Abstract:
:The acyloxyalkyl derivatives of a model anti-HBV dinucleotide were synthesized and evaluated as orally bioavailable prodrugs. Our studies have led to the identification of the first orally bioavailable dinucleotide prodrugs for further therapeutic development against the hepatitis B virus (HBV).
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Coughlin JE,Padmanabhan S,Zhang G,Kirk CJ,Govardhan CP,Korba BE,O'Loughlin K,Green CE,Mirsalis J,Morrey JD,Iyer RPdoi
10.1016/j.bmcl.2010.01.010subject
Has Abstractpub_date
2010-03-01 00:00:00pages
1783-6issue
5eissn
0960-894Xissn
1464-3405pii
S0960-894X(10)00012-0journal_volume
20pub_type
杂志文章abstract::To develop more effective antitumor steroidal drugs, we synthesized a library including twenty-two novel cytotoxic 2-alkyloxyl substituted (25R)-spirostan-1,4,6-triene-3-ones and corresponding 1,2,3-triazoles through an abnormal monoepoxide ring-opening/elimination and 'click' reactions. After the cytotoxic evaluation...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2015.06.028
更新日期:2015-09-01 00:00:00
abstract::Cell penetrating peptide TAT was introduced into doxorubicin structure. Synthesized doxorubicin-TAT conjugate showed different intracellular distribution pattern and cell killing activity from those of free doxorubicin. Unlike free doxorubicin, doxorubicin-TAT conjugate was highly permeable to drug-resistant cells and...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2005.07.087
更新日期:2005-11-15 00:00:00
abstract::All the stereoisomers of 2-(2-carboxy-3,3-difluorocyclopropyl)glycines (F2CCGs) were synthesized in enantiomerically pure forms using (R)-2,3-O-isopropyl-ideneglyceraldehyde as a chiral precursor. L-F2CCG-I, one of the stereoisomers corresponding to an extended form of L-glutamate was found to be a potent agonist for ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(98)00338-2
更新日期:1998-08-04 00:00:00
abstract::The 1,2,3-triazole ring fused with pyridine/pyrimidine was explored as new template for the identification of potential antimicrobial agents. The regioselective synthesis of these pre-designed N-heteroarenes was achieved via exploring the application of Buchwald's strategy (i.e. C-N bond formation/reduction/diazotizat...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.09.021
更新日期:2018-11-01 00:00:00
abstract::Twelve dimeric peptidomimetics 1 were prepared via a divergent-convergent strategy. These peptidomimetics incorporated the same amino acids as i +1 and i + 2 residues in key beta-turns of the neurotrophin NT-3. Cytosensor microphysiometry was used to gauge the effects of the dimers 1 on cells that overexpress the NT-3...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(00)00618-1
更新日期:2001-01-22 00:00:00
abstract::The general strategy and rationale underlying the design of COPD therapeutics that possess protease inhibitory activity and are also capable of releasing a species that attenuates inflammation by inhibiting caspase-1, are described. The synthesis and in vitro biochemical evaluation of a dual function molecule that seq...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2010.12.033
更新日期:2011-05-15 00:00:00
abstract::Following the recent disclosure of 3-methyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4-(1,2,2-trimethyl-propyl) ester as a potent and selective mGluR1 non-competitive antagonist, the use of a doubly (13)C-labeled analogue to identify, and consequently prevent, metabolically labile positions is reported. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2006.11.039
更新日期:2007-02-15 00:00:00
abstract::The vertebrate Cys-loop family of ligand-gated ion channels (LGICs) are comprised of nicotinic acetylcholine (nAChR), serotonin type 3 (5-HT3R), γ-aminobutyric acid (GABAAR), and glycine (GlyR) receptors. Here, we review efforts to discover selective small molecules targeting one or more Cys-loop receptors, with a foc...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章,评审
doi:10.1016/j.bmcl.2017.04.073
更新日期:2017-08-01 00:00:00
abstract::In the search for nicotinic acetylcholine receptor (nAChRs) agonists with a selective affinity for the homomeric alpha7 channels, we carried out the virtual screening of a test set of potential nicotinic ligands, and adopted a simplified MM-PBSA approach to estimate their relative binding free energy values. By means ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2009.09.073
