Optimization of the enzymatic synthesis of O-glycan core 2 structure by use of a genetic algorithm.

abstract：:5-Carboxamido-1,3,2-dioxaphosphorinanes have been identified as potent inhibitors of microsomal triglyceride-transfer protein. The 1,3,2-dioxaphosphorine functionality acted as a neutral and stable replacement for piperidine and piperidine N-oxide. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sulsky R,Robl JA,Biller SA,Harrity TW,Wetterau J,Connolly F,Jolibois K,Kunselman L

更新日期：2004-10-18 00:00:00

abstract：:Retinoid X Receptor (RXR) specific ligands are currently being investigated for the treatment of metabolic diseases such as type II diabetes. We report the synthesis of conformationally locked retinoids, which are potent RXR selective ligands, and the attempted synthesis of 9-cyclopropyl locked analogs of RA and 9-cis...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vuligonda V,Garst ME,Chandraratna RA

更新日期：1999-02-22 00:00:00

abstract：:In an effort to identify novel, broad-spectrum inhibitors against the metallo-β-lactamases (MβLs), several N-heterocyclic derivatives were tested as inhibitors of MβLs CcrA, ImiS, and L1, which are representative enzymes from the distinct MβL subclasses. Three N-heterocyclic dicarboxylic acid derivatives were competit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Feng L,Yang KW,Zhou LS,Xiao JM,Yang X,Zhai L,Zhang YL,Crowder MW

更新日期：2012-08-15 00:00:00

abstract：:In this letter, we describe the first synthesis of two recently isolated flavones 5-carbomethoxymethyl-7-hydroxy-2-pentylchromone (3a), 5-carboethoxymethyl-4',7-dihydroxyflavone (3b) and their derivatives (3c-t), evaluated for their antimicrobial, antioxidant and anticancer activities. Most of the synthesized compound...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kamal A,Murty JN,Viswanath A,Sujitha P,Ganesh Kumar C

更新日期：2012-07-15 00:00:00

abstract：:A serendipitous discovery that the metalloprotease binding profile of a novel class of 2-carboxamide-3-hydroxamic acid piperidines could be significantly attenuated by the modification of the unexplored P1 substituent enabled the design and synthesis of a novel 2-carboxamide-1-hydroxamic acid cyclohexyl scaffold core ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Burns DM,Li YL,Shi E,He C,Xu M,Zhuo J,Zhang C,Qian DQ,Li Y,Wynn R,Covington MB,Katiyar K,Marando CA,Fridman JS,Scherle P,Friedman S,Metcalf B,Yao W

更新日期：2009-07-01 00:00:00

abstract：:A series of 1,7-diaminoisoquinolinamines, that are expected to mediate antimalarial activity by the same mechanism employed by the chalcones, were produced. Six 7-benzylamino-1-isoquinolinamines were found to be submicromolar inhibitors in vitro of drug-resistant Plasmodium falciparum, with the best possessing activit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gutteridge CE,Hoffman MM,Bhattacharjee AK,Milhous WK,Gerena L

更新日期：2011-01-15 00:00:00

abstract：:A series of phenoxy benzoxaboroles were synthesized and screened for their inhibitory activity against PDE4 and cytokine release. 5-(4-Cyanophenoxy)-2,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2728) showed potent activity both in vitro and in vivo. This compound is now in clinical development for the topical treatment ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Akama T,Baker SJ,Zhang YK,Hernandez V,Zhou H,Sanders V,Freund Y,Kimura R,Maples KR,Plattner JJ

更新日期：2009-04-15 00:00:00

abstract：:We have increased the potency of imidazo[1,2-b]pyridazine derivatives as IKKβ inhibitors with two strategies. One is to enhance the activity in cell-based assay by adjusting the polarity of molecules to improve permeability. Another is to increase the affinity for IKKβ by the introduction of additional substituents ba...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shimizu H,Yasumatsu I,Hamada T,Yoneda Y,Yamasaki T,Tanaka S,Toki T,Yokoyama M,Morishita K,Iimura S

更新日期：2011-02-01 00:00:00

abstract：:This communication describes the high-throughput screen of a diverse library of 50,000 small molecules against Escherichia coli dihydrofolate reductase to detect inhibitors. Sixty-two compounds were identified as having significant inhibitory activity against the enzyme. Secondary screening of these revealed twelve mo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zolli-Juran M,Cechetto JD,Hartlen R,Daigle DM,Brown ED

更新日期：2003-08-04 00:00:00

abstract：:Cyclic nucleotide phosphodiesterase IV (PDE IV) inhibitors find utility in asthma and Chronic Obstructive Pulmonary Disease (COPD) therapy. A series of 29 thieno[3,2-d]pyrimidines with affinity for PDE IV was subjected to three dimensional quantitative structure activity relationship (3D-QSAR) studies using comparativ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chakraborti AK,Gopalakrishnan B,Sobhia ME,Malde A

