Abstract：
:Computational ligand-protein docking is routinely used for binding mode prediction. We have quantified the effect of considering multiple docking solutions on the success rate of obtaining the crystallographic binding mode. By selection of a small set of representatives, the experimentally observed binding mode can be predicted with a higher probability after a ligand-protein docking simulation. The proportion of correctly predicted complexes improved from 69% to 87% when five distinct binding modes were considered.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Källblad P,Mancera RL,Todorov NPdoi
10.1021/jm0498147keywords:
subject
Has Abstractpub_date
2004-06-17 00:00:00pages
3334-7issue
13eissn
0022-2623issn
1520-4804journal_volume
47pub_type
信件abstract：:3',5'-Diamino-3',5'-dideoxythymidine (7) was synthesized via a nine-step synthesis from thymidine in good overall yield. 3'-Amino-3'-deoxythymidine (8) and 5'-amino-5'-deoxythymidine (12) were prepared with a minor modification of the procedure reported by Horwitz and co-workers. Although the 5'-amino analogue 12 had ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：
更新日期：1978-01-01 00:00:00
abstract：:Focal adhesion kinase (FAK) is a nonreceptor kinase that is overexpressed in many types of tumors. We developed a novel cancer-therapy approach, targeting the main autophosphorylation site of FAK, Y397, by computer modeling and screening of the National Cancer Institute (NCI) small molecule compounds database. More th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800483v
更新日期：2008-12-11 00:00:00
abstract：:By applying a novel cell- and caspase-based HTS assay, 2-amino-3-cyano-7-(dimethylamino)-4-(3-methoxy-4,5-methylenedioxyphenyl)-4H-chromene (1a) has been identified as a potent apoptosis inducer. Compound 1a was found to induce nuclear fragmentation and PARP cleavage, as well as to arrest cells at the G(2)/M stage and...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049640t
更新日期：2004-12-02 00:00:00
abstract：:Photodynamic therapy uses a combination of light, oxygen, and a photosensitizer to induce the death of malignant cells. To improve the selectivity of a photosensitizer toward cancerous cells that express gonadotropin-releasing hormone (GnRH) receptors, protoporphyrin IX (PpIX) was conjugated to a GnRH agonist, [d-Lys6...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020535y
更新日期：2003-09-11 00:00:00
abstract：:1-Methyl-5-(3-azido-2,3-dideoxy-beta-D-erythro-pentofuranosyl)uracil (C-AZT), a C-nucleoside isostere of the potent anti-AIDS nucleoside 3'-azido-3'-deoxythymidine (AZT), was synthesized. 1-Methyl-2'-deoxy-5'-O-tritylpseudouridine (2a) was oxidized with CrO3/pyridine/Ac2O complex to 1-methyl-5-(5-O-trityl-beta-D-glyce...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00169a030
更新日期：1990-07-01 00:00:00
abstract：:Ionotropic glutamate receptors (iGluRs) constitute a family of ligand-gated ion channels that are essential for mediating fast synaptic transmission in the central nervous system. This study presents a high-resolution X-ray structure of the competitive antagonist (S)-2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-4-isox...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020989v
更新日期：2003-01-16 00:00:00
abstract：:Polyadenosine diphosphoribose glycohydrolase (PARG) catalyzes the intracellular hydrolysis of adenosine diphosphoribose polymers. Because structure-activity data are lacking for PARG, the specific inhibitor adenosine diphosphate (hydroxymethyl)pyrrolidinediol (ADP-HPD) was utilized to determine the effects of structur...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020541u
更新日期：2003-09-25 00:00:00
abstract：:Analogues of the anticonvulsant agent milacemide (1,2-(n-pentylamino)acetamide), in which the carboxamide group is changed to a nitrile (2), a carbethoxy group (3), a carboxylic acid (4), a cyanomethyl group (5), and a trifluoromethyl group (6), were synthesized and tested as substrates and inactivators of monoamine o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00056a004
更新日期：1993-02-19 00:00:00
