Abstract：
:Here we report on a novel fluorescent analog of phenytoin as a potential inhibitor of neuropathic pain with potential use as an imaging agent. Compound 2 incorporated a heptyl side chain and dansyl moiety onto the parent compound phenytoin and produced greater displacement of BTX from sodium channels and greater functional blockade with greatly reduced toxicity. Compound 2 reduced mechano-allodynia in a rat model of neuropathic pain and was visualized ex vivo in sensory neuron axons with two-photon microscopy. These results suggest a promising strategy for developing novel sodium channel inhibitors with imaging capabilities.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Walls TH,Grindrod SC,Beraud D,Zhang L,Baheti AR,Dakshanamurthy S,Patel MK,Brown ML,MacArthur LHdoi
10.1016/j.bmc.2012.06.042subject
Has Abstractpub_date
2012-09-01 00:00:00pages
5269-76issue
17eissn
0968-0896issn
1464-3391pii
S0968-0896(12)00529-9journal_volume
20pub_type
杂志文章abstract：:A novel series of homo- and heterodimeric ligands containing κ/μ agonist and μ agonist/antagonist pharmacophores joined by a 10-carbon ester linker chain were synthesized and evaluated for their in vitro binding affinity at κ, μ, and δ opioid receptors, and their functional activities were determined at κ and μ recept...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2011.03.052
更新日期：2011-05-01 00:00:00
abstract：:Leucyl-tRNA synthetase (LRS) plays an important role in amino acid-dependent mTORC1 signaling, which is known to be associated with cellular metabolism and proliferation. Therefore, LRS-targeting small molecules that can suppress mTORC1 activation may provide an alternative strategy to current anticancer therapy. In t...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2019.01.037
更新日期：2019-03-15 00:00:00
abstract：:Tuberculosis is today amongst the worldwide health threats. As resistant strains of Mycobacterium tuberculosis have slowly emerged, treatment failure is too often a fact, especially in countries lacking the necessary health care organisation to provide the long and costly treatment adapted to patients. Because of lack...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1016/j.bmc.2007.01.030
更新日期：2007-04-01 00:00:00
abstract：:We report a theoretical approach, at the M05-2x/6-311+G(d) level, to explain the affinity of indazoles for nitric oxide synthases using a simplified model of porphyrin. The theoretical E(rel)=E(i) stacking-E(i) apical values correlate with the experimental inhibition percents allowing to predict that 3,7-dinitro-1H-in...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2009.10.006
更新日期：2009-12-01 00:00:00
abstract：:Antioxidant activity in α- and β-chitosan at a wide range of molecular weight (Mw) and chitosan concentration (CS) was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, reducing ability, chelating ability, and hydroxyl radical scavenging activity. The form of chitosan (FC) had significant...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2012.03.020
更新日期：2012-05-01 00:00:00
abstract：:Purine inhibitors of cyclin-dependent kinases (CDK) seem to be a potential anticancer drug candidate as one of the first representatives, roscovitine, is passing Phase II clinical trials for cancer and glomerulonephritis. In this article, we describe a novel modification of the purine scaffold influencing CDK2 inhibit...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2005.06.007
更新日期：2005-09-15 00:00:00
abstract：:A series of anacardic acid analogues possessing different side chains viz. phenolic, branched, and alicyclic were synthesized and their antibacterial activity tested against methicillin-resistant Staphylococcus aureus (MRSA). The maximum activity against this bacterium occurred with the branched side-chain analogue, 6...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2007.06.022
更新日期：2007-09-15 00:00:00
abstract：:In lead optimization efforts starting from the tetrahydroisoquinoline (S)-1, we identified 2-{[(2R)-2-hydroxypropyl]amino}-1-[(1S)-8-methoxy-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl]ethanone ((1S)-8t) as a novel orally active small-molecule N-type calcium channel blocker without CYP inhibition liability. CYP3A4 inhibi...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2015.05.053
更新日期：2015-08-01 00:00:00
