Abstract:
:The synthesis of 3-deoxydihydrolycoricidine, a key element toward elucidation of the pancratistatin anticancer pharmacophore, is described. Biological evaluation of this compound showed it to be significantly less active against tumor cells than pancratistatin. In addition to those features previously identified, the requirement of a 2,3,4-triol functionalized ring-C is now definitely established as the minimum pharmacophoric element for potent anticancer activity.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
McNulty J,Larichev V,Pandey Sdoi
10.1016/j.bmcl.2005.08.024subject
Has Abstractpub_date
2005-12-01 00:00:00pages
5315-8issue
23eissn
0960-894Xissn
1464-3405pii
S0960-894X(05)01042-5journal_volume
15pub_type
杂志文章abstract::2'-O-[N-(4-Aminobutylcarbamoyl)]uridine (U(abcm)) was synthesized and incorporated into oligonucleotides. The oligonucleotides incorporating U(abcm) formed more stable duplexes with their complementary and mismatched RNAs than those containing 2'-O-carbamoyluridine (U(cm)). The stability of duplex with a U(abcm)-rG ba...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2012.02.012
更新日期:2012-04-01 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
pub_type: 杂志文章
doi:10.1016/j.bmcl.2008.07.011
更新日期:2008-08-15 00:00:00
abstract::New ligands for in vivo brain imaging of serotonin transporter (SERT) with single photon emission tomography (SPECT) were prepared and evaluated. An efficient synthesis and radiolabeling of a biphenylthiol, FLIP-IDAM, 4, was accomplished. The affinity of FLIP-IDAM was evaluated by an in vitro inhibitory binding assay ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2012.11.043
更新日期:2013-02-01 00:00:00
abstract::Protein-protein interactions (PPIs) present a formidable challenge to medicinal chemistry. The extended and open nature of many binding sites at protein interfaces has made it difficult to find useful chemical matter by traditional screening methods using standard screening libraries. This Digest focuses on the progre...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章,评审
doi:10.1016/j.bmcl.2015.04.089
更新日期:2015-06-15 00:00:00
abstract::The discovery and optimization of a novel series of prolinol-derived GHSR agonists is described. This series emerged from a 11,520-member solid-phase library targeting the GPCR protein superfamily, and the rapid optimization of low micromolar hits into single-digit nanomolar leads can be attributed to the solid-phase ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2008.07.120
更新日期:2008-09-15 00:00:00
abstract::Two new merosesquiterpenes, verruculides A (1) and B (2), were isolated from a culture broth of the Indonesian ascidian-derived Penicillium verruculosum TPU1311, together with three known congeners, chrodrimanins A (3), B (4), and H (5). The structures of 1 and 2 were assigned on the basis of their spectroscopic data ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2015.06.026
更新日期:2015-08-15 00:00:00
abstract::The design, synthesis, and enzyme kinetics evaluation of a transition-state inhibitor of glyoxalase-I is described. The union of the hydroxamic acid zinc-chelator with a urea isostere for the glu-cys amide bond led to a glutathione analog which retained inhibitory potency toward glyoxalase-I while possessing resistanc...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2006.08.121
更新日期:2006-12-01 00:00:00
abstract::Synthesis and structure-activity relationships (SAR) of a novel series of vasopressin V(1b) (V(3)) antagonists are described. 2-(4-Oxo-2-aryl-quinazolin-3(4H)-yl)acetamides have been identified with low nanomolar affinity for the V(1b) receptor and good selectivity with respect to related receptors V(1a), V(2) and oxy...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2010.12.081
更新日期:2011-03-15 00:00:00
abstract::A variety of P4 motifs have been examined to increase the binding affinity and in vitro anticoagulant potency of our biphenyl 1-(2-naphthyl)-1H-pyrazole-5-carboxylamide-based fXa inhibitors. Highly potent 2-naphthyl-P1 fXa inhibitors (K(i)< or =2 nM) with improved in vitro anticoagulant activity (2xTG< or =1 microM) a...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2003.12.053
更新日期:2004-03-08 00:00:00