abstract：:Novel benzo[d]oxazol-2(3H)-one derivatives were designed and synthesized, and their affinities against sigma receptors were evaluated. On the basis of 31 compounds, a three-dimensional pharmacophore model for the sigma(1) receptor binding site was developed using the Catalyst 4.9 software package. The best 3D pharmaco...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900366z
更新日期：2009-09-10 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：:PRMT3 catalyzes the asymmetric dimethylation of arginine residues of various proteins. It is crucial for maturation of ribosomes and has been implicated in several diseases. We recently disclosed a highly potent, selective, and cell-active allosteric inhibitor of PRMT3, compound 4. Here, we report comprehensive struct...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01674
更新日期：2018-02-08 00:00:00
abstract：:Two series of halogenated sulfonamides have been prepared. The first consists of mono/dihalogenated sulfanilamides, whereas the second one consists of the mono/dihalogenated aminobenzolamides, incorporating equal or different halogens (F, Cl, Br, and I). These sulfonamides have been synthesized from the corresponding ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm021123s
更新日期：2003-05-22 00:00:00
abstract：:Dual target inhibitors against COX-2 and LTA(4)H were designed by adding functional groups from a marketed COX-2 inhibitor, Nimesulide, to an existing LTA(4)H inhibitor 1-(2-(4-phenoxyphenoxy) ethyl) pyrrolidine. A series of phenoxyphenyl pyrrolidine compounds were synthesized and tested for their inhibition activitie...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200063s
更新日期：2011-05-26 00:00:00
abstract：:A series of thymidylate synthetase inhibitors was synthesized, some of which were potential irreversible inhibitors. 5-Formyl-2'-deoxyuridine (9) and its dithiolane derivative 11 were prepared by condensation of the bis(trimethylsilyl) derivative of 5-formyluracil dimethyl acetal and the protected chloro sugar followe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00229a010
更新日期：1976-07-01 00:00:00
abstract：:A new computational method for the in situ generation of small molecules within the binding site of a protein is described. The method has been evaluated using two well-studied systems, dihydrofolate reductase and thymidylate synthase. The method has also been used to guide improvements to inhibitors of HIV-1 protease...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00003a010
更新日期：1995-02-03 00:00:00
abstract：:In this work, we introduce a four-step scoring and filtering procedure, furnishing target specific virtual screening (TS-VS), which serves to minimize false positives resulting from conformational artifacts of the docking process and is optimized to converge on novel chemotypes of estrogen receptor alpha (ERalpha). As...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0700262
更新日期：2007-11-01 00:00:00
abstract：:cis-4-Hydroperoxycyclophosphamide (5) undergoes facile reaction with aqueous phosphate or Tris buffers at pH 7-8 and 30 degrees C. The kinetics of 5 are complex, and the trans-4-hydroperoxy isomer 6 is produced and subsequently disappears over the course of the reaction. Addition of hydrogen peroxide to the reaction m...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00370a009
更新日期：1984-04-01 00:00:00
abstract：:In the present investigation, the last two possible modes of generating conformationally semirigid diacylglycerol (DAG) analogues embedded into five-membered ring lactones as templates III and IV are investigated. The first two templates studied in previous investigations corresponded to 2-deoxyribonolactone (template...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm960525v
更新日期：1996-12-06 00:00:00
abstract：:A series of indolylsulfonylcinnamic hydroxamates has been synthesized. Compound 12, (E)-3-(3-((1H-pyrrolo[2,3-b]pyridin-1-yl)sulfonyl)phenyl)-N-hydroxyacrylamide, which has a 7-azaindole core cap, was shown to have antiproliferative activity against KB, H460, PC3, HSC-3, HONE-1, A549, MCF-7, TSGH, MKN45, HT29, and HCT...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401899x
更新日期：2014-05-22 00:00:00
abstract：:Monoamine oxidase (MAO) exists in two forms distinguishable by substrate specificity. Inhibition of MAO A is believed to be responsible for the antidepressant activity of MAO inhibitors. A group of N-arylacetamides are highly specific inhibitors of MAO A, some with IC50 values in the 10-100 nM range. The requirements ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00039a021
