Abstract：
:Isolated hepatocytes carry out the N-demethylation of dansylamide at near linear rates for up to 8 h. This reaction was measured by following the release of tritium into water on hydroxylation of 3H-labeled methyl groups. The competitive inhibition of dansylamide by dansylated amino acids was studied in this system as an example of competing drug metabolism in a series of compounds which are identical around the site of metabolism and different remote to that site. A correlation between lipid solubility and the Ki was not found over the entire range of substrate analogues. While most of the high Km inhibitors seem to correlate with lipid solubility, the highly lipophilic derivatives of the leucines and phenylalanine are in a separate group. Lipid solubilities of the dansylated amino acids were little affected by changes in pH and thus behaved as "essential nonelectrolytes".
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Hayes JS,Brendel Kdoi
10.1021/jm00233a013keywords:
subject
Has Abstractpub_date
1976-11-01 00:00:00pages
1324-8issue
11eissn
0022-2623issn
1520-4804journal_volume
19pub_type
杂志文章abstract：:Compound 1 (SKI-606, bosutinib), a 7-alkoxy-4-[(2,4-dichloro-5-methoxyphenyl)amino]-3-quinolinecarbonitrile, is a potent inhibitor of Src kinase activity. We previously reported that analogs of 1 with thiophene groups at C-7 retained the Src activity of the parent compound. The corresponding C-7 furan analogs were pre...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm061031t
更新日期：2006-12-28 00:00:00
abstract：:Newly synthesized benzamide derivatives were evaluated for their inhibitory activity against histone deacetylase. The structure of these derivatives was unrelated to the known inhibitors, and IC(50) values of the active compounds were in the range of 2-50 microM. Structure-activity relationship on the benzanilide moie...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980565u
更新日期：1999-07-29 00:00:00
abstract：:Sansalvamide A, a cyclic depsipeptide isolated from a marine fungus of the genus Fusarium, is composed of four hydrophobic amino acids (Phe, two Leu, Val) and one hydroxy acid ((S)-2-hydroxy-4-methylpentanoic acid; O-Leu) with five stereogenic centers all having S-stereochemistry. We have recently synthesized the corr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm048952t
更新日期：2005-05-19 00:00:00
abstract：:Novel lavendamycins including two water soluble derivatives were synthesized via short and efficient methods. Pictet-Spengler condensation of 7-N-acylamino-2-formylquinoline-5,8-diones with tryptophans produced lavendamycin esters or amides 11-17. Lavendamycins 18-21 were obtained, respectively, by further transformat...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0304414
更新日期：2003-12-18 00:00:00
abstract：:Human immunodeficiency virus (HIV) infection is now pandemic. Targeting HIV-1 reverse transcriptase (HIV-1 RT) has been considered as one of the most successful targets for the development of anti-HIV treatment. Among the HIV-1 RT inhibitors, non-nucleoside reverse transcriptase inhibitors (NNRTIs) have gained a defin...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b00843
更新日期：2019-05-23 00:00:00
abstract：:The modulation of the endocannabinoid system is emerging as a viable avenue for the treatment of neurodegeneration, being involved in neuroprotective and anti-inflammatory processes. In particular, indirectly enhancing endocannabinoid signaling to therapeutic levels through FAAH inhibition might be beneficial for neur...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00609
更新日期：2016-07-14 00:00:00
abstract：:3',5'-Cyclic adenosine monophosphate (cAMP) is a pivotal second messenger that regulates numerous biological processes under physiological and pathological conditions, including cancer, diabetes, heart failure, inflammation, and neurological disorders. In the past, all effects of cAMP were initially believed to be med...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/jm401425e
更新日期：2014-05-08 00:00:00
abstract：:The calothrixins are quinone-based natural products isolated from Calothrix cyanobacteria which show potent antiproliferative properties against several cancer cell lines. Preliminary mechanistic studies suggest that the biological mode of action of the calothrixins may be linked to their ability to undergo redox cycl...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049625o
更新日期：2004-09-23 00:00:00
abstract：:Valproic acid (VPA) is a major antiepileptic drug (AED); however, its use is limited by two life-threatening side effects: teratogenicity and hepatotoxicity. Several constitutional isomers of VPA and their amide and urea derivatives were synthesized and evaluated in three different anticonvulsant animal models and a m...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm7009233
更新日期：2007-12-13 00:00:00
abstract：:The kinome-wide virtual profiling of small molecules with high-dimensional structure-activity data is a challenging task in drug discovery. Here, we present a virtual profiling model against a panel of 391 kinases based on large-scale bioactivity data and the multitask deep neural network algorithm. The obtained model...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00855
更新日期：2020-08-27 00:00:00
abstract：:A series of 6-alkyl-3 beta-benzyl-2-[(methoxycarbonyl)methyl]tropane analogues were synthesized and evaluated as cocaine binding site ligands at the dopamine transporter (DAT). The in vitro affinity (Ki) for the DAT of the 6-alkyl-3 beta-benzyl-2-[(methoxycarbonyl) methyl]tropane analogues was determined by inhibition...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970549h
更新日期：1997-12-19 00:00:00
abstract：:The final stages of polio eradication are proving more difficult than the early phases, and the development of effective drugs and treatments is considered a priority; thus, the research is ongoing. A screening of our in-house chemical library against poliovirus Sabin strains led to the identification of compounds 5 a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01482
更新日期：2019-01-24 00:00:00
abstract：:Sepsis is characterized by a systemic inflammatory response syndrome. Derivatives of indole have been reported to exhibit diverse biological activities. This study reports on the design and synthesis of a new series of indole-2-carboxamide derivatives, which are screened for their anti-inflammatory activities in RAW 2...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b02006
更新日期：2016-05-26 00:00:00
