Abstract:
:We identified and tested bisphosphonates as inhibitors of a protozoan molecular target. Computational modeling studies demonstrated that these compounds are mimics of the natural substrate of the enzyme. The most potent bisphosphonates in vitro are pamidronate and risedronate, which inhibit the purine transferase from Trypanosoma cruzi in the micromolar range.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Fernández D,Wenck MA,Craig SP 3rd,Delfino JMdoi
10.1016/j.bmcl.2004.06.042subject
Has Abstractpub_date
2004-09-06 00:00:00pages
4501-4issue
17eissn
0960-894Xissn
1464-3405pii
S0960894X04007978journal_volume
14pub_type
杂志文章abstract::The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome associated coronavirus (SARS-CoV) is vital for SARS-CoV replication and is a promising drug target. Structure based virtual screening of 308307 chemical compounds was performed using the computation tool Autodock 3.0.5 on a WISDOM Production Environm...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.03.034
更新日期:2011-05-15 00:00:00
abstract::In the previous article we demonstrated how certain CCK2R-selective anthranilic amides could be structurally modified to afford high-affinity, selective CCK1R activity. We now describe our efforts at modulating and optimizing the CCK1R and CCK2R affinities aimed at producing compounds with good pharmacokinetics proper...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2009.09.065
更新日期:2009-11-15 00:00:00
abstract::A novel series of aminopyrimidine IKK2 inhibitors have been developed which show excellent in vitro inhibition of this enzyme and good selectivity over the IKK1 isoform. The relative potency and selectivity of these compounds has been rationalized using QSAR and structure-based modelling. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2003.10.047
更新日期:2004-01-19 00:00:00
abstract::Neutral fluorescent active di-pyrene modified gamma-cyclodextrin (1) was synthesized in order to discriminate with single and double strand DNA (ssDNA and dsDNA, respectively) with high selectivity. The binding and selectivity of 1 for dsDNA was indicated by increase of the fluorescent intensity in an addition of dsDN...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2010.04.066
更新日期:2010-06-01 00:00:00
abstract::The reaction mechanisms of hypochlorous acid (HOCl) with several tryptophan and tryptamine derivatives, previously reported to scavenge this powerful oxidant, was investigated to determine whether ionic or radical pathways were involved. For this purpose, the reaction of tryptamine and tryptophan derivatives with HOCl...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2010.09.067
更新日期:2010-11-15 00:00:00
abstract::A new class of O-arylmandelic acid PPAR agonists show excellent anti-hyperglycemic efficacy in a db/db mouse model of DM2. These PPARalpha-weighted agonists do not show the typical PPARgamma associated side effects of BAT proliferation and cardiac hypertrophy in a rat tolerability assay. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(03)00702-9
更新日期:2003-10-06 00:00:00
abstract::A number of molecular recognition features have been exploited in structure-based design of selective Cathepsin inhibitors. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2009.06.090
更新日期:2009-08-15 00:00:00
abstract::We designed and synthesized novel δ opioid receptor (DOR) agonists 3a-i with an azatricyclodecane skeleton, which was a novel structural class of DOR agonists. Among them, 3b exhibited high values of binding affinity and potent agonistic activity for the DOR that were approximately equivalent to those of 2 which bore ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2017.05.072
更新日期:2017-08-01 00:00:00
abstract::We report herein the design and synthesis of a series of novel ciprofloxacin (CPFX) derivatives with remarkable improvement in lipophilicity by introducing a substituted benzyl moiety to the N atom on the C-7 piperazine ring of CPFX. Antimycobacterial and antibacterial activity of the newly synthesized compounds was e...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2012.07.040
更新日期:2012-09-15 00:00:00
abstract::An Mg2+ and ATP dependent beta-lactam synthetase (BLS) catalyses formation of a beta-lactam ring during the biosynthesis of clavulanic acid, an important beta-lactamase inhibitor. An epimeric mixture of a 2-methylated derivative of the natural BLS substrate N2-(2-carboxyethyl)-L-arginine was synthesised and found to b...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(01)00806-x
更新日期:2002-02-25 00:00:00
abstract::Amidino-phenoxy quinoline derivatives represent a new class of potent thrombin inhibitors with good selectivity and remarkably low molecular weight (M(W): 335-391). X-ray analyses of thrombin-bound inhibitors revealed that enzyme inhibition is mainly based on hydrophobic interactions. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(03)00442-6
更新日期:2003-07-21 00:00:00
abstract::A series of seventeen tetrazole derivatives of 1,7,7-trimethyl-[2.2.1]bicycloheptane were synthesized using click chemistry methodology and characterized by spectral data. Studies of cytotoxicity and in vitro antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells of the compounds obtained w...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2017.03.051
更新日期:2017-05-15 00:00:00
abstract::New adjuvants of warfarin anticoagulant activity have been developed. These compounds, which are 1,4-methano-1,2,3,4-tetrahydroanthracene-9,10-diol derivatives, act synergistically with warfarin to potentiate its anticoagulant effect. None of the compounds tested is an effective oral anticoagulant in the absence of wa...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2010.01.123
更新日期:2010-03-15 00:00:00
abstract::IkappaB kinase beta (IKK-beta) is a serine-threonine protein kinase critically involved in the activation of the transcription factor Nuclear Factor kappa B (NF-kappaB) in response to various inflammatory stimuli. We have identified a small molecule inhibitor of IKK-beta. Optimization of the lead compound resulted in ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(02)01046-6
