Abstract：
:A select series of methyl ether derivatives of vancomcyin aglycon were prepared and examined for antimicrobial activity against vancomycin-sensitive Staphylococcus aureus and vancomycin-resistant Enterococci faecalis as well as their binding affinity for D-Ala-D-Ala and D-Ala-D-Lac. The intent of the study was to elucidate the role selected key methyl groups may play in the improvement of the in vitro antimicrobial profile of the tetra methyl ether derivative of vancomycin aglycon against vancomycin-resistant Enterococci faecalis previously reported. In these studies, methodology for selective derivatization of the A-, B-, and D-ring was developed that defines the relative reactivity of the four phenols of vancomycin aglycon, providing a foundation for future efforts for site-directed modification of the vancomycin aglycon core.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Crane CM,Pierce JG,Leung SS,Tirado-Rives J,Jorgensen WL,Boger DLdoi
10.1021/jm100946esubject
Has Abstractpub_date
2010-10-14 00:00:00pages
7229-35issue
19eissn
0022-2623issn
1520-4804journal_volume
53pub_type
杂志文章abstract：:A series of 9-hydrazono-4H-pyrido[1,2-a]pyrimidin-4-ones was prepared. The compounds were evaluated in the rat passive cutaneous anaphylaxis test for antiallergic activity. Structure-activity relationship studies revealed that the presence of a monosubstituted hydrazone moiety in position 9 and an unsubstituted 2-posi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00362a008
更新日期：1983-08-01 00:00:00
abstract：:Plasmodium falciparum lactate dehydrogenase (pfLDH) is a key enzyme for energy generation of malarial parasites and is a potential antimalarial chemotherapeutic target. It is known that the oxamate moiety, a pyruvate analog, alone shows higher inhibition against pfLDH than human LDHs, suggesting that it can be used fo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070336k
更新日期：2007-08-09 00:00:00
abstract：:A series of N-(cyclopropylmethyl)-14 beta-substituted-normorphine analogues was synthesized and tested for opioid agonist and antagonist activity in the guinea pig ileum and mouse vas deferens preparations. The 14 beta-bromo compound proved to be a pure antagonist equal in potency to naloxone in the guinea pig ileum a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00134a018
更新日期：1981-02-01 00:00:00
abstract：:The results of a high-throughput screening assay using the DENV-2 replicon showed that the 2,4-diaminoquinazoline derivative 4a has a high dengue virus inhibitory activity (EC(50) = 0.15 μM). A series of 2,4-diaminoquinazoline derivatives based on 4a as a lead compound were synthesized and subjected to structure-antid...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm2015952
更新日期：2012-04-12 00:00:00
abstract：:Pironetin, the only crystallographically confirmed natural product to target α-tubulin, displays potent cytotoxic activity against sensitive and resistant A2780 ovarian cancer cell lines but is only marginally active in vivo. We now report that pironetin has a short half-life (<7 min) in human liver microsomes, sugges...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01774
更新日期：2019-02-14 00:00:00
abstract：:SAR exploration at P1' using an anti-succinate-based macrocyclic hydroxamic acid as a template led to the identification of several bulky biphenylmethyl P1' derivatives which confer potent porcine TACE and anti-TNF-alpha cellular activities with high selectivity versus most of the MMPs screened. Our studies demonstrat...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0155502
更新日期：2001-10-11 00:00:00
abstract：:The functional in vitro study of the enantiomers of imidazolines 4-7 highlighted the role played by the nature of the ortho phenyl substituent in determining the preferred α(2C)-AR configuration. Indeed, the (S) enantiomers of 4-6 or (R) enantiomer of 7 behave as eutomers and activate this subtype as full agonists; th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100977d
更新日期：2010-11-11 00:00:00
abstract：:Treatment of a methanolic solution of 4-hydroxy-1-beta-D-ribofuranosyl-2-pyridinone (3-deazauridine, 1) with diazomethane gave 2-methoxy-1-beta-D-ribofuranosyl-4-pyridinone (2) and 4-methoxy-1-beta-D-ribofuranosyl-2-pyridinone (3a) in an approximate ratio of 1:2. Analogous treatment of 1 with diazomethane in the prese...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00245a005
更新日期：1975-11-01 00:00:00
