Abstract:
:The chelating drugs BAL (2,3-dimercaptopropanol), EDTA (ethylenediaminetetraacetic acid), and penicillamine (2-amino-3-mercapto-3-methylbutanoic acid), which are used for metal poisoning, are toxic and there is a real need for alternatives, especially for severe cases. A novel approach for treatment of heavy-metal poisoning is under investigation in our group. The approach utilizes the synthesis of chelating microspheres specific for the desired metallic compound. The microspheres are suggested for use in severe cases by means of hemoperfusion, as a first aid, and then by oral administration. As a model this approach was tried for mercury poisoning. Polymercaptal microspheres of 0.8 micrometer average size were synthesized. The microspheres have a high surface area, have a high affinity toward organic and inorganic mercury compounds, and can compete easily with albumin and cysteine in the ability to bind mercury compounds. These microspheres also were encapsulated with agarose--a blood compatible polymer--and were tried successfully for plasma perfusion (in 10 min, 40% of CH3HgCl and of HgCl2 were removed from 20 ppm of poisoned plasma).
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Margel Sdoi
10.1021/jm00142a028subject
Has Abstractpub_date
1981-10-01 00:00:00pages
1263-6issue
10eissn
0022-2623issn
1520-4804journal_volume
24pub_type
杂志文章abstract::A series of 3-(4-acylaminopiperazin-1-ylalkyl)indoles was synthesized and tested for antihypertensive activity. Compounds with no substituents in the indole portion of the molecule were generally most effective in lowering blood pressure in the spontaneous hypertensive rat model. Of these several analogues were very p...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00221a024
更新日期:1977-11-01 00:00:00
abstract::A series of analogues of 4,5-bis(((N-methylcarbamoyl)oxy)methyl)-1-methyl-2-(methylthio)-im idazole (1, carmethizole) were synthesized. The chemical reactivities of the analogues (as electrophiles) were evaluated and related to the antitumor activity (in vivo and in vitro). Changes in the alkylthio moiety had a signif...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00075a017
更新日期:1993-11-12 00:00:00
abstract::Vitamin D receptor (VDR) antagonists prevent the VDR activation function helix 12 from folding into its active conformation, thus affecting coactivator recruitment and antagonizing the transcriptional regulation induced by 1α,25-dihydroxyvitamin D3. Here, we report the crystal structure of the zebrafish VDR ligand-bin...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.0c00656
更新日期:2020-09-10 00:00:00
abstract::A cell-free assay was developed for the orphan nuclear receptor LXRalpha that measures the ligand-dependent recruitment of a peptide from the steroid receptor coactivator 1 (SRC1) to the nuclear receptor. Using this ligand-sensing assay (LiSA), the structural requirements for activation of the receptor by oxysterols a...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm0004749
更新日期:2001-03-15 00:00:00
abstract::A series of 2- and 3-aminobenzanilides derived from ring-alkylated anilines were prepared and evaluated for anticonvulsant activity. These benzanilides were prepared in the course of studies designed to determine the relationship between the benzamide structure and anticonvulsant effects. The compounds were tested in ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00158a038
更新日期:1986-08-01 00:00:00
abstract::Glucuronidation and transporter-mediated efflux into bile are important in the elimination of xeno- and endobiotics, including the natural biladienone pigment bilirubin. The mechanisms of these processes and the structural factors that dictate whether cholephilic compounds are excreted directly in bile or require prio...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm0609521
更新日期:2007-02-08 00:00:00
abstract::A number of indole-3-glyoxylamides have previously been reported as tubulin polymerization inhibitors, although none has yet been successfully developed clinically. We report here a new series of related compounds, modified according to a strategy of reducing aromatic ring count and introducing a greater degree of sat...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.5b01312
更新日期:2015-12-10 00:00:00
abstract::Thrombin, a serine protease, plays a central role in the initiation and propagation of thrombotic events. An extensive search for new thrombin inhibitors was performed, using an unconventional approach. Screening of small basic molecules for binding in the recognition pocket of thrombin led to the discovery of (aminoi...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00049a008