更新日期：2003-04-17 00:00:00

abstract：:Zoanthamines are a family of marine alkaloids that have complex heptacyclic structures and are reported to be interleukin-6 modulators. While the structure of zoanthamines, especially the ABC-ring portion, is similar to that of steroids, the CDEFG-ring portion, composed of aminoacetal and lactone core, is a unique str...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hirai G,Oguri H,Hayashi M,Koyama K,Koizumi Y,Moharram SM,Hirama M

更新日期：2004-05-17 00:00:00

abstract：:To discover new natural-product-based insecticidal agents, a series of novel oxime derivatives of podophyllotoxin-based phenazines modified in the C, D and E rings of podophyllotoxin were prepared and tested as insecticidal agents against the pre-third-instar larvae of oriental armyworm, Mythimna separata (Walker) in ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhi X,Yang C,Yu X,Xu H

更新日期：2014-12-15 00:00:00

abstract：:Building on our initial work, we have identified additional novel inhibitors of sphingosine kinase-1 (SK1). These new analogs address the shortcomings found in our previously reported compounds. Inhibitors 51 and 54 demonstrated oral bioavailability in a rat PK study. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xiang Y,Hirth B,Kane JL Jr,Liao J,Noson KD,Yee C,Asmussen G,Fitzgerald M,Klaus C,Booker M

更新日期：2010-08-01 00:00:00

abstract：:The synthesis and inhibitory activity against MraY of a series of simplified analogues of liposidomycins are described. These compounds were mainly obtained by performing parallel synthesis in the 6'-position of a scaffold that gathers key features found necessary for the binding to MraY. Thus, inhibitory activity was...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dini C,Didier-Laurent S,Drochon N,Feteanu S,Guillot JC,Monti F,Uridat E,Zhang J,Aszodi J

更新日期：2002-04-22 00:00:00

abstract：:A short synthetic route to the first beta-l-ribo configured locked nucleic acid (LNA), that is, 2'-amino-beta-l-LNA thymine phosphoramidite 6, has been developed from bicyclic nucleoside 1. Incorporation of 2'-amino-beta-l-LNA thymine monomers into alpha-DNA strands results in probes forming stable duplexes with compl...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kumar TS,Ostergaard ME,Sharma PK,Nielsen P,Wengel J,Hrdlicka PJ

更新日期：2009-05-01 00:00:00

abstract：:A novel series of kappa (kappa) opioid receptor agonists were synthesized by incorporating the key structural features of known kappa opioid agonists while replacing the aryl acetamide portion with substituted amino acid conjugates. Compounds 3j (Ki = 6.7 nM), 3k (Ki = 3.6 nM), 3l (Ki = 4.6 nM), 3m (Ki = 0.83 nM) and ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kumar V,Guo D,Daubert JD,Cassel JA,DeHaven RN,Mansson E,DeHaven-Hudkins DL,Maycock AL

更新日期：2005-03-01 00:00:00

abstract：:Total synthesis of human chymase inhibitor methyllinderone has been achieved in only four steps with an overall yield of 21% from dimethyl squarate. We developed an efficient synthetic method for obtaining methyllinderone derivatives and found the active compound. In addition, we propose the inhibition mechanism of th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Aoyama Y,Konoike T,Kanda A,Naya N,Nakajima M

更新日期：2001-07-09 00:00:00

abstract：:We synthesized novel water-soluble and orally active taxane analogues, 7-deoxy-9beta-dihydro-9,10-O-acetal taxanes. Cytotoxicities of the synthetic compounds were greater than those of paclitaxel and docetaxel, especially against resistant cancer cell lines expressing P-glycoprotein. In addition, some compounds showed...

journal_title：Bioorganic & medicinal chemistry letters

authors： Takeda Y,Yoshino T,Uoto K,Chiba J,Ishiyama T,Iwahana M,Jimbo T,Tanaka N,Terasawa H,Soga T

更新日期：2003-01-20 00:00:00

abstract：:Structure- and ligand-based virtual-screening methods (docking, 2D- and 3D-similarity searching) were analyzed for their effectiveness in virtual screening against FFAR2. To evaluate the performance of these methods, retrospective virtual screening was performed. Statistical quality of the methods was evaluated by BED...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fells JI,Ai X,Weinglass A,Feng W,Lei Y,Finley M,Hoveyda HR,Fraser GL,Machacek M

更新日期：2020-11-01 00:00:00

abstract：:The cross talk between different membrane receptors is the source of increasing research. We designed and synthesized a new hetero-bivalent ligand that has antagonist properties on both A(1) adenosine and mu opiate receptors with a K(i) of 0.8+/-0.05 and 0.7+/-0.03 microM, respectively. This hybrid molecule increases ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mathew SC,Ghosh N,By Y,Berthault A,Virolleaud MA,Carrega L,Chouraqui G,Commeiras L,Condo J,Attolini M,Gaudel-Siri A,Ruf J,Parrain JL,Rodriguez J,Guieu R

