Abstract:
:The donor-acceptor interaction between a tertiary amine and an aldehyde, first observed among a select class of alkaloids, was deliberately established in a peptidomimetic (1a-c) to mimic features of the two principal transition states of peptide hydrolysis. Compounds 1a-c show preferential adoption in methanol and water of a 'folded' conformation displaying the interaction. Proportions of the folded form in MeOH range from 45% to 70% and can reach 84% in buffer. Significantly, three tendencies for the folded/unfolded equilibrium are observed: increasing solubility and polarity of the medium and decreasing temperature results in a higher extent of folding. In the absence of any parameter set available for this weak bond, no modeling studies were conducted to aid in the design of 1a-c. The successful straightforward synthesis of 1 and its folding and inhibition results with HIV-1 peptidase using FRET technology encourage studies to further pre-organize candidate molecules and to screen the structure space by modeling and parallel combinatorial chemistry.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Gautier A,Pitrat D,Hasserodt Jdoi
10.1016/j.bmc.2006.01.031subject
Has Abstractpub_date
2006-06-01 00:00:00pages
3835-47issue
11eissn
0968-0896issn
1464-3391pii
S0968-0896(06)00067-8journal_volume
14pub_type
杂志文章abstract::Twenty-eight tetraketones (1-28) with variable substituents at C-7 were synthesized and evaluated as tyrosinase inhibitors. Remarkably compounds 25 (IC(50)=2.06 microM), 11 (IC(50)=2.09 microM), 15 (IC(50)=2.61 microM), and 27 (IC(50)=3.19 microM) were found to be the most active compounds of the series, even better t...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2005.08.029
更新日期:2006-01-15 00:00:00
abstract::We have recently reported that a series of (E)-8-styrylcaffeines and (E)-2-styrylbenzimidazoles are moderate to very potent competitive inhibitors of monoamine oxidase B (MAO-B). The most potent member of the series was found to be (E)-8-(3-chlorostyryl)caffeine (CSC) with an enzyme-inhibitor dissociation constant (K(...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.03.046
更新日期:2007-06-01 00:00:00
abstract::Deoxyhypusine synthase catalyzes the first step in the posttranslational biosynthesis of the unusual amino acid hypusine [N epsilon-(4-amino-2-hydroxybutyl)lysine] in eukaryotic translation initiation factor 5A (eIF-5A). eIF-5A and its single hypusine residue are essential for cell proliferation. Two series of 1,7-dia...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(97)10030-x
更新日期:1998-03-01 00:00:00
abstract::Both the enantiomeric forms of DAU 5750, a novel muscarinic receptor antagonist, have been synthesized in order to assess the relevance of configurational/conformational features for high affinity binding to muscarinic receptor subtypes. The attribution of absolute stereochemistry and conformational analysis by means ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(00)82089-1
更新日期:1994-12-01 00:00:00
abstract::Colorectal cancer is the third and fourth leading cause of cancer in males and females, respectively. Flavonoids, including chalcones, are secondary metabolites in plants that exhibit diverse biological activities, including antibacterial, antimalarial, and antitumor activities. In order to find potent and novel chemo...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2013.09.014
更新日期:2013-11-15 00:00:00
abstract::Conformationally constrained analogue synthesis was undertaken to aid in pharmacophore mapping and 3D-QSAR analysis of nitrobenzylmercaptopurine riboside (NBMPR) congeners as equilibriative nucleoside transporter 1 (ENT1) inhibitors. In our previous study [J. Med. Chem. 2003, 46, 831-837], novel regioisomeric nitro-1,...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.01.044
更新日期:2008-04-01 00:00:00
abstract::Several N-substituted quindolines were made to further evaluate the role of N-alkylation on the activity of indoloquinolines as antifungal agents. While N-5 substitution is required for these activities, N-10 alkylation alone leads to inactive products but is tolerated in the presence of N-5 alkyl groups. It was also ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2005.04.008
更新日期:2005-06-02 00:00:00
abstract::Substituted goniothalamins containing cyclopropane-groups were efficiently prepared in high yields and good selectivity. Antiproliferative activity was measured on three human cancer cell lines (A549, MCF-7, HBL-100), to show which of the structural elements of goniothalamins is mandatory for cytotoxicity. We found th...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2017.02.004
