Cyclic imides as potent and selective alpha-1A adrenergic receptor antagonists.

abstract：:A single-step sensing system was developed to visually detect ligands of a cleavase-like RNA aptazyme at room temperature using aptazyme-tethered gold nanoparticles, the electrosteric stability of which was adjusted by increasing their diameter. In this system, the ligand induces self-cleavage of the aptazyme on gold ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ogawa A

更新日期：2011-01-01 00:00:00

abstract：:A novel series of 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives targeting VEGFR-2, PDGFR-β and c-Kit kinases were designed and synthesized. The molecular design was based on the SAR features of indolin-2-ones as kinase inhibitors. SAR study of the series allowed us to identify compounds possessing more pot...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ding L,Tang F,Huang W,Jin Q,Shen H,Wei P

更新日期：2013-10-15 00:00:00

abstract：:To explore the hydrophobic groove subsite within the CB1 cannabinoid receptor we have designed and synthesized a group of tail-substituted anandamide analogs. Our design involves the introduction of aryl or heterocyclic ring as terminal substituents that are connected to the last cis-arachidonyl double bond through al...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yao F,Li C,Vadivel SK,Bowman AL,Makriyannis A

更新日期：2008-11-15 00:00:00

abstract：:A new series of indole-based antagonists of the PGD(2) receptor subtype 1 (DP1 receptor) was identified and the progress of the structure-activity relationship study to the identification of potent and selective antagonists is presented. Selective DP1 antagonists with high potency and selectivity were prepared. Of par...

journal_title：Bioorganic & medicinal chemistry letters

authors： Beaulieu C,Guay D,Wang Z,Leblanc Y,Roy P,Dufresne C,Zamboni R,Berthelette C,Day S,Tsou N,Denis D,Greig G,Mathieu MC,O'Neill G

更新日期：2008-04-15 00:00:00

abstract：:A series of compounds originally derived from the vascular endothelial growth factor receptor tyrosine kinase inhibitor, SU5416, was synthesized and evaluated. The most potent compound in this series, compound 7, structurally resembles the potent anti-microtubule agent Combretastatin A-4, inhibited tubulin polymerizat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li PK,Xiao Z,Hu Z,Pandit B,Sun Y,Sackett DL,Werbovetz K,Lewis A,Johnsamuel J

更新日期：2005-12-15 00:00:00

abstract：:The expression of epidermal growth factor receptor (EGFR) across a wide range of tumor cells has attracted attention for use as a tumor marker in drug delivery systems. Therefore, binding molecules with the ability to target EGFR have been developed. Among them, we focused on affibodies that are binding proteins deriv...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nishimura Y,Ezawa R,Ishii J,Ogino C,Kondo A

更新日期：2017-01-15 00:00:00

abstract：:A series of N-phenylnicotinamides (1-40) were designed and evaluated in vitro for their COX inhibitory activities. Most of the synthesized compounds were proved to be potent and selective inhibitors of COX-1. Compound 28 showed the most potent COX-1 inhibitory activity (COX-1 IC(50) = 0.68 ± 0.07 μM) and good selectiv...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shi L,Li ZL,Yang Y,Zhu ZW,Zhu HL

更新日期：2011-01-01 00:00:00

abstract：:Pimavanserin is a selective serotonin 2A receptor (5-HT2AR) inverse agonist that has shown promise for treatment of psychotic symptoms in patients with Parkinson's disease. Here, we detail the (11)C-labeling and subsequently evaluate pimavanserin as a PET-radioligand in pigs. [(11)C]Pimavanserin was obtained by N-meth...

journal_title：Bioorganic & medicinal chemistry letters

authors： Andersen VL,Hansen HD,Herth MM,Dyssegaard A,Knudsen GM,Kristensen JL

更新日期：2015-03-01 00:00:00

abstract：:Chemoselective purification technologies have seen great success in biomolecule isolation, with a classic example being the genetically-encoded His tag utilized to enrich desired proteins from a crude lysate. We sought to translate this purification tactic into a powerful tool for the isolation of natural products and...

journal_title：Bioorganic & medicinal chemistry letters

authors： Trader DJ,Carlson EE

更新日期：2015-11-01 00:00:00

abstract：:In the course of a study of 6-N-amino-substituted analogues of NB-506 (1), a more potent anticancer drug, J-109,404 (2), in which the formyl group of NB-506 was replaced with a 1,3-dihydroxypropane group, was reported. A study of further modification in the positions of two hydroxyl groups at the indole rings of 2 res...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ohkubo M,Nishimura T,Honma T,Nishimura I,Ito S,Yoshinari T,Suda HA,Morishima H,Nishimura S

更新日期：1999-12-06 00:00:00

abstract：:Metal complexing anions represent an important class of inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The first inhibition study of the transmembrane isozymes CA XII (tumor-associated) and XIV with anions is reported. These isozymes showed inhibition profiles with physiologic/non-physiologic ani...

