for the delivery of cytotoxic drugs and imaging agents. Native neurotensin (NT) is a tridecapeptide that binds to NTR and induces tumor growth. Unfortunately, NT has a short plasma half-life, which hinders its use for in...

journal_title：Journal of medicinal chemistry

authors： Achilefu S,Srinivasan A,Schmidt MA,Jimenez HN,Bugaj JE,Erion JL

更新日期：2003-07-17 00:00:00

abstract：:Plasmodium falciparum lactate dehydrogenase (pfLDH) is a key enzyme for energy generation of malarial parasites and is a potential antimalarial chemotherapeutic target. It is known that the oxamate moiety, a pyruvate analog, alone shows higher inhibition against pfLDH than human LDHs, suggesting that it can be used fo...

journal_title：Journal of medicinal chemistry

authors： Choi SR,Pradhan A,Hammond NL,Chittiboyina AG,Tekwani BL,Avery MA

更新日期：2007-08-09 00:00:00

abstract：:The 3,4-dichloro-N-(1-(dimethylamino)cyclohexyl)methyl benzamide scaffold was studied as a template for 18F-positron emission tomography (18F-PET) radiotracer development emphasizing sensitivity to changes in opioid receptor (OR) occupancy over high affinity. Agonist potency, binding affinity, and relevant pharmacolog...

journal_title：Journal of medicinal chemistry

authors： Ott J,Spilhaug MM,Maschauer S,Rafique W,Jakobsson JE,Hartvig K,Hübner H,Gmeiner P,Prante O,Riss PJ

更新日期：2020-09-10 00:00:00

abstract：:1-beta-D-Arabinofuranosylthymine (aThy; ara-T) is a potent selective anti herpes simplex virus drug. Its anhydro analogue, 2,2'-anhydro-aThy, was shown to be 9-fold less active and at least 3-fold less toxic than aThy. This compound was relatively stable at physiological pH and in strong acid but was rapidly hydrolyze...

journal_title：Journal of medicinal chemistry

authors： Harrison DH,Schinazi RF,Rubin BH

更新日期：1982-12-01 00:00:00

abstract：:A computational chemistry study has been performed on a series of tetrahydropyrimidine-2-ones (THPs) as HIV-1 protease (HIV-1 PR) inhibitors. The present investigation focuses on the correlation of inhibitor-enzyme complexation energies (E(compl)), inhibitor solvation energies E(solv)[I], and both polar and nonpolar b...

journal_title：Journal of medicinal chemistry

authors： Nair AC,Jayatilleke P,Wang X,Miertus S,Welsh WJ

更新日期：2002-02-14 00:00:00

abstract：:The early and later eluting [(99m)TcO]depreotide products on RP-HPLC were confirmed to be the anti and syn diastereomers, respectively, based on proton NMR and circular dichroism spectroscopy. NMR provided evidence of a folded, conformationally constrained structure for the syn diastereomer. The syn diastereomer is pr...

journal_title：Journal of medicinal chemistry

authors： Cyr JE,Pearson DA,Nelson CA,Lyons BA,Zheng Y,Bartis J,He J,Cantorias MV,Howell RC,Francesconi LC

更新日期：2007-09-06 00:00:00

abstract：:A structure-activity relationship for symmetrical cyanine inhibitors of human tau aggregation was elaborated using a filter trap assay. Antagonist activity depended on cyanine heterocycle, polymethine bridge length, and the nature of meso- and N-substituents. One potent member of the series, 3,3'-diethyl-9-methylthiac...

journal_title：Journal of medicinal chemistry

authors： Chang E,Congdon EE,Honson NS,Duff KE,Kuret J

更新日期：2009-06-11 00:00:00

abstract：:A series of novel 3-quinolinecarboxylic acid derivatives have been prepared and their antibacterial activity evaluated. These derivatives are characterized by fluorine attached to the 6-position and substituted amino groups appended to the 1- and 7-positions. Structure-activity relationship studies indicate that antib...

journal_title：Journal of medicinal chemistry

authors： Wentland MP,Bailey DM,Cornett JB,Dobson RA,Powles RG,Wagner RB

更新日期：1984-09-01 00:00:00

abstract：:Inhibition of growth hormone (GH) and prolactin (PRL) release from the anterior pituitary gland is mediated through somatostatin receptor subtypes sst2 and sst5. It has been found that somatostatin (SS) analogues that are selective for both receptor subtypes are more effective at inhibiting GH and PRL release than mon...

journal_title：Journal of medicinal chemistry

authors： Moore SB,van der Hoek J,de Capua A,van Koetsveld PM,Hofland LJ,Lamberts SW,Goodman M

更新日期：2005-10-20 00:00:00