In vitro cytotoxic activities of 2-alkyl-4,6-diheteroalkyl-1,3,5-triazines: new molecules in anticancer research.

abstract：:Photodynamic therapy (PDT) as a rising platform of the cancer treatment method is receiving increased attention. Through systematic evaluation of halogen substitution on aza-4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes (BODIPY), we have found that monoiodo-derived aza-BODIPYs provided greater efficacy than other haloge...

journal_title：Journal of medicinal chemistry

authors： Yu Z,Zhou J,Ji X,Lin G,Xu S,Dong X,Zhao W

更新日期：2020-09-10 00:00:00

abstract：:Antibiotic resistance is one of the biggest threats to public health, and new antibacterial agents hence are in an urgent need to combat infectious diseases caused by multidrug-resistant (MDR) pathogens. Utilizing dimerization strategy, we rationally designed and efficiently synthesized a new series of small molecule ...

journal_title：Journal of medicinal chemistry

authors： Niu Y,Wang M,Cao Y,Nimmagadda A,Hu J,Wu Y,Cai J,Ye XS

更新日期：2018-04-12 00:00:00

abstract：:5-Bromotryptophan (5-BrTrp) is the most potent amino acid derivative reported in the literature to inhibit the gelation of hemoglobin S (from sickle cell anemia patients). Trp-Trp is also more potent than Trp as an antigelation agent. Therefore, we have prepared a series of dipeptides containing 5-BrTrp and evaluated ...

journal_title：Journal of medicinal chemistry

authors： De Croos PZ,Sangdee P,Stockwell BL,Kar L,Thompson EB,Johnson ME,Currie BL

更新日期：1990-12-01 00:00:00

abstract：:The structure of fenoterol, a beta2-adrenoceptor agonist used in therapy, has been joined with furoxan NO-donor moieties to give new NO-donor beta2-agonists. The furazan analogues, devoid of the property to release NO, were also synthesized for comparison. All the compounds retained beta2-agonistic activity at micromo...

journal_title：Journal of medicinal chemistry

authors： Buonsanti MF,Bertinaria M,Stilo AD,Cena C,Fruttero R,Gasco A

更新日期：2007-10-04 00:00:00

abstract：:Structural genomics will yield an immense number of protein three-dimensional structures in the near future. Automated theoretical methodologies are needed to exploit this information and are likely to play a pivotal role in drug discovery. Here, we present a fully automated, efficient docking methodology that does no...

journal_title：Journal of medicinal chemistry

authors： Glick M,Grant GH,Richards WG

更新日期：2002-10-10 00:00:00

abstract：:As the number of cases and cancer-related deaths are projected to rise in upcoming years, it is urgent to find ways to prevent or treat cancer. As such, food-derived products have gained attention as potential chemopreventive agents due to their availability, safety, and low cost. Isothiocyanates, the breakdown produc...

journal_title：Journal of medicinal chemistry

authors： Frieben EE,Amin S,Sharma AK

更新日期：2019-06-13 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：:(+/-)-7-Aminosulfonyl-3-fluoromethyl-1,2,3,4-tetrahydroisoquinoline (7) is one of the most potent and selective inhibitors of phenylethanolamine N-methyltransferase (PNMT) reported to date, but a blood-brain barrier (BBB) model indicates that it cannot penetrate the BBB. To increase the lipophilicity of 7 by addition ...

journal_title：Journal of medicinal chemistry

authors： Romero FA,Vodonick SM,Criscione KR,McLeish MJ,Grunewald GL

更新日期：2004-08-26 00:00:00

abstract：:There is currently no ideal radiotracer for imaging of protein synthesis rate (PSR) by positron emission tomography (PET). Existing fluorine-18-labeled amino acid-based radiotracers predominantly visualize amino acid transporter processes, and in many cases they are not incorporated into nascent proteins at all. Other...

journal_title：Journal of medicinal chemistry

authors： Betts HM,Milicevic Sephton S,Tong C,Awais RO,Hill PJ,Perkins AC,Aigbirhio FI

更新日期：2016-10-27 00:00:00

abstract：:As a mitotic-specific target widely deregulated in various human cancers, polo-like kinase 1 (Plk1) has been extensively explored for anticancer activity and drug discovery. Although multiple catalytic domain inhibitors were tested in preclinical and clinical studies, their efficacies are limited by dose-limiting cyto...

journal_title：Journal of medicinal chemistry

authors： Alverez CN,Park JE,Toti KS,Xia Y,Krausz KW,Rai G,Bang JK,Gonzalez FJ,Jacobson KA,Lee KS

更新日期：2020-11-25 00:00:00

abstract：:Improvement in the therapeutic index of doxorubicin, a cytotoxic molecule, has been sought through its chemical conjugation to short (15-23 amino acid) peptide sequences called Vectocell peptides. Vectocell peptides are highly charged drug delivery peptides and display a number of characteristics that make them attrac...

journal_title：Journal of medicinal chemistry

authors： Meyer-Losic F,Quinonero J,Dubois V,Alluis B,Dechambre M,Michel M,Cailler F,Fernandez AM,Trouet A,Kearsey J