abstract：:The major mechanism by which the serotonin neurotoxin 5,6-dihydroxytryptamine (5,6-DHT) expresses its neurodegenerative action may involve alkylation of biological nucleophiles by the electrophilic quinoid autoxidation products. To determine the relative importance of various sites on these autoxidation products towar...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00147a027
更新日期：1985-09-01 00:00:00
abstract：:The increasing prevalence of diabetes has accelerated the search for new drugs derived from natural sources. To define the functional features of two such families of compounds, the flavonols and the ethyl caffeates, we have determined the high-resolution structures of representative inhibitors in complex with human p...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm301273u
更新日期：2012-11-26 00:00:00
abstract：:The photolabile (diazomethyl)carbonyl function was introduced into the 8-position of 2-(N,N-di-n-propyl-amino)-1,2,3,4-tetrahydronaphthalene in three ways, resulting in the ether 8-[[(diazomethyl)carbonyl]methoxy]-2-(N,N-di-n-propylamino)-1,2,3,4- tetrahydronaphthalene (2), the ester 8-(diazoacetoxy)-2-(N,N-di-n-propy...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00165a011
更新日期：1990-03-01 00:00:00
abstract：:A series of substituted 3-aryl- and hydroxy-3-aryloctahydropyrido[2,1-c][1,4]oxazines has been synthesized for purposes of investigating potentially useful CNS pharmacological actions of this novel heterocyclic system. The preferred conformation of the bicyclic system of the parent compounds, 1 and 2, has been shown t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00203a010
更新日期：1978-05-01 00:00:00
abstract：:The use of privileged structures in drug discovery has proven to be an effective strategy, allowing the generation of innovative hits/leads and successful optimization processes. Chromone is recognized as a privileged structure and a useful template for the design of novel compounds with potential pharmacological inte...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.6b01720
更新日期：2017-10-12 00:00:00
abstract：:Dysfunction of monoacylglycerol lipase (MAGL) is associated with several psychopathological disorders, including drug addiction and neurodegenerative diseases. Herein we design, synthesize, and evaluate several irreversible fluorine-containing MAGL inhibitors for positron emission tomography (PET) ligand development. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00936
更新日期：2019-10-10 00:00:00
abstract：:Fatty acid synthase (FAS) is necessary for growth and survival of tumor cells and is a promising drug target for oncology. Here, we report on the syntheses and activity of novel inhibitors of the thioesterase domain of FAS. Using the structure of orlistat as a starting point, which contains a beta-lactone as the centr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800321h
更新日期：2008-09-11 00:00:00
abstract：:Three series of 4-anilino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic esters were synthesized as part of a program to study potential anti-Leishmania drugs. These compounds were obtained by a condensation reaction of 4-chloro-1H-pyrazolo[3,4-b]pyridine with several aniline derivatives. Some of them were also obtained by a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0401006
更新日期：2004-10-21 00:00:00
abstract：:Discovery of novel effective and safe antimalarials has been traditionally focused on targeting erythrocytic parasite stages that cause clinical symptoms. However, elimination of malaria parasites from the human population will be facilitated by intervention at different life-cycle stages of the parasite, including th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm4011466
更新日期：2013-10-10 00:00:00
abstract：:We describe the preparation and evaluation of a novel series of glycine transporter 1 (GlyT1) inhibitors derived from a high-throughput screening hit. The SAR studies resulted in the discovery of 3-biphenyl-4-yl-4-(2-fluorophenyl)-5-isopropyl-4H-1,2,4-triazole (6p). A pharmacokinetic study was also conducted and revea...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm101031u
更新日期：2011-01-13 00:00:00
abstract：:A molecular model of the alpha3beta2 nAChR lumen channel was constructed and hydrophobic clefts were observed near the receptor gate. Docking simulations indicated that ligand-nAChR complexes were formed by hydrophobic interactions with the cleft and hydrogen bond interactions. The equilibrium constants and associatio...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070784s
更新日期：2007-11-29 00:00:00