abstract::A series of 1-substituted-3-(6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrazoles 14a-ae, 16a, 16b, and 21a-c has been prepared and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(4-methoxyphen...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.08.064
更新日期:2011-10-15 00:00:00
abstract::N-Substituted cyclam-amino acid conjugates have been synthesised both in solution and on the solid phase. The DNA binding affinity of these species has been studied: the nature of the amino acid strongly influences the change in melting temperature suggesting that simple cyclam-peptide conjugates could interact with D...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2008.03.045
更新日期:2008-05-01 00:00:00
abstract::Antibiotic resistance has prompted efforts to discover antibiotics with novel mechanisms of action. FtsZ is an essential protein for bacterial cell division, and has been viewed as an attractive target for the development of new antibiotics. Sanguinarine is a benzophenanthridine alkaloid that prevents cytokinesis in b...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2012.09.097
更新日期:2012-12-01 00:00:00
abstract::Novel ligands, NBEA, NBPA, NETA, NE3TA, and NE3TA-Bn, were synthesized and evaluated as potential chelators of copper radioisotopes for use in targeted positron emission tomography (PET) imaging or radiation therapy. The new ligands were radiolabeled with (64)Cu, and in vitro stability of the radiolabeled complexes wa...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2007.09.052
更新日期:2007-11-15 00:00:00
abstract::A simple and green chemistry procedure for the synthesis of dihydropyrimidinones using heteropoly acid mediated cyclocondensation reaction is described. This method provides an efficient and much improved modification of the original Biginelli reaction reported in 1893, in terms of high yields, and short reaction time...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2006.01.087
更新日期:2006-05-01 00:00:00
abstract::The Gram-negative bacterium Acinetobacter baumannii is an opportunistic pathogen in humans and infections are poorly treated by current therapy. Recent emergence of multi-drug resistant strains and the lack of new antibiotics demand an immediate action for development of new anti-Acinetobacter agents. To this end, oxi...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2014.11.020
更新日期:2015-01-15 00:00:00
abstract::Several strychnobrasiline derivatives have been synthesized to overcome the lack of in vivo reversal activity of the parent compound. In the present study, N(a)-deacetyl-ferrocenoyl-strychnobrasiline was synthesized by condensing N(a)-deacetyl-strychnobrasiline with ferrocenic acid previously treated with oxalyl chlor...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2004.11.067
更新日期:2005-02-15 00:00:00
abstract::VanX, a Zn(II)-dependent D-ala-D-ala dipeptidase, is essential for vancomycin resistance in Enterococcus faecium. The enzymatic activity of VanX was previously found to be inhibited competitively by 2-{[(1-aminoethyl) (hydroxy) phosphoryl]oxy} propanoic acid (1B). Here we report the synthesis and characterization of s...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.10.094
更新日期:2012-01-01 00:00:00
abstract::Cyclic azobenzene carboxylic acid was synthesized using a shortened route. After reaction with D-threolinol, the resulting cyclic azobenzene-D-threolinol (cAB-Thr) building block was transformed into the corresponding DMTr-protected phosphoramidite, and incorporated into oligodeoxynucleotides at various positions and ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2015.10.043
更新日期:2015-12-01 00:00:00
abstract::Type-2 diabetes (T2D) is a complex metabolic disease characterized by insulin resistance in the liver and peripheral tissues accompanied by a defect in pancreatic beta-cell. Since their discovery three subtypes of Peroxisomes Proliferators Activated Receptors were identified namely PPARalpha, PPARgamma and PPARbeta/(d...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2008.01.067
更新日期:2008-03-01 00:00:00