abstract：:Green photosynthetic bacteria have unique light-harvesting antenna systems called chlorosomes. Chlorobaculum tepidum, a model organism of the bacteria, biosynthesized monogalactosyl- and rhamnosylgalactosyldiacylglycerides possessing a methylene-bridged palmitoleyl group characterized by a cis-substituted cyclopropane...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2013.04.030
更新日期：2013-07-01 00:00:00
abstract：:The Thermotoga maritima aldolase gene has been cloned into a T7 expression vector and overexpressed in Escherichia coli. The preparation yields 470 UL(-1) of enzyme at a specific activity of 9.4 U mg(-1). During retroaldol cleavage of KDPG, the enzyme shows a k(cat) that decreases with decreasing temperature. A more t...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(01)00307-8
更新日期：2002-03-01 00:00:00
abstract：:Multifaceted roles of vascular endothelial growth factor (VEGF)-neuropilin-1 (NRP1) interaction have been implicated in cancer, but reports on small-molecule inhibitors of VEGF-NRP1 interaction are scarce. Herein, we describe the identification of 1, a novel nonpeptide small-molecule NRP1 antagonist with moderate acti...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2019.115183
更新日期：2020-01-01 00:00:00
abstract：:A series of eight N-2-phenylethylphosphonyl derivatives of glutamic acid was prepared to determine if the inhibitory potency of a phenylethylphosphonyl derivative of glutamic acid against prostate-specific membrane antigen (PSMA) could be improved through rational substitutions on the phenyl ring. The design of these ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2005.07.056
更新日期：2006-01-01 00:00:00
abstract：:Magnetic resonance imaging (MRI) contrast agents are effective tools in both medical diagnosis and life science research. Various smart contrast agents have been developed for the visualization of biological phenomena. These contrast agents have molecular switches that increase or reduce MRI signal intensity in respon...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2011.12.005
更新日期：2012-01-15 00:00:00
abstract：:The preparation of a novel series of N-aryl CBI derivatives in which an aryl substituent could be used to predictably modulate the reactivity of the resulting CC-1065/duocarmycin alkylation subunit analogue is detailed and its extension to a unique series of N-alkenyl derivatives is reported. The N-aryl derivatives we...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2004.08.032
更新日期：2004-11-15 00:00:00
abstract：:A series of hydroxycarbazole derivatives were synthesized and evaluated for PPAR alpha/gamma dual agonist as well as antioxidant activities. While most compounds showed good antioxidant activity, some compounds were identified as potential PPAR alpha/gamma dual agonists as well. Compounds 10a and 16 were found to be a...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2005.04.018
更新日期：2005-07-01 00:00:00
abstract：:The preparation of a series of novel 6-(beta-D-ribofuranosyl)-2-alkyl/aryl-6H-imidazo[1,2-c]pyrimidin-5-one nucleosides and the 2-nitrile nucleosides, 6-(beta-D-ribofuranosyl)-5-oxo-5,6-dihydro-imidazo[1,2-c]pyrimidine-2-carbonitrile and 2R and 2S isomers of 6-(beta-D-ribofuranosyl)-5-oxo-2,3,5,6-tetrahydro-imidazo[1,...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2004.05.017
更新日期：2004-08-01 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：:A series of novel cinnamic acyl sulfonamide derivatives (9a-16e) have been designed and synthesized and their biological activities were also evaluated as potential tubulin polymerization inhibitors. Among all the compounds, 10c showed the most potent growth inhibitory activity against B16-F10 cancer cell line in vitr...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2011.06.088
更新日期：2011-08-15 00:00:00
abstract：:Twenty analogues of the natural antitumor agent dolastatin 11, including majusculamide C, were synthesized and tested for cytotoxicity against human cancer cells and stimulation of actin polymerization. Only analogues containing the 30-membered ring were active. Molecular modeling and NMR evidence showed the low-energ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2005.04.040
更新日期：2005-07-01 00:00:00
abstract：:3-Amino-2-hydroxy-propionaldehydes [H2NCH(R)CHOHCHO with R = H, i-Bu, CH2Ph] were designed as metallo-aminopeptidase inhibitors based on the metal active site chelation concept. These compounds were found to be micromolar inhibitors of aminopeptidase-M (AP-M, EC 3.4.11.2) with potencies similar to bestatin (Ki = 3.5 m...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/0968-0896(96)00115-0