journal_title：Bioorganic & medicinal chemistry letters

authors： Innocenti A,Vullo D,Pastorek J,Scozzafava A,Pastorekova S,Nishimori I,Supuran CT

更新日期：2007-03-15 00:00:00

abstract：:Optimisation of affinity, chemical stability, metabolic stability and solubility led from a chemically labile HTS hit 1 to mGlu5 receptor antagonists (24-26) with high affinity for the allosteric MPEP binding site, improved microsomal metabolic stability and anxiolytic-like activity in vivo as assessed by the Vogel co...

journal_title：Bioorganic & medicinal chemistry letters

authors： Büttelmann B,Peters JU,Ceccarelli S,Kolczewski S,Vieira E,Prinssen EP,Spooren W,Schuler F,Huwyler J,Porter RH,Jaeschke G

更新日期：2006-04-01 00:00:00

abstract：:Recently, a disulfide-based cyclic RGD peptide called iRGD, that is, c(CRGDKGPDC), has been reported to interact with both integrin and neuropilin-1 receptors for cellular and deep tissue penetration to improve the imaging sensitivity and therapeutic efficacy. In this study, two new near-infrared fluorescent iRGD conj...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ye Y,Zhu L,Ma Y,Niu G,Chen X

更新日期：2011-02-15 00:00:00

abstract：:Optimization of clearance of adenosine inhibitors of bacterial NAD(+)-dependent DNA ligase is discussed. To reduce Cytochrome P-450-mediated metabolic clearance, many strategies were explored; however, most modifications resulted in compounds with reduced antibacterial activity and/or unchanged total clearance. The al...

journal_title：Bioorganic & medicinal chemistry letters

authors： Stokes SS,Gowravaram M,Huynh H,Lu M,Mullen GB,Chen B,Albert R,O'Shea TJ,Rooney MT,Hu H,Newman JV,Mills SD

更新日期：2012-01-01 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 structure-activity relationship (SAR) of the vinyl pyridine region of himbacine derived thrombin receptor (PAR-1) antagonists is described. A 2-vinylpyridyl ring substituted with an aryl or a heteroaryl group at the 5-position showed the best overall PAR-1 affinity and pharmacokinetic properties. One of the newly ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xia Y,Chackalamannil S,Clasby M,Doller D,Eagen K,Greenlee WJ,Tsai H,Agans-Fantuzzi J,Ahn HS,Boykow GC,Hsieh Y,Lunn CA,Chintala M

更新日期：2007-08-15 00:00:00

abstract：:The 1,3-dipolar cycloaddition of azomethine ylides derived from substituted isatins and 1,3-thiazolane-4-carboxylic acid to a series of 1-methyl-3,5-bis[(E)-arylmethylidene]-tetrahydro-4(1H)-pyridinones afforded novel spiro-pyrrolothiazoles chemo-, regio- and stereoselectively in quantitative yields. These compounds w...

journal_title：Bioorganic & medicinal chemistry letters

authors： Karthikeyan SV,Bala BD,Raja VP,Perumal S,Yogeeswari P,Sriram D

更新日期：2010-01-01 00:00:00

abstract：:The targeted delivery of taxoids, in the form of taxane-antibody immunoconjugates, requires the preparation of taxoids containing moieties suitable for their conjugation to monoclonal antibodies. A series of taxoids incorporating a disulfide-containing linker at various positions of the taxoid framework have been prep...

journal_title：Bioorganic & medicinal chemistry letters

authors： Miller ML,Roller EE,Wu X,Leece BA,Goldmacher VS,Chari RV,Ojima I

更新日期：2004-08-02 00:00:00

abstract：:We describe here a novel 4-amino-2-cyanopyrimidine scaffold for nonpeptidomimetic cathepsin S selective inhibitors. Some of the synthesized compounds have sub-nanomolar potency and high selectivity toward cathepsin S along with promising pharmacokinetic and physicochemical properties. The key structural features of th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Irie O,Yokokawa F,Ehara T,Iwasaki A,Iwaki Y,Hitomi Y,Konishi K,Kishida M,Toyao A,Masuya K,Gunji H,Sakaki J,Iwasaki G,Hirao H,Kanazawa T,Tanabe K,Kosaka T,Hart TW,Hallett A

更新日期：2008-08-15 00:00:00

abstract：:The syntheses and biological profiles of sulfoximine-based Vioxx analogs 2 are described. Interesting data have been obtained for 2a, which shows a selective COX-2 inhibition (albeit not as strong as Vioxx itself) exhibiting reduced hERG activity compare to the parent sulfone Vioxx (1). ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park SJ,Buschmann H,Bolm C

更新日期：2011-08-15 00:00:00

abstract：:Ligand efficient fragments binding to PDK1 were identified by an NMR fragment-based screening approach. Computational modeling of the fragments bound to the active site led to the design and synthesis of a series of novel 6,7-disubstituted thienopyrimidin-4-one compounds, with low micromolar inhibitory activity agains...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee AC,Ramanujulu PM,Poulsen A,Williams M,Blanchard S,Ma DM,Bonday Z,Goh KL,Goh KC,Goh MK,Wood J,Dymock BW