更新日期：2006-11-16 00:00:00

abstract：:Indoleamine 2,3-dioxygenase (IDO-1) is emerging as an important new therapeutic target for the treatment of cancer, neurological disorders, and other diseases that are characterized by pathological tryptophan metabolism. However, only a few structural classes are known to be IDO-1 inhibitors. In this study, a natural ...

journal_title：Journal of medicinal chemistry

authors： Yang S,Li X,Hu F,Li Y,Yang Y,Yan J,Kuang C,Yang Q

更新日期：2013-11-14 00:00:00

abstract：:The concept of molecular hybridization led us to discover a novel series of coumarin-dihydropyridine hybrids that have potent osteoblastic bone formation in vitro and that prevent ovariectomy-induced bone loss in vivo. In this context, among all the compounds screened for alkaline phosphatase activity, four compounds ...

journal_title：Journal of medicinal chemistry

authors： Sashidhara KV,Kumar M,Khedgikar V,Kushwaha P,Modukuri RK,Kumar A,Gautam J,Singh D,Sridhar B,Trivedi R

更新日期：2013-01-10 00:00:00

abstract：:Ether-linked glycero-alpha- and beta-D-glucopyranosides and glycero-1-thio-alpha- and beta-D-glucopyranosides have been synthesized by modifications of the Königs-Knorr procedure, and their antitumor activities have been evaluated. The bioactivities of these compounds have been evaluated in five different cell lines (...

journal_title：Journal of medicinal chemistry

authors： Guivisdalsky PN,Bittman R,Smith Z,Blank ML,Snyder F,Howard S,Salari H

更新日期：1990-09-01 00:00:00

abstract：:Tocainide and related optically active chiral alpha-aminoanilides were synthesized and tested in vivo via the hot plate test to evaluate their central analgesic action. The aims of the study were to verify if a) the increase in lipophilicity, obtained by the introduction of an alkyl group on the steric center (3f-i), ...

journal_title：Journal of medicinal chemistry

authors： Corbo F,Franchini C,Lentini G,Muraglia M,Ghelardini C,Matucci R,Galeotti N,Vivoli E,Tortorella V

更新日期：2007-04-19 00:00:00

abstract：:A series of [(heteroarylamino)phenyl]alkanoic acids having pyridine, quinoline, or pyrimidine as the heteroaryl moiety was prepared as potential antiinflammatory agents. Among them, 2-[4-(2-pyridylamino)phenyl]propionic acid (14b) showed excellent antiinflammatory and analgesic activities with less tendency to cause g...

journal_title：Journal of medicinal chemistry

authors： Hino K,Nakamura H,Nagai Y,Uno H,Nishimura H

更新日期：1983-02-01 00:00:00

abstract：:Fragment-based drug design exploits initial screening of low molecular weight compounds and their concomitant affinity improvement. The multitude of possible chemical modifications highlights the necessity to obtain structural information about the binding mode of a fragment. Herein we describe a novel NMR methodology...

journal_title：Journal of medicinal chemistry

authors： Geist L,Mayer M,Cockcroft XL,Wolkerstorfer B,Kessler D,Engelhardt H,McConnell DB,Konrat R

更新日期：2017-11-09 00:00:00

abstract：:A practical combination of comparative modeling and NMR spectroscopy was used to generate a three-dimensional structure of the response regulator protein, Spo0F. The backbone structure obtained compares to the Spo0F Y13S mutant X-ray structure with an rmsd of 2.0 A. We provide results which suggest that structures obt...

journal_title：Journal of medicinal chemistry

authors： Podlogar BL,Leo GC,McDonnell PA,Loughney DA,Caldwell GW,Barrett JF

更新日期：1997-10-10 00:00:00

abstract：:A series of antiviral basic quinolinonyl diketo acid derivatives were developed as inhibitors of HIV-1 IN. Compounds 12d,f,i inhibited HIV-1 IN with IC50 values below 100 nM for strand transfer and showed a 2 order of magnitude selectivity over 3'-processing. These strand transfer selective inhibitors also inhibited H...

journal_title：Journal of medicinal chemistry

authors： Costi R,Métifiot M,Chung S,Cuzzucoli Crucitti G,Maddali K,Pescatori L,Messore A,Madia VN,Pupo G,Scipione L,Tortorella S,Di Leva FS,Cosconati S,Marinelli L,Novellino E,Le Grice SF,Corona A,Pommier Y,Marchand C,Di San

更新日期：2014-04-24 00:00:00

abstract：:A series of conformationally locked N-glycosides having a cis-1,2-fused pyranose-1,3-oxazoline-2-thione structure and bearing different substituents at the exocyclic sulfur has been prepared. The polyhydroxylated bicyclic system was built in only three steps by treatment of the corresponding readily available 1,2-anhy...

journal_title：Journal of medicinal chemistry

authors： Castilla J,Rísquez R,Cruz D,Higaki K,Nanba E,Ohno K,Suzuki Y,Díaz Y,Ortiz Mellet C,García Fernández JM,Castillón S

