Abstract：
:A series of N-(cyclopropylmethyl)-14 beta-substituted-normorphine analogues was synthesized and tested for opioid agonist and antagonist activity in the guinea pig ileum and mouse vas deferens preparations. The 14 beta-bromo compound proved to be a pure antagonist equal in potency to naloxone in the guinea pig ileum assay. In contrast to N-(cyclopropylmethyl)-14 beta-hydroxynormorphine which was a pure antagonist, the corresponding sulfur analogue was about equal to nalorphine in agonist and antagonist potency.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Osei-Gyimah P,Archer S,Gillan MG,Kosterlitz HWdoi
10.1021/jm00134a018subject
Has Abstractpub_date
1981-02-01 00:00:00pages
212-4issue
2eissn
0022-2623issn
1520-4804journal_volume
24pub_type
杂志文章abstract：:In pursuit of truncated glucagon analogues that can interact with the glucagon receptor with substantial binding affinity, 23 truncated glucagon analogues have been designed and synthesized. These truncated analogues consist of several fragments of glucagon with 11 or 12 amino acid residues (1-4), conformationally con...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm000453e
更新日期：2001-04-26 00:00:00
abstract：:The natural abundance 13C magnetic resonance spectra of a series of sulfonamide drugs(sulfanilamide, sulfaguanidine,sulfathiazole, sulfasuxidine, sulfadiazine, sulfamerazine, sulfamethiazine, and sulfapyridine) have been determined at 25.15 MHz employing the pulse Fourier transform technique. The chemical shefts have ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00239a014
更新日期：1975-05-01 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：:Molecular docking studies of carbohydrate derivatives in protein binding sites are often challenging because of water-mediated interactions and the inherent flexibility of the many terminal hydroxyl groups. Using the recognition process between heat-labile enterotoxin from Escherichia coli and ganglioside GM1 as a par...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980472c
更新日期：1999-05-20 00:00:00
abstract：:A series of N-alkyl-3-[m-(trifluoromethyl)phenyl]-5-hydroxy-2-pyrrolidinones and N-alkyl-3-(trifluoromethyl)-cinnamamides were prepared and screened in a series of tests designed to detect potential sleep inducers. The more active members of the series were evaluated for their ability to induce sleep in Cebus monkeys....
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00379a007
更新日期：1985-01-01 00:00:00
abstract：:2-[[(2-Pyridyl)methyl]thio]-1H-benzimidazoles (2, sulfides) exhibit antibacterial properties that are selective for Helicobacter spp., but they also have an inherent susceptibility to metabolic oxidation to furnish 2-[[(2-pyridyl)methyl]sulfinyl]-1H-benzimidazoles (1), which act as proton pump inhibitors (PPIs). We ha...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0208673
更新日期：2002-09-12 00:00:00
abstract：:The discovery of selective endothelin (ET) receptor antagonists will facilitate identification of the physiological and pathological roles for ET and its isopeptides. Structure-activity studies of the C-terminal hexapeptide of ET have been carried out to elucidate those amino acids important for receptor binding and a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00070a001
更新日期：1993-09-03 00:00:00
abstract：:Water-ligand observed via gradient spectroscopy (WaterLOGSY) represents a powerful method for primary NMR screening in the identification of compounds interacting with macromolecules, including proteins and DNA or RNA fragments. The method is useful for the detection of compounds binding to a receptor with binding aff...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm011122k
更新日期：2002-06-06 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：:In a study of nonsteroidal antiinflammatory and analgesic agents, a series of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones-and 3-(substituted phenyl)triazolo[4,5-b]pyridines was prepared. Many of the imidazolones were alkylated on the free nitrogen. In a modified Randall-Selitto analgesic assay, the ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00207a023
更新日期：1978-09-01 00:00:00
abstract：:Screening in mixtures is a common approach for increasing the efficiency of high-throughput screening. Here we investigate how the "compound load" of mixtures influences promiscuous aggregate-based inhibition. We screened 764 molecules individually and in mixtures of 10 at 5 miccroM each, comparing the observed inhibi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060029z
更新日期：2006-04-06 00:00:00
abstract：:A series of 2,2-dimethyl-3,3-diphenyl-propanamides as novel glucocorticoid receptor modulators is reported. SAR exploration led to the identification of 4-hydroxyphenyl propanamide derivatives displaying good agonist activity in GR-mediated transrepression assays and reduced agonist activity in GR-mediated transactiva...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100957a
更新日期：2010-12-09 00:00:00
abstract：:In order to determine the influence of a 6alpha-methyl group activity, the 6alpha-methyl derivative of digitoxigenin 3-acetate 14 was prepared and pharmacologically tested in comparison with digitoxigenen 3-acetate. The synthesis of 6alpha-methyldigitoxigenin 3-acetate (14) was performed starting from 21-hydroxy-4-pre...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00246a020
更新日期：1975-12-01 00:00:00
abstract：:2,4-Diaminoquinazoline antifolates with a lipophilic side chain at the 5-position, and in one case with a classical (p-aminobenzoyl)-L-glutamate side chain, were synthesized as potentially selective inhibitors of a site-directed mutant of human dihydrofolate reductase (DHFR) containing phenylalanine instead of leucine...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00005a002
更新日期：1995-03-03 00:00:00
abstract：:Three ellipticine-estradiol conjugates were synthesized in an effort to target the cytotoxicity of ellipticine to estrogen-receptor positive cells. The three conjugates were prepared with linker chains extending from the 17 alpha position of the estradiol to N-2 (compound 3), N-6 (compound 4), and C-9 (compound 5) pos...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9602930
