Abstract：
:Forty-eight heterocyclic amino acid trimers, analogues of distamycin, with a number of features that enhance lipophilicity are described. They contain alkyl or cycloalkyl groups larger than methyl; some are N-terminated by acetamide or methoxybenzamide and are C-terminated by dimethylaminopropyl or aliphatic heterocylic aminopropyl substituents. The ability of these compounds to bind principally to AT tracts of DNA has been evaluated using capillary zone electrophoresis. Significant antimicrobial activity against key organisms such as MRSA and Candida albicans is shown by several compounds, especially those containing a thiazole. Moreover, these compounds have low toxicity with respect to several mammalian cell lines.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Khalaf AI,Waigh RD,Drummond AJ,Pringle B,McGroarty I,Skellern GG,Suckling CJdoi
10.1021/jm031089xkeywords:
subject
Has Abstractpub_date
2004-04-08 00:00:00pages
2133-56issue
8eissn
0022-2623issn
1520-4804journal_volume
47pub_type
杂志文章abstract：:Thirty compounds related to the selective dopamine-autoreceptor agonist 3-(3-hydroxyphenyl)-N-n-propylpiperidine have been synthesized and tested for central dopamine-autoreceptor stimulating activity. The 3-(3-hydroxyphenyl)piperidine moiety seems indispensable for high potency and selectivity. Introduction of an add...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00144a021
更新日期：1981-12-01 00:00:00
abstract：:Anthrax lethal factor (LF) is a critical virulence factor in the pathogenesis of anthrax. A structure-activity relationship (SAR) of potential lethal factor inhibitors (LFi) is presented in which the zinc-binding group (ZBG), linker, and backbone moieties for a series of hydroxypyrone-based compounds were systematical...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm8013212
更新日期：2009-02-26 00:00:00
abstract：:Utilizing NNC 26-9100 (11) as a structural lead, a variety of nonpeptide derivatives of somatostatin were synthesized and evaluated for sst2 and sst4 receptor binding affinity. A novel thiourea scaffold was utilized to attach (1) a heteroaromatic nucleus to mimic the Trp8 residue, (2) a nonheteroaromatic nucleus to mi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980118e
更新日期：1998-11-19 00:00:00
abstract：:We have identified a novel series of antidiabetic N-(2-benzoylphenyl)-L-tyrosine derivatives which are potent, selective PPARgamma agonists. Through the use of in vitro PPARgamma binding and functional assays (2S)-3-(4-(benzyloxy)phenyl)-2-((1-methyl-3-oxo-3-phenylpropenyl)+ ++amin o)propionic acid (2) was identified ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9804127
更新日期：1998-12-03 00:00:00
abstract：:Three monomethylated derivatives of 4'-hydroxyacetanilide (acetaminophen) were prepared in order to compare their cytotoxic potential and analgesic activity with that of acetaminophen. Only 4'-hydroxy-N-methylacetanilide (N-methylacetaminophen) was devoid of cytotoxic effects to hepatic tissue of mice. Results of comp...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00159a029
更新日期：1986-09-01 00:00:00
abstract：:Multidrug resistance (MDR) is a major cause of failure in cancer chemotherapy. P-glycoprotein (P-gp), a promiscuous drug efflux pump, has been extensively studied for its association with MDR due to overexpression in cancer cells. Several P-gp inhibitors or modulators have been investigated in clinical trials in hope ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.7b01457
更新日期：2018-06-28 00:00:00
abstract：:The trans-(3,4)-dimethyl-4-(3-hydroxyphenyl)piperidines are a unique class of opioid antagonists that have recently provided selective antagonists for mu-opioid receptors (MOR) and kappa-opioid receptors (KOR). Molecular modeling indicated a strong structural similarity between the parent of this series and 2-amino-1,...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm040807s
更新日期：2004-10-07 00:00:00
abstract：:A series of pseudodipeptide amides are described that inhibit Ras protein farnesyltransferase (PFTase). These inhibitors are truncated versions of the C-terminal tetrapeptide (CAAX motif) of Ras that serves as the signal sequence for PFTase-catalyzed protein farnesylation. In contrast to CAAX peptidomimetics previousl...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00020a010