更新日期：2012-06-15 00:00:00

abstract：:Epothilone A reacted with hydrohalic acids to C12-C13 halohydrin regioisomers (ratios: 2:1-4:1), whereas epothilone B gave under the same conditions the isomerically pure C12 halo C13 hydroxy derivative. With non-nucleophilic Brønstedt acids and with Lewis acids a highly solvent dependent product distribution and some...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sefkow M,Kiffe M,Höfle G

更新日期：1998-11-03 00:00:00

abstract：:New bis-pyridinium oxime reactivators connected with a CH(2)CH(2)OCH(2)CH(2) linker between two pyridinium rings were designed and synthesized. In the test of their potency to reactivate AChE inhibited by cyclosarin, the bis-pyridinium oxime 6b achieved reactivation potency higher than 10% at the lower concentration 1...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim TH,Kuca K,Jun D,Jung YS

更新日期：2005-06-02 00:00:00

abstract：:Fragment-based NMR screening of a small literature focused library led to identification of a historical thrombin/FactorXa building block, 17A, that was found to be a ROCK-I inhibitor. In the absence of an X-ray structure, fragment growth afforded 6-substituted isoquinolin-1-amine derivatives which were profiled in th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ray P,Wright J,Adam J,Bennett J,Boucharens S,Black D,Cook A,Brown AR,Epemolu O,Fletcher D,Haunso A,Huggett M,Jones P,Laats S,Lyons A,Mestres J,de Man J,Morphy R,Rankovic Z,Sherborne B,Sherry L,van Straten N,We

更新日期：2011-01-01 00:00:00

abstract：:Acyl derivatives of 4-(aminomethyl)-N-hydroxybenzamide are potent sub-type selective HDAC6 inhibitors. Constrained heterocyclic analogs based on 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine show further enhanced HDAC6 selectivity and inhibitory activity in cells. Homology models suggest that the heterocyclic spacer can mo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Blackburn C,Barrett C,Brunson M,Chin J,England D,Garcia K,Gigstad K,Gould A,Gutierrez J,Hoar K,Rowland RS,Tsu C,Ringeling J,Wager K,Xu H

更新日期：2014-12-01 00:00:00

abstract：:The identification of a novel hit compound inhibitor of the protein-protein interaction between the influenza RNA-polymerase PA and PB1 subunits has been accomplished by means of high-throughput screening. A small family of structurally related molecules has been synthesized and biologically evaluated with most of the...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kessler U,Castagnolo D,Pagano M,Deodato D,Bernardini M,Pilger B,Ranadheera C,Botta M

更新日期：2013-10-15 00:00:00

abstract：:The first biological target for the natural product complanadine A has been determined. The pseudosymmetric alkaloid functions as a selective agonist for the Mas-related G protein-coupled receptor X2 (MrgprX2), a G protein-coupled receptor that is highly expressed in neurons. Given the potential of MrgprX2 to function...

journal_title：Bioorganic & medicinal chemistry letters

authors： Johnson T,Siegel D

更新日期：2014-08-01 00:00:00

abstract：:In this work, we have designed cyclic peptides (cIBL, cIBR, cIBC, CH4 and CH7) derived from the parent IB peptide (ICAM-1(1-21)) that are inhibitors of ICAM-1/LFA-1-mediated T-cell adhesion to Caco-2 cell monolayers. Cyclic peptide cIBR has the best activity of any of the peptides evaluated. The active ICAM-1 peptides...

journal_title：Bioorganic & medicinal chemistry letters

authors： Anderson ME,Yakovleva T,Hu Y,Siahaan TJ

更新日期：2004-03-22 00:00:00

abstract：:A series of fluconazole analogues 5-20 incorporating azaindole and indole moieties were prepared using oxirane intermediates synthesized under microwave irradiation. All of the compounds were evaluated in vitro against two clinically important fungi, Candida albicans and Aspergillus fumigatus. Four derivatives 6, 13, ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lebouvier N,Pagniez F,Duflos M,Le Pape P,Na YM,Le Baut G,Le Borgne M

更新日期：2007-07-01 00:00:00

abstract：:In an effort to identify a potential back-up to apixaban (Eliquis®), we explored a series of diversified P4 moieties. Several analogs with substituted gem-dimethyl moieties replacing the terminal lactam of apixaban were identified which demonstrated potent FXa binding affinity (FXa Ki), good human plasma anticoagulant...

journal_title：Bioorganic & medicinal chemistry letters

authors： Orwat MJ,Qiao JX,He K,Rendina AR,Luettgen JM,Rossi KA,Xin B,Knabb RM,Wexler RR,Lam PY,Pinto DJ

更新日期：2014-08-01 00:00:00