更新日期:2009-11-15 00:00:00
abstract::A series of [4,6-(substituted aryl)-2-thioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-acetic acid (4a-r) has been synthesized by the base catalyzed condensation of beta-aroylpropionic acid, thiourea with aldehyde in ethanol. Structures of the new compound were established on the basis of (1)H NMR and IR spectral data. Anti-...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2004.01.039
更新日期:2004-04-05 00:00:00
abstract::Various substituted indazole and benzoxazolone amino acids were investigated as d-tyrosine surrogates in highly potent CGRP receptor antagonists. Compound 3, derived from the 7-methylindazole core, afforded a 30-fold increase in CGRP binding potency compared with its unsubstituted indazole analog 1. When dosed at 0.03...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.01.011
更新日期:2013-03-15 00:00:00
abstract::Several shortened peptide analogues of the N-terminal domain of GPR1, an orphan G protein-coupled receptor (GPCR), were prepared and their anti-HIV-1 activities were evaluated. Some of the prepared compounds, especially sulfated derivatives, showed potent inhibitory activity against a broad range of HIV-1, including T...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(01)00503-0
更新日期:2001-10-08 00:00:00
abstract::We report the synthesis of a series of C9 and N5Ac modified analogs of 2,3-didehydro-N-acetyl-neuraminic acid (DANA) and their inhibitory potency for the human neuraminidase 3 (NEU3) enzyme. We were able to generate a small library of compounds through the synthesis of azide derivatives of DANA, followed by Cu-catalyz...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2010.09.111
更新日期:2010-12-15 00:00:00
abstract::New inhibitors of palmitoyl-CoA oxidation are based on the introduction of nitrogen heterocycles in the 'Western Portion' of the molecule. SAR studies led to the discovery of CVT-4325 (shown), a potent FOXi (IC50=380 nM rat mitochondria) with favorable PK properties (F=93%, t(1/2)=13.6h, dog). ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2004.09.077
更新日期:2004-12-20 00:00:00
abstract::Herein we report the optimization efforts to ameliorate the potent CYP3A4 time-dependent inhibition (TDI) and low aqueous solubility exhibited by a previously identified lead compound from our NAMPT inhibitor program (1, GNE-617). Metabolite identification studies pinpointed the imidazopyridine moiety present in 1 as ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2014.12.026
更新日期:2015-02-01 00:00:00
abstract::Pd(II), Cu(II) and Zn(II) complexes (1-3) based on 4'-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-2,2':6',2″-terpyridine were synthesized and characterized by UV, IR, NMR, EPR, HRMS, elemental analyses, and molar conductivity measurements. The cytotoxicity of these complexes against HL-60, BGC-823, KB, Bel-7402, A549, Hela, ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.07.003
更新日期:2013-09-15 00:00:00
abstract::The screening for new inhibitors of steroid sulfatase requires an efficient test system. To overcome the shortcomings of the available discontinuous fluorimetric assay, several coumarin-type compounds were investigated as potential new substrates. 3,4-Benzocoumarin 7-O-sulfate was found to have appropriate substrate p...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(00)00144-x
更新日期:2000-05-01 00:00:00
abstract::Protein geranylgeranylation is a type of post-translational modification that aids in the localization of proteins to the plasma member where they elicit cellular signals. To better understand the isoprenoid requirements of GGTase-I, a series of aryl-modified geranylgeranyl diphosphate analogs were synthesized and scr...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2016.06.034
更新日期:2016-08-01 00:00:00
abstract::Oxidative-stress induces inflammatory diseases. Further, infections caused by drug-resistant microbial strains are on the rise. This necessitates the discovery of novel small-molecules for intervention therapy. A series of 3-(2,3-dichlorophenyl)-1-(aryl)prop-2-en-1-ones are synthesized as intermediates via Claisen-Sch...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2017.06.063
更新日期:2017-08-15 00:00:00
