Abstract：
:Three monomethylated derivatives of 4'-hydroxyacetanilide (acetaminophen) were prepared in order to compare their cytotoxic potential and analgesic activity with that of acetaminophen. Only 4'-hydroxy-N-methylacetanilide (N-methylacetaminophen) was devoid of cytotoxic effects to hepatic tissue of mice. Results of comparative tissue distribution studies and metabolism studies both in vivo and in vitro in mice indicate that the disposition of N-methylacetaminophen is similar to that of acetaminophen except that it is not oxidized to a toxic metabolite. In contrast, 3'-methyl-4'-hydroxyacetanilide (3-methylacetaminophen) is as hepatotoxic as acetaminophen in mice while 2'-methyl-4'-hydroxyacetanilide (2-methylacetaminophen) is less hepatotoxic. The analgesic potency of the analogues seems to parallel their hepatotoxic potential, and both activities parallel the oxidation potentials in this series of compounds.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Harvison PJ,Forte AJ,Nelson SDdoi
10.1021/jm00159a029subject
Has Abstractpub_date
1986-09-01 00:00:00pages
1737-43issue
9eissn
0022-2623issn
1520-4804journal_volume
29pub_type
杂志文章abstract：:Novel antibiotics are urgently needed to combat the rise of infections due to drug-resistant microorganisms. Numerous natural nucleosides and their synthetically modified analogues have been reported to have moderate to good antibiotic activity against different bacterial and fungal strains. Nucleoside-based compounds...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.6b00325
更新日期：2016-12-08 00:00:00
abstract：:As the number of cases and cancer-related deaths are projected to rise in upcoming years, it is urgent to find ways to prevent or treat cancer. As such, food-derived products have gained attention as potential chemopreventive agents due to their availability, safety, and low cost. Isothiocyanates, the breakdown produc...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.8b01698
更新日期：2019-06-13 00:00:00
abstract：:A series of derivatives of the antimycobacterial natural product pyridomycin have been prepared with the C2 side chain attached to the macrocyclic core structure by a C-C single bond, in place of the synthetically more demanding enol ester double bond found in the natural product. Hydrophobic C2 substituents of suffic...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01457
更新日期：2020-02-13 00:00:00
abstract：:The in vivo antitumor activity and in vitro metabolic dealkylation have been measured for an homologous series of 3-alkyl-1-(4-carbamoylphenyl)-3-methyltriazenes and have been compared with their partition coefficients. This investigation has shown that the extent of oxidative metabolism in vitro and the antitumor act...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00373a011
更新日期：1984-07-01 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：:Several optically active N-(indol-3-ylglyoxylyl)amino acid derivatives were synthesized and tested for [3H]flunitrazepam displacing activity in bovine brain membranes. IC50 values were measured and revealed that the D form of the amino acid moiety of the compounds was more potent than both the L form and racemic form,...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00132a004
更新日期：1989-12-01 00:00:00
abstract：:A novel series of potent chiral inhibitors of histone deacetylase (HDAC) is described that contains an oxazoline capping group and a N-(2-aminophenyl)-benzamide unit. Among several new inhibitors of this type exhibiting Class I selectivity and potent inhibition of HDAC3-NCoR2, in vitro assays for the inhibition of HDA...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b00545
更新日期：2015-09-10 00:00:00
abstract：:The early and later eluting [(99m)TcO]depreotide products on RP-HPLC were confirmed to be the anti and syn diastereomers, respectively, based on proton NMR and circular dichroism spectroscopy. NMR provided evidence of a folded, conformationally constrained structure for the syn diastereomer. The syn diastereomer is pr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060887v
更新日期：2007-09-06 00:00:00
abstract：:(3-Phenyl-7-flavonoxy)propanolamines have been shown to exhibit antihypertensive activity in spontaneously hypertensive rats. Although they are structurally similar to classical beta-adrenergic blocking compounds, their activity is not due to inhibition of beta-adrenoceptors. In the present study, a series of simple f...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00121a034
更新日期：1989-01-01 00:00:00
abstract：:Two molecules with known growth hormone secretagogue (GHS) agonist activity were used as templates to computationally screen approximately 80000 compounds. A total of 108 candidate compounds were selected, and five of them were found to be active in the low-micromolar range in both cell-based and direct binding assays...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm040103i
更新日期：2004-08-12 00:00:00
abstract：:A series of nonsteroidal compounds, 2-(p-chlorobenzyl)-3-aryl-6- methoxybenzofurans derived from the 2-(p-chlorobenzyl)-6-methoxy-3(2H)-benzofuranones has been synthesized. The key steps in the synthesis were reactions of 2-(p-chlorobenzyl)-6-methoxy-3(2H)-benzofuranones with the arylorganometallic reagents followed b...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00086a002
更新日期：1992-04-17 00:00:00
abstract：:A series of novel thiazolo[4,5- d]pyrimidin-7(6 H)-ones (3aa-3eq) were designed, synthesized, and evaluated as the type I positive allosteric modulators of human α7 nAChR expressed in Xenopus ooctyes by a two-electrode voltage clamp. The structure-activity relationship analysis identified the compound 3ea as a potent ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01492
更新日期：2019-01-10 00:00:00
abstract：:Bioorthogonal chemistry has become one of the main driving forces in current chemical biology, inspiring the search for novel biocompatible chemospecific reactions for the past decade. Alongside the well-established labeling strategies that originated the bioorthogonal paradigm, we have recently proposed the use of he...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500531z
更新日期：2014-06-26 00:00:00
abstract：:Novel pyridine- and pyrimidine-based allosteric inhibitors are reported that achieve PDE4D subtype selectivity through recognition of a single amino acid difference on a key regulatory domain, known as UCR2, that opens and closes over the catalytic site for cAMP hydrolysis. The design and optimization of lead compound...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00193
更新日期：2019-05-23 00:00:00
abstract：:The ester methyl [4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetate (1) (R1 = OMe) had previously been identified as the most interesting member of a series of selective beta 3-adrenergic agonists of brown adipose tissue and thermogenesis in the rat. In vivo it acts mainly via the related acid 1 (R1 = OH)....