更新日期:1994-11-11 00:00:00
abstract::Thiol-containing diketopiperazines have been recently identified as novel heterocyclic inhibitors of matrix metalloproteinase (MMPs). The compounds described had similar activities against the MMPs collagenase-1 and gelatinase-B. An inhibitor that showed greater than 10-fold selectivity for collagenase-1 over gelatina...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm980475p
更新日期:1999-04-22 00:00:00
abstract::Although cyclooxygenase-1 (COX-1) inhibition is thought to be a major mechanism of gastric damage by nonsteroidal anti-inflammatory drugs (NSAIDs), some COX-1-selective inhibitors exhibit strong analgesic effects without causing gastric damage. However, it is not clear whether their analgesic effects are attributable ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm701191z
更新日期:2008-04-24 00:00:00
abstract::Use of automated synthesis led to the discovery of several 6-membered nitrogen heterocycles as replacements for the N-isoxazolyl substituent present in the 1-naphthalenesulfonamides endothelin-A (ETA) antagonist 5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesu lfo namides (BMS 182874). In each of these ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm9604585
更新日期:1997-03-14 00:00:00
abstract::Increasing evidence suggests that iron plays an important role in tissue damage both during chronic iron overload diseases (i.e., hemochromatosis) and when, in the absence of actual tissue iron overload, iron is delocalized from specific carriers or intracellular sites (inflammation, neurodegenerative diseases, postis...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm021022u
更新日期:2002-12-19 00:00:00
abstract::The hPepT1-mediated transport properties of a series of 11 synthesized beta- and gamma-peptides have been studied in Caco-2 cells. The results show that several of the compounds interact with the peptide transporter, but only two beta-dipeptides act as substrates and are transported across the cell monolayers. These t...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm070148u
更新日期:2007-10-18 00:00:00
abstract::We report compounds 5 (CG416) and 6 (CG428) as two first-in-class tropomyosin receptor kinase (TRK) degraders that target the intracellular kinase domain of TRK. Degraders 5 and 6 reduced levels of the tropomyosin 3 (TPM3)-TRKA fusion protein in KM12 colorectal carcinoma cells and inhibited downstream PLCγ1 signaling ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.0c01342
更新日期:2020-12-10 00:00:00
abstract::With the aim of increasing therapeutic indexes of novel cyclic depsinonapeptide pseudomycins, we synthesized and evaluated a series of mono-, di-, and trioxodioxolenylmethyl carbamate prodrugs (2 and 4) of pseudomycin B 1 and pseudomycin C' 3. It is rather encouraging to note that several members of the newly synthesi...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm000425w
更新日期:2001-08-02 00:00:00
abstract::In 1994, following work from this laboratory, it was reported that estrone-3-O-sulfamate irreversibly inhibits a new potential hormone-dependent cancer target steroid sulfatase (STS). Subsequent drug discovery projects were initiated to develop the core aryl O-sulfamate pharmacophore that, over some 20 years, have led...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.5b00386
更新日期:2015-10-08 00:00:00
abstract::A series of new nitrogen-carbon-linked (azolylphenyl)oxazolidinone antibacterial agents has been prepared in an effort to expand the spectrum of activity of this class of antibiotics to include Gram-negative organisms. Pyrrole, pyrazole, imidazole, triazole, and tetrazole moieties have been used to replace the morphol...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm990373e
更新日期:2000-03-09 00:00:00
abstract::The preparation, determination of isomeric configuration, and antifungal properties of (E)-1-(5-chlorothien-2-yl)-2-(1H-imidazol-1-yl)ethanone 2,6-dichlorophenylhydrazone hydrochloride (1) are described. In vitro, compound 1 has been shown to have activity against Candida albicans comparable with miconazole. When admi...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00357a023
更新日期:1983-03-01 00:00:00
abstract::Three N-C8-bridged analogues 4-6 of the opiate etorphine (3) were synthesized and evaluated for opiate agonism and antagonism. In each case ring closure was effected by intramolecular N-alkylation with a suitably developed C8 side chain. Another key synthetic step was the selective monoprotection of diol 11, which all...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00394a016