更新日期：1995-09-29 00:00:00
abstract：:The 3C-like proteinase (3CL(pro)) of severe acute respiratory syndrome (SARS) coronavirus is a key target for structure-based drug design against this viral infection. The enzyme recognizes peptide substrates with a glutamine residue at the P1 site. A series of keto-glutamine analogues with a phthalhydrazido group at ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0494873
更新日期：2004-12-02 00:00:00
abstract：:The resurgence of tuberculosis (TB), the incidence of drug-resistant strains of Mycobacterium tuberculosis (MTB), and the coinfection between TB and HIV have led to serious infections, high mortality, and a global health threat, resulting in the urgent search for new classes of antimycobacterial agents. Herein, we rep...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm901235p
更新日期：2010-01-28 00:00:00
abstract：:Aldehyde dehydrogenase (ALDH) activity is commonly used as a marker to identify cancer stem-like cells. The three ALDH1A isoforms have all been individually implicated in cancer stem-like cells and in chemoresistance; however, which isoform is preferentially expressed varies between cell lines. We sought to explore th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b00930
更新日期：2018-10-11 00:00:00
abstract：:A new series of quinazolinone derivatives was synthesized and evaluated as nonimidazole H 3 receptor inverse agonists. 2-Methyl-3-(4-[[3-(1-pyrrolidinyl)propyl]oxy]phenyl)-5-(trifluoromethyl)-4(3 H)-quinazolinone ( 1) was identified as a promising derivative for further evaluation following optimization of key paramet...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm8003834
更新日期：2008-08-14 00:00:00
abstract：:Although intravenously administered antiplatelet fibrinogen receptor (GPIIb/IIIa) antagonists have become established in the acute-care clinical setting for the prevention of thrombosis, orally administered drugs for chronic use are still under development. Herein, we present details from our exploration of structure-...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990418b
更新日期：1999-12-16 00:00:00
abstract：:The synthesis of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and analogues is reported. Their cytotoxic activity was evaluated according to protocols available at the National Cancer Institute (NCI), Bethesda, MD. The action of selected compounds was examined for potential inhibition of tubulin as...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm2012694
更新日期：2012-03-08 00:00:00
abstract：:Prealbumin is a major thyroxine binding protein in blood that has been well studied crystallographically and has also been proposed as a model for the thyroxine nuclear receptor in tissue. The high-affinity T4 binding site in prealbumin gave a linear plot on Scatchard analysis. The interactions of selected polychlorin...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00155a010
更新日期：1986-05-01 00:00:00
abstract：:Elevated plasma levels of low-density lipoprotein (LDL) cholesterol are a major risk factor for atherosclerosis leading to coronary artery disease (CAD), which remains the main cause of mortality in Western society. We believe that by preventing the reabsorption of bile acids, a minimally absorbed apical sodium-codepe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm040215+
更新日期：2005-09-08 00:00:00
abstract：:A series of 2'- and 3'-fluorinated 2',3'-dideoxynucleosides and 3'-azido-2',3'-dideoxynucleosides were synthesized and evaluated for their inhibitory activity against human immunodeficiency virus-1 (HIV-1) replication in MT-4 cells. Neither conversion of 3'-fluoro- or 3'-azido-2',3'-dideoxyadenosine to the correspondi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00128a013
更新日期：1989-08-01 00:00:00
abstract：:Design of small-molecule inhibitors (MDM2 inhibitors) to block the MDM2-p53 protein-protein interaction has been pursued as a new cancer therapeutic strategy. In recent years, potent, selective, and efficacious MDM2 inhibitors have been successfully obtained and seven such compounds have been advanced into early phase...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/jm501092z
