Abstract：
:Multidrug resistance-associated protein 1 (MRP1/ABCC1) is a very promiscuous transporter. Herein we used topological polar surface area (TPSA), a descriptor defined as the sum of surfaces of polar atoms in a molecule, to analyze drug transport by MRP1. We suggested that compounds with high TPSA are transported while those with low TPSA are not. The conjugation to GSH increases TPSA values favoring transport. A strong correlation between TPSA and transport properties (K(m)) was also found.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Fernandes J,Gattass CRdoi
10.1021/jm801389msubject
Has Abstractpub_date
2009-02-26 00:00:00pages
1214-8issue
4eissn
0022-2623issn
1520-4804pii
10.1021/jm801389mjournal_volume
52pub_type
杂志文章abstract：:The binding constants of 15 phenothiazine derivatives to bovine serum albumin were obtained by a circular dichroic probe technique; The lipophilicity of the drugs, measured by a reversed-phase thin-layer technique using oleyl alcohol and methanol-water mixtures as the solvents, is expressed as RMw. The binding constan...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00213a022
更新日期：1977-03-01 00:00:00
abstract：:Some small molecules, often hits from screening, form aggregates in solution that inhibit many enzymes. In contrast, drugs are thought to act specifically. To investigate this assumption, 50 unrelated drugs were tested for promiscuous inhibition via aggregation. Each drug was tested against three unrelated model enzym...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030191r
更新日期：2003-10-09 00:00:00
abstract：:Naturally occurring carbapenem antibiotics having a double bond in the side chain, when refluxed in chloroform containing quarternary alkylammonium halides, were converted into Z isomers in high yields. The mechanism of this new equilibration involves intramolecular proton transfer from the carboxylic acid to the carb...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00359a600
更新日期：1983-05-01 00:00:00
abstract：:Inhibitors of adenosine deaminase (ADA, EC 3.5.4.4) are potential therapeutic agents for the treatment of various health disorders. Several highly potent inhibitors were previously identified, yet they exhibit unacceptable toxicities. We performed a SAR study involving a series of C2 or C8 substituted purine-riboside ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm101286g
更新日期：2011-01-13 00:00:00
abstract：:Using a combination of in silico and experimental approaches, we present evidence that the G-quadruplex (G4) motif (an alternative higher-order DNA conformation) has regulatory potential. Genome-wide analyses of 99980 human, chimpanzee, mouse, and rat promoters showed enrichment of sequence with potential to adopt G4 ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800448a
更新日期：2008-09-25 00:00:00
abstract：:The design, synthesis, and activity of a novel series of 2,5-substituted tryptamine derivatives at vascular 5HT1B-like receptors is described. Several important auxiliary binding sites of the 5HT1B-like receptor have been proposed following various modifications to the 2-substituent and especially to the methylene- or...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9605849
更新日期：1997-07-18 00:00:00
abstract：:The antibacterial 4H-4-oxoquinolizines were introduced recently to overcome bacterial resistance to fluoroquinolones. They exhibit potent antibacterial activity against Gram-positive, Gram-negative, and anaerobic organisms and are highly active against some quinolone-resistant bacteria including quinolone-resistant MR...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990191k
更新日期：1999-10-07 00:00:00
abstract：:Although the illness malaria is caused by the asexual blood stages, the presence of gametocytes is directly responsible for the infection of the vector Anopheles, thus perpetuating the plasmodial cycle. Fight against malaria is more than ever a current problem, and the solution will probably go through the development...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm3005898
更新日期：2012-12-13 00:00:00