更新日期:2017-11-15 00:00:00
abstract::A novel series of arylsulfonamide derivatives of (aryloxy)propyl piperidines was designed to obtain potent 5-HT7R antagonists. Among the compounds evaluated herein, 3-chloro-N-{1-[3-(1,1-biphenyl-2-yloxy)2-hydroxypropyl]piperidin-4-yl}benzenesulfonamide (25) exhibited antagonistic properties at 5-HT7R and showed selec...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2017.03.057
更新日期:2017-05-15 00:00:00
abstract::The purpose of this study was to synthesize two new positron emission tomography (PET) probes, N-(4-(2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl)phenyl)-9,10-dihydro-5-[¹⁸F]fluoroethoxy-9-oxo-4-acridine carboxamide ([¹⁸F]3) and quinoline-3-carboxylic acid [2-(4-{2-[7-(2-[¹⁸F]fluoroethoxy)-6-methoxy-3,4-d...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2010.12.004
更新日期:2011-01-15 00:00:00
abstract::Antagonizing transcriptional activity of farnesoid X receptor (FXR) in the intestine has been reported as an effective means for the treatment of nonalcoholic fatty liver disease, type 2 diabetes and obesity. We describe herein that the building blocks necessary to maintain the antagonism of our chemotype were investi...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2019.04.029
更新日期:2019-06-01 00:00:00
abstract::Racemic ethyl 2-benzyl-3-(tert-butylsulfonyl)propionate (1) and racemic ethyl 2-benzyl-3-[[1-methyl-1-((morpholin-4-yl)carbonyl)ethyl]sulfonyl] propionate (3) were enantioselectively hydrolyzed by subtilisin Carlsberg generating the respective (S)-acids used as building blocks for renin inhibitors. The esters were rea...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/0968-0896(94)80007-3
更新日期:1994-06-01 00:00:00
abstract::A set of new muscarinic antagonists, bridged bicyclic derivatives of 2,2-diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine (1), was synthesized and tested to evaluate their affinity and selectivity for M(1), M(2), M(3) and M(4) receptor subtypes. The conformational constraint of 1 in a bicyclic structure, and the varia...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(03)00431-0
更新日期:2003-09-01 00:00:00
abstract::A series of thiophene-containing non-amidine factor Xa inhibitors is described. Simple methyl-substituted thiophene analogs were relatively weak inhibitors. However, introduction of hydrophilic substituents at C-4 or C-5 of the thiophene afforded inhibitors with low nanomolar potency. Optimization of the thiophene sub...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2006.12.019
更新日期:2007-03-01 00:00:00
abstract::A series of new isoxazolyl, triazolyl and phenyl based 3-thiophen-2-yl-quinoline derivatives were synthesized adopting click chemistry approach. In addition, the synthesis of new useful synthon, (2-chloroquinolin-3-yl) (thiophen-2-yl) methanol, is reported. The obtained compounds were characterized by spectral data an...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2019.07.042
更新日期:2019-10-01 00:00:00
abstract::Three novel peptidomimetic phosphinate inhibitors have been synthesized and evaluated as inhibitors of matrix metalloproteinases MMP-2 and MMP-8. Their IC50 values are in the micromolar range, and one of them showed to be the most effective inhibitor of MMP-2. The differences in binding affinities for MMP-2 and MMP-8 ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2005.04.079
更新日期:2005-08-01 00:00:00
abstract::(R)-1-(10,11-Dihydro-dibenzo[b,f]azepin-5-yl)-3-methylamino-propan-2-ol ((R)-OHDMI) and (S,S)-1-cyclopentyl-2-(5-fluoro-2-methoxy-phenyl)-1-morpholin-2-yl-ethanol (CFMME) were synthesized and found to be potent inhibitors of norepinephrine reuptake. Each was labelled efficiently in its methyl group with carbon-11 (t(1...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2006.10.065
更新日期:2007-01-15 00:00:00
abstract::Amyloid-β (Aβ) and tau protein are two crucial hallmarks in Alzheimer's disease (AD). Their aggregation forms are thought to be toxic to the neurons in the brain. A series of new 1,2,3,4-tetrahydro-1-acridone analogues were designed, synthesized, and evaluated as potential dual inhibitors for Aβ and tau aggregation. I...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2018.08.007
更新日期:2018-09-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2020.115960
更新日期:2021-01-02 00:00:00