abstract::Dihydroquinolines have been synthesized and have been shown to be potent n-NOS inhibitors. Selectivity versus e-NOS was increased to approximately 100-fold through appropriate substitution at the benzene ring. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(02)00481-x
更新日期:2002-09-16 00:00:00
abstract::A new series of 5-(1-aryl-3-methyl-1H-pyrazol-4-yl)-1H-tetrazole derivatives (4a-m) and their precursor 1-aryl-3-methyl-1H-pyrazole-4-carbonitriles (3a-m) were synthesized and evaluated as antileishmanials against Leishmania braziliensis and Leishmania amazonensis promastigotes in vitro. In parallel, the cytotoxicity ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.09.062
更新日期:2013-12-01 00:00:00
abstract::p38alpha Mitogen Activated Protein Kinase (MAP kinase) is an intracellular soluble serine threonine kinase. p38alpha kinase is activated in response to cellular stresses, growth factors and cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha). The central role of p38alpha activation in se...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(03)00653-x
更新日期:2003-09-15 00:00:00
abstract::A simple and versatile method for preparation of (D)-Phe-Pro peptidomimetic bicyclic thiazolidine lactams is presented. These bicyclic lactams have chemical diversity alpha to the lactam carbonyl and, when linked to electrophilic arginines, provide potent thrombin inhibitors. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(99)00130-4
更新日期:1999-04-05 00:00:00
abstract::Using the X-ray crystal structure of an amide-based progesterone receptor (PR) partial agonist bound to the PR ligand binding domain, a novel PR partial agonist class containing a pyrrolidine ring was designed. Members of this class of N-alkylpyrrolidines demonstrate potent and highly selective partial agonism of the ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2009.06.055
更新日期:2009-08-15 00:00:00
abstract::We describe the synthesis and binding affinities on D(2), 5-HT(2A) and 5-HT(2C) receptors of 6-aminomethyl-6,7-dihydro-1H-indazol-4(5H)-ones and 6-aminomethyl-6,7-dihydro-3-methyl-benzo[d]isoxazol-4(5H)-ones, as conformationally constrained butyrophenone analogues. One of the new compounds showed good in vitro binding...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2007.06.045
更新日期:2007-09-01 00:00:00
abstract::Two closely related scaffolds were identified through an uHTS campaign as desirable starting points for the development of Rho-Kinase (ROCK) inhibitors. Here, we describe our hit-to-lead evaluation process which culminated in the rapid discovery of potent leads such as 22 which successfully demonstrated an early in vi...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2010.04.070
更新日期:2010-06-01 00:00:00
abstract::A series of substituted 2-(aminoheteroaryl)-thiazole-5-carboxamide analogs have been synthesized as novel, potent inhibitors of the Src-family kinase p56Lck. Among them, compound 2 displayed superior in vitro potency and excellent in vivo efficacy. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2004.09.093
更新日期:2004-12-20 00:00:00
abstract::Naphthalimide-derived azoles as a new type of antimicrobial agents were synthesized and evaluated for their efficiency in vitro against eight bacteria and two fungi by two fold serial dilution technique. Most title compounds exhibited good antimicrobial potency with low MIC values ranging from 1 to 16μg/mL. Notably, s...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.05.042
更新日期:2011-07-15 00:00:00
abstract::MDM2 and MDMX are oncoproteins that negatively regulate the activity and stability of the tumor suppressor protein p53. The inhibitors of protein-protein interactions (PPIs) of MDM2-p53 and MDMX-p53 represent potential anticancer agents. In this study, a novel approach for identifying MDM2-p53 and MDMX-p53 PPI inhibit...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.04.094
更新日期:2013-07-01 00:00:00
abstract::A series of 43, 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues (D01-D43) were analysed using Petra, Osiris, Molinspiration and ALOGPS (POMA) to identify pharmacophore, toxicity prediction, lipophilicity and bioactivity. All the compounds were evaluated for anti-HIV activity. 3-(4-Chloroph...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2012.09.108
更新日期:2012-12-01 00:00:00