abstract：:The DEDDh family of exonucleases plays essential roles in DNA and RNA metabolism in all kingdoms of life. Several viral and human DEDDh exonucleases can serve as antiviral drug targets due to their critical roles in virus replication. Here using RNase T and CRN-4 as the model systems, we identify potential inhibitors ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00794
更新日期：2016-09-08 00:00:00
abstract：:The cancer research community has begun to address the in silico modeling approaches, such as quantitative structure-activity relationships (QSAR), as an important alternative tool for screening potential anticancer drugs. With the compilation of a large dataset of nucleosides synthesized in our laboratories, or elsew...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm061445m
更新日期：2007-04-05 00:00:00
abstract：:Since the identification of the dopamine D(4) receptor subtype and speculations about its possible involvement in schizophrenia, much work has been put into development of selective D(4) ligands. These selective ligands may be effective antipsychotics without extrapyramidal side effects. This work describes the synthe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm031111m
更新日期：2004-06-03 00:00:00
abstract：:A series of triarylethylene compounds related to 4-hydroxyclomiphene (2) in which the vinyl Cl substituent was replaced by ethyl (5), Br (6), H (7), CN (8), or NO2 (9) substituents were synthesized to facilitate studies of the molecular actions of synthetic nonsteroidal antiestrogens. The relative binding affinities o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00162a014
更新日期：1986-12-01 00:00:00
abstract：:N-Substituted cis-4a-(3-hydroxyphenyl)-8a-methyloctahydroisoquinolines (6a-g) were designed and synthesized as conformationally constrained analogues of the trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine (4) class of opioid receptor pure antagonists. The methyloctahydroisoquinolines 6a-g can exist in conformations w...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm058261c
更新日期：2005-12-29 00:00:00
abstract：:Analogues of [Leu10]NKA4-10 were synthesized in which each of the amide bonds was sequentially replaced with the reduced amide psi (CH2NH) bond to determine the effect of this structural modification on the antagonism of NKA binding to the HUB NK2 receptor. [psi (CH2-NH)9,Leu10]NKA4-10 (6) retained significant affinit...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00099a024
更新日期：1992-10-16 00:00:00
abstract：:A series of 3-hydroxy-substituted analogues (3-7) of the mu selective opioid antagonist cyprodime has been synthesized in order to evaluate the role of a hydroxy group at C-3 concerning mu opioid antagonist selectivity. Compounds 3-7 were tested in bioassays (electrical stimulated mouse vas deferens preparation and my...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00016a010
更新日期：1995-08-04 00:00:00
abstract：:Exposure of dopamine to an excess of linoleic acid 13-hydroperoxide (13-hydroperoxyoctadecadienoic acid) in the presence of ferrous ions in Tris buffer, pH 7.4, resulted in a relatively fast, oxygen-independent reaction exhibiting first-order kinetics with respect to both catecholamine and metal concentrations. Produc...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970099t
更新日期：1997-07-04 00:00:00
abstract：:A number of 7-[(1,3-dihydroxy-2-propoxy)methyl]pyrrolo[2,3d-d]pyrimidine derivatives that are structurally related to toyocamycin and sangivamycin and the seco nucleosides of tubercidin, toyocamycin, and sangivamycin were prepared and tested for their biological activity. Treatment of the sodium salt of 4-amino-6-brom...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00122a019
更新日期：1989-02-01 00:00:00
abstract：:A series of the anti-HIV nucleoside conjugates of either (1-O-alkyl) and thioether (1-S-alkyl) lipids linked by a pyrophosphate diester bond has been synthesized as micelle-forming prodrugs of the nucleosides to improve their therapeutic efficiency. These include AZT 5'-diphosphate-rac-1-S-octadecyl-2-O-palmitoyl-1-th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm950620o
更新日期：1996-04-26 00:00:00
abstract：:The synthesis of a series of 2-chloro- or 2-fluoro-9-(2-substituted-2-deoxy-beta-D-arabinofuranosyl)adenines (4g-n) is described. New compounds were prepared from either 2-chloroadenosine or 2-fluoroadenosine by first blocking the 3'- and 5'-hydroxyls as the tetraisopropyldisiloxane derivatives. Activation of O-2' by ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00397a024
更新日期：1988-02-01 00:00:00
