Abstract：
:A series of 5-nitrofuran-2- and 3-carboxamides bearing alkylating side-chains has been synthesized and tested for their ability to radiosensitize selectively hypoxic Chinese hamster cells (V79) to the lethal effects of ionizing radiation and also for their ability to act directly and selectively as cytotoxic drugs on hypoxic V79 cells. The compounds were extremely efficient radiosensitizers of such cells in vitro and were more efficient than known nitroimidazoles of similar type. Their efficiencies as radiosensitizers correlated with their high electron affinity (E7(1] as measured by pulse-radiolysis. However the compounds showed little radiosensitizing activity towards KHT sarcomas in C3H mice. The compounds in this series of nitrofurans were generally more toxic towards hypoxic cells than towards oxic cells in vitro but were less effective upon the basis of a differential effect than were similar nitroimidazoles reported previously.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Naylor MA,Stephens MA,Cole S,Threadgill MD,Stratford IJ,O'Neill P,Fielden EM,Adams GEdoi
10.1021/jm00171a027subject
Has Abstractpub_date
1990-09-01 00:00:00pages
2508-13issue
9eissn
0022-2623issn
1520-4804journal_volume
33pub_type
杂志文章abstract：:Building on insights gained from the discovery of the antimalarial ozonide arterolane (OZ277), we now describe the structure-activity relationship (SAR) of the antimalarial ozonide artefenomel (OZ439). Primary and secondary amino ozonides had higher metabolic stabilities than tertiary amino ozonides, consistent with t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b01586
更新日期：2017-04-13 00:00:00
abstract：:Polycomb Repressive Complex 2 (PRC2) modulates the chromatin structure and transcriptional repression by trimethylation lysine 27 of histone H3 (H3K27me3), a process that necessitates the protein-protein interaction (PPI) between the catalytic subunit EZH2 and EED. Deregulated PRC2 is intimately involved in tumorigene...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501230c
更新日期：2014-11-26 00:00:00
abstract：:Various semicarbazones derived from aryl aldehydes, phenylalkyl aldehydes, and phenylalkyl ketones as well as some related compounds were evaluated for anticonvulsant activity. Most of the compounds displayed anticonvulsant activity in the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00068a001
更新日期：1993-08-06 00:00:00
abstract：:Natural lipid nanocarriers, exosomes, carry cell-signaling materials such as DNA and RNA for intercellular communications. Exosomes derived from cancer cells contribute to the progression and metastasis of cancer cells by transferring oncogenic signaling molecules to neighboring and remote premetastatic sites. Therefo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01508
更新日期：2019-02-28 00:00:00
abstract：:A general method for synthesis of 2 beta-alkenyl penam sulfones has been developed. The new compounds inhibited most of the common types of beta-lactamase. The level of activity depended very strongly on the nature of the substituent in the 2 beta-alkenyl group. The inhibited species formed with the beta-lactamase fro...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9601967
更新日期：1996-09-13 00:00:00
abstract：:The development of a novel class of nonsteroidal human progesterone receptor (hPR) agonists, 5-aryl-1,2-dihydro-5H-chromeno[3,4-f]quinolines 2, is described. The introduction of a 5-aryl group into the 1,2-dihydrocoumarino[3,4-f]quinoline core 1 is the key for progestational activities. The structure-activity relation...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9705768
更新日期：1998-01-29 00:00:00
abstract：:The binding affinities of a selected series of Gd(III) chelates bearing bile acid residues, potential hepatospecific MRI contrast agents, to a liver cytosolic bile acid transporter, have been determined through relaxivity measurements. The Ln(III) complexes of compound 1 were selected for further NMR structural analys...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070397i
更新日期：2007-11-01 00:00:00
abstract：:125I-labeled (E)-18-iodo-17-octadecenoic acid (13) has been prepared and evaluated in rats to determine the myocardial uptake and retention and degree of in vivo deiodination of this model iodovinyl-substituted fatty acid, which contains no structural perturbation to inhibit metabolism. This new agent was prepared by ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00367a021
更新日期：1984-01-01 00:00:00
abstract：:The bioavailability of aromatic azaheterocyclic drugs can be affected by the activity of aldehyde oxidase (AO). Susceptibility to AO metabolism is difficult to predict computationally and can be complicated in vivo by differences between species. Here we report the use of bis(((difluoromethyl)sulfinyl)oxy)zinc (DFMS) ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm4017976
更新日期：2014-02-27 00:00:00
abstract：:Two-bivalent ligands (P-X-P) containing the beta-naltrexamine pharmacophore (P) and a connecting oligoethylene glycol spanner (X) were synthesized and evaluated for narcotic antagonistic activity in the guinea pig ileum (GPI) and mouse vas deferens (MVD). The bivalent ligand 2 whose spanner contains three ethylene uni...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00349a016
更新日期：1982-07-01 00:00:00
abstract：:High-throughput file screening against inhibition of human lung PDE4 led to the discovery of 3-ethyl-1-(4-fluorophenyl)-6-phenyl-7-oxo-4, 5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine (11) as a novel PDE4 inhibitor. Subsequent SAR development, using an eosinophil PDE assay, led to analogues up to 50-fold more potent tha...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9800090
更新日期：1998-06-18 00:00:00
abstract：:We have previously shown [Cys-Trp-Arg-Nva-Arg-Tyr-NH(2)](2), 1, to be a moderately selective neuropeptide Y (NPY) Y(4) receptor agonist. Toward improving the selectivity and potency for Y(4) receptors, we studied the effects of dimerizing H-Trp-Arg-Nva-Arg-Tyr-NH(2) using various diamino-dicarboxylic acids containing ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm050907d
更新日期：2006-04-20 00:00:00
abstract：:A series of 6-benzoxazinylpyridazin-3-ones was prepared and evaluated for inhibition of cardiac phosphodiesterase (PDE) fraction III in vitro and for positive inotropic activity in vivo. 6-[3,4-Dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl]-2,3,4,5-tetrahydro-5 - methylpyridazin-3-one (bemoradan) was found to be an extremely ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00163a061