abstract：:Several 1,2-dihydro-5-(substituted phenyl)-2(1H)-pyridinones were synthesized and evaluated for inotropic activity. 1,2-Dihydro-5-[4-(1H-imidazol-1-yl)phenyl]-6-methyl-2-oxo-3- pyridinecarbonitrile (5a) and the corresponding unsubstituted analogue 14a were the most potent positive inotropic agents in this series. Alth...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00389a011
更新日期：1987-06-01 00:00:00
abstract：:(Trimethylsilyl)acetylene was coupled with 1-(2,3,5-tri-O-acetyl-beta-D- arabinofuranosyl)-5-iodouracil to give 1- (2,3,5-tri-O-acetyl-beta-D-arabinofuranosyl)-5-[2-(trimethylsilyl)eth yny l] uracil. Lindlar hydrogenation of 4 gave 1-(2,3,4-tri-O-acetyl-beta-D-arabinofuranosyl)-5(Z)-[2- (trimethylsilyl)vinyl]uracil. T...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00111a050
更新日期：1991-07-01 00:00:00
abstract：:The binding structures of 11 human oxidosqualene cyclase inhibitors designed as cholesterol-lowering agents were determined for the squalene-hopene cyclase from Alicyclobacillus acidocaldarius, which is the only structurally known homologue of the human enzyme. The complexes were produced by cocrystallization, and the...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0211218
更新日期：2003-05-22 00:00:00
abstract：:Several imidazolylphenyl sulfamate and (imidazolylphenoxy)alkyl sulfamate derivatives were synthesized and evaluated as topically active carbonic anhydrase inhibitors. Water solubility, pKa, carbonic anhydrase inhibition, and partition coefficient for the compounds were measured. Sulfamic acid 2-[4-(1H-imidazol-1-yl)p...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00104a003
更新日期：1992-12-25 00:00:00
abstract：:Polyamine transport is elevated in many tumor types, suggesting that toxic polyamine-drug conjugates could be targeted to cancer cells via the polyamine transporter (PAT). We have previously reported the use of Chinese hamster ovary (CHO) cells and its PAT-deficient mutant cell line, CHO-MG, to screen anthracene-polya...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm701198s
更新日期：2008-01-24 00:00:00
abstract：:Much has been discussed about the proper physicochemical properties (e.g., molecular weight, hydrophobicity, etc.) that should be considered when utilizing fragment leads in drug design. However, little has been reported as to what emphasis, if any, should be placed on the potency of the resulting fragment leads. In t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060511h
更新日期：2006-11-30 00:00:00
abstract：:Regioisomeric 3-carboxyisoxazolinyl prolines [CIP-A (+/-)-6 and CIP-B (+/-)-7] and 3-hydroxyisoxazolinyl prolines [(+/-)-8 and (+/-)-9] were synthesized and assayed for glutamate receptor activity. The tests were carried out in vitro by means of receptor binding techniques, second messenger assays, and the rat cortica...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm991081g
更新日期：1999-10-07 00:00:00
abstract：:We recently introduced sulfated pentagalloylglucopyranoside (SPGG) as an allosteric inhibitor of factor XIa (FXIa) (Al-Horani et al., J. Med Chem. 2013, 56, 867-878). To better understand the SPGG-FXIa interaction, we utilized eight SPGG variants and a range of biochemical techniques. The results reveal that SPGG's su...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500311e
更新日期：2014-06-12 00:00:00
abstract：:Tuberculosis (TB) is a major health problem worldwide. We herein report a new class of pyrimidine nucleosides as potent inhibitors of Mycobacterium tuberculosis (M. tuberculosis). Various 2'- or 3'-halogeno derivatives of pyrimidine nucleosides containing uracil, 5-fluorouracil, and thymine bases were synthesized and ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100165w
更新日期：2010-05-27 00:00:00
abstract：:N delta-Acyl derivatives of the potent folylpolyglutamate synthetase (FPGS) inhibitor N alpha-(4-amino-4-deoxypteroyl)-L-ornithine (APA-L-Orn) were synthesized from N alpha-(4-amino-4-deoxy-N10-formylpteroyl)-L-ornithine by reaction with an N-(acyloxy)succinimide or acyl anhydride, followed by deformylation with base....
