Abstract:
:A new route to 17 beta-substituted-6-azaandrost-4-en-3-ones, potent dual inhibitors of type 1 and 2 steroidal 5 alpha-reductase, is described.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Sharp MJ,Fang FGdoi
10.1016/s0960-894x(98)00611-8subject
Has Abstractpub_date
1998-12-01 00:00:00pages
3291-4issue
23eissn
0960-894Xissn
1464-3405pii
S0960894X98006118journal_volume
8pub_type
杂志文章abstract::Inhibition of BCR-ABL tyrosine kinase activity has shown to be essential for the treatment of chronic myelogenous leukemia (CML). However, drug resistance has quickly arisen in recent clinical trials for STI571 (Gleevec), which is the first approved drug of CML by inhibiting ABL tyrosine kinase. It is desirable to dev...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2003.08.014
更新日期:2003-11-03 00:00:00
abstract::STAT3 is a promising molecular target for the design of new anticancer drugs. In this paper, we report the design and synthesis of a conformationally constrained macrocyclic peptidomimetic 2 via click chemistry. Compound 2 was determined to bind to STAT3 with a K(i) value of 7.3 microM in a competitive fluorescence-po...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2007.04.096
更新日期:2007-07-15 00:00:00
abstract::(1H-Pyridin-4-ylidene)amines containing lipophilic side chains at the imine nitrogen atom were prepared as potential clopidol isosteres in the development of antimalarials. Their antiplasmodial activity was evaluated in vitro against the Plasmodium falciparum W2 (chloroquine-resistant) and FCR3 (atovaquone-resistant) ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2009.05.017
更新日期:2009-07-01 00:00:00
abstract::The rational design, syntheses and evaluation of potent sulfonamidopyrrolidin-2-one-based factor Xa inhibitors incorporating aminoindane and phenylpyrrolidine P4 motifs are described. These series delivered highly potent anticoagulant compounds with excellent oral pharmacokinetic profiles; however, significant time de...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.01.131
更新日期:2011-03-15 00:00:00
abstract::Histone deacetylase (HDAC) inhibitors modulate various cellular functions including proliferation, differentiation, and apoptosis. Vorinostat (SuberAniloHydroxamic Acid, SAHA) is the first HDAC inhibitor approved by FDA for cancer treatment. However, SAHA distributes in cancer tissue and normal tissue in similar level...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2017.01.025
更新日期:2017-02-15 00:00:00
abstract::Sialidases are key virulence factors that remove sialic acid from host cell surface glycans, thus unmasking receptors to facilitate bacterial adherence and colonization. In this study, we report the isolation and characterization of novel inhibitors of the Streptococcus pneumoniae sialidases NanA, NanB, and NanC from ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2017.05.055
更新日期:2017-07-15 00:00:00
abstract::We describe here the generation of a lead compound and its optimization studies that led to the identification of a novel GPR119 agonist. Based on a spirocyclic cyclohexane structure reported in our previous work, we identified compound 8 as a lead compound, being guided by ligand-lipophilicity efficiency (LLE), which...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.12.041
更新日期:2019-02-01 00:00:00
abstract::Poly(ADP-ribose) polymerases (PARPs) play significant roles in various cellular functions including DNA repair and control of RNA transcription. PARP inhibitors have been demonstrated to potentiate the effect of cytotoxic agents or radiation in a number of animal tumor models. Utilizing a benzimidazole carboxamide sca...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2008.06.023
更新日期:2008-07-15 00:00:00
abstract::Breast cancer is the most common malignancy among females, and cancer invasion and metastasis are the leading causes of cancer death in breast cancer patients. Pterostilbene, a naturally occurring dimethylether analogue of resveratrol, has been demonstrated to possess anti-cancer effects. However, inhibitory effects o...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.12.115
更新日期:2014-02-15 00:00:00
abstract::Amiodarone (Cordarone, Wyeth-Ayerst Pharmaceuticals) is a clinically available drug used to treat a wide variety of cardiac arrhythmias. We report here the synthesis and characterization of a panel of potential amiodarone metabolites that have significant structural similarity to thyroid hormone and its metabolites th...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2008.08.013
更新日期:2008-11-15 00:00:00
abstract::A potent and novel class of product-like inhibitors of the HCV NS3 protease was discovered by employing a phosphinic acid as a carboxylate isostere. The replicon activity and pharmacokinetic profile of this series of compounds was optimized by exploring the substitution of the phosphinic acid, as well as conformationa...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.04.125
更新日期:2011-06-15 00:00:00
abstract::A series of 5-(piperidinylethyloxy)quinoline 5-HT(1) receptor ligands have been studied by elaboration of the series of dual 5-HT(1)-SSRIs reported previously. These new compounds display a different in vitro pharmacological profile with potent affinity across the 5-HT(1A), 5-HT(1B) and 5-HT(1D) receptors and selectiv...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2008.11.052
更新日期:2009-01-15 00:00:00
abstract::We have synthesized a novel vitamin D receptor agonist VS-105 ((1R,3R)-5-((E)-2-((3αS,7αS)-1-((R)-1-((S)-3-hydroxy-2,3-dimethylbutoxy)ethyl)-7α-methyldihydro-1H-inden-4(2H,5H,6H,7H,7αH)-ylidene)ethylidene)-2-methylenecyclohexane-1,3-diol). Preparation of a-ring phenylphosphine oxide 11, followed by Wittig-Horner coupl...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.08.076
更新日期:2013-11-01 00:00:00
abstract::In this letter, we report our efforts to design, synthesize and evaluate biological activities of a series of novel hybridized compounds containing 1-tetrazole and 4-pyridinyl-1,2,4-triazole-3-one. An analysis of structure-activity data indicates that the target compounds with bulky and hydrophobic side chains exhibit...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2017.12.040