更新日期：1996-08-01 00:00:00
abstract：:Bioassay-guided fractionation of a cytotoxic EtOAc extract of the fungal strain, Chaetomium globosum, inhabiting the rhizosphere of the Christmas cactus, Opuntia leptocaulis, of the Sonoran desert afforded a new dihydroxanthenone, globosuxanthone A (1), a new tetrahydroxanthenone, globosuxanthone B (2), two new xantho...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2006.07.048
更新日期：2006-12-01 00:00:00
abstract：:The proteolytic release, or shedding, of a cell surface protein can serve a regulatory role; the process liberates a soluble form of the protein into circulation while downregulating its cell surface concentration. The characteristics that render a protein susceptible to proteolytic cleavage are not known. We hypothes...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(98)00122-9
更新日期：1998-08-01 00:00:00
abstract：:Melanin concentrating hormone (MCH) receptor antagonists have been proposed as potential treatments of obesity. MCH receptor antagonists with a biphenylamine subunit have been reported previously at Schering-Plough. Herein, we report the discovery of bicyclo[4.1.0]heptanes as replacements for the middle phenyl ring of...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2005.12.046
更新日期：2006-05-15 00:00:00
abstract：:A series of 4'-[(benzimidazole-1-yl)methyl]biphenyl-2-sulfonamide derivatives (Ia-Il) were synthesized and biologically evaluated. It was found that Ig, the most active compound, antagonized both Ang II AT(1) and endothelin ET(A) receptors (AT(1) IC(50)=8.5, ET(A) IC(50)=8.9 nM), and was more potent than losartan in R...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2012.06.011
更新日期：2012-08-01 00:00:00
abstract：:An unusual class of diterpenoid natural products, 'cycloterpenals' (with a central cyclohexadienal core), that arise in nature by condensation of retinoids and other isoprenes, have been isolated from a variety of organisms including marine sponges as well as from the human eye. A milk whey protein has also demonstrat...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2008.07.030
更新日期：2008-08-15 00:00:00
abstract：:Canavan disease is a fatal neurological disorder caused by defects in the metabolism of N-acetyl-l-aspartate (NAA). Recent work has shown that the devastating symptoms of this disorder are correlated with the elevated levels of NAA observed in these patients, caused as a consequence of the inability of mutated forms o...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2016.11.060
更新日期：2017-02-01 00:00:00
abstract：:We examined the properties of RNA analogues containing 2'-deoxy-2'-alpha-fluorouridine (1) or 2'-O-methyluridine (2) as inhibitors against human RNase L, that cleaves a single-stranded RNA in the presence of 2',5'-linked oligoadenylate (2-5A). The RNA analogue, FF, containing two molecules of 1 in place of uridine eff...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2003.08.025
更新日期：2003-11-17 00:00:00
abstract：:A new series of synthetic flavones, thioflavones, and flavanones has been synthesized and evaluated as potential inhibitors of monoamine oxidase isoforms (MAO-A and -B). The most active series is the flavanone one with higher selective inhibitory activity against MAO-B. Some of these flavanones (mainly the most effect...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2009.12.029
更新日期：2010-02-01 00:00:00
abstract：:The synthesis and anticonvulsant properties of new N-Mannich bases of 3-phenyl- (9a-d), 3-(2-chlorophenyl)- (10a-d), 3-(3-chlorophenyl)- (11a-d) and 3-(4-chlorophenyl)-pyrrolidine-2,5-diones (12a-d) were described. The key synthetic strategies involve the formation of 3-substituted pyrrolidine-2,5-diones (5-8), and th...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2013.07.029
更新日期：2013-11-01 00:00:00
abstract：:A linear quantitative structure-activity relationship (QSAR) model is presented for modeling and predicting induction of apoptosis by 4-aryl-4H-chromenes. The model was produced by using the multiple linear regression (MLR) technique on a database that consists of 43 recently discovered 4-aryl-4H-chromenes. Among the ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2006.05.061
更新日期：2006-10-01 00:00:00