更新日期:2003-03-10 00:00:00
abstract::Two thermostable α-carbonic anhydrases (α-CAs) isolated from thermophilic Sulfurihydrogenibium spp., namely SspCA (from S. yellowstonensis) and SazCA (from S. azorense), were shown in a previous work to possess interesting complementary properties. SspCA was shown to have an exceptional thermal stability, whereas SazC...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2015.02.068
更新日期:2015-05-01 00:00:00
abstract::We report the synthesis and properties of two new seminaphthorhodafluor (SNARF) derivatives, SNARF-F and SNARF-Cl. Both these derivatives exhibit typical red shifts of absorption and fluorescence, and higher cell permeability as compared to traditional SNARF, while the pH-dependent dual-emission characteristics are we...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.01.105
更新日期:2011-03-15 00:00:00
abstract::This Letter describes the discovery of a number of functionalized bisimidazoles bearing a cyclohexylphenyl, piperidylphenyl, or bicyclo[2,2,2]octylphenyl motif as HCV NS5A inhibitors. Compounds 2c, 4b and 6 have demonstrated low single-digit nM potency in gt-1a replicon and double-digit pM potency in gt-1b replicon, r...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2014.10.057
更新日期:2014-12-15 00:00:00
abstract::The synthesis and inhibitory activities of 10 potential inhibitors of Pfmrk, a Plasmodium falciparum cyclin-dependent protein kinase, are described. The most potent inhibitor is a 3-phenyl-quinolinone compound with an IC(50) value of 18 microM. It is the first compound reported to inhibit Pfmrk at the micro molar rang...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(01)00578-9
更新日期:2001-11-05 00:00:00
abstract::Chemical modifications are essential to improve metabolic stability and pharmacokinetic properties of siRNA to enable their systemic delivery. We investigated the effect of combing the phosphorothioate (PS) modification with metabolically stable phosphate analog (E)-5'-vinylphosphonate and GalNAc cluster conjugation o...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2016.04.063
更新日期:2016-06-15 00:00:00
abstract::We have previously reported the essential structure of the opioid κ receptor agonist nalfurafine hydrochloride (TRK-820) for binding to the κ receptor. In the course of this study, we focused on the effect of the substituent at 17-N in nalfurafine on the binding affinity for the κ receptor. The exchange of the 17-N su...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2012.10.100
更新日期:2013-01-01 00:00:00
abstract::New carbon-11 labeled D-luciferin analogs D-luciferin [(11)C]methyl ester ([(11)C]LMEster, [(11)C]1) and D-luciferin [(11)C]methyl ether ([(11)C]LMEther, [(11)C]2) were synthesized in 25-55% radiochemical yield. PET studies with [(11)C]LMEster and [(11)C]LMEther demonstrate a lower retention of the C-11 label at 45 mi...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2005.09.082
更新日期:2006-01-15 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
pub_type: 杂志文章
doi:10.1016/j.bmcl.2010.11.099
更新日期:2011-01-15 00:00:00
abstract::A series of novel pyrimido[1,2-b]indazoles 5, 7 have been prepared from 3-trifluoromethyl-5-phenyl-2,6-dicyano anilines 1 via novel indazole regioisomers 3 and 4 through a facile strategy. Specific examples were evaluated for anticancer activity in vitro and found to exhibit promising activity against A-549 cell lines...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2007.03.087
更新日期:2007-06-15 00:00:00
abstract::Two series of 5-phenyl furocoumarin derivatives were designed and prepared based on our previous research. All new compounds were characterized by (1)H NMR, (13)C NMR and mass spectra. Furthermore, they were screened for their vasodilatory activity on the mesenteric artery of Sprague-Dawley rats, and they all presente...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2015.11.056
更新日期:2016-01-15 00:00:00
abstract::The discovery and SAR of a series of potent renin inhibitors possessing a novel biaryl scaffold are described herein. Molecular modeling revealed that the cyclopropylamide spacer present in 1 can be replaced by a simple, substituted aromatic ring such as a toluene in 2. The resulting compounds exhibit subnanomolar ren...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2010.07.127
更新日期:2010-10-01 00:00:00
abstract::The design and parallel synthesis of potent, small molecule partial agonists of Neuromedin B receptor based on the 3-amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxylic acid amide core is described. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2004.04.045
更新日期:2004-06-21 00:00:00
abstract::Synthesis and biological evaluation of novel and potent cyclohexylamine-based histamine H3 receptor inverse agonists are described. Compounds in this newly identified series exhibited subnanomolar binding affinities for human receptor and no significant interaction with hERG channel. One derivative (10t) demonstrated ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.06.102
更新日期:2011-09-15 00:00:00
abstract::TGR5 is a member of G protein-coupled receptor (GPCR) superfamily, a promising molecular target for metabolic diseases. Activation of TGR5 promotes secretion of glucagon-like peptide-1 (GLP-1), which activates insulin secretion. A series of 2-thio-imidazole derivatives have been identified as novel, potent and orally ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.04.011
更新日期:2018-06-01 00:00:00
abstract::The design, synthesis, and IMPDH inhibitory activity of a series of phosphonic acid-containing analogues of mycophenolic acid are described. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2006.03.097
更新日期:2006-07-01 00:00:00
abstract::The synthesis and biological activity of amino acid functionalized beta-carboline derivatives, which are structurally related to azatoxin and the tryprostatins, are reported. These compounds were assayed for their growth inhibition properties in H520 and PC3 cell lines and were examined for their abilities to inhibit ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(01)00136-6
更新日期:2001-05-21 00:00:00