更新日期：2009-12-01 00:00:00

abstract：:A new class of non-ionic amphiphilic molecules suitable for biological purposes, especially extraction of membrane proteins, is reported. Such surfactants were prepared in two steps: addition of alkyl or fluoroalkyl mercaptan on Tris(hydroxymethyl)acrylamidomethane (THAM) derivatives, followed by the oxydation of sulf...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barthélémy P,Maurizis JC,Lacombe JM,Pucci B

更新日期：1998-06-16 00:00:00

abstract：:The side chain benzylic methylene is a critical element for the vanilloid activity of resiniferatoxin (2a, RTX), and introduction of branching, oxygen functions, or isosteric substitution at this center proved detrimental, with a decrease of potency of 2-3 orders of magnitude compared to the natural product. Conversel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Appendino G,Ech-Chahad A,Minassi A,De Petrocellis L,Di Marzo V

更新日期：2010-01-01 00:00:00

abstract：:While a correlation between blockade of the orexin 2 receptor (OX2R) with either a dual orexin receptor antagonist (DORA) or a selective orexin 2 receptor antagonist (2-SORA) and a decrease of wakefulness is well established, less is known about selective blockade of the orexin 1 receptor (OX1R). Therefore, a highly s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Stump CA,Cooke AJ,Bruno J,Cabalu TD,Gotter AL,Harell CM,Kuduk SD,McDonald TP,O'Brien J,Renger JJ,Williams PD,Winrow CJ,Coleman PJ

更新日期：2016-12-01 00:00:00

abstract：:We have designed and synthesized econazole-derived nitroimidazoles to investigate the antitubercular activity of the nitroimidazole compounds. The introduction of a nitro group at the 4-position of the imidazole on econazole abolished the antitubercular activity. However, alcoholic nitroimidazoles 4 and 6 compounds we...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee SH,Kim S,Yun MH,Lee YS,Cho SN,Oh T,Kim P

更新日期：2011-03-01 00:00:00

abstract：:Prothrombin is a vitamin K-dependent serine protease and plays pivotal roles in both procoagulant and anticoagulant pathway of hemostasis. In this study, prothrombin purified from porcine plasma was modified through PEGylation at N-terminal residue using 40 kDa PEG-phenyl-isothiocyanate (PIT-PEG40K). The monoPEGylated...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhou JG,Chen YM

更新日期：2011-06-01 00:00:00

abstract：:In the course of our research aimed at the discovery of metabolic stable pleuromutilin derivatives with more potent antibacterial activity against Gram-positive pathogens than previous analogues, a series of compounds bearing a purine ring were prepared and evaluated. From SAR studies, we identified two promising comp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hirokawa Y,Kinoshita H,Tanaka T,Nakamura T,Fujimoto K,Kashimoto S,Kojima T,Kato S

更新日期：2008-06-15 00:00:00

abstract：:Benzylamides of pentanedioic acid were identified as inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) by high-throughput screening. Optimisation to 2-adamantyl amides yielded inhibitors with single digit nanomolar IC(50)s on the 11beta-HSD1 human isoform. The hydroxy adamantyl amide lead compound...

journal_title：Bioorganic & medicinal chemistry letters

authors： Roche D,Carniato D,Leriche C,Lepifre F,Christmann-Franck S,Graedler U,Charon C,Bozec S,Doare L,Schmidlin F,Lecomte M,Valeur E

更新日期：2009-05-15 00:00:00

abstract：:We report here a simple entry into naphtho[2,3-d]isoxazole-4,9-dione system containing a EWG in position 3 using the readily available 2,3-dichloro-1,4-naphthoquinone and nitromethyl derivatives in the presence of base. Antifungal activity of synthesised naphthoquinones was evaluated against ATCC and PYCC reference st...

journal_title：Bioorganic & medicinal chemistry letters

authors： Santos MM,Faria N,Iley J,Coles SJ,Hursthouse MB,Martins ML,Moreira R

更新日期：2010-01-01 00:00:00

abstract：:Based on lead compound 1 identified from the patent literature, we developed novel patentable BACE-1 inhibitors by introducing a cyclic amine scaffold. Extensive SAR studies on both pyrrolidines and piperidines ultimately led to inhibitor 2f, one of the most potent inhibitors synthesized to date. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Iserloh U,Wu Y,Cumming JN,Pan J,Wang LY,Stamford AW,Kennedy ME,Kuvelkar R,Chen X,Parker EM,Strickland C,Voigt J

更新日期：2008-01-01 00:00:00

abstract：:Proanthocyanidins are oligomers of catechins that exhibit potent antioxidative activity and inhibit binding of oxidized low-density lipoprotein (OxLDL) to the lectin-like oxidized LDL receptor (LOX-1), which is involved in the onset and development of arteriosclerosis. Previous attempts aimed at developing proanthocya...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mizuno M,Nakanishi I,Matsumoto KI,Fukuhara K

更新日期：2017-11-15 00:00:00