更新日期：1994-06-24 00:00:00
abstract：:Continuing structure-activity studies on the anticonvulsant activity of analogs of N-(benzyloxy)-2-azaspiro[4.4]nonane-1,3-dione (2a), which displayed anti-electroshock seizure (MES) activity and a protective index (TD50/ED50) of > 4.5 are reported. An in-depth analysis of this moiety was studied employing the Topliss...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00075a005
更新日期：1993-11-12 00:00:00
abstract：:The preparation and plasma lipid altering characteristics of a series of 4H-3,1-benzoxazin-4-ones are described. Hypocholesterolemic, hypotriglyceridemic, and high-density-lipoprotein elevating properties are found for derivatives bearing a 4-(1,1-dimethylethyl)phenyl group at the 2-position, and this activity is disp...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00121a047
更新日期：1989-01-01 00:00:00
abstract：:Success in discovering bioactive peptide mimetics is often limited by the difficulties in correctly transposing known binding elements of the active peptide onto a small and metabolically more stable scaffold while maintaining bioactivity. Here we describe a scanning approach using a library of pyranose-based peptidom...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm1002777
更新日期：2010-08-12 00:00:00
abstract：:A structure-guided design approach using a homology model of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) was used to improve the potency of a series of imidazopyridazine inhibitors as potential antimalarial agents. This resulted in high affinity compounds with PfCDPK1 enzyme IC50 values less tha...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500342d
更新日期：2014-04-24 00:00:00
abstract：:A series of potent nonpeptide inhibitors of the HIV protease have been identified. Using the structure of compound 3 bound to the HIV protease, bis tertiary amide inhibitor 9 was designed and prepared. Compound 9 was found to be about 17 times more potent than 3, and the structure of the protein-ligand complex of 9 re...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm960092w
更新日期：1996-07-05 00:00:00
abstract：:Some glycine, leucine and phenylalanine dipeptide derivatives of the transport inhibitory, tricycloaliphatic alpha-amino acid, adamantanine (1), have been synthesized using classical methods of peptide synthesis with the aim of improving the latter's bioavailability. Although test doses of glycyladamantanine and L-leu...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00242a013
更新日期：1975-08-01 00:00:00
abstract：:The synthesis, pharmacological evaluation, and structure-activity relationships (SARs) of a series of novel pyrroloquinoxalines and heteroaromatic-related derivatives are described. The new pyrroloquinoxaline-related ligands were tested in rat cortex, a tissue expressing high density of 5-HT(3) receptors, and on NG108...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990151g
更新日期：1999-10-21 00:00:00
abstract：:(E)-Vinylphosphonate ((E)-VP), a metabolically stable phosphate mimic at the 5'-end of the antisense strand, enhances the in vivo potency of siRNA. Here we describe a straightforward synthetic approach to incorporate a nucleotide carrying a vinylphosphonate (VP) moiety at the 5'-end of oligonucleotides under standard ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01147
更新日期：2018-02-08 00:00:00
abstract：:The discovery of 8-(5,8-dichloro-1,2,3,4-tetrahydro-naphthalen-2-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one, 1a, as a high-affinity ligand for the human ORL1 (orphanin FQ/nociceptin) receptor led to the synthesis of a series of optimized ligands. These compounds exhibit high affinity for the human ORL1 receptor, e...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm991129q
更新日期：2000-04-06 00:00:00
abstract：:A series of substituted (E)-3-(4-oxo-4H-quinazolin-3-yl)-2-propenoic acids was prepared and evaluated in the rat passive cutaneous anaphylaxis (PCA) test for antiallergic activity. Alkoxy, alkylthio, and isopropyl substituents at the 6- or 8-positions provided highly potent compounds. Conversion to the Z isomer, reduc...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00357a018
更新日期：1983-03-01 00:00:00