abstract::In the present study, we describe the synthesis of a novel set of pyridine/pyridinium-type fullerene derivatives. The products were assessed for human immunodeficiency virus-reverse transcriptase inhibition activities. All novel fullerene derivatives showed potent human immunodeficiency virus-reverse transcriptase inh...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2015.05.086
更新日期:2015-08-15 00:00:00
abstract::A series of indene analogs of the H(1)-antihistamine (-)-R-dimethindene was evaluated for selectivity in the search for potentially improved sedative-hypnotics. Variation of the 6-substitutent in the indene core in combination with a pendant electron rich heterocycle led to the identification of several potent H(1)-an...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2010.02.055
更新日期:2010-04-15 00:00:00
abstract::A new halicyclamine derivative, tetradehydrohalicyclamine B (1), was isolated from the marine sponge Acanthostrongylophora ingens, along with halicyclamine B (2) as proteasome inhibitors. Compound 1 is the second example found to have a pyridinium ring in the halicyclamine family. Although the relative configuration o...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.11.028
更新日期:2019-01-01 00:00:00
abstract::Two analogues possessing steric hindered substituents on C-15 of arenastatin A (1), a potent cytotoxic spongean depsipeptide, were synthesized and shown to enhance stability in mouse serum. Notably, 15-tert-butylanalogue (6) with higher cytotoxicity exhibited in vivo anti-tumor activity through iv administration diffe...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2004.02.080
更新日期:2004-05-17 00:00:00
abstract::In order to exploit cyclophilin as a potential target for neurological drug design, we demonstrate in this presentation that several nonimmunosuppressant analogues of cyclosporin A, modified at the various positions in the 'effector' domain, are equipotent nerve growth agents compared to cyclosporin A. Our results sug...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2004.06.028
更新日期:2004-09-06 00:00:00
abstract::The synthesis and pharmacological profile of a novel series of 7-methoxy-furo[2,3-c]pyridine-4-carboxamides is described. Some of these compounds were found to be potent inhibitors of phosphodiesterase type 4 (PDE4). ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(01)00786-7
更新日期:2002-02-11 00:00:00
abstract::The synthesis of N-(O,O-diisopropylphosphoryl)-benzyltetrahydroisoquinoline (3) has been achieved in a 'one pot' procedure from imine (2) and diisopropyl-phosphorochloridate (1) generated in situ (POCl3 + iPrOH). Compound 3 is the first benzyltetrahydroisoquinoline derivative found to be a potent inhibitor of mitochon...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(00)00262-6
更新日期:2000-07-03 00:00:00
abstract::In the search for spin labelled intercalators of general use to construct DNA-binding conjugates, 6-chloro-2-[(1-oxyl-2,2,5,5-tetramethyl- pyrrolin-3-yl)methyloxy]-9-phenoxy-acridine 5, has been prepared. This key-intermediate reacts with amines to give the corresponding labelled 9-amino substituted acridines. Compara...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(98)00089-4
更新日期:1998-03-17 00:00:00
abstract::A series of 6/7-mono and disubstituted quinolone-3-carboxamide derivatives (1-12) were synthesized and their in vitro methemoglobin producing capacity have been delineated. The compounds 5, 6, 9 and 10 showed minimum methemoglobin toxicity. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(98)00688-x
更新日期:1999-01-04 00:00:00
abstract::A series of alpha-alkyl-alpha-amino-beta-sulphone hydroxamates was prepared and evaluated for potency versus MMP-2 and MMP-13, and for selectivity versus MMP-1. Low nanomolar potency was obtained with selectivity versus MMP-1 ranging from >10 to >1000. Selected compounds were orally bioavailable. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(01)00557-1
更新日期:2001-10-22 00:00:00
abstract::The synthesis and SAR of a series of 6-(4-(substituted)phenyl)-2-aminopyridines as inhibitors of nitric oxide synthase are described. Compound 3a from this series shows potent and selective inhibition of the human nNOS isoform, with pharmacokinetics sufficient to provide in vivo inhibition of nNOS activity. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(99)00432-1
更新日期:1999-09-06 00:00:00