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00402a013
更新日期：1988-07-01 00:00:00
abstract：:Modern rational drug design not only deals with the search for ligands binding to interesting and promising validated targets but also aims to identify the function and ligands of yet uncharacterized proteins having impact on different diseases. Additionally, it contributes to the design of inhibitors with distinct se...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00078
更新日期：2016-05-12 00:00:00
abstract：:Certain spiders contain large pools of polyamine toxins, which are putative pharmacological tools awaiting further discovery. Here we present a general synthesis strategy for this class of toxins and prepare five structurally varied polyamine toxins. Electrophysiological testing at three ionotropic glutamate receptor ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm301255m
更新日期：2012-11-26 00:00:00
abstract：:A unique, dual-function, photoactivatable anticancer prodrug, RuEuL, has been tailored that features a ruthenium(II) complex linked to a cyclen-europium chelate via a π-conjugated bridge. Under irradiation at 488 nm, the dark-inactive prodrug undergoes photodissociation, releasing the DNA-damaging ruthenium species. U...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01162
更新日期：2017-11-09 00:00:00
abstract：:Treatment of a protected 9-(5, 6-dideoxy-beta-D-ribo-hex-5-ynofuranosyl)adenine derivative with silver nitrate and N-iodosuccinimide (NIS) and deprotection gave the 6'-iodo acetylenic nucleoside analogue 3c. Halogenation of 3-O-benzoyl-5,6-dideoxy-1, 2-O-isopropylidene-alpha-D-ribo-hex-5-enofuranose gave 6-halo acetyl...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980163m
更新日期：1998-09-24 00:00:00
abstract：:A series of novel 1'-methylxanthene-9-spiro-4'-piperidines has been prepared in the search for opiate analgesics with improved pharmacological properties. It has been found that introduction of a hydroxyl group into the 4-position of the xanthenespiropiperidine nucleus produces a potent mu-opiate agonist. The structur...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00130a022
更新日期：1989-10-01 00:00:00
abstract：:9,10-Didehydro-6-methyl-8beta-arylergolines 2, in which the carboxyl group of lysergic acid and isolysergic acid is replaced by various aryl groups, were prepared in two steps by alkylation of aromatic substrates with the tetracyclic allylic alcohol 3, followed by aromatization with MnO2. The new ergolines 2 have mode...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00218a025
更新日期：1977-08-01 00:00:00
abstract：:The polyhalogenated benzimidazole nucleosides 2,5, 6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) and the 2-bromo analogue (BDCRB) were synthesized in our laboratory and established as potent and selective inhibitors of human cytomegalovirus (HCMV) with a novel mode of action. In an effort to study the behav...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990290y
更新日期：2000-06-15 00:00:00
abstract：:The high secretion rate of 18-hydroxydeoxycorticosterone in hypertensives and the steroids implication as a mineralocorticoid has led to the synthesis of potential di-, tetra-, and hexahydro metabolites of it and 18-hydroxy-progesterone. These potential metabolites have been synthesized by reduction of the double bond...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00380a014
更新日期：1985-02-01 00:00:00
abstract：:Very few nonpeptide oxytocin agonists have currently been reported, and none of them seem suitable for the in vivo investigation of the oxytocin mediated functions. In an attempt to rationalize the design of better tools, we have systematically studied the structural determinants of the affinity and efficacy of repres...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm901084f
更新日期：2010-02-25 00:00:00
abstract：:The principle of bioisosterism-similarly shaped molecules are more likely to share biological properties than are other molecules-has long helped to guide drug discovery. An algorithmic implementation of this principle, based on shape comparisons of a single rule-generated "topomer" conformation per molecule, had been...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990159q
更新日期：1999-09-23 00:00:00
abstract：:Methodology is presented for assembling fluorescently labeled bivalent molecules from monovalent constituents, without side chain protection or coupling agents. To illustrate the procedure, a series of bivalent peptidomimetics directed toward the Trk receptors were prepared and screened via fluorescent activated cell ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm034103e
更新日期：2003-08-14 00:00:00
abstract：:Analogues of luliberin containing an alpha-azaamino acid in position 6, 9, or 10 (I--XIV) have been synthesized by the solution method of peptide synthesis. Two nonaza analogues, [D-Phe6]- and [D-Ser(But)6,des-Gly-NH2(10),Pro-ethylamide9]luliberin, were also synthesized for comparison. The ovulation-inducing activity ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00208a004
更新日期：1978-10-01 00:00:00