更新日期:1987-11-01 00:00:00
abstract::Due to their role in many important signaling pathways, phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are attractive targets for the development of experimental therapeutics for cancer, metabolic, and immunological disorders. Recent efforts to develop small molecule inhibitors for these lipid kinases resulted i...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.0c00227
更新日期:2020-05-14 00:00:00
abstract::Condensation of cyanothioacetamide (4) with ethyl alpha-(ethoxymethylene)acetoacetate (5b), ethyl 4-ethoxy-2-(ethoxymethylene)-3-oxobutanoate (5c), ethyl 2-(ethoxymethylene)-3-oxo-4-phenylpropanoate (5d) afforded exclusively the corresponding 6-substituted pyridines (6b-d). Cyclization of 4 with 3-carbethoxybutane-2,4...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00401a023
更新日期:1988-06-01 00:00:00
abstract::Factors influencing dose potency of 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) analogues in L1210 assays have been investigated by multiple regression analysis. The dependent variable was D40, the dose to provide 40% life extension in L1210 tests. Independent variables examined were chromatographic Rm val...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00137a009
更新日期:1981-05-01 00:00:00
abstract::Tumors have evolved a variety of methods to reprogram conventional metabolic pathways to favor their own nutritional needs, including glutaminolysis, the first step of which is the hydrolysis of glutamine to glutamate by the amidohydrolase glutaminase 1 (GLS1). A GLS1 inhibitor could potentially target certain cancers...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.9b00260
更新日期:2019-07-25 00:00:00
abstract::In the treatment of cardiovascular diseases, it could be of therapeutic interest to associate the hypotensive effects resulting from the inhibition of angiotensin II formation, ensured by endothelial angiotensin-converting enzyme (ACE), with the diuretic and natriuretic responses due to the protection of the endogenou...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00034a005
更新日期:1994-04-15 00:00:00
abstract::Various hydrophilic pyrazine-bis(carboxamides) derived from 3,5-diamino-pyrazine-2,5-dicarboxylic acid bearing neutral and anionic groups were prepared and evaluated for use as fluorescent glomerular filtration rate (GFR) tracer agents. Among these, the dianionic d-serine pyrazine derivatives 2d and 2j, and the neutra...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm200257k
更新日期:2011-07-28 00:00:00
abstract::The development of pharmacotherapeutic treatments of psychostimulant abuse has remained a challenge, despite significant efforts made toward relevant mechanistic targets, such as the dopamine transporter (DAT). The atypical DAT inhibitors have received attention due to their promising pharmacological profiles in anima...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.6b01373
更新日期:2016-12-08 00:00:00
abstract::Melanin concentrating hormone (MCH) is involved in regulation of food intake and energy homeostasis. Antagonists of the MCH receptor are expected to affect food intake and weight gain, making MCH-R1 an attractive target for obesity treatment. Herein, we report the discovery of a novel, orally active series of MCH-R1 a...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm049035q
更新日期:2005-04-07 00:00:00
abstract::A series of pyridinyltetrahydropyridine derivatives was synthesized and evaluated as adrenoceptor and tetrabenazine antagonists. 4-(3-Fluoro-2-pyridinyl)-1,2,5,6-tetrahydropyridine proved to be the most potent and selective alpha 2-adrenoceptor antagonist of the series as measured in vitro by displacement of [3H]cloni...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00375a017
更新日期:1984-09-01 00:00:00
abstract::From the whole plant of Euphorbia peplus L., five new diterpenes based on a jatrophane skeleton (pepluanins A-E, 1-5) were isolated, together with two known analogues (6 and 7), which served to divulge in detail the structure-activity relationships within this class of P-glycoprotein inhibitors. The results revealed t...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm030951y
更新日期:2004-02-12 00:00:00
abstract::There is urgent need for new therapeutic strategies to fight the global threat of antibiotic resistance. The focus of this Perspective is on chemical agents that target the most common mechanisms of antibiotic resistance such as enzymatic inactivation of antibiotics, changes in cell permeability, and induction/activat...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.7b00215
更新日期:2017-10-26 00:00:00