abstract：:Here we describe the synthesis and structure-activity relationship for a class of pyrazoline-containing dihydroquinolone negative allosteric modulators of the NMDA receptor that show strong subunit selectivity for GluN2C- and GluN2D-containing receptors over GluN2A- and GluN2B-containing receptors. Several members of ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm400652r
更新日期：2013-08-22 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 natural dibenzylbutyrolactone type lignanolide (-)-arctigenin (2), an inhibitor of human immunodeficiency virus type-1 (HIV-1) replication in infected human cell systems, was found to suppress the integration of proviral DNA into the cellular DNA genome. In the present study 2 was tested with purified HIV-1 integr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm950387u
更新日期：1996-01-05 00:00:00
abstract：:A practical combination of comparative modeling and NMR spectroscopy was used to generate a three-dimensional structure of the response regulator protein, Spo0F. The backbone structure obtained compares to the Spo0F Y13S mutant X-ray structure with an rmsd of 2.0 A. We provide results which suggest that structures obt...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970156i
更新日期：1997-10-10 00:00:00
abstract：:Botulinum neurotoxins (BoNT) are the most potent toxins known and a significant bioterrorist threat. Few small molecule compounds have been identified that are active in cell-based or animal models, potentially due to toxin enzyme plasticity. Here we screened commercially available quinolinols, as well as synthesized ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm4012164
更新日期：2014-02-13 00:00:00
abstract：:Several esters of beta-carboline-3-carboxylic acid were synthesized and tested in respect to their affinity for the benzodiazepine receptor in bovine cortex membranes. Out of these derivatives, the methyl, ethyl, and n-propyl ester were clearly the most potent, while the n-butyl, benzyl, and 3-pyridylmethyl ester were...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00358a008
更新日期：1983-04-01 00:00:00
abstract：:Small-molecule fluorescence imaging in the second near-infrared (NIR-II, 1000-1700 nm) window has gained increasing interest in clinical application. Till now, very few studies have been exploited in the small-molecule fluorophores with both excitation and emission in the NIR-II window. Inspired by the indocyanine gre...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01682
更新日期：2019-02-28 00:00:00
abstract：:Protein phosphorylation is the most significant post-translational modification for regulating cellular activities, but site-specific modulation of phosphorylation is still challenging. Using three-dimensional NMR spectra, molecular dynamics simulations, and alanine mutations, we identified that the interaction networ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01290
更新日期：2020-11-25 00:00:00
abstract：:Here we report on the design, synthesis, and biological characterization of novel κ opioid (KOP) receptor ligands of diphenethylamines. In opioid receptor binding and functional assays, the N-cyclobutylmethyl substituted derivative 4 (HS665) showed the highest affinity and selectivity for the KOP receptor and KOP agon...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm301258w
更新日期：2012-11-26 00:00:00
abstract：:Several compounds having portions of the camptothecin ring system were prepared. These compounds were screened against L1210 lymphoid leukemia with negative results. Two of the analogs which contained the pyridine and hydroxylactone D and E rings were also screened for inhibition of DNA and RNA syntheses in HeLa cells...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00239a024
更新日期：1975-05-01 00:00:00
abstract：:We present Fleksy, a new approach to consider both ligand and receptor flexibility in small molecule docking. Pivotal to our method is the use of a receptor ensemble to describe protein flexibility. To construct these ensembles, we use a backbone-dependent rotamer library and implement the concept of interaction sampl...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070593p
更新日期：2007-12-27 00:00:00
abstract：:Various lines of evidence, including molecular modeling studies, imply that the endoethylenic bridge of 3,8-diazabicyclo[3.2. 1]octanes (DBO, 1) plays an essential role in modulating affinity toward mu opioid receptors. This hypothesis, together with the remarkable analgesic properties observed for N(3) propionyl, N(8...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm991140q
更新日期：2000-06-01 00:00:00
abstract：:DL-(1-Amino-2-propenyl)phosphonic acid was synthesized through the sequential oxidation, sulfoxide elimination, and deprotection of diphenyl [1-[(benzyloxycarbonyl)amino]-3-(phenylthio)propyl] phosphonate. This analogue of vinylglycine is a strong inhibitor of the alanine racemases from Pseudomonas aeruginosa and Stre...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00154a024
更新日期：1986-04-01 00:00:00
abstract：:A series of (fluorobenzyl)triazolo[4,5-c]pyridines was synthesized and tested for activity against maximal electroshock-induced seizures in rodents. The most promising compound, 14 (BW 534U87), which is a carbon-nitrogen isoster of a purine anticonvulsant, has a profile in rodents that suggests 14 will be free of emes...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00020a030
更新日期：1995-09-29 00:00:00
abstract：:N,N-Dialkylated leucine enkephalin analogues containing melphalan (Mel) in place of Phe4 were synthesized as potentially irreversible antagonists of the delta opioid receptor. These compounds, along with the corresponding Phe4 peptides, were tested for both agonist and antagonist activity in the GPI and MVD smooth mus...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00392a025
更新日期：1987-09-01 00:00:00
abstract：:As part of a study on the structure-activity relationship of antitumor-active tropolone derivatives, a series of bistropone analogues, related to potently active bistropolone 1a, were synthesized and tested for their antitumor activity in in vitro (KB cell) and in vivo (leukemia P388 in mice) systems. The methoxytropo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00390a022
更新日期：1987-07-01 00:00:00
abstract：:We present an analysis of the chemical fragments from lead-like ligands in the Protein Data Bank (PDB) that form hydrogen bonds to the side chains of Asp, Glu, Arg, and His, which are the most common residues found in ligand binding sites. A fragment is defined as the largest ring assembly containing the atoms involve...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm901696w
更新日期：2010-04-22 00:00:00