更新日期：1996-08-16 00:00:00
abstract：:A novel class of artemisinin analogs, N-alkyl-11-aza-9-desmethylartemisinins 17-29, were synthesized via ozonolysis and acid-catalyzed cyclization of precursor amides 5-16. These amides were prepared through condensation of an activated ester of the known intermediate acid 2 with the corresponding primary amine. The a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00026a011
更新日期：1995-12-22 00:00:00
abstract：:Several laboratories have demonstrated that activation of drug metabolism by P450s may occur via a mechanism that resembles allosterism from an enzyme kinetic standpoint. Because the effector drug binding site may be located in the same P450 binding pocket where the drug substrate is located, the ability to find and c...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060706p
更新日期：2007-03-22 00:00:00
abstract：:Inhibition of the cell cycle kinase, cyclin-dependent kinase-4 (Cdk4), is expected to provide an effective method for the treatment of proliferative diseases such as cancer. The pyrido[2,3-d]pyrimidin-7-one template has been identified previously as a privileged structure for the inhibition of ATP-dependent kinases, a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049355+
更新日期：2005-04-07 00:00:00
abstract：:9,11-Secoestradiol (9) and 11-hydroxy-9,11-secoestradiol (12) have been synthesized starting from 17-acetoxyestradiol 3-methyl ether (1) and found to possess significant antifertility activity in rats. 3-Methoxy-9,11-seco-9-oxo-17beta-acetoxyestra-1,3,5(10)-trien-11-oic acid (2), prepared by CrO3 oxidation of 1, on h...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00241a026
更新日期：1975-07-01 00:00:00
abstract：:New therapies are needed for the treatment of toxoplasmosis, which is a disease caused by the protozoan parasite Toxoplasma gondii. To this end, we previously developed a potent and selective inhibitor (compound 1) of Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) that possesses antitoxoplasmosis activ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00760
更新日期：2016-07-14 00:00:00
abstract：:The synthesis of a novel series of antitussive agents is described. Two series of amino-substituted tetra- and hexahydrodibenzofurans were prepared and examined for antitussive activity in the guinea pig after cough elicited by electrical stimulation of the vagus nerve. A significant level of activity, comparable with...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00212a003
更新日期：1977-02-01 00:00:00
abstract：:KEAP1 is the key regulator of the NRF2-mediated cytoprotective response, and increasingly recognized as a target for diseases involving oxidative stress. Pharmacological intervention has focused on molecules that decrease NRF2-ubiquitination through covalent modification of KEAP1 cysteine residues, but such electrophi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00228
更新日期：2016-04-28 00:00:00
abstract：:A three-dimensional common feature pharmacophore model was developed using the X-ray structure of RT/non-nucleoside inhibitor (NNRTI) complexes. Starting from the pharmacophore hypothesis and the structure of the lead compound TBZ, new NNRTIs were designed and synthesized, having the benzimidazol-2-one system as a sca...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049279a
更新日期：2005-05-05 00:00:00
abstract：:The synthesis and in vitro and in vivo antibreast and antiprostate cancers activities of novel C-4 heteroaryl 13-cis-retinamides that modulate Mnk-eIF4E and AR signaling are discussed. Modifications of the C-4 heteroaryl substituents reveal that the 1H-imidazole is essential for high anticancer activity. The most pote...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501792c
更新日期：2015-02-26 00:00:00
abstract：:A series of 3,6-disubstituted pyridazino[4,3-c]isoquinolines were synthesized and tested for their ability to inhibit the binding of [3H]diazepam to rat brain receptors in vitro. Compounds bearing a phenyl, 4-methoxyphenyl, or methyl group at position 3 and a dialkylamino group at position 6 showed the highest affinit...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00147a034
更新日期：1985-09-01 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：:Continuing studies on the chemical modification of the previously reported novel tripeptide SP antagonist, N alpha-[N alpha-[N alpha- (tert-butyloxycarbonyl)glutaminyl]-N1-formyl-D-tryptophyl]phenylalanine benzyl ester [Boc-Gln-D-Trp-(CHO)-Phe-OBzl (1)], are described herein. We initially investigated the stability of...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00095a013
更新日期：1992-08-21 00:00:00
abstract：:Chemical probes are small molecules designed to bind to a specific protein and disrupt the proteins function. Although many inhibitors are reported for human carbonic anhydrase (CA) enzymes, few may be considered useful as chemical probes as they exhibit broad action against the 12 catalytically active CA isozymes. In...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b01228
更新日期：2015-09-24 00:00:00
abstract：:New 2-[2'-(dimethylamino)ethyl]-3H-dibenz[de,h]isoquinoline-1,3-diones with substituents at the 6- and 7-positions were prepared. Nucleophilic aromatic displacement was a key reaction in the syntheses. Ten of the new compounds were more potent than the unsubstituted compound, azonafide, in a panel of tumor cells inclu...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm950742g
更新日期：1996-04-12 00:00:00
abstract：:Malaria continues to be a major global health problem, being particularly devastating in the African population under the age of five. Artemisinin-based combination therapies (ACTs) are the first-line treatment recommended by the WHO to treat Plasmodium falciparum malaria, but clinical resistance against them has alre...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b00114
更新日期：2015-06-11 00:00:00