更新日期：2015-02-12 00:00:00
abstract：:We present a comprehensive study of the performance of fast scoring functions for library docking using the program FlexX as the docking engine. Four scoring functions, among them two recently developed knowledge-based potentials, are evaluated on seven target proteins whose binding sites represent a wide range of siz...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0003992
更新日期：2001-03-29 00:00:00
abstract：:From the results of our previous physicochemical studies of polyamine-nucleic acid interactions, we concluded that polyamine analogues in cisoidal conformation are capable of wrapping around the major groove of the double helix, of displacing natural polyamines from their nucleic acid binding sites, and of inhibiting ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm000310s
更新日期：2001-02-01 00:00:00
abstract：:N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme and an attractive drug target in parasitic infections such as malaria. We have previously reported that 2-(3-(piperidin-4-yloxy)benzo[b]thiophen-2-yl)-5-((1,3,5-trimethyl-1H-pyrazol-4-yl)methyl)-1,3,4-oxadiazole (34c) is a high affinity inhibitor of both P...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500066b
更新日期：2014-03-27 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：:The plant metabolite 3,4,5-tri-O-galloylquinic acid methyl ester (TGAME, compound 6) was synthesized, and its potential effect on calcium oxalate monohydrate (COM) crystal binding to the surface of Madin-Darby canine kidney cells type I (MDCKI) and crystal growth in a Drosophila melanogaster Malpighian tubule (MT) mod...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01566
更新日期：2018-02-22 00:00:00
abstract：:2-(p-Nitrophenyl)-4-isopropylmorphine (V), an analog of 1-(p-nitrophenyl)-2-isopropylaminoethanol (INPEA, I) in which the OCHCHN chain of I is locked in a morpholine ring, loses the beta-receptor blocking activity of I on various isolated preparations. The same ineffectiveness is observed in the O-methyl (II), N-methy...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00242a016
更新日期：1975-08-01 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：:Polymeric nanoparticles (PNPs) may efficiently deliver in vivo therapeutics to tumors when conjugated to specific targeting agents. Gint4.T aptamer specifically recognizes platelet-derived growth factor receptor β and can cross the blood-brain barrier (BBB). We synthesized Gint4.T-conjugated PNPs able of high uptake i...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b00527
更新日期：2017-05-25 00:00:00
abstract：:Although there are many estrogen receptor antagonists with improved tissue selectivity profiles compared with tamoxifen, optimal tissue selectivity has not yet been demonstrated. As such there is still a need for additional diversity and new chemical scaffolds to allow for exploration of improved tissue selectivity. H...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020536q
更新日期：2003-04-10 00:00:00
abstract：:New 5'-O-carbonate prodrugs of zidovudine (AZT) have been synthesized in order to enhance its uptake by HIV-1 infected cells, to improve its anti-HIV potency, and to optimize the intramolecular cyclic rearrangement process related to the 5'-O-(4-hydroxybutyl) carbonate moiety. Evidence of this prodrug rearrangement wa...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010863i
更新日期：2001-08-30 00:00:00
abstract：:Sulfur mustard (SM) is a highly toxic chemical warfare agent. A satisfactory treatment regimen is not yet available for this toxicant. In a search for an effective antidote against SM, a series of novel S-2(omega-aminoalkylamino)ethyl alkyl/aryl thioethers [H(2)N(CH(2))(n)()NHCH(2)CH(2)SR], where R = alky, alicyclic, ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030099v
更新日期：2004-07-15 00:00:00
abstract：:A new class of acyclic adenosine analogues is described which exhibit broad-spectrum antiviral activity and are apparently targeted at S-adenosyl-L-homocysteine hydrolase. The compounds are all alkyl (i.e., methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, 2-methylpropyl, tert-butyl, 1-pentyl, 3-methylbutyl, 1-octy...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00381a004
更新日期：1985-03-01 00:00:00