更新日期：2012-08-09 00:00:00

abstract：:N6-isopentenyladenosine (i6A), a modified nucleoside belonging to the cytokinin family, has shown in humans many biological actions, including antitumoral effects through the modulation of the farnesyl pyrophosphate synthase (FPPS) activity. To investigate the relationship between i6A and FPPS, we undertook an inverse...

journal_title：Journal of medicinal chemistry

authors： Scrima M,Lauro G,Grimaldi M,Di Marino S,Tosco A,Picardi P,Gazzerro P,Riccio R,Novellino E,Bifulco M,Bifulco G,D'Ursi AM

更新日期：2014-09-25 00:00:00

abstract：:Thalidomide, 2-(2,6-dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione, has been shown to inhibit angiogenesis, the formation of new blood vessels from existing vasculature. As a result, there is renewed interest in this drug as a potential therapy for solid tumors. Thalidomide forms a number of metabolites and has been ...

journal_title：Journal of medicinal chemistry

authors： Lepper ER,Ng SS,Gütschow M,Weiss M,Hauschildt S,Hecker TK,Luzzio FA,Eger K,Figg WD

更新日期：2004-04-22 00:00:00

abstract：:Vitamin D receptor (VDR) antagonists prevent the VDR activation function helix 12 from folding into its active conformation, thus affecting coactivator recruitment and antagonizing the transcriptional regulation induced by 1α,25-dihydroxyvitamin D3. Here, we report the crystal structure of the zebrafish VDR ligand-bin...

journal_title：Journal of medicinal chemistry

authors： Belorusova AY,Chalhoub S,Rovito D,Rochel N

更新日期：2020-09-10 00:00:00

abstract：:The antimicrobial and cytotoxic properties of a series of 9,10-dihydrophenanthrenes structurally related to juncusol (1a), a postulated phytoalexin with confirmed cytotoxic properties, are detailed. Two simple 9,10-dihydrophenanthrenes, 2,7-dihydroxy-3,8-dimethyl-9,10-dihydrophenanthrene (2h, desvinyljuncusol) and 2-h...

journal_title：Journal of medicinal chemistry

authors： Boger DL,Mitscher LA,Mullican MD,Drake SD,Kitos P

更新日期：1985-10-01 00:00:00

abstract：:Tertiary EGFRC797S mutation induced resistance against osimertinib (1) is an emerging "unmet clinical need" for non-small-cell lung cancer (NSCLC) patients. A series of 5-methylpyrimidopyridone derivatives were designed and synthesized as new selective EGFRL858R/T790M/C797S inhibitors. A representative compound, 8r-B,...

journal_title：Journal of medicinal chemistry

authors： Shen J,Zhang T,Zhu SJ,Sun M,Tong L,Lai M,Zhang R,Xu W,Wu R,Ding J,Yun CH,Xie H,Lu X,Ding K

更新日期：2019-08-08 00:00:00

abstract：:Assembly of human immunodeficiency virus (HIV-1) represents an attractive target for antiretroviral therapy which is not exploited by currently available drugs. We established high-throughput screening for assembly inhibitors based on competition of small molecules for the binding of a known dodecapeptide assembly inh...

journal_title：Journal of medicinal chemistry

authors： Machara A,Lux V,Kožíšek M,Grantz Šašková K,Štěpánek O,Kotora M,Parkan K,Pávová M,Glass B,Sehr P,Lewis J,Müller B,Kräusslich HG,Konvalinka J

更新日期：2016-01-28 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：:Lofexidine, an alpha 2-agonist, has central hypotensive activity and peripheral intestinal antisecretory activity. Analogues were synthesized with increased polarity in an attempt to prevent penetration of the blood-brain barrier. The compounds were evaluated in the cholera toxin treated ligated jejunum of the rat and...

journal_title：Journal of medicinal chemistry

authors： Moormann AE,Pitzele BS,Jones PH,Gullikson GW,Albin D,Yu SS,Bianchi RG,Sanguinetti EL,Rubin B,Grebner M

更新日期：1990-02-01 00:00:00

abstract：:Fatty acid synthase (FAS) is necessary for growth and survival of tumor cells and is a promising drug target for oncology. Here, we report on the syntheses and activity of novel inhibitors of the thioesterase domain of FAS. Using the structure of orlistat as a starting point, which contains a beta-lactone as the centr...

journal_title：Journal of medicinal chemistry

authors： Richardson RD,Ma G,Oyola Y,Zancanella M,Knowles LM,Cieplak P,Romo D,Smith JW

更新日期：2008-09-11 00:00:00

abstract：:Although the illness malaria is caused by the asexual blood stages, the presence of gametocytes is directly responsible for the infection of the vector Anopheles, thus perpetuating the plasmodial cycle. Fight against malaria is more than ever a current problem, and the solution will probably go through the development...

journal_title：Journal of medicinal chemistry

authors： Dechy-Cabaret O,Benoit-Vical F

更新日期：2012-12-13 00:00:00