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00088a010
更新日期：1992-05-15 00:00:00
abstract：:In a previously described chimeric peptide, we reported that the multifunctional opioid/neuropeptide FF (NPFF) receptor agonist 0 (BN-9) produced antinociception for 1.5 h after supraspinal administration. Herein, four cyclic disulfide analogs containing l- and/or d-type cysteine at positions 2 and 5 were synthesized....
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01367
更新日期：2020-12-24 00:00:00
abstract：:In this paper, a peptide substrate (Pep8) of TSSK1 is identified. Using Pep8 as a substrate, two homogeneous and efficient assays for TSSK1 inhibitors screening have been developed, including luminescent kinase assay and LC-MS-based high-throughput assay. Two classes of compounds were identified that are able to effic...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9002846
更新日期：2009-07-23 00:00:00
abstract：:The formation of intramolecular hydrogen bonds has a very pronounced effect on molecular structure and properties. We study both aspects in detail with the aim of enabling a more rational use of this class of interactions in medicinal chemistry. On the basis of exhaustive searches in crystal structure databases, we de...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100087s
更新日期：2010-03-25 00:00:00
abstract：:In the present work, we have designed and synthesized a series of arachidonic acid derivatives of general structure I which have been characterized as highly potent and selective inhibitors of anandamide transporter (IC(50) = 24-0.8 microM, K(i) > 1000-5000 nM for CB(1) and CB(2) cannabinoid receptors and vanilloid VR...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm015545y
更新日期：2001-12-20 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：:Collective experience in structure-based lead progression has found electrostatic interactions to be more difficult to optimize than shape-based ones. A major reason for this is that the net electrostatic contribution observed includes a significant nonintuitive desolvation component in addition to the more intuitive ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm051105l
更新日期：2006-04-20 00:00:00
abstract：:Selective inhibition of neuronal nitric oxide synthase (nNOS) has been shown to prevent brain injury and is important for the treatment of various neurodegenerative disorders. This study shows that not only greater inhibitory potency and isozyme selectivity but more druglike properties can be achieved by fragment hopp...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm801220a
更新日期：2009-02-12 00:00:00
abstract：:The agonist selectivities of central (medullary) and peripheral (vascular) alpha-adrenoceptors were compared in order to investigate a possible similarity among these two alpha-adrenoceptor populations. Linear regression equations were derived between the alpha-adrenergic potencies, mediated by these two types of alph...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00137a006
更新日期：1981-05-01 00:00:00
abstract：:Isoform-selective antagonists of the lysophosphatidic acid (LPA) G-protein coupled receptors (GPCRs) have important potential uses in cell biology and clinical applications. Novel phosphonothioate and fluoromethylene phosphonate analogues of carbacyclic phosphatidic acid (ccPA) were prepared by chemical synthesis. The...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060351+
更新日期：2006-08-24 00:00:00
abstract：:A series of new, structurally simple trichostatin A (TSA)-like straight chain hydroxamates were prepared and evaluated for their ability to inhibit partially purified human histone deacetylase 1 (HDAC-1). Some of these compounds such as 8m, 8n, 12, and 15b exhibited potent HDAC inhibitory activity with low nanomolar I...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020154k
更新日期：2002-06-20 00:00:00
abstract：:Neutrophil serine proteases, proteinase 3 (PR3) and human neutrophil elastase (HNE), are considered as targets for chronic inflammatory diseases. Despite sharing high sequence similarity, the two enzymes have different substrate specificities and functions. While a plethora of HNE inhibitors exist, PR3 specific inhibi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500782s
更新日期：2014-11-26 00:00:00
abstract：:The antineoplastic constituents of Combretum caffrum (Eckl. and Zeyh) Kuntze (Combretaceae family), a species indigenous to South Africa, have been investigated. Subsequently we isolated a series of closely related bibenzyls, stilbenes, and phenanthrenes from C. caffrum. Some of the stilbenes proved to be potent antim...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00010a011
更新日期：1995-05-12 00:00:00
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：:Starting from the lead isodaphnetin, a natural product inhibitor of DPP-4 discovered through a target fishing docking based approach, a series of novel 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine derivatives as potent DPP-4 inhibitors are rationally designed utilizing highly efficient 3D molecular similarity based...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00505
更新日期：2016-07-28 00:00:00
abstract：:The chemical synthesis and structure-activity relationships of a novel series of 17beta-glucocorticoid butyrolactones possessing either a 16alpha,17alpha-isopropylidene or -butylidene group are described. The sulfur-linked gamma-lactone group was incorporated onto the 17beta-position of the androstane nucleus via Bart...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm001035c
更新日期：2001-02-15 00:00:00