更新日期：1990-01-01 00:00:00
abstract：:A number of analogues of thapsigargin have been synthesized by alkylating or acylating O-11 and O-12 in the lactol obtained by reducing thapsigargicin. Introduction of alpha-disposed substituents decreased the Ca(2+)-ATPase inhibitory potency of the analogue, whereas the enzyme was more tolerant toward beta-disposed s...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00002a009
更新日期：1995-01-20 00:00:00
abstract：:Interesting analgesic activity approaching that of meperidine and codeine was observed in standard animal models for 8-chloro-3,4-dihydro-5-methoxy-2-pyrrolidinomethylnaphthalene (compound 7). This compound was orally effective and its analgesic activity was not reversed by the opiate antagonist, naloxone. A limited n...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00201a004
更新日期：1978-03-01 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：:The discovery of inhibitors of bromodomain and extra terminal domain (BET) has achieved great progress, and at least seven inhibitors have progressed into clinical trials for the treatment of cancer or inflammatory diseases. Here, we describe the identification, optimization, and evaluation of benzo[cd]indol-2(1H)-one...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b01511
更新日期：2016-02-25 00:00:00
abstract：:Necrosis is the main mode of cell death, which leads to multiple clinical conditions affecting hundreds of millions of people worldwide. Its molecular mechanisms are poorly understood, hampering therapeutics development. Here, we identify key proteolytic activities essential for necrosis using various biochemical appr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01683
更新日期：2021-01-31 00:00:00
abstract：:Indirubins have been identified as potent ATP-competitive protein kinase inhibitors. Structural modifications in the 5- and 3'-position have been extensively investigated, but the impact of substituents in 5'-position is not equally well-studied. Here, we report the synthesis of new indirubin 3'- and 5'-derivatives in...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b00324
更新日期：2017-06-22 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：:We herein report a new category of 5-substituted pyrimidine nucleosides as potent inhibitors of mycobacteria. A series of 5-alkynyl derivatives of 2'-deoxyuridine (1-8), 2'-deoxycytidine (9-14), uridine (15-17), and 2'-O-methyluridine (18, 19) were synthesized and evaluated for their antimycobacterial activity in vitr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm058167w
更新日期：2005-11-03 00:00:00
abstract：:The synthesis and biological activities of four novel bispyridinium cyclophanes as choline kinase (ChoK) inhibitors are presented. Their synthetic methodology has been optimized according to dilution, temperature, and reaction time and provides pure bispyridinium cyclophanes in high yields very easily. One of these cy...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030792i
更新日期：2003-08-14 00:00:00
abstract：:We present an RP-HPLC method, for the determination of logPoct values for neutral drugs, which combines ease of operation with high accuracy and which has been shown to work for a set of 36 molecules comprised largely of drugs. The general features of the method are as follows: (i) compound sparing (< or = 1 mL of a 3...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0000822
更新日期：2000-07-27 00:00:00
abstract：:Dipeptidyl peptidase IV (DPP-IV) inhibition has the potential to become a valuable therapy for type 2 diabetes. The synthesis and structure-activity relationship of a new DPP-IV inhibitor class, N-substituted-glycyl-2-cyanopyrrolidines, are described as well as the path that led from clinical development compound 1-[2...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030091l
更新日期：2003-06-19 00:00:00
abstract：:The discovery of potent and pan-genotypic HCV NS5A inhibitors faces many challenges including the significant diversity among genotypes, substantial potency shift conferred on some key resistance-associated variants, inconsistent SARs between different genotypes and mutants, and the lacking of models of inhibitor/prot...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b01234
更新日期：2016-11-23 00:00:00
abstract：:Comparative binding energy analysis, a technique to derive receptor-based three-dimensional quantitative structure-activity relationships (3D-QSAR), is herein extended to consider both affinity and selectivity in the derivation of the QSAR model. The extension is based on allowing multiple structurally related recepto...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060350h
更新日期：2006-10-19 00:00:00
abstract：:The synthesis of a new class of multisubstrate adduct inhibitors of polyamine biosynthesis has been investigated. The first target compound, designed to inhibit spermidine synthase, was obtained and proved to be a very potent inhibitor of that enzyme. Two synthetic routes to effect the coupling of the polyamine spermi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00014a023
更新日期：1995-07-07 00:00:00
abstract：:The academic setting provides an environment that may foster success in the discovery of certain types of small molecule tools while proving less suitable in others. For example, small molecule probes for poorly understood systems, those that exploit a specific resident expertise, and those whose commercial return is ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/jm400132d
更新日期：2013-09-26 00:00:00
abstract：:N-Methylation of two retinoidal amide compounds, 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benz oic acid (3, Am80) and 4-[[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl)carbonyl]amino]benzoic acid (5, Am580), resulted in the disappearance of their potent differentiation-inducing act...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00130a011
更新日期：1989-10-01 00:00:00
abstract：:Mutations of isocitrate dehydrogenase 1 (IDH1) are frequently found in certain cancers such as glioma. Different from the wild-type (WT) IDH1, the mutant enzymes catalyze the reduction of α-ketoglutaric acid to d-2-hydroxyglutaric acid (D2HG), leading to cancer initiation. Several 1-hydroxypyridin-2-one compounds were...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500660f
更新日期：2014-10-23 00:00:00