abstract::The amyloid-like fibril is considered to be a macromolecular self-assemblage with a highly-ordered quaternary structure, in which numerous beta-stranded polypeptide chains align regularly. Therefore, this kind of fibril has the potential to be engineered into proteinaceous materials, although conformational alteration...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2003.11.022
更新日期:2004-02-15 00:00:00
abstract::In recent years, inhibition of HDAC6 became a promising therapeutic strategy for the treatment of cancer and HDAC6 inhibitors were considered to be potent anti-cancer agents. In this work, celecoxib showed moderate degree of HDAC6 inhibition activity and selectivity in preliminary enzyme inhibition activity assay. A s...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2017.08.029
更新日期:2018-05-01 00:00:00
abstract::Investigation of the bark of Croton eluteria Bennett for biologically active compounds has led to the isolation of the new prenylbisabolane 3, whose structure was assessed by spectroscopic methods. The corresponding known enone 4 and the eudesmane sesquiterpene 2 were also obtained. Compound 3 proved active in selecti...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2005.04.025
更新日期:2005-07-01 00:00:00
abstract::Endogenous opioid peptides consist of a conserved amino acid residue of Phe(3) and Phe(4), although their binding modes for opioid receptors have not been elucidated in detail. Endomorphin-2, which is highly selective and specific for the mu opioid receptor, possesses two Phe residues at the consecutive positions 3 an...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.03.009
更新日期:2007-06-01 00:00:00
abstract::Ten 1-phenyl-1H-pyrazolo[3,4-b]pyridine derivatives connected by a linker group to benzenesulfonamide moieties with different substituents in the 4-position were synthesized and assayed against Plasmodium falciparum. These ten compounds exhibited activity in vitro against the chloroquine-resistant clone W2 with IC50 v...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2016.07.049
更新日期:2016-09-15 00:00:00
abstract::Recent reports show that the natural beta-diketone curcumin displays important biological properties regarding the intercellular adhesion molecule-1 (ICAM-1), which plays a critical role in the immune responses and inflammation. In this study the ICAM-1 inhibitory activity of beta-diketone compounds, which are curcumi...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2009.07.064
更新日期:2009-09-01 00:00:00
abstract::Ionophoric properties of dipyrazolic crowns and podands containing a 1,3-bis(1H-pyrazol-1-yl)propane unit in their structure are described. They show selectivity of ammonium vs alkali cations and interesting norepinephrine transport rates. A molecular modelling study has been used to elucidate the superstructures of t...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(96)00250-7
更新日期:1997-02-01 00:00:00
abstract::The carcinogenic activity has been investigated by using a topological substructural molecular design approach (TOPS-MODE). A discriminant model was developed to predict the carcinogenic and noncarcinogenic activity on a data set of 189 compounds. The percentage of correct classification was 76.32%. The predictive pow...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2005.01.035
更新日期:2005-04-01 00:00:00
abstract::The beta-amino acid, (S)-ethyl-3-amino-4-pentynoate, is a chiral synthon used in the synthesis of xemilofiban hydrochloride, an anti-platelet agent. A biocatalytic approach was developed to resolve (R)- and (S)-enantiomers of ethyl 3-amino-4-pentynoate in enantiomerically pure form employing the enzyme Penicillin acyl...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(99)00155-8
更新日期:1999-10-01 00:00:00
abstract::We have developed esonarimod, (+/-)-2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid, as a new antirheumatic drug. Now we describe herein the preparation of the enantiomers of (+/-)-deacetylesonarimod, the pharmaceutically active metabolites of esonarimod, and comparison of their antirheumatic activities. No s...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(02)00084-6
更新日期:2002-08-01 00:00:00
abstract::A new series of selective PDE4D inhibitors has been designed and synthesized by replacing 3-methoxy group with 3-difluoromethoxy isoster moiety in our previously reported cathecolic structures. All compounds showed a good PDE4D3 inhibitory activity, most of them being inactive toward other PDE4 isoforms (PDE4A4, PDE4B...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2015.04.027
更新日期:2015-07-01 00:00:00