更新日期:2018-02-01 00:00:00
abstract::A series of 4'-hydroxyphenyl-aryl-carbaldehyde oximes (5b) was prepared and found to have high affinity (4nM) and modest selectivity (39-fold) for estrogen receptor-beta (ERbeta). Substitution of one of the core rings of the scaffold based around these novel ligands further expanded our knowledge in the quest toward a...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2006.11.066
更新日期:2007-02-15 00:00:00
abstract::A series of leinamycin derivatives were synthesized and evaluated for antitumor activity. Modifications at C-8 and C-9 positions revealed a broad structure-activity relationship in vitro and some derivatives showed potent antiproliferative activity against HeLa S3 cells. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(98)00133-4
更新日期:1998-04-21 00:00:00
abstract::Two new γ-lactones, aspergilactones A (1) and B (2), were discovered along with two known compounds, annularin A (3) and pericoterpenoid A (4), from a culture of the sponge-associated fungus Aspergillus sp. LS45. The planar structures of 1-4 were characterized using comprehensive spectroscopic methods and comparison w...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2019.04.051
更新日期:2019-07-01 00:00:00
abstract::The novel analysis method consisting of size-exclusion chromatography (SEC) and HRMS analysis was firstly applied in the discovery of potential inhibitors towards cancer drug targets. With vascular endothelial growth factor receptor (VEGFR-2) as a target, dynamic combinatorial libraries (DCLs) were prepared by reactin...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2016.02.063
更新日期:2016-04-01 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 weak, UDP-competitive antagonist of the pyrimidinergic receptor P2RY(14) with a naphthoic acid core was identified through high-throughput screening. Optimization provided compounds with improved potency but poor pharmacokinetics. Acylglucuronidation was determined to be the major route of metabolism. Increasing the...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.03.081
更新日期:2011-05-15 00:00:00
abstract::The present report describes our efforts to convert an existing LXR agonist into an LXR antagonist using a structure-based approach. A series of benzenesulfonamides was synthesized based on structural modification of a known LXR agonist and was determined to be potent dual liver X receptor (LXR α/β) ligands. Herein we...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2012.07.048
更新日期:2012-09-15 00:00:00
abstract::A series of novel 5-trans-hydroxyadamantan-2-yl-5,6,7,8-tetrahydropyrazolo[4,3-c]azepin-4(1H)-ones that inhibit 11beta-hydroxysteroid dehydrogenase type 1 are described. We discovered these 7-membered cyclic amide derivatives by introducing a distinctive linker through pharmacophore analysis of known ligands included ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.01.090
更新日期:2013-03-15 00:00:00
abstract::Based on the favorable antiviral profiles of 4'-substituted nucleosides, novel 1-(2'-deoxy-2'-fluoro-4'-C-ethynyl-beta-D-arabinofuranosyl)-uracil (1a), -thymine (1b), and -cytosine (2) analogs were synthesized. Compounds 1b and 2 exhibited potent anti-HIV-1 activity with IC(50) values of 86 and 1.34 nM, respectively, ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2010.05.090
更新日期:2010-07-15 00:00:00
abstract::The synthesis and biological evaluation of a series of novel isobenzofuran-based compounds are described. The compounds were evaluated for their immunosuppressive effects of T-cell proliferation and IMPDH type II inhibitor activity in vitro, as well as their structure-activity relationships were assessed. Several comp...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.11.078
更新日期:2012-01-01 00:00:00
abstract::Here we report a novel class of peptides-d-diaminopropionic acids (Dap)-for gene delivery. These peptides have attractive properties for gene delivery, and the advantage that they can be easily manipulated in relation to their composition, abiding with tailored-design. We characterized the toxicological and biophysica...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2012.06.103
更新日期:2012-09-01 00:00:00
abstract::New N-(1,2-diphenylethyl)piperazines 6 are disclosed as dual serotonin and noradrenaline reuptake inhibitors (SNRI) which may have potential in treating stress urinary incontinence (SUI). In this Letter, we present new data for SNRI PF-526014 (4) including performance in a canine in vivo model of SUI, cardiovascular a...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2010.04.052
更新日期:2010-06-15 00:00:00
abstract::Phenanthrene imidazoles 26 and 44 have been identified as novel potent, selective and orally active mPGES-1 inhibitors. These inhibitors are significantly more potent than the previously reported chlorophenanthrene imidazole 1 (MF63) with a human whole blood IC50 of 0.20 and 0.14 microM, respectively. It exhibited a s...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2009.08.085
更新日期:2009-10-15 00:00:00
abstract::The syntheses of 7-chloro-4-(substituted amino) quinolines (2-22) and their antifilarial activities are delineated. Some of the screened compounds have shown promising filarial response and sterilization effect on female Acanthocheilonema viteae in rodents. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(00)00255-9
更新日期:2000-07-03 00:00:00
abstract::We synthesized DL-shikonin, shikonin, alkanin, and their cyclo-derivatives and acyl-derivatives. These compounds have low cytotoxicity, as well as inhibitory activity against the telomerase enzyme, except cyclo-derivatives. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(02)00158-0
更新日期:2002-05-20 00:00:00
abstract::GTP cyclohydrolase (GCYH-I) is an enzyme in the folate biosynthesis pathway that has not been previously exploited as an antibiotic target, although several pathogens including N. gonorrhoeae use a form of the enzyme GCYH-IB that is structurally distinct from the human homologue GCYH-IA. A comparison of the crystal st...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2019.126818
更新日期:2020-01